Clinico-Pathological Characteristics, Management, and Prognostic Factors of Patients with Uterine Carcinosarcoma: a Retrospective Analysis.

Uterine carcinosarcoma is a rare, highly aggressive, rapidly progressing neoplasm associated with a poor prognosis. It comprises 1-5% of all uterine malignancies but accounts for 16.4% of all deaths caused by uterine malignancies. There is a definite paucity of data available from the Indian subcontinent. Hence, we retrospectively conducted this study to analyze the clinical and pathological characteristics and outcomes of women with uterine carcinosarcoma in the past 10 years managed at the tertiary care center. This is a retrospective study of women with histologically proven uterine carcinosarcoma treated at a tertiary cancer center in South India between August 2009 and April 2019. Inpatient and outpatient records were reviewed; clinicopathological data were collected; and follow-up and survival data were ascertained. Over a period of 10 years, 20 patients were diagnosed with uterine carcinosarcoma. The majority of patients were postmenopausal (80%). Post-menopausal bleeding was the main presenting complaint in about 80% of patients. More than two-thirds of patients presented in the early stage (stage I, 55%; stage II, 20%). All patients underwent staging laparotomy. Patients with good performance status (85%) received adjuvant concurrent chemoradiotherapy and chemotherapy. At a median follow-up of 40 months, 7 (35%) patients were alive, out of which 6 are disease-free and 1 had a recurrence. The event-free survival at a median follow-up of 40 months was 40% and the overall survival was 48.5%. The outcome did not significantly differ based on the age, tumor histology (heterologous versus homologous), stage, and depth of myometrial invasion. Uterine carcinosarcoma, though rare, needs to be recognized as a distinct entity, and treated aggressively. Surgery is the cornerstone of therapy. Adjuvant concurrent chemoradiation and chemotherapy improve local control and may delay recurrence, but have shown little survival advantage. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on this tumor.

Phase II Trial on the Feasibility of Single-Dose Intraoperative Intraperitoneal Carboplatin in Advanced Epithelial Ovarian Cancer Following Optimal Cytoreductive Surgery.

To evaluate the feasibility administering single-dose intraoperative intraperitoneal carboplatin (IP) in advanced epithelial ovarian cancer (EOC) after optimal primary or interval debulking surgery. A phase II non-randomized prospective study conducted at a regional cancer institute from January 2015 to December 2019. The advanced high-grade epithelial ovarian cancer FIGO stage IIIB-IVA was included. A total of 86 consented patients with optimal primary and interval cytoreductive surgeries received single-dose intraoperative IP carboplatin. The immediate (< 6 h), early (6-48 h), and late (48 h-21 days) perioperative complications were recorded and analyzed. The severity of adverse events was graded on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). A total of 86 patients received single-dose intra-operative IP carboplatin during the study period. The 12 (14%) patients underwent primary debulking surgery and 74(86%) interval debulking surgery (IDS). The 13 (15.1%) patients underwent laparoscopic/robotic IDS. All the patients tolerated the intraperitoneal carboplatin well with no or minimal adverse events. Three cases (3.5%) needed resuturing for the burst abdomen, three cases (3.5%) had paralytic ileus for 3-4 days, one case (1.2%) underwent re-explorative laparotomy for hemorrhage, and one case (1.2%) mortality due to due late sepsis. The 84 (97.7%) of 86 cases received scheduled IV chemotherapy on time. Single-dose intraoperative IP carboplatin is a feasible procedure with no or minimal manageable morbidity. The procedure is user friendly combining the prognostic benefits of IP chemotherapy with assurance of earliest timely administration of chemotherapy in advanced EOC. Our study is a hypothesis generating for the future clinical trials comparing single-dose NIPEC versus HIPEC in advanced EOC.

Impact of Optimal Therapy and Prognostic Factors in Malignant Germ Cell Tumors of Ovary: 20 Years' Institutional Experience.

The objective of this study is to analyze the impact of clinicopathological and treatment-related factors on survival in patients with malignant ovarian germ cell tumor. A total of 253 patients of ovarian germ cell malignancy were retrospectively reviewed during 2000-2019. Out of these, 111 had primary treatment at our institute, which is a dedicated regional cancer center. The remaining 142 were operated elsewhere and were referred to us for adjuvant chemotherapy or with recurrent disease. The clinicopathological and treatment-related characteristics were analyzed for association with tumor persistence/recurrence or death. Among them, 107 were dysgerminomas; 60 had endodermal sinus tumor, 53 mixed germ cell tumors, and 31 immature teratoma; and one each had embryoma and primitive germ cell tumor. The median follow-up period was 19 months (range 0-214). Median time to recurrence or progression was 5 months. Forty-nine patients (19.4%) had a recurrence and there were 16 (6.3%) deaths. Five-year disease-free-survival was 71.3% and 5-year overall survival rate was 88.1%, for the entire cohort. Disease-free-survival was 90.4% and overall survival was 92.1% for patients entirely treated at the reporting institute. Sub-group analysis based on treatment adequacy showed that survival rate was 91.0% in patients who had timely and complete initial treatment versus 78.3% in patients where treatment was incomplete or delayed (p = 0.032). Factors affecting relapse were tumor histology, absence of surgical staging, presence of residual disease, inadequate response to chemotherapy, treatment outside reporting institute, and incomplete/delayed chemotherapy. Significant factors adversely affecting survival were presence of post-operative residual disease, tumor histology, incomplete response to chemotherapy, and inadequate/delayed treatment at primary setting. There was no statistically significant difference based on disease stage and whether fertility-sparing surgery or non-fertility-sparing surgery was performed. Prognosis of ovarian germ cell malignancies is excellent with timely, optimal treatment. The outcome improves significantly if managed adequately in the primary setting, involving dedicated gynecologic oncologists.

Low-Grade Serous Ovarian Carcinoma: a Retrospective Study from a Tertiary Cancer Institute.

The aim of this study was to evaluate the clinico-pathological behaviour and treatment patterns of low-grade serous carcinomas (LGSC) of ovary treated at a regional cancer centre. A retrospective analysis was done for the histopathology-proven cases of low-grade serous ovarian carcinoma, treated at a tertiary cancer institute between January, 2010, and September, 2019. There were 28 patients identified from the medical records with low-grade serous ovarian carcinoma. Median age of the patients was 43 years [22-79 years]. Average BMI was 22.3 ± 4.0 kg/m2 [range 15.2-31.2]. Twenty-one (75%) were parous and 7 (25%) were non-parous women. Median CA125 level was 188 IU/ml [range 6-14,187 IU/ml]. Ten (35.7%) patients had primary surgery elsewhere and 8 (80%) out of these patients had to undergo repeat staging. Fertility sparing surgery (FSS) was offered to 4 (14.3%) patients. Five (17.8%) patients had received neoadjuvant chemotherapy for advanced disease and poor performance status. Almost 82.2% (23) of the patients had no macroscopic residual disease at the primary surgery. According to International Federation of Obstetrics and Gynaecologists (FIGO) stage for ovarian carcinoma, there were 7 (25%), 6 (21.4%), 13 (46.4%), and 2 (7.1%) patients in the stages I, II, III, and IV respectively. Post-operative adjuvant chemotherapy was offered to 7 (25%), hormonal therapy (anastrozole/tamoxifen) to 7 (25%), and rest of 14 (50%) patients were under surveillance. Median follow-up time for the study group was 36 months. Overall survival (OS) and disease-free survival (DFS) at 2 years was 96.4% and 89.1%, respectively. Low-grade serous carcinomas of ovary differ biologically from high-grade serous ovarian carcinoma. Surgery is the cornerstone of the treatment. Further research is needed to understand the behaviour of these tumours for effective treatment strategies in future.

Growing Teratoma Syndrome a Rare Clinical Entity: Two Decades Management Experience from the Regional Cancer Institute.

To study the clinical, biochemical, radiological, pathological characteristics, surgical treatment details, and follow-up of growing teratoma syndrome (GTS) patients. This is a retrospective study of GTS treated in the Department of Gynaecological Oncology at a regional cancer institute from March 2000 to March 2020. A total of 303 cases of germ cell ovarian cancers were treated, and 8 (2.6%) of 303 cases recurred as GTS during this period. The patients presenting with recurrent GTS were studied for clinical, radiological, tumor markers, surgical management, histopathology, and post-operative follow-up details that were analyzed retrospectively. The Kaplan-Meier curve was used for the survival analysis. The 8 out of 303 cases of germ cell ovarian cancers recurred as GTS and the incidence rate is 2.6% during this period. In the six (75%) of eight cases, the histopathology report was immature teratoma ovaries. The five cases (62.5%) were in advanced stage. All the eight recurrent GTS cases received optimal surgical cytoreduction. The overall disease-free survival is 85.7% and one patient has recurrence after the surgery for GTS at 23rd month of follow-up visit. All the patients are alive till date. The GTS represents a rare clinical and pathological phenomenon. Nevertheless, GTS should be considered as one of the differential diagnosis in young patients having normal tumor markers with recurrent carcinomatosis following the primary treatment germ cell tumors of ovaries. The optimal cytoreduction of recurrent GTS leads to prolonged survival and possible cure in young patients.

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.

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.

Primary carcinoma of the fallopian tube: a review of a single institution experience of 8 cases.

AIMS AND OBJECTIVES: To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel. MATERIALS AND METHODS: A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013. RESULTS: 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15-21 months) and mean overall survival of 27 months (range 22-36 months). CONCLUSION: The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.