Nicholas Reed

Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)

The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p=0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.

ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors.

ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Jejunum and Ileum.

a Department of Surgery, Medical University of Vienna, Vienna , Austria; b Department of Hepatology and Gastroenterology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin , Germany; c Centro de Oncologia, Hospital Sírio Libanês, São Paulo , Brazil; d Department of Endocrinology and Metabolism, Hadassah University Hospital, Mevasseret Tsion , Israel; e Department of Endocrinology, Erciyes University Medical School, Kayseri , Turkey; f Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen University Hospital, Copenhagen , Denmark; g Department of Medical Sciences, Endocrine Oncology Unit, University Hospital, Uppsala , Sweden; h Institute of Pathology, University of Bern, Bern , Switzerland; i Neuroendocrine Tumour Unit, Royal Free Hospital, London , UK; j Department of Clinical Oncology, Institute Alexander Fleming, Buenos Aires , Argentina; k National NET Centre, St. Vincent’s University and Department of Clinical Medicine, St. James Hospital and Trinity College, Dublin , Ireland; l Department of Internal Medicine, Division of Nuclear Medicine, Erasmus Medical Center, Rotterdam , The Netherlands; m Beatson Oncology Centre, Gartnavel General Hospital, Glasgow , UK; n Department of Surgery, CHU Robert Debré, Reims , France

Docetaxel and Cisplatin in Combination as First-Line Chemotherapy for Advanced Epithelial Ovarian Cancer

PURPOSE A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2)). RESULTS No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patients wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.

Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: a study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer—Gynaecological Cancer Group)

BACKGROUND No standard treatment options are available for patients with advanced, recurrent or metastatic vulvar carcinoma not amenable for locoregional treatment. PATIENTS AND METHODS In this phase II study, patients with advanced vulvar cancer received paclitaxel (Taxol) every 3 weeks for up to 10 cycles. Primary objective was response rate. Secondary objectives were response duration and toxicity. Response evaluation was assessed by World Health Organisation criteria, toxicity according to Common Toxicity Criteria. RESULTS Thirty-one women from 10 institutions were included, with a median age of 64 (range 47-84), of which 29 were assessable for response. On study patients received a median of four cycles (range 1-10). SAFETY Grade 3 and 4 neutropenia was seen in eight patients (8/29 = 27.6%), which in one patient resulted in neutropenic fever and treatment-related death. Further treatment-related grade 3/4 toxicity includes fatigue in three patients (10.3%) and neuropathy in one patient (3.4%). EFFICACY Overall response was 13.8% (n = 4; two complete responses + two partial responses). With a median follow-up of 24 months, median PFS was 2.6 months (95%confidence interval 2.04-4.21). CONCLUSION Paclitaxel shows moderate activity for local control in advanced vulvar cancer.

Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in partially platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial

BACKGROUND To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. PATIENTS AND METHODS CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. RESULTS A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). CONCLUSION Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.BACKGROUND To perform a subset analysis of patients with partially platinum-sensitive recurrent ovarian cancer (ROC) who received either CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) in the CALYPSO trial. PATIENTS AND METHODS CALYPSO, an international phase III, non-inferiority trial, enrolled women with ROC that relapsed >6 months following first- or second-line therapy. Patients were randomized to CD or CP. Patients with a treatment-free interval of >6 and ≤ 12 months were evaluated for progression-free survival (PFS), the primary end point of CALYPSO trial, and safety. RESULTS A total of 344 partially platinum-sensitive patients were included (N = 161, CD and N = 183, CP). The hazard ratio for PFS was 0.73 (95% confidence interval: 0.58-0.90; P = 0.004 for superiority) in favor of CD. Median PFS times were 9.4 months (CD) and 8.8 months (CP). Toxicities more common with CP versus CD included grade 3/4 neutropenia (50% versus 39%; P = 0.015), grade 2 alopecia (86% versus 9%; P < 0.001), neuropathy and hypersensitivity reactions. Hand-foot syndrome was more common with CD; however, grade 3/4 reactions were low (one patient in each arm). CONCLUSION Carboplatin-PLD has a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC and should be considered an effective treatment option for these patients.

Ovarian cancer in elderly patients: carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in late relapse: a Gynecologic Cancer Intergroup (GCIG) CALYPSO sub-study

BACKGROUND CALYPSO (CAeLYx in Platinum Sensitive Ovarian) patients compared carboplatin-pegylated liposomal doxorubicin (C-PLD) with carboplatin-paclitaxel (C-P) in patients with late-relapsing recurrent ovarian cancer (ROC). We analyzed outcomes in patients ≥70 years. PATIENTS AND METHODS Nine hundred and seventy-six patients with taxane-pretreated ROC relapsing >6 months after first- or second-line platinum-based therapy were randomly assigned to 4-weekly C area under the curve (AUC) 5 plus PLD 30 mg/m(2) or 3-weekly C AUC 5 plus P 175 mg/m(2) for six or more cycles. RESULTS One hundred and fifty-seven (16%) patients ≥70 years (median: 74 years, C-PLD; 73 years, C-P; range 70-82 years) were included (n = 71, C-PLD; n = 86, C-P). In comparing elderly and younger, elderly patients experienced fewer grade ≥2 allergic reactions (P = 0.005) but more grade ≥2 sensory neuropathy (P = 0.007). Myelosuppression did not differ with age. Elderly patients completed planned treatment as frequently as younger (79%, C-PLD; 82%, C-P). In comparing arms within elderly patients, C-P was associated with more grade ≥2 alopecia, sensory neuropathy, arthralgia/myalgia (P < 0.001 for all), severe leukopenia plus febrile neutropenia; C-PLD was associated with more grade ≥2 hand-foot syndrome (P = 0.005). Median progression-free survival was 11.6 months (C-PLD) and 10.3 months (C-P; P = 0.44). CONCLUSIONS Patients ≥70 years experienced more neuropathy, with a higher incidence in the C-P arm. Similar to all study patients, C-PLD provided a better therapeutic index with less toxicity than C-P in elderly women with platinum-sensitive ROC.

ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas)

ENETS Consensus Guidelines for Neuroendocrine Neoplasms of the Appendix (Excluding Goblet Cell Carcinomas)

Quality assurance for radical hysterectomy for cervical cancer: the view of the European Organization for Research and Treatment of Cancer—Gynecological Cancer Group (EORTC-GCG)

Radical hysterectomy combined with a pelvic lymphadenectomy or chemoradiation are traditionally the mainstays of treatment of International Federation of Gynecology and Obstetrics stages Ia2-IIa cervical cancer. The quality of radical surgery for cervical cancer influences local tumor control and survival. Hence, it is important to optimize and ensure the quality of surgical care for cervical cancer patients. In this paper, we discuss factors that are related to outcome after radical hysterectomy and propose a set of quality indicators that can be used to audit and improve the quality of surgical care for cervical cancer patients.

Gynecologic Cancer InterGroup (GCIG) consensus review for uterine and ovarian carcinosarcoma.

Abstract Carcinosarcomas (also known as malignant mixed müllerian tumors) are rare and highly aggressive epithelial malignancies that contain both malignant sarcomatous and carcinomatous elements. Uterine carcinosarcomas (UCs) are uncommon with approximately more than 35% presenting with extra uterine disease at diagnosis. Up to 90% ovarian carcinosarcomas (OCs) will have disease that has spread beyond the ovary. Prognosis for localized stage disease is poor with a high risk of recurrences, both local and distant, occurring within 1 year. The survival of women with advanced UC or OC is worse than survival of endometrioid or high-grade serous histologies. No improvement in survival rates has been observed in the past few decades with an overall median survival of less than 2 years. Currently, there is no clear evidence to establish consensus guidelines for therapeutic management of carcinosarcomas. Until recently, gynecological carcinosarcomas were considered as a subtype of sarcoma and treated as such. However, carcinosarcomas are now known to be metaplastic carcinomas and so should be treated as endometrial or ovarian high-risk carcinomas, despite the lack of specific data. For UCs, a comprehensive approach to management is recommended with complete surgical staging followed by systemic chemotherapy in patients with both early and advanced stage disease. Active agents include paraplatin, cisplatin, ifosfamide, and paclitaxel. The combination of carboplatin-paclitaxel is the most commonly used regimen in the adjuvant and advanced setting. Adjuvant radiotherapy (external beam irradiation and/or vaginal brachytherapy) has not shown any overall survival benefit but has been reported to decrease local recurrences. For OCs and for other ovarian epithelial cancer, the mainstay of treatment remains cytoreductive surgical effort followed, even in early stage, by platinum-based chemotherapy, usually carboplatin-paclitaxel.