Significant Predictor Of Overall Survival Research Articles

Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

6590 Background: Epidemiologic studies suggest that Hispanic patients with renal cell carcinoma (RCC) have worse outcomes than non-Hispanic White patients (NHW). It is unclear if this disparity is related to inherent biological differences or patients’ social determinants of health (SDOH). Utilizing the International Metastatic Renal Cell Carcinoma Database (IMDC) of patients with RCC primarily receiving care at academic medical centers, we investigated outcomes of Hispanic and NHW patients with advanced RCC. Methods: Eligible patients included patients who self-reported being non-Black Hispanic or NHW with locally advanced or metastatic RCC initiating systemic therapy. The primary endpoint was overall survival (OS) and secondary endpoint was time to treatment failure (TTF) for the first-line therapy. Kaplan Meier curves were constructed for OS and TTF. Cox regression was used to estimate hazard ratios (HR) adjusted for confounding variables. Results: The cohort included 1,563 patients, of which 181 (11.6%) were Hispanic. Most patients were male (74%) with clear cell histology (82%). IMDC risk groups were 18%, 58%, 24% for favorable, intermediate, and poor risk, respectively, and were similar by ethnic groups. Compared to NHW, Hispanic patients were younger at diagnosis (median 57 vs 59 years, p = 0.036), less likely to have > 1 metastatic site (61% vs 77%, p < 0.001) and bone metastases (24% vs 33%, p = 0.009). 1,178 patients (124 Hispanic vs. 1,054 NWH) received treatment before 2018, 385 patients (57 Hispanic vs. 328 NWH) received treatment during or after 2018. With regards to first line therapy, the majority received tyrosine kinase inhibitor (TKI) monotherapy (70%), 10% received immunotherapy (IO) + IO, 9% received TKI + IO, 4% received IO monotherapy, and 8% received other treatments. Median TTF was 7.8 months (95% Confidence Interval (CI): 6.2-9.0) in Hispanic patients and 7.5 months (95% CI: 6.9-8.1) in NHW patients. On multivariable analysis, there was no significant difference in TTF between Hispanic and NHW patients (HR 1.05, 95% CI: 0.89-1.25, p = 0.558). Significant predictors of TTF were presence of unfavorable site of metastases, histology, IMDC risk group, and therapy type. Median OS was 38.0 months (95% CI: 28.1-59.2) in Hispanic patients and 35.7 months (95% CI: 31.9-39.2) in NHW patients. On multivariable analysis, there was no significant difference in OS between Hispanic and NHW patients (HR 1.07, 95% CI: 0.87-1.32, p = 0.544). Significant predictors of OS were number of metastatic sites, presence of unfavorable metastasis, histology, IMDC risk group, and therapy type. Conclusions: In this analysis, we did not detect a difference in OS or TTF for Hispanic patients with RCC. Our data suggest that access to care (as available in a tertiary cancer hospital) can mitigate the historic difference in outcomes in Hispanic versus NWH patients.

The effect and therapeutic compliance of adjuvant therapy in patients with cholangiocarcinoma after R0 resection: a retrospective study.

This study aimed to compare clinical outcomes between surveillance and adjuvant therapy (AT) groups after R0 resection for cholangiocarcinoma (CCA). A total of 154 patients who underwent R0 resection for CCA at the Daegu Catholic University Medical Center between January 2010 and December 2019 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed. The median follow-up duration was 899 days. There were 109 patients in the AT group and 45 patients in the surveillance group. The patients in the AT group were younger (67 years vs. 74 years, p<0.001) and included more males (64.2% vs. 46.7%, p=0.044). The proportion of patients with stage III CCA was larger in the AT group than in the surveillance group (13.8% vs. 2.2%, p=0.005). In addition, AT did not improve OS (5-year OS rate, 69.3% in the AT group vs. 64.2% in the surveillance group, p=0.806) or PFS (5-year PFS rate, 42.6% in the AT group vs. 48.9% in the surveillance group, p=0.113). In multivariate analysis using the Cox proportional hazards model, stage III CCA (hazard ratio [HR], 10.81; 95% confidence interval [CI], 2.92-40.00; p<0.001) was a significant predictor of OS. American Society of Anesthesiologists classification II (HR, 0.50; 95% CI, 0.31-0.81; p=0.005), and American Joint Committee on Cancer stages II (HR, 3.14; 95% CI, 1.25-7.89; p=0.015) and III (HR, 8.08; 95% CI, 2.80-23.32; p<0.001) were independent predictors of PFS. AT after R0 resection for CCA did not improve OS or PFS.

Outcome of 177 Lu-PSMA Radionuclide Treatment in Advanced Prostate Cancer and Its Association With Clinical Parameters : A Single-Center Experience.

This study was set out to analyze the efficacy and safety of 177 Lu-PSMA-617 (LuPSMA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Progressive mCRPC patients who received at least 1 cycle of LuPSMA therapy were evaluated retrospectively. Demographic, clinic, and histopathological data were documented. Treatment efficacy was determined based on biochemical response criteria (Prostate Cancer Clinical Trial Working Group 3), and toxicity rates were defined based on CTCAE v4.03. The prognostic significance of laboratory/clinical data and 68 Ga-PSMA PET/CT quantitative results were analyzed using SPSS Version 24.0. One hundred patients (median prostate-specific antigen [PSA] level, 75.7 ng/mL) who met the eligibility criteria were identified. The median number of cycles received per patient was 3 (range, 1-9). After the first cycles of LuPSMA, biochemical partial response, biochemical stable disease, and biochemical progressive disease were observed in 31%, 36%, and 33% of patients, respectively. Any PSA decline was determined in 60% of patients. After the fourth cycle of treatment, biochemical partial response, biochemical stable disease, and biochemical progressive disease were defined in 48%, 26%, and 26% of patients, respectively. The median overall survival (OS) from the first cycle of LuPSMA was 14 months. Patients who had any PSA response after the first cycle had significantly longer OS than nonresponders (median OS: 17 vs 9 months; P ≤ 0.001). Total PSMA-derived tumor volume ( P = 0.004), total PSMA activity per lesion ( P = 0.01), PSA ( P = 0.007), alkaline phosphatase ( P = 0.002), lactate dehydrogenase ( P < 0.001), and hemoglobin ( P < 0.001) were significant prognostic factors for OS in univariate Cox regression analysis. LuPSMA therapy is a favorable treatment for mCRPC with remarkable therapeutic efficacy and low toxicity rates, even in progressive disease under standard therapies. Baseline PSMA-based tumor burden, PSA, alkaline phosphatase, lactate dehydrogenase, and hemoglobin were significant predictors of OS and can be useful for selection of the best candidate for LuPSMA therapy.

Significant impact of cachexia index on the outcomes after hepatic resection for colorectal liver metastases.

The purpose of this study was to investigate the relation between preoperative cachexia index (CXI) and long-term outcomes in patients with colorectal liver metastases (CRLM) after hepatic resection. In all,118 patients who underwent hepatic resection for CRLM were analyzed retrospectively. The relationship between CXI and the long-term outcomes in patients after hepatic resection was investigated. CXI was calculated based on preoperative skeletal muscle index, serum albumin level, and neutrophil-lymphocyte ratio. The multivariate analysis showed that extrahepatic lesion (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.48-5.53, P < .01) and high CXI (HR 0.44, 95% CI 0.20-0.98, P=.04) were independent and significant predictors of disease-free survival. Moreover, extrahepatic lesion (HR 2.32, 95% CI 1.03-5.22, P=.04), high CXI (HR 0.17, 95% CI 0.05-0.57, P < .01), and curability R 1 or 2 (HR 3.29, 95% CI 1.23-8.78, P=.02) were independent and significant predictors of overall survival. CXI is a useful prognostic factor for disease-free survival and overall survival after hepatic resection in CRLM patients.

Prognosis of resected non-small cell lung cancer with pleural plaques on intrathoracic findings

BackgroundThe prognosis of patients with lung cancer who demonstrate pleural plaques intraoperatively, which may be associated with exposure to asbestos, is unclear. Here, we compared the clinicopathological characteristics and prognosis of these patients to those of patients without pleural plaques.MethodsWe included patients who underwent curative-intent resection for non-small cell lung cancer. We retrospectively investigated the relationship of intrathoracic findings of pleural plaques with clinicopathological features and prognosis.ResultsPleural plaques were found in 121/701 patients (17.3%) during surgery. The incidence of squamous cell carcinoma (P < 0.001) and the pathological stage (P = 0.021) were higher in patients with pleural plaques. Overall survival was significantly worse in patients with pleural plaques (5-year rate; 64.5% vs. 79.3%; P < 0.001), and the same finding was noted in clinical stage I patients (5-year rate; 64.8% vs. 83.4%; P < 0.001). In multivariable analysis, the presence of pleural plaques was a significant predictor of overall survival in patients with clinical stage I (hazard ratio, 1.643; P = 0.036). In the analysis among patients with emphysema more severe than Goddard score 5 points or interstitial pneumonia, overall survival was significantly worse in those with pleural plaques than in those without pleural plaques (5-year rate; 66.3% vs. 49.5%; P < 0.001).ConclusionsPatients with non-small cell lung cancer who underwent resection and demonstrated pleural plaques intraoperatively had a significantly worse prognosis. It is important to recognize the presence of pleural plaques intraoperatively, and our findings will be useful in determining the treatment and follow-up strategy for such patients with lung cancer and pleural plaques on intrathoracic examination.

Prognostic Factors for Outcomes of Allogeneic HSCT for Children and Adolescents/Young Adults With CML in the TKI Era

The breakthrough effects of tyrosine kinase inhibitors (TKIs) have lessened indications for allogeneic hematopoietic stem cell transplantation (HSCT) in chronic myeloid leukemia (CML). However, HSCT is still attractive for children and adolescents/young adults (AYAs) requiring lifelong TKI therapy. Nevertheless, little has been reported on the outcomes of large clinical studies of HSCT targeting these age groups. This study aimed to identify prognostic factors for the outcomes of HSCT, including reduced-intensity conditioning (RIC)-HSCT, for children and AYAs with CML in the TKI era. We performed a registry analysis for 200 patients with CML aged <30 years who underwent pretransplant TKI therapy from the observational nationwide database established by the Japanese Society for Transplantation and Cellular Therapy. The patients received bone marrow (BM), peripheral blood (PB), or cord blood (CB) from either related or unrelated donors. The indication for HSCT for individual patients was determined by the institution according to European LeukemiaNet recommendations and other guidelines. The 5-year overall survival (OS) rates for patients with chronic phase (CP) (n = 124), accelerated phase (AP) (n = 23), and blastic phase (BP) (n = 53) at diagnosis were 82.8%, 71.1%, and 73.3%, respectively, with no significant difference (P =.3293). The strongest predictor of engraftment was transplant source, with CB (hazard ratio [HR], 0.33) and PB (HR, 2.00) (compared with BM) being independent unfavorable and favorable predictors, respectively. Transplant source was also an independent predictor of chronic GVHD, with PB (HR, 1.81) and CB (HR, 0.39) (compared with BM) being unfavorable and favorable predictors, respectively. The strongest predictor of OS rate for patients with CP at diagnosis was disease phase at HSCT, with second or greater CP, AP, or BP (HR, 2.81) (compared with first CP [CP1]) being an unfavorable predictor. In addition, patients with CP at diagnosis who had major and complete molecular responses at HSCT had excellent outcomes, with 5-year OS rates of 100% and 94.4%, respectively. The 5-year OS rate was compared between RIC (n = 31) and myeloablative conditioning (MAC) (n = 58) in patients with CP1, both of which were 89.3%, with no significant difference (P = .9440). On univariate analysis for the RIC cohort with CP at diagnosis, the age at HSCT (HR, 1.27) (increase per year) and the time from diagnosis to HSCT (HR, 1.83) (increase per year) were significant predictors for OS. Our study demonstrates that RIC may be an appropriate alternative to MAC for children and AYAs with CP1. As for the transplant source, we recommend first selecting BM because of a higher engraftment rate compared to CB and a lower incidence of chronic GVHD compared to PB. Although HSCT in the status of a major molecular response is desirable, it is not advisable to continue TKI pointlessly long because age at HSCT and timing of HSCT are prognostic factors that determine survival. The decision to perform RIC-HSCT instead of continuing TKI should be carefully made, considering the possibility of transplant-related complications.

The impact of S-1 for the patient with lymph nodal metastasis biliary tract cancer as adjuvant chemotherapy: a multicenter database analysis.

Although adjuvant chemotherapy is expected to improve the prognosis for patients with biliary tract cancer after curative resection, there is limited evidence regarding the efficacy and prognostic factors of adjuvant chemotherapy. We investigated the effective subgroups for whom adjuvant chemotherapy with S-1 in biliary tract cancer patients. 413 patients who underwent curative resection for biliary tract cancer at our four affiliated hospitals between 2009 and 2019 were included in this study. The association of adjuvant chemotherapy with long-term outcomes in overall and patient subgroups were investigated by univariate and multivariate analyses. Among overall patients, adjuvant chemotherapy with S-1 did not improve disease free survival (p = 0.29) and overall survival (p = 0.83). In thesubgroup analysis, adjuvant chemotherapy with S-1 improved both disease-free and overall survival in patients with lymph node metastasis, advanced Stage (III and IV), and microscopic residual tumor. In 135 patients with lymph node metastasis, adjuvant chemotherapy with S-1 was given in 67 patients (50%). In the patients with lymph node metastasis, preoperative bile duct drainage (p = 0.01) and adjuvant chemotherapy (p = 0.04) were independent and significant predictors of disease-free survival, while preoperative bile duct drainage (p = 0.03), tumor differentiation (p = 0.03), and adjuvant chemotherapy (p = 0.03) were independent and significant predictors of overall survival. After resection of biliary tract cancer, adjuvant chemotherapy with S-1 appears to benefit those who had lymph node metastasis.

Prognostic Impact of Primary Tumor Extent and Postoperative Radiation Facility Location in Major Salivary Gland Malignancies.

IntroductionThe treatment of primary salivary malignancies often requires a multimodality approach. The purpose of this analysis was to evaluate the interaction between primary tumor extent and the treatment location of postoperative radiotherapy (PORT) in patients with primary salivary malignancies with respect to survival outcomes.MethodsPatients with primary salivary malignancies who underwent upfront surgery followed by radiation were queried in the National Cancer Database (NCDB). Patients were stratified by pathologic T stage and whether PORT was performed at the same or different facility as the definitive surgery. Survival outcomes were compared using the Kaplan-Meier method and Cox proportional hazards regression.ResultsA total of 5,553 patients were selected, of which 1,159 had pathologic T4 (pT4) tumors. Patients who received PORT at the same facility compared with a different facility demonstrated superior overall survival (OS) on log-rank analysis (p=0.003). On subgroup analysis, patients with pT4 tumors had superior OS (p=0.015), whereas patients with smaller T1-3 tumors did not. PORT receipt at the same surgical facility was not a significant predictor of OS on multivariable analysis when all patients were included (p=0.057). However, among patients with pT4 tumors, OS was improved in patients who got PORT at the same facility as their surgery (p=0.015), with 10-year survival rates of 38.3 (95% confidence interval (CI): 33%-44%) versus 31% (95%CI: 24%-38%).ConclusionOS was improved in patients with primary salivary malignancies who received PORT at the same facility as their surgery, but the difference appears to be primarily driven by patients with pT4 primary tumors.

High-resolution Melting Analysis for NOTCH1 c.7541-7542delCT Mutation in Chronic Lymphocytic Leukemia: Prognostic Significance in Egyptian Patients.

The present study aimed to detect the prevalence of NOTCH1 c.7541-7542delCT mutation in Egyptian CLL patients using HRM assay and to assess its relation to patients' survival. The study included 50 newly diagnosed treatment-naïve CLL patients and 50 age and sex matched healthy controls. NOTCH1 c.7541-7542delCT mutation was detected using High-resolution melting (HRM) assay and direct Sanger sequencing. Outcome parameters included progression free survival (PFS) and overall survival (OS). NOTCH1 c.7541-7542delCT mutation was detected in 5 (10.0%) of CLL patients. No controls had NOTCH1 c.7541-7542delCT mutation. Similar results were obtained by direct Sanger sequencing yielding a sensitivity and specificity of 100.0% for HRM in detection of NOTCH1 c.7541-7542delCT mutation in the studied patients. In univariate analysis, predictors of OS included Trisomy 12, high LDH, presence of NOTCH1 c.7541-7542delCT mutation and lack of CR. In multivariate analysis, only lack of CR was found as a significant predictor of OS. HRM analysis is a sensitive method for detection of NOTCH1 c.7541-7542delCT mutation in CLL patients. This mutation may be linked to poor disease prognosis.

Real-world evidence of cisplatin versus carboplatin in patients with locally advanced nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: A multicenter analysis.

Though concurrent chemoradiotherapy (CCRT) with cisplatin remains a standard of care for patients with locally advanced nasopharyngeal carcinoma (LA-NPC), carboplatin has alternatively been used without sufficient supportive evidences. Thus, we evaluated an efficacy and tolerability of carboplatin CCRT compared with cisplatin in LA-NPC patients. Patients with LA-NPC treated with CCRT were identified through the Thai multicenter head and neck cancer database. Patient tolerability and survival were analyzed and compared between regimens. Survivals were calculated by using the Kaplan-Meier method, and compared by the log-rank test. A p-value of<0.05 was considered statistically significant. A total of 135 of 980 patients (13.8%) were treated with carboplatin. Patients treated with carboplatin were significantly associated with older age (p<0.001), smoking (p=0.003), more comorbidity (p=0.014), kidney disease (p=0.016), and lower baseline creatinine clearance (p<0.001). Intensity-modulated radiation therapy was used significantly more in the cisplatin group than carboplatin group (p<0.001). Patients who received carboplatin were associated with delay (p=0.049) and hospitalization (p=0.006), whereas cisplatin CCRT had more dose reduction (p=0.001). Patients treated with cisplatin had CCRT interruption from grade 3-4 mucositis (p=0.019) more than carboplatin, whereas carboplatin had more grade 3-4 thrombocytopenia (p<0.001). The 5-year overall survival (OS) of patients treated with cisplatin and carboplatin was 59% and 49%, respectively (p=0.128). Cisplatin or carboplatin CCRT was not a significant predictor for OS and locoregional recurrence-free survival in multivariate analysis. Carboplatin CCRT provided acceptable efficacy and tolerability profiles in real-world practice. Carboplatin should be considered as an alternative regimen, particularly in cisplatin-ineligible patients with LA-NPC treated with CCRT.

Sarcopenia with systemic inflammation can predict survival in patients with hepatocellular carcinoma undergoing curative resection.

This study aimed to examine the prognostic significance of sarcopenia combined with systemic inflammation in patients who underwent curative hepatectomy for hepatocellular carcinoma (HCC). Between January 2010 and July 2019, we identified 159 patients with HCC who underwent curative hepatectomy at three institutional centers. We retrospectively analyzed clinicopathological outcomes, surgical outcomes, platelet lymphocyte ratio (PLR) as a systemic inflammatory marker, and computed tomography (CT)-assessed sarcopenia at the third lumbar vertebra level (L3). Sarcopenia was noted in 74 (46.5%) of 159 patients and was significantly associated with male sex, low body mass index (BMI), and high PLR. In the multivariate analysis, sarcopenia [hazard ratio (HR): 2.127, P=0.026] and high PLR (HR: 1.971, P=0.038) were associated with a decrease in overall survival (OS) but not in recurrence-free survival (RFS). The combination of sarcopenia and PLR status stratified the 5-year OS into 82.0% (non-sarcopenia and a low PLR), 68.3% (sarcopenia or a high PLR), and 44.4% (sarcopenia and a high PLR) (P=0.001). In the multivariate analysis, "sarcopenia and a high PLR" and "sarcopenia or a high PLR" were revealed to be significant predictors of OS (HR: 4.300, P=0.001 and HR: 2.723, P=0.010, respectively). Sarcopenia and high PLR were significantly associated with poor OS. The combination of these two factors may be useful for predicting survival of patients with HCC undergoing curative hepatectomy.

External validation of Pentafecta in patients undergoing laparoscopic radical cystectomy: results from a high-volume center

BackgroundTo investigate whether Pentafecta is suitable for bladder cancer patients receiving laparoscopic radical cystectomy (LRC).MethodsFrom November 2013 to December 2020, muscle invasive Bladder Cancer (MIBC) and non-muscle invasive Bladder Cancer (NMIBC) patients who received LRC and urinary diversion were retrospectively analyzed. Pentafecta was defined as meeting five criteria: negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year. Analyze the achievement of five criteria and compare the overall survival (OS) of Pentafecta group with non-attainment group. Multivariable Cox’s regression was performed to evaluate the impact of Pentafecta on OS. Multivariable logistic regression was performed to explore the effect of surgical experience on Pentafecta attainment.ResultsA total of 340 patients were included, negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year were observed in 95.3%, 30.3%, 83.8%, 75.0% and 85.6% of patients, respectively. Pentafecta group had a significantly longer OS than the non-attainment group (P = 0.027). The group with 10–15 LNs removed and meeting the other four criteria had a similar OS to group with ≥ 16 LNs removed (Pentafecta group) (5-year OS: 67.3% vs 72.7%, P = 0.861). Pentafecta (HR = 0.33, P = 0.011), positive lymph nodes (HR = 2.08, P = 0.028) and MIBC (HR = 3.70, P < 0.001) were all significant predictors of OS in multivariable Cox’s regression. Surgical experience (OR = 1.05, P < 0.001), conduit (OR = 2.09, P = 0.047) and neobladder (OR = 2.47, P = 0.048) were all independent predictors of Pentafecta attainment in multivariable logistic regression.ConclusionsPentafecta is suitable for bladder cancer patients receiving LRC and has the potential to be a valuable tool for evaluating the quality of LRC. Based on Pentafecta analysis, removing 10 LNs instead of 16 LNs as the one of the five criteria may be more appropriate for bladder cancer patients.

SWOG S1314: A randomized phase II study of co-expression extrapolation (COXEN) with neoadjuvant chemotherapy for localized, muscle-invasive bladder cancer with overall survival follow up.

536 Background: This trial evaluated COXEN, a gene expression model, as a predictive biomarker in muscle-invasive bladder cancer (BC) patients randomized to Gemcitabine-Cisplatin (GC) or dose-dense Methotrexate-Vinblastine-Adriamycin/doxorubicin-Cisplatin (ddMVAC). Primary results correlating COXEN with pathologic response at surgery have been reported. This secondary analysis includes progression-free (PFS) and overall survival (OS). Methods: Eligibility included Stage cT2-T4a N0 M0, urothelial BC (mixed histology allowed), ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy. 237 patients were randomized between ddMVAC, given every 14 days for 4 cycles, and GC, given every 21 days for 4 cycles. Cox regression was used to evaluate COXEN score or treatment arm association with PFS and OS, adjusting for stratification factors (stage and PS). Results: 167 patients were included in the primary COXEN analysis all having either at least 3 cycles of chemo and surgery within 100 days of last chemo or having progressed while receiving chemo. The COXEN scores were not significantly prognostic for OS or PFS in their respective arms; the COXEN GC score was a significant predictor for OS in pooled arms. OS and PFS data are shown for both scores in the table. In the intent to treat analysis (n=227), there was no significant difference in OS or PFS for ddMVAC versus GC (for OS, HR =0.87, 95% CI 0.54-1.40), p = 0.57); for PFS (HR= 0.76 95% CI 0.58-1.01, p = 0.055). Association of path response with OS will be presented. Conclusions: The COXEN GC score may be prognostic of survival in those receiving platinum-based neoadjuvant treatment. The randomized, prospective design provides estimates of OS and PFS for GC and ddMVAC that appear comparable, but this phase II trial is underpowered for definitive comparisons. The prospective data and correlative samples from S1314 will allow for further assessment of COXEN and other RNA and DNA based predictive and prognostic biomarkers. Clinical trial information: NCT02177695. [Table: see text]

Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy

The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5–117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.

Association between Overall Survival and Activities of Daily Living in Patients with Spinal Bone Metastases.

Objective: This study aimed to investigate the association between overall survival (OS) and activities of daily living (ADL) in patients with skeletal-related events. In this study, 265 patients whose clinical parameters were available before radiotherapy were investigated. Methods: Age, sex, ADL, pain, the primary site, spinal level of bone metastases, spinal instability, treatment strategy, including chemotherapy or palliative treatment, and OS were investigated. ADL patients with a Barthel index of ≥90 were classified as the high ADL group, while those with a score < 90 were classified as the low ADL group. For OS, patients surviving ≥160 days were classified as the non-poor prognosis group, and those who survived <160 days were classified as the poor prognosis group. Results: Age, sex, ADL, pain, the primary site, and treatment strategy for OS were different between the two groups (p < 0.1). Logistic regression analysis revealed that ADL, the primary site, and treatment strategy were significant predictors of OS (p < 0.05). High ADL, breast cancer, and chemotherapy had a positive effect on OS. Conclusions: It is suggested that improvements may be obtained by performing rehabilitation interventions to maintain and improve ADL, by constructing a system for monitoring spinal bone metastases with images before ADL decreases, and by performing interventions such as changes in treatment methods such as RT or surgery at appropriate times.

BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.

BackgroundMismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC.Materials/MethodsThis was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type.ResultsThere were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis.Conclusion BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Natural history of patients with advanced cholangiocarcinoma and FGFR2 gene fusions/rearrangements.

391 Background: Cholangiocarcinoma (CCA) is a rare malignancy associated with poor survival. Molecular profiling is important to inform treatment choices and FGFR2 fusions or other rearrangements are common, occurring in 10–16% of patients with intrahepatic CCA (iCCA). There is limited real-world data on the natural history of patients with advanced CCA and FGFR2 fusions/rearrangements receiving therapies for advanced disease. The primary objective of this retrospective, observational natural history study was to compare real-world overall survival in patients with advanced CCA and FGFR2 fusions/rearrangements vs. those with wild-type (WT) FGFR2 from the index date of diagnosis of advanced CCA to date of death. A secondary objective was to analyze overall survival in the subgroup of patients with CCA and FGFR2 fusions/rearrangements from the index date of start of second-line therapy to date of death. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine clinico-genomic database. Data originated from approx. 280 US cancer clinics (̃800 sites of care). Patients were ≥18 years of age, had chart-confirmed advanced CCA, comprehensive genomic profiling demonstrating FGFR2 fusion/rearrangement, and had ≥2 visits within the Flatiron Health network since January 1, 2011. Results: As of May 2020, 571 patients met the inclusion criteria; 75 patients with FGFR2 fusions/rearrangements (median age 63 years; 64% female; 95% iCCA; 68% stage IV at initial diagnosis), and 496 patients with WT FGFR2 (median age 65 years; 48% female; 74% iCCA; 55% stage IV at initial diagnosis). Median overall survival from the index date of diagnosis was numerically higher, but not statistically different, for patients with FGFR2 fusions/rearrangements vs. WT FGFR2 (12.1 months [95% CI 8.5−17.1] vs. 7.1 months [95% CI 5.7−8.8]; log rank p = 0.184). 50 patients with FGFR2 fusions/rearrangements (median age 62 years; 70% female; 94% iCCA; 70% stage IV at diagnosis) received second-line therapy. Median real-world overall survival from the index date of second-line therapy was 8.5 months (95% CI 4.1−12.4 months). Conclusions: These real-world overall survival findings did not demonstrate a survival advantage for patients with CCA and FGFR2 fusions/rearrangements vs. WT FGFR2 receiving therapies for advanced disease, although a non-significant trend towards longer overall survival was observed in patients with FGFR2 fusions/rearrangements. FGFR2 status was not a significant predictor of overall survival after adjusting for potential prognostic covariates. An additional analysis is ongoing to compare overall survival from the start of second-line therapy in patients with advanced CCA and FGFR2 fusions/rearrangements vs. those with WT FGFR2.

Role of miR-15b/16–2 cluster network in endometrial cancer: An in silico pathway and prognostic analysis

Endometrial cancer (EC) is the second most common cancer in women. A large number of human cancers exhibit dysregulation of microRNA expression including EC. MiR-15b/16–2 is one of the best-known miRNA clusters that is expressed in many types of cancer tissues. Herein, we analyzed the expression of individual miR-15b/16–2 cluster members, its paralogues, and their target network analysis, as well as their prognostic significance in EC. UALCAN and GEPIA2 were used to analyze the expression of the individual members of the cluster. The gene target was predicted through miRTarBase, and the genes were then compared through the TCGA-UCEC dataset. The differential gene expression and network analysis identified 175 DEGs associated with critical cancer-related pathways. The prognostic significance and metastatic prediction were carried out using GEPIA2 and HCMDB tools. In UCEC patient samples, miR- 15b/16–2 cluster expression is negatively correlated with the overall survival of the patients. The uterus-specific miRNA-lncRNA, miRNA-circRNA, and miRNA-sncRNA networks of miR- 15b/16–2 cluster contain 1164 edges and nodes consisting of 5 sncRNA, 124 circRNA, and 1552 genes. The DEGs analysis led to the identification of SIPA1L2, PDCD1, CCNJ, ENTPD7, PLEKHA5, NPAS3, DPH5, BTF3, NPAS3, SENP2, and CCND3 as a significant predictor of overall survival in UCEC patients. The analysis of metastasis found 24 genes significantly associated with brain and lymph node metastasis. The analysis of drug-gene interactions revealed 267 FDA-approved drugs for treating cancers. Our data provided novel insight on the miR-15b/16–2 cluster role in EC and prioritized the findings for experimental verification. Besides, more comprehensive clinical and mechanistic studies are needed to confirm our findings in endometrial cancer.

Nasopharyngeal cancer: Incidence and prognosis of human papillomavirus and Epstein-Barr virus association at a single North American institution.

The prognostication of Epstein-Barr virus (EBV) and human papillomavirus (HPV) status in nasopharyngeal cancer (NPC) is unclear. This retrospective study analyzed NPC from 2000 to 2019. Seventy-eight patients were included: 43 EBV+ , 12 HPV+ , 23 EBV- /HPV- , and 0 EBV+ /HPV+ . All p16+ tumors were also positive for HPV-CISH. Baseline characteristics were not different between groups except age, N-classification, and Karnofsky Performance Scale (KPS) (p < 0.05). For EBV+ , HPV+ , and EBV- /HPV- respectively, 3-year overall survival (OS) was 89.9%, 69.8%, and 52.5% (p=0.006). EBV- /HPV- status was significantly associated with worse OS but not freedom from progression (FFP) on univariate analysis, and did not remain a significant predictor of OS after adjusting for KPS, age, and group stage. EBV+ NPC tumors were seen in younger, healthier patients than HPV+ and EBV- tumors, and there were no cases of coinfection. The association of viral status with OS was insignificant after adjusting for KPS and age.

Inflammation-based Prognostic Score as a Prognostic Biomarker in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With Nivolumab Therapy.

The inflammation-based prognostic score (IBPS) has attracted attention recently as a prognostic biomarker for head and neck cancer patients. However, as the IBPS often changes after anticancer drug therapy, its independent prognostic value remains controversial. We aimed to investigate the relationship between the IBPS and prognosis in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC) treated with nivolumab, and investigate changes in the IBPS before and after nivolumab treatment. Total of 164 patients with RMHNSCC received nivolumab therapy were retrospectively analyzed. Univariate analysis among the 164 patients revealed that the performance status (PS), immune-related adverse event (irAE) status, pre- and post-therapy Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and post-eosinophil count, were all significant predictors of overall survival (OS) (p<0.05). A multivariate analysis revealed that PS, irAEs, post-GPS, post-NLR, post-CAR, and post-eosinophil count were independent prognostic factors for overall survival. Post-treatment factors were identified as independent prognostic factors for RMHNSCC and can more accurately predict prognosis compared to nivolumab-treated RMHNSCC pre-treatment factors.