Integrated Clinical and Genomic Models to Predict Optimal Cytoreduction in High Grade Serous Ovarian Cancer

Background: Advanced high grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery either primarily or after chemotherapy is based on a surgeon’s clinical assessment and prediction of an optimal outcome. Optimal surgery is correlated with improved overall survival. This clinical assessment results in an optimal surgery approximately 70% of the time. We hypothesize that this prediction can be improved by using biological tumor data to predict optimal cytoreduction.Methods: With access to a large biobank of ovarian cancer tumors, we obtained genomic data on 83 patients encompassing gene expression, exon expression, long non-coding RNA, micro RNA, single nucleotide variants, copy number variation, DNA methylation, and fusion transcripts. We then used machine learning to incorporate this data with pre-operative clinical information to create predictive models which successfully predicted whether or not a patient’s cytoreductive surgery would have an optimal outcome. These models were then validated within The Cancer Genome Atlas (TCGA) HGSC database. Results: Of the 124 models created and validated, 21 performed at least equal if not better than our historical clinical rate of optimal debulking in advanced-stage HGSC as a control, 78%. Conclusions: This is the first time tumor genomic data has been used to predict surgical outcome in ovarian cancer. Prospective validation of these models could result in improving our ability to objectively predict which patients will undergo optimal cytoreduction and, therefore, improve our ovarian cancer outcomes.

Comparing the Effectiveness of the Treatment with Neoadjuvant Chemotherapy Followed By Interval Debulking and Primary Debulking Followed By Adjuvant Chemotherapy in Advanced Stage Malignant Ovarian Tumors: A Rural Based Study

Background: Advanced epithelial ovarian cancer is also a poorly prognosed condition with elevated death rate The management of advanced ovarian carcinoma is surgical debulking which is followed by adjuvant chemotherapy. Prognosis reflects primarily on the level of cytoreduction obtained in primary surgery. In order to enhance survival, attempts are therefore being made to increase the optimal rates of surgical cytoreduction. NACT has emerged as an important treatment modality. The reasoning behind the NACT protocol is to make advanced untreatable disease operable, increase resection rates of optimal cyto reduction (R0) and promote organ preservation. The application of neo adjuvant chemotherapy will structurally reduce the load of the tumour because of the chemo sensitive nature of the ovarian tissue and enable a greater optimal cytoreduction rate for surgery and an increase in overall survival. Methods: This observational and retrospective study was conducted from 2018-2020, including 71 patients who visited the oncology clinic of OBGY department at AVBRH. Only those who have already diagnosed as stage III and IV ovarian neoplasms and who received primary debulking surgery followed by adjuvant chemotherapy along with neo adjuvant chemotherapy followed by interval de-bulking surgery were included to study the better treatment outcome in terms of intra-operative and post-operative complications and over all and survival without progression in these patients with a follow-up of 2 years. Results: The statistical difference in ooverall survival and progression free survival between primary debulking and NAC / IDS groups was >0.005.But intra operative findings like blood loss, residual disease. Bowel bladder injury, surgery time & post-operative morbidity were less in NAC/IDS group with P value <0.005. Conclusion: In patients having cytoreducible disease which is non optimal or low performance status, NAC / IDS is also a reasonably secure and may be an alternative method for achieving optimal cytoreduction. Investigations aimed at appropriately selecting patients to be treated with NAC and to search for the proper opportunity to conduct IDS can have much better benefits for patients having advanced EOC. It should be underscored that the study is limited to patients with stage 3c or 4 disease.

What is the Effect of Splenic Involvement Sites in Advanced Ovarian, Tubal and Peritoneal Epithelial Cancer on Overall Survival?

Purpose: In this study, we evaluated the significance of parenchymal, hilar, and capsular involvement of the spleen with regard to the overall survival of patients who required a splenectomy during cytoreduction procedures for primary or recurrent cancer. Methods: This study includes data from 287 patients who underwent a splenectomy during optimal cytoreduction in epithelial ovarian, tubal, and peritoneal cancers. Spleen involvement regions were divided into four main groups, and the groups were classified as capsule, hilus, capsule + hilus, and other region involvement (paranchyma ± other(s) involvement site). The overall survivals of these four groups were compared.Results: The mean age of the study group was 57.9 years, and the mean follow-up period of the patients was 43.2 months. The splenic involvement site was most frequently observed as hilus + capsule (42.2% n:121). Splenic parenchymal involvement was present in 27.9% (n: 80) of the patients. The overall survival for patients was 42 months. In the subgroup analysis, the worst overall survival was found in the group with capsule involvement at 33 months.Conclusion: While parenchymal involvement of the spleen was considered to be stage IV according to FIGO staging, we could not detect low overall survival in patients with parenchymal involvement in our study. Our study, which has the largest number in the literature examining the relationship between splenic involvement and overall survival, can provide a remarkable perspective on the relationship between parenchymal involvement of the spleen and prognosis.

Epithelial Ovarian Cancer: Real-World Outcomes

Introduction Ovarian cancer is the third most common cancer and the second most common cause of death among gynecological cancers in Indian women. Ovarian cancer is heterogeneous, among them, epithelial ovarian cancer (EOC) is the most common. Primary cytoreductive surgery along with six to eight cycles of a combination of platinum and taxanes chemotherapy is the cornerstone of first-line treatment in EOC. This study was done to find clinicopathological factors affecting survival outcomes with first-line therapy in EOC in a real-world setting. Objectives This study was aimed to find factors affecting progression-free survival (PFS) and overall survival (OS) with first-line treatment in EOC. Materials and Methods We conducted a single-center retrospective study. We screened all the patients diagnosed with ovarian cancer from January 2015 till December 2019. We locked data in August 2019. Eligible patients were histologically confirmed EOC who underwent primary cytoreduction or received more than or equal to two cycles of chemotherapy or both. Patients who had received first-line treatment at another hospital were excluded. Results Patients demographics and clinical characteristics: between January 5, 2015 to August 31, 2019, 435 patients with a diagnosis of ovarian malignancy were registered at our center. Among them, 406 (82%) had EOC, 290 (64%) newly diagnosed, and fulfilling eligibility criteria were included in the final analysis. The median age of the cohort was 53 years (range: 21–89 years) and 157 patients (54%) were >50 years of age (the Eastern Oncology Cooperative Group Performance status was ≥ 2 in 124 patients [43%]; median duration of symptoms was 3 months; and stage III/IV: 240 [83%]). Grading of the tumor was available in 240 patients of which 219 (91%) were of high grade. Subtyping was available in 272 patients (94%) of which the serous subtype was the most common constituting 228 patients (79%).Treatment Most patients received chemotherapy (n = 283 [98%]) as the first modality of treatment (neoadjuvant/adjuvant and palliative). As neoadjuvant (NACT) in 130 patients (45%) and as adjuvant following surgery in 81 patients (29%). The most common chemotherapy regimen was a combination of carboplatin and paclitaxel in 256 patients (88%). Among 290 patients 218 (75%) underwent cytoreductive surgery. Among them, optimal cytoreduction was achieved in 108 patients (52%). Optimal cytoreduction rate (OCR) with upfront surgery and after NACT was 44 and 53%, respectively (Chi-square test: 0.86; p = 0.35).Survival The median follow-up of the study was 17 months (range: 10–28 months) and it was 20 months (range: 12–35 months) for patients who were alive. At last, follow-up, 149 patients (51%) had progressed and 109 (38%) died. The estimated median PFS and OS were 19 months (95% CI: 16.1–21.0) and 39 months (95% CI: 29.0–48.8), respectively. On multivariate analysis, primary surgery (HR: 0.1, 95% CI: 0.06–0.21; p-value: <0.001) and early-stage disease (HR: 0.2, 95% CI: 0.1–0.6; p-value 0.04) were associated with superior PFS and primary surgery (HR: 0.1, 95% CI: 0.09–0.2; p-value: <0.001) was associated with superior OS. Conclusion Primary surgery (upfront or interval) was associated with improved survival. Newer agents like bevacizumab, poly-ADP (adenosine diphosphate)-ribose polymerase inhibitors and HIPEC should be incorporated precisely into first line of therapy to improve outcomes.

The clinical and pathological characteristics and survival of patients with advanced ovarian cancer

Introduction: Ovarian cancer has the highest mortality rate of all gynaecologic malignancies. The aim of this study was the evaluation of the clinical pathological characteristics and survival analysis of primarily operated patients with advanced stages of malignant epithelial ovarian tumour. Methods: The research was conducted as a cohort study with 59 patients with FIGO stage III and IV, which were primarily operated between 1 January 2008 and 31 December 2010 (three years). Age, comorbidities, BMI, presence of ascites, the level of the marker CA-125, histopathology and FIGO stage were analysed. The survival rate was estimated at the level of 1, 3 and 5 years. Results: The median age was 53 years (range 29-86). The most common histopathological type was serous (66.1 %) and the most common FIGO stage was 3a (49.2 %). Optimal cytoreduction was performed in 35.5 % of patients, 84.7 % of patients survived for one year, 44.1 % three years and 37.3 % for five years. The median survival was 26.25 months (range 0-91). Chi-square test showed significant difference between the number of months of survival and: the value of CA125 (t = 2.004, p = 0.050), cytoreduction (p < 0.001) and FIGO stage (p < 0.01). Conclusion: According to the results of this study, optimal cytoreduction and FIGO stage significantly influence survival (p < 0.001). Optimal cytoreduction (< 2 cm of residual disease) had the highest prognostic value for survival. A total five-year survival in this study was 37.3 %.