Management Of Advanced Ovarian Carcinoma Research Articles

Successful Implementation of HITOC and HIPEC in the Management of Advanced Ovarian Carcinoma with Pleural and Peritoneal Carcinomatosis.

This case report details the application and outcomes of a novel therapeutic approach involving hyperthermic intraperitoneal chemotherapy (HIPEC) and hyperthermic intrathoracic chemotherapy (HITOC) in a single patient diagnosed with advanced ovarian neoplasm. The treatment protocol included pleural cytoreductive surgery (CRS) and HITOC followed by a second surgical intervention consisting of peritoneal CRS and HIPEC. HIPEC targeted the intraperitoneal space with heated chemotherapy, while HITOC extended the thermal perfusion to the thoracic cavity. The patient has shown significant progression in disease-free survival over one year and eight months of observation, demonstrating lower recurrence rates and an overall survival outcome exceeding expectations based on conventional therapy outcomes. The combined modality demonstrated a manageable toxicity profile, with no significant increase in peri- or postoperative complications observed.

Mathematical modeling of the early modeled CA-125 longitudinal kinetics (KELIM-PARP) as a pragmatic indicator of rucaparib efficacy in patients with recurrent ovarian carcinoma in ARIEL2 & STUDY 10.

PARP inhibitors (PARPi) have revolutionized the management of advanced ovarian carcinoma, and were investigated as forefront treatment in recurrent disease. The objective was to explore if mathematical modeling of the early longitudinal CA-125 kinetics could be used as a pragmatic indicator of the subsequent rucaparib efficacy, like it is for platinum-based chemotherapy. The datasets of ARIEL2 and Study 10 involving recurrent HGOC patients treated with rucaparib were retrospectively investigated. The same strategy as those successfully developed for platinum chemotherapy, based on CA-125 ELIMination rate constant K (KELIM™), was implemented. Individual values of rucaparib-adjusted KELIM (KELIM-PARP) were estimated based on the longitudinal CA-125 kinetics during the first 100 treatment days, and then scored as favorable (KELIM-PARP ≥1.0) or unfavorable (KELIM-PARP <1.0). The prognostic value of KELIM-PARP regarding treatment efficacy (radiological response, and progression-free survival (PFS)) was assessed using univariable/multivariable analyses, with respect to platinum-sensitivity and homologous recombination deficiency (HRD) status. The data from 476 patients were assessed. The CA-125 longitudinal kinetics during the first 100-treatment days could be accurately assessed using the KELIM-PARP model. In patients with platinum-sensitive diseases, BRCA mutational status KELIM-PARP score and were associated with subsequent complete/partial radiological responses (KELIM-PARP: odds-ratio=2.81, 95% CI 1.86-4.52), and PFS (KELIM-PARP: hazard-ratio=0.67, 95% CI 0.50-0.91). The patients with BRCA-wild type cancer and favorable KELIM-PARP experienced long PFS with rucaparib regardless of HRD. In platinum-resistant disease patients, KELIM-PARP was associated with subsequent radiological response (odds-ratio=2.80, 95% CI 1.82-4.72). This proof-of-concept study confirms the early CA-125 longitudinal kinetics during rucaparib in recurrent HGOC patients are assessable by mathematical modeling, to generate individual a KELIM-PARP score associated with the subsequent efficacy. This pragmatic strategy might be useful for selecting the patients for PARPi-based combination regimens, when identifying efficacy biomarker is challenging. Further assessment of this hypothesis is warranted. The present study was supported by Clovis Oncology with a grant to academic research association.

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.&#x0D; 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.&#x0D; Results: The statistical difference in ooverall survival and progression free survival between primary debulking and NAC / IDS groups was &gt;0.005.But intra operative findings like blood loss, residual disease. Bowel bladder injury, surgery time &amp; post-operative morbidity were less in NAC/IDS group with P value &lt;0.005.&#x0D; 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.

Video-assisted thoracic surgery in the primary management of advanced ovarian carcinoma with moderate to large pleural effusions: A Memorial Sloan Kettering Cancer Center Team Ovary Study

ObjectivesWe assessed the utility of video-assisted thoracic surgery (VATS) in defining extent of intrathoracic disease in advanced ovarian carcinoma with moderate-to-large pleural effusions. MethodsBeginning in 2001, VATS was performed on all patients with suspected advanced ovarian carcinoma and moderate-to-large pleural effusions, evaluating for macroscopic intrathoracic disease. The algorithm recommended primary debulking surgery (PDS) for ≤1 cm, neoadjuvant chemotherapy (NACT)/interval debulking surgery (IDS) for >1 cm intrathoracic disease. We reviewed records of patients undergoing VATS from 10/01–01/19. Differences between treatment groups were tested using standard statistical techniques. ResultsOne-hundred patients met eligibility criteria (median age, 60; median CA-125 level, 1158 U/mL; medium serum albumin, 3.8 g/dL). Macroscopic pleural disease was found in 70 (70%). After VATS, 50 (50%) underwent attempted PDS (PDS group), 50 (50%) received NACT (NACT/IDS group). Forty-seven (94%) underwent IDS. Median overall survival (OS) for the entire cohort (n = 100) was 44.5 months (95% CI: 37.8–51.7). The PDS group had significantly longer survival than the NACT/IDS group [45.8 (95% CI: 40.5–87.8) vs. 37.4 months (95% CI: 33.3–45.2); p = .016]. On multivariable analysis, macroscopic intrathoracic disease (HR 2.18, 95% CI: 1.14–4.18; p = .019) and age ≥ 65 (HR 1.98, 95% CI: 1.16–3.40; p = .013) were independently associated with elevated death risk. Patients with the best outcome had no macroscopic disease at VATS and underwent PDS (median OS, 87.8 months). ConclusionsVATS is useful in therapeutic decision-making for PDS vs. NACT/IDS in advanced ovarian cancer with moderate-to-large pleural effusions.

Angiogenesis-related gene profile to predict outcome to multimodal therapy in advanced ovarian carcinoma.

5078 Background: Management of advanced ovarian carcinoma (AOC) involves surgery in order to achieve surgical cytoreduction followed by platinum (C) – paclitaxel (P) chemotherapy. A complete clinical remission is achieved in 40% to 50% of patients. Parameters such as age, extent of residual disease after surgery, and the histopathological subtypes are imperfect predictors of response. Angiogenesis plays a major role in ovarian carcinogenesis and progression. The aim of this study is to build a profile able to predict clinical response to multimodal first-line therapy. Methods: 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a C plus P regimen were included. RNAs were collected from formalin-fixed paraffin-embedded AOC samples. Expression levels of 82 angiogenesis related genes were measured using quantitative real time polymerase chain reaction. Clinical response was evaluated using CT after the completion of multimodal therapy. Statistical analysis was performed using a regression method to generate multiple models based on the significant genes. The accuracy of the models was evaluated using Receiver Operating Characteristic (ROC) curves. The Akaike Information Criterion based selection was used to find the most accurate one. Results: The median age at diagnosis was 53 years (range, 21 to 82 years). All patients had advanced disease (FIGO stages III/IV). Most of them had FIGO stage III (51, 83.6%), grade 3 tumors (35, 57.4%), and serous histology (42, 68.9%). 52 patients (85.2%) achieved an initial response (complete response or partial response by RECIST criteria) to this therapy. We found an independent model able to predict response to therapy comprising 8 genes with an Area Under the Curve (AUC) of 0.955 (p < 0.001). Leave-one-out cross validation was applied to avoid overfitting of the model, obtaining a corrected AUC of 0.880, 95%IC: 0,776-0,985. Conclusions: It is possible to generate a predictive model of clinical response for ovarian cancer based on angiogenesis related genes using formalin-fixed paraffin-embedded samples. Although these results are promising, they should be validated prospectively in larger series of ovarian cancer patients. No significant financial relationships to disclose.

Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute

Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P < .0002), while the main prognostic factor for disease-free survival was histological tumor type (P < .0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR = 2.2 for suboptimal surgery), menopausal status (RR = 1.47 for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR = 0.72). Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.

An immunohistochemical and morphological analysis of post-chemotherapy ovarian carcinoma

Aims:Traditional management of advanced ovarian carcinoma is surgical debulking followed by chemotherapy; however, there is an increasing tendency for neoadjuvant chemotherapy followed by surgery. The morphology of ovarian carcinoma following...

Intérêt des exérèses digestives dans le traitement des cancers évolués de l’ovaire

Aim of the study: Digestive surgery is often necessary for surgical management of advanced ovarian carcinoma. Patients and methods: In a series of 62 patients with stage III ovarian carcinoma, postoperative morbidity and mortality, overall survival after 5 years and disease-free survival after 2 years were studied and corelated with several patients criteria (age, stage of the disease, residual disease, type of surgery, CA 125 normalisation delay, postoperative complications and hospital stay). Patients were divided into two groups according to the surgical treatment. The first group ( n=17) included patients treated by gynecologic and digestive surgery, the second group ( n=45) included patients treated by gynecologic surgery only. All patients were proposed for chemotherapy included platyn salt. Mean age was 60 years (range: 20–83). The stage of the cancer was stage IIIa in 7 cases, stage IIIb in ten and stage IIIc in 45. Results: Postoperative mortality was 3.5% (2/62). Postoperative morbidity was 26% (13/62). No statistical differences were noted for hospital stay, general morbidity, surgical morbidity when a gastric resection or a colon resections or a splenectomy were performed. Overall survival at 5 years was 56%. Residual disease less than 2 cm 3 is the only prognostic factor for overall survival (56% vs 23% 〚 P=0.03〛) and disease-free survival (86% vs 46% 〚 P=0.02〛). Conclusion: This study including 62 patients confirmed the prognostic significance of extensive cytoreductive surgery for treatment in advanced ovarian epithelial cancer without increasing the postoperative morbidy and mortality.

Up date in the management of advanced ovarian carcinoma

2. Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 2.1. Primary surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 2.2. Interval debulking surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 2.3. Second-look surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 2.4. Palliative surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

553 - The integration of consolidation whole abdominal irradiation in the multi-modality management of advanced ovarian carcinoma: Long-term results

553 - The integration of consolidation whole abdominal irradiation in the multi-modality management of advanced ovarian carcinoma: Long-term results

A Phase II Trial of High-Dose Mitoxantrone, Carboplatin, and Cyclophosphamide with Autologous Bone Marrow Rescue for Recurrent Epithelial Ovarian Carcinoma: Analysis of Risk Factors for Clinical Outcome

Despite high initial response rates to platinum-based chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in the hematologic malignancies and lymphomas with high-dose therapy and bone marrow transplantation (BMT) when used early, suggesting that this therapy may also be of value in ovarian carcinoma. As a prelude to the use of high-dose chemotherapy with BMT early in the management of advanced ovarian carcinoma, we evaluated a new high-dose regimen in patients with relapsed/refractory ovarian carcinoma to define toxicities and responses. Thirty patients were treated, of whom 20 were platinum resistant and 22 had >1 cm maximum diameter disease. They received mitoxantrone (75 mg/m2), carboplatin (1500 mg/m2), and cyclophosphamide (120 mg/kg), followed by an autologous BMT. Overall, 89% responded, with clinical complete responses seen in 88 vs 47% (P = 0.06) of platinum-sensitive vs -resistant disease. There was only one early death (3.3%) due to Aspergillus pneumonia. Median survival for all 30 patients was 29 months, and at 3 years 23% are alive without disease. There was a 10.1- vs 5.1-month progression-free survival for patients with platinum-sensitive versus -resistant disease, and at a median follow-up of 12 months, 80% of the platinum-sensitive patients are alive. This regimen is safe, and for platinum-sensitive disease appears superior to other salvage therapies. Its use should be explored earlier in the management of advanced ovarian carcinoma.

Long-term follow-up of patients with advanced ovarian carcinoma treated with chemotherapy

The evolution of the management of advanced ovarian carcinoma over the last fifteen years has resulted from a number of well-designed randomized trials involving large numbers of patients. A critical review of long-term follow-up of patients entered onto eleven major randomized trials of advanced ovarian carcinoma has been performed. In the pre-platinum era no long-term survival benefit was obtained with combination compared with single agent chemotherapy. When adding cisplatin to front-line therapy at least a short-term gain in terms of superior response rate and progression-free intervals is obtained compared with non-cisplatin combination chemotherapy. Survival data are more difficult to assess due to the use of cisplatin-containing salvage therapy. Cisplatin-based combination therapy also offers enhanced patient benefit when compared with cisplatin alone. A slight advantage favouring anthracycline-containing therapy is observed, whereas no advantage is obtained with alternating cisplatin and non-cisplatin regimens or by adding BCG. Platinum-based combination chemotherapy is clearly associated with improved response rates and progression-free survival and, at least in some studies, better overall survival. At least six cycles of therapy should be given. Such approaches should yield long-term survival rates of 10% or better for patients with large-volume disease and 20% or better for small-volume disease.

The Integration of Whole Abdominal Radiotherapy and Intraperitoneal Cisplatin into the Primary Management of Advanced Ovarian Carcinoma

Eleven women with Stages III and IV epithelial ovarian carcinomas were entered into a protocol consisting of concurrent whole abdominal radiotherapy and intraperitoneal cisplatin followed by additional intraperitoneal cisplatin. The entire abdomen received 20 Gy in 20 fractions with no renal or hepatic shielding. Intraperitoneal cisplatin dosage was 20 mg/m2 weekly during radiation and 90 mg/m2 monthly thereafter for an additional three courses. Patients with Stages IIIC and IV had a median survival of 18 months and a two-year actuarial survival of 32%. Primary failure sites were the abdomen, pleura, and lymph nodes. Acute toxicity during radiotherapy was comparable to patients treated with radiation alone. No chronic renal, hepatic, or enteric complications were observed. Although the protocol did not have substantial efficacy in advanced disease, its toxicity was moderate enough to consider its use in less advanced cancers with peritoneal metastases. In particular, the protocol can be considered for women with ovarian cancer with no gross residuum and for women with papillary serous carcinoma of the uterine corpus.

Surgery, chemotherapy and whole abdominal radiotherapy in the management of advanced ovarian carcinoma

A pilot study on 35 women was performed to determine the feasibility of giving whole abdominal radiotherapy after surgery and chemotherapy for Stage III and IV ovarian adenocarcinoma. The planned duration of therapy was only 6 months from diagnosis. Chemotherapy consisted of four courses of cis-platinum 100 mg/m2 alternating every 10-12 days with four courses of methotrexate 300 mg/m2 and cyclophosphamide 500 mg/m2 followed by folinic acid rescue. Twenty-nine of 35 (83%) patients were shown at second look surgery after chemotherapy to have residual tumour deposits no more than 2 cm in diameter. The usual radiotherapy dose was 2400 cGy in 20 fractions over approximately 4 to 5 weeks, with kidney shielding, and was generally well tolerated. Three patients failed to complete radiotherapy, two because of progressive disease and one because of persistent nausea and vomiting. During radiotherapy the white blood count fell below 2.0 X 10(9)/litre in seven patients (26%), and in eight patients (30%) the platelet count fell below 75 X 10(9)/litre. However, the white blood count nadir of 1.5 X 10(9)/litre was reached by 1300 cGy and the platelet nadir of 45 X 10(9)/litre was reached by 1400 cGy and both then levelled or recovered despite continuing radiotherapy. The median follow up since diagnosis is 26 months. Four of 12 patients with no tumour detected at second look operation have relapsed compared with 13 of 15 patients who had detectable tumour. Toxicity of this multi-modality therapy was acceptable.

Second-look operations in the planned management of advanced ovarian carcinoma

Second-look operations were done in 65 patients as part of a planned management program of advanced ovarian cancer. All patients received chemotherapy with cisplatin, and only those who had a good clinical regression after an incomplete initial surgical procedure were subjected to a second operation. At second-look operations, 16 patients (25%) had no macroscopic tumor (surgical complete remission), and these patients have a 72% probability of surviving 5 years. In 49 patients (75%), considerable regression had occurred but macroscopic disease was still present. Incomplete or complete removal of residual disease was possible in 38 cases (58%), but survival curves suggest that removal of all macroscopic residual disease at second-look operations did not improve survival expectancy. In the other 11 cases (17%), although there was slight improvement in the extent of disease, further surgical resection was not possible and the survival expectancy in these cases was very poor.

Management of Advanced Ovarian Carcinoma

Management of Advanced Ovarian Carcinoma