Cancer-Up-to-Date

MAY ; The Month of Skin Cancer Prevention

2006-05-19T16:45:00.000-07:00

May is National Melanoma/Skin Cancer Detection and Prevention Month. More than 1 million people are diagnosed with skin cancer each year. While most cases are highly treatable when caught early, the disease is still expected to claim more than 10,000 American lives in 2006.

* Squamous and basal cell cancers make up the majority of the 1 million-plus skin cancer cases diagnosed each year.

* More than 62,000 people will be diagnosed with melanoma in 2006.

* Of the 10,710 skin cancer deaths this year, melanoma is expected to account for nearly 8,000 of them.

* The 5-year relative survival rate for patients with melanoma is 92 percent.

* Skin cancer symptoms include any change on the skin or to a mole; a sore that won't heal; or growing lumps, often with a rough surface.

To stay sun safe, remember to think about:
* Applying a sun block with a rating of SPF 15 or higher
* Reapplying sun block every two hours, and immediately after swimming or heavy perspiration * Providing additional protection by wearing a broad rimmed hat, sunglasses, long-sleeved shirts and pants
* Avoiding excessive exposure to the sun, especially during the peak hours of 10 a.m. to 4 p.m.

Recognizing changes on the skin is key for early detection and treatment of skin cancers. The American Cancer Society recommends using the ABCD rule to help determine when a skin or mole change should be seen by a physician:

A for asymmetry: one half is differently shaped than the other
B for border irregularity: jagged or blurred edges
C for color: the pigmentation may not be consistent
D for diameter: moles greater than six millimeters (the size of a pencil eraser)
People who experience any of these symptoms should notify their physician immediately.

Burkitt ( Part 4) More on C-MYC

2006-05-02T01:54:00.000-07:00

C-Myc influences the transcription of a variety of proteins involved in cell cycle regulation, apoptosis, cell growth, cell adhesion, and differentiation.

Burkitt ( Part 3)

2006-04-25T01:23:00.000-07:00

- A defining feature of Burkitt’s lymphoma is the presence of a translocation between the c-myc gene and the IgH gene (found in 80% of cases [t(8;14)]) or between c-myc and the gene for either the kappa or lambda light chain (IgL) in the remaining 20% [t(2;8) or t(8;22), respectively].

- c-myc rearrangement is a pivotal event in lymphomagenesis; it results in a perpetually proliferative state. It has wide ranging effects on progression through the cell cycle, cellular differentiation, apoptosis, and cell adhesion.

Burkitt ( Part Two)

2006-04-21T05:18:00.000-07:00

WHO Classification:

- Endemic: African children, usually 4–7 years old, involving the bones of the jaw and other facial bones.EBV is found in nearly all cases

- Sporadic: worldwide, The abdomen, especially the ileocecal area, is the most common site of involvement. Neoplastic cells are EBV+ in 15%–30% of cases.

- Immunodeficiency-associated : shares some pathogenetic features with endemic Burkitt’s lymphoma , often involves lymph nodes, bone marrow, and extranodal sites, most often in the abdomen.

Burkitt ( Part one)

2006-04-18T15:39:00.000-07:00

- In the middle of the last century, when Denis Burkitt, a surgeon, was working in central Africa in Kampala, he noted children with grossly distorted faces, with lesions involving one or both sides of the face and upper and lower jaws, sometimes accompanied by proptosis.

- In 1961, Burkitt made the acquaintance of Epstein, an experimental pathologist, and shared samples of the lymphoma with him. Within these lymphomas, Epstein and colleagues identified the virus that has come to be known as Epstein-Barr virus (EBV); this was the first description of a virus involved in the pathogenesis of a tumor in humans.

-In present-day Africa, Burkitt’s lymphoma continues to account for most childhood malignancies

Burkitt’s lymphoma, sporadic, with classical morphology, involving the tonsil of a child. (A): There is a diffuse infiltrate of atypical lymphoid cells with numerous mitoses and a prominent starry-sky pattern because of the presence of multiple tingible body macrophages. (B): High-power magnification shows that the neoplastic cells are medium-sized, round, and uniform, with nuclei that are similar in size to or slightly smaller than the nuclei of the tingible body macrophages.

To Be Continued....

Statins & Cancer Treatment

2006-04-17T03:36:00.000-07:00

- Increasing evidence suggests that statins might enhance the antitumor activity of various cytokines and chemotherapeutic agents.

- Synergistic interactions have also been reported between statins and chemotherapeutic agents such as cisplatin, 5-fluorouracil (5-FU), and doxorubicin.

- Lovastatin has also been shown to enhance paclitaxel-induced apoptosis in human leukemia cell lines .

- in addition to increasing the antitumor effect, lovastatin treatment was also associated with a lower risk for doxorubicin-associated cardiotoxicity .

HOWEVER

- Pravastatin therapy as a treatment option for advanced hepatocellular carcinoma was not associated with a significantly better overall survival rate.

In terms of High Dose Statin Therapy Safety in Cancer Patients

- In a phase I trial of lovastatin (2–45 mg/kg per day) in patients with solid tumors, no adverse side effects were seen with doses up to 25 mg/kg per day.

- Another phase I/II study also showed that lovastatin (20, 25, or 30 mg/kg for 7 days in cycles repeated monthly) was well tolerated in patients with malignant gliomas

These data suggest that high-dose lovastatin is well tolerated and might have modest anticancer activity, especially in the treatment of brain tumors. In contrast, the antitumor activity of high-dose lovastatin has not been shown in patients with advanced gastric adenocarcinoma .

Questions to be Answered :

- the tumor types most susceptible to statin therapy have yet to be determined.
- it is not known which statins are most effective for cancer prevention and treatment.
- the optimal statin regimen has yet to be defined

In summary, statins may be beneficial for the prevention and treatment of cancer. Now is the time for appropriately designed clinical trials to underpin the promising data of pre-existing studies.

source: Katja Hindlera, Charles S. Cleelandb, Edgardo Riverac, Charles D. Collarda. The Role of Statins in Cancer Therapy . The Oncologist, Vol. 11, No. 3, 306-315, March 2006

Statins & Cancer

2006-04-16T03:35:00.000-07:00

****
Statin-associated carcinogenicity in most of these studies was limited to dosages much higher than that commonly used to treat hypercholesterolemia in humans.

- simvastatin administered at a dose approximately 250 times higher than the dose normally used to treat hypercholesterolemia caused thyroid hypertrophy and follicular cell adenomas in rat strains
- lovastatin administration at high dosage levels (500 mg/kg per day) was associated with a higher incidence of hepatocellular and pulmonary cancers
- fluvastatin was found to be associated with a higher risk for thyroid neoplasms and forestomach papillomas in rodents

***
Confusing :

- A cohort study of more than 12,488 men and women ; inverse association between cholesterol level and cancer incidence, including lung, colorectal, pancreatic, and bladder cancers, and leukemia

On the other hand:

- tendency toward a higher number of cancer deaths in participants treated with cholesterol-lowering agents.( Several studies)

The Role of Statins in Cancer Therapy

2006-03-23T11:29:00.000-08:00

Increasing evidence suggests that statins might be useful for cancer prevention and/or treatment through their interactions with essential cellular functions, such as cell proliferation and differentiation For example, both in vitro and in vivo studies have demonstrated that statins inhibit tumor growth and induce apoptosis in a variety of tumor cells, including melanoma,glioma,neuroblastoma,and leukemia cell lines .

ANTITUMOR EFFECTS OF STATINS

-Inhibition of Tumor Cell Growth
Statins reduce not only serum cholesterol levels but also mevalonate synthesis by inhibiting HMG-CoA reductase.
Mevalonate is a precursor of several major products regulating the cell cycle, including dolichol, geranylpyrophosphate (GPP) and farnesyl-pyrophosphate (FPP).
Statins inhibit dolichol, GPP and FPP production, and block tumor cell growth in vitro and in vivo.

-Inhibition of Angiogenesis
There is growing evidence that the effects of statins on angiogenesis are concentration dependent. Weis et al. showed that low concentrations (0.5 mg/kg per day) of cerivastatin and atorvastatin enhanced endothelial cell proliferation, whereas high concentrations (2.5 mg/kg per day) significantly inhibited angiogenesis

-Induction of Apoptosis
Lovastatin induces a profound apoptotic response in cells derived from juvenile monomyelocytic leukemia, pediatric solid malignancies (e.g., rhabdomyosarcoma and medulloblastoma), malignant mesothelioma, astrocytoma, and squamous cell carcinoma of the cervix, head, and neck.
Proposed mechanisms for statin-mediated apoptosis include an upregulation of proapoptotic protein expression (e.g., Bax, Bim) combined with decreased anti-apoptotic protein expression (e.g., Bcl-2)

-Repression of Tumor Metastases
statins impair the metastatic potential of tumor cells by inhibiting cell migration, attachment to the extracellular matrix, and invasion of the basement membrane. In addition to reducing endothelial leukocyte adhesion molecule (e.g., E-selectin) and matrix metalloproteinase (MMP)-9 expression statins have been shown to inhibit epithelial growth factor–induced tumor cell invasion.

To be continued ...

The Role of Mammography is Uncertain

2006-03-10T01:14:00.000-08:00

There is no agreed protocol for the use of mammography in evaluating the male breast. As a result, the tendency is to use the mammography more often than required. In order to define the role of mammography in men, we carried out a retrospective analysis of all male patients referred to the breast clinic with a history of breast lump between January 2001 and December 2003. The impact of mammography in the evaluation of male breast cancer cases was studied.

A total of 220 male patients were referred to the breast clinic during this period. Of these, 134 men had a mammographic examination, with majority (96%) being performed prior to their consultation with the breast clinician as per the clinic protocol. Nine patients under the age of 35 years also had a mammographic evaluation. There were 4 cases of breast cancer diagnosed during this period. Breast cancer was suspected in all patients on clinical examination and was confirmed by biopsy.

Breast cancer in men can be suspected on clinical examination in the majority of cases. Mammography appears unnecessary in most men and should not be used as a routine imaging procedure. One should consider imaging only those with clinically suspicious breast lumps to avoid unnecessary imaging particularly in young male patients.

source: Hanavadi S, Monypenny IJ, Mansel RE. Is mammography overused in male patients?Breast. 2006 Feb;15(1):123-6. Epub 2005 Apr 19.

Male Breast Cancer

2006-02-28T00:46:00.000-08:00

*In 2005, an estimated 1,690 new cases of male breast cancer will be diagnosed in the U.S., and 460 men will die as a result of breast cancer

*mean age at diagnosis: 67

*Breast cancer in men has been increasing; the incidence has climbed 26% over the past 25 years.

*Testicular abnormalities such as undescended testes, congenital inguinal hernia, orchiectomy, orchitis, and infertility have been consistently associated with elevations in breast cancer risk

*Benign breast conditions, including history of breast trauma and nipple discharge, have also been reported to increase risk

*males with Klinefelter’s syndrome a 50-fold greater risk over the general male population.

*In series of high-risk families undergoing genetic testing, 10%–16% of men with breast cancer have been reported to have BRCA1 mutations.

*Mutations in the BRCA2 gene are more frequent in males with breast cancer, with 4%–16% of men with breast cancer reported to be mutation carriers in population-based series.

*93.7% of male breast cancers are ductal or unclassified carcinomas, 2.6% are papillary, 1.8% are mucinous, and only 1.5% are lobular.

*Approximately 90% of male breast cancers express the estrogen receptor, and 81% express the progesterone receptor.

*The most common presenting symptoms in male breast cancer patients are a painless subareolar lump, nipple retraction, and bleeding from the nipple.

*Mammography can be helpful in differentiating gynecomastia from malignant breast disease.

*Tumor size and lymph node involvement are two clear prognostic factors for male patients with breast cancer. Tumors measuring 2–5 cm have a 40% higher risk of death than men with tumors <2 cm in maximum diameter.

*Overall survival rates are lower for men, but this is due to an older age at diagnosis and more advanced disease at presentation.

*Most men are treated with modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy.

*Adjuvant chemotherapy is used to treat male patients who have a substantial risk of recurrence and death from breast cancer.

Thrombotic Complications of Central Venous Catheters in Cancer Patients

2006-02-25T11:44:00.000-08:00

Types of CVCs
Short-term devices (1–14 days)
percutaneous internal jugular, subclavian, femoral lines
peripherally inserted central catheters (PICCs)

Long-term devices (months-years)
surgically tunneled catheters (Hickman, Broviac, Groshong, Quinton)
totally implanted venous access devices (Mediport, Infus-a-Port® [Horizon Medical Products, Manchester, GA], Port-a-Cath® [Sims-Deltec, Inc., St. Paul, MN])

A major advance in oncology and in long-term alimentation has been the development of a number of long-term catheters that may remain in position for months or years.

Incidence of complications of CVCs

Early
Arrhythmia (13%)
Arterial puncture(2.8%–3.8%)
Malposition of reservoir(2%)
Pneumothorax(1%–1.8%)
Wound dehiscence(1.5%)
Hemorrhage(1.1%–1.2 %)
Failure of insertion(1.2%)

Late
Infection(4%–38%)
Catheter fracture and embolization(3%)
Migration of catheter tip(7.4%)
Thrombosis(~41%) (range 12%–74%)
asymptomatic(~29%) (range 5%–62%)
symptomatic(~12% )(range 5%–41%)
Sequelae of CVC thrombosis
postphlebitic syndrome)15%–35%)
pulmonary embolization(~11%) (range 7%–31%)
symptomatic(~6%) (range 3%–14%)
asymptomatic(~5%) (range 3%–15%)

The presence of malignancy seems to result in a higher rate of CVC thrombosis than the lack of malignancy. In oncology patients, there is also some suggestion that some types of malignancy may be associated with higher rates of CVC thrombosis. 45% of patients with adenocarcinoma of the lung developed symptomatic CVC thrombosis.

The type of chemotherapy does appear to be related to the rate of CVC thrombosis. Clotting occurred in 6 of 11 (55%) catheters through which sclerosing chemotherapy was infused, but in only 9 of 29 (31%) infused with nonsclerosing chemotherapy

The position of the catheter in the vascular system is a major determinate of CVC-related thrombosis.Placement of the catheter tip high in the superior vena cava (SVC) results in a higher incidence of thrombosis than when the catheter tip is placed low in the SVC.In addition, CVCs inserted from the left subclavian vein clotted more commonly than did CVCs inserted from the right subclavian vein.

The number of catheter lumens is a major predictor of catheter thrombosis.

The most common procedure used to reduce CVC-related thrombosis is the routine flushing of catheter ports with unfractionated heparin (UFH) or other substancesSurprisingly, recent studies show that a simple saline flush is as effective as a 100-unit UFH flush in this regard

The majority of studies suggest that low-dose warfarin is effective in preventing CVC-related thrombosis:
1990 randomized trial , Bern et al, 1mg/d warfarin vs. no therapy , duration : 90 days, 9.5% thrombosis rate for warfarin group vs. 32.5% for control group.

Use of Heparin:
Randomized, Monreal et al, 2500 U/d Dalteparin vs No therapy, duration : 90 days, 6% thrombosis rate for heparin group vs 62% for control group.
The only other relevant data on the use of heparin to prevent CVC-related thrombosis come from a meta-analysis of 14 studies by Randolph et al.Only two of those studies were with oncology patients, and the rest were with patients who had a wide range of catheters placed for various indications and procedures. What is striking about this meta-analysis is that various prophylactic heparin doses, ranging from standard UFH to LMWH, decreased the relative rate of thrombosis to 0.43, the relative rate of bacterial colonization to 0.18, and the relative rate of bacteremia to 0.26. The lower rates of infectious complications again confirm the association of thrombosis with infection.

Limitation for Anitcoagulation Therapy:

There is a genuine concern about using warfarin in potentially thrombocytopenic or anorectic chemotherapy patients.

The heparins also have some disadvantages. There is the major inconvenience of daily subcutaneous injections of standard heparin or LMWH. Also, in the asthenic or elderly cancer patient with a reduced glomerular filtration rate, even low prophylactic doses of LMWH may accumulate and cause bleeding. This effect is amplified in patients with reduced renal function due to disease or chemotherapy.

Source: David J. Kuter Thrombotic Complications of Central Venous Catheters in Cancer PatientsOncologist, Apr 2004; 9: 207 - 216 ; doi:10.1634/theoncologist.9-2-207

Renal Safety and Efficacy of i.v. Bisphosphonates in Patients with Skeletal Metastases Treated for up to 10 Years

2006-02-24T05:43:00.000-08:00

Introduction :

*the American Society of Clinical Oncology (ASCO) recommends pamidronate disodium (Aredia®; Novartis Pharmaceuticals Corporation, East Hanover, NJ,) and zoledronic acid (Zometa®; Novartis Pharmaceuticals Corporation) for treating skeletal metastases in breast cancer and multiple myeloma (MM) patients

* zoledronic acid is the first BP with proven efficacy in the treatment of bone metastases from solid tumors other than breast carcinoma

* All BPs have the potential for adversely affecting renal function; indeed, sporadic episodes of acute and subacute renal failure have been described for several i.v. BPs

* Accurate renal function monitoring is recommended for the use of i.v. BPs

* there are few renal safety data compiled from studies encompassing >2 years of i.v. BP administration

Materials/Methods:

* documented skeletal metastases and who received i.v. BPs (pamidronate and/or zoledronic acid) for at least 24 months were eligible. (pamidronate disodium, 90 mg (2–3 hours), or zoledronic acid, 4 mg (15-minute infusion), every 3–4 weeks. )

* measurements of serum creatinine (SCr), included the baseline level, the last-available value (either at the end of treatment or at the time of analysis for patients still receiving BPs), and the highest peak level observed during treatment

* renal toxicity was graduated according to National Cancer Institute-Common Toxicity Criteria, version 2.0 (NCI-CTC, v2.0): grade 1, SCr greater than the upper limit of normal (ULN) – 1.5 x ULN; grade 2, SCr >1.5–3.0 x ULN; grade 3, SCr >3.0–6.0 x ULN; grade 4, SCr >6.0 x ULN.

Results :

* Fifty-seven patients ( breast cancer (n = 48), MM (n = 7), renal cell carcinoma (RCC, n=1), and prostate cancer (n=1)) .

* median age = 57

* 43 patients : Pamidronate and after that Zoledronic
* 11 patients : Zoledronic
* 3 patients: Pamidronate

* Medican duration of BP therapy: 34 months

* The reasons for cessation of BP therapy consisted of: increase in SCr level (2 mg/dl) (n = 1); physician decision because of stable disease (n = 6); and jaw osteonecrosis (n = 3). Ten patients died of progressive disease.

* Median baseline SCr: 0.82
* Median end of treatment SCr: 0.89

* Significant differences were detected between both the baseline and final values (p < .001) and the baseline and peak values observed (p < .00001) * notable increases in SCr levels were recorded in 7 of 57 patients . Among the seven patients, one patient ceased treatment because of physician decision, while six continued BP therapy; in two patients, SCr levels regained the normal ranges, and in four, SCr levels did not increase upon subsequent BP therapy. * Three breast cancer patients developed osteonecrosis of the jaw *

Discussion :

* The efficacy and safety of pamidronate disodium, zoledronic acid, and i.v. ibandronate for up to 2 years of treatment were demonstrated in large, randomized trials in patients with bone metastases from breast cancer, MM, and prostate cancer, and other tumors.

* In the past few years, a growing number of cases of jaw osteonecrosis has been reported in patients undergoing BP therapy [22, 23]. This complication was, in general, observed in patients treated with RT for head and neck cancer; other risk factors for osteonecrosis are long-term steroid therapy, cytotoxic chemotherapy, dental or sinus infections, and trauma. The incidence of this complication ranges from 0.03% to 6.2%.Interestingly, in our study population, jaw osteonecrosis occurred in three of nine breast cancer patients treated with chemotherapy plus trastuzumab, while none of 19 breast cancer patients treated with chemotherapy alone developed this complication.

* In conclusion, the increase in SCr level observed in 12% of our patients (albeit not clinically meaningful) supports a recommendation for monitoring renal function.

Source: Renal Safety and Efficacy of i.v. Bisphosphonates in Patients with Skeletal Metastases Treated for up to 10 Years Valentina Guarneria, Sara Donatib, Massimiliano Nicolinia, Simona Giovannellia, Roberto D’Amicoa, Pier Franco Contea
a Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy; b Division of Medical Oncology, St. Chiara University Hospital, Pisa, Italy
The Oncologist, Vol. 10, No. 10, 842-848, November 2005; doi:10.1634/theoncologist.10-10-842

2006-02-14T11:20:00.000-08:00

Top 25 Articles Published in 2005

The following articles published in 2005 were accessed most frequently from the JAMA Web site.

Original Contribution Excess Deaths Associated With Underweight, Overweight, and ObesityKatherine M. Flegal; Barry I. Graubard; David F. Williamson; Mitchell H. GailJAMA. 2005;293:1861-1867.ABSTRACT FULL TEXT

Original Contribution Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction: A Randomized TrialMichael L. Dansinger; Joi Augustin Gleason; John L. Griffith; Harry P. Selker; Ernst J. SchaeferJAMA. 2005;293:43-53.ABSTRACT FULL TEXT

Original Contribution Role of Computerized Physician Order Entry Systems in Facilitating Medication ErrorsRoss Koppel; Joshua P. Metlay; Abigail Cohen; Brian Abaluck; A. Russell Localio; Stephen E. Kimmel; Brian L. Strom JAMA. 2005;293:1197-1203.ABSTRACT FULL TEXT

Clinical Review Fetal Pain: A Systematic Multidisciplinary Review of the EvidenceSusan J. Lee; Henry J. Peter Ralston; Eleanor A. Drey; John Colin Partridge; Mark A. RosenJAMA. 2005;294:947-954.ABSTRACT FULL TEXT

Original Contribution Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled TrialThe HOPE and HOPE-TOO Trial InvestigatorsJAMA. 2005;293:1338-1347.ABSTRACT FULL TEXT

Original Contribution Meat Consumption and Risk of Colorectal CancerAnn Chao; Michael J. Thun; Cari J. Connell; Marjorie L. McCullough; Eric J. Jacobs; W. Dana Flanders; Carmen Rodriguez; Rashmi Sinha; Eugenia E. CalleJAMA. 2005;293:172-182.ABSTRACT FULL TEXT
Original ContributionHigh-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary Prevention After Myocardial Infarction: The IDEAL Study: A Randomized Controlled TrialTerje R. Pedersen; Ole Faergeman; John J. P. Kastelein; Anders G. Olsson; Matti J. Tikkanen; Ingar Holme; Mogens Lytken Larsen; Fredrik S. Bendiksen; Christina Lindahl; Michael Szarek; John Tsai; for the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study GroupJAMA. 2005;294:2437-2445.ABSTRACT FULL TEXT

Special Communication Five Years After To Err Is Human: What Have We Learned?Lucian L. Leape; Donald M. BerwickJAMA. 2005;293:2384-2390.ABSTRACT FULL TEXT

Original Contribution Contradicted and Initially Stronger Effects in Highly Cited Clinical ResearchJohn P. A. IoannidisJAMA. 2005;294;218-228.ABSTRACT FULL TEXT

Original ContributionEffect of Muraglitazar on Death and Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes MellitusSteven E. Nissen; Kathy Wolski; Eric J. TopolJAMA. 2005;294:2581-2586.ABSTRACT FULL TEXT

Clinical Review A Simplified Approach to the Management of Non-ST-Segment Elevation Acute Coronary SyndromesTy J. Gluckman; Molly Sachdev; Steven P. Schulman; Roger S. BlumenthalJAMA. 2005;293:349-357.ABSTRACT FULL TEXT

Original Contribution Early Mortality Among Medicare Beneficiaries Undergoing Bariatric Surgical ProceduresDavid R. Flum; Leon Salem; Jo Ann Broeckel Elrod; E. Patchen Dellinger; Allen Cheadle; Leighton ChanJAMA. 2005;294:1903-1908.ABSTRACT FULL TEXT

Original Contribution Consumption of Vegetables and Fruits and Risk of Breast CancerCarla H. van Gils; Petra H. M. Peeters; H. Bas Bueno-de-Mesquita; Hendriek C. Boshuizen; Petra H. Lahmann; Francoise Clavel-Chapelon; Anne Thiebaut; Emmanuelle Kesse; Sabina Sieri; Domenico Palli; Rosario Tumino; Salvatore Panico; Paolo Vineis; Carlos A. Gonzalez; Eva Ardanaz; Maria-Jose Sanchez; Pilar Amiano; Carmen Navarro; Jose R. Quiros; Timothy J. Key; Naomi Allen; Kay-Tee Khaw; Sheila A. Bingham; Theodora Psaltopoulou; Maria Koliva; Antonia Trichopoulou; Gabriele Nagel; Jakob Linseisen; Heiner Boeing; Goran Berglund; Elisabet Wirfalt; Goran Hallmans; Per Lenner; Kim Overvad; Anne Tjonneland; Anja Olsen; Eiliv Lund; Dagrun Engeset; Elin Alsaker; Teresa Norat; Rudolf Kaaks; Nadia Slimani; Elio RiboliJAMA. 2005;293:183-193.ABSTRACT FULL TEXT

Clinical Review Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia: A Review of the EvidenceKaycee M. Sink; Karen F. Holden; Kristine YaffeJAMA. 2005;293:596-608.ABSTRACT FULL TEXT

Original Contribution Quality of Cardiopulmonary Resuscitation During Out-of-Hospital Cardiac ArrestLars Wik; Jo Kramer-Johansen; Helge Myklebust; Hallstein Sorebo; Leif Svensson; Bob Fellows; Petter Andreas SteenJAMA. 2005;293:299-304.ABSTRACT FULL TEXT

Original Contribution Effects of Estrogen With and Without Progestin on Urinary IncontinenceSusan L. Hendrix; Barbara B. Cochrane; Ingrid E. Nygaard; Victoria L. Handa; Vanessa M. Barnabei; Cheryl Iglesia; Aaron Aragaki; Michelle J. Naughton; Robert B. Wallace; S. Gene McNeeleyJAMA. 2005;293:935-948.ABSTRACT FULL TEXT

Original Contribution Neurobehavioral Performance of Residents After Heavy Night Call vs After Alcohol IngestionJ. Todd Arnedt; Judith Owens; Megan Crouch; Jessica Stahl; Mary A. CarskadonJAMA. 2005;294:1025-1033.ABSTRACT FULL TEXT

Original Contribution Ximelagatran vs Low-Molecular-Weight Heparin and Warfarin for the Treatment of Deep Vein Thrombosis: A Randomized TrialJean-Noel Fiessinger; Menno V. Huisman; Bruce L. Davidson; Henri Bounameaux; Charles W. Francis; Henry Eriksson; Torbjorn Lundstrom; Scott D. Berkowitz; Per Nystrom; Mona Thorsen; Jeffrey S. Ginsberg; for the THRIVE Treatment Study InvestigatorsJAMA. 2005;293:681-689.ABSTRACT FULL TEXT

Original Contribution Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women's Health Study: A Randomized Controlled TrialI-Min Lee; Nancy R. Cook; J. Michael Gaziano; David Gordon; Paul M Ridker; JoAnn E. Manson; Charles H. Hennekens; Julie E. BuringJAMA. 2005;294:56-65.ABSTRACT FULL TEXT

Review Short-term Risk of Death After Treatment With Nesiritide for Decompensated Heart Failure: A Pooled Analysis of Randomized Controlled TrialsJonathan D. Sackner-Bernstein; Marcin Kowalski; Marshal Fox; Keith AaronsonJAMA. 2005;293:1900-1905.ABSTRACT FULL TEXT

Review Coffee Consumption and Risk of Type 2 Diabetes: A Systematic ReviewRob M. van Dam; Frank B. HuJAMA. 2005;294:97-104.ABSTRACT FULL TEXT

Original Contribution 20-Year Outcomes Following Conservative Management of Clinically Localized Prostate CancerPeter C. Albertsen; James A. Hanley; Judith FineJAMA. 2005;293:2095-2101.ABSTRACT FULL TEXT

Clinical Review Preventing Foot Ulcers in Patients With DiabetesNalini Singh; David G. Armstrong; Benjamin A. LipskyJAMA. 2005;293:217-228.ABSTRACT FULL TEXT

Clinical Review Outcomes of Routine Episiotomy: A Systematic ReviewKatherine Hartmann; Meera Viswanathan; Rachel Palmieri; Gerald Gartlehner; John Thorp; Kathleen N. LohrJAMA. 2005;293:2141-2148.ABSTRACT FULL TEXT

Clinical Review Screening for Breast CancerJoann G. Elmore; Katrina Armstrong; Constance D. Lehman; Suzanne W. FletcherJAMA. 2005;293:1245-1256.ABSTRACT FULL TEXT

Cancer Trends Progress Report - 2005 Update

2006-02-09T15:09:00.000-08:00

The Cancer Trends Progress Report, first issued in 2001 as the Cancer Progress Report, summarizes our nation’s progress against cancer in relation to Healthy People 2010 targets set forth by the Department of Health and Human Services. The report includes key measures of progress along the cancer control continuum and uses national trend data to illustrate where advancements have been made.

Report Highlights
Major Conclusions

The nation is making progress toward major cancer-related Healthy People 2010 targets.

Death rates for the four most common cancers (prostate, breast, lung, and colorectal), as well as for all cancers combined, continue to decline.

The rate of cancer incidence has been relatively stable since the mid 1990s.

Some prevention behaviors have shown improvement. Adult smoking is down dramatically since the 1960s, although rates fell only slightly in the 1990s. Alcohol and fat consumption are headed down, while fruit and vegetable consumption is up only slightly since about 1990.

Youth smoking was on the rise during much of the 1990s, but has shown declines since 1997.

The use of screening tests for breast and cervical cancers is high and remained stable between 2000 and 2003. Screening for colorectal cancer remains low, despite its proven effectiveness, though use is increasing.

People are doing slightly more to protect themselves from the sun.

The nation is losing ground in other important areas that demand attention.

The incidence of cancers of the breast in women and of prostate and testis in men, as well as leukemia, non-Hodgkin lymphoma, myeloma, melanoma of skin, and cancers of the thyroid, kidney, and esophagus is rising.

Lung cancer death rates in women continue to rise, but not as rapidly as before.

More people are overweight and obese, and leisure time physical activity is increasing only slightly.

Cancer treatment spending continues to rise along with total health care spending.

Unexplained cancer-related health disparities remain among population subgroups. For example, Blacks and people with low socioeconomic status have the highest rates of both new cancers and cancer deaths.

The chapters are:

Trends at a glance
Prevention
Treatment
Early Detection
Life after cancer
Diagnosis
End of life.

You can find the link of Cancer Trends 2005 in the left.

Feb 4; World Cancer Day; Childhood cancer

2006-02-03T09:36:00.000-08:00

World Cancer Day is an annual event that marks the anniversary of the first World Summit Against Cancer for the New Millennium, which was held in Paris on February 4, 2000.

The International Union Against Cancer (UICC) and its member organizations are dedicating “World Cancer Day 2006” to childhood cancer. World Cancer Day will take place on Saturday, February 4, 2006.

Each year, more than 160,000 children are diagnosed with cancer, and it is estimated that 90,000 will eventually die of their disease. Although childhood cancers represent a small percentage of all cancers, most of them can be cured if prompt and essential treatment is accessible. However, as 80% of children with cancer live in developing countries where access to information, early detection and effective care and treatment is difficult, more than one in two of these children diagnosed with cancer will die.

Cancer History Class !

2006-01-27T20:32:00.000-08:00

Oldest Descriptions of Cancer

Cancer has afflicted humans throughout recorded history. It is no surprise that from the dawn of history doctors have written about cancer. Some of the earliest evidence of cancer is found among fossilized bone tumors, human mummies in ancient Egypt, and ancient manuscripts. Bone remains of mummies have revealed growths suggestive of the bone cancer, osteosarcoma. In other cases, bony skull destruction as seen in cancer of the head and neck has been found.Our oldest description of cancer (although the term cancer was not used) was discovered in Egypt and dates back to approximately 1600 B.C. The Edwin Smith Papyrus, or writing, describes 8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called "the fire drill." The writing says about the disease, "There is no treatment."

Origin of the Word Cancer

The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 B.C.), considered the "Father of Medicine." Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab. Carcinoma is the most common type of cancer.

Renaissance Period

During the Renaissance, beginning in the 15th century, scientists in Italy developed a greater understanding of the human body. Scientists such as Galileo and Newton began to use the scientific method, which later began to be used to study disease. Autopsies, performed by Harvey (1628), allowed an understanding of the circulation of blood through the heart and body that had remained a mystery.In 1761, Giovanni Morgagni of Padua was the first to do something considered routine today. He performed autopsies to relate the patient's illness to the pathologic findings after death. This laid the foundation for scientific oncology, the study of cancer.The famous Scottish surgeon John Hunter (1728-1793) suggested that some cancers might be cured by surgery and described how the surgeon might decide which cancers to operate on. If the tumor had not invaded nearby tissue and was "moveable," he said, "There is no impropriety in removing it."A century later the development of anesthesia allowed surgery to flourish and the classic cancer operations such as radical mastectomy were developed.

Nineteenth Century

The 19th century saw the birth of scientific oncology with the discovery and use of the modern microscope. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer. As Morgagni had correlated the autopsy findings observed with the unaided eye with the clinical course of illness, so Virchow correlated the microscopic pathology.This method not only allowed a better understanding of the damage cancer had done to a patient but also laid the foundation for the development of cancer surgery. Body tissues removed by the surgeon could now be examined and a precise diagnosis made. In addition, the pathologist could tell the surgeon whether the operation had completely removed the tumor.

Source: American Cancer Society

Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis

2006-01-18T20:15:00.000-08:00

Non-Hodgkin lymphoma (NHL) is a group of heterogeneous diseases characterised by the malignant transformation of healthy lymphoid cells

Several epidemiological studies have associated alcohol consumption with NHL, although results have been inconsistent.

The International Lymphoma Epidemiology Consortium (InterLymph) is a voluntary case-control consortium established in 2000 to facilitate collaboration among major epidemiological studies of lymphoma worldwide.We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by type of alcoholic beverage and by disease subtype.

* Pooled analysis of original data from nine case-control studies identified through InterLymph

*From Jan 1 1990 to Jan 1 2004.

* Total of 9 participant studies

* Requesting original questionnaires; descriptions of study methods; and a dataset that excluded personal identifiers and included variables on alcohol consumption, case or control status, NHL subtype for cases, sex, age, ethnic origin, body-mass index, history of NHL in a first-degree relative, cigarette smoking, and socioeconomic status

* HIVs have been excluded.

* Non Drinkers: those who consumed alcohol less than once a month as an adult

*Ever Drinkers:those who consumed alcohol more than once per month as an adult

*Current/Former Drinking Status: at least 2 years before the date of diagnosis in cases or interview in controls.

* Potential Confounding Factors: Sex, age, ethnic origin, body-mass index, family history of NHL, cigarette smoking, and socioeconomic status

* Cases: 6492 , Controls: 8683

* Median age: 58

* In the pooled data, drinkers had a significantly lower risk of NHL than did non-drinkers (OR=0.83)

*The effect of alcohol on risk of NHL varied with B cell NHL subtype with the lowest risk noted for Burkitt's lymphoma

*suggests that people who drink alcoholic beverages have a lower risk of NHL than those who do not.

*NO dose-response relation for increasing frequency and duration of consumption, or total lifetime consumption

*The potential protective effects of alcohol could be due to its immunomodulatory effects, which have been investigated mainly in people who consume very high amounts of alcohol, including alcoholics.

*light to moderate consumption of alcohol has been associated with increased insulin sensitivity,39, 40 and 41 whereas heavy alcohol use might impair insulin sensitivity.42 Because diabetes has been associated with increased risk of NHL,43 alcohol might reduce the risk of NHL indirectly by increasing insulin sensitivity in otherwise healthy individuals.

*Our definition of usual adult consumption might not have accurately recorded current or recent consumption, weakening the effect. Moreover, the absence of a dose-response relation for duration of consumption might be expected if only current or recent exposure changes risk, as these data suggest, or might indicate a spurious relation by an unknown NHL risk factor.

*Although cases in this pooled analysis had histologically confirmed NHL, central review of all cases by a team of study pathologists was not feasible, and thus NHL classification rules might have differed between studies and some disease misclassification could have occurred for analyses by NHL subtype.

Source:
Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis.
The Lancet Oncology, Volume 6, Issue 7, Pages 469-476 (July 2005)
L. Morton, T. Zheng, T. Holford, E. Holly, B. Chiu, A. Costantini, E. Stagnaro, E. Willett, L. Dal Maso, D. Serraino Ellen T Chang ScDj, Wendy Cozen DOk, ProfScott Davis PhDl, ProfRichard K Severson PhDm, ProfLeslie Bernstein PhDk, ProfSusan T Mayne PhDa, ProfFred R Dee MDn, James R Cerhan MDo, Patricia Hartge ScDb and for the InterLymph Consortium

Lung Cancer Highlights from ASCO 2005

2006-01-12T19:33:00.000-08:00

Exciting news regarding lung cancer was presented at the American Society of Clinical Oncology (ASCO) 2005 Annual Meeting held in Orlando, FL.

ADVANCED NON-SMALL CELL LUNG CANCER

Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without bevacizumab (NSC #704865) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC): An Eastern Cooperative Oncology Group (ECOG) Trial - E4599
A.B. Sandler, R. Gray, J. Brahmer, A. Dowlati, J.H. Schiller, M.C. Perry, D.H. Johnson

July 2001 to April 2004 ,
878 patients ,
Randomized,
Group A: 2 drug therapy,
Group B: 3 drug therapy,
Primary end point: overall survival
Secondary end points were response rate, time to progression, and toxicity

At the 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO), Dr. Sandler reported the results of the second interim analysis, performed after 469 (72.2%) of the 650 deaths required for final analysis.

Results: significant advantage for patients in the bevacizumab arm in terms of median survival (12.5 months vs. 10.2 months; p = .0075). In addition, patients treated with bevacizumab had a significantly greater response rate (27% vs. 10%; p < .0001) and a significantly longer progression-free survival time (6.4 months vs. 4.5 months; p < .0001). Both regimens were well tolerated; a higher incidence of bleeding was associated with bevacizumab administration (4.5% vs. 0.7%).

A randomized phase III trial comparing bexarotene/cisplatin/vinorelbine versus cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic nonsmall cell lung cancer (NSCLC)
J. Jassem, P. Zatloukal, R. Ramlau, P. Schwarzenberger, S. Orlov, J. Rodrigues-Pereira, G. Temperley, M. Mabry, A. Negro-Vilar, Z. Dziewanowska, SPIRIT I Lung Cancer Study Group

Randomized phase III trial comparing bexarotene/carboplatin/paclitaxel versus carboplatin/paclitaxel in chemotherapy-naive patients with advanced or metastatic nonsmall cell lung cancer (NSCLC)
G.R. Blumenschein, F. Khuri, U. Gatzemeier, W.H. Miller, J. von Pawel, J.R. Rigas, R.S. Herbst, Z. Dziewanowska, A. Negro-Vilar, M. Mabry, SPIRIT II Lung Cancer Study Group

These trials were conducted to assess the role of bexarotene in combination with chemotherapy as first-line treatment in advanced NSCLC.

Bexarotene is a novel, oral, multitargeted synthetic agent that binds specifically to retinoid X receptors. It belongs to a family of drugs called rexinoids and is currently approved by the U.S. Food and Drug Administration for the treatment of cutaneous manifestations of T-cell lymphoma in patients who are refractory to at least one prior line of systemic therapy

*1,225 previously untreated advanced NSCLC patients
*Randomized
Group A: Recieve chemotherapy without Bexarotene,
Group B: Recive chemotherapy with Bexarotent,

Chemotherapy in first research: cisplatin (Platinol®; Bristol-Myers Squibb) (100 mg/m2) on day 1 plus vinorelbine (25 mg/m2) on days 1, 8, 15, and 22 i.v. every 4 weeks

Chemotherapy in second research: carboplatin (AUC, 6) plus paclitaxel (200 mg/m2) on day 1 i.v. every 3 weeks

Results: No Better Efficacy

Commentary

Until ASCO 2005, the only standard first-line treatment for patients with advanced NSCLC and good performance status was a two-drug, platinum-based regimen, with either cisplatin or carboplatin combined with a third-generation agent (paclitaxel, gemcitabine [Gemzar®; Eli Lilly and Company, Indianapolis, http://www.lilly.com], docetaxel [Taxotere®; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com], or vinorelbine).

After ASCO 2005, based on the randomized phase III ECOG trial 4599, a two-drug, platinum-based regimen plus bevacizumab is the new standard of care for selected nonsquamous NSCLC patients. That study is a milestone in the history of lung cancer treatment. It is the first randomized trial in the past decade to show a survival advantage in first-line NSCLC, the first randomized trial to show a survival advantage adding a third drug, and the first randomized trial to show a survival advantage with the addition of a molecularly targeted agent to standard chemotherapy in this setting.

Successes and failures of the teachable moment

2005-12-28T12:56:00.000-08:00

Smoking cessation in cancer patients

The diagnosis of cancer is underused as a teachable moment to encourage smoking cessation among patients, family members, and significant others. The medical, psychosocial, and general health benefits of smoking cessation for cancer patients provide a clear rationale for intervention. Moreover, patient knowledge of these benefits may increase motivation to stop smoking and help those who quit to remain abstinent

For the major cancer treatment modalities - radiation therapy, chemotherapy, and surgery - smoking has been found to diminish treatment effectiveness, exacerbate side effects, and interfere with wound healing. Moreover, smoking is a risk factor for a wide range of pulmonary, cardiovascular, infectious, and wound-related complications.Because smoking increases the hepatic metabolism of many drugs, continued smoking may decrease the therapeutic effectiveness of chemotherapy and many other medications used to treat cancer patients current smokers undergoing transverse rectus abdominis myocutaneous (TRAM) flap procedures for breast reconstruction have an increased risk of flap necrosis, abdominal flap necrosis, and hernia

Continued smoking after diagnosis has been found to negatively affect overall survival in patients with lung, head and neck, prostate,and cervical cancers.

Continued smoking is known to increase the risk of developing a second primary malignancy at both the initial tumor site and other sites

A range of intervention components, drawn from extensive research on smoking cessation in the general population and in other patient groups, is readily applicable to cancer patients. Although more research is clearly needed to empirically test smoking cessation interventions with cancer patients, encouraging results have been demonstrated with brief physician-delivered advice and nurse-delivered hospital cessation programs. More intensive interventions, combining elements of behavioral therapy and pharmacotherapy, have been developed for cancer patients but have not yet been extensively tested.

At the initial consultation session, it is strongly recommended that physicians inquire about and document a patient's smoking history, current smoking status, and willingness to make a quit attempt (if applicable). The primary elements of smoking history to obtain include current smoking status, number of cigarettes smoked daily, age at which smoking began, number of years smoked, cessation history, other forms of tobacco use, degree of addiction, and readiness to quit. In addition, smoking behaviors should be routinely evaluated and documented at each follow-up visit. For patients who have a recent smoking history, consideration should be given to the use of biochemical verification of smoking status (e.g., expired carbon monoxide levels or urine, saliva, or serum cotinine levels). This practice not only would allow physicians to have more accurate data with which to guide complicated treatment decisions (e.g., those related to surgery and radiation therapy) but also may facilitate a more candid discussion of motivational factors and individual barriers to quitting

Source :

Successes and failures of the teachable moment: Smoking cessation in cancer patients (p 17-27) Ellen R. Gritz, Michelle Cororve Fingeret, Damon J. Vidrine, Amy B. Lazev, Netri V. Mehta, Gregory P. Reece Published Online: 28 Nov 2005 DOI: 10.1002/cncr.21598

One of THE Best Papers of 2005

2005-12-16T22:58:00.000-08:00

Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer
Edward H. Romond, M.D., Edith A. Perez, M.D., John Bryant, Ph.D., Vera J. Suman, Ph.D., Charles E. Geyer, Jr., M.D., Nancy E. Davidson, M.D., Elizabeth Tan-Chiu, M.D., Silvana Martino, D.O., Soonmyung Paik, M.D., Peter A. Kaufman, M.D., Sandra M. Swain, M.D., Thomas M. Pisansky, M.D., Louis Fehrenbacher, M.D., Leila A. Kutteh, M.D., Victor G. Vogel, M.D., Daniel W. Visscher, M.D., Greg Yothers, Ph.D., Robert B. Jenkins, M.D., Ph.D., Ann M. Brown, Sc.D., Shaker R. Dakhil, M.D., Eleftherios P. Mamounas, M.D., M.P.H., Wilma L. Lingle, Ph.D., Pamela M. Klein, M.D., James N. Ingle, M.D., and Norman Wolmark, M.D.

ABSTRACT

Background
We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.

Methods
The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2).

The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C).

The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.

Results
By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001).>disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015).

The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.

Conclusions
Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 [ClinicalTrials.gov] and NCT00005970 [ClinicalTrials.gov] .)

Year 2005 & Cancer

2005-12-16T15:58:00.000-08:00

The Clinical Proteomics Technologies Initiative launched this year, for instance, will improve the technologies used in proteomics research - a field that is offering new avenues for early detection and diagnosis. There also is The Cancer Genome Atlas Pilot Project, which will yield information about genetic determinants of susceptibility to cancer while laying the groundwork for a full-scale understanding of the genetic etiology of cancer. And the establishment of the NCI Alliance for Nanotechnology in Cancer, including Centers of Excellence and new training programs, will explore new worlds of diagnosis and treatment.

Within the other parts of our portfolio, an important project completed this year was the work of the Clinical Trials Working Group, which produced 22 recommendations for reworking the NCI clinical trials program to make it more effective and efficient. In May, NCI also made an unprecedented commitment to addressing disparities in cancer care with the launch of the Community Networks Program (CNP). The $95 million CNP will help to implement community-based projects aimed at reducing disparities in underserved populations.

Large-scale clinical trials in 2005 yielded results that will have profound effects in preventing and treating many cancers. For example, three different clinical trials showed that adding trastuzumab to chemotherapy significantly reduced the risk of recurrence in women with early-stage, HER-2 positive breast cancer. Results from the Lung Health Study showed that intensive smoking-cessation programs not only can help people stop smoking, but, for those who do quit, can significantly improve long-term survival. Stunning results were seen in an HPV vaccine trial, demonstrating that most cases of cervical cancer can be prevented, which will have important implications in underdeveloped countries. And in September, results from the DMIST trial demonstrated that a subset of women can significantly benefit from digital mammography.

In the laboratory, there were numerous studies that yielded noteworthy results, often using ingenious techniques or novel approaches. Researchers from NCI and the University of Minnesota, for example, published a study demonstrating how employing "jumping DNA" called transposons in mouse models may enable us to identify new cancer genes.

In addition, researchers from the University of Michigan studying prostate cancer identified for the first time, the presence of a commonly fused gene in a solid tumor. The researchers believe other solid tumors may also harbor common translocations, which could serve as biomarkers of disease.
These are just samples of the outstanding work being done every day by cancer researchers.

Eliminating the suffering and death due to cancer by 2015 is a bold and ambitious goal, but this past year has demonstrated progress that gives us hope.

Dr. Andrew C. von Eschenbach

Director, National Cancer Institute

Cardiotoxicity of cytotoxic drugs

2005-12-13T13:24:00.000-08:00

Cardiotoxicity includes a wide range of cardiac effects from small changes in blood pressure and

arrhythmias to cardiomyopathy. In literature different mechanisms of chemotherapy induced cardiotoxicity are postulated including cellular damage due to the formation of free oxygen radicals and the induction of immunogenic reactions with the presence of antigen presenting cells in the heart.3 Moreover, the influence of the cytotoxic agent on certain phospholipids, especially cardiolipin, may also explain the development of cardiotoxicity.4

The anthracyclines, such as doxorubicin and epirubicin, are potent cytotoxic drugs but their
clinical use is often limited by their cardiotoxic side effects.

Other cytotoxic drugs that have reported cardiotoxicity include 5-fluorouracil, capecitabine, mitoxantrone, cisplatin, the taxoids paclitaxel and docetaxel and newer drugs such as
the monoclonal antibody trastuzumab.

Anthracyclines

have been reported to cause cardiomyopathy, congestive heart failure and ECG alterations (e.g.
nonspecific ST-T changes, decreased QRS voltage and prolongation of QT interval).

Early onset effects occur within one year after start of the anthracycline therapy
Late onset effects can occur up to 20 years after completion of anthracycline therapy

Risk factors

Cumulative dose, age, prior irradiation, concomitant administration of other chemotherapeutics
and underlying heart disease are considered as being risk factors for anthracycline Cardiotoxicity.

Cumulative dose seems to be the most important risk factor. Above a cumulative dose of 450–550 mg/m2 doxorubicin, cardiomyopathy and congestive heart failure occur most frequently.

Monitoring and markers of cardiotoxicity

Routine cardiac imaging studies (echocardiogram or multiple gated acquisition scans) can be used to identify (sub)clinical myocardial dysfunction. Endomyocardial biopsy directly measures the presence and extent of fibrosis due to anthracycline cardiotoxicity.

In children treated with anthracyclines elevation of troponin T was found. These elevations
were, however, well below those observed in patients with myocardial infarction

Mechanisms

Oxidative stress hypothesis

The most common hypothesis for the mechanism by which anthracyclines cause cardiotoxicity includes the formation of free radicals and superoxides.

The specific susceptibility of the cardiac cells to the oxidative stress would be due to relatively low levels of antioxidant enzymes in the heart

Protection

Considering the essential role of iron and the doxorubicin–iron complex, iron chelators have
been developed to circumvent anthracycline induced cardiotoxicity

Dexrazoxane (ICRF-187) was found to be the most promising agent. After being tested in animals.

The FDA has approved dexrazoxane for use in adults if cumulative doses of doxorubicin
exceed 300 mg/m2.

Lipid lowering agents

Lipid lowering agents also seem to be able to lower the cardiotoxic effects of anthracyclines.56 When rats were concomitantly treated with doxorubicin and the lipid lowering and antioxidant agent probucol, an increase in the antioxidant enzymes superoxide dismutase and glutathione peroxidase activities and a decrease in lipid peroxidation were found. According to the oxidative stress theory this improvement of antioxidant state of the heart could possibly lead to a better myocardial structure and function.28;57 Recently, Feleszko et al.58 showed both a potentiation of antitumour activity and a cardioprotective effect by the cholesterol lowering HMG coenzyme. A reductase inhibitor lovastatin in mice treated with doxorubicin.

Source:
COMPLICATIONS OF TREATMENT
Cardiotoxicity of cytotoxic drugs
Kirsten J. M. Schimmel , , a, Dick J. Richel b, Renée B. A. van den Brink c and Henk-Jan Guchelaar d
Cancer Treatment Reviews Volume 30, Issue 2 , April 2004, Pages 181-191

New drug for advanced pancreatic cancer

2005-12-13T02:58:00.000-08:00

FDA Approves Drug for Advanced Pancreatic Cancer
Combination Is First New Therapy in a Decade
Article date: 2005/11/07

On November 3, the US Food and Drug Administration (FDA) approved the combination of Tarceva (erlotinib) and Gemzar (gemcitabine) as first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer who had not already undergone chemotherapy treatment. Gemzar alone has been the most commonly used treatment in this situation .

Tarceva was previously approved to treat lung cancer. It is the first drug to be approved in almost a decade for advanced pancreatic cancer.
The treatment is not a cure, but in a clinical trial, it was found to help extend life expectancy slightly for patients with this aggressive disease.

In the trial, researchers from the National Cancer Institute of Canada gave 569 patients with advanced pancreatic cancer either the combination therapy or Gemzar alone. At the end of a year, 24% of the patients receiving both Gemzar and Tarceva were alive, compared to 17% of the group receiving Gemzar alone.

The progression-free survival (the time before the cancer started growing again) for those treated with the combination therapy was 3.75 months, or 6 days longer than for the pancreatic cancer patients who received Gemzar alone. The median overall survival for the Tarceva/Gemzar group was 6.4 months, about 2 weeks longer than those receiving Gemzar only.

The most common side effects of Tarceva are rash and diarrhea, but the drug has also been linked to infrequent cases of a serious lung disorder.

Pancreatic cancer is very difficult to treat. Each year, about 32,000 Americans are diagnosed with pancreatic cancer, and about the same number will die of the disease. Pancreatic cancer is responsible for only about 2% of newly diagnosed cancers in this country, but it is the fourth-leading cause of cancer death.

The high date rate is due in part to the aggressive nature of the disease as well as the difficulty in diagnosing it early enough to treat. Symptoms don't usually appear until the disease is well-progressed. Patients could die within months of diagnosis.
ACS News Center stories are provided as a source of cancer-related news and are not intended to be used as press releases.

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gemcitabine

Trade Name(s):Gemzar

Type of Drug:Gemcitabine belongs to a general group of chemotherapy drugs known as antimetabolites. It is used to treat pancreatic cancer, breast cancer (along with paclitaxel), and lung cancer (along with cisplatin), and may be used for other cancers as well.

How Drug Works:Gemcitabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids. This stops the growth of cancer cells, causing the cells to die.

How Drug Is Given:Gemcitabine is given as an injection in a vein over 30 minutes. For pancreatic cancer, gemcitabine is given once a week for up to 7 weeks to start. Then it is given once a week for 3 weeks, and 1 week without treatment. This is repeated every 4 weeks. When given for breast cancer, it usually is given once a week for 2 weeks, then 1 week off. When given for lung cancer or other cancers, it usually is given weekly for 3 weeks, then 1 week off. The dose depends on your size, your blood counts, and the cancer being treated.

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erlotinib

Trade Name(s):Tarceva, OSI-774

Type of Drug:Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in molecular targeted therapy. It is one of a new group of drugs that targets tiny flaws in the cellÃ‚Â’s communication machinery. It is used to treat non-small cell lung cancer. It is also being studied in many other cancers including breast cancer.

How Drug Works:Erlotinib blocks the EGFR tyrosine kinase protein in the cancer cell from getting a message that tells the cell to grow and divide. This causes the cells to stop growing.

How Drug Is Given:Erlotinib is a pill taken by mouth. Take the dose each day as directed with a large glass of water, at least one hour before or two hours after a meal. For lung cancer patients, the recommended starting dose is 150 mg each day. For people in clinical trials, the dose may depend on your size and the study protocol. Keep the medicine in a tightly closed container away from heat and moisture and out of the reach of children and pets.

NCI CHALLENGE GOAL 2015: Eliminating Death and Suffering Due to Cancer

2005-12-12T23:47:00.000-08:00

Early in 2003, as the Director of the National Cancer Institute, I announced our Challenge Goal to the Nation - to eliminate the suffering and death due to cancer by 2015. Since that time, we at NCI have worked internally and with the national scientific, medical, and lay community to identify the critical elements required to reach this goal. Our proposed strategic investments for Fiscal Year 2006 reflect our recognition that the only way we will achieve our Challenge Goal is to capitalize on the most promising opportunities, remove any barriers that might be impeding progress, and ensure that laboratory discoveries are validated in clinical trials and reach the patient or the person at risk for cancer.

Exponential advances in cancer research are defining, with ever increasing specificity, the many genetic, molecular, and cellular events that influence the cancer process. We now understand cancer as an ongoing process that can be interrupted at many stages from susceptibility to initiation to disease progression. We are translating this new knowledge into innovative, evidence-based strategies to prevent cancer from developing, eliminate it early when it does occur, and modulate its devastating effects.

With the cancer Biomedical Informatics Grid (caBIG), we are using the power of information technology to connect all cancer researchers to data and analytical tools that will dramatically improve research efficiency. We are advancing imaging technologies to detect tumors early when they are easier to treat, to guide therapy or surgery, and to monitor in real time the molecular effects of therapeutic interventions. Image-guided interventions are used, not only to aid in the successful treatment of some cancers and precancerous lesions, but also to provide minimally invasive, well tolerated therapies that eliminate or transform cancers into well managed diseases.

Recent advances in proteomics and the technology of mass spectrometry allow for unprecedented analysis of the body's proteins to define the biomarkers of cancer. Identifying the proteins associated with cancers will allow us to employ recent advances in molecularly targeted imaging to locate very small tumors and interrogate their molecular features. Drugs attached to agents that seek out the proteins on cancer cells will direct therapy exactly where it is needed, without damage to surrounding healthy cells.

We are also developing prevention drugs and vaccines. More easily administered strategies like these hold promise for tremendous benefit to people at high risk for certain types of cancer. For example, the cervical cancer vaccines now under development may ultimately save hundreds of thousands of lives around the world every year.
Advances gained through cancer initiatives will translate into progress for other serious diseases as well. The new National Advanced Technologies Initiative for Cancer, for example, will build national scale public-private coordination that will have far reaching benefits for cancer as well as many other diseases.

Our 2015 Challenge Goal is an urgent call to action that will require a concerted, collaborative effort by the entire community. At NCI, we believe that the Goal is within our grasp, and we are prepared to stretch the boundaries of science, imagination, and human will to achieve success.

Andrew C. von Eschenbach, M.D.
Director, National Cancer InstituteOctober 2004

Recently submitted paper

2005-12-12T17:13:00.000-08:00

Psychosocial Problems Among Lung Cancer Patients

Armin Shahrokni, MD[1]
Karen L.Clark, MS[2]
Matthew Loscalzo, MSW[3]
James Zabora, Sc.D [4]
Karlyn BrintzenhofeSzoc, DSW[5]
Georgia Sadler, PhD[6]

Keywords: Lung Cancer, Distress, Psychosocial Problems, BSI-18

Abstract

Background:
Based on evidence that the diagnosis and treatment of cancer is associated with substantial physical, psychological and social morbidity for patients and previous studies on psychosocial problems in cancer patients showing the highest distress among patients with lung cancer, we further investigate the psychosocial problems among patients with lung cancer.

Method:
Lung cancer patients (151) who were recruited from Johns Hopkins Cancer Institute, from 1998 to 2002, completed BSI-18 and Problem Check List (PCL). Socio-demographic characteristics were collected from patients’ clinical files.

Results
Fatigue (36.40%) and pain (30.50%) were the two most common problems encountered by lung cancer patients (Pain was significantly associated with general distress (r=0.26, p <. 01), somatization (r=0.35, p <. 01) and depression (r=0.22, p <. 01). Problems with transportation were significantly associated with depression (r=0.21, p<. 01) and somatization (r=0.23, p <. 01). 44.55% of patients had level of general distress at or above a level of serious distress that warranted therapeutic interventions. Problems with managing emotions and pain significantly predicted general distress (p< .01), accounting for 13% of the variance. Problems with managing emotions and applying for medical insurance/assistance significantly predicted depression, (p < .01), accounting for 16% of the variance. Marital status and pain accounted for 18% of the variance in somatization, (p<. 01). Conclusion:
These findings support that almost half of patients with lung cancer patients will develop significant distress (that warranted therapeutic interventions) over the course of their treatment.. Recognizing social and environmental factors like transportation and insurance on patients’ distress is another finding of this study.

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[1] Department of Community Outreach, UCSD Moores Cancer Center
[2] Department of Community Outreach, UCSD Moores Cancer Center
[3] Department of Patient and Family Support, UCSD Moores Cancer Center
[4] Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland
[5] Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, Maryland
[6]Department of Community Outreach, UCSD Moores Cancer Center

Kidney Cancer

2005-12-12T13:45:00.000-08:00

Patients with renal cell carcinoma typically present with a suspicious mass involving the kidney that has been visualized by a radiographic study, often a computed tomographic (CT) scan.
Common complaints that lead to the detection of a renal mass are hematuria, flank mass, and flank pain

A thorough physical examination should be performed with special attention for the detection of supraclavicular adenopathy, an abdominal mass, lower extremity edema, a varicocele, or
subcutaneous nodules. Laboratory evaluation includes a complete blood cell count, comprehensive metabolic panel (including serum calcium, liver function studies, LDH, and serum creatinine), coagulation profile, and urinalysis. Computed tomography of the abdomen and pelvis, and a chest radiograph are essential studies in the initial work-up. A CT scan of
the chest is obtained when the chest radiograph is abnormal or progressive disease is suspected.

Primary Therapy and Staging

Patients with locally advanced,unresectable tumors, as well as most patients with evidence of
distant metastases, should have a CT-guided needle biopsy of the kidney or other accessible sites for diagnosis, or undergo cytoreductive nephrectomy for diagnosis

The important prognostic determinants of 5-year survival are the local extent of the tumor, presence of regional nodal metastases, and evidence of metastatic disease at presentation

Nephrectomy

A radical nephrectomy - defined, as a perifascial resection of the kidney, perirenal fat, regional lymph nodes, and ipsilateral adrenal gland - remains the mainstay of surgical resection

Radical nephrectomy also is the treatment of choice if the tumor has extended into the inferior vena cava.

Management Following Nephrectomy

After radical nephrectomy, 20% to 30% of patients with localized tumors relapse. Lung metastasis is the most common site of distant recurrence, occurring in 50% to 60% of patients

No systemic therapy has been shown to reduce the likelihood of relapse.

Follow-up for patients with completely resected disease includes an abdominal CT scan obtained approximately 4 to 6 months after surgery to serve as a baseline

Management of Stage IV Disease

Patients with hematuria or other symptoms related to the primary tumor may be considered for palliative nephrectomy. Immunotherapy is appropriate for patients with good performance status.

Two randomized trials showed benefit of cytoreductive nephrectomy following interferon therapy. The Southwest Oncology Group (SWOG 8949) randomized patients receiving interferon therapy for metastatic disease to nephrectomy or no nephrectomy. The results
of this study show a longer survival rate in patients who had nephrectomy following interferon therapy compared to interferon therapy alone. Median survival favored the surgery group plus
interferon in combined analysis of two randomized trials (13.6 months vs. 7.8 months for interferon alone).

Targeted Agents for the Treatment of Advanced Renal Cell Carcinoma

2005-12-12T02:14:00.000-08:00

Metastatic RCC is currently one of the most treatment- resistant malignancies. Classic cytotoxic chemotherapy is reported to have little antitumor activity in RCC.2 Vinblastine, for example,
had a long history of reported activity and still is used occasionally, but in a multiinstitutional study using rigorous response assessment, only 1 objective response was observed in 80 patients

Immunotherapy with interferon-alpha (IFN-) or interleukin-2 (IL-2) is generally considered the standard of care in RCC. Objective response rates with IFN-range from 10% to 15%, and in Phase III studies, improvements in median survival of only 3–7 months compared with placebo-equivalent therapy have been reported

The prognosis for patients with advanced RCC is extremely poor. The median survival
period is approximately 10 months,8 and the 5-year survival rate is less than 10%.

Angiogenesis is essential for tumor growth, and Folkman21 demonstrated that neovascularization is required for tumors to grow beyond 1–2 mm in greatest dimension, and for metastasis to occur. Angiogenesis is a complex multistage process involving many stimulatory and inhibitory factors, the most established of which is the VEGF/vascular endothelial growth factor receptor (VEGFR) system.

In RCC, serum levels of the most common circulating forms of VEGF have been shown to predict metastatic potential in patients with organ-confined clear cell RCC

PDGF also mediates angiogenic effects and,importantly, may play a role in the later stages of
blood vessel formation via an ability to recruit and support the growth of pericytes

TGF-, another HIF-inducible factor, is a major ligand for the epidermal
growth factor receptor (EGFR), and, upon binding, induces important cellular responses (proliferation, survival, differentiation, migration, adhesion).

Raf/MEK/ERK pathway is a ubiquitous signaling module that forms a link between extracellular
signals and effector molecules in the cytoplasm and nucleus that contribute to cell ifferentiation,
proliferation, and survival. Constitutive activation of Raf/MEK/ERK in RCC was demonstrated

Drug Names Target

Bevacizumab VEGF

BAY 43-9006 VEGFR, PDGFR, Raf kinase

PTK787 VEGFR-1, VEGFR-2, VEGFR-3

SU011248 VEGFR, PDGFR, FLT3, KIT

Gefitinib EGFR

Cetuximab EGFR

Erlotinib EGFR

ABX-EGF EGFR

ISIS-5132 Raf-1

CI-1040 MEK

CCI-779 MTOR

Fewer Breast Cancer Patients to Get Chemo

2005-12-11T21:03:00.000-08:00

By MARILYNN MARCHIONE, AP Medical Writer Sun Dec 11,12:43 AM ET
SAN ANTONIO - For years, doctors have known exactly what to do with breast cancer patients like Eva Ossorio: Poison them. Blasting women with toxic chemicals was considered the best way to save their lives. The bigger the cancer or the more it had spread, the more vile liquid doctors pumped into their veins to try to kill it. But there's been a sea change in the last year.

Guidelines recently adopted in Europe and similar ones unveiled this weekend at a conference in Texas will result in far fewer women getting chemotherapy in the future.

The new advice calls for choosing a treatment based on each woman's particular type of tumor.
"In the past, we made all decisions based on how big the tumor was and whether the lymph nodes were involved. If you had a lot of cancer, you got treated one way, and if you had a little cancer, you got treated another way," said Dr. Eric Winer of the Dana-Farber Cancer Center in Boston.

Under the new rules, hormone status — whether a tumor's growth depends on estrogen or progesterone — becomes the single most important factor in picking treatment.
That is why Ossorio, a 62-year-old nurse in San Antonio, last week was started on a hormone blocker rather than the chemo she formerly would have been given for her relatively large tumor. She was relieved.

"I don't care if I die tomorrow. I decided I didn't want chemotherapy," she said.
Women have reason to dread it. Chemo is a sledgehammer, killing all rapidly dividing cells whether they are out-of-control cancerous ones or healthy ones that naturally grow quickly, like those lining the mouth and stomach. That's why chemo causes hair loss, nausea and mouth sores.

But the worst part is, it only helps about 15 percent of those who get it after the usual surgery to remove their tumors. Roughly 25 percent get worse despite chemo. A whopping 60 percent would have been fine with hormones alone.
"For the vast majority of patients, we probably overtreat," said Dr. William Gradishar of Northwestern University in Chicago.

"It's not that chemotherapy is not of value, it's that the value is smaller in women with hormone-driven disease," said Dr. Robert Carlson, a Stanford University physician who led the U.S. guideline-writing group. "We're trying to determine if the benefit is so small that we should not be recommending chemotherapy."

Several developments in recent years help doctors pick who really needs it.
First is the realization that breast cancers have different causes, arise from different types of cells, are driven by different genes, and tend to be different in women before or after menopause.
"Breast cancer must be understood as an umbrella of diseases," said Dr. Antonio Wolff of Johns Hopkins Medical Institute in Baltimore.
For example, three-fourths of postmenopausal women have tumors fueled by estrogen, called ER-positive disease. Drugs that block this hormone, like tamoxifen and a newer class of medications called aromatase inhibitors, work against those cancers — whether they have spread to lymph nodes or not.

On the other hand, women before menopause often have tumors that are ER-negative and orchestrated by bad genes. Hormones don't help in that case; these women benefit most from chemotherapy.

If hormone drugs are ball-peen hammers compared to chemotherapy, a medication like Herceptin is an even more refined tool. It targets the one-fourth of breast cancers that have too much of a protein on cell surfaces called HER-2 and leaves healthy cells alone.
A woman's HER-2 status is the next factor doctors will consider, after hormone status, in choosing treatments under the new guidelines.

You can see the possibilities: half of HER-2 tumors are ER-positive, but only 10 percent of ER-positive tumors are HER-2-negative.

These aren't black-and-white distinctions, either. Tumors can be weakly ER-positive or negative; same thing for HER-2.

New high-tech lab tests help doctors sort it out. They measure the activity of dozens of genes and reveal which ones are most active and what treatments would work best.
One such test, Oncotype DX, has found its way into more and more doctors' offices since presentations at the Texas cancer meeting last year showed its ability to predict which women benefit from tamoxifen and which do best on chemo.

Ossorio's doctor ordered the test because she thought it would convince Ossorio to have chemo. Surprisingly, it revealed chemo was very unlikely to help.
The test is expensive — $3,400 — but many insurers cover it because it often prevents even more costly and unnecessary chemo, as it did for Ossorio.

Dr. Larry Norton, breast cancer chief at Memorial Sloan-Kettering Cancer Center in New York, uses it when situations are complex and treatment choices aren't obvious. He compares it to lab tests that pinpoint a germ so the right antibiotic can be prescribed.

"In the old days, people just said 'pneumonia.' Now we say 'what organism?' and that lets us identify how to treat the disease," he said.

But relying on factors like hormone and HER-2 status makes the accuracy of lab tests a life-or-death matter. Doctors warn about the wide variation in the quality of such tests, whether low- or high-tech.

"The right (test) is the one that is done right," not which type of test is chosen, Wolff told doctors at the Texas meeting who had come to learn about the U.S. guidelines. The new guidance was developed by the National Comprehensive Cancer Network, a group of leading cancer treatment centers, in cooperation with the American Cancer Society'

Prevalence of Burnout in the U.S. Oncology Community:Results of a 2003 Survey

2005-12-11T00:57:00.000-08:00

Medical professionals in general and practitioners of oncology specifically face a host of highly stressful issues on a daily basis during the routine practice of their profession

The end result of these stresses is reflected in high rates of burnout among medical practitioners.Mount describes burnout as the end result of stress in one’s professional life that
ultimately results in apathy, suspicion, self-protection, disillusion,and depression

Given the ever-changing stresses associated with the practice of medicine, we felt it was important to reassess the level of burnout among U.S. oncologists to understand any changes that may have occurred in the oncology community in recent times.

The survey was sent via e-mail on three separate occasions to a database of 7,715 U.S. oncologists maintained by the Network for Medical Communication and Research of all U.S

The questionnaire comprised a total of 22 questions. The demographics of the responding population was explored in 15 questions and the physicians were asked to prioritize their presumptive causes for, adverse effects from, and potential solutions to their signs of burnout.

As a group, 61.7% (95% CI, 59.39% to 63.95%) of the physicians stated that they had signs of burnout, and 83.2% felt that they detected signs of burnout in their colleagues. Seventyseven
percent of physicians reporting burnout felt that their signs of burnout were becoming more apparent.

the top three signs reported for feelings of burnout included frustration (78%), emotional exhaustion (69%), and lack of satisfaction with their work (50%).

The top three mechanisms for alleviating burnout were felt to be more time away from the office, fewer patients to care for,and increased attendance at professional meetings—which were
also ranked as their most favored means for obtaining medical education, followed by print sources and the Internet.

In this analysis, we identified 12 primary factors that were significantly associated with burnout. Specifically, community oncologists experienced significantly more burnout than academic oncologists. Burnout was more prevalent in oncologists who spent more of their time on patient care, with increasing hours per week on patient care, and with greater numbers of patients seen per week. Similarly, those involved with more administrative activities also demonstrated significantly more burnout. In terms of length of oncology service, those between 10 and 25 years after completing their oncology training demonstrated the highest level of burnout

Source

Sexuality and Fertility after Cancer

2005-12-05T20:44:00.000-08:00

Although not every cancer survivor cares about remaining sexually active, long-term sexual dysfunction has been documented in at least 50% of those treated for breast, prostate, colorectal or gynecological cancer

The most common sexual problems after cancer treatment include loss of desire for sex in men or women, erectile dysfunction (ED) in men, and pain with sexual activity in women.

Cancer treatments may damage one or more of the physiological systems needed for a healthy sexual response, including hormonal, vascular, neurologic, and psychological elements of sexual function. Treatment also may entail removal or direct damage to parts of the reproductive organs.

In men, radical surgery to treat cancer of the prostate, bladder, or rectum has been modified to spare nerves that direct blood flow into the penis. Nevertheless, rates of recovery of firm erections after surgery are far lower in large, long-term surveys than suggested by reports from selected cohorts in academic medical centers Attempts at nerve-sparing radical cystectomy and rectal cancer surgery have also yielded disappointing rates of recovery of erections.6,7 The benefits of nerve-sparing may be limited by fibrosis that builds in the soft tissue of the penis after surgery8 or by concomitant injury to the vascular bed of the penis.

Despite use of newer modalities such as brachytherapy or computer-guided external beam treatment, rates of ED after radiation therapy increase over time so that by 5-year follow-up they equal those after radical surgery

Well-controlled studies of large populations of women have shown that benign hysterectomy, including removal of the cervix, does not impair women’s sexual pleasure or capacity to reach orgasm After radical hysterectomy alone for cervical cancer, most sexual problems with pain or difficulty reaching orgasm resolve by a year after surgery. In contrast to men, women who have radical cystectomy or surgery to remove rectal cancer have similar sexual function to healthy controls.6,12 If pelvic surgery impairs vaginal expansion and lubrication, it seems that women can compensate by using estrogen replacement or water-based lubricants. Hormonal deficits related to cancer treatment are a far less frequent cause of male sexual dysfunction

Women treated with both hysterectomy and postoperative radiation for endometrial cancer have rates of vaginal stenosis as high as 55%, causing significant sexual problems

One predictor of successful sexual rehabilitation is having a sexually functional partner who still desires sex, 5 suggesting that simply being able to have firmer erections does not automatically result in more frequent and pleasurable sex

Despite promising results with using testosterone patches to treat low desire,20 female cancer survivors have to consider their risk for breast cancer that may be potentiated by such therapy High endogenous testosterone is a very strong risk factor for breast cancer in postmenopausal and premenopausal women,28,29 and may also promote systemic breast cancer in women treated for localized disease.30 Hormonal factors also appear to exacerbate the already highly elevated risk of breast cancer in women who received chest irradiation before puberty or were treated for childhood sarcoma

Sperm banking has been available to men before cancer treatment for many years but became much more practical with the success in the early 1990s of in vitro fertilization with intracytoplasmic sperm injection, since only a few live sperm needed to survive freezing and
thawing to be used in assisted reproductive treatments

The major barriers to referring men for sperm banking, cited by half of physician respondents, included lack of time to discuss the topic in a busy clinic, the belief that most patients could not afford to bank sperm (a problem cited only by 7% of men who did not bank sperm38),
and not knowing where to find a convenient sperm bank

Not only is better communication about fertility preservation strongly needed between patient and hematologist/oncologists, but organizations need to develop practice guidelines on when it is appropriate to bring up infertility, how to discuss new modalities that remain experimental and often involve large out-of-pocket costs to the patient, and what options should be offered by cancer centers.49 The advocacy organization Fertile Hope has made an excellent start in
developing patient education materials (www.fertilehope.org).

Anemia in the Elderly: A Public Health Crisis in Hematology

2005-12-05T20:43:00.000-08:00

The NHANES III study indicated that as many as 3,000,000 people in the United States aged 65 or over may be anemic, and that even when “mild” anemia is present, it either causes and/or is associated with both significant functional impairment and, perhaps, increased patient mortality

Using the World Health Organization (WHO) definition of anemia (< 13g Hb/dL for men and < 12 g Hb/dL for women), 11.0% of men and 10.2% of women were anemic according to the NHANES III data set the difference between the prevalence of anemia in elderly, non-Hispanic blacks versus elderly, non-Hispanic whites was 27.8% versus 9.0%

Three general causes for anemia in the elderly, nearly equal in frequency, emerged from the NHANES III study.1 These are 1) anemias due to blood loss/nutritional deficiencies (34%), 2) anemias associated with chronic illness/inflammation or chronic renal failure (32%), and 3) unexplained anemias (34%)

Successful reticulocyte and hemoglobin response to therapeutic iron currently provides a high level of specificity to the diagnosis of iron deficiency anemia. It should be remembered that in elderly patients, however, oral iron might be inadequately absorbed for several reasons, including Helicobacter pylori infection.

Hepcidin appears to play a central role in the pathogenesis of the anemia of chronic disease, but is extremely difficult to measure in the serum.

A suggestion of the importance of an altered inflammatory response as an important cause of anemia in the elderly is suggested by the data from Artz et al, who showed that 27/60 cases (45%) anemias in a nursing home population were idiopathic in nature and characterized by average erythropoietin levels of 14.6 mU/mL, and average IL-6 levels were 8.5 pg/mL.12 Are such patients reflective of a unique "anemia of aging"? The above data also suggest that agents that help control inflammatory dysregulation might be of therapeutic benefit in this situation. However, would there be unintended consequences (e.g., increased infection rate or cancer incidence)?

Findings from the Baltimore Longitudinal Study on 150 individuals (W. Erschler, unpublished data) indicate that erythropoietin production increases with age among those who maintain hemoglobin levels at 14 g/dL or higher and remains constant over time, even in patients who develop diabetes or hypertension. This suggests deficiencies may occur, at least in some individuals, in the hypoxia/erythropoietin sensing mechanism with age that require increased erythropoietin production to maintain normal erythrocyte production.

The use of erythropoietin in the elderly may have both positive (e.g., lessened end-organ damage due to ischemic events) and negative (e.g., increased blood pressure) consequences. The use of synthetic erythropoietin and investigational agents that stimulate endogenous erythropoietin (e.g., hematide, FG 22156) are of clear interest in this patient group.

Table 3. Evaluation of anemia in the elderly for the clinical hematologist: a practical approach.

Always useful
Anemia-oriented history and physical examination, with particular emphasis on co-morbid conditions associated with anemia and drug history
CBC/diff/plt, absolute reticulocyte count, smear review
Tests of iron stores (Fe/TIBC, ferritin, soluble transferrin receptor)
Tests of B12 deficiency; serum levels of cobalamin, methylmalonic acid, and serum homocysteine
Chemistry panel (using calculated creatinine clearance)
Serum erythropoietin (with caveat for what represents a "normal" erythropoeitin in an elderly person)

Sometimes useful
TSH, serum testosterone
Tests of inflammation ( e.g. ESR, C reactive protein)
Bone marrow aspiration and biopsy, cytogenetics (particularly if myelodysplastic syndrome is suspected)
RBC or serum folate level
Specialized tests of erythrocyte physiology (e.g., RBC mass determination, serum interleukin-6 determination)

The Story of Vioxx

2005-12-05T20:42:00.000-08:00

The discovery of the second, rapidly inducible COX isoform in the early 1990s afforded an opportunity to suppress PG formation in a more targeted fashion by designing inhibitors with higher affinity for COX-2 than for COX-1, the coxibs. The underlying hypothesis—sometimes referred to as the ‘COX-2 hypothesis’—was that inflammatory prostaglandins are primarily derived from COX-2, while prostaglandins formed by COX-1 have generally homeostatic roles, including the protection of the gastrointestinal mucosa.

all coxibs were indeed shown to cause less gastroduodenal ulcerations than comparator tNSAIDs, as visualized by endoscopy.2 Celecoxib (Celebrex, Pfizer) and rofecoxib (Vioxx, Merck) were approved by the FDA in 1999, valdecoxib (Bextra, Pfizer) in 2001
the coxibs achieved sales of about $9 billion by the time of the withdrawal of rofecoxib in September 2004

Concurrent with the clinical development of the coxibs, it was recognized that—in contrast to the initial hypothesis—COX-2-derived prostaglandins mediate not only pain and inflammation, but also affect vascular function, thrombosis and blood pressure.8,9 Thus, COX-2 inhibitors depress the vascular biosynthesis of PGI2, leaving platelet COX-1-derived TxA2 unaffected—in contrast to tNSAIDs or aspirin, which inhibit both COX-1 and COX-2.8,9 The actions of PGI2 oppose all mediators that stimulate platelets, elevate blood pressure, and accelerate atherogenesis, including TxA2.10–12 Thus, drug selectivity for inhibition of COX-2 may increase the likelihood of hypertension, myocardial infarction and stroke

Products of the COX pathway have established relevance in clinical syndromes of vascular occlusion. Thus, aspirin reduces the secondary incidence of myocardial infarction, stroke and important vascular events by roughly 25%.20 Suppression of the major product of platelet COX-1, TxA2, which is a potent platelet activator, vasoconstrictor, and mitogen,21 is the basis of cardioprotection by aspirin

The possibility that selective inhibitors of COX-2 may increase cardiovascular risk was raised in 1999 based on observations that both rofecoxib and celecoxib reduced PGI2 formation in healthy individuals by about 70% without concurrent inhibition of platelet function

The elevation of blood pressure by the COX-inhibitors is a more indirect mechanism by which they may accelerate atherogenesis and increase cardiovascular risk. It is well recognized that tNSAIDs and coxibs can induce sodium retention, edema and hypertension.29,30 However, it remains unclear whether the coxibs differ from tNSAIDs in their effects on blood pressure regulation

The first clinical evidence of a cardiovascular hazard of the coxibs arose when a 5-fold higher incidence of myocardial infarction was observed in the rofecoxib group as compared to the naproxen comparator group of the VIGOR study, the prospective trial designed to assess rofecoxib’s gastrointestinal safety.4 Approximately 8000 rheumatoid arthritis patients were treated either with rofecoxib or naproxen with a median follow-up of 9 months. The gastrointestinal event rate was reduced from 4.5 to 2.1 per 100 patient-years by rofecoxib. The study population would probably be considered medium cardiovascular risk at baseline—with chronic rheumatoid inflammation as an independent risk factor. Two explanations for the adverse cardiovascular outcome were discussed at the time—aside from the possibility that this was due to chance:2 (i) a reduction of the cardiovascular event rate in the control group by a cardioprotective effect of naproxen; and/or (ii) a cardiovascular hazard of rofecoxib

It seems more plausible that this coincided with a cardiovascular hazard of rofecoxib. In contrast to rofecoxib, no excess cardiovascular risk was initially associated with celecoxib therapy in its gastrointestinal safety study, the CLASS trial.6 However, in this study the use of low-dose aspirin was allowed and one of the tNSAID comparators was diclofenac, which is similar to celecoxib in its degree of COX-2 selectivity

The trial that led to the withdrawal of rofecoxib—the Adenomatous Polyp Prevention on Vioxx (APPROVe) study, a placebo controlled cancer prevention trial of approximately 2600 patients—detected the cardiovascular risk only after a much longer time of drug exposure.13 It was stopped at 36 months of treatment when a twofold increase in the cardiovascular event rate (rofecoxib: 1.5% vs placebo: 0.78%) was noticed

Both the US Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) concluded that rofecoxib, valdecoxib and celecoxib conveyed a small (1%–2%), but absolute risk of cardiovascular adverse events. Rofecoxib and valdecoxib have been withdrawn from the market in the US and Europe. The FDA applied a "black box" warning to celecoxib, which remains on the market, and the EMEA imposed restrictions on celecoxib (and on etoricoxib, which is on the market in some European countries), and it is possible that new coxibs will be introduced to the market probably with similar restrictions.

update on pathogenesis of atherosclerosis

2005-12-05T20:41:00.000-08:00

Pathogenesis of Atherosclerosis
Mark A. Crowther

The earliest visible lesion of atherosclerosis is the fatty streak, which is due to an accumulation of lipid-laden foam cells in the intimal layer of the artery. With time, the fatty streak evolves into a fibrous plaque, the hallmark of established atherosclerosis.

Atherosclerosis is likely initiated when endothelial cells over-express adhesion molecules in response to turbulent flow in the setting of an unfavorable serum lipid profile. Animals fed a pro-atherogenic diet rapidly overexpress vascular cell adhesion molecule-1 (VCAM-1). Li3 demonstrated that expression of VCAM-1 on endothelial surfaces was an early, and necessary, step in the pathogenesis of atherosclerosis

Once initiated, many mediators of inflammation have been described to influence the development of the atherosclerotic plaque. For example, CD40L elaborated within the plaque has been shown to increase the expression of tissue factor (and thus, presumably increase the likelihood of thrombosis) in atherosclerotic plaques; anti-CD40L abrogates evolution of established atherosclerotic lesions in animal models Inflammatory mediators expressed by smooth cells within the atherosclerotic plaque include, but are not limited to, interleukin (IL)-1ß, tumor necrosis factor (TNF) and ß, IL-6, M-CSF, MCP-1, IL-18 and CD-40L

atherosclerosis-prone mice lacking MCP-1 or M-CSF are less likely to develop progressive atherosclerosis than wild-type mice.

Given the importance of the inflammatory cascade in pathogenesis of atherosclerosis clinical interest has focused on the development of markers of risk; predominant among these is C reactive protein (CRP) and fibrinogen. Activities of CRP in experimental models are protean and include decreased endothelial nitric oxide (NO) and prostacyclin secretion, increased MCP associated chemotaxis, increased IL-8 and increased MMP-1 activity

Peroxisome proliferator-activated receptors (PPARs)9 have emerged as important anti-atherogeneic targets; endothelial-specific roles of PPAR- include inhibition of adhesion molecules, including VCAM-1, increased endothelial NO release, reduced foam cell formation, and reduced uptake of glycated LDL and triglyceride-rich remnant lipoproteins.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, widely known as the "statins," appear, in clinical studies, to have anti-atherogenic effects in excess of those likely to occur due to improved lipid status Thus, statins induce release of anti-atherogenic cytokines (such as IL-4 and IL-10) and diminish expression of pro-atherogenic cytokines, such as IL-6, IFN- and TNF- in macrophages.12 Statins also reduce expression of MCP-1 and other mediators in a variety of models of atherogenesis.

An Update of the Management of Multiple Myeloma:The Changing Landscap

2005-12-05T20:36:00.000-08:00

The International Myeloma Working Group has published new criteria for the diagnosis of symptomatic myeloma, which include the detection of ≥ 10% plasma cells in the bone marrow (or tissue biopsy),a monoclonal protein in the serum or urine and the presence of end-organ damage. Hypercalcemia, renal insufficiency, anemia or bone lesions (referred to by the acronym “CRAB”) each fulfill the definition of end-organ injury1
β2-microglobulin (β2M) level and serum albumin level. Patients with stage I disease have a β2M level <>Strategies to improve the outcome of ASCT).
Improved induction regimens
-Integration of novel agents
Improved pre-ASCT conditioning regimens
-Escalation of melphalan dose
-Integration of novel agents
Tandem ASCT
Improved post-ASCT measures
-Maintenance therapy
Alpha interferon
Corticosteroids
Thalidomide
Combination chemotherapy
Novel agents
-Allogeneic SCT
Immunotherapy
-Vaccines
Source: Hematology 2005

2005-12-05T20:35:00.000-08:00

The American Society of Hematology (ASH) Image Bank is intended to serve as a comprehensive reference and teaching tool that is widely accessible to physicians and hematology students around the world. The images are presented in a digital, case-based format that allows both the images and text to be searched, cross-referenced, and hyper-linked to other cases as well as other educational resources, including Hematology, the Society's annual meeting Education Program Book, the ASH Teaching Cases and the syllabus from the ASH Self-Assessment Program. In addition to the case studies, the Image Bank includes a collection of basic atlas images. This project is a major outreach effort to the clinical and academic community, defined as members of ASH, internists, clinical pathologists, pediatricians, hematologists and oncologists.

American Society of Hematology , Image Bank.

PSA & Prostate Cancer

2005-12-05T20:34:00.000-08:00

Besides prostate cancer, ejaculation and prostate manipulation can raise serum PSA levels as well, so the test should be performed at least 48 hours after these events. Additionally, the test repeated if increased levels are noted, particularly if the value is close to the threshold.
The effect of the 5-alpha reductase inhibitor finasteride on serum PSA levels has been well documented in several studies. This class of drug results in an average decrease of 50% in serum PSA levels after 6 to 12 months. However, this effect is tremendously variable. saw palmetto, may contain hytoestrogenic compounds that may affect serum PSA levels.
Nevertheless, patients should be asked specifically about their use of supplements such as saw palmetto.

source:NCCN2005

Explanatory models of and attitudes towards cancer in different cultures

2005-12-05T20:31:00.000-08:00

Explanatory models of and attitudes towards cancer in different cultures
Simon Dein
Culture determines the different ways that patients understand cancer, the ways they explain it, and their
attitudes towards it. These factors affect the patient’s emotional response to the disease and health behaviour in terms of prevention and treatment. In this paper we review the explanatory models for cancer in several cultural groups. These models range from metaphysical to interpersonal and physical. Cultural explanations of health and health behaviour could detract from social and economic factors that might be more important as determinants of these behaviours.

Lancet Oncol 2004; 5: 119–24