Dana Farber Webchat: The Latest in Ovarian Cancer Treatment & Research

The latest developments in ovarian cancer treatment and research are addressed in the video below via a Dana-Farber Cancer Institute webchat that was conducted on September 16, 2014.

The Susan F. Smith Center for Women’s Cancers at the Dana-Farber Cancer Institute conducted a live video webchat panel with Ursula Matulonis, M.D., medical director of the Gynecologic Oncology Program, and gynecologic oncologists Panos Konstantinopoulos, M.D., Ph.D., and Susana Campos, M.D., MPH. The live webchat was held on September 16, 2014.

The general webchat topics addressed by the Dana-Farber doctors are listed below. For your convenience, we also provided the approximate video start time associated with each discussion topic. The entire video runs 49 minutes and 20 seconds.

  • Various types/subtypes of ovarian cancer and treatment differences. [1:40 minutes]
  • CA-125 and other ovarian cancer biomarkers. [5:10 minutes]
  • Areas of ongoing ovarian cancer research. [9:28 minutes]
  • Ovarian cancer treatment alternatives to standard of care chemotherapy. [13:55 minutes]
  • PARP Inhibitors & Immunotherapy. [15:03 minutes]
  • Mechanisms to reverse platinum drug resistance. [17:15 minutes]
  • Correlation between ovarian cancer and HPV (Human papillomavirus). [19:30 minutes]
  • The use of clinical trials for the treatment of ovarian cancer. [19:43 minutes]
  • Stage 1 ovarian cancer prognosis. [21:47 minutes]
  • Gene mutations related to hereditary ovarian cancer risk. [22:55 minutes]
  • Treatment options for platinum drug refractory/resistant ovarian cancer. [25:27 minutes]
  • Treatment of BRCA gene-mutated ovarian cancer patients. [27:50 minutes]
  • Ovarian cancer prevention. [30:18 minutes]
  • Promising treatments for ovarian clear cell cancer. [31:43 minutes]
  • Proper nutrition during and after ovarian cancer treatment. [33:47 minutes]
  • Symptoms associated with an ovarian cancer recurrence. [35:06 minutes]
  • Ovarian neuroendocrine cancer. [36:16 minutes]
  • Small-cell ovarian cancer. [39:22 minutes]
  • Origin of ovarian cancer. [42:41 minutes]
  • Treatment options for isolated or limited recurrent ovarian cancer tumors/lesions. [45:26 minutes]
  • Closing: Most Exciting Ovarian Cancer Developments. [47:07 minutes]

 

Novel “Jantibody Fusion Protein” Cancer Vaccine Holds Promise Against Ovarian Cancer

A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma.

A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma. Investigators from the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center (VIC) report in the Journal of Hematology & Oncology that a protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.

“Some approaches to creating cancer vaccines begin by extracting a patient’s own immune cells, priming them with tumor antigens and returning them to the patient, a process that is complex and expensive,” says Mark Poznansky, M.D., Ph.D., director of the MGH Vaccine and Immunotherapy Center and senior author of the report. “Our study describes a very practical, potentially broadly applicable and low-cost approach that could be used by oncologists everywhere, not just in facilities able to harvest and handle patient’s cells.”

The MGH team’s vaccine stimulates the patient’s own dendritic cells, a type of immune cell that monitors an organism’s internal environment for the presence of viruses or bacteria, ingests and digests pathogens encountered, and displays antigens from those pathogens on their surface to direct the activity of other immune cells. As noted above, existing cancer vaccines that use dendritic cells require extracting cells from a patient’s blood, treating them with an engineered protein or nucleic acid that combines tumor antigens with immune-stimulating molecules, and returning the activated dendritic cells to the patient.

Fusion protein activates immune cells against tumors The Jantibody fusion protein, combining an antibody fragment targeting an antigen found on tumor cells with an immune-response-inducing protein (MTBhsp70), activates dendritic cells against several tumor antigens and induces a number of T-cell-based immune responses. (Jianping Yuan, PhD, MGH Vaccine and Immunotherapy Center)

Fusion protein activates immune cells against tumors. The Jantibody fusion protein, combining an antibody fragment targeting an antigen found on tumor cells with an immune-response-inducing protein (MTBhsp70), activates dendritic cells against several tumor antigens and induces a number of T-cell-based immune responses. (Jianping Yuan, PhD, MGH Vaccine and Immunotherapy Center)

The approach developed by the MGH team starts with the engineered protein, which in this case fuses an antibody fragment targeting a protein called mesothelin – expressed on the surface of such tumors as mesothelioma, ovarian cancer and pancreatic cancer – to a protein from the tuberculosis bacteria that stimulates the activity of dendritic and other immune cells. In this system, the dendritic cells are activated and targeted against tumor cells while remaining inside the patient’s body.

In the experiments described in the paper, the MGH team confirmed that their mesothelin-targeting fusion protein binds to mesothelin on either ovarian cancer or mesothelioma cells, activates dendritic cells, and enhances the cells’ processing and presentation of several different tumor antigens, inducing a number of T-cell-based immune responses. In mouse models of both tumors, treatment with the fusion protein significantly slowed tumor growth and extended survival, probably through the activity of cytotoxic CD8 T cells.

“Many patients with advanced cancers don’t have enough functioning immune cells to be harvested to make a vaccine, but our protein can be made in unlimited amounts to work with the immune cells patients have remaining,” explains study co-author Jeffrey Gelfand, MD, senior scientist at the Vaccine and Immunotherapy Center. “We have created a potentially much less expensive approach to making a therapeutic cancer vaccine that, while targeting a single tumor antigen, generates an immune response against multiple antigens. Now if we can combine this with newly-described ways to remove the immune system’s “brakes” – regulatory functions that normally suppress persistent T-cell activity – the combination could dramatically enhance cancer immunotherapy.”

Poznansky adds that the tumors that might be treated with the mesothelin-targeting vaccine – ovarian cancer, pancreatic cancer and mesothelioma – all have poor survival rates. “Immunotherapy is generally nontoxic, so this vaccine has the potential of safely extending survival and reducing the effects of these tumors, possibly even cutting the risk of recurrence. We believe that this approach could ultimately be used to target any type of cancer and are currently investigating an improved targeting approach using personalized antigens.” The MGH team just received a two-year grant from the Department of Defense Congressionally Directed Medical Research Program to continue their research.

Poznansky is an associate professor of Medicine, and Gelfand is a clinical professor of Medicine at Harvard Medical School. Jianping Yuan, Ph.D., of the MGH Vaccine and Immunotherapy Center (VIC) is the lead author of the Journal of Hematology and Oncology report. Additional co-authors include Pierre LeBlanc, Ph.D., Satoshi Kashiwagi M.D., Ph.D., Timothy Brauns, and Svetlana Korochkina, Ph.D., MGH VIC; and Nathalie Scholler, M.D., Ph.D., University of Pennsylvania School of Medicine.

The authors dedicate their report to Janet Gelfand, the wife of Jeffrey Gelfand, who died of ovarian cancer in 2006 and inspired their investigation. In her honor they named their tumor-targeting fusion protein “Jantibody.” Support for the study includes grants from the Edmund Lynch Jr. Cancer Fund, Arthur Luxenberg Esq., Perry Weitz Esq., the VIC Mesothelioma Research and Resource Program, and the Friends of VIC Fund.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Sources:

  • Novel cancer vaccine holds promise against ovarian cancer, mesothelioma — Antigen-targeting fusion protein should be less expensive, more accessible than current approaches, Massachusetts General Hospital, Press Release, March 5, 2014.
  • Yuan J et al., A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesotheliomaJ Hematol Oncol. 2014 Feb 24;7(1):15. doi: 10.1186/1756-8722-7-15. (Abstract – PMID: 24565018; Full Text – PMCID: PMC3943805)

2011 ASCO Annual Meeting Abstracts (Including Ovarian Cancer) Made Publicly Available Today

More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

The meeting will be held June 3-7, 2011 at McCormick Place located in Chicago, Illinois. This meeting will be the platform for the release of thousands of scientific abstracts — highly anticipated research news for many people, including patients, caregivers, and the general public. Today, many of those abstracts were made publicly available online (see below).

The 2011 Annual Meeting will center on a theme of “Patients, Pathways, Progress.” The theme, which was selected by ASCO President George W. Sledge, Jr., M.D., promises to:

  • Represent “patients first,” said Dr. Sledge. “Everything we do as a Society has, as its eventual goal, the reduction of cancer mortality and morbidity. We’re on the front line in the war against cancer.”
  • Focus on the molecular, clinical and research pathways that are used to find, develop and implement new treatments for people living with cancer.
  • Celebrate the progress that has already been made in the treatment of cancer, while also reaffirming ASCO’s commitment to aggressive advancements in cancer research in the future.
News announced during the Annual Meeting will include the latest findings from cancer clinical trials, including new drug studies that could change current standards of care. ASCO shares this timely information with the public in a variety of ways. Free patient-friendly summaries of research news highlights from this year’s Annual Meeting will be available via ASCO’s patient information website, Cancer.Net (www.cancer.net). Cancer.Net will post scientific news as soon as it becomes publicly available, on both its homepage and its ASCO Annual Meetings section. The offerings on Cancer.Net include:
  • Easy-to-read summaries that put the top scientific news into context for patients.
  • Videos and podcasts of national and international cancer experts, breaking down the science into specific disease areas and explaining what the studies mean for people with cancer.
  • A news archive from previous ASCO Annual Meetings, which is searchable by year or disease type.

To receive ASCO Annual Meeting breaking news via email, you can sign up now to receive special editions of the newsletter Inside Cancer.Net. You can also follow Cancer.Net on Facebook or Twitter, where real-time updates will also be posted.

Medical abstracts from this year’s meeting were released today at 6:00 P.M. EDT/3:00 P.M. PDT, and additional studies will be released each day of the event in June.

The abstract categories released today, which may be of interest to an ovarian cancer survivor, include the following:

Cancer Prevention/Epidemiology

Developmental Therapeutics – Clinical Pharmacology and Immunotherapy

Gynecologic Cancer

2011 SGO Annual Meeting: Ovarian Cancer Abstracts Selected For Presentation

The March 2011 supplemental issue of Gynecologic Oncology sets forth the ovarian cancer and ovarian cancer-related medical abstracts selected by the Society of Gynecologic Oncologists for presentation at its 42nd Annual Meeting on Women’s Cancer™, which is being held in Orlando, Florida from March 6-9, 2011.

The Society of Gynecologic Oncologists (SGO) is hosting its 42nd Annual Meeting on Women’s Cancer™ (March 6–9, 2011) in Orlando, Florida. The SGO Annual Meeting attracts more than 1,700 gynecologic oncologists and other health professional from around the world.

In connection with this premier gynecologic cancer event, 651 abstracts, and 27 surgical films were submitted for consideration. After careful discussion and deliberation, the SGO selected 51 abstracts for oral presentation (27 Plenary session papers, 24 Focused Plenary papers, and 42 Featured Posters, presented in a new, electronic format), along with 227 for poster presentation. Of the 27 surgical films originally submitted, five films were selected for presentation during a featured Focused Plenary session.

The ovarian cancer abstracts listed below were obtained from the March 2011 supplemental issue of Gynecologic Oncology. Each abstract bears the number that it was assigned in the Gynecologic Oncology journal table of contents.

Please note that we provide below (under the heading “Additional Information”) Adobe Reader PDF copies of the 2011 SGO Annual Meeting program summary and the medical abstract booklet (includes all gynecologic cancer topics). If you require a free copy of the Adobe Reader software, please visit http://get.adobe.com/reader/otherversions/.

For your convenience, we listed the 2011 SGO Annual Meeting ovarian cancer abstracts under the following subject matter headings:  (1) ovarian cancer symptoms, (2) ovarian cancer screening, (3) pathology, (4) ovarian cancer staging, (5) chemotherapy, (6) diagnostic and prognostic biomarkers, (7) clinical trial drugs and results, (8) hereditary breast & ovarian cancer syndrome (BRCA gene deficiencies & Lynch Syndrome), (9) gynecologic practice, (10) gynecologic surgery, (11) genetic/molecular profiling, (12) immunotherapy, (13) medical imaging, (14) preclinical studies – general, (15) preclinical studies – potential therapeutic targets, (16) palliative and supportive care, (17) rare ovarian cancers, (18) survival data, (19) survivorship, (20) other, (21) late breaking abstracts.

Ovarian Cancer Symptoms

142. Utility of symptom index in women at increased risk for ovarian cancer. (SGO Abstract #140)

184. Symptom-triggered screening for ovarian cancer: A pilot study of feasibility and acceptability. (SGO Abstract #182)

187. Women without ovarian cancer reporting disease-specific symptoms. (SGO Abstract #185)

Ovarian Cancer Screening

12. Ovarian cancer: Predictors of primary care physicians’ referral to gynecologic oncologists. (SGO Abstract #10)

84. Long-term survival of patients with epithelial ovarian cancer detected by sonographic screening. (SGO Abstract #82)

90. Significant endometrial pathology detected during a transvaginal ultrasound screening trial for ovarian cancer. (SGO Abstract #88)

109. Detection of the tissue-derived biomarker peroxiredoxin 1 in serum of patients with ovarian cancer: A biomarker feasibility study. (SGO Abstract #107)

113. Epithelial ovarian cancer tumor microenvironment is a favorable biomarker resource. (SGO Abstract #111)

127. Stop and smell the volatile organic compounds: A novel breath-based bioassay for detection of ovarian cancer. (SGO Abstract #125)

144. Incidental gynecologic FDG-PET/CT findings in women with a history of breast cancer. (SGO Abstract #142)

156. Discovery of novel monoclonal antibodies (MC1–MC6) to detect ovarian cancer in serum and differentiate it from benign tumors. (SGO Abstract #154)

158. Evaluation of the risk of ovarian malignancy algorithm (ROMA) in women with a pelvic mass presenting to general gynecologists. (SGO Abstract #156)

162. Human epididymis protein 4 increases specificity for the detection of invasive epithelial ovarian cancer in premenopausal women presenting with an adnexal mass. (SGO Abstract #160)

163. Identification of biomarkers to improve specificity in preoperative assessment of ovarian tumor for risk of cancer. (SGO Abstract #161)

171. OVA1 has high sensitivity in identifying ovarian malignancy compared with preoperative assessment and CA-125. (SGO Abstract #169)

172. OVA1 improves the sensitivity of the ACOG referral guidelines for an ovarian mass. (SGO Abstract #170)

182. Sonographic predictors of ovarian malignancy. (SGO Abstract #180)

237. Management of complex pelvic masses using the OVA1 test: A decision analysis. (SGO Abstract #235)

241. Three-dimensional power doppler angiography as a three-step technique for differential diagnosis of adnexal masses: A prospective study. (SGO Abstract #239)

Pathology

145. Accuracy of frozen-section diagnosis of ovarian borderline tumor. (SGO Abstract #143)

Ovarian Cancer Staging

31. Should stage IIIC ovarian cancer be further stratified by intraperitoneal versus retroperitoneal-only disease? A Gynecologic Oncology Group study. (SGO Abstract #29)

173. Peritoneal staging biopsies in early-stage ovarian cancer: Are they necessary? (SGO Abstract #171)

Chemotherapy

29. Treatment of chemotherapy-induced anemia in patients with ovarian cancer: Does the use of erythropoiesis-stimulating agents worsen survival? (SGO Abstract #27)

69. Intraperitoneal chemotherapy for recurrent ovarian cancer appears efficacious with high completion rates and low complications. (SGO Abstract #67)

174. Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer. (SGO Abstract #172)

177. Sequencing of therapy and outcomes associated with use of neoadjuvant chemotherapy in advanced epithelial ovarian cancer in the Medicare population. (SGO Abstract #175)

179. Should we treat patients with ovarian cancer with positive retroperitoneal lymph nodes with intraperitoneal chemotherapy? Impact of lymph node status in women undergoing intraperitoneal chemotherapy. (SGO Abstract #177)

229. Predictors and effects of reduced relative dose intensity in women receiving their primary course of chemotherapy for ovarian cancer. (SGO Abstract #227)

Diagnostic & Prognostic Biomarkers

128. Stress and the metastatic switch in epithelial ovarian carcinoma. (SGO Abstract #126)

130. The cytoskeletal gateway for tumor aggressiveness in ovarian cancer is driven by class III β-tubulin. (SGO Abstract #128)

134. True blood: Platelets as a biomarker of ovarian cancer recurrence. (SGO Abstract #132)

148. CA-125 changes can predict optimal interval cytoreduction in patients with advanced-stage epithelial ovarian cancer treated with neoadjuvant chemotherapy. (SGO Abstract #146)

149. CA-125 surveillance for women with ovarian, fallopian tube or primary peritoneal cancers: What do survivors think? (SGO Abstract #147)

150. Calretinin as a prognostic indicator in granulosa cell tumor. (SGO Abstract #148)

135. Tumor expression of the type I insulin-like growth factor receptor is an independent prognostic factor in epithelial ovarian cancer. (SGO Abstract #133)

147. C-terminal binding protein 2: A potential marker for response to histone deacetylase inhibitors in epithelial ovarian cancer. (SGO Abstract #145)

157. Elevated serum adiponectin levels correlate with survival in epithelial ovarian cancers. (SGO Abstract #155)

175. Prognostic impact of prechemotherapy HE4 and CA-125 levels in patients with ovarian cancer. (SGO Abstract #175)

178. Serum HE4 level is an independent risk factor of surgical outcome and prognosis of epithelial ovarian cancer. (SGO Abstract #176)

Clinical Trial Drugs & Results

8. MicroRNA as a novel predictor of response to bevacizumab in recurrent serous ovarian cancer: An analysis of The Cancer Genome Atlas. (SGO Abstract #6)

9. Prospective investigation of risk factors for gastrointestinal adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer: A Gynecologic Oncology Group study. (SGO Abstract #7)

10. First in human trial of the poly(ADP)-ribose polymerase inhibitor MK-4827 in patients with advanced cancer with antitumor activity in BRCA-deficient and sporadic ovarian cancers.  (SGO Abstract #8)

30. An economic analysis of intravenous carboplatin plus dose-dense weekly paclitaxel versus intravenous carboplatin plus every three-weeks paclitaxel in the upfront treatment of ovarian cancer. (SGO Abstract #28)

51. BRCA1-deficient tumors demonstrate enhanced cytotoxicity and T-cell recruitment following doxil treatment. (SGO Abstract #49)

54. A novel combination of a MEK inhibitor and fulvestrant shows synergistic antitumor activity in estrogen receptor-positive ovarian carcinoma. (SGO Abstract #52)

68. An economic analysis of bevacizumab in recurrent treatment of ovarian cancer. (SGO Abstract #66)

71. A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer. (SGO Abstract #69)

72. A phase I clinical trial of a novel infectivity-enhanced suicide gene adenovirus with gene transfer imaging capacity in patients with recurrent gynecologic cancer. (SGO Abstract #70)

73. A phase I study of a novel lipopolymer-based interleukin-12 gene therapeutic in combination with chemotherapy for the treatment of platinum-sensitive recurrent ovarian cancer. (SGO Abstract #71)

74. AMG 386 combined with either pegylated liposomal doxorubicin or topotecan in patients with advanced ovarian cancer: Results from a phase Ib study. (SGO Abstract #72)

86. Pressure to respond: Hypertension predicts clinical benefit from bevacizumab in recurrent ovarian cancer. (SGO Abstract #84)

152. Changes in tumor blood flow as estimated by dynamic-contrast MRI may predict activity of single-agent bevacizumab in recurrent epithelial ovarian cancer and primary peritoneal cancer: An exploratory analysis of a Gynecologic Oncology Group phase II trial. (SGO Abstract #150)

153. Comparing overall survival in patients with epithelial ovarian, primary peritoneal or fallopian tube cancer who received chemotherapy alone versus neoadjuvant chemotherapy followed by delayed primary debulking. (SGO Abstract #151)

154. Consolidation paclitaxel is more cost-effective than bevacizumab following upfront treatment of advanced ovarian cancer. (SGO Abstract #152)

193. Pegylated liposomal doxorubicin with bevacizumab in the treatment of platinum-resistant ovarian cancer: Toxicity profile results. (SGO Abstract #191)

194. Phase II Trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. (SGO Abstract #192)

195. A phase I/II trial of IDD-6, an autologous dendritic cell vaccine for women with advanced ovarian cancer in remission. (SGO Abstract #193)

183. STAC: A phase II study of carboplatin/paclitaxel/bevacizumab followed by randomization to either bevacizumab alone or erlotinib and bevacizumab in the upfront management of patients with ovarian, fallopian tube or peritoneal cancer. (SGO Abstract #181)

228. Is it more cost-effective to use bevacizumab in the primary treatment setting or at recurrence? An economic analysis. (SGO Abstract #226)

240. The use of bevacizumab and cytotoxic and consolidation chemotherapy for the upfront treatment of advanced ovarian cancer: Practice patterns among medical and gynecologic oncology SGO members. (SGO Abstract #238)

Hereditary Breast & Ovarian Cancer Syndrome (BRCA gene deficiencies & Lynch Syndrome)

39. BRCAness profile of ovarian cancer predicts disease recurrence. (SGO Abstract #37)

52. A history of breast carcinoma predicts worse survival in BRCA1 and BRCA2 mutation carriers with ovarian carcinoma. (SGO Abstract #52)

137. Does genetic counseling for women at high risk of harboring a deleterious BRCA mutation alter risk-reduction strategies and cancer surveillance behaviors? (SGO Abstract #135)

138. Hereditary breast and ovarian cancer syndrome based on family history alone and implications for patients with serous carcinoma. (SGO Abstract #138)

139. Management and clinical outcomes of women with BRCA1/2 mutations found to have occult cancers at the time of risk-reducing salpingo-oophorectomy. (SGO Abstract #137)

141. The impact of BRCA testing on surgical treatment decisions for patients with breast cancer. (SGO Abstract #139)

136. Compliance with recommended genetic counseling for Lynch syndrome: Room for improvement. (SGO Abstract #134)

Gynecologic Practice

81. Availability of gynecologic oncologists for ovarian cancer care. (SGO Abstract #79)

Gynecologic Surgery

19. Single-port paraaortic lymph node dissection. (SGO Abstract #17)

20. Robotic nerve-sparing radical hysterectomy type C1. (SGO Abstract #18)

21. Urinary reconstruction after pelvic exenteration: Modified Indiana pouch. (SGO Abstract #19)

22. Intrathoracic cytoreductive surgery by video-assisted thoracic surgery in advanced ovarian carcinoma. (SGO Abstract #20)

26. Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer. (SGO Abstract #24)

28. Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. (SGO Abstract #26)

33. Does the bedside assistant matter in robotic surgery: An analysis of patient outcomes in gynecologic oncology. (SGO Abstract #31)

48. Defining the limits of radical cytoreductive surgery for ovarian cancer. (SGO Abstract #46)

87. Prognostic impact of lymphadenectomy in clinically early-stage ovarian malignant germ cell tumor. (SGO Abstract #85)

93. Secondary cytoreductive surgery: A key tool in the management of recurrent ovarian sex cord–stromal tumors. (SGO Abstract #91)

146. Advanced-stage ovarian cancer metastases to sigmoid colon mesenteric lymph nodes: Clinical consideration of tumor spread and biologic behavior. (SGO Abstract #144)

155. Cytoreductive surgery for serous ovarian cancer in patients 75 years and older. (SGO Abstract #153)

168. Intraperitoneal catheters placed at the time of bowel surgery: A review of complications. (SGO Abstract #166)

169. Laparoscopic versus laparotomic surgical staging for early-stage epithelial ovarian cancer. (SGO Abstract #167)

170. Oncologic and reproductive outcomes of cystectomy compared with oophorectomy as treatment for borderline ovarian tumor. (SGO Abstract #168)

180. Significance of perioperative infectious disease in patients with ovarian cancer. (SGO Abstract #178)

185. The feasibility of mediastinal lymphadenectomy in the management of advanced and recurrent ovarian carcinoma. (SGO Abstract #183)

235. Incidence of venous thromboembolism after robotic surgery for gynecologic malignancy: Is dual prophylaxis necessary? (SGO Abstract #233)

286. Charlson’s index: A validation study to predict surgical adverse events in gynecologic oncology. (SGO Abstract #284)

288. Cost-effectiveness of extended postoperative venous thromboembolism prophylaxis in gynecologic pncology patients. (SGO Abstract #286)

302. Integration of and training for robot-assisted surgery in a gynecologic oncology fellowship program. (SGO Abstract #300)

303. Outcomes of patients with gynecologic malignancies undergoing video-assisted thorascopic surgery and pleurodesis for malignant pleural effusion. (SGO Abstract #301)

304. Perioperative and pathologic outcomes following robot-assisted laparoscopic versus abdominal management of ovarian cancer. (SGO Abstract #302)

307. Predictive risk factors for prolonged hospitalizations after gynecologic laparoscopic surgery. (SGO Abstract #305)

309. Robot-assisted surgery for gynecologic cancer: A systematic review. (SGO Abstract #307)

310. Robotic radical hysterectomy: Extent of tumor resection and operative outcomes compared with laparoscopy and exploratory laparotomy. (SGO Abstract #308)

315. Utilization of specialized postoperative services in a comprehensive surgical cytoreduction program. (SGO Abstract #313)

Genetic/Molecular Profiling

5. A 3’ UTR KRAS variant as a biomarker of poor outcome and chemotherapy resistance in ovarian cancer. (SGO Abstract #3)

15. XPC single-nucleotide polymorphisms correlate with prolonged progression-free survival in advanced ovarian cancer. (SGO Abstract #13)

16. Genomewide methylation analyses reveal a prominent role of HINF1 network genes, via hypomethylation, in ovarian clear cell carcinoma. (SGO Abstract #14)

49. Loss of ARID1A is a frequent event in clear cell and endometrioid ovarian cancers. (SGO Abstract #47)

53. Genetic variants in the mammalian target of rapamycin (mTOR) signaling pathway as predictors of clinical response and survival in women with ovarian cancer. (SGO Abstract #51)

55. BAD apoptosis pathway expression and survival from cancer. (SGO Abstract #53)

59. Molecular profiling of advanced pelvic serous carcinoma associated with serous tubal intraepithelial carcinoma. (SGO Abstract #57)

82. Biologic roles of tumor and endothelial delta-like ligand 4 in ovarian cancer. (SGO Abstract #80)

85. MicroRNA 101 inhibits ovarian cancer xenografts by relieving the chromatin-mediated transcriptional repression of p21waf1/cip1. (SGO Abstract #83)

102. Association between global DNA hypomethylation in leukocytes and risk of ovarian cancer. (SGO Abstract #100)

103. Cisplatin, carboplatin, and paclitaxel: Unique and common pathways that underlie ovarian cancer response. (SGO Abstract #101)

106. Comparison of mTOR and HIF pathway alterations in the clear cell carcinoma variant of kidney, ovary and endometrium. (SGO Abstract #104)

107. Concordant gene expression profiles in matched primary and recurrent serous ovarian cancers predict platinum response. (SGO Abstract #105)

111. Differential microRNA expression in cis-platinum-resistant versus -sensitive ovarian cancer cell lines. (SGO Abstract #109)

112. DNA methylation markers associated with serous ovarian cancer subtypes. (SGO Abstract #110)

118. MicroRNA and messenger RNA pathways associated with ovarian cancer cell sensitivity to topotecan, gemcitabine and doxorubicin. (SGO Abstract #116)

119. Molecular profiling of patients with curatively treated advanced serous ovarian carcinoma from The Cancer Genome Atlas. (SGO Abstract #117)

125. Proteomic analysis demonstrates that BRCA1-deficient epithelial ovarian cancer cell lines activate alternative pathways following exposure to cisplatin. (SGO Abstract #123)

132. The tumor suppressor KLF6, lost in a majority of ovarian cancer cases, represses VEGF expression levels. (SGO Abstract #130)

126. Quantitative PCR array identification of microRNA clusters associated with epithelial ovarian cancer chemoresistance. (SGO Abstract #124)

160. Genes functionally regulated by methylation in ovarian cancer are involved in cell proliferation, development and morphogenesis. (SGO Abstract #158)

181. Single-nucleotide polymorphism in DNA repair and drug resistance genes alone or in combination in epithelail ovarian cancer. (SGO Abstract #179)

278. Expression patterns of p53 and p21 cell cycle regulators and clinical outcome in women with pure gynecologic sarcomas. (SGO Abstract #276)

Immunotherapy

98. Ab-IL2 fusion proteins mediate NK cell immune synapse formation in epithelial ovarian cancer by polarizing CD25 to the target cell–effector cell interface. (SGO Abstract #96)

124. Proteasome inhibition increases death receptors and decreases major histocompatibility complex I expression: Pathways to exploit in natural killer cell immunotherapy. (SGO Abstract #122)

Medical Imaging

164. Impact of FDG-PET in suspected recurrent ovarian cancer and optimization of patient selection for cytoreductive surgery. (SGO Abstract #162)

294. The clinical and financial implications of MRI of pelvic masses. (SGO Abstract #292)

Preclinical Studies

11. A unique microRNA locus at 19q13.41 sensitizes epithelial ovarian cancers to chemotherapy. (SGO Abstract #9)

14. Common single-nucleotide polymorphisms in the BNC2, HOXD1 and MERIT40 regions contribute significantly to racial differences in ovarian cancer incidence. (SGO Abstract #12)

46. Development of a preclinical serous ovarian cancer mouse model. (SGO Abstract #44)

56. Examination of matched primary and recurrent ovarian cancer specimens supports the cancer stem cell hypothesis. (SGO Abstract #54)

58. Modeling of early events in serous carcinogenesis: Molecular prerequisites for transformation of fallopian tube epithelial cells. (SGO Abstract #56)

101. Antiproliferative activity of a phenolic extract from a native Chilean Amaranthaceae plant in drug-resistant ovarian cancer cell lines. (SGO Abstract #99)

115. Identification and characterization of CD44+/CD24–ovarian cancer stem cell properties and their correlation with survival. (SGO Abstract #113)

Preclinical Studies – Potential Therapeutic Targets

57. Hypoxia-mediated activation of signal transducer and activator of transcription 3 (STAT3) in ovarian cancer: A novel therapeutic strategy using HO-3867, a STAT3 inhibitor (and novel curcumin analog). (SGO Abstract #55)

61. The ubiquitin ligase EDD mediates platinum resistance and is a target for therapy in epithelial ovarian cancer. (SGO Abstract #59)

97. A novel hedgehog pathway smoothened inhibitor (BMS-833923) demonstrates in vitro synergy with carboplatin in ovarian cancer cells. (SGO Abstract #95)

100. AMPK activation mimics glucose deprivation and induces cytotoxicity in ovarian cancer cells. (SGO Abstract #98)

104. Clinical significance of vascular cell adhesion molecule 1 (VCAM-1) in the ovarian cancer microenvironment. (SGO Abstract #102)

105. Combined erbB/VEGFR blockade has improved anticancer activity over single-pathway inhibition in ovarian cancer in vivo. (SGO Abstract #103)

114. EZH2 expression correlates with increased angiogenesis in ovarian carcinoma. (SGO Abstract #112)

116. Induction of apoptosis in cisplatin-resistant ovarian cancer cells by G-1, a specific agonist of the G-protein-coupled estrogen receptor GPR30. (SGO Abstract #114)

120. Neuropilin-1 blockade in the tumor microenvironment reduces tumor growth. (SGO Abstract #118)

129. Targeting the hedgehog pathway reverses taxane resistance in ovarian cancer. (SGO Abstract #127)

121. Ovarian cancer lymph node metastases express unique cellular structure and adhesion genes. (SGO Abstract #119)

122. Overexpression of fibroblast growth factor 1 and fibroblast growth factor receptor 4 in high-grade serous ovarian carcinoma: Correlation with survival and implications for therapeutic targeting. (SGO Abstract #120)

131. The pattern of H3K56 acetylation expression in ovarian cancer. (SGO Abstract #129)

133. Thinking outside of the tumor: Targeting the ovarian cancer microenvironment. (SGO Abstract #131)

161. Horm-A domain-containing protein 1 (HORMAD1) and outcomes in patients with ovarian cancer. (SGO Abstract #159)

165. Influence of the novel histone deacetylase inhibitor panobinostat (LBH589) on the growth of ovarian cancer. (SGO Abstract #163)

166. Inhibition of stress-induced phosphoprotein 1 decreases proliferation of ovarian cancer cell lines. (SGO Abstract #164)

167. Insulin-like growth factor receptor 1 pathway signature correlates with adverse clinical outcome in ovarian cancer. (SGO Abstract #165)

230. Therapeutic synergy and resensitization of drug-resistant ovarian carcinoma to cisplatin by HO-3867. (SGO Abstract #228)

Palliative & Supportive Care

159. Factors associated with hospice use in ovarian cancer. (SGO Abstract #226)

190. Age-related preferences regarding end-of-life care discussions among gynecologic oncology patients. (SGO Abstract #188)

192. Palliative care education in gynecologic oncology: A survey of the fellows. (SGO Abstract #190)

Rare Ovarian Cancers

151. Carcinosarcoma of the ovary: A case–control study. (SGO Abstract #149)

Survival Data

80. Ten-year relative survival for epithelial ovarian cancer. (SGO Abstract #78)

83. Impact of beta blockers on epithelial ovarian cancer survival. (SGO Abstract #81)

176. Revisiting the issue of race-related outcomes in patients with stage IIIC papillary serous ovarian cancer who receive similar treatment. (SGO Abstract #174)

186. The impact of diabetes on survival in women with ovarian cancer. (SGO Abstract #184)

284. Survival following ovarian versus uterine carcinosarcoma. (SGO Abstract #282)

285. The unique natural history of mucinous tumors of the ovary. (SGO Abstract #283)

292. Stage IC ovarian cancer: Tumor rupture versus ovarian surface involvement. (SGO Abstract #290)

Survivorship

191. Menopausal symptoms and use of hormone replacement therapy: The gynecologic cancer survivors’ perspective. (SGO Abstract #189)

Other

4. From guidelines to the front line: Only a minority of the Medicare population with advanced epithelial ovarian cancer receive optimal therapy. (SGO Abstract #2)

32. Efficacy of influenza vaccination in women with ovarian cancer. (SGO Abstract #30)

91. Women with invasive gynecologic malignancies are more than 12 times as likely to commit suicide as are women in the general population. (SGO Abstract #89)

231. Attrition of first-time faculty in gynecologic oncology: Is there a difference between men and women? (SGO Abstract #229)

238. Relative impact of cost drivers on the increasing expense of inpatient gynecologic oncology care. (SGO Abstract #236)

Late-Breaking Abstracts

About Society of Gynecologic Oncologists (SGO)

The SGO is a national medical specialty organization of physicians and allied healthcare professionals who are trained in the comprehensive management of women with malignancies of the reproductive tract. Its purpose is to improve the care of women with gynecologic cancer by encouraging research, disseminating knowledge which will raise the standards of practice in the prevention and treatment of gynecologic malignancies, and cooperating with other organizations interested in women’s health care, oncology and related fields. The Society’s membership, totaling more than 1,400, is primarily comprised of gynecologic oncologists, as well as other related medical specialists including medical oncologists, radiation oncologists, nurses, social workers and pathologists. SGO members provide multidisciplinary cancer treatment including chemotherapy, radiation therapy, surgery and supportive care. More information on the SGO can be found at www.sgo.org.

About Gynecologic Oncologists

Gynecologic oncologists are physicians committed to the comprehensive treatment of women with cancer. After completing four years of medical school and four years of residency in obstetrics and gynecology, these physicians pursue an additional three to four years of training in gynecologic oncology through a rigorous fellowship program overseen by the American Board of Obstetrics and Gynecology. Gynecologic oncologists are not only trained to be skilled surgeons capable of performing wide-ranging cancer operations, but they are also trained in prescribing the appropriate chemotherapy for those conditions and/or radiation therapy when indicated. Frequently, gynecologic oncologists are involved in research studies and clinical trials that are aimed at finding more effective and less toxic treatments to further advance the field and improve cure rates.

Studies on outcomes from gynecologic cancers demonstrate that women treated by a gynecologic oncologist have a better likelihood of prolonged survival compared to care rendered by non-specialists. Due to their extensive training and expertise, gynecologic oncologists often serve as the “team captain” who coordinates all aspects of a woman’s cancer care and recovery. Gynecologic oncologists understand the impact of cancer and its treatments on all aspects of women’s lives including future childbearing, sexuality, physical and emotional well-being—and the impact cancer can have on the patient’s whole family.

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Additional Information:


President of M.D. Anderson Outlines 10 Steps To Achieve Progress Against Cancer.

“The Houston Chronicle recently published a commentary by John Mendelsohn, M.D., president of M. D. Anderson, outlining actions the nation should take to achieve great progress against cancer. … Here are 10 steps we can take to ensure that deaths decrease more rapidly, the ranks of survivors swell, and an even greater number of cancers are prevented in the first place. …”

“Ten Pieces Help Solve Cancer Puzzle

John Mendelsohn, M.D., President, The University of Texas M.D. Anderson Cancer Center

John Mendelsohn, M.D., President, The University of Texas M.D. Anderson Cancer Center

The Houston Chronicle recently published a commentary by John Mendelsohn, M.D., president of M. D. Anderson, outlining actions the nation should take to achieve great progress against cancer.

An American diagnosed with cancer today is very likely to join the growing ranks of survivors, who are estimated to total 12 million and will reach 18 million by 2020. The five-year survival rate for all forms of cancer combined has risen to 66%, more than double what it was 50 years ago.

Along with the improving five-year survival rates, the cancer death rate has been falling by 1% to 2% annually since 1990.

According to the World Health Organization, cancer will be the leading worldwide cause of death in 2010. Over 40% of Americans will develop cancer during their lifetime.

While survival rates improve and death rates fall, cancer still accounts for one in every five deaths in the U.S., and cost this nation $89.0 billion in direct medical costs and another $18.2 billion in lost productivity during the illness in 2007, according to the National Institutes of Health.

Here are 10 steps we can take to ensure that deaths decrease more rapidly, the ranks of survivors swell, and an even greater number of cancers are prevented in the first place.

#1.  Therapeutic cancer research should focus on human genetics and the regulation of gene expression.

Cancer is a disease of cells that have either inherited or acquired abnormalities in the activities of critical genes and the proteins for which they code. Most cancers involve several abnormally functioning genes – not just one – which makes understanding and treating cancer terribly complex. The good news is that screening for genes and their products can be done with new techniques that accomplish in days what once took years.

Knowledge of the human genome and mechanisms regulating gene expression, advances in technology, experience from clinical trials, and a greater understanding of the impact of environmental factors have led to exciting new research approaches to cancer treatment, all of which are being pursued at M. D. Anderson:

  • Targeted therapies.  These therapies are designed to counteract the growth and survival of cancer cells by modifying, replacing or correcting abnormally functioning genes or their RNA and protein products, and by attacking abnormal biochemical pathways within these cells.
  • Molecular markers.  Identifying the presence of particular abnormal genes and proteins in a patient’s cancer cells, or in the blood, will enable physicians to select the treatments most likely to be effective for that individual patient.
  • Molecular imaging.  New diagnostic imaging technologies that detect genetic and molecular abnormalities in cancers in individual patients can help select optimal therapy and determine the effectiveness of treatment within hours.
  • Angiogenesis.  Anti-angiogenesis agents and inhibitors of other normal tissues that surround cancers can starve the cancer cells of their blood supply and deprive them of essential growth-promoting factors which must come from the tumor’s environment.
  • Immunotherapy. Discovering ways to elicit or boost immune responses in cancer patients may target destruction of cancer cells and lead to the development of cancer vaccines.

#2.  Better tests to predict cancer risk and enable earlier detection must be developed.

New predictive tests, based on abnormalities in blood, other body fluids or tissue samples, will be able to detect abnormalities in the structure or expression of cancer-related genes and proteins. Such tests may predict the risk of cancer in individuals and could detect early cancer years before any symptoms are present.

The prostate-specific antigen test for prostate cancer currently is the best known marker test to detect the possible presence of early cancer before it has spread. Abnormalities in the BRCA 1 and BRCA 2 genes predict a high risk for breast cancer, which can guide the decisions of physicians and patients on preventive measures. Many more gene-based predictors are needed to further our progress in risk assessment and early detection.

#3.  More cancers can and must be prevented.

In an ideal world, cancer “care” would begin with risk assessment and counseling of a person when no malignant disease is present. Risk factors include both inherited or acquired genetic abnormalities and those related to lifestyle and the environment.

The largest risk factor for cancer is tobacco smoking, which accounts for nearly one-third of all cancer deaths. Tobacco use should be discouraged with cost disincentives, and medical management of discontinuing tobacco use must be reimbursed by government and private sector payors.

Cancer risk assessment should be followed by appropriate interventions (either behavioral or medical) at a pre-malignant stage, before a cancer develops. Diagnosis and treatment of a confirmed cancer would occur only when these preventive measures fail.

A full understanding of cancer requires research to identify more completely the genetic, environmental, lifestyle and social factors that contribute to the varying types and rates of cancer in different groups in this country and around the world. A common cancer in Japan or India, for example, often is not a common cancer in the U.S. When prostate cancer occurs in African-Americans it is more severe than in Caucasians. A better understanding of the factors that influence differences in cancer incidence and deaths will provide important clues to preventing cancer in diverse populations worldwide.

#4.  The needs of cancer survivors must become a priority.

Surviving cancer means many things: reducing pain, disability and stress related to the cancer or the side effects of therapy; helping patients and their loved ones lead a full life from diagnosis forward; preventing a second primary cancer or recurrence of the original cancer; treating a difficult cancer optimally to ensure achieving the most healthy years possible, and more.  Since many more patients are surviving their cancers – or living much longer with cancer – helping them manage all the consequences of their disease and its treatment is critically important.  It is an area ripe for innovative research and for improvement in delivery of care.

#5.  We must train future researchers and providers of cancer care.

Shortages are predicted in the supply of physicians, nurses and technically trained support staff needed to provide expert care for patients with cancer.  On top of this, patient numbers are projected to increase.  We are heading toward a “perfect storm” unless we ramp up our training programs for cancer professionals at all levels.   The pipeline for academic researchers in cancer also is threatened due to the increasing difficulty in obtaining peer-reviewed research funding. We must designate more funding from the NIH and other sources specifically for promising young investigators, to enable them to initiate their careers.

#6.  Federal funding for research should be increased.

After growing by nearly 100% from 1998-2002, the National Cancer Institute budget has been in decline for the past four years. Through budget cuts and the effects of inflation, the NCI budget has lost approximately 12% of its purchasing power.  Important programs in tobacco control, cancer survivorship and support for interdisciplinary research have had significant cuts.  The average age at which a biomedical researcher receives his or her first R01 grant (the gold standard) now stands at 42, hardly an inducement to pursue this field. This shrinks the pipeline of talented young Americans who are interested in careers in science, but can find easier paths to more promising careers elsewhere.  Lack of adequate funding also discourages seasoned scientists with outstanding track records of contributions from undertaking innovative, but risky research projects.  The U.S. leadership in biomedical research could be lost.

Biomedical research in academic institutions needs steady funding that at least keeps up with inflation and enables continued growth.

#7.  The pace of clinical research must accelerate.

As research ideas move from the laboratory to patients, they must be assessed in clinical trials to test their safety and efficacy. Clinical trials are complicated, lengthy and expensive, and they often require large numbers of patients.  Further steps must be taken to ensure that efficient and cost-effective clinical trials are designed to measure, in addition to outcomes, the effects of new agents on the intended molecular targets. Innovative therapies should move forward more rapidly from the laboratory into clinical trials.

The public needs to be better educated about clinical trials, which in many cases may provide them with access to the best care available.  Greater participation in trials will speed up drug development, in addition to providing patients with the best options if standard treatments fail.  The potential risks and benefits of clinical trials must continue to be fully disclosed to the patients involved, and the trials must continue to be carefully monitored.

The issue of how to pay for clinical trials must be addressed. The non-experimental portion of the costs of care in clinical trials currently are borne in part by Medicare, and should be covered fully by all payors. The experimental portion of costs of care should be covered by the owner of the new drug, who stands to benefit from a new indication for therapeutic use.

#8.  New partnerships will encourage drug and device development.

One way to shorten the time for drug and device development is to encourage and reward collaboration among research institutions, and collaboration between academia and industry.  Increasingly, partnerships are required to bring together sufficient expertise and resources needed to confront the complex challenges of treating cancer. There is enormous opportunity here, but many challenges, as well.

Academic institutions already do collaborate, but we need new ways to stimulate increased participation in cooperative enterprises.

Traditionally, academic institutions have worked with biotech and pharmaceutical companies by conducting sponsored research and participating in clinical trials.  By forming more collaborative alliances during the preclinical and translational phases prior to entering the clinic, industry and academia can build on each other’s strengths to safely speed drug development to the bedside. The challenge is that this must be done with agreements that involve sharing, but also protect the property rights and independence of both parties.

The results of all clinical trials must be reported completely and accurately, without any influence from conflicts of interest and with full disclosure of potential conflicts of interest.

#9. We must provide access to cancer care for everyone who lives in the U.S.

More than 47 million Americans are uninsured, and many others are underinsured for major illnesses like cancer. Others are uninsurable because of a prior illness such as cancer.  And many are indigent, so that payment for care is totally impossible.

Depending on where they live and what they can afford, Americans have unequal access to quality cancer care. Treatment options vary significantly nationwide. We must find better ways to disseminate the best standards of high-quality care from leading medical centers to widespread community practice throughout the country.

Cancer incidence and deaths vary tremendously among ethnic and economic groups in this country. We need to address the causes of disparities in health outcomes and move to eliminate them.

We are unique among Western countries in not providing direct access to medical care for all who live here. There is consensus today among most Americans and both political parties that this is unacceptable.  Especially for catastrophic illnesses like cancer, we must create an insurance system that guarantees access to care.

A number of proposals involving income tax rebates, vouchers, insurance mandates and expanded government insurance programs address this issue. Whatever system is selected should ensure access and include mechanisms for caring for underserved Americans.  The solution will require give-and-take among major stakeholders, many of which benefit from the status quo.  However, the social and economic costs have risen to the point that we have no choice.

#10.  Greater attention must be paid to enhancing the quality of cancer care and reducing costs.

New therapies and medical instruments are expensive to develop and are a major contributor to the rising cost of medical care in the U.S.  The current payment system rewards procedures, tests and treatments rather than outcomes.  At the same time, cancer prevention measures and services are not widely covered.  A new system of payment must be designed to reward outcomes, as well as the use of prevention services.

Quality of care can be improved and costs can be reduced by increasing our efforts to reduce medical errors and to prescribe diagnostic tests and treatments only on the basis of objective evidence of efficacy.

A standardized electronic medical record, accessible nationwide, is essential to ensuring quality care for patients who see multiple providers at multiple sites, and we are far behind many other nations.  Beyond that, a national electronic medical record could provide enormous opportunities for reducing overhead costs, identifying factors contributing to many illnesses (including cancer), determining optimal treatment and detecting uncommon side effects of treatment.

What the future holds in store.

I am optimistic. I see a future in which more cancers are prevented, more are cured and, when not curable, more are managed as effectively as other chronic, life-long diseases. I see a future in which deaths due to cancer continue to decrease.

Achieving that vision will require greater collaboration among academic institutions, government, industry and the public.  Barriers to quality care must be removed.  Tobacco use must be eradicated.  Research must have increased funding.  Mindful that our priority focus is on the patient, we must continue to speed the pace of bringing scientific breakthroughs from the laboratory to the bedside.

M. D. Anderson resources:

John Mendelsohn, M.D.”

Primary SourceTen Pieces Help Solve Cancer Puzzle, by John Mendelsohn, M.D., Feature Article, The University of Texas M.D. Anderson Cancer Center Cancer News, Mar. 2009.

IL-7 Boosts Immune Response in Cancer Patients

” … [Recombinant human interleukin-7] rhIL-7 appears to be an effective T cell growth factor with “immune rejuvenating” properties, suggesting that it is effective in augmenting immune reactivity in hosts with impaired immunity due to any number of factors, including age, chemotherapy, and infectious disease, the authors note. In patients with both intact and deficient immune systems, the capacity of rhIL-7 to augment responses to weak antigens and to increase T cell cycling without expanding T regulatory cells might be clinically exploitable in the context of immunotherapy regimens for cancer and/or chronic infection, they write.”

“Data from a preliminary study suggest that recombinant human interleukin (r-hIL)-7 can enhance and broaden immune responses in patients with impaired immunity due to lymphocyte depletion.

The results of the phase 1 trial, published online June 23 in The Journal of Experimental Medicine, showed that when given to cancer patients, rhIL-7 induced a dramatic polyclonal prolonged expansion of CD4+ and CD8+ T cells, which in turn caused a significant broadening of circulating T cell receptor repertoire diversity. These effects were mediated primarily through an increase in peripheral T cell cycling and augmented cell survival.

Lymphopenia induced by cytotoxic chemotherapy, or pathologies such as HIV infection, can significantly weaken immune function; as a physiologic immuno-enhancer, IL-7 can enhance the restoration of T cells. CD4+ T cell recovery in adults who have experienced severe depletion requires the reemergence of a pool of naive T cells, which generally takes 18 to 24 months and might only occur in people younger than 40 to 45 years. Thus, the authors note, a strategy that can accelerate or promote the recovery of a widely diverse T cell repertoire in older people might be useful for a large number of clinical applications.

‘We know that IL-7 can enhance tumor vaccines in animals, so that would be a clear avenue of research,’ said lead author Claude Sportès, MD, senior staff clinician at the National Cancer Institute‘s Center for Cancer Research, Experimental Transplantation and Immunology Branch, in Bethesda, Maryland. ‘But it wouldn’t only have to be tumor vaccines. Hopefully we will have a trial underway in the not-too-distant future looking at how it can enhance anti-viral and other immunizations, particularly in the elderly.’

Treatment with IL-7 therapy exerted a marked effect on T cell immune reconstitution during preliminary trials with animal models. It also appeared to augment effector and memory responses to vaccination in mice; in preclinical models, IL-7 therapy was able to augment anti-tumor responses that might improve survival when combined with anti-tumor vaccines.

‘In older individuals, therapy with IL-7 could lead to a rejuvenation of the phenotype,’ explained Dr. Sportès in an interview. ‘This in turn can lead to better vaccine responses in general and, in oncology, better tumor vaccine responses.’

The implications for rhIL-7 are potentially vast, and there are many promising therapeutic avenues. ‘But as often happens in medicine,’ he cautioned, ‘things can be very promising at this stage and then fizzle out.’

First Human Trial

In this phase 1 dose-escalation study, the first initiated in a human population, Dr. Sportès and colleagues evaluated the effects of IL-7 therapy on human lymphocytes in 16 patients, between the ages of 20 to 71 years, with nonhematologic, nonlymphoid refractory cancer. The doses, extrapolated from previous mouse and primate studies, were 3, 10, 30, and 60 μg/kg, and were administered by subcutaneous injection every other day for 14 days, for a total of 8 doses.

They found that after a very transient decrease, the numbers of circulating lymphocytes and CD4+ and CD8+ T cells increased in a dose-dependent manner. At the highest dose levels, increases approached 300% for CD4+ and exceeded 400% for CD8+ T cells. Overall, the treatment induced widespread T cell cycling and was able to expand the T cell pool in human patients while preserving T cell function.

Treatment with rhIL-7 also seems to have advantages over rhIL-2, explained Dr. Sportès. The expanded T cells retained significant functional capacity, and the CD4+ T cell expansion was not accompanied by a disproportionate increase in T regulatory cells, a phenomenon that has been observed after rhIL-2 therapy. Previous data have shown that in vivo IL-2 administration in humans has minimal effects on CD8+ T cell numbers, whereas rhIL-7 effects on CD8+ T cell expansion are at least comparable to the effects on CD4+ T cells.

The researchers noted that rhIL-7 increases T cell receptor repertoire diversity, and that although it appears to selectively expand CD4+ recent thymic emigrants, naive cells, and central-memory populations, it did not have the same effect on effector T cells.

The details of the clinical trial will be the focus of a separate paper, said Dr. Sportès. ‘But it was well tolerated and we went to full-dose escalation.’

“Immune Rejuvenating” Properties

rhIL-7 appears to be an effective T cell growth factor with “immune rejuvenating” properties, suggesting that it is effective in augmenting immune reactivity in hosts with impaired immunity due to any number of factors, including age, chemotherapy, and infectious disease, the authors note.

In patients with both intact and deficient immune systems, the capacity of rhIL-7 to augment responses to weak antigens and to increase T cell cycling without expanding T regulatory cells might be clinically exploitable in the context of immunotherapy regimens for cancer and/or chronic infection, they write.”

[Quoted Source: IL-7 Therapy Boosts Immune Response in Cancer Patients, by Roxanne Nelson, Medscape Medical News, Medscape Today, July 4, 2008 (summarizing the findings of Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets; Sportes, C. et. al., J Exp Med. 2008 Jun 23. Epub ahead of print]