Dennis Chi

Survival impact and prognostic factors of secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: a systematic review and trial-level meta-analysis

Secondary cytoreductive surgery is considered for selected patients with recurrent ovarian cancer. Although evidence supports its impact on progression-free survival, its effect on overall survival remains controversial. This study aims to identify patient sub-groups that benefit most from secondary cytoreductive surgery. A systematic review and trial-level meta-analysis of randomized controlled trials published through March 2025 was conducted. The primary end points were pooled hazard ratio (HR) for overall survival and progression-free survival comparing secondary cytoreductive surgery plus chemotherapy versus chemotherapy alone. Sub-group analyses were performed based on histology, platinum-free interval, number of recurrent lesions, individualized model or Arbeitsgemeinschaft Gynäkologische Onkologie score, and residual disease status. Three randomized controlled trials involving 1249 patients were included in this meta-analysis. Patients with favorable validated selection scores (positive Arbeitsgemeinschaft Gynäkologische Onkologie or individualized model ≤4.7) showed significantly improved overall survival (HR 0.79, 95% confidence interval [CI] 0.66 to 0.96). Complete resection was associated with significantly better overall survival (HR 0.53, 95% CI 0.43 to 0.64) and progression-free survival (HR 0.51, 95% CI 0.42 to 0.61) than patients who had residual disease. A progression-free survival benefit was also observed in the non-high-grade serous histology (HR 0.52, 95% CI 0.38 to 0.72). In patients with a platinum-free interval of 6 to 12 months (SOC-1, 6-16 months), there was a significant trend toward improved overall survival (HR 0.70, 95% CI 0.55 to 0.91). Secondary cytoreductive surgery significantly improves progression-free survival and provides an overall survival benefit in carefully selected patients, particularly, those with a high likelihood of complete resection, favorable surgical selection scores, and a shorter platinum-free interval (<16 months). These findings highlight the critical role of patient selection and surgical completeness in optimizing outcomes for recurrent ovarian cancer.

Evaluating the risk of diaphragmatic hernia following left diaphragm resections during cytoreductive surgery for ovarian cancer: a Memorial Sloan Kettering Cancer Center Team Ovary study

To determine the incidence rate and risk factors associated with the development of diaphragm hernias following left diaphragm procedures at the time of ovarian cancer cytoreduction. We retrospectively reviewed data from patients diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who underwent any timeframe of cytoreductive surgery (primary, interval, secondary, tertiary) at our institution from December 2010 to September 2024. Patients were included if they underwent left diaphragm peritonectomy or resection as part of their cytoreductive surgery. The diagnosis of left diaphragm hernia was made by computed tomography of the chest either as an incidental finding during follow-up surveillance or during work-up for symptomatology. We utilized statistical analysis with descriptive proportions with interquartile ranges. A total of 267 patients with ovarian cancer underwent a left diaphragm peritonectomy or resection as part of their cytoreductive surgery at our institution and were included in the study. The overall median age was 62 years (interquartile range; 52-70) and body mass index 24.9 kg/m Diaphragmatic hernias occurred most often following the setting of concurrent splenectomy; however, splenectomy was not a statistically significant risk factor. These findings provide meaningful insight into the frequency and clinical context in which this complication may arise, addressing a critical knowledge gap in the surgical management of patients with ovarian cancer who require upper abdominal and thoracic procedures.

Optimizing Mainstreaming of Genetic Testing in Parallel With Ovarian and Endometrial Cancer Tumor Testing: How Do We Maximize Our Impact?

PURPOSE Although germline genetic testing (GT) is recommended for all patients with ovarian cancer (OC) and some patients with endometrial cancer (EC), uptake remains low with multiple barriers. Our center performs GT in parallel with somatic testing via a targeted sequencing assay (MSK-IMPACT) and initiates testing in oncology clinics (mainstreaming). We sought to optimize our GT processes for OC/EC. METHODS We performed a quality improvement study to evaluate our GT processes within gynecologic surgery/medical oncology clinics. All eligible patients with newly diagnosed OC/EC were identified for GT and tracked in a REDCap database. Clinical data and GT rates were collected by the study team, who reviewed data for qualitative themes. RESULTS From February 2023 to April 2023, we identified 116 patients with newly diagnosed OC (n = 57) and EC (n = 59). Patients were mostly White (62%); English was the preferred language for 90%. GT was performed in 52 (91%) patients with OC (seven external, 45 MSK-IMPACT) and in 44 (75%) patients with EC (three external, 41 MSK-IMPACT). GT results were available within 3 months for 100% and 95% of patients with OC and EC, respectively. Reasons for not undergoing GT included being missed by the clinical team where there was no record that GT was recommended, feeling overwhelmed, financial and privacy concerns, and language barriers. In qualitative review, we found that resources were concentrated in the initial visit with little follow-up to encourage GT at subsequent points of care. CONCLUSION A mainstreaming approach that couples somatic and germline GT resulted in high testing rates in OC/EC; however, barriers were identified. Processes that encourage GT at multiple care points and allow self-directed, multilingual digital consenting should be piloted.

A pre-operative scoring model to estimate the risk of blood transfusion over an ovarian cancer debulking surgery (BLOODS score): a Memorial Sloan Kettering Cancer Center Team Ovary study

To develop a pre-operative tool to estimate the risk of peri-operative packed red blood cell transfusion in primary debulking surgery. We retrospectively reviewed an institutional database to identify patients who underwent primary debulking surgery for ovarian cancer at a single center between January 1, 2001 and May 31, 2019. Receiver operating characteristic curve and area under the receiver operating characteristic curve (AUC) were calculated. Five-fold cross-validation was applied to the multivariate model. Significant variables were assigned a 'BLOODS' (BLood transfusion Over an Ovarian cancer Debulking Surgery) score of +1 if present. A total BLOODS score was calculated for each patient, and the odds of receiving a transfusion was determined for each score. Overall, 1566 patients met eligibility criteria; 800 (51%) underwent a peri-operative blood transfusion. Odds ratios (OR) were statistically significant for American Society of Anesthesiologists scores of 3 and 4 (OR 1.34, 95% confidence interval (95% CI) 1.09 to 1.63), pre-operative levels of cancer antigen 125 (CA125) (OR 2.43, 95% CI 1.98 to 2.99), platelets (OR 1.59, 95% CI 1.45 to 1.74), obesity (OR 0.76, 95% CI 0.60 to 0.96), presence of carcinomatosis (OR 2.45, 95% CI 1.93 to 3.11), bulky upper abdominal disease (OR 2.86, 95% CI 2.32 to 3.54), pre-operative serum albumin level (OR 0.31, 95% CI 0.24 to 0.40), and pre-operative hemoglobin level (OR 0.56, 95% CI 0.51 to 0.61). The corrected AUC was 0.748 (95% CI 0.693 to 0.804). BLOODS scores of 0 and 5 corresponded to 11% and 73% odds, respectively, of receiving a peri-operative blood transfusion. We developed a universal pre-operative scoring system, the BLOODS score, to help identify patients with ovarian cancer who would benefit from surgical planning and blood-saving techniques. The BLOODS score was directly proportional to the American Society of Anesthesiologists score, presence of upper abdominal disease, carcinomatosis, CA125 level, and platelets level. We believe this model can help physicians with surgical planning and can benefit patient outcomes.

ARIA II: a randomized controlled trial of near-infrared Angiography during RectosIgmoid resection and Anastomosis in women with ovarian cancer

Ovarian cancer with extensive metastatic disease involving pelvic structures often requires rectosigmoid resection for complete gross resection; however, it is associated with increased surgical morbidity. There are limited data, and none in ovarian cancer, on near-infrared assessment of perfusion in rectosigmoid resections with anastomosis. To compare the rate of pelvic complications (pelvic abscesses, anastomotic leaks, and infections) within 30 days of surgery with and without near-infrared assessment of perfusion at time of rectosigmoid resection and re-anastomosis in patients undergoing cytoreductive surgery for ovarian cancer. We hypothesize the use of near-infrared technology (intravenous indocyanine green and endoscopic near-infrared fluorescence imaging), compared with standard intra-operative assessment, to evaluate anastomotic perfusion at time of rectosigmoid resection and re-anastomosis will result in lower rates of post-operative pelvic complications. This is a planned multicenter randomized controlled trial. Patients who undergo rectosigmoid resection as part of their ovarian cytoreductive surgery will be randomized 1:1 to standard assessment of anastomosis with the surgeon's usual technique (control arm) or assessment with near-infrared angiography using indocyanine green and endoscopic fluorescence imaging (experimental arm). Randomization will occur after rectosigmoid resection has been completed and the surgeon declares their plan to create a diverting ostomy. Randomization will be stratified by plan for diverting ostomy. Main inclusion criteria include patients with primary or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are scheduled for cytoreductive surgery with suspected need for low-anterior rectosigmoid resection. Rate of 30-day post-operative pelvic complications. 310 (155 per arm) ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Q2 2027 and Q4 2027, respectively. NCT04878094.

Extra-abdominal cytoreductive techniques in ovarian cancer: how far can (should) we go?

Complex surgery is an essential component in the management of advanced ovarian cancer. Furthermore, achieving complete gross resection in cytoreductive surgery appears to be associated with significant survival benefits in patients with advanced ovarian cancer. The goal of this review is to demonstrate the advancement of surgical techniques in gynecologic oncology surgery, including resection of disease within the intrathoracic and inguinal regions. This progress has expanded the option of surgery to more patients, especially those who would have previously been deemed inoperable. In this review we describe the most notable studies and reports of surgical resection of ovarian cancer involving cardiophrenic/supradiaphragmatic lymph nodes, mediastinum, lung pleura or parenchyma, and the inguinal region. We also describe the growing role that video-assisted thoracic surgery has played in advanced ovarian cancer diagnosis and management. The studies, series, and reports described demonstrate that comprehensive surgical procedures outside of the abdomen or pelvis can be both safe and feasible in properly selected patients. They also suggest that resection of disease outside of the abdomen or pelvis may benefit appropriately selected patients. Future studies are necessary to identify which patients may benefit most from upfront surgery versus neoadjuvant chemotherapy when ovarian cancer metastasis is present in the thoracic or inguinal regions.

Safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism in women who undergo neoadjuvant chemotherapy for advanced ovarian cancer

We sought to investigate the safety and feasibility of therapeutic anticoagulation for newly diagnosed venous thromboembolism among women who undergo neoadjuvant chemotherapy for the treatment of advanced ovarian cancer. A retrospective study using data extrapolated from a prospectively maintained institutional database was used to identify all patients with ovarian cancer who underwent neoadjuvant chemotherapy from April 2015 through September 2018 at our institution. All patients who received therapeutic anticoagulation for newly diagnosed venous thromboembolism at initial diagnosis or during neoadjuvant chemotherapy were included. Of 290 patients who underwent neoadjuvant chemotherapy for advanced ovarian cancer during the study period, 67 (23%) had newly diagnosed venous thromboembolism at the time of initial diagnosis or developed venous thromboembolism during neoadjuvant chemotherapy. Of these 67 patients, 64 (96%) received therapeutic anticoagulation. A total of 13 (20%) of 64 patients who underwent therapeutic anticoagulation experienced a bleeding episode while on anticoagulation; 4 (31%) of the 13 events were of major severity. Three patients developed major internal bleeding in the peritoneal cavity, and one patient suffered from a major vaginal bleeding episode. All four patients were hospitalized (range, 5-11 days) and received ≥2 units of red blood cells for anemia. None of these patients died from fatal bleeding or had to delay starting chemotherapy. Of note, all four patients received low-molecular-weight heparin via subcutaneous injection. Overall, 13 (20%) of 64 patients required an anticoagulant dose reduction, mostly due to weight loss or new bleeding episodes. Therapeutic anticoagulation in this setting appeared safe, with a low risk of major bleeding complications. Furthermore, anticoagulation did not result in delay of chemotherapy or cytoreductive surgery.

Germline Pathogenic Variants and Genetic Counseling by Ancestry in Patients With Epithelial Ovarian Cancer

Mutations in ovarian cancer risk genes are found in women of diverse ancestries, supporting genetic testing for ALL

An overview of the current debate between using minimally invasive surgery versus laparotomy for interval cytoreductive surgery in epithelial ovarian cancer

The standard of care for treatment of advanced-stage epithelial ovarian cancer is primarily surgery followed by platinum-based chemotherapy, with the operative goal to achieve complete gross resection. Cytoreductive surgeries for epithelial ovarian cancer historically were performed via open laparotomy; however, as minimally invasive techniques became more widely accepted within gynecologic oncology, interest in employing this approach in the setting of cytoreductive surgery for epithelial ovarian cancer has grown. The purpose of this review was to examine the current debate between the use of minimally invasive surgery versus laparotomy as an approach to interval cytoreductive surgery in advanced epithelial ovarian cancer. While numerous retrospective and feasibility studies have found comparable outcomes with respect to complete gross residual disease, progression-free survival, and overall survival between minimally invasive and laparotomy approaches to interval cytoreductive surgery for epithelial ovarian cancer, methodological challenges limit the utility of these data. Given potential risks of underestimating disease burden and failing to achieve complete resection using a minimally invasive approach, further rigorous studies are needed to evaluate the safety and efficacy of minimally invasive surgery in this setting and to better define the subset of patients who would receive the greatest benefit from a minimally invasive approach.

Why was GOG-0213 a negative trial?

Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery

Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) confers similar outcomes as primary debulking surgery and chemotherapy. Little is known about patients who receive NACT but do not undergo debulking surgery. Our aim was to characterize these patients. We prospectively identified patients with newly diagnosed stage III/IV ovarian cancer treated with NACT from 7/1/15-12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis. Of 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66-6.72; p<0.001), after adjustment for age, CCI, and dose reductions. A significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

Significance The optimal timing of surgery/chemotherapy and the benefits of earlier diagnosis of HGSC remain controversial. We developed a mathematical framework of tumor dynamics, populated the model with primary clinical data, and reliably recapitulated clinical observations. Our model predicts that 1) PDS is superior to NACT with relatively small tumor burden and when complete debulking is feasible, 2) timely adjuvant chemotherapy is critical for the outcome of PDS with &lt;1-mm residual tumors, 3) earlier detection of relapse is unlikely beneficial with current therapies, and 4) earlier detection of primary HGSC could have substantial benefit. These results provide insights into the evolutionary dynamics of HGSC, argue for new clinical trials to optimize therapy, and are potentially applicable to other tumor types.

Posterior pelvic exenteration, a crucial component in the surgeon’s toolbox for optimizing surgical cytoreduction for advanced ovarian cancer

Gynecologic Survivorship Tool: Development, Implementation, and Symptom Outcomes

PURPOSE To describe the development and implementation of a new digital health clinical tool (Gynecologic Survivorship Tool [GST]) for symptom management of women surgically treated for gynecologic cancer; to assess its feasibility; and to conduct a retrospective review of the data. MATERIALS AND METHODS The GST was developed on the basis of a comprehensive review of the literature, multidisciplinary expert opinion, and feedback from women with a history of gynecologic cancer. It is composed of 17 questions addressing six main categories—gynecologic health (abnormal bleeding/pain), lymphedema, vaginal/vulvar dryness, sexual health, menopause (hot flushes/sleep difficulties), and bowel/urinary issues. An electronic version using the Memorial Sloan Kettering Cancer Center Engage platform was piloted in two clinics for patients with endometrial or cervical cancer. Health information was generated into clinical summaries and identified concerns for actionable response. Associations of symptom and survey time point were assessed by longitudinal models using generalized estimating equations. RESULTS From January 1, 2019, to February 29, 2020, 3,357 GST assessments were assigned to 1,405 patients, with a 71% completion rate (90% within 5 minutes). Sixty-eight percent were performed at home via a patient portal, 32% at follow-ups using a clinic iPad. The most common symptoms were bowel problems, swelling/fluid, pain during examination, vaginal or vulvar dryness, and vaginal bleeding. Implementation challenges included improving patient compliance and ensuring that reports were reviewed by all clinical teams. We developed screening e-mails detailing patients whose assessments were due, planned training sessions for multidisciplinary teams, and incorporated feedback on methods for reviewing symptoms reports. CONCLUSION The GST demonstrated feasibility, a high completion rate, and minimal time commitment. It was an effective electronic reporting mechanism for patients, enabling the medical team to develop specific strategies for alleviating bothersome symptoms during follow-up.

A prospective comparison of resectability scores to enhance preoperative decision-making in the primary management of advanced ovarian cancer: a Memorial Sloan Kettering Cancer Center Team Ovary study

To compare cytoreductive outcomes of 2 published algorithms used to triage patients with ovarian cancer to primary debulking surgery versus diagnostic laparoscopy or neoadjuvant chemotherapy. This prospective comparative study was conducted from August 1, 2021, to January 31, 2025. All patients with suspected advanced ovarian cancer who were eligible for primary debulking surgery on initial evaluation were identified. Imaging was reviewed utilizing a standardized radiology synoptic report. Data from the synoptic report were combined with clinical factors to determine a Resectability Score using 1 of 2 algorithms, Resectability Score 1.0 (RS1.0) and Resectability Score 2.0 (RS2.0). The algorithms include different clinical and radiologic variables; both generate low- and high-risk scores, with high-risk scores indicating a greater likelihood of suboptimal primary debulking surgery. In high-risk cases, laparoscopic evaluation of resectability was recommended, but management was based on surgeon's discretion. Of 237 patients identified, 200 had primary debulking surgery with final pathology confirming epithelial ovarian carcinoma. Of 144 patients (72%) who underwent laparotomy and primary debulking surgery, 110 (76%) were triaged directly to surgery and 34 (24%) first underwent diagnostic laparoscopy; 120 (83%) had complete gross resection, 135 (94%) had residual disease ≤1 cm, and 9 (6%) had residual disease >1 cm. Of 56 patients (28%) who underwent neoadjuvant chemotherapy, 43 (77%) first underwent diagnostic laparoscopy, and 13 (23%) were triaged directly to chemotherapy. Among all patients, 44 (22%) had high-risk scores using RS1.0 and 54 (27%) using RS2.0. RS2.0 more frequently predicted the ability to and inability to achieve complete gross resection (p > .05). RS2.0 more accurately identified high-risk disease warranting neoadjuvant chemotherapy (p = .035). Most surgeons (73%) preferred RS2.0, citing ease of use and faster calculation time. RS2.0 demonstrated favorable predictive accuracy for complete gross resection and was preferred among surgeons. The favorable complete gross resection rate (83%) highlights the value of individualized preoperative triage for primary debulking surgery versus neoadjuvant chemotherapy.

Assessing the clinical value of pre-operative imaging in endometrial carcinoma by symptoms and low-risk versus high-risk histology

This study aimed to assess the concordance between pre-operative imaging results and intra-operative findings in patients with endometrial carcinoma, based on pre-operative risk stratification and the clinical indication for obtaining imaging. We identified all patients who had surgery for newly diagnosed endometrial carcinoma at our institution from January 2017 to January 2021 and categorized them as low or high risk. We reviewed pre-operative images or radiologic evidence of extra-uterine disease and correlated with intra-operative findings, and we categorized the findings as true positive or false negative. We identified a total of 1970 patients for this analysis. Within the study cohort, 1247 tumors (63.3%) were low-risk histology, 719 (36.5%) were high-risk histology, and 4 patients (0.2%) had no pre-operative biopsy. Pre-operative imaging was performed for 676 low-risk (54.2%) and 700 high-risk patients (97.4%) (p <.001) and detected the presence of extra-uterine disease in 50 of 676 low-risk (7.4%) and 140 of 700 high-risk patients (20%). In the low-risk cohort, there was radiologic evidence of extra-uterine disease present for 12 of 60 patients (20%) with an abnormal exam or ultrasound, 16 of 126 patients (12.7%) with symptoms or a delayed diagnosis, and 16 of 490 asymptomatic patients (3.3%). In the high-risk cohort, there was radiologic evidence of extra-uterine disease present for 32 of 66 patients (48.5%) with symptoms or a delayed diagnosis, 21 of 46 patients (45.7%) with an abnormal exam or ultrasound, and 84 of 583 asymptomatic patients (14.4%). A total of 122 of 1376 patients (8.9%) had a change in clinical management based on pre-operative imaging findings: 32 of 676 (4.7%) low-risk and 90 of 700 high-risk patients (12.9%). Over 90% of patients with low-risk tumors had no findings suspicious for metastatic disease on pre-operative imaging, indicating limited utility in that cohort. However, pre-operative imaging yielded clinically meaningful information in patients with high-risk histology, particularly, those with symptoms, delayed diagnosis, or concerning exam findings.

A Study of Intra-operative Imaging in Women With Ovarian Cancer

The purpose of this study is to find out whether using the PINPOINT imaging system intra-operatively can reduce the risk of anastomotic leaks and other complications after surgery for ovarian cancer, compared with standard intra-operative assessments alone. The PINPOINT endoscopic fluorescence imaging system uses a special camera and a fluorescent (glowing) dye that can evaluate the blood flow of the bowel in real-time. If there is an area that appears concerning, the surgeon can correct the problem during the procedure.