A Prospective Study on Metronomic Scheduling of Non-chemotherapeutic Drugs in Advanced Epithelial Ovarian Cancers.

The objectives of this study are to assess the role of non-chemotherapeutic combination of drugs as maintenance therapy, after standard treatment, for advanced epithelial ovarian cancers (EOC) and to determine the recurrence-free survival (RFS) and cancer-specific survival (CSS). One hundred women with advanced high-grade EOC who had completed standard treatment by primary/interval debulking surgery followed by adjuvant chemotherapy were randomised to either receive (study group) or not to receive (control group) the non-chemotherapeutic maintenance therapy (oral metformin, anastrozole, aspirin, atorvastatin, vitamin D, injection zoledronic acid). Both groups were followed up, and trends of RFS and CSS were analysed. One hundred patients were analysed. Median RFS was 18 months (95% CI: 13-24) in study group versus 16 (95% CI: 14-20) in the control group (P value = 0.57). Median CSS in the study group was lesser than that in the control group (47 months (95% CI: 31-68) versus 51 (95% CI: 32-66), P value = 0.76). Five-year CSS was not significantly different between the groups (47% study vs 40% control, P value = 0.51). The use of combination of non-chemotherapeutic drugs as maintenance therapy was found to have no significant impact on the survival or reduction of recurrences in patients with advanced epithelial ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01261-w.

Role of salvage therapy in chemo resistant or recurrent high-risk gestational trophoblastic neoplasm.

OBJECTIVES: To assess the importance of salvage therapy in the management of high-risk gestational trophoblastic neoplasia (HR GTN) after failure of first line multiagent chemotherapy. METHODS: This retrospective study involving women with HR GTN treated at Kidwai cancer institute from 2000 to 2015. Initial chemotherapy consisted of etoposide, methotrexate with folinic acid, actinomycin D, cyclophosphamide and vincristine (EMA-CO). Thirty one patients who had incomplete response or relapsed were treated with various drug combinations employing etoposide and platinum agents. Adjuvant surgery and radiation were used in selected patients. Clinical response, survival and factors affecting outcomes were analysed. RESULTS: Thirty one (37.8%) of the 82 patients developed resistance or relapsed after EMA-CO.Of these 25 (80.6%) had lasting complete response to salvage therapy. Salvage chemotherapy included, EMA EP alone in-15, EMA EP followed with BIP in-1, EMAEP followed with VAC in-2, EMA EP followed by TC and VAC in-1, EMA EP followed by TC in-6, TC followed by IA in-1 patient. Irradiation was given to 6 patients for brain metastasis, 1 for spine metastasis, 1 for pelvic tumor, and 1 for mediastinal mass. Operative procedures were hysterectomy in 9, conservative uterine tumour resection in 4 and excision of resistant lung lesion in one. Median follow up 25 (80.6%) patients was 2 years. Complete response to salvage therapy was seen in 25 (80.6%) patients. Overall survival after salvage therapy was 87.1% with median follow up of 2 years. Remission and survival was significantly influenced by ßhCG level at the start of salvage therapy (p<0.001 and 0.006) but not with the stage or with WHO score. CONCLUSIONS: Salvage therapy with platinum/etoposide based drug regimens in conjunction with surgery and radiation, was successful in achieving significant cure and survival in HR-GTN patients.

Revised FIGO staging for carcinoma of the cervix uteri.

OBJECTIVE: To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent. METHODS: Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations. RESULTS: In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2-4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care. CONCLUSION: The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions.

Gastrointestinal Stromal Tumor Mimicking as Ovarian Tumor in Gynaecologic Oncology.

To report the clinical presentation and outcomes of a series of patients who presented with abdominal/pelvic mass or pelvic pain and were diagnosed with a gastrointestinal stromal tumor (GIST). Retrospective data were collected of all patients who presented with an abdominal/pelvic mass or pelvic pain between January 2010 and July 2015 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. The event free survival and overall survival was calculated for all patients using Kaplan Meier curve (SPSS19-SPSS Inc. USA). A total ten patients were identified with GIST during the study period. Eight of ten patients had a tumor in the small intestine, one in sigmoid colon and one in base of small bowel mesentry. The mean tumor size was 13.9 cm (range, 3.9 to 24 cm). A complete resection was achieved in all 10 patients. No patient had distance metastasis. There were no intraoperative complications. One patient developed postoperative intestinal fistula and was managed conservatively. All patients were treated with imatinib after surgery. The mean follow-up time was 18 months (range, 2 to 47 months). The seven of the 10 patients (70 %) with no evidence of disease, two (20 %) lost follow up and one patient developed recurrence during follow up period and was started on sunitinib and patient died during follow up period because of disease. Gastrointestinal stromal tumors should be considered in the differential diagnosis of patients presenting with an abdominal/pelvic mass or pelvic pain in Gynaecologic oncology department. In such unusual circumstances the complete resection and appropriate adjuvant treatment results in complete durable remission.

Refractory Gestational Trophoblastic Neoplasia: A Novel Drug Combination With Paclitaxel and Carboplatin Produces Durable Complete Remission.

OBJECTIVE: The aim of this study was to evaluate the results with novel drug combination consisting of paclitaxel and carboplatin (PC) for salvage of refractory high-risk gestational trophoblastic neoplasia (GTN) previously treated with EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine) and EMA-EP (etoposide, methotrexate, actinomycin, and cisplatin) regimens. STUDY DESIGN: This was a prospective study conducted at a regional cancer institute from 2008 to 2012. The study group received the combination of paclitaxel (175 mg/m) and carboplatin (area under the curve, 6) intravenously every 3 weeks. After undetectable ß-subunit of human chorionic gonadotropin values are achieved, 2 courses of additional chemotherapy were administered to reduce the risk of relapse. They were followed up and assessed by clinical examination, monthly ß-subunit of human chorionic gonadotropin for a minimum of 24 months. The event-free survival and overall survival were calculated for all patients using Kaplan-Meier curve (SPSS version 19; SPSS Inc). RESULTS: A total of 65 persistent GTN patients were treated during the study period. Eight (12.3%) of 65 patients having refractory GTN were treated with PC regimen. The initial International Federation of Gynecology and Obstetrics staging in the study group was stage I disease in 1 (12.5%), stage III in 4 (50%), and stage IV in 3 (37.5%) patients. According to the World Health Organization prognostic risk scores, 1 patient was in the low-risk group (12.5%), and 7 patients were in the high-risk group (87.5%). The study group received a total 35 courses of the combination PC. The median number of courses for each patient was 4.4. The complications include mucositis in 3 patients and thrombocytopenia, febrile neutropenia, and transient hepatic dysfunction in other patients. Six (75%) of 8 patients had good response, whereas 2 patients had progression. Five patients (62.5%) are in remission at median 30 months' follow-up, and 3 (37.5%) of 8 patients have died. CONCLUSION: The combination of paclitaxel and carboplatin (PC) regimen produces durable complete remission and manageable side effect profile in patients with refractory GTN previously treated extensively with frontline chemotherapies.

Immature teratoma of ovary--outcome following primary and secondary surgery: study of a single institution cohort.

OBJECTIVE: To analyse the clinical presentation, treatment - primary and secondary debulking and outcomes with focus on recurrences in ovarian immature teratoma. STUDY DESIGN: This is a single institution, retrospective analysis of 24 women who presented to a gynecologic oncology unit from 1999 to 2011 with ovarian immature teratoma. Patient's clinical presentation, operative and chemotherapy details were included in a database. Follow up details regarding recurrence and management and future outcomes were also noted. Overall survival was calculated from the date of registration to last follow up or date of death. Survival curve was constructed by Kaplan-Meier method. RESULTS: Immature teratoma accounted for 11% of 218 malignant germ cell tumors. Of the 24 patients, pain was the predominant symptom and abdominal mass was the commonest clinical presentation. Sixteen out of 24 patients presented in Stage I and grade 3 tumors were found in 43% of patients. Six patients had only unilateral salpingo oophorectomy and no staging procedure. Twelve patients underwent staging, with omentectomy being the commonest procedure. All but one, had cisplatin based combination chemotherapy. Six patients underwent secondary debulking of recurrence. Most recurrences were recorded in Stage III, higher grade tumors. With secondary cytoreduction and platinum based chemotherapy, it was possible to salvage most recurrences as well. Overall survival after a mean follow-up of 39 months was 91.6%. CONCLUSION: Majority of the patients did well with conservative surgery in terms of survival, menstrual and reproductive function. Platinum based chemotherapy was indicated in higher grade and higher stage tumors as recurrences commonly occurred in this subgroup of patients. Recurrences could be salvaged with selected secondary cytoreduction and platinum based chemotherapy.

Primary peritoneal carcinoma: regional cancer institute experience.

Primary peritoneal serous carcinoma (PPSC) is a rare malignancy that arises primarily from peritoneal surface epithelium. However there are limited studies on these tumors even in world literature. To study the clinical, pathologic profile, outcome and prognostic features of PPSC. A 5 year retrospective study of PPSC diagnosed and treated at our centre was conducted. The pathological specimen of PPSC diagnosed from January 2008 to December 2012 were reviewed by gynaeconcopathologists. The diagnosis was based on GOG criteria, complemented with IHC. Majority of the patients underwent upfront de-bulking surgery. Postoperatively, six cycles of combination chemotherapy with paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) was administered every 3 weekly. These patients were analysed for progression free survival (PFS), this was correlated with stage and surgical adequacy. The median age of presentation was 56 years. The total number of ovarian cancers treated during study period was 374. The 30 cases were clinically suspected to have primary peritoneal carcinoma (PPC) on pre- and intra-operatve gross findings, but further evaluation with histopathological examination, IHC and GOG criteria revealed only 10 cases were genuine PPSC. The remaing 20 cases; 13 were found to poorly differentiated ovarian carcinomas, six were primary fallopian tube carcinoma and one was appendicular carcinoma. The 10 (2.7 %) cases of the 374 were eligible for the PPSC analysis. The two (20 %) of the 10 cases had family history of breast and ovarian cancers, two (20 %) cases were diagnosed as abdominal tuberculosis (TB) prior referral to our centre. Radiological presentation includes gross ascites, with omental caking and normal adenexa. The eight (80 %) of 10 cases presented with stage IIIC and other two cases (20 %) with stage IV disease. The eight (80 %) of 10 cases underwent upfront surgery; six (75 %) of these eight cases had optimal cytoreduction, i.e. residual disease (RD) <1 cm or no visible disease (R0) and other two (25 %) suboptimal cytoreduction. The two (20 %) of 10 cases with stage IV disease received neoadjuvant chemotherapy (NACT) followed by interval cytoreduction. After debulking surgery the most useful IHC marker include CK7+, CK20-, CA125+, WT-1+, and GCDFP- . At median follow up of 24 months (range 3-60 months), the median progression free survival (PFS) was 22 months, while the estimated 5 year PFS was 18 %. Stage IV disease and suboptimal surgery had poor outcome. The PPSC presents with advanced stage disease and are observed to be misdiagnosed abdominal TB in tropical countries. The GOG criteria and IHC complement the diagnosis. These have poor outcome despite optimal care, highlighting need for larger studies on this disease.

The risk and pattern of pelvic and para aortic lymph nodal metastasis in patients with intermediate and high risk endometrial cancer.

There is a continuous debate about the extent and prognostic value of retroperitoneal lymphadenectomy in endometrial cancer. Systematic pelvic and para-aortic lymphadenectomy in endometrial cancer provides a more accurate assessment of neoplastic spread and may help in better individualization of patients for adjuvant therapy. To evaluate the risk and pattern of retroperitoneal lymph nodes metastasis in patients with endometrial cancers having intermediate and high risk factors for nodal metastasis and recurrence. We conducted a prospective nonrandomized study of 62 cases of high risk endometrial cancers examined and treated at our regional cancer institute between the years 2008 and 2012. The inclusion criteria: The intermediate risk; all patients having grade 3 or undifferentiated adenocarcinomas with less than half MI and the grade 1, 2 tumors having more than half MI with tumor size >2 cm. The high risk group; all the patients having grade 3 or undifferentiated adenocarcinomas with more than half MI, the grade 1, 2 tumors with lymph vascular space invasion (LVSI) or cervical stromal invasion as depicted by pre-operative MRI. The type 2 histology uterine papillary serous, clear cell and squamous cell carcinomas. The patients staging was carried out according to the classification established by the FIGO for endometrial cancer in 2009. The Chi-square test was used to analyze the correlation between tumor grade, myometrial invasion, size of the lesion and lymph nodes metastasis and Fisher's correction done whenever the frequency distribution was less than five. The patients mean age was 58.3 (range 31 to 76 years). A total of 118 endometrial cancer patients were treated during the study period. The 56 (47.5 %) patients belonged to low risk and 62 (52.5 %) patients belonged to high risk endometrial cancers. The 52 of 62 cases were eligible for the analysis. The 10 patients' were excluded from further analysis as the post operative specimens final histopathologic examinations in nine cases revealed carcinosarcoma uterus and one case with yolk sac tumor of endometrium. The total 17(32.7 %) of 52 cases had retroperitoneal nodes metastasis; nine of 17 (52.9 %) in this group had both pelvic and para-aortic lymph nodal metastasis and one of 17 (5.9 %) had isolated para-aortic lymph nodal metastasis. The high grade tumors (grade 3) revealed 41.4 % pelvic and 20.7 % para-aortic lymph nodes metastasis and there was statistically significant higher nodal metastasis in both pelvic and para-aortic lymph nodes with increasing depth of myometrial invasion (P = 0.0119 and P = 0.0001) and increasing size of the lesion. (P = 0.04 and P = 0.0501). The intermediate and high risk endometrial cancer is associated with greater degree of lymph node metastasis. A complete surgical staging which involves extrafascial hysterectomy or a type 3 radical hysterectomy when there is a cervical involvement, along with bilateral salphingo-oophorectomy, pelvic, para-aortic lymphadenectomy and an omentectomy when indicated as in the present study, is a valuable modality of treatment in intermediate and high risk cases of endometrial cancers for determining the prognosis and appropriate categorization of these women for adjuvant therapy. It is also possible to achieve a complete surgical staging in these groups of women with acceptable morbidity when performed by a trained gynaecologic oncologist.