Time Of Interval Debulking Surgery Research Articles

Role of systematic lymphadenectomy at the time of interval debulking surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection

ObjectiveTo evaluate the role of systematic lymphadenectomy at the time of interval cytoreductive surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection.MethodsThe National Cancer DataBase was...

Intraperitoneal and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Ovarian Cancer.

In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0-1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery.

Timing of interval debulking surgery and postoperative chemotherapy after neoadjuvant chemotherapy in advanced epithelial ovarian cancer: a multicenter real-world study

BackgroundTo investigate the prognostic relevance of the time to interval debulking surgery (TTS) and the time to postoperative adjuvant chemotherapy (TTC) after the completion of neoadjuvant chemotherapy (NACT).MethodsA retrospective real-word study included 658 patients with histologically confirmed advanced epithelial ovarian cancer who received NACT at seven tertiary hospitals in China from June 2008 to June 2020. TTS was defined as the time interval from the completion of NACT to the time of interval debulking surgery (IDS). TTC was defined as the time interval from the completion of NACT to the initiation of postoperative adjuvant chemotherapy (PACT).ResultsThe median TTS and TTC were 25 (IQR, 20–29) and 40 (IQR, 33–49) days, respectively. Patients with TTS > 25 days were older (55 vs. 53 years, P = 0.012) and received more NACT cycles (median, 3 vs. 2, P = 0.002). Similar results were observed in patients with TTC > 40 days. In the multivariate analyses, TTS and TTC were not associated with PFS when stratified by median, quartile, or integrated as continuous variables (all P > 0.05). However, TTS and TTC were significantly associated with worse OS when stratified by median (P = 0.018 and 0.018, respectively), quartile (P = 0.169, 0.014, 0.027 and 0.012, 0.001, 0.033, respectively), or integrated as continuous variables (P = 0.018 and 0.011, respectively). Similarly, increasing TTS and TTC intervals were associated with a higher risk of death (Ptrend = 0.016 and 0.031, respectively) but not with recurrence (Ptrend = 0.103 and 0.381, respectively).ConclusionThe delays of IDS and PACT after the completion of NACT have adverse impacts on OS but no impacts on PFS, which indicates that reducing delays of IDS and PACT might ameliorate the outcomes of ovarian cancer patients treated with NACT.

Comprehensive HRD testing in epithelial ovarian cancer: A further step toward personalized therapy decisions.

e17591 Background: HRD testing in ovarian cancer to date is predominately based on dichotomizing scores defining HR-deficiency and -proficiency. We herein provide a new comprehensive approach to test HR-status, which aims to assess HRD in a qualitative and quantitative manner. Methods: In addition to a 153-gene NGS panel, quantitative HRD was assessed in a “real-life” collective of 108 “high-grade”, stage III/IV ovarian cancer specimens. The readout of the assay integrates a LoH score, based on the algorithm of Swisher et al. and an Aneuploidy Normalized Telomeric Imbalance- (ANTI) score, adapted from the Birkbak et al. Telomeric Allelic Imbalance- (TAI) score. Besides numerical HRD values, clinical thresholds for both parameters were determined based on platinum-response at first recurrence according to platinum-free interval, and integrated into a HRD score ( [LoH/optimal cutoff] + [ANTI/optimal cutoff]) resulting in an optimal clinical cutoff of 1.95 (40. percentile). Results: All BRCAmut tumor specimens (n = 42) exhibited HRD scores above the derived cutoff (median: 3.00 (95%CI 2.65; 3.80)). Tumors with HRD scores above the cutoff were associated with improved PFS and OS in the whole collective (HR 0.334 (0.210–0.532) and 0.237 (0.123-0.459), respectively) and in the subgroup of BRCAwt patients (n = 66) (HR 0.282 (0.142–0.563) and 0.160 (0.048–0.536), respectively). In addition, a high HRD score was associated with a longer platinum-free interval ( &lt; 6 mo: 1.32 (0.92–1.44), ≥ 6 mo: 2.09 (1.18–3.24)). Residual disease after primary debulking surgery (n = 81) was associated with lower HRD scores (p = 0.029) which was apparently not based on differences in the amount or localization of intraperitoneal tumor spread (p = 0.802). However, patients exhibiting miliary, confluent tumor spread had significantly lower HRD scores compared to a more nodular and, more easy to remove type of carcinomatosis (median: 1.09 (95%CI 0.81; 1.40) and 2.83 (95%CI 2.07; 3.51); p &lt; 0.001). In neoadjuvant treated patients (n = 27) morphologically assessed vitality in remaining disease at the time of interval debulking surgery inversely correlated with HRD scores (p &lt; 0.001), whereby highest HRD scores were assessed in the 3% of patients exhibiting a complete pathologic response. In addition, comparing testing performance to the CA-125 ELIMination Rate Constant K (KELIM) score revealed a notably higher correlation of HRD to residual tumor vitality (-0.900; p &lt; 0.001 versus -0.614; p &lt; 0.001). Conclusions: Clinical validation of the herein provided new comprehensive HRD test in a “real-life” collective underscores its relevance in predicting ovarian cancer patients’ clinical outcome. From the clinical point of view, furthermore, our test is relevant to predict ( i) response to neoadjuvant treatment, and ( ii) surgical outcome. Its a priori integration could be a further step towards a more precise therapy decision strategy.

Tissue is the issue: Chemotherapy response score (CRS) is most predictive of response to neoadjuvant chemotherapy in advanced, high grade serous ovarian cancer (HGSOC) (488)

Tissue is the issue: Chemotherapy response score (CRS) is most predictive of response to neoadjuvant chemotherapy in advanced, high grade serous ovarian cancer (HGSOC) (488)

Tumor-infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment ovarian cancer during neoadjuvant chemotherapy (254)

Objectives: To investigate the dynamic changes of tumor immune microenvironment (TME) by evaluating lymphocyte infiltration before and after neoadjuvant chemotherapy (NACT) in patients with advanced-stage ovarian cancer. Methods: We conducted whole-transcriptome sequencing coupled with immunohistochemistry of 147 patients, including 140 pairs of serial tumor samples collected before NACT and at the time of interval debulking surgery (IDS). PD-L1 expression was determined by using a combined positive score (CPS). Tumor-infiltrating lymphocytes (TIL) were assessed by standardized methods according to the guidelines of the International TIL working group. Results: All the patients had high-grade serous carcinoma and were treated with platinum-based chemotherapy. High pre-NACT PD-L1 level (CPS ≥ 10%) was associated with worse progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.038). High pre-NACT TIL level (>20%) was associated with better PFS (p = 0.039) and trend of better OS (p = 0.077). Post-NACT PD-L1 and TIL levels were not associated with survival outcomes. PD-L1 level (p = 0.001) and TIL level (p <0.001) were significantly increased before and after NACT. An increase in TIL in response to NACT was associated with shorter PFS compared to patients with decreased TIL levels (p = 0.020). A change in the PD-L1 level had no impact on the prognosis. In whole-transcriptome sequencing, stromal score (p = 8.6e-0.7), immune score (p = 4e-0.6), and CYT score (p = 2.1e-0.5) were significantly increased after NACT. Conclusions: Pre-NACT TIL level was associated with a survival benefit in advanced-stage ovarian cancer. By contrast, increased TIL level was an adverse prognostic factor for survival outcomes. Further research is needed to find a patient group that can benefit from immunotherapy in the NACT setting. Objectives: To investigate the dynamic changes of tumor immune microenvironment (TME) by evaluating lymphocyte infiltration before and after neoadjuvant chemotherapy (NACT) in patients with advanced-stage ovarian cancer. Methods: We conducted whole-transcriptome sequencing coupled with immunohistochemistry of 147 patients, including 140 pairs of serial tumor samples collected before NACT and at the time of interval debulking surgery (IDS). PD-L1 expression was determined by using a combined positive score (CPS). Tumor-infiltrating lymphocytes (TIL) were assessed by standardized methods according to the guidelines of the International TIL working group. Results: All the patients had high-grade serous carcinoma and were treated with platinum-based chemotherapy. High pre-NACT PD-L1 level (CPS ≥ 10%) was associated with worse progression-free survival (PFS, p < 0.001) and overall survival (OS, p = 0.038). High pre-NACT TIL level (>20%) was associated with better PFS (p = 0.039) and trend of better OS (p = 0.077). Post-NACT PD-L1 and TIL levels were not associated with survival outcomes. PD-L1 level (p = 0.001) and TIL level (p <0.001) were significantly increased before and after NACT. An increase in TIL in response to NACT was associated with shorter PFS compared to patients with decreased TIL levels (p = 0.020). A change in the PD-L1 level had no impact on the prognosis. In whole-transcriptome sequencing, stromal score (p = 8.6e-0.7), immune score (p = 4e-0.6), and CYT score (p = 2.1e-0.5) were significantly increased after NACT. Conclusions: Pre-NACT TIL level was associated with a survival benefit in advanced-stage ovarian cancer. By contrast, increased TIL level was an adverse prognostic factor for survival outcomes. Further research is needed to find a patient group that can benefit from immunotherapy in the NACT setting.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study

BackgroundThe mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer.MethodsFrom the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed.ResultsOverall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032).ConclusionsNAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with “platinum-resistant recurrence”. Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

Systematic lymph node dissection during interval debulking surgery for advanced epithelial ovarian cancer: a systematic review and meta-analysis.

ObjectiveTo evaluate the efficacy and safety of systematic lymph node dissection (SyLND) at the time of interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC).MethodsSystematic literature review of studies including AEOC patients undergoing SyLND versus selective lymph node dissection (SeLND) or no lymph node dissection (NoLND) after neoadjuvant chemotherapy (NACT). Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included severe postoperative complications, lymphocele, lymphedema, blood loss, blood transfusions, operative time, and hospital stay.ResultsNine retrospective studies met the eligibility criteria, involving a total of 1,660 patients: 827 (49.8%) SyLND, 490 (29.5%) SeLND, and 343 (20.7%) NoLND. The pooled estimated hazard ratios (HR) for PFS and OS were, respectively, 0.88 (95% confidence interval [CI]=0.65–1.20; p=0.43) and 0.80 (95% CI=0.50–1.30; p=0.37). The pooled estimated odds ratios (ORs) for severe postoperative complications, lymphocele, lymphedema, and blood transfusions were, respectively, 1.83 (95% CI=1.19–2.82; p=0.006), 3.38 (95% CI=1.71–6.70; p<0.001), 7.23 (95% CI=3.40–15.36; p<0.0001), and 1.22 (95% CI=0.50–2.96; p=0.67).ConclusionDespite the heterogeneity in the study designs, SyLND after NACT failed to demonstrate a significant improvement in PFS and OS and resulted in a higher risk of severe postoperative complications.Trial RegistrationPROSPERO Identifier: CRD42022303577

Impact of residual disease at interval debulking surgery on platinum resistance and patterns of recurrence for advanced-stage ovarian cancer

ObjectiveTo evaluate the impact of size and distribution of residual disease after interval debulking surgery on the timing and patterns of recurrence for patients with advanced-stage epithelial ovarian cancer.MethodsPatient demographics...

Pilot experience using tumor-based next generation sequencing increases compliance and reduces barriers for ovarian cancer genetic testing

<h3>Objectives:</h3> Although hereditary risk assessment is advised for all ovarian/tubal/peritoneal (OTP) cancer patients, a variety of barriers limit universal compliance. A workflow using tumor-based next generation sequencing (NGS) germline testing implemented by the pathologist at the time of primary or interval debulking surgery. The objective of this study is to report compliance and turnaround time of a pilot workflow of germline testing via tumor-based NGS in OTP cancer. may reduce some of these barriers. <h3>Methods:</h3> We identified all patients with a new diagnosis of epithelial OTP carcinoma who underwent primary or interval debulking surgery from January to August 2020. All patients were recommended to undergo tumor and germline sequencing, either through our institutional NGS platform or through commercial sequencing. We compared time to results as well as influence of results on maintenance/second-line therapy. <h3>Results:</h3> We identified 35 patients with a median age of 61 (range 29-78) and a median follow-up time of 5 months (range 0-13). Our stage breakdown included 8 Stage I, 4 Stage II, 20 Stage III, and 3 Stage IV patients. A total of 24 patients had high grade serous carcinoma, with 5 endometrioid, 3 clear cell, 2 mucinous, and one high grade NOS tumor. A total of 11 patients underwent interval debulking surgery after neoadjuvant chemotherapy. All but 2 (94.2%) of patients received a genetic counseling referral. A total of 2 patients did not have sequencing performed, while 1 patient did not have enough tumor for sequencing at the time of interval debulking surgery. A total of 10 patients had both tumor and germline sequencing performed at the time of tumor testing, while 20 others had tumor only sequencing. For those patients who did not have a known hereditary germline mutation prior to surgery, the mean turnaround time for germline genetic testing results was 26.5 days (range 19-51) in the NGS + germline group whereas the median turnaround time after commercial testing was 75 days (regardless of primary or interval debulking, range 19-202), p=0.006. A total of 5 patients were identified as germline carriers of the <i>BRCA1</i> or <i>BRCA2</i> mutation, with 1 addition germline finding of a pathogenic variant in ATM. An additional 5 patients had somatic pathogenic mutations in homologous recombination repair pathway genes, all of whom are receiving or being considered for PARP inhibitor maintenance after primary treatment. <h3>Conclusions:</h3> Combining somatic and germline tumor testing at the time of staging/debulking surgery requires upfront coordination with pathology and patient consent, but streamlines the genetic testing process to improve testing rates allow timely results for treatment planning. This approach may also identify additional patients with homologous recombination deficient tumors through simultaneous somatic mutation assessment.

Impact of systematic lymphadenectomy at the time of interval debulking surgery on the survival of patients with advanced-stage epithelial ovarian carcinoma following neoadjuvant chemotherapy

<h3>Objectives:</h3> In light of evidence from the LION trial, we aimed to evaluate the impact of systematic lymphadenectomy (LN) at the time of interval debulking surgery (IDS) for patients with advanced stage epithelial ovarian carcinoma. <h3>Methods:</h3> Patients with stage III-IV epithelial ovarian carcinoma without a history of another tumor who underwent neoadjuvant chemotherapy and underwent interval debulking with complete gross resection (CGR) were identified in the National Cancer Database (2010-2015). Based on pathology report patients who did not undergo any lymphadenectomy and those who underwent systematic lymphadenectomy (defined as at least 20 lymph nodes removed) were selected for further analysis. Median overall survival was compared with the log-rank test and a Cox multivariate model was constructed to control for confounders. <h3>Results:</h3> A total of 1060 patients who met the inclusion criteria were identified. Median patient age was 64 years while the majority had serous tumors (95.8%) and did not have co-morbidities (79.2%). Systematic LND was performed for 125 (11.8%) patients with a median of 29 LNs (range 20-72) removed. Rate of positive LNs was 62.4%, while median number of positive LN was 5 (range 1-28). Patients who underwent systematic LND had higher rate of unplanned readmission (8.9% vs 1.6%, p<0.001), and median hospital stay (6 vs 4 days, p<0.001). Median OS for patients who did not undergo LND was 40.38 months compared to 44.19 for those who underwent systematic LND, p=0.40. After controlling for patient age, insurance status, race, presence of comorbidities, tumor histology, and disease stage, performance of systematic LND was not associated with better survival (HR: 0.98, 95% CI: 0.80, 1.19). Lastly, median overall survival of patients with positive LNs (n=78) was 40.05 months. <h3>Conclusions:</h3> Systematic lymphadenectomy is rarely performed at the time of interval debulking surgery and was not associated with a survival benefit.

Bowel resection at the time of interval cytoreductive surgery for advanced ovarian cancer adversely impacts survival: results from two orthogonal cohorts

<h3>Objectives:</h3> To evaluate the survival impact of bowel resection at the time of interval debulking surgery (IDS) for primary advanced epithelial ovarian cancer (EOC). <h3>Methods:</h3> Patients with stage IIIC or IV EOC, diagnosed after 2010, who underwent neoadjuvant chemotherapy followed by IDS were identified from a single institution tumor registry (SITR) and from the National Cancer Data Base (NCDB). Kaplan-Meier survival analysis and Cox proportional hazards models were performed comparing outcomes for patients who underwent bowel resection to those that did not. Overall survival over three years after patients started neoadjuvant chemotherapy was compared between patients who did and did not undergo bowel resection. This study used two distinct datasets which collected varying post-operative outcomes– thus some findings were not able to be compared directly. Progression free survival (PFS) and peri-operative outcomes were evaluated in the SITR only. <h3>Results:</h3> In total, 195 patients met inclusion criteria from the SITR; 9,824 met criteria from the NCDB. The rates of at least one bowel resection were identical between the two cohorts: 43 (22%) and 2,126 (22%). The rates of R0 resection were also similar: 52% and 45%. Sub-optimal resection (residual disease >1cm) was 4% among SITR and 24% among the NCDB; these rates were not different between bowel resection and non-bowel resection cohorts. Patients that required bowel resection had worse three-year survival in both cohorts. Hazard ratio (HR) for death with bowel resection was 2.13 (p<0.01) among SITR and 1.15 (p<0.01) among NCDB controlling for age, R0 resection, and stage of disease. The NCDB survival analysis also controlled for Charlson-Deyo Score. Progression free survival (PFS) was only calculated from SITR and did not differ between groups (HR 1.0, p=1.0). Among the SITR cohort, patients who underwent bowel resection were found to experience significant perioperative complications [intensive care unit admission, acute kidney injury, ileus, surgical injury to bowel or urinary tract, post-operative infection], HR 3.44 (p<0.01), and longer hospital stay (median stay 7.5 vs. 4 days, p<0.01). Among the NCDB cohort, bowel resection was associated with increased rates of unplanned hospital readmission within 30 days of surgery (OR 1.9, p<0.001). <h3>Conclusions:</h3> We demonstrate in both a single academic institution and in a national cohort a significantly increased risk of 3-year mortality among patients who undergo bowel resection at the time of IDS. Identifying modifiable risk factors that contribute to bowel resection and decreasing the related sequelae of bowel resections for patients undergoing IDS is warranted.

Sarcopenia is a predictor of chemotherapy response score at the time of interval debulking surgery in advanced epithelial ovarian carcinoma

<h3>Objectives:</h3> To examine the relationship between sarcopenia as measured by skeletal muscle index (SMI) on CT and chemotherapy outcomes and pathologic response after neoadjuvant chemotherapy (NACT) in patients with advanced epithelial ovarian carcinoma (EOC). <h3>Methods:</h3> Our institutional database was retrospectively queried for all women with advanced EOC who underwent NACT between 2007-2020. Demographic and clinical variables including number of NACT cycles, dose reductions, and dose delays were collected. Treatment response by 3-tier pathologic chemotherapy response score (CRS) and residual disease at time of interval cytoreductive surgery were recorded. Pre-treatment and post-treatment contrast enhanced CT scans were reviewed by two subspecialty radiologists to determine baseline and post-treatment SMI. SMI was calculated by dividing total psoas muscle and paraspinal muscle area (m²) (measured at the level of L4 vertebrae by height (cm²) squared. Patients were stratified to account for change in SMI after NACT and grouped into patients with >2% decrease in SMI (group 1) and increase or ≤2% decrease in SMI (group 2). SMI was also analyzed as a continuous variable for association with demographic and clinical factors by Kruskal-Wallis test/Spearman's correlation (results summarized as median [25th, 75th percentiles]). <h3>Results:</h3> Among 77 patients who met inclusion criteria, there were no significant differences between stage at diagnosis, baseline performance status, frailty scores, number of NACT cycles, histology, or tumor grade between the two groups. However, pretreatment Ca125 was higher in patients in group 2 (p=0.031). When SMI was analyzed as a continuous variable, age at diagnosis was negatively associated with higher SMI (-0.47, (-0.63, -0.28, p=<0.001). Number of completed NACT cycles was negatively associated with higher SMI -0.23 (-0.43, -0.0, p=0.048). Lower CRS, indicating no/minimal chemotherapy response at the time of interval cytoreduction was associated with lower SMI (0.45, (0.01, 0.75), p=0.043) despite no difference in residual disease. <h3>Conclusions:</h3> Sarcopenia as measured by SMI is associated with older age and increased number of NACT cycles in our patient population. Additionally, sarcopenia was predictive of lower chemotherapy response at the time of interval cytoreduction. Data collection is ongoing to further delineate the relationship between sarcopenia and response to NACT.

If looks could kill: morphologic subtypes of high-grade serous ovarian cancer

<h3>Objectives:</h3> Despite similar histologic appearance amongst high-grade serous ovarian cancers (HGSOC), anecdotally there are differences in gross appearance. However, no systematic framework to classify morphologic differences exists. Therefore, we aimed to determine whether high-grade serous ovarian cancers (HGSOC) can be reliably divided into distinct gross morphologic subtypes and to assess clinical outcomes and molecular features of these subtypes. <h3>Methods:</h3> A retrospective review was performed of video-recordings from patients who underwent laparoscopic assessment of disease burden prior to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). Video recordings were reviewed by at least 2 physicians. A total of 4 sites (diaphragm, omentum, peritoneum, and pelvis) were assessed and classified as type I (deep, infiltrative disease with distortion of surrounding tissue) or type II (superficial, exophytic disease bordered by normal tissue). Tumor tissues from 16 of these chemotherapy-naïve patients were analyzed by multi-platform omics (RNA sequencing, proteomics). Clinical outcomes were assessed utilizing a prospectively collected database and compared by morphology using t-test or Fisher's exact test. <h3>Results:</h3> Of the 99 evaluable patients, 60 exhibited uniform morphology at all involved metastatic sites (65% type I and 35% type II), and 81 exhibited a predominating morphology (58% type I and 42% type II). A total of 164 images were reviewed by a third physician with 83.5% inter-rater concordance (κ=0.6446). Patients with uniform type 1 (n=34)tumor morphology were more likely to exhibit an excellent response to NACT (defined as radiologic or CA-125 complete response) than those with type II (n=16) tumor morphology (47% vs 18%, p=0.13). Patients with type II predominant tumor morphology had a significantly higher estimated blood loss at the time of interval debulking surgery (p=0.008) as well as longer operative time (p=0.03) compared with type I tumor morphology. Patients with complete type II morphology were more likely to have a modified Fagotti score of <8 (p=0.026), and thus were more likely to be triaged to PDS. On histopathologic review of 7 type I cases and 4 type II cases, no obvious histo-pathological pattern dominated either type. We identified distinct molecular differences between the 2 types, including increased TGF-β expression in type I and increased MYC expression in type II. Type I tumors seem to have abundant stroma and are immunologically active, whereas type II tumors seem to be dominated by cancer cells, have little stroma, and are immunologically cold. <h3>Conclusions:</h3> There are at least two distinct gross morphological patterns of HGSOC with unique molecular differences and responses to chemotherapy. These findings could have major clinical implications for tailored therapeutic strategies.

What can we learn from the 10 mm lymph node size cut-off on the CT in advanced ovarian cancer at the time of interval debulking surgery?

IntroductionThe benefit of a systematic lymphadenectomy is still debated in patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. Materiel and methodsA retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005 and 2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. Results158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at ‘high risk’ (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. ConclusionPresence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

Chemotherapy response score is a prognostic tool in advanced stage endometrial cancer patients treated with neoadjuvant chemotherapy

Chemotherapy response score (CRS) applied to omental metastases obtained at the time of interval debulking surgery (IDS) has been used to quantify response to neoadjuvant chemotherapy (NACT) in advanced stage ovarian cancer patients. The score has been correlated with both progression free survival (PFS) and overall survival (OS). This CRS score has not been studied in advanced stage endometrial cancer. The objectives of the current study are 1) to apply the CRS to omental and adnexal metastases obtained at IDS of advanced stage endometrial cancer patients and 2) to investigate the association between the CRS score and surgical outcome, PFS and OS.

No residual disease at the time of interval debulking surgery: It is all or nothing

No residual disease at the time of interval debulking surgery: It is all or nothing

Chemotherapy response score as a prognostic tool in advanced-stage endometrial cancer patients treated with neoadjuvant chemotherapy.

e18095 Background: Chemotherapy response score (CRS) applied to omental metastases obtained at the time of interval debulking surgery (IDS) has been used to quantify response to neoadjuvant chemotherapy (NACT) in advanced stage ovarian cancer patients. The score has been correlated with both progression free survival (PFS) and overall survival (OS). This CRS score has not been studied in advanced stage endometrial cancer. The aim of the current study is 1) to apply the CRS to omental and adnexal metastases obtained at IDS of advanced stage endometrial cancer patients and 2) to investigate the association between the CRS score and surgical outcome, PFS and OS. Methods: Patients with clinical stage III-IV endometrial cancer (endometrioid, serous, clear cell, carcinosarcoma) were identified through the endometrial cancer database, billing data and tumor board notes (2003-2019) from the University of Chicago. Patients were included if they received NACT followed by IDS (R0 no gross residual, optimal &lt; 1 cm residual or suboptimal ≥ 1 cm residual disease). Patients who received pre-operative radiotherapy were excluded. Pathology specimens from primary and metastatic sites were reviewed by the study pathologist blinded to clinical outcome. Histologic specimens from the omental and adnexal metastases were assigned a single quantitative score of 1 (no/minimal tumor response), 2 (appreciable tumor response with viable tumor) or 3 (complete/near complete response) using the CRS system as previously described by Bohm et al (JCO 2015; 33:2457-63). Results: A total of 40 patients were available for analysis. Median age 63.5, median BMI 32 kg/m2. There is a significant association between omental CRS and optimal IDS (p = 0.029) but no significant association between the adnexal CRS and optimal IDS (p = 0.145). Cox regression analysis identified CRS omentum [2: HR = 0.095, p = 0.001; 3 HR = 0.088, p = 0.004] and CRS adnexa [2: HR = 0.24, p = 0.007] predictive of PFS. There was not enough evidence to comment on any association between CRS with OS. Conclusions: Omental CRS2, CRS3 are associated with optimal IDS. Omental CRS2, CRS3 and adnexal CRS2 are prognostic for improved PFS in stage III – IV endometrial cancer patients after neoadjuvant chemotherapy. [Table: see text]

Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.

Despite its widespread use, until recently, there was no randomized evidence for hyperthermic intraperitoneal chemotherapy (HIPEC) versus surgery without HIPEC for ovarian cancer. Recently, a Dutch study (OVHIPEC) reported benefits in both progression-free survival (PFS) and overall survival (OS) gained from the use of HIPEC at the time of interval debulking surgery (IDS) for stage III ovarian carcinoma, whereas a Korean randomized trial failed to show a benefit of HIPEC for patients with ovarian cancer undergoing primary debulking surgery or IDS. In colorectal cancer, 2 randomized trials failed to show an improvement in survival with HIPEC. In addition to these contradictory results, there are a number of aspects of the Dutch OVHIPEC trial in ovarian cancer that can be criticized. Some criticisms include a reduction of the number of patients needed to be randomized because of too slow accrual; much lower PFS and OS in both arms than expected according to the statistical plan; the small size of the study, with imbalances between the 2 arms (eg, more low-grade tumors in the HIPEC arm); the timing of randomization before the start of IDS; the lack of clear inclusion criteria for neoadjuvant chemotherapy; and the heterogeneity of the results, with the largest effect shown at the smaller centers. Furthermore, it is questionable whether the adverse events were reported completely. In conclusion, data about HIPEC for ovarian cancer in general are not convincing, and they do not change the standard of care, which remains for ovarian cancer surgery and intravenous chemotherapy.