Standard Debulking Research Articles

Randomized phase II trial of patient-specific dendritic cell vaccines loaded with autologous tumor antigens versus autologous monocytes in patients with primary advanced ovarian cancer.

TPS10 Background: With standard debulking surgery and combination chemotherapy (adjuvant ± neoadjuvant) the 5-year survival for women with newly diagnosed advanced epithelial ovarian cancer (stage III or IV) is less than 40%. After completion of primary therapy there is an opportunity to introduce an immunotherapy modality in an effort to improve long-term survival. In patients with metastatic melanoma, patient-specific vaccines consisting of autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) derived from a short-term autologous tumor cell line were associated with minimal toxicity and a 5-year survival of 50% in a single arm trial, and more than doubled median survival (43 vs. 20 months) in a randomized trial. Newly diagnosed patients with ovarian cancer might benefit from addition of such patient-specific therapeutic vaccines (DC-ATA) to standard therapy. Methods: This is a double-blind, 2:1 randomized trial comparing adjunctive treatment with DC-ATA to autologous monocytes (MC) in patients with newly diagnosed stage III or IV epithelial cancer of the ovary, fallopian tube, or peritoneum. Patients eligible for randomization are those who have completed or discontinued standard primary therapy, have a Karnofsky performance status ≥70, have an autologous tumor cell line, and have a monocyte product from which DC can be derived. The tumor cell line is derived from fresh tumor; MC are derived from leukapheresis, and MC are converted to DC by incubation with GM-CSF and IL-4. Patients are stratified by whether there is no evidence of disease at completion of primary therapy, and then are randomized, typically 6 to 7 months after tumor collection. Treatment can begin about 4 weeks from randomization. The trial has been open at a single site since mid-November 2017; the first tumor was collected in December. Appropriate tumor samples have been submitted from 11 patients and all 11 have resulted in cell lines. The first patient was randomized in May 2018. As of October 2018 four patients had been randomized and all four had started treatment. Additional clinical sites are being initiated. Clinical trial information: NCT02033616.

The Impact of Extensive Cytoreductive Surgery for Ovarian Cancer on the Histopathology Laboratory Workload

Objectives: Cytoreductive surgery is the principal management for ovarian cancer. Recently there has been progressive change to more extensive cytoreductive surgery (ECS) as evidence shows this improves patient prognosis. The aim of this study is to investigate the change in histopathology work load with change in surgical practice for the treatment of ovarian cancer patients at Hammersmith Hospital, UK. Materials and methods: Specimens for patients with ovarian cancer (n=116) were selected and classified into three groups: (i) standard debulking surgery; (ii) a mix of standard debulking and ECS and (iii) ECS only. The types of specimens and numbers of blocks in each group were studied. Results: Post-hoc analysis demonstrates a statistically significant increase in the number of specimens per case from standard debulking to the mixed group (p<0.0001) and to the ECS group (p<0.0001). There is also a statistically significant increase in the number of blocks from standard debulking to the mixed (p<0.0001) and to the ECS groups (p<0.0001). Conclusion: The study shows there is a significant increase in the histopathology workload with the shift from standard to extensive cytoreductive surgery, as well as increase in the complexity and range of specimens sent for histopathological examination. It is essential that centres opting for a shift to ECS ensure that adequate provisions and resources are in place to accommodate these changes.

The influence of upper abdominal surgery on perioperative morbidity and mortality in patients with advanced ovarian cancer FIGO III and FIGO IV

Kuhn W, Florack G, Roder J, Schmalfeldt B, Pache L, Rust M, Ulm K, Spathe K, Janicke F, Siewert JR, Graeff H. The influence of upper abdominal surgery on peri-operative morbidity and mortality in patients with advanced ovarian cancer FIGO III and FIGO IV. Int J Gynecol Cancer 1998; 8: 56-63. Tumor debulking procedures are routinely performed in advanced ovarian cancer patients, however, data on perioperative morbidity and mOCtality due to specific organ-oriented procedures are few. In a retrospective analysis, peri-operative morbidity and mortality as well as overall survival were analyzed in patients with advanced ovarian cancer. 41 patients (group A) underwent upper abdominal surgery. In 66 patients (group B), standard debulking procedure without upper abdominal SUCgery was performed. All data of surgical and peri-operative intensive care therapy differed significantly in both groups (P 〈 0.01). The morbidity was also significantly different. In group A, serious complications (including mortality) were significantly more often seen in patients undergoing splenectomy, cholecystectomy and partial pancreatic resection (n = 23) than in patients requiring only resection of the diaphragmatiC peritoneum (n = 18) (P = 0.045). Tumor-free patients in both groups had a longer median survival time than patients with residual tumor (group A: 71 vs. 15 months; group B: 〉 60 vs. 17 months, P 〈 0.01). Resection of tumorous diaphragmatic peritoneum suggests that survival improves if complete tumor removal is feasible. Other forms of upper abdominal surgery, including splenectomy and partial pancreatic resection, have a high rate of morbidity and mortality and probably no benefit in terms of survival. Therefore the risk-benefit ratio of these latter procedures has to be evaluated separately in each case.

Preoperative evaluation of pelvic masses with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography

Objective: To prospectively evaluate the diagnostic value of combined 18F-fluorodeoxyglucose position emission tomography and computed tomography (FDG-PET/CT) to discriminate malignant or borderline malignant tumors from benign pelvic masses. Methods: A prospective study of 30 women with suspected ovarian cancer who presented from July 2006 through August 2007. Selection was based on evidence from ultrasound, magnetic resonance imaging, and rising tumor marker levels. All patients underwent FDG-PET/CT prior to standard debulking surgery for a pelvic mass. Results: The sensitivity and specificity of FDG-PET/CT to detect malignant or borderline malignant pelvic tumors were 71.4% and 81.3%, respectively. The sensitivity and specificity of FDG-PET/CT to detect ovarian cancer were 100% and 85.0%, respectively. The maximum standardized uptake value in borderline tumors was significantly lower compared with malignant tumors, but not significantly different compared with benign tumors. Conclusion: FDG-PET/CT had a high diagnostic value in differentiating between malignant and benign tumors, and a low diagnostic value in differentiating between borderline malignant and benign tumors.

Phase II study of paclitaxel poliglumex (PPX) /carboplatin (C) for 1st line induction and maintenance therapy of stage III/IV ovarian or primary peritoneal carcinoma

5012 Background: C/paclitaxel (P) treatment, with a 70% complete response rate based on CA 125, is standard induction therapy for ovarian cancer. PPX (XYOTAX), a macromolecular drug conjugate that links P with a biodegradable polymer, poly-L-glutamic acid, is water soluble and can be administered as a 10 min infusion. Eliminating the need for CremophorEL reduces the risk of hypersensitivity reactions, even without premedication. The safety and efficacy of PPX/C for induction therapy followed by single agent PPX for maintenance therapy were evaluated. Methods: 82 patients (pts) with newly diagnosed stage III/IV ovarian or primary peritoneal carcinoma who had standard debulking surgery for their disease were enrolled. Pts received induction therapy of C (AUC 6) + 175 (62 pts) or 210 mg/m2 (20 pts) PPX as a 10 min IV infusion Q3 weeks. Pts with ≥stable disease after 4–6 cycles receive single-agent maintenance therapy (175 mg/m2 PPX, Q4 weeks X 12). NCI CTC (v 2) is used to assess safety. Response is based on CA 125 (Rustin Criteria) and RECIST. Results: 82 pts have completed induction treatment. Preliminary efficacy data are available for 67 pts, safety data for 28. Ages range from 38–83 years. Based on CA 125 levels, response rate after induction was 95% (54 CR, 10 PR). Grade 3 neuropathy occurred in 7/23 pts at 210 mg/m2 and resulted in withdrawal in 6 pts. As a result, the dose of PPX was reduced to 175 mg/m2 for subsequent patients. Grade 4 neuropathy has not been reported. No anaphylaxis occurred. Upon completion of maintenance therapy, time to progression, overall survival, and optimal maintenance dosing will be evaluated. Preliminary data suggest that a reduction in dose to avoid neuropathy may be required to allow completion of an 18 month treatment regimen. Conclusion: Treatment of pts with ovarian cancer with PPX/C produced a high response rate following surgical debulking. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics Cell Therapeutics

Novel, dose intensive, single-agent cisplatin in the first-line management of advanced stage ovarian cancer.

Cisplatin-based combination chemotherapy is the current standard chemotherapy for the management of advanced stage, epithelial ovarian cancer. However, correlation has been demonstrated previously between dose intensity and response for cisplatin, but not for the other cytotoxic drugs commonly used. We treated 46 consecutive, newly diagnosed patients following standard debulking laparotomy with cisplatin 60 mg m-2 every 2 weeks for a total of 8 cycles. Survival and toxicity were compared with those of a similar cohort of 24 consecutive, newly diagnosed patients treated with cisplatin 75 mg m-2 plus cyclophosphamide 600 mg m-2 every 4 weeks for 6 cycles, at the same institution immediately prior to the current cohort. The single-agent cisplatin cohort received a mean relative cisplatin-equivalent dose intensity of 1.43 compared with a received mean relative cisplatin-equivalent dose intensity of 0.88 in the combination chemotherapy cohort, a 62.5% increase in the cisplatin dose intensity. At 2 years, 69% of the patients receiving single-agent cisplatin were alive, compared with 38% of the group receiving the combination chemotherapy (P = 0.014). Alopecia (P < 0.00001) and myelosuppression (P < 0.0000001) were markedly less in the patient group receiving single-agent cisplatin. There was no significant difference in the incidence of neurotoxicity (P = 0.28) or nephrotoxicity (P = 0.38) between the two patient groups. In summary, relatively dose intensive, single-agent cisplatin given in a biweekly schedule for the first-line management of advanced stage, ovarian cancer produced a survival advantage compared with the previous combination cyclophosphamide/platinum combination chemotherapy. This novel therapy takes one-third less time to complete and causes fewer side effects than the current standard of combination cyclophosphamide and cisplatin.

Carbon dioxide laser vaporization of diaphragmatic metastases for cytoreduction of ovarian epithelial cancer

Three patients with International Federation of Gynecology and Obstetrics state IIIC ovarian adenocarcinoma underwent CO2 laser vaporization of large-volume (5-6 cm) and miliary right hemidiaphragmatic metastases at the conclusion of standard debulking surgery to effect optimal cytoreduction. Destruction of diaphragmatic metastases was accomplished rapidly with no added morbidity or blood loss. The hand-held CO2 laser is a useful modality for removal of isolated large- and small-volume diaphragmatic disease, particularly if only the peritoneum is involved, and avoids the morbidity that may accompany entry into the pleural space.