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Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy. [ABSTRACT FROM AUTHOR]

The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%–45%) by investigator assessment and 35% (19%–55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%–56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%–93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0–8.5) months and 21.3 (11.7–32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3–4, 77%). One patient died from treatment-related hypovolemic shock. Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status. • We evaluated lenvatinib plus pembrolizumab as fourth-line therapy in 31 patients with advanced ovarian cancer. • Lenvatinib plus pembrolizumab had an objective response rate of 35% by blinded independent central review in this population. • Median duration of response by blinded independent central review was 9.2 (1.5+ to 37.8+) months. • Median progression-free survival was 6.2 months and median overall survival was 21.3 months. • Treatment-related adverse events occurred in 94% of patients (grade 3–4, 77%; grade 5, 3%). [ABSTRACT FROM AUTHOR]

The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLE mut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p =.003 and p =.001) and NSMP (p =.020 and p =.049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p =.033) and death (p =.008) in p53abn endometrial cancer patients. Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer. • Patients with p53abn endometrial cancer showed the highest rate of positive peritoneal cytology. • Positive peritoneal cytology is associated with worse oncological outcome in NSMP and p53abn endometrial cancer patients. • In women with p53abn endometrial cancer, positive peritoneal cytology is an independent predictor of recurrence and death. [ABSTRACT FROM AUTHOR]

Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m2) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS). This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage. Demographic, clinicopathologic and treatment outcomes were collected and analyzed. RT patients (n = 39, 15%) had a higher BMI (p = 0.004), older age (p < 0.001), more life-limiting comorbidities (LLC) (p < 0.001), larger tumor size (p = 0.001), and higher clinical stage (p = 0.013) compared to RH patients (n = 221, 85%). On multivariable survival analysis there was no difference in OS based on treatment modality; significant predictors of worse OS were larger tumor size, higher number of LLC and recurrence. Among the RH group, obese patients had a longer operative time (p = 0.01) and more LLC (p = 0.02); there were no differences in demographic or clinicopathologic characteristics, operative outcomes, RFS or OS compared to non-obese patients. In this cohort of RH-eligible cervical cancer patients, BMI was independently associated with disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no difference in RFS or OS when compared to non-obese patients. Thus, the decision for disposition to RT should not be based on obesity alone. • The preferred treatment of early-stage cervical cancer in patients with obesity is undefined. • Obesity is associated with disposition to primary radiation therapy in patients who are candidates for radical hysterectomy. • This study and previous have indicated safety and feasibility of radical hysterectomy in carefully selected obese patients. • Though radical hysterectomy in obese patients may be more technically difficult, outcomes are not different. • The decision for disposition to radiation therapy in early-stage cervical cancer should not be based on obesity alone. [ABSTRACT FROM AUTHOR]

An important question in determining long-term prognosis for women with ovarian cancer is whether risk of death changes the longer a woman lives. Large real-world datasets permit assessment of conditional survival (CS) given both prior overall survival (OS) and real-world progression-free survival (rwPFS). Using a longitudinal dataset from US oncology centers, this study included 6778 women with ovarian cancer. We calculated CS rates as the Kaplan-Meier probability of surviving an additional 1 or 5 years, given no mortality (OS) or disease progression (rwPFS) event in the previous 0.5–5 years since first-line chemotherapy initiation, adjusted for factors associated with OS based on multivariable Cox regression. Median study follow-up was 9 years (range, 1–44) from first-line initiation to data cutoff (17-Feb-2021). Median OS was 58.0 months (95% CI, 54.9–60.8); median rwPFS was 18.4 months (17.4–19.4). The adjusted 1-year CS rate (ie, rate of 1 year additional survival) did not vary based on time alive, whereas the adjusted 5-year CS rate increased from 48.5% (47.0%–50.1%) for women who had already survived 6 months to 66.4% (63.3%–69.6%) for those already surviving 5 years (thus surviving 10 years total). The adjusted 1-year CS rate increased from 90.4% (89.5%–91.4%) with no rwPFS event at 6 months to 97.6% (96.4%–98.8%) with no rwPFS event at 5 years; adjusted 5-year CS rate increased from 53.7% (52.0%–55.5%) to 85.0% (81.2%–88.9%), respectively. This analysis extends the concept of CS by also conditioning on time progression-free. Patients with longer rwPFS experience longer survival than patients with shorter rwPFS. • Women with ovarian cancer have an increasing probability of survival with increasing time survived after the diagnosis. • Conditional survival (CS) is the probability of surviving + y years, given already having survived x years post-diagnosis. • The 5-year CS rate increased from 54% for survival with no disease progression at 6 mos to 85% with no progression at 5 yrs. • The prognosis for ovarian cancer improved substantially with time for women alive without disease progression. [ABSTRACT FROM AUTHOR]

It is unclear whether nonsmall cell lung cancer (NSCLC) is associated with more aggressive disease and worse overall survival (OS) among younger patients. The aim of this study is to evaluate outcomes in young patients. We hypothesize that young age is associated with more advanced disease upon presentation, but better OS. We identified patients with NSCLC from 2004 to 2018 in the National Cancer Database. Patients were categorized in 3 groups: age≤50, 51-84, and ≥85 y. The outcomes were OS, stage IV NSCLC and clinical nodal metastasis. OS was analyzed using multivariate cox and Kaplan–Meier analysis accounting for stage, comorbidities, and other factors. The association of age, presentation with stage IV NSCLC and node positivity was analyzed using multivariate logistic regression. In total 1,651,744 patients were identified: 92,506 (5.57%) age ≤50, 1,477,723 (88.90%) age 51-84, and 91,964 (5.53%) age ≥85. Multivariate model showed stage IV NSCLC was associated with age ≤50 (OR 1.17 (1.15-1.20) P < 0.001) and ≥85 (odds ratio (OR) 1.03 (1.02-1.04) P < 0.001). Clinical lymph node positivity was associated with age ≤50 (OR 1.27 (1.23-1.30) P < 0.001). Relative to patients 51-84, the ≤50 group was associated with better survival in Stage I (hazard ratio (HR) 0.61 versus 1.00), stage II (HR 1.12 versus 1.50), stage III (HR 2.12 versus 2.53), and stage IV (HR 6.65 versus 7.53). Patients ≤50-y-old present with more advanced NSCLC, but better OS compared to patients 51-84. These findings suggest the need for increased awareness regarding NSCLC among age groups seen as low risk. [ABSTRACT FROM AUTHOR]

We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based chemotherapy (PC) for endometrial cancer (EC). A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test. Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25–3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01–4.18, p = 0.04). In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients. • Many patients will use antibiotics and/or a proton pump inhibitor at time of adjuvant therapy for endometrial cancer. • PPI use at time of adjuvant platinum-based chemotherapy is independently associated with worse outcomes. • Antibiotic use at time of adjuvant platinum-based chemotherapy was associated with worse survival on univariate analysis. [ABSTRACT FROM AUTHOR]

Prior studies have demonstrated survival differences between Black women with endometrial cancer (EC) born in the US and Caribbean. Our objective was to determine if country of birth influences EC overall survival (OS) in disaggregated subpopulations of Black women. Using the Florida Cancer Data System, women with EC diagnosed from 1981 to 2017 were identified. Demographic and clinical information were abstracted. Women who self-identified as Black and born in the US (USB), Jamaica (JBB), or Haiti (HBB) were included. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods with significance set at p < 0.05. 3817 women met the inclusion criteria. Compared to USB, JBB and HBB had more high-grade histologies, more advanced stage disease, had a greater proportion of uninsured or Medicaid insured, and had a higher proportion of women who received chemotherapy (all p < 0.05). In multivariate analyses, age (HR 1.03 [1.02–1.05]), regional stage (HR 1.52 [1.22–1.89]), distant stage (HR 3.73 [2.84–4.89]), lymphovascular space invasion (HR 1.96 [1.61–2.39]), receipt of surgery (HR 0.47 [0.29–0.75]), and receipt of chemotherapy (HR 0.77 [0.62–0.95]) were independently associated with OS. Compared to USB, Haitian nativity was an independent negative predictor of OS when evaluating all histologies together (HR 1.54 [1.18–2.00]) and for endometrioid EC specifically (HR 1.77 [1.10–2.83]). Among women with serous EC, HBB had markedly worse median OS (18.5 months [13.4–46.5]) relative to USB (29.9 months [26.3–35.9]) and JBB (41.0 months, [34.1–82.6], p = 0.013). Country of birth is associated with endometrial cancer survival in Black women, with HBB demonstrating worse outcomes. • Intra-racial disaggregation provides additional insight into health disparities found in women with endometrial cancer (EC). • Jamaican and Haitian-born Black women in the US have higher rates of high-grade EC than US-born Black women. • Haitian-born Black women in the US with serous EC experience worse overall survival than women born in Jamaica and the US. [ABSTRACT FROM AUTHOR]

The dependent coverage mandate in the 2010 Affordable Care Act (ACA) allows young adults to stay on a parent's private insurance through age 26. While this mandate is associated with gains in insurance and early-stage cancer diagnosis, its long-term impact on survival is unknown. To compare insurance coverage, stage at diagnosis, and overall survival in patients with gynecologic cancer before and after the ACA's dependent coverage mandate. Using difference-in-differences (DiD) analysis, we conducted a retrospective cohort study comparing outcomes before and after the implementation of the ACA's dependent coverage mandate in young patients with gynecologic cancer, ages 18–26 years (exposure group) to patients ages 27–35 (control group). We analyzed insurance coverage, stage at diagnosis, and 1, 2, and 3-year overall survival, adjusted for age and comorbidities, utilizing the 2004–2017 National Cancer Database. IRB exemption was obtained. A total of 3553 cases pre-reform and 4535 cases post-reform were identified for patients 18–26 years compared to 14,420 pre-reform and 19,821 post-reform for patients age 27–35. The ACA's dependent coverage mandate was associated with significant gains in insurance (DiD 2%, 95% CI 0.6–3.5) and early-stage diagnosis (3.1%, 95% CI 0.6–5.7). The ACA's dependent coverage mandate was associated with significant gains in 3-year survival (2.4%, 95% CI 0.4–4.3) and non-significant gains in 1 and 2-year survival. The ACA's dependent coverage mandate is associated with improvements in early-stage diagnosis and survival for young patients with gynecologic cancer. Maintaining insurance gains—and expanding to the remaining uninsured—are critical for the health of young patients with gynecologic cancer. • The Affordable Care Act's dependent coverage mandate was associated with long-term gains in insurance coverage and early-stage cancer diagnosis. • The ACA's dependent coverage mandate was associated with improved 3-year survival for young patients with gynecologic cancer. • Expansion of insurance coverage to the remaining 29 million uninsured may improve cancer outcomes. [ABSTRACT FROM AUTHOR]

We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years. We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001–12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S (x + y)/ S (x). Confidence intervals were estimated using a variation of Greenwood's formula. Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25–95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%–32%)—75% (95% CI: 68%–82%) for stage I/II disease, 22% (95% CI: 19%–26%) for stage III, and 6.9% (95% CI: 3.9%–12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%–70%); for those ≥65 years, it was 48% (95% CI: 38%–57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%–94%); stage III, 58% (95% CI: 50%–66%); and stage IV, 26% (95% CI: 12%–42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%–91%), 42% (95% CI: 30%–53%), and 29% (95% CI: 7%–56%), respectively. For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods. • Traditional 5-year overall survival rates do not account for changes in survival probability over time. • For survivors with ovarian cancer, survival probability strongly depends upon the amount of time elapsed since diagnosis. • Ten-year conditional probability of survival (CPS) gives a more accurate prediction of survival than conventional methods. • CPS can be utilized to benefit patient counseling and prospective trial planning. [ABSTRACT FROM AUTHOR]

Incidence of colorectal cancer (CRC) among young patients has increased in the last 20 y often with more aggressive tumor biology. It is unclear if age < 50 y is an independent factor for shorter overall survival in CRC patients. Our objective was to determine if younger age at diagnosis was associated with worse overall survival. This study used the National Cancer Data Base (2004-2016), retrospectively reviewing patients who underwent surgical resection for CRC. Patients were limited to only those without comorbidities and primary outcome was overall survival for all patients. Older patients have worse overall survival as compared to younger patients at a lower stage of disease (I and II) after adjusting for tumor location, gender, histology, stage, and systemic chemotherapy (< 36 y old versus 36-55 y old hazard ratio [HR] 1.16, confidence interval [CI] 1.03-1.29). This survival benefit is eliminated at a higher stage of disease, stage III in 36-55 y old versus < 36 y old (HR 0.96 [CI 0.90-1.03.99]) and stage IV (HR 0.94 [CI 0.89-0.99]). Older patients (aged > 36 y) have worse overall survival at a lower stage of disease, but the survival among all age groups was similar for stage III or IV disease in CRC. [ABSTRACT FROM AUTHOR]

The objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS). This is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board. 217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86–135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1. After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08–2.28) and death(HR = 1.99 (95% CI 1.01–3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046–3.512, p = 0.035). Patients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making. • KELIM score may be a marker of chemosensitivity in patients with ovarian cancer treated with neoadjuvant chemotherapy. • Patients with a KELIM<1 had a lower progression free- and overall survival compared to patients with KELIM ≥1. • Patients with KELIM<1 had higher risk of disease progression and death compared to patients with KELIM ≥1. • BRCA positive mutation status was independently associated with a higher KELIM score. • Patients with KELIM<1 were more likely to have platinum-resistant disease and worse progression free- and overall survival. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is the most common blood cancer in adults. Patients' 5-year overall survival is less than 30% thus having a poor prognosis. To date, the development of novel target therapies is still necessary to ameliorate patients' survival. Antibody-drug conjugates (ADCs) represent a promising class of drugs for the treatment of AML. CD33 is highly expressed on AML cells, and the FDA-approved CD33-targeted ADC drug-gemtuzumab ozogamicin (GO) has proved the feasibility of CD33-targeted ADC drug design. In this study, we constructed a novel CD33-targeted ADC drug composed of a humanized anti-CD33 antibody and oridonin as a payload with a cleaved chemical linker. Oridonin is a natural product that has great cancer therapy potential while its poor bioavailability and targeting ability limited its clinical use. Herein, we demonstrated that antiCD33-oridonin specifically delivered oridonin in AML cells improved AML cells killing ability of oridonin. Meanwhile, it did not show any non-specific toxicity on CD33 negative cells. In summary, we developed a novel AML targeting ADC with clinical application potential, and therefore provided a new solution for the druggability improvement of oridonin. • We designed and expressed a humanized antiCD33 antibody-oridonin conjugate for acute myeloid leukemia therapy. • We designed and synthesized a new chemical cleavable linker for antibody-drug conjugates. • The antiCD33-oridonin ameliorated cell-killing ability and safety of oridonin. • The antiCD33-oridonin improved the potential clinical application of oridonin and provided a new conjugation strategy. [ABSTRACT FROM AUTHOR]

To determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer. Data were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy. Of 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99). The prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits. • Risk calculator redefines prognosis in early stage high risk epithelial ovarian cancer. • Cohort of patients identified by the calculator may not benefit from adjuvant treatment. • A simplified calculator of age, stage, histology, and grade is also predictive of treatment benefit. [ABSTRACT FROM AUTHOR]

• SVR and RFE were used to construct a quantitative prediction model of the OS. • 70 RNAs were determined as important factors influencing the OS. • 18 RNAs were identified as hub RNAs closely determining the OS. Researches on the prognosis of pancreatic cancer is of great significance to improve the patient treatment effect and survival. Current researches mainly focus on the prediction of the survival status and the determination of prognostic markers. Each patient has its own characteristics, there is no report about the prediction of survival time. However, accurate prediction of survival time is critical for personalized medicine. In this paper, a hybrid algorithm of Support Vector Regression (SVR) and Recursive Feature Elimination (RFE) was used to construct a quantitative prediction model of Overall Survival (OS) for pancreatic cancer patients, 70 RNAs related to OS were determined, including 33 mRNAs, 28 lncRNAs, and 9 miRNAs. The results of 10-fold cross-validation (R2 is 0.9693) and the generalization ability (R2 is 0.9666) showed that the model has reliable predictive performance and these 70 RNAs are important factors influencing the OS of pancreatic cancer patients. To further study the relationship between RNA-RNA interaction and the survival, competitive endogenous RNA (ceRNA) regulation network was constructed. Degree centrality, betweenness centrality and closeness centrality of nodes in the ceRNA network showed that hsa-mir-570, hsa-mir-944, hsa-mir-6506, hsa-mir-3136, MMP16, PLGLB2, HPGD, FUT1, MFSD2A, SULT1E1, SLC13A5, ZNF488, F2RL2, TNFRSF8, TNFSF11, FHDC1, ISLR2 and THSD7B are hub nodes, which are key RNAs closely determining the OS of pancreatic cancer patients [ABSTRACT FROM AUTHOR]

We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS). We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual <1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany. A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival. The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm. • The size of residual tumors after surgery is evaluated surgically and radiologically for advanced ovarian cancer (AOC). • The incorporation of the two assessments is more accurate to predict prognosis of optimal debulked, high-grade serous AOC. • No gross residual on postoperative CT shows better survival in patients optimal debulked, high-grade serous AOC. [ABSTRACT FROM AUTHOR]

Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%–44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675–0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients. • The 5-year post-recurrence disease-specific survival (PR-DSS) rate was 39.1% in patients with early-stage cervical cancer. • The strongest factors for PR-DSS were primary tumour size and the presence of symptoms at diagnosis of recurrence. • The presence of symptoms at recurrence remained a significant prognostic factor after correction for lead-time bias. • PR-DSS was best in patients without LN involvement or LVSI suffering from solitary asymptomatic recurrence. [ABSTRACT FROM AUTHOR]

To report 20-year trends in incidence and survival of vulvar cancer in Korea. Using data from the Korean Central Cancer Registry, age-standardized incidence rates (ASRs) and annual percentage changes (APCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method, and conditional net survival (CNS) was calculated. A total of 2221 patients was diagnosed with vulvar cancer during the 1999–2018 period, with an ASR of 0.32 per 100,000 person-years. Among the cases, 51.4% were squamous cell carcinoma (SqCC), 21.3% were Paget disease, and 8.6% were basal cell carcinoma (BCC). There was an increase in incidence for all vulvar cancer (APC 2.4%, 95% CI 1.8–3.0). However, although BCC (APC 7.0%, 95% CI 3.3–10.8) and Paget disease (APC 5.9%, 95% CI 4.2–7.6) increased, SqCC did not (APC 0.2%, 95% CI -0.8–1.2). There was an increase in incidence in all age groups. The 5Y NS was 74.0% overall, and it did not improve significantly during the study period. The 5Y CNS of vulvar cancer increased continuously with time survived: from 74.0% (71.4–76.4) at baseline to 98.1% (95% CI, 85.4–99.8) at 5 years after diagnosis. The incidence of vulvar cancer in Korea showed a different pattern from those in the US and Europe: SqCC incidence was relatively low and remained stable, but the incidence of BCC and Paget's disease increased. Survival did not improve in the past two decades. Patients can be considered cured after surviving for 5 years. • The incidence of vulvar cancer in Korea showed a different pattern from those in the US and Europe • Incidence of squamous cell carcinoma incidence was relatively low and remained stable • Incidence of basal cell carcinoma and Paget's disease increased. • Survival did not improve in the past two decades. • Patients can be considered cured after surviving for 5 years. [ABSTRACT FROM AUTHOR]

The goal of the study was to confirm whether preoperative controlling nutritional status (CONUT) was a prognostic factor in early-stage cervical cancer patients with high-risk factors after surgery and postoperative concurrent chemoradiotherapy (CCRT). Between 2004 and 2015, a total of 698 patients who were treated with surgery and postoperative CCRT were included in this retrospective study. The prescribed dose for postoperative radiotherapy was 45–50.4 Gy in 25–28 fractions and the concurrent chemotherapy regimen contained cisplatin or paclitaxel. Based on the receiver operating characteristic (ROC) analysis, the patients were classified into low (<3) and high (≥3) CONUT groups. Of all study patients, 471 (67.5%) patients were included in the low CONUT group. The low CONUT group had significantly better 5-year disease-free survival (DFS) and overall survival (OS) than the high CONUT group (p<0.001 and p = 0.001, respectively). A high CONUT score was significantly associated with lymph node metastasis, parametrial invasion, and poorer nutritional status, including lower body mass index (BMI) and lower prognostic nutritional index (PNI) score (p<0.05, respectively). The CONUT score was an independent predictor of DFS and OS in multivariate analysis. Notably, the CONUT score still efficiently stratified DFS in the high PNI score group (P = 0.001). The preoperative high CONUT scores indicated poor prognosis for early-stage cervical cancer patients with high-risk factors treated with surgery and postoperative CCRT. In clinical practice, patients with high CONUT score should be considered to receive consolidation chemotherapy. • Controlling nutritional status (CONUT) score was underutilized in early-stage cervical cancer with high-risk factors. • The preoperative CONUT score was a useful marker for predicting prognosis. • The high CONUT score predicted poor prognosis for early-stage cervical cancer patients with high-risk factors. • Patients with high CONUT score should be considered to receive consolidation chemotherapy after adjuvant therapy. [ABSTRACT FROM AUTHOR]

Previous studies have evaluated the prognostic factors of patients with stage IIIB cervical cancer. However, there was only one study evaluating the relationship between LTI (lower third of vaginal invasion) and the prognosis of the patients with stage IIIB cervical cancer. Our research aimed to assess different therapeutic outcomes of the stage IIIB CCP (cervical cancer patients) with or without LTI. From December 2007 to December 2014, patients with FIGO (International Federation of Gynecology and Obstetrics, 2009) stage IIIB cervical cancer admitted and treated in Zhejiang Cancer Hospital were enrolled and evaluated in this retrospective research. Different clinicopathological variables and treatment outcomes were analyzed by using multivariate and univariate Cox regression models and chi-square or Fisher's exact test. The number of enrolled patients was 622, among which 74 cases were with LTI and 548 without. The two- and five-year OS (overall survival) rates in non-LTI group were 79.9% and 58.9%, and the OS rates in LTI group were 68.9% and 38.8%, respectively (P = 0.001). The two- and five-year PFS (progression-free survival) rates in non-LTI group were 63.3% and 53.1%, and the PFS rates in LTI group were 45.9% and 37.0% respectively (P = 0.002). Multivariate Cox regression analysis indicated that histological type, total treatment time, hydronephrosis, and treatment protocol were factors significantly affecting the PFS rates in stage IIIB CCP, and OS rates were associated with histological type, hydronephrosis, treatment protocol, and LTI. Our study showed that stage IIIB CCP with LTI had worse prognosis than those without LTI. • Our study evaluated that stage IIIB CCP with LTI had poorer survival than those without LTI. • There were several factors affecting the survival rates in stage IIIB CCP, like histological type and so on. • According to multivariate Cox regression analysis, LTI was the factor affecting the OS in stage IIIB CCP. [ABSTRACT FROM AUTHOR]

Around 15% of epithelial ovarian cancer (EOC) patients (pts) harbor a germline BRCA1 or 2 mutation, showing different features than BRCA wild-type pts. The clinical and pathological features of an Italian BRCA mutated EOC cohort were described. We retrospectively analyzed clinical, pathological and mutational data from a cohort of Italian BRCA mutated EOC pts. treated in 15 MITO centers between 1995 and 2017. Three-hundred thirty-one pts. were recorded. Two-hundred forty (72%) and 91 (27.5%) pts. harbored a BRCA1 and BRCA2 mutation, respectively. Median age at diagnosis was 52 years. The most frequent diagnosis was a high grade serous FIGO III or IV EOC and platinum doublet in first-line was administered to almost all pts. Fifty-three % of them had no residual disease (R = 0) at surgery. Median progression-free-survival (mPFS) after first-line chemotherapy was 29 months. Expected percentage of pts. alive at 5 years was 72.5% (CI 60.2–80.8%) and R = 0 predicted a significantly longer overall survival (OS). Sixty-six pts. (19,9%) had both an EOC and a breast cancer (BC) diagnosis. The first diagnosis was BC in 81,8% of cases with a mean interval between the two diagnoses (IBTDs) of 132.4 months. Mutational data show that the founder mutation c.5266dupC in BRCA1 was the most frequently recorded. This is the largest Italian BRCA mutEOC cohort. The only predictor of longer OS was R = 0. EOC pts. that developed subsequently a BC are long-term survivors. • This is the largest Italian BRCAmut Epithelial Ovarian Cancer (EOC) cohort, with 331 women diagnosed between 1995 and 2017. • The most frequent diagnosis was FIGO stage III/IV high grade serous EOC. • Expected percentage of patients alive at 5 years was 72.5% (CI 60.2–80.8%). • R = 0 at surgery was correlated with a longer OS. • EOC patients that developed a subsequent BC were long-term survivors. [ABSTRACT FROM AUTHOR]

• Female had severe metabolic gene and pathway dysregulation than male in HCC patients. • Deregulated metabolic genes mainly involved in amino acid and carbohydrate metabolism. • Upregulated ALDH1A2 independently increased overall survival risk in HCC patients. • Over-expressed GATA3 and TAL1 may activate ALDH1A2, then affect metabolic pathways. Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) with laparoscopic (LAP) or laparotomic (OPEN) radical hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN were reported. Results: There were 6,477 unique references identified from initial search, from which 27 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =670) versus LAP (n =1057) was 1.12 (95% CI:0.87-1.44; p=0.39; I2=0%), and ROBOT (n =3320) versus OPEN (n =11,991) was 1.13 (95% CI:0.89-1.44; p=0.31; I2=47%). The weighted HR for OS for ROBOT (n =746) versus LAP (n =1082) was 1.01 (95% CI: 0.56-1.80; p=098; I2=46%) and ROBOT (n =3945) versus OPEN (n =13,050) was 1.18 (95% CI: 0.99-1.41; p=0.06; I2=32%). Conclusions: Compared to OPEN and LAP radical hysterectomy, the studies show that ROBOT radical hysterectomy does not result in worse oncologic outcomes with respect to DFS and OS. The noted outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/ S (x). Confidence intervals (CIs) were estimated using a variation of Greenwood's formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS. [ABSTRACT FROM AUTHOR]

Objectives: To compare overall survival (OS) in women with endometrial cancer who received hysterectomies with and without oophorectomies. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) Research Plus dataset. The sample included endometrial cancer women aged 18 and above diagnosed between 2014 to 2018 (n =52,680) who had hysterectomies with oophorectomies (ovary removed) and without oophorectomies (ovary retained). Histology of endometrial cancer included low-grade and high-grade endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma, carcinosarcoma, and mixed type. Kaplan-Meier curves, log-rank comparisons, and Cox regression analyses were used to evaluate OS. Results: There were 97.4% patients (n =51,324) who had oophorectomies while 2.6% (n =1,356) did not. Mean age was 62.7 years; the majority were White (79.6%, n =41,941), stage I (78.8%, n =41,496), and endometrioid type (78.1%, n =41,142). Adjuvant therapies were radiation (28.3%, n =14,893), chemotherapy (22.6%, n =11,930), and combined radiation/chemotherapy (12.5%, n =6,598). There were 5,051 deaths (9.6%) among which 119 deaths (0.2%) were in the ovary retained group while 4,943 deaths (9.4%) were in the ovary removed group. In the whole sample, OS did not differ between the two groups (p=0.14). In those with late-stage endometrial cancer (stages III and IV), there were lower hazards for OS (HR:0.75, 95% CI: 0.58-0.97, p=0.03) in the ovary removed group. In those with early-stage endometrial cancer (stages I and II), the OS did not differ between the two groups (p=0.21). Conclusions: Oophorectomy in late-stage endometrial cancer patients who received hysterectomy was associated with improved OS. However, oophorectomy in early-stage endometrial cancer patients was not associated with improved OS. Fertility-sparing surgery may be considered for those in early-stage endometrial cancer who desire to preserve ovary function. Further studies are needed to confirm when oophorectomy is indicated in endometrial cancer patients with ovarian activity. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a nomogram for the overall survival of epithelial ovarian cancer based on the National Union of Real- World Gynecological Oncology Research and Patient Management Platform (NUWA) in China. Methods: We enrolled patients with pathologically confirmed primary epithelial ovarian cancer in the NUWA platform between 2004 and 2018 as a training cohort to develop a nomogram. The cut-off for follow-up was December 2020. Patients with a history of other tumors or missing values of any variable were excluded. Variables were selected by univariate and multivariate Cox proportional hazard regression. Significant factors were applied to establish a nomogram to predict 3-year and 5-year survival, assessed by C-statistic and calibration curves. A testing cohort from SEER Database was applied to externally validate the nomogram by bootstrap resampling. Statistical analysis was conducted by SPSS version 26.0 (IL, USA) and R version 4.1.1 (www.r-project.org). Results: A total of 1262 primary epithelial ovarian cancer patients were filtered out from 5003 ovarian cancer patients in the NUWA platform. Total 10594 of 125682 patients in the SEER Database were screened out accordingly. Baseline age, histotype, histological grade, FIGO stage, longest diameter of the primary tumor, and residual disease after primary surgery were significant risk factors (p <0.05). Compared with serous cancer, the hazard ratio (HR) of mucinous, endometrioid, clear cell, other epithelial cancer were 3.391 (95% CI: 2.201-5.223), 1.642 (95% CI: 1.045-2.580), 3.127 (95% CI: 2.134-4.582), and 2.071 (95% CI: 1.486-2.885), respectively. The HR of advanced stage and high grade of disease (FIGO stage III-IV vs I-II, High grade vs Low/moderate grade) were 1.921 (95% CI: 1.226-3.010) and 1.407 (95% CI: 1.048-1.889), respectively. Patients who received optimal (R1), suboptimal (R2) cytoreduction, and those who didn't receive primary debulking surgery had a higher risk of death compared to those without the residual disease (R0), with HRs of 5.530 (95% CI: 3.575-8.555), 7.757 (95% CI: 5.101-11.796) and 9.975 (95% CI: 5.831-17.063), respectively. For continuous variables, the HR of baseline age (years) was 1.024 (95% CI: 1.013-1.036), and the HR of the longest diameter of the primary tumor (cm) was 1.030 (95% CI: 1.007-1.054). The C-statistic values of the nomogram (Figure 1) in the training and testing cohorts were 0.771 (95% CI: 0.748-0.794) and 0.726 (95% CI: 0.718-0.734), respectively. The slopes of calibration curves of 3-year and 5-year survival in the training cohort were 1.165 (95% CI: 0.990-1.340) and 0.955 (95% CI: 0.920-0.990), respectively, whereas, in the testing cohort, these were 1.355 (95% CI: 1.108-1.602) and 1.374 (95% CI: 1.103-1.644), respectively. [Display omitted] Conclusions: The discrimination and goodness of fit of the nomogram indicated its predictive value for the survival of epithelial ovarian cancer in China. Furthermore, the nomogram also obtains certain values in external validation, which implies its feasibility in different populations. [ABSTRACT FROM AUTHOR]

Objective To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC). Methods Data were analyzed for all patients with stage IIIB–IV EOC who underwent primary cytoreduction from 1/2001–1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0–1, 2–3, and ≥ 4. Clinical and survival outcomes were assessed and compared. Results We identified 567 patients; 199 (35%) had an ACCI of 0–1, 271 (48%) had an ACCI of 2–3, and 97 (17%) had an ACCI of ≥ 4. The ACCI was significantly associated with the rate of complete gross resection (0–1 = 44%, 2–3 = 32%, and ≥ 4 = 32%; p = 0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p = 0.84) or major (18% vs 19% vs 16%, p = 0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0–1, 2–3, and ≥ 4 was 20.3, 16, and 15.4 months, respectively (p = 0.02). Median OS for patients with an ACCI of 0–1, 2–3, and ≥ 4 was 65.3, 49.9, and 42.3 months, respectively (p < 0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p = 0.02) and OS (p < 0.001). Conclusions The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age–comorbidity covariate. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) is being increasingly utilized in gynecologic and breast cancers. Multidisciplinary Molecular Tumor Board (MTB) may guide an N-of-One approach in order to maximize matched treatment; however, outcome data are limited. We evaluate the effect of the degree of matching patients to treatment and concordance with MTB recommendations on oncologic outcomes, including overall response rate (ORR), clinical benefit rate (CBR) (stable disease ≥6 months/partial or complete remission), progression-free survival (PFS), and overall survival (OS). 164 consecutive gynecologic and breast cancer patients presented at MTB from December 2012-September 2018 were assessed for clinicopathologic data, NGS results, MTB recommendations, therapy received, and oncologic outcomes. Matching score (MS), defined as percentage of alterations targeted by treatment out of total number of pathogenic alterations, and concordance with MTB recommendations were analyzed in context of oncologic outcomes. Disease site, age, and number of prior lines of therapy were considered as covariates in univariate analysis and included in multivariate analysis if p<0.2. 113 women were evaluable for treatment after MTB; 54% received matched therapy. Patients with MS > 40% had higher ORR (30.8% vs. 7.1%; p=0.001) and CBR (73.1% vs. 31.2%; p<0.001) (Figure 1), PFS (HR 0.51, 95% CI 0.31, 0.85; p=0.002), and a trend toward improved OS (HR=0.64, 95% CI 0.34, 1.25; p=0.082) in univariate analysis. Higher MS was associated with improved ORR (HR 5.9, 95% CI 1.8, 19.0; p=0.003), CBR (HR 4.8, 95% CI 1.7, 13.4; p=0.003), and PFS (HR 0.5, 95% CI 0.3, 0.8; p=0.006) in multivariate analyses. Higher concordance with MTB recommendations was significantly associated with improved median PFS (9.0 months for complete concordance; 6.0 months for partial concordance; 4.0 months for no concordance; p=0.004) and OS (17.1 months complete concordance, 17.8 months partial concordance, 10.8 months no concordance; p=0.046). Patients who received completely MTB-concordant treatment had higher MS (p<0.001). In multivariate analysis comparing all vs none for concordance with MTB recommendations, PFS (HR 9.5; 95% CI 2.6, 35.0; p=0.001) and OS (HR 8.8, 95% CI 2.4, 33.2; p=0.001) remained significant. [Display omitted] Concordance with MTB recommendations resulted in higher degrees of matched therapy and was associated with improved oncologic outcomes in gynecologic and breast cancer patients. [ABSTRACT FROM AUTHOR]

Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p<0.0001) and significantly less recurrences (68.1% vs 94.9%, p=0.002) compared to STS. Logistic regression model including age at diagnosis, germline BRCA mutation status, stage and histologic type showed that increased age lowers the odds for long term survivorship (OR-0.929 per 1 year of age, p=0.008). Endometroid carcinoma, compared to serous histology, lowers the odds for LTS as well (OR-0.295, p=0.046). Surprisingly, germline BRCA1 mutation carriers are 5.5 times more likely to survive more than 7 years compared to non-carriers (OR-5.508, p=0.034). Germline BRCA2 mutations do not change the odds for LTS compared to non-carriers p=0.99. Patients diagnosed at stage III have a significantly higher chance of long-term survivorship compared to stage IV, as previously reported for primary-debulked HGSOC patients (OR-7.89, p=0.016). [Display omitted] Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions. [ABSTRACT FROM AUTHOR]

To determine the impact of treatment with poly-adenosine ribose phosphatase inhibitors (PARPi) on the response to subsequent platinum-based chemotherapy in recurrent, platinum-sensitive BRCA -mutated epithelial ovarian, peritoneal, or fallopian cancer (BRCA m) patients. A retrospective, single-institution cohort study of patients with BRCA m who received treatment with multiple platinum regimens. Electronic medical records were reviewed to identify BRCA m patients who received subsequent platinum-based chemotherapy following PARPis from 12/15/2011-5/5/2020. Response to subsequent therapy and progression-free survival (PFS) was determined. The PFS of BRCA m patients was compared to non -BRCA m who were treated with platinum following a PARPi. Among 241 BRCA m patients 152 recurred. One hundred and fifteen platinum sensitive BRCA m patients received a second-line platinum regimen with 108 being PARPi naïve and 7 PARPi exposed. The median PFS was 2.4 times longer after 2nd line platinum-based therapy for patients who did not receive a PARPi, p=0.005. Fifty-five platinum-sensitive BRCA m patients received a third-line platinum regimen with 42 PARPi naïve and 13 PARPi exposed. The median PFS was 2.3 times longer for 3rd line platinum regimens for BRCA m patients who did not receive a PARPi, p<0.001) (HR 3.72 [1.81-7.64]. Collectively, among the 20 PARPi exposed patients the PFS to a 2nd or 3rd line platinum was significantly worse at 8.0 months vs 19.1 months HR 4.01 [2.25,7.16] p<0.001 (Figure 1). Response and PFS for PARPi exposed BRCA m patients after a platinum regimen were similar when patients were stratified by platinum-free intervals (PFI) of 6-12, 12-24 and >24 months (Figure 2). The response and PFS to a platinum regimen following a PARPi were similar between BRCA mutated and non-mutated patients (Figure 3). [Display omitted] Among BRCA m patients, PARPi exposure significantly reduced PFS following 2nd and 3rd line platinum based chemotherapy. Prior exposure to PARPi nullifies well established predictors of response to subsequent platinum-based chemotherapy (platinum-free interval and BRCA mutational status. The routine use of PARP for maintenance should be questioned until PARPi overall survival data is mature. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) procedures with laparoscopy (LAP) and laparo- tomic (OPEN) hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN and LAP were reported. Results: There were 6,477 unique references identified from initial search from which 19 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =1152) versus LAP (n =1029) was 0.94 (95% CI: 0.71-1.26; p=0.68; I2=0%), and ROBOT (n =887) versus OPEN (n =1035) was 0.84 (95% CI: 0.64-1.11; p=0.22; I2=0%). The weighted HR for OS for ROBOT (n =4675) versus LAP (n =2643) was 0.98 (95% CI: 0.82-1.16; p=0.78; I2=0%) and ROBOT (n =27,647) versus OPEN (n =23,923) was 0.77 (95% CI: 0.71-0.83; p<0.0001; I2=18%). Conclusions: When compared with OPEN and LAP hysterectomy, ROBOT hysterectomy does not result in worse oncologic outcomes with respect to DFS and shows improved OS results compared to OPEN. The noted improved outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Objectives: Therapy for early-stage epithelial ovarian cancer (EOC) involves complete surgical staging with or without adjuvant chemotherapy. The current international multi-center study aimed to investigate the long-term survival of different histological subtypes for stage I EOC. Methods: A multi-center cohort study was performed among all patients with FIGO stage I (IA-IC3) EOC treated at four European referral centers between 1985 and 2021. Overall survival (OS) and progression-free (PFS) survival were compared between the different stage I groups using Kaplan-Meier survival curves. Results: A total of 1115 patients met the inclusion criteria. Of them, 48.4% (n =540) were in stage IA, 6.6% (n =73) stage IB, and 45% (n =502) stage IC: stage IC1 54% (n =271), stage IC2 31.5% (n =158), and stage IC3 14.5% (n =73). The predominant histologic subtypes included highgrade serous (25.4%), low-grade endometrioid (24.8%), and clear cell (19%). Complete surgical staging, including lymphadenectomy, was performed in 62.1%, and 60% received adjuvant platinum-based chemotherapy. The median follow-up was 48 months. The median five-year (5y) OS and PFS rates were 94% and 86%, respectively, with no difference between stage IA and IB. However, a significantly better OS and PFS were observed for stage IA as compared to stage IC (p=0.007 and p<0.001, respectively). Considering histologic subtypes, a significant better PFS was documented for low-grade mucinous and low-grade endometrioid subgroup (HR: 0.22; 95% CI: 0.09-0.45, p=0.001; HR: 0.49; 95% CI: 0.29-0.83, p=0.007, respectively), as well a better OS for the latter (HR: 0.43; 95% CI: 0.22-0.86, p=0.017). In stage IA-B, the different histology subtypes showed a comparable prognosis (5y: OS: 96% and PFS: 92%), with the exception of a worsened OS for high-grade mucinous cases (HR: 5.90; 95% CI: 1.55-22.4, p=0.009). Among stage IC, the histologic subgroups showed comparable OS (5y 92%), but significantly better PFS for low-grade mucinous and low-grade endometrioid subtypes (HR: 0.21; 95% CI: 0.05-0.86, p=0.031; HR: 0.44; 95% CI: 0.23-0.84, p=0.013, respectively). In the subgroup of high-grade serous ovarian cancer patients in stage IC disease, the chemotherapy with carboplatin/paclitaxel seems to be superior compared to single-agent platinum (5y OS: 100% vs 83%; p=0.009). In multivariate analysis, partial staging procedure (compared to complete) was found as risk factor for worsen PFS (HR: 1.73; 95% CI: 1.13-2.66, p=0.012), while low-grade endometrioid histology (compared to high-grade serous) showed better outcome regarding OS (HR: 0.46; 95% CI: 0.22-0.95, p=0.036) and PFS (HR: 0.42; 95% CI: 0.25-0.73, p=0.002). Conclusions: Overall, stage I ovarian cancer patients treated in referral centers exhibited an excellent prognosis regardless of the histologic type. Histologic subtype and quality of surgical treatment affect the prognosis. Our data suggest platinum-based combination chemotherapy for the subgroup of FIGO stage IC high-grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the interaction between pathologic and histologic features and impact on overall survival (OS) among patients with endometrial cancer classified by the four molecular subtypes, identified by The Cancer Genome Atlas (TCGA). Methods: Using TCGA's Pan-Cancer Atlas accessed via the cBioPortal, we identified patients with endometrioid or serous endometrial cancer. Patients with available molecular data were included in our analysis. We recorded available outcomes data, and FIGO stage and pathologic factors were manually extracted from surgical pathology reports. OS was compared among groups using Kaplan-Meier curves. Results: A total of 507 patients with molecularly subtyped endometrioid or serous endometrial cancers were identified. FIGO stage was inferred using surgical pathology reports, and data regarding LVSI and histologic grade were available in 467 patients. Tumors were categorized as POLE hypermutated (43/467; 9.2%), microsatellite instable (MSI) hypermutated (139/467; 29.8%), copy number low (CN-low) (142/467; 30.4%), and CN-high (143/467; 30.6%). While molecular subtype was significantly correlated with OS among the entire study population (p <0.0001), this correlation was only significant among stage III tumors when divided by FIGO stages (n =100, p = 0.012). Increasing histologic grade was associated with worse OS among patients with CN-low tumors (5-year survival: G1 100%, G2 88%, G3 59.4%; p = 0.0051) but not among patients with other TCGA molecular subtypes or low-grade tumors. Of the 73 patients with CN-high tumors with LVSI, 32 (43.8%) were node-positive. Of the 35 patients with CN-low tumors with LVSI, four (11.4%) were node-positive. The presence of LVSI was associated with worse OS than those without LVSI among patients with CN-high (3-year survival rate: 56.9% vs 83.1%, p = 0.0048) and CN-low (3-year survival rate: 88.5% vs 94.4%, p = 0.0024) tumors. Conclusions: In this cohort of patients with endometrioid and serous endometrial cancer from the TCGA, the presence of LVSI was associated with worse OS among patients with CN-low and CN-high tumors. Patients with CN-low tumors with LVSI were less likely to be node positive than patients with CN-high tumors with LVSI. Increasing histologic grade was associated with worse OS only among patients with CN-low tumors. These data support a combined molecular histopathologic classification for prognosis in endometrial cancer. [ABSTRACT FROM AUTHOR]

Objectives: Surgery is the mainstay of treatment for early-stage vulvar cancer. Adjuvant radiation is thought to improve survival for patients with positive margins; however, recent studies have called this into question. We aimed to evaluate the association of adjuvant radiation and margin status with overall survival in a contemporary cohort. Methods: A retrospective cohort study was performed among women with vulvar cancer identified from the National Cancer Database between 2004 and 2017. Patients with stage I and II disease, with a tumor diameter ≤4cm, and squamous histology who underwent lymph node assessment were included. Bivariable tests were used to examine associations. Cox proportional hazard regression was used to evaluate the effect of adjuvant radiation on overall survival. Results: Of 9,567 patients with early-stage squamous vulvar cancer who underwent lymph node assessment, 7.4% had positive margins (n = 709). Among those with positive margins, 27.9% received adjuvant radiation. Receipt of adjuvant radiation was not associated with older age, non-White race, or lack of insurance; however, it was associated with stage II disease (32.8% vs 20.0%), higher grade (21.7% vs 15.1%), and lymph vascular space invasion (18.8% vs 11.7%, all p<0.04). Moreover, receipt of adjuvant radiation was not associated with improved overall survival in patients with positive margins (HR: 1.01, 95% CI: 0.73-1.40). This did not change after adjustment for stage, grade, and presence of lymph vascular space invasion (HR: 0.70, 95% CI: 0.43-1.16). Conclusions: Adjuvant radiation did not improve overall survival in patients with early-stage squamous vulvar cancer and positive margins. [ABSTRACT FROM AUTHOR]

Abstract: Objectives. : Total parenteral nutrition (TPN) for terminal ovarian cancer patients remains controversial. In this study, we compared survival from time of terminal intestinal obstruction (TIO) diagnosis in patients who received TPN versus those who did not. Methods. : A historical cohort of 55 patients with stage IIIC/IV epithelial ovarian cancer hospitalized for TIO between 1994 and 2002 was studied. All patients were previously treated with paclitaxel/platinum following cytoreductive surgery. Exposure was administration of TPN after TIO. The primary outcome was survival from TIO diagnosis to death. Number of chemotherapy cycles completed after TIO diagnosis, major complications of TPN, and demographics were measured. Survival analysis was performed using Kaplan–Meier methods. Results. : The median survival from time of TIO diagnosis was 72 days (range 16–485) for patients receiving TPN and 41.0 days (range 4–133) for those not receiving TPN (P = 0.05), but no difference in survival was observed when adjusting for chemotherapy. Overall survival [median 23 (range 6–67) vs. 35 months (range 8–67), P = 0.03] was shorter for the TPN group. Demographic data were similar in both groups. Patients receiving TPN after obstruction were more likely to undergo concurrent chemotherapy (64 vs. 26%, P = 0.004). One major TPN-related complication was found. Conclusions. : Ovarian cancer patients with TIO receiving TPN had a median survival benefit of 4 weeks. This benefit decreased when patients were treated with concurrent chemotherapy. Issues of cost, quality of life, and human values need to be investigated to assess the full impact of TPN in this patient population. [Copyright &y& Elsevier]

Evaluate the outcomes of patients with endometrial cancer managed at minority-serving hospitals. The National Cancer Database was accessed, and patients diagnosed between 2004 and 2016 with a uterine, ovarian or cervical tumor with known race were identified. Minority-serving hospitals (MSH) were defined as those with the highest percentage (>75th percentile) of Hispanic, Black and Asian patients while non-MSH were defined at those with the lowest (<25% percentile) percentage. Patients without a history of another tumor, diagnosed with endometrial cancer, and who were managed at a single facility were identified. Patients managed at an MSH or a non-MSH were selected for analysis. Clinico-pathological and treatment characteristics were compared while overall survival was evaluated after controlling for confounders with the construction of a Cox multivariate model. A total of 1,312 facilities reporting patients with gynecologic malignancies were identified. In MSH and non-MSH hospitals, an average of 46.89% and 2.63% of patients were minorities, respectively. A total of 111222 patients with endometrial cancer who met the inclusion criteria were identified; 62.7% and 38.3% were managed at an MSH and a non-MSH hospital, respectively. Compared to patients managed at non-MSH those managed at an MSH were more likely to have comorbidities (74.2% vs 72.6%, p<0.001) and stage III-IV disease (21.4% vs 15.3%, p<0.001), while they were less likely to have endometrioid tumors (79.9% vs 88.3%, p<0.001) and private insurance (46.6% vs 49.1%, p<0.001). After controlling for insurance status, comorbidities, patient age and disease stage, patients who underwent surgery at an MSH had higher odds of unplanned 30-day readmission (OR: 1.17, 95% CI: 1.09, 1.28), 90-day mortality (OR: 1.24, 95% CI: 1.10, 1.40) and prolonged hospitalization (defined as hospital stay >10 days) (OR: 1.41, 95% CI: 1.30, 1.55). For patients with apparent-early stage disease, after controlling for age, insurance, histology and comorbidities, those who had a hysterectomy at an MSH had similar odds of undergoing minimally-invasive surgery (OR: 0.97, 95% CI: 0.93, 1.01). Patients with non-endometrioid tumors (OR: 0.90, 95% CI: 0.78, 1.05) or apparent stage IB, grade 2/3 endometrioid tumors (OR: 1.06, 95% CI: 0.92, 1.22) had similar odds of undergoing lymphadenectomy. Patients with stage III-IV disease, who were managed at an MSH had lower odds of receiving chemotherapy (OR: 0.90, 95% CI: 0.84, 0.96) after controlling for insurance, age, comorbidities and histology. After controlling for patient age, insurance status, comorbidities, histology, receipt of chemotherapy and radiation therapy and disease stage, treatment at an MSH was associated with worse survival (HR: 1.12, 95% CI: 1.09, 1.15) compared to treatment at a non-MSH. Significant disparities exist in the management, perioperative outcomes and survival of patients with endometrial cancer managed at MSH. [ABSTRACT FROM AUTHOR]

Biomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited. Data were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses. A higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p =.017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p <.001). In chemotherapy-only cohort, dNLR was also correlated with DCR and OS. Higher dNLR level was correlated with worse outcomes, suggesting that dNLR may help risk-group stratification and assist disease management strategies as a prognostic biomarker for non-colorectal GI patients receiving ICB. [ABSTRACT FROM AUTHOR]