Aditi Bhatt

Multisocietal Consensus on the Use of Cytoreductive Surgery and HIPEC for the Treatment of Epithelial Ovarian Cancer: A GRADE Approach for Evidence Evaluation and Recommendation

ABSTRACTIntroductionThe locoregional treatment of high grade serous ovarian cancer (HGSOC) comprises of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recent evidence form randomized trials, has led to controversy related to the use of HIPEC in addition to interval CRS (iCRS) and the role of secondary CRS (sCRS) in patients with the first platinum‐sensitive recurrence from high‐grade serous ovarian cancer (HGSOC). This multi‐society consensus, coordinated by the Peritoneal Surface Oncology Group International (PSOGI) with inputs from ISSPP, SSO, ESSO, and IGCS, evaluated the role of these interventions using the GRADE ADOLOPMENT methodology.Patients and MethodsAn international expert panel reviewed evidence for the use of HIPEC in addition to iCRS in stage 3 high grade serous ovarian cancer (HGSOC) and the role of sCRS for patients with platinum‐sensitive recurrent HGSOC. A systematic review assessed randomized controlled trials (RCTs) for recurrence‐free survival (RFS), overall survival (OS), safety, and quality of life (QoL). Recommendations were formulated using the GRADE Evidence‐to‐Decision framework.ResultsHIPEC in addition to iCRS was strongly recommended based on the results of the OVHIPEC‐1 trial, which showed significant benefit in RFS (3.5 months) and OS (12 months) without increasing the grade 3–4 morbidity. For the first platinum‐sensitive recurrence, a conditional recommendation was made either for sCRS with systemic therapy or systemic therapy alone, reflecting variability in trial outcomes due to heterogeneity in the patient population in the trials and lack of surgical standardization.ConclusionThis consensus highlights the benefits of HIPEC in addition of iCRS and key factors that limit its wide‐spread use. It underlines the need for individualized decision‐making while selecting patients for sCRS. Future research integrating advanced systemic therapies is essential to refine these recommendations and provide equitable access to these complex locoregional treatments.

The Significance of the Morphological Appearance of Peritoneal Lesions on Imaging in Patients With Peritoneal Malignancies—A Report From Phase 1 of the PRECINCT Study

ABSTRACTBackground and AimThis is a report from Phase 1 of the prospective, observational, PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumours) study, in which we studied the incidence of disease at pathological evaluation in different morphological appearances of peritoneal malignancies (PM) on imaging.MethodsRadiological findings were captured in a specific format that included a description of the morphological appearance of PM and a correlation performed with pathological findings.ResultsIn 630 patients enroled at seven centres (September 2022–December 2023), 24 morphological terms were used. Among prespecified terms (N = 8 used in 6350 [92.2%] regions), scalloping was pathologically positive in 93.5%, confluent disease in 78.8%, tumour nodules in 69.6%, thickening in 66.1%, infiltration in 56.3%. Among unspecified appearances (N = 16) for 540 (7.8%) regions, ‘enhancement’ was positive in 41.5%, micronodules in 65.3% and nodularity in 60.2%. Hierarchal clustering placed gastric cancer and rare tumours together and colorectal cancer, ovarian cancer and peritoneal mesothelioma in one cluster.ConclusionsThe incidence of disease at pathological evaluation for most morphological appearances was high (> 50%). Morphological description should be provided in routine radiology reports. A set of standardized terms with their description should be developed by a consensus among experienced radiologists.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Epithelial Ovarian Cancer

We report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals: To define the indications for HIPEC To identify the most suitable HIPEC regimens for each indication in EOC To identify areas of future research on HIPEC To provide recommendations for some aspects of perioperative care for HIPEC METHODS: The Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations. Seventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC. The results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.

ASO Author Reflections: Which HIPEC Regimens Should be Used in Patients with Epithelial Ovarian Cancer? In the Clinic and in Randomized Trials

Distribution of residual disease in the peritoneum following neoadjuvant chemotherapy in advanced epithelial ovarian cancer and its potential therapeutic implications

Residual disease in 'normal appearing' peritoneum is seen in nearly 30% of the patients following neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. The goal was to study the sequence of response in different regions, the commonest sites of occult residual disease, its incidence in different peritoneal regions and the potential therapeutic implications of these. This was a prospective multi-centre study (July 2018-June 2019). Pathological evaluation of cytoreductive surgery specimens was performed according to a fixed protocol. Prevalence of residual disease in different regions was used to study patterns of response and distribution of residual disease. In 85 patients treated between July 2018 to June 2019, microscopic disease in 'normal appearing' peritoneal regions was seen in 22 (25.2%) and in normal peritoneum around tumor nodules in 30 (35.2%) patients. Regions 4 and 8 of Sugarbaker's PCI had the highest incidence of occult disease and regions 9 and 10 the lowest. The response to chemotherapy occurred in a similar manner in over 95%- the least common site of residual disease was the small bowel mesentery, followed by upper regions (regions 1-3), omentum and middle regions (regions 0, 4, 8), lower regions (regions 5-7) and lastly the ovaries. During interval CRS, based on the disease mapping provided in this manuscript, regions that have a high probability of residual disease should be explored and dissected. Complete resection of involved the peritoneal region can completely address the occult disease. The role of resection of the entire region as well as 'normal appearing' parietal peritoneal regions should be prospectively evaluated.

Total Parietal Peritonectomy Can Be Performed with Acceptable Morbidity for Patients with Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: Results From a Prospective Multi-centric Study

Total parietal peritonectomy (TPP) removes areas of "normal-appearing" parietal peritoneum bearing microscopic residual disease and has the potential to improve survival of patients undergoing interval cytoreductive surgery (CRS) for advanced serous epithelial ovarian cancer. This report presents the morbidity outcomes for the first 50 patients enrolled in TORPEDO (CTRI/2018/12/016789), a prospective study. All the patients underwent a TPP during interval CRS. A surgical protocol that includes a description of the boundaries for each of the five peritonectomies was followed. The common toxicology criteria for adverse events (CTCAE) classification was used to record 90-day morbidity and mortality. The median Peritoneal Cancer Index (PCI) for 50 patients was 15 (range, 5-37). A complete cytoreduction (CC-0 resection) was obtained in 80%, a CC-1 resection in 16%. A bowel resection was performed in 70% of the patients. Grade 3 or 4 complications were seen in 11 patients (22%), and one patient died within 90 days after surgery due to intraperitoneal hemorrhage. The most common complications were postoperative fluid collection requiring aspiration (n = 5), intraperitoneal hemorrhage (n = 2), abdominal wound dehiscence (n = 2), pseudo-obstruction (n = 1), urinary sepsis (n = 2), and ileostomy-related complications (n = 2). No bowel fistulas or anastomotic leaks occurred. Microscopic disease in 'normal appearing' peritoneum adjacent to tumor nodules was observed in 46% of the patients, and in regions given a lesion score of 0 in 34%. The parietal peritoneal regions (0-8) had a higher incidence of residual disease (p < 0.001) and occult disease (p < 0.001). During interval CRS, TPP can be performed with acceptable morbidity and mortality. The pathologic findings further support this therapeutic rationale. Survival outcomes should determine the future role of such a procedure in routine clinical practice.

ASO Author Reflections: Total Parietal Peritonectomy During Interval Cytoreductive Surgery for Advanced Ovarian Cancer—Proof-of-Principle and Analysis of Morbidity

Extent and distribution of peritoneal disease in patients undergoing cytoreductive surgery for first platinum sensitive recurrence in ovarian cancer and its potential therapeutic implications

Selected patients with platinum sensitive recurrent ovarian cancer may benefit from cytoreductive surgery (CRS). The aim was to study the pattern of peritoneal involvement in these patients that has not been done before. A comparison was made between the surgical and pathological findings in 60 patients undergoing salvage CRS from July 2018 to December 2019. The sites of residual disease, correlation with surgical and pathological peritoneal cancer index (PCI), small bowel involvement and regional lymph node involvement were studied. Fifty-eight (96.6%) had serous carcinoma and 2 (3.4%) clear cell carcinoma. The median surgical PCI (sPCI) was 7 [range 0-27] and median pathological PCI (pPCI) 4 [range 0-21]. CC-0 resection was performed in 81.6%. The upper regions (region 1,2,3) were the commonest sites of residual disease (63.3%) followed by lower regions (region 5,6,7) in 55.0%, middle regions (regions 0,4,8) in 53.3% and small bowel regions (regions 9-12) in 26.6%. Small bowel involvement was associated with a higher sPCI and pPCI (p < 0.001 for both). Regional nodes were involved in 46.6%. A pathological complete response was seen in 8 (13.3%) patients of which 2 had residual disease in regional nodes. Microscopic disease in 'normal appearing' peritoneum was seen in 21%. The parietal peritoneum was the commonest site of recurrence. Small bowel involvement occurred late and was associated with more extensive disease. Regional lymph node involvement was seen nearly 50% and was a common site for occult disease. The role of more extensive parietal peritoneal resection for recurrent disease should be evaluated prospectively.

Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study

Introduction Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. Methods and analysis There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied. Ethics and dissemination The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128). Trial registration number CTRI/2020/09/027709; Pre-results.

Comments on “Effect of HIPEC according to HRD/BRCAwt genomic profile in stage III ovarian cancer: Results from the phase III OVHIPEC trial”

Perioperative outcomes and platinum resistant recurrence in patients undergoing systematic, protocol-based, total parietal peritonectomy during interval cytoreductive surgery for advanced ovarian cancer: results of the TORPEDO study

The TORPEDO (CTRI/2018/12/016789) is the single-arm, prospective, interventional study evaluating the role of a total parietal peritonectomy (TPP) in patients undergoing interval cytoreductive surgery (iCRS). In this manuscript, we report the perioperative outcomes and platinum resistant recurrence (PRR) in 218 patients enrolled in the study. A TPP was performed in all patients undergoing iCRS irrespective of the residual disease extent. hyperthermic intraperitoneal chemotherapy (HIPEC) was performed as per the clinician's discretion with 75 mg/m² of cisplatin. Maintenance therapy was also used at the discretion of the treating clinicians. From 9th December 2018 to 31st July 2022 (recruitment complete), 218 patients were enrolled at 4 medical centers in India. The median surgical peritoneal cancer index was 14 and a complete gross resection was achieved in 95.8%. HIPEC was performed in 130 (59.6%) patients. The 90-day major morbidity was 17.4% and 2.7% patients died within 90 days of surgery. Adjuvant chemotherapy was delayed beyond 6 weeks in 7.3%. At a median follow-up of 19 months (95% confidence interval [CI]=15.9-35 months), 101 (46.3%) recurrences and 19 (8.7%) deaths had occurred. The median progression-free survival was 22 months (95% CI=17-35 months) and the median overall survival (OS) not reached. Platinum resistant recurrence was observed in 6.4%. The projected 3-year OS was 81.5% and in 80 patients treated before may 2020, it was 77.5%. The morbidity and mortality of TPP with or without HIPEC performed during iCRS is acceptable. The incidence was of PRR is low. Early survival results are encouraging and warrant conduction of a randomized controlled trial comparing TPP with conventional surgery.