Amanika Kumar

Body mass index and chemotherapy completion among patients with newly diagnosed ovarian cancer

Abstract Background Several ovarian cancer studies have suggested that a body mass index (BMI) of 30 or higher is associated with lower compliance with National Comprehensive Cancer Network–recommended chemotherapy but primarily involved treatment before 2012, when dose capping was recommended for patients with higher body surface areas. Updated analyses in the contemporary treatment era are warranted. Methods In a retrospective cohort of patients with newly diagnosed ovarian cancer receiving curative-intent carboplatin plus paclitaxel in the Yale-Smilow Cancer Network (2012-2022), we evaluated BMI at diagnosis in relation to relative dose intensity (RDI)—the ratio of completed chemotherapy dose intensity to the National Comprehensive Cancer Network–recommended dose intensity—which reflects dose modification both before and during treatment. We also assessed starting RDI (which reflects modifications before treatment) and received RDI (which reflects modifications during treatment). Data on hospitalizations and hematological chemotoxicities were collected. We examined the association between BMI (<25, 25-30, ≥30) and chemotherapy completion, hospitalizations, and toxicities using multivariable linear and logistic regressions. Results Among 327 patients, the average RDI was 79.7%, and 44.3% had an RDI below 85%. Mean (SD) starting and received RDI were 97.9% (9.1%) and 81.8% (25.7%), respectively. Higher BMI was associated with higher RDI (Paggregate = .03) and received RDI (Paggregate = .04). Body mass index was not associated with starting RDI, dose reductions, delays, hospitalizations, or hematological toxicities. Conclusions Among patients with ovarian cancer treated since 2012, the overall RDI was low. Relative dose intensity was higher among patients with a BMI of 25 or higher compared with a BMI below 25. Most dose modifications occurred during treatment and not before initiation. Studies with body composition data and interventions that maximize chemotherapy completion during treatment are warranted.

Measuring the impact of specific surgical complications after ovarian cancer cytoreductive surgery on short-term outcomes

Objective We sought to measure the impact of specific peri-operative complications after primary cytoreductive surgery on relevant patient outcomes and use of resources. Methods A cohort of patients with advanced ovarian cancer who underwent primary cytoreductive surgery at two institutions (2006–2016) were studied. Specific known complications (‘exposures’) within 30 days of surgery were evaluated to determine the impact on outcomes. Exposures included bowel leak, superficial surgical site infection, deep surgical site infection, venous thromboembolic event, and cardiac event. Outcomes were prolonged lengths of stay, readmission or non-home discharge, reoperation, organ failure, delay to adjuvant chemotherapy, and 90-day mortality. Population attributable risk (PAR) was used to estimate the proportion of adverse outcomes that could be prevented by elimination of a causal exposure and considers both the strength of the association and the prevalence of the complication; adjusted PARs (aPAR) were calculated using adjusted relative risks (aRR) adjusted for stage (IIIC vs IV) and American Society of Anesthesiology score (<3 vs ≥3). Results A cohort of 892 patients was included. Each of the evaluated exposures had an impact on readmission/non-home discharge (aPAR range 5.3 to 13.5). A venous thromboembolic event was significantly associated with 90-day mortality (aRR=2.9 (95% CI 1.3 to 6.7); aPAR=8.6 (95% CI −1.8 to 19.1)) and organ failure (aRR=4.7 (95% CI 2.3 to 9.5); aPAR=13.9 (95% CI 2.8 to 25.1)). Similarly, a cardiac event was most strongly associated with organ failure and was very impactful (aPAR=19.0 (95% CI 6.8 to 31.1)). Bowel leak was a major contributor to poor outcome, including reoperation (aPAR=45.5 (95% CI 34.3 to 56.6)), organ failure (aPAR=13.6 (95% CI 2.6 to 24.6)), readmission/non-home discharge (aPAR=5.3 (95% CI 1.6 to 9.0)), delay to adjuvant chemotherapy (aPAR=5.9 (95% CI 2.3 to 9.4)), and prolonged lengths of stay (aPAR=13.0 (95% CI 9.1 to 16.9)). Conclusion Going beyond reporting complications using common scales to measure their genuine impact provides important information for providers, patients, and payers. We report that less frequent exposures, including a venous thromboembolic event, cardiac events, and bowel leaks, have a high impact on patients and use of resources.

A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies

Abstract Purpose: AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared with sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers. Patients and Methods: A 3+3 phase I trial was conducted with three potential dose levels in patients with previously treated endometrial, cervical, and platinum-resistant ovarian cancer to ascertain the recommended phase II dose (RP2D). AB160 was administered intravenously on days 1, 8, and 15 of a 28-day cycle (ABX 75–175 mg/m2, BEV 30–70 mg/m2). Pharmacokinetic analyses were performed. Results: No dose-limiting toxicities (DLT) were seen among the three dose levels tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% confidence interval, 16.3%–61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies. Conclusions: The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2).

Trends and current aspects of reconstructive surgery for gynecological cancers

Gynecologic cancers can lead to gynecologic tract destruction with extension into both the gastrointestinal and urinary tracts. Recurrent disease can also affect the surrounding bony pelvis and pelvic musculature. As opposed to advanced ovarian cancer, where cytoreduction is the goal, in these scenarios, an oncologic approach to achieve negative margins is critical for benefit. Surgeries aimed at achieving a R0 resection in gynecologic oncology can have a significant impact on pelvic anatomy, and require reconstruction. Overall, it appears that these types of radical surgery are less frequently performed; however, when required, multidisciplinary teams at high-volume centers can potentially improve short-term morbidity. There are few data to examine the long-term, quality-of-life outcomes after reconstruction following oncologic resection in advanced and recurrent gynecologic cancers. In this review we outline considerations and approaches for reconstruction after surgery for gynecologic cancers. We also discuss areas of innovation, including minimally invasive surgery and the use of 3D surgical anatomy models for improved surgical planning.In the era of 'less is more', pelvic exenteration in gynecologic oncology is still indicated when there are no other curative-intent alternatives in persistent or recurrent gynecological malignancies confined to the pelvis or with otherwise unmanageable symptoms from fistula or radiation necrosis. Pelvic exenteration is one of the most destructive procedures performed on an elective basis, which inevitably carries a significant psychologic, sexual, physical, and emotional burden for the patient and caregivers. Such complex ultraradical surgery, which requires removal of the vagina, vulva, urinary tract, and/or gastrointestinal tract, subsequently needs creative and complex reconstructive procedures. The additional removal of sidewall or perineal structures, like pelvic floor muscles/vulva, or portions of the musculoskeletal pelvis, and the inclusion of intra-operative radiation further complicates reconstruction. This review paper will focus on the reconstruction aspects following pelvic exenteration, including options for urinary tract restoration, reconstruction of the vulva and vagina, as well as how to fill large empty spaces in the pelvis. While the predominant gastrointestinal outcome after exenteration in gynecologic oncology is an end colostomy, we also present some novel new options for gastrointestinal tract reconstruction at the end.

Clear cell adenocarcinoma of Müllerian origin in a patient with germline SMARCA4 mutation

Re-Evaluating Chemotherapy Dosing Strategies for Ovarian Cancer: Impact of Sarcopenia

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Impact of comorbidities and extent of lymphadenectomy on quality of life in endometrial cancer patients treated with minimally invasive surgery in the era of sentinel lymph nodes

To identify predictors of quality of life (QoL) among patients who undergo surgical staging with sentinel lymph node (SLN) biopsy or lymphadenectomy for endometrial cancer. Patients who underwent minimally invasive surgery for primary endometrial cancer at the Mayo Clinic from October 2013 to June 2016 were mailed a 30-item QoL in Cancer survey (QLQ-C30) and a validated 13-item lower extremity lymphedema screening questionnaire. Patients who answered <50% of the items or had a pre-operative history of lymphedema were excluded. Multivariable linear regression models were fit to evaluate predictors of QoL using inverse-probability of treatment weighting to adjust for differences at the time of the surgery between the lymphadenectomy and SLN groups. The 221 patients included in the analysis were stratified into two groups: patients who underwent (1) bilateral lymphadenectomy as 'backup' after SLN mapping (lymphadenectomy group; n=101) or (2) SLN removal with or without side-specific lymphadenectomy (SLN group; n=120). On multivariable analysis, obesity, lower extremity lymphedema, and kidney disease had significant (p<0.05) and clinically meaningful negative impacts on global QoL. Declines in average adjusted global QoL scores were marked (19.7 points lower) in patients with BMI ≥40 kg/m Lower extremity lymphedema coupled with obesity predicts poorer QoL in patients who undergo surgical staging for endometrial cancer. In this population, reduction of lower extremity lymphedema by performing SLN instead of lymphadenectomy and earlier targeted interventions may improve patients' QoL. Future research focusing on targeted interventions is needed.

The Quality of Life after Endometrial Cancer Study: Baseline Characteristics and Patient-Reported Outcomes

Endometrial cancer (EC) patients make up the second largest group of female cancer survivors. Patient-reported outcomes (PROs) including quality of life (QOL) and sexual function and satisfaction (SF and S) are critical facets of survivorship. This prospective, longitudinal study assesses associations between baseline characteristics and PROs after treatment. Herein, we report the baseline clinical characteristics and PROs prior to treatment initiation. Outcomes post-treatment over time will be reported separately. Patients with planned surgery for EC were prospectively enrolled in 2019–2021 and administered the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC Module (EN24), Patient-Reported Outcomes Measurement Information System (PROMIS), and the Mayo Clinic lower extremity lymphedema (LEL) questionnaire. This study enrolled 198 patients with a mean (SD) age of 63.6 (9.8) years and body mass index of 35.5 (8.3) kg/m2. No significant differences in the PROs for the QOL were seen when compared to the reference means (SD) except for the lower interest in sexual activity (31.9 (9.8) vs. 47.5 (SE0.70)) and lower fatigue (21.3 (19.8) vs. 31.7 (25.9)). Increased obesity was associated with an increased likelihood of LEL (p &lt; 0.01) and multiple QOL scales, including poorer global health status (p &lt; 0.01) and physical functioning (p &lt; 0.01). Prior to treatment initiation for EC, the patients had a similar QOL compared to that of the general population. The patients with increasing obesity, a known risk factor for EC, had worse overall global health status and physical functioning. A better understanding of these QOL measures is imperative for earlier identification and intervention of patients at risk of chronic impairments from EC treatment.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer

The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer. A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3-7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1-2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99). The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

Endometrial cancer with positive sentinel lymph nodes: pathologic characteristics of metastases as predictors of extent of lymphatic dissemination and prognosis

To assess predictors of extensive lymph node dissemination and non-vaginal recurrence in patients with endometrial cancer with positive sentinel lymph nodes (SLNs). Patients with endometrial cancer who underwent primary surgery with SLN mapping and had at least one positive node between October 2013 and May 2019 were included. Positive SLNs were reviewed, and cases were classified according to the location of the metastasis (extracapsular vs intracapsular), and the size of the largest SLN metastasis (isolated tumor cells, micrometastasis, macrometastasis). Associations were assessed based on fitting logistic regression models and Cox proportional hazards models. A total of 103 patients met the inclusion criteria: including 36 (34.9%) with isolated tumor cells, 27 (26.2%) with micrometastasis, and 40 (38.8%) with macrometastasis. Notably, 71.4% of patients exhibiting extracapsular SLN metastases had multiple positive SLNs (p=0.008). Extracapsular invasion (adjusted odds ratio (aOR) 5.81, 95% CI 1.4 to 23.6) and age (aOR=1.8, 95% CI 1.1 to 3.0) emerged as independent predictors of multiple positive SLNs. Among the 38 patients who underwent a backup pelvic lymphadenectomy, 18 (47.4%) presented with positive pelvic non-SLNs, a phenomenon more prevalent in patients with macrometastasis (p=0.004).Independent predictors of non-vaginal recurrence included SLN macrometastasis (adjusted hazard ratio (aHR) 3.3, 95% CI 1.3 to 8.3), non-endometrioid histology (aHR=3.7, 95% CI 1.5 to 9.3), and cervical stromal invasion (aHR=5.5, 95% CI 2.0 to 14.9). Among the 34 patients with isolated tumor cells and endometrioid histology, 3 (9%) experienced a recurrence, all of whom had not received any adjuvant chemotherapy or external beam radiotherapy. Patients with positive SLN macrometastasis are independently associated with extensive lymphatic dissemination and distant recurrences. The risk of multiple positive SLNs increases with the extracapsular location of the SLN metastasis and with age. Independent uterine pathologic predictors of non-vaginal recurrence are non-endometrioid histology and cervical stromal invasion.

Multi-center, international endometrial cancer consortium highlights

The multi-center, international consortium on endometrial cancer held in January 2025 at Mayo Clinic in Rochester, Minnesota brought together leading experts in gynecologic oncology to explore the latest advancements in the understanding, diagnosis, and treatment of endometrial cancer. Discussions centered on key topics, including updates in molecular testing and disease staging, emerging treatment strategies for advanced and recurrent disease, fertility-sparing management, and critical pathology challenges, particularly, the assessment of lympho-vascular space invasion. Each topic was examined in dedicated working group sessions, fostering in-depth exchanges to identify research priorities and develop actionable strategies. This summary highlights the central themes and insights from the meeting, outlining a roadmap for future advancements in the field. By promoting inter-disciplinary collaboration, the meeting laid the foundation for future research, policy recommendations, and clinical innovations aimed at improving patient outcomes.

Comparison of the Contracted Accordion, Expanded Accordion, and Clavien-Dindo complication grading scales after ovarian cancer cytoreduction

To compare the ability of current complication reporting scales (Contracted Accordion Scale, Expanded Accordion Scale, Clavien-Dindo Scale) to reflect the severity of patient outcomes after cytoreductive surgery for ovarian cancer. We included all patients undergoing primary debulking surgery for stage IIIC/IV ovarian cancer from 2006 to 2016 at two expert centers for ovarian cancer. Complications within 30 days of surgery were graded according to three scales. Outcomes included length of stay, mortality (90-day), and delayed initiation of chemotherapy (>42 days after surgery). Correlations were assessed using the Spearman rank correlation, and comparisons between groups were evaluated using the Wilcoxon rank-sum test and the χ Among the 892 patients, 185 (20.7%) patients had a grade 3 or higher complication per all scales. Patients with grade 3 or higher complications (compared with those with none, grade 1 or grade 2) had longer length of stay, higher 90-day mortality, and delayed initiation of chemotherapy. The expanded scales (Expanded Accordion Scale and Clavien Dindo Scale) provided a more refined characterization of outcome compared with the Contracted Accordion Scale. However, mortality was actually found to be as high as 25.0% for grade 5 complications using the Expanded Accordion Scale. Patients with organ failure or requiring an invasive procedure had significantly worse outcomes than those without either complication, highlighting the importance of separating these events. All three scales demonstrated general correlation with important outcomes after ovarian cancer surgery. However, the expanded scales (Clavien Dindo Scale and Expanded Accordion Scale) used important events commonly encountered after cytoreductive surgery, provided a more refined view of the severity of complications, and should be used in reporting outcomes in ovarian cancer.

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer

Abstract Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)–based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Response to: Correspondence on “Quality is more important than quantity: pre-operative sarcopenia is associated with poor survival in advanced ovarian cancer” by Maccio and Madeddu