Infiltrative pattern of invasion is independently associated with shorter survival and desmoplastic stroma markers FAP and THBS2 in mucinous ovarian carcinoma.

AIMS: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer histotype with generally good prognosis when diagnosed at an early stage. However, MOC with the infiltrative pattern of invasion has a worse prognosis, although to date studies have not been large enough to control for covariables. Data on reproducibility of classifying the invasion pattern are limited, as are molecular correlates for infiltrative invasion. We hypothesized that the invasion pattern would be associated with an aberrant tumour microenvironment. METHODS AND RESULTS: Four subspecialty pathologists assessed interobserver reproducibility of the pattern of invasion in 134 MOC. Immunohistochemistry on fibroblast activation protein (FAP) and THBS2 was performed on 98 cases. Association with survival was tested using Cox regression. The average interobserver agreement for the infiltrative pattern was moderate (kappa 0.60, agreement 86.3%). After reproducibility review, 24/134 MOC (18%) were determined to have the infiltrative pattern and this was associated with a higher risk of death, independent of FIGO stage, grade, and patient age in a time-dependent manner (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 3.0-34.5). High stromal expression of FAP and THBS2 was more common in infiltrative MOC (FAP: 60%, THBS2: 58%, both P < 0.001) and associated with survival (multivariate HR for FAP: 1.5 [95% CI 1.1-2.1] and THBS2: 1.91 [95% CI 1.1-3.2]). CONCLUSIONS: The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

POLE-mutated Endometrial "Carcinosarcoma".

The molecular subtype classification of endometrial carcinomas has conceptually changed our approach to this disease. However, open questions remain about how to integrate certain histotype diagnoses with the molecular subtype. We report 2 cases with morphologic suspicion for endometrial carcinosarcoma, that still fell short of the essential criteria for diagnosing carcinosarcoma. On subsequent molecular testing pathogenic POLE mutations were detected and a descriptive diagnosis of endometrial endometrioid carcinomas, low-grade with a homologous sarcoma component was rendered. This challenges the existence of POLE-mutated "carcinosarcoma."

TP53 as a Diagnostic Aid in the Distinction of Ovarian Mucinous Borderline Tumors From Mucinous Carcinoma.

Ovarian mucinous borderline tumors (MBTs) are clinically managed as benign neoplasms while the management of ovarian mucinous carcinomas (MC) is dependent on tumor stage. Despite the standardization of sampling of ovarian mucinous neoplasms, limited interobserver reproducibility between MBT and MC persists. Based on our recent finding that abnormal TP53 expression is associated with unfavorable outcome in MBT, we hypothesized that TP53 status might improve the reproducible distinction of MBT from MC. A virtual slide set of 85 consecutive ovarian mucinous neoplasms received at a single institution, with each case represented by 3 full sections, were reviewed by 3 pathologists in 2 iterations. The initial assessment was based solely on morphologic review, while the second iteration was performed with knowledge of TP53 status. The reproducibility of a trinary categorization (MBT, MBT with intraepithelial carcinoma [IEC], MC) significantly improved from a κ of 0.60 based on the initial morphologic assessment to a κ of 0.76 (t-test, P =0.0042) after consideration of TP53 immunohistochemistry (IHC) results. Six out of 85 patients died of disease, and in 2 of them, at least 1 pathologist assessed MBT with IEC and not MC even after integration of TP53 IHC. With the integration of TP53 IHC, substantial interobserver agreement for MBT and MC can be reached, particularly in cases with an uncertain degree of confluent growth. TP53 IHC can also be used to highlight and support the presence of IEC in MBT, however, discordances remained in 2 cases with adverse outcome.

Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P =0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P =0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival ( P =0.103) or progression-free survival ( P =0.240) at 5 yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P =0.025)] but not overall survival ( P =0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.

BACKGROUND: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. METHODS: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. RESULTS: Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant. CONCLUSION: We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer.

WHAT IS THIS SUMMARY ABOUT?: Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study. WHAT WERE THE RESULTS?: The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects. WHAT DO THE RESULTS MEAN?: The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients.

p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial.

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLE wildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n = 89, 68%), followed by null (n = 12, 9%) and cytoplasmic (n = 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLE mutations and/or MMRd (n = 22/27; p < 0.001). Agreement between p53 IHC and TP53 NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC).

Management of Gynecologic Cancer During COVID-19 Pandemic: South Asian Perspective.

Management of gynecological cancers has suffered during the pandemic, partly due to lockdown and partly due to directing resources to manage COVID-19 patients. Modification of gynecological cancer management during this pandemic is recommended. Cervical cancer patients who present with stage IA1 disease can have a delay of up to 8 weeks for surgical treatment, considering the slow tumor growth rate. Women with stages IA2, IB1, IB2, IIA1 must undergo radical hysterectomy and lymphadenectomy within 6 to 8 weeks. In areas where surgical treatment is not available, patients should be referred for radiation therapy/areas with adequate surgical expertise. The surgical option is attractive for early cancers during the COVID era, as it involves a single visit compared to the multiple visits required for chemoradiation. The value of lymph node staging needs to be reconsidered. Neoadjuvant chemotherapy should be given preference over primary cytoreductive surgery for advanced ovarian cancers. Surgeries, which demand extended surgical time such as Hyperthermic Intraperitoneal Chemotherapy and pelvic exenterations, should be avoided during this pandemic. For patients scheduled for interval surgery after two or three neoadjuvant cycles, six cycles of chemotherapy should be considered before surgery is performed. For early-stage, low-grade endometrial cancer, consideration should be given to medical management until surgery is possible. The above recommendations have been made keeping in mind the geography, patient load, and availability of resources available to health care providers from southeast Asia. They might not be applicable globally and every practitioner should take call regarding patient's management as per availability of resources and loco-regional circumstances. The implementation of recommended international guidelines for the management of gynecologic cancers should take precedence. Each modification to the standard approach should be approved by a multidisciplinary team depending on the condition of the patients and the locoregional circumstances.

Prognostic and Theranostic Biomarkers in Ovarian Clear Cell Carcinoma.

In this study, we aimed to test whether prognostic biomarkers can achieve a clinically relevant stratification of patients with stage I ovarian clear cell carcinoma (OCCC) and to survey the expression of 10 selected actionable targets (theranostic biomarkers) in stage II to IV cases. From the population-based Alberta Ovarian Tumor Type study, 160 samples of OCCC were evaluated by immunohistochemistry and/or silver-enhanced in situ hybridization for the status of 5 prognostic (p53, p16, IGF2BP3, CCNE1, FOLR1) and 10 theranostic biomarkers (ALK, BRAF V600E, ERBB2, ER, MET, MMR, PR, ROS1, NTRK1-3, VEGFR2). Kaplan-Meier survival analyses were performed. Cases with abnormal p53 or combined p16/IFG2BP3 abnormal expression identified a small subset of patients (6/54 cases) with stage I OCCC with an aggressive course (5-yr ovarian cancer-specific survival of 33.3%, compared with 91.5% in the other stage I cases). Among theranostic targets, ERBB2 amplification was present in 11/158 (7%) of OCCC, while MET was ubiquitously expressed in OCCC similar to a variety of normal control tissues. ER/PR showed a low prevalence of expression. No abnormal expression was detected for any of the other targets. We propose a combination of 3 biomarkers (p53, p16, IGF2BP3) to predict prognosis and the potential need for adjuvant therapy for patients with stage I OCCC. This finding requires replication in larger cohorts. In addition, OCCC could be tested for ERBB2 amplification for inclusion in gynecological basket trials targeting this alteration.

Equivalent Survival of p53 Mutated Endometrial Endometrioid Carcinoma Grade 3 and Endometrial Serous Carcinoma.

TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada. Mutant-type p53 expression, including overexpression, complete absence, or cytoplasmic expression, was distinguished from the wild-type pattern. Statistical associations with clinico-pathological parameter, other key biomarkers, and survival analyses were performed. P53 mutant-type immunohistochemistry was observed in all 126 ESC and in 47/200 (23.5%) EEC3. ESC and p53 mutated EEC3 had an unfavorable outcome compared with p53 wild-type EEC3 (hazard ratio=2.37, 95% confidence interval=1.48-3.80, P=0.003, hazard ratio=2.19, 95% confidence interval=1.16-4.12, P=0.016, respectively) in multivariable analyses adjusted for age, stage, center, and presence of lymph-vascular invasion. There was no significant difference in survival between ESC and p53 mutated EEC3 in multivariable analysis. Furthermore, p53 mutated EEC3 and ESC almost completely overlapped in univariate survival analysis when mismatch repair (MMR)-deficient cases were excluded, which suggests that EEC3 harboring combined MMR deficiency and TP53 mutations behave more according to the MMR status. Significant differences between p53 mutated MMR-proficient EEC3 and ESC in PTEN and p16 expression status remained. p53 mutated, MMR-proficient EEC3 and ESC have overlapping survival significantly different from p53 wild-type EEC3, which justifies a similar treatment with current non-targeted standard therapy. Although this is so, separate classification should continue due to biological differences that will become important for future targeted therapy.

Patient-Reported Symptom Burden Near the End of Life in Patients With Gynaecologic Cancers.

OBJECTIVE: There are limited data on patient-reported outcomes near the end of life in patients with gynaecologic cancers. This study aimed to assess the symptom burden in the last 6 months of life in a real-world cohort. METHODS: Patients diagnosed with metastatic gynaecologic malignancies from 2016 to 2019 who completed the revised Edmonton Symptom Assessment System (ESASr) questionnaire within 6 months of death in a large Canadian province were identified. Patient-reported symptom scores were categorized as none to mild (0-3) and moderate to severe (4-10). Individual symptoms were subsequently grouped into physical, psychological, and total subscores. The severity of symptoms was further analyzed for any associations with age, time to death, and primary tumour site (ovarian vs. uterocervical and vulvovaginal). RESULTS: We identified 107 patients with gynaecologic malignancies including 59 ovarian, 29 uterocervical, and 19 vulvovaginal cancers. The median ages at diagnosis and questionnaire completion were 64 and 65 years, respectively. The median time from completing the ESASr questionnaire to death was 65 days. Overall, physical and psychological symptoms were moderate to severe in 57.9% and 40.2% of patients, respectively. Among the individual symptoms, tiredness was the most commonly reported moderate to severe symptom (74.9%), while shortness of breath was least commonly reported (31.6%). While physical (P < 0.001) and total symptom (P = 0.009) subscores were more likely to be moderate to severe in intensity as death approached, the psychological subscore (P = 0.744) had no relationship with time to death. Longer time to death was predictive of lower physical (P = 0.002) and total symptom (P = 0.002) subscores, while a primary uterocervical cancer site was associated with a lower psychological symptom subscore (P = 0.042). CONCLUSIONS: In the real-world setting, unique symptom trajectories can emerge for patients with gynaecologic cancer near the end of life. Knowledge of these specific symptom patterns can help inform the development and delivery of targeted palliative interventions to improve quality of life for these patients.

PIK3CA mutation and CNV status and post-chemoradiotherapy survival in patients with cervical cancer.

PURPOSE: This study aimed to describe the prognostic value of PI3K/AKT pathway mutations in a large cohort of patients with cervical cancer. EXPERIMENTAL DESIGN: Patients with pre-treatment archival specimens, diagnosed with FIGO stages IB-IVA cervical cancer between 1998 and 2014 and treated with radical, curative intent chemoradiotherapy (CRT) at a single center were identified. Mutational status was determined by next generation sequencing and PIK3CA copy number (CNV) was assessed by digital PCR. RESULTS: 190 patients with available pre-treatment tumor specimens were identified. Median OS and PFS were 57.4 and 46.0 months, respectively. A total of 161 tumors were successfully sequenced; 60 (37.3%) had PI3K/AKT pathway mutations, with 50 (30.1%) having PIK3CA hotspot mutations. PIK3CA CNV gain was noted in 79 (59.2%) of the 154 successfully analyzed. On univariate analysis, PIK3CA mutation was associated with poor OS (HR 1.73; 95% CI: 1.03-2.92; p = .037) but not PFS (HR 1.38; 0.84-2.28; p = .204). Absence of any PI3K/AKT pathway mutation was associated with improved OS (HR 1.68; 1.01-2.81; p = .046) but not PFS (HR 1.50; 0.93-2.43; p = .202). Associations were not maintained when adjusting for clinical factors. On univariate analysis, PIK3CA mutation positive, CNV normal tumors were associated with poorer OS (HR 2.55; 1.18-5.50; p = .017) and trend to worse PFS (HR 1.87; 0.90-3.83; p = .094) when compared to those with CNV gain and wildtype PIK3CA. CONCLUSIONS: PI3K/AKT pathway mutations are common in cervical cancer. Consideration of PIK3CA mutational status with CNV status may be important in predicting outcome in cervical cancer patients.

Factors Affecting Overall Survival in Premenopausal Women With Uterine Leiomyosarcoma: A Retrospective Analysis With Long-Term Follow-Up.

OBJECTIVE: Premenopausal women with uterine leiomyosarcoma experience different issues than menopausal women with this malignancy. This study evaluated the clinical profile and factors affecting survival outcomes in premenopausal women with uterine leiomyosarcoma. METHODS: We conducted a retrospective analysis of patients with uterine leiomyosarcoma, diagnosed between January 2008 and December 2016. Data were collected from the Alberta Cancer Registry, which reflects all patients in the province. Thirty-eight patients were included in the study, of whom 21 were alive on the last date of review (31 December, 2019). RESULTS: The median follow-up period was 86 months. Mean patient age was 44.6 ± 5.7 years. The 5-year survival rate was 34.2%; 45% of patients presented with stage I or II disease and 55%, with stage III or IV. There was no clinical suspicion of malignancy prior to surgery in about 60% of cases. Ovarian preservation was performed in about 34% of cases. Forty-five percent of patients had received chemotherapy and 26%, radiotherapy. Almost 90% had unspecified leiomyosarcoma. Univariate analysis of factors likely to affect overall survival showed that older age at diagnosis (HR 1.19; 95% CI 1.05-1.34, P = 0.005), lymphovascular invasion (HR 9.81; 95% CI 2.88-33.51, P = 0.00), and no radiation therapy (HR 2.60; 95% CI 0.99-6.87, P = 0.05) were associated with worse overall survival. A multivariate analysis of these risk factors showed only lymphovascular invasion of the tumour to be a significant risk factor affecting overall survival. (HR 18.07; 95% CI 4.23-77.15, P =0.00). CONCLUSION: Multivariate analysis showed lymphovascular invasion of tumour to be a significant risk factor affecting overall survival in premenopausal women with uterine leiomyosarcoma. Ovarian preservation, lymph node positivity, age, treatment strategy, hormone receptor status, and grade of tumour were not found out to be significant prognostic variables.

Impact of transversus abdominis plane blocks versus non-steroidal anti-inflammatory on post-operative opioid use in ERAS ovarian cancer surgery.

BACKGROUND: Treatment of ovarian cancer often requires extensive surgical resection. The transversus abdominis plane (TAP) block has been utilized in benign gynecologic surgery to decrease post-operative pain and opioid use. We hypothesized that TAP blocks would decrease total opioid use in the first 24 hours and decrease length of stay following staging and cytoreductive surgery for ovarian cancer compared with either no local anesthetic or local wound infiltration alone. METHODS: All patients undergoing surgery for ovarian cancer from November 2016 to June 2017 were included in this retrospective cohort study. Median opioid use at 24, 48, and 72 hours post-operatively, as well as length of stay, were assessed. Multivariate median regression analysis was performed to adjust for potential confounders: post-operative non-steroidal anti-inflammatory drug (NSAID) usage, pre-operative opioid consumption, and extent of cytoreductive surgery. Length of stay was compared using Cox regression analysis. RESULTS: One-hundred-and-twenty patients were included in the analysis. Eighty-two patients had a TAP block, while 38 did not. After adjusting for potential confounders there was no difference in median 24 hours opioid consumption (p=0.29) or length of stay (HR 0.95, p=0.78) between patients receiving TAP block compared with those without. After adjusting for potential confounders, patients receiving scheduled NSAIDs had a 2.6-fold greater likelihood of being discharged (p<0.0005) and a significant reduction in median opioid use at 24 hours (23.5 vs 14.5 mg) (p=0.017) compared with those patients without NSAIDs. DISCUSSION: Post-operative administration of NSAIDs, but not TAP block, was associated with a decrease in post-operative opioid use and length of stay following surgery for ovarian cancer. Further investigation into alternative regional anesthetics for Enhanced Recovery after Surgery (ERAS) protocols is warranted.

The Impact of Gynaecological Tumour Board Rounds on Patient Care.

OBJECTIVE: The goal of this study was to determine the impact of tumour board rounds (TBRs) on the additional management of patients with gynaecologic malignancy. METHODS: A retrospective chart review of 1604 patients discussed between January 2011 and December 2013 at gynaecologic TBRs was conducted to determine the frequency and type of diagnostic discrepancies found post-TBRs and their potential impact on additional patient management. A discrepancy was defined as major if it affected patient management by cancelling, initiating, or modifying treatment; otherwise, the discrepancy was minor. Data collected included patients' demographics, pre- and post-TBR diagnoses, and management. RESULTS: The patients' mean age was 57.6 ± 14.1. Endometrial disease accounted for (43%) of the TBRs. The remaining sites were ovarian (25%), cervical (23%), and others (9%). Overall, 13.2% (n = 212) had a discrepancy; 3.4% (n = 54) of these discrepancies were major, and 9.9% (n = 158) were minor. Most major discrepancies related to changes in the tumours' primary site or stage, and most minor discrepancies were related to changes in tumour histotype. Among the 54 (25.5%) major discrepancies, 18 (33.3%) occurred in patients who had their additional management cancelled, 17 (31.5%) required chemotherapy, 4 (7.4%) required a change in the chemotherapy regimen, 10 (18.5%) required additional surgery, and 5 (9.3%) required chemoradiation. CONCLUSION: The 13% frequency of discrepancies, approximately 26% of which were major and resulted in changes in patient management, highlights the importance of TBRs as a quality tool.

Examining Survival Outcomes of 852 Women With Advanced Ovarian Cancer: A Multi-institutional Cohort Study.

INTRODUCTION: This study examines patterns of clinical practice in the management of women with advanced high-grade serous ovarian carcinoma (HGSC). METHODS: A total of 852 patients with advanced HGSC were included in this retrospective cohort analysis. Patients underwent primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT). Wilcoxon rank-sum test and χ test were applied. Univariate- and multivariate-analyses were performed, and survival outcomes were measured using Kaplan-Meier curves. RESULTS: A total of 449 (53%) of 852 patients underwent PCS, and 403(47%) of 852 patients underwent NACT. The median 5-year overall survival (OS) was 3.89 in PCS and 2.48 in NACT. Patients with 0 mm residual had OS of 4.66, compared with 1- to 9-mm residual (OS = 2.80) and 10-mm residual or longer (OS = 2.50). The survival advantage harbored by the extent of surgical cytoreduction was more pronounced in PCS compared with NACT (P < 0.001). Patients who had PCS with 1- to 9-mm residual had similar OS to NACT patients with 0-mm residual (P = 0.17) and superior OS to NACT with 1- to 9-mm residual (P < 0.001). CONCLUSIONS: In this multicenter study, 53% of women with advanced HGSC seen by a gynecologic oncologist were selected for PCS. Survival was longer in patients who underwent PCS than patients who underwent NACT. Within each group, survival was highest in those who had complete cytoreduction to 0-mm residual disease. We believe all patients with advanced HGSC should be assessed by a gynecologic oncologist for the feasibility of surgical resection. Primary cytoreductive surgery should be the favorable treatment modality with the goal of complete resection to 0 mm residual disease. Importantly, if 0 mm residual is not feasible, PCS to a residual of 1 to 9 mm should be attempted given the survival advantage in this group over patients who were treated with NACT.

Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8+ T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8+ T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8+ T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.

Neoadjuvant chemotherapy and chemotherapy cycle number: A national multicentre study.

OBJECTIVES: Six cycles of consolidation chemotherapy have become the standard for ovarian cancer treatment regimen following primary cytoreduction, yet with neoadjuvant chemotherapy (NAC), only 3 consolidation cycles are used. This study examines the effects of number of chemotherapy cycles in women with ovarian cancer that are being treated with neoadjuvant chemotherapy. In addition, we examined the effect of number of cycles on survival on consolidation and total chemotherapy. METHODS: All patients with stage IIIC and IV high grade serous carcinoma (HGSC) were identified at 4 major Canadian cancer centers treated with NAC. A retrospective chart review was conducted using the medical charts and registry databases. RESULTS: 403 NAC patients were identified. 47% had zero residual disease. Chemotherapy cycles were divided into <3cycles or ≥4cycles for NAC and consolidation treatments and analyzed with multivariate analysis. 139/403 (34.5%) received ≥4cycles of NAC and had a worse prognosis than <3cycles (p=0.011). 70/403 (17.4%) received ≥4cycles of consolidation treatment and there was no difference in survival (p=0.33) CONCLUSION: Women with advanced HGSC are managed with a combination of surgery and chemotherapy. This is a study of a homogenous cohort of patients with stage IIIC or IV high grade serous cancers who received NAC. ≥4cycles of NAC had a worse outcome than <3cycles likely due to poor prognostic factors or poor response. The number of consolidation cycles did not appear to make a difference in overall survival.

A Comparison of Survival Outcomes in Advanced Serous Ovarian Cancer Patients Treated With Primary Debulking Surgery Versus Neoadjuvant Chemotherapy.

OBJECTIVE: The management of women with advanced-stage serous ovarian cancer includes a combination of surgery and chemotherapy. The choice of treatment with primary debulking surgery or neoadjuvant chemotherapy varies by institution. The objective of this study was to report 5-year survival outcomes for ovarian cancer patients treated at a single institution with primary debulking surgery or neoadjuvant chemotherapy. METHODS: This study included a retrospective chart review of 303 patients with stage IIIC or IV serous ovarian carcinoma diagnosed in Calgary, Canada. The patients were categorized into 1 of the 2 treatment arms: primary debulking surgery or neoadjuvant chemotherapy. The 5-year ovarian cancer-specific survival rates were estimated using Kaplan-Meier curves. RESULTS: Among the 303 eligible patients, 142 patients (47%) underwent primary debulking surgery, and 161 patients (53%) were treated with neoadjuvant chemotherapy. Five-year survival was better for patients undergoing primary debulking surgery (39%) than for patients who received neoadjuvant chemotherapy (27%; P = 0.02). Women with no residual disease experienced better overall survival than those with any residual disease (47% vs. 26%, respectively; P = 0.0002). This difference was significant for those who had primary debulking surgery (P = 0.0004) but not for the patients who received neoadjuvant chemotherapy (P = 0.09). Women who received intraperitoneal chemotherapy had better overall survival as compared with patients who received intravenous chemotherapy (44% vs 30%, respectively; P = 0.002). CONCLUSIONS: Our findings suggest that among women with no residual disease, survival is better among those who undergo primary debulking surgery than treatment with neoadjuvant chemotherapy. The latter should be reserved for women who are deemed not to be candidates for primary debulking surgery.