April 2004

	Virtual Journal Club
	Volume 3, Number 4 – April, 2004
	The following articles appeared in this month's issues of the surveyed journals. Articles that seem to be of most interest to the practicing gynecologic oncologist are included. The journals that are surveyed are New England Journal of Medicine, Journal of Clinical Oncology, Gynecologic Oncology, Cancer, American Journal of Obstetrics and Gynecology, Lancet, Cancer Research, Obstetrics and Gynecology, Journal of the National Cancer Institute, Journal of the American Medical Association and American Journal of Surgical Pathology. The participants in this program are the active clinical fellows at Memorial Hospital: Mario Leitao, Christopher Awtrey, Sarah Ferguson, Alan Schlaerth, Destin Black and Margrit Juretzka. The managing editor is Douglas Levine. Comments, questions, complaints and suggestions are always welcome, please E-mail us at: VJC@smgo.org or click here. To subscribe or unsubscribe to the VJC, click here. *Gynecologic Oncology* – Christopher Awtrey Title: The benefits of a gynecologic oncologist: a pattern of care study for endometrial cancer treatment Authors: P. Y. Roland , F. J. Kelly , C. Y. Kulwicki , P. Blitzer , M. Curcio and J. W. Orr, Jr. Source: Gynecologic Oncology, Volume 93, Issue 1, April 2004, Pages 125-130 Summary: This study examined a group of endometrial cancer patients treated within a single health system where the operations were performed by either a gynecologic oncologist (GYO) or a gynecologist (GYN), who was assisted by a general surgeon some of the time. The goal of the study was to identify differences in the approach of care that these patients received. From Jan 1998 to December 2000 the GYO group treated 101 patients with endometrial cancer and the GYN group treated 104 patients. Patients who underwent surgery by a GYO were more likely to be surgically staged than in the GYN group 94% vs 45%. In patients at higher risk for extra-uterine disease, those with invasion or G 2 or 3 tumors, GYO treated patients were staged 95.7% versus only 18.8% of the time in the GYN group. There was also a higher average LN yield per patient in the GYO group 19.5 versus 7.7 in the GYN group. Patients with disease limited to the uterus were treated with adjuvant RT in none of the GYO group and in 18% of the GYN group. The authors conclude that gynecologic oncologist provide care for patients that is more comprehensive, efficient and limits the need for adjuvant RT which is associated with potential morbidity. Click here for abstract from Gynecologic Oncology Return to top of page *Journal of Clinical Oncology* - Mario Leitao Title: Outcome of High-Risk Stage IC, Grade 3, Compared With Stage I Endometrial Carcinoma Patients: The Postoperative Radiation Therapy in Endometrial Carcinoma Trial Authors: Creutzberg, Carien L., van Putten, Wim L.J., Warlam-Rodenhuis, Carla C., van den Bergh, Alfons C.M., De Winter, Karin A.J., Koper, Peter C.M., Lybeert, Marnix L.M., Slot, Annerie, Lutgens, Ludy C.H.W., Stenfert Kroese, Marika C., Beerman, Henk, van Lent, Mat Source: J Clin Oncol 2004 22: 1234-1241 Summary: This is another report of patients from the PORTEC trial. The authors looked at the outcomes of patients who were stage IC, grade 3 endometrial cancers and compared them to stage IC, grade 1 or 2, and stage IB, grade 2 or 3. All stage IC, grade 3 patients were not eligible for randomization and all received pelvic radiotherapy but they were followed. This group was compared to patients who were randomized and received pelvic radiotherapy. None of these patients were comprehensively surgically staged. Overall survival at 5 years was 58% for the stage IC, grade 3 patients, compared with 74% for those with stage IB, grade 3 and 83% to 85% for grades 1 to 2 disease (p<0.001). Grade 3 was the most important adverse prognostic factor for relapse and death. The role of adjuvant radiotherapy can not be addressed by this report. Click here for abstract from JCO Title: Intravenous Iron Optimizes the Response to Recombinant Human Erythropoietin in Cancer Patients With Chemotherapy-Related Anemia: A Multicenter, Open-Label, Randomized Trial Authors: Auerbach, Michael, Ballard, Harold, Trout, J. Richard, McIlwain, Marilyn, Ackerman, Alan, Bahrain, Huzefa, Balan, Stefan, Barker, Lance, Rana, Jeevindra Source: J Clin Oncol 2004 22: 1301-1307 Summary: This is a prospective randomized trial of patients with chemotherapy-related anemia. 157 patients were randomized to one of 4 groups with all groups receiving epogen 40,000U SC qwk: (1) no-iron; (2)oral iron; (3) iron dextran weekly bolus; and (4) iron dextran infusion. All treatment groups showed significant increases in Hgb levels from baseline. Mean Hgb increases for both IV iron groups were significantly higher than the no-iron and oral iron groups. No difference was seen between the no-iron group and oral iron or between the two IV iron groups. Both IV iron groups also showed increased QOL scores. Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added. Click here for abstract from JCO Return to top of page Journal of the National Cancer Institute – Alan Schlaerth Title: Projected Clinical Benefits and Cost-effectiveness of a Human Papillomavirus 16/18 Vaccine Authors: Sue J. Goldie, Michele Kohli, Daniel Grima, Milton C. Weinstein, Thomas C. Wright, F. Xavier Bosch, and Eduardo Franco Source: J Natl Cancer Inst 2004; 96: 604-615 Summary: Using a computer-based model of the natural history of HPV and cervical cancer, the authors assessed the clinical benefits and cost-effectiveness of introducing an HPV 16/18 vaccine in a population with an organized cervical cancer screening program. Accounting for vaccine efficacy, waning immunity, and prevention issues, the model showed that the most effective strategy would combine vaccination at age 12 with triennial cytologic screening beginning at age 25. This triennial strategy reduces absolute lifetime risk of cervical cancer by 94% compared to no intervention in their model. The authors conclude that vaccination programs which include a later age screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources. Click here for abstract from JNCI Return to top of page Obstetrics and Gynecology – Margrit Juretzka Title: Atypical Squamous Cells of Undetermined Significance in Girls and Women Authors: Wright, Jason D., Pinto, Anil B., Powell, Matthew A., Lu, Danielle W., Gao, Feng, Pinto, Karen R Source: Obstet Gynecol 2004 103: 632-638 Summary: This retrospective review of ASCUS cytology in 535 adolescents and women aged 10-19 yrs examined outcomes of follow-up. Pathologic follow-up was available in 398 patients with a mean follow-up of 19 months. Sixty-four percent demonstrated no abnormalities, persistent ASCUS was found in 16%, LGSIL in 11% and HGSIL in 9% of patients. The authors note that the rate of squamous intraepithelial lesions/CIN is similar to that of older adults and suggest that these patients warrant similar close follow-up. Click here for abstract from OB/GYN Return to top of page American Journal of Obstetrics and Gynecology – Sarah Ferguson Title: RAS/RAF mutation and defective DNA mismatch repair in endometrial cancers Authors: David G. Mutch, Matthew A. Powell, Mary Ann Mallon and Paul J. Goodfellow Source: American Journal of Obstetrics and Gynecology, Volume 190, Issue 4, April 2004, Pages 935-939 Summary: Abnormalities in DNA mismatch repair genes are frequently found in endometrial cancers. This study looked at the rate of RAS/BRAF mutations in endometrial cancer based on their mismatch repair status. Four hundred and forty one endometrial tumors were characterized for microsatellite instability (MSI). A tumor was classified as MSI-high (MSI-H) if two or more markers showed instability and MSI-low (MSI-L) if only one marker showed instability. All MSH-H tumors were evaluated for MLH1 promotor methylation. There were 146 tumors evaluated for KRAS2 and BRAF mutations. There were 35(24%) with KRAS2 mutations but only one BRAF mutation identified in microsatellite positive endometrial cancers. Of the tumors that were found to be MSI-H and had MLH1 promotor methylation, 24(29.6%) had KRAS2 mutations. The difference in mutation rate between MSI-H and MSI-L approached statistical significance (p = 0.06). The investigators concluded that the development of endometrial cancer is different than colon cancer since mutations in KRAS2 and not BRAF are associated mismatch repair abnormalities. Click here for abstract from AM J OB/GYN Title: Prediction of optimal versus suboptimal cytoreduction of advanced-stage serous ovarian cancer with the use of microarrays Authors: Andrew Berchuck, Edwin S. Iversen, Johnathan M. Lancaster, Holly K. Dressman, Mike West, Joseph R. Nevins and Jeffrey R. Marks Source: American Journal of Obstetrics and Gynecology, Volume 190, Issue 4, April 2004, Pages 910-923 Summary: The objective of this study was to determine if gene expression profiles could identify optimally and suboptimally debulked ovarian cancers. Total RNA from 44 (19 optimal; 25 suboptimal) serous ovarian tumors of advanced stage were evaluated using the Affymetrix U133A microarray with over 22,000 probe sets. The top 120 genes most associated with debulking were determined and these genes were then used to develop a predictive model. They used a leave-one-out cross validation method to test their model. Thirty two genes were identified that could distinguish between optimal and suboptimal debulking with 73% accuracy. Click here for abstract from AM J OB/GYN Return to top of page New England Journal of Medicine – Mario Leitao Nothing of interest this month Journal of the American Medical Association – Margrit Juretzka Nothing of interest this month *Cancer* – Destin Black Nothing of interest this month Lancet – Sarah Ferguson Nothing of interest this month *Cancer Research* – Destin Black Nothing of interest this month American Journal of Surgical Pathology – Alan Schlaerth Title: Grading Ovarian Serous Carcinoma Using a Two-Tier System Authors: Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, and EG Silva Source: Am J Surg Path. Vol. 28, Number 4, April 2004: 496-504 Summary: This study evaluated 100 patients with ovarian serous carcinomas based on a two tiered system distinguished by nuclear atypia and mitotic rate. Fifty patients with low grade ovarian serous carcinomas who had <12 mitoses/10 hpf and mild to moderate atypia were compared to fifty patients with high grade serous carcinomas whose pathology noted >12 mitoses/ 10 hpf and severe atypia. Of the low grade serous carcinomas, 37 patients died at a median of 4.2 years. Twelve patients were alive, 8 with disease, 4 without disease. 46 patients with high grade serous carcinomas died at a median of 1.7 years with four alive with disease at 4 year followup. The authors contend that this two tiered system is easier to classify, yields better reproducibility than FIGO grading systems, although additional studies are necessary for validation. Click here for abstract from AM J Surg Path Return to top of page This issue of the Virtual Journal Club is sponsored by GlaxoSmithKline.