Treatment-related Survival Research Articles

Treatment-related survival patterns in diffuse intrinsic pontine glioma using a historical cohort: A report from the European Society for Pediatric Oncology DIPG/DMG Registry.

Our aim is to investigate the association of treatment with survival in patients with diffuse intrinsic pontine glioma (DIPG) by examining 6 historical treatment paths. We retrospectively analyzed data from 409 patients with radiologically centrally reviewed DIPG, sourced from the German Society of Pediatric Oncology and Hematology HIT-HGG trial database and the SIOPE-DIPG/DMG Registry. Survival outcomes were estimated using the Kaplan-Meier method, and univariable and multivariable Cox proportional hazard models were estimated to study treatment effects. The median overall survival (OS) from diagnosis was 11.2 months (95% confidence interval [CI], 10.5-11.9). Patients who by choice received no frontline treatment had an OS of 3.0 months (95% CI, 2.0-4.0), while those treated with radiation therapy (RT) alone had a median OS of 10.4 months (95% CI, 9.1-11.8). Those receiving RT combined with chemotherapy had the longest median OS of 11.7 months (95% CI, 10.8-12.6). The median post-progression survival (PPS) was 4.1 months (95% CI, 3.5-4.7). Patients who relapsed and did not receive treatment had a PPS of 2.2 months (95% CI, 1.8-2.6), while those treated with chemotherapy alone had a PPS of 4.4 months (95% CI, 3.7-5.0), and those who underwent reirradiation, with or without chemotherapy, had the longest survival after relapse of 6.6 months (95% CI, 5.3-8.0). Treatment differences remained significant in multivariable analysis adjusted for age and symptom duration in both diagnosis and relapse setting. This study shows increased survival outcomes associated with radiation and chemotherapy treatment or a combination thereof, at diagnosis and relapse, in a historical DIPG cohort.

Pembrolizumab (Anti-PD-1) in the management of malignant pleural mesothelioma: A systematic review of the current literature

Malignant pleural mesothelioma is an infrequent and aggressive type of cancer that is difficult to treat, and standard therapies have shown limited effectiveness. There have been recent advances in the development of targeted therapies for malignant pleural mesothelioma, including immunotherapy with pembrolizumab. This is a systematic review of the current role of pembrolizumab in the treatment of this disease. A systematic search was conducted through the databases and search engines. The eligible studies to be included were those that primarily focused on the outcomes of treating this disease with pembrolizumab, regardless of study design, line of therapy, mode of therapy, and ECOG performance status. After the initial and full-text screenings, 15 studies were reviewed. The number of cases was 454 with a mean age of 68.13 years, of which males (79.7%) were the predominant gender. Most of the cases were affected by epithelioid mesothelioma (76.7%). Pembrolizumab had been used as the first line of treatment in 62 (13.7%) cases. In 92.73% of cases, the therapy mode was pembrolizumab monotherapy. A total of 68 different adverse events were recorded. The most commonly associated adverse events were fatigue (14.8%), pruritis/rash (13.7%), and diarrhea (9.7%). Two patients died due to adverse events. The overall objective response was 17.8%, stable disease was 35.7%, progression-free survival was about 47.6% with a mean of 4.73 months, and 117 cases (25.8%) could reach treatment-related survival. Pembrolizumab can serve as a viable alternative in the management of malignant pleural mesothelioma, offering satisfactory outcomes and acceptable safety profiles

Patient-specific comorbidities as prognostic variables for survival inmyelofibrosis.

Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient-specific comorbidities have influence on treatment-related survival and are considered in clinical contexts but have not been routinely incorporated into current prognostic models. We hypothesized that patient-specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary myelofibrosis with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995 and 2016 were identified within Vanderbilt's Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (eg, Dynamic International Prognostic Scoring System [DIPSS], DIPSS plus, Genetics-Based Prognostic Scoring System, Mutation-Enhanced International Prognostic Scoring System 70+) and comorbidities through EHR chart extraction and next-generation sequencing on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR], 4.3; 95% confidence interval [95% CI], 2.1-8.9; P= .0001), intracranial hemorrhage (HR, 28.7; 95% CI, 7.0-116.8; P= 2.83e-06), invasive fungal infection (HR, 41.2; 95% CI,7.2-235.2; P= 2.90e-05), and chronic encephalopathy (HR, 15.1; 95% CI, 3.8-59.4; P=.0001). The extended DIPSS model including all 4 significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI, 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI, 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (eg, DIPSS) and other clinical and pathologic factors (eg, comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.

Management and Outcomes of Older Patients (Age ≥ 70 Years) with Advanced Soft Tissue Sarcoma and Role of Geriatric Assessment and Oncological Multidimensional Prognostic Index (Onco-MPI) in a Real-World Setting.

Background: Incidences of soft tissue sarcomas (STS) steadily increase with age. Yet, despite the high prevalence in advanced age, older patients (pts) are underrepresented in sarcoma clinical trials and evidence-based guidelines for chemotherapy are lacking. International oncological societies suggest using geriatric tools to evaluate older patients with cancer to optimise treatment indication. Comprehensive geriatric assessment (CGA) is a multidimensional assessment of older subjects, based on which pts can be classified as fit, vulnerable or frail. Onco-MPI (multidimensional prognostic index) is a CGA-based score which also considers tumour characteristics, classifying pts into three risk groups of death at one year: high-risk, intermediate-risk and low-risk. Methods: This is a single-centre retrospective study which aims at describing real-word management and outcomes of older pts with advanced stage STS and at assessing the ability of CGA and onco-MPI to predict survival in these pts. Consecutive pts with advanced stage STS aged 70 years or older and treated at the Istituto Oncologico Veneto from January 2009 to June 2020 were retrieved from a prospectively maintained database. Pts' demographics, CGA assessments and tumour characteristics were analysed. Statistical analysis was performed with R version 3.4.3 Results: Out of 101 pts, with a median age of 77 years, 76 received chemotherapy (75.3%), which was anthracycline-based for 46 pts (60.5%). Anthracyclines were used in a higher proportion in fit pts (58.9% fit vs. 45.1% vulnerable vs. 12.5% frail pts). Frail pts and pts in the onco-MPI high-risk group experienced a higher rate of chemotherapy-related toxicities. Median OS was 13.8 months (95% CI 11.3-17.7 months). According to CGA, the median OS was 19.53 months (95% CI 15.23-36.8) for fit pts, 12.83 months (95% CI 9.7-17.5) for vulnerable and 7.75 months (95% CI 2.73-30) for frail pts (p = 0.005). Onco-MPI confirmed a predictive value for 1-year survival with intermediate risk pts not reaching a median OS at 1 year, and high-risk pts having a median one-year OS of 11.5 months (95%CI 9.7-NA), p = 0.02. In multivariate analysis, onco-MPI and CGA were associated with survival (high risk onco-MPI: HR 5.5, 95%CI 1.25-24.7 p = 0.02; fitness at CGA HR 0.552 95% 0.314-0.973; p = 0.040) as well as chemotherapy use (HR 0.24, 95% CI 0.11-0.51, p < 0.005). Conclusions: Both CGA and onco-MPI retain prognostic value for survival in pts with metastatic STS. Pts frail/vulnerable at CGA and pts within the onco-MPI high risk category should be offered an oncogeriatric management approach in order to optimise treatment-related survival and reduce toxicity.

Safety and feasibility of laterally extended endopelvic resection for sarcoma in the female genital tract: a prospective cohort study.

ObjectiveThis study aims to evaluate the safety and feasibility of laterally extended endopelvic resection (LEER) for sarcoma in the female genital tract.MethodsWe prospectively recruited gynecologic cancer patients with sarcoma arising from female genital tract who underwent LEER at Seoul National University Hospital from December 2016 to March 2021. Clinicopathologic characteristics, surgical outcomes including postoperative complications and pain control, and survival outcomes of the patients were investigated.ResultsA total of nine patients were registered for this study. The median age was 56 years. Carcinosarcoma (n=2, 22%), leiomyosarcoma (n=2, 22%), and undifferentiated uterine sarcoma (n=2, 22%) were common histology types. Complete resection was achieved in 88.9%. The most common location of pelvic sidewall tumors was infra-iliac acetabulum (66.7%). The pathologic outcome showed a median tumor size of 9.0 cm and internal iliac vessel resection with pelvic sidewall muscle was performed in all patients. The median estimated blood loss was 1,600 mL (range, 300–22,300), and the patients were postoperatively admitted to the intensive care unit for median 1 day (range, 0–8). Complete response was observed in 44.4% (4/9) in radiologic studies after LEER, and median progression-free survival, treatment-related survival, and overall survival were 3.3, 19.6, and 98.9 months, respectively.ConclusionLEER was feasible and safe in treating recurrent sarcoma presenting pelvic sidewall invasion with acceptable survival outcomes and manageable postoperative complications.

PD25-06 VARIATION IN COMMUNICATION OF COMPETING RISKS OF MORTALITY IN PROSTATE CANCER TREATMENT CONSULTATIONS

You have accessJournal of UrologyCME1 May 2022PD25-06 VARIATION IN COMMUNICATION OF COMPETING RISKS OF MORTALITY IN PROSTATE CANCER TREATMENT CONSULTATIONS Aurash Naser-Tavakolian, Rebecca Gale, Michael Luu, Abhishek Venkataramana, Dmitry Khodyakov, Jennifer Anger, Edwin Posadas, Howard Sandler, Brennan Spiegel, Stephen Freedland, and Timothy Daskivich Aurash Naser-TavakolianAurash Naser-Tavakolian More articles by this author , Rebecca GaleRebecca Gale More articles by this author , Michael LuuMichael Luu More articles by this author , Abhishek VenkataramanaAbhishek Venkataramana More articles by this author , Dmitry KhodyakovDmitry Khodyakov More articles by this author , Jennifer AngerJennifer Anger More articles by this author , Edwin PosadasEdwin Posadas More articles by this author , Howard SandlerHoward Sandler More articles by this author , Brennan SpiegelBrennan Spiegel More articles by this author , Stephen FreedlandStephen Freedland More articles by this author , and Timothy DaskivichTimothy Daskivich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002567.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with prostate cancer prefer patient-specific, quantitative assessments of longevity in shared decision making. We sought to qualitatively characterize how physicians communicate the three components of competing risks—life expectancy, cancer prognosis, and treatment-related survival benefit—in treatment consultations. METHODS: Conversation related to life expectancy, cancer prognosis, and treatment-related survival benefit was identified in transcripts from treatment consultations of 42 men with low- and intermediate-risk disease across 10 providers (4 urologists, 2 radiation oncologists, and 4 medical oncologists). Consensus of multiple reviewers noted the most detailed mode of communication used to describe each component of competing risks throughout the consultation. RESULTS: Physicians frequently failed to provide patient-specific, quantitative estimates of both life expectancy and cancer mortality. Life expectancy was omitted in 17% of consultations, expressed as a generalization (e.g. “long”/”short”) in 17%, rough number of years in 31%, probability of mortality/survival at an arbitrary timepoint in 17%, and in only 19% as a specific number of years. Cancer mortality was omitted in 24% of consultations, expressed as a generalization in 7%, years of expected life in 2%, probability at an arbitrary timepoint in 40%, and in only 21% as the probability at the patient’s life expectancy. Treatment-related survival benefit was often omitted; cancer mortality was reported without treatment in 38%, with treatment in 10%, and in only 29% both with and without treatment. Illustrative quotes for these modes of communication are provided in Table 1. Physicians achieved “trifecta”—(1) quantifying probability of cancer mortality (2) with and without treatment (3) at the patient’s life expectancy—in only 14% of consultations. CONCLUSIONS: Physicians often fail to adequately quantify competing risks. We recommend the “trifecta” approach for communicating competing risks, reporting (1) probability of cancer mortality (2) with and without treatment (3) at the patient’s life expectancy. Source of Funding: This work was supported by Career Development Award (K08 CA230155 to TJD) from the National Cancer Institute © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e423 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aurash Naser-Tavakolian More articles by this author Rebecca Gale More articles by this author Michael Luu More articles by this author Abhishek Venkataramana More articles by this author Dmitry Khodyakov More articles by this author Jennifer Anger More articles by this author Edwin Posadas More articles by this author Howard Sandler More articles by this author Brennan Spiegel More articles by this author Stephen Freedland More articles by this author Timothy Daskivich More articles by this author Expand All Advertisement PDF DownloadLoading ...

Variation in Communication of Competing Risks of Mortality in Prostate Cancer Treatment Consultations.

Men with prostate cancer prefer patient-specific, quantitative assessments of longevity in shared decision making. We sought to characterize how physicians communicate the 3 components of competing risks-life expectancy (LE), cancer prognosis and treatment-related survival benefit-in treatment consultations. Conversation related to LE, cancer prognosis and treatment-related survival benefit was identified in transcripts from treatment consultations of 42 men with low- and intermediate-risk disease across 10 multidisciplinary providers. Consensus of qualitative coding by multiple reviewers noted the most detailed mode of communication used to describe each throughout the consultation. Physicians frequently failed to provide patient-specific, quantitative estimates of LE and cancer mortality. LE was omitted in 17% of consultations, expressed as a generalization (eg "long"/"short") in 17%, rough number of years in 31%, probability of mortality/survival at an arbitrary timepoint in 17% and in only 19% as a specific number of years. Cancer mortality was omitted in 24% of consultations, expressed as a generalization in 7%, years of expected life in 2%, probability at no/arbitrary timepoint in 40% and in only 26% as the probability at LE. Treatment-related survival benefit was often omitted; cancer mortality was reported without treatment in 38%, with treatment in 10% and in only 29% both with and without treatment. Physicians achieved "trifecta"-1) quantifying probability of cancer mortality 2) with and without treatment 3) at the patient's LE-in only 14% of consultations. Physicians often fail to adequately quantify competing risks. We recommend the "trifecta" approach, reporting 1) probability of cancer mortality 2) with and without treatment 3) at the patient's LE.

Abstract P3-12-17: Breast cancer treatment related survival gains in the African breast cancer - Disparities in outcomes study

Abstract Background: Breast cancer (BC) survival in Low and Middle Income Countries (LMICs), and particularly Sub Saharan Africa (SSA), is low and incidence rates are increasing. Accordingly, an almost 90% increase in annual BC mortality is projected to occur until 2040. The WHO Breast Cancer Global Initiative named comprehensive breast cancer treatment as one of three main pillars to reduce BC mortality. Here, we present the urgently needed up-to-date benchmark estimates of treatment effects on BC survival in SSA using data from the African Breast Cancer Disparities in Outcomes (ABC-DO) study.Methods: Since 2014 the hospital-recruited ABC-DO cohort follows-up women diagnosed with BC in five SSA countries. Socio-demographic, diagnostic, treatment and mortality data were obtained from medical records and via three-monthly follow-up calls with the patient. Cox proportional hazard models were fitted to estimate 5-year overall survival related to treatment initiation (surgery or systemic therapy) and treatment completion as time varying variates (surgery and systemic therapy completed) stratified by country and ethnicity and separate for localised and regional tumours. All models were adjusted for age, tumour grade, tumour size, node positivity, HIV status, and socioeconomic status. Results: Of 1699 ABC-DO women with invasive non-metastatic BC, 89% initiated BC treatment (from 72% in Nigeria to 100% in South African white women). Potentially curative treatment (surgery plus systemic therapy) was initiated by 63%, 22% initiated systemic treatment and 5 % only surgery. Initiated systemic therapy was completed by 49% of patients (from 16% in Nigeria to 70 % in South African black women). Median time to first treatment was 1.4 (IQR: 0.8–3) months and differed between countries (from 1.1 (0.6–1.7) in Namibian non-black to 3 (1.5–4.3) in Uganda). After 5 years, 49% (0.44 (CI: 0.31 – 0.62) ) of women initiating any treatment and 59% (0.39 (0.27 – 0.56) of women receiving surgery and initiating systemic treatment were still alive compared to 20% of women receiving no treatment. Conclusion: Timely and comprehensive BC treatment are needed to increase the very low survival rates in SSA. Citation Format: Milena Foerster, Eva Kantelhardt, MD, Pauline Boucheron, Isabel dos-Santos-Silva, PhD, Valerie McCormack, the ABC-DO study team. Breast cancer treatment related survival gains in the African breast cancer - Disparities in outcomes study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-17.

Prognostic importance of SUVmax values evaluated by 18F-FDG-PET/CT before nivolumab treatment in patients with metastatic renal cell carcinoma.

Nivolumab is a monoclonal antibody that binds to the programmed death-1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2. High response rates have been achieved with its use in the treatment of metastatic renal cell carcinoma (mRCC). We aimed to determine a relationship between 18-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG-PET/CT) performed before nivolumab treatment and treatment-related survival. Between 2014 and 2021, 32 patients who received nivolumab and had pre-treatment 18F-FDG-PET/CT evaluation were included in this retrospective study. The total SUV<inf>max</inf> (sum of SUV<inf>max</inf>) of all tumoral foci and the lesion with the highest SUVmax value were recorded. The relationship of these values with progression-free survival (PFS) and overall survival (OS) was evaluated. The median highest SUV<inf>max</inf> and sum of SUV<inf>max</inf> values were found as 14.4 and 41.4, respectively. PFS and OS were longer in the group with a sum of SUVmax value below 41.4 compared to the group with a higher group (OS, median 9.52 vs. 4.2 months [P=0.018]; PFS, median 9.6 vs. 3 months [P=0.003], respectively). In the group with the highest SUV<inf>max</inf> value below 14.4, PFS was evaluated as statistically significant compared to the higher group (PFS, median 16.74 vs. 3.3 months [P=0.004]), while OS was not found to be statistically significant (OS, median 25.45 vs. 16.74 months (P=0.110)). Our study showed that there might be a relationship between SUVmax values and PFS and OS. The SUV<inf>max</inf> values before nivolumab treatment can be used to predict prognosis and survival in mRCC patients.

Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy

PurposeOur study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion.MethodsBetween 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose–volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0 × 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan–Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses.ResultsA total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5–55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS.ConclusionAlthough iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer

BackgroundTreatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer.MethodsConsecutive patients with locally advanced (T2 ≥ 4 cm—T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann–Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS).ResultsWBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia.ConclusionsSarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose–response relationships.

Abstract 2528: Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415

Abstract Background: Prostate cancer is the most common cancer among men. Monitoring of patient-reported outcomes (PROs) can enhance provider-patient communication, promote better decision-making, and improve survival. Geospatial factors, namely rurality and neighborhood socioeconomic deprivation, could influence the experience across cancer treatment, thus impacting PROs and survival. This study examined associations of rurality, neighborhood socioeconomic deprivation (Area Deprivation Index [ADI]) with cancer treatment-related PROs and survival in men with prostate cancer. Methods: Data from men with prostate cancer in the trial NRG Oncology/RTOG 0415 were analyzed. In this trial, 1092 men were randomized to receive conventional radiotherapy (RT) or hypofractionated RT. Patients had Gleason scores of 2-6 and prostate-specific antigen of &amp;lt;10 ng/mL. Rurality was categorized as urban vs rural using Rural-Urban Continuum Codes via patient zip codes. Neighborhood socioeconomic deprivation was assessed by the ADI calculated via the American Community Survey by patient zip codes. The Expanded Prostate Cancer Index Composite (EPIC) measures cancer-specific quality of life (QOL); Hopkins Symptom Checklist measures anxiety and depression; EuroQoL-5 Dimension (EQ-5D) VAS and Index scores assess general health. All PROs were measured at baseline before and 6, 12, 24 and 60 months after RT. Overall survival (OS) and disease-free survival (DFS) were assessed using Cox proportional hazards models. Mixed effects models and generalized estimating equations were used to analyze PROs. Results: We analyzed 751 patients with complete data. Patients from the ADI 25% most deprived neighborhoods (vs. the other 75% of neighborhoods) were more likely to be non-white, unmarried and from rural areas. At baseline, patients from the most deprived areas had worse EPIC bowel score (P=0.011), worse sexual score (P=0.042) and worse hormonal score (P=0.015); patients from the most deprived areas had worse self-care (P=0.04) and more pain (P=0.047). Patients from rural areas had worse EPIC urinary score (P=0.03) and sexual score (P=0.003). Longitudinal analyses showed that ADI 25% most deprived areas (β=4.05, P=0.001) and rural areas (β=-5.70, P=0.003) were associated with worse EQ-5D VAS score. Compared to the 75% less deprived neighborhoods and urban, the ADI 25% most deprived neighborhoods and rural areas respectively had 47% (HR=1.466, P=0.033) and 93% (HR=1.925, P=0.026) relative increase in risk of recurrence or death (DFS). No differences were seen in OS. Conclusions: Patients with prostate cancer from the most deprived neighborhoods and rural areas had low QOL at baseline, poor general health and DFS. Interventions should target populations from socioeconomic deprived neighborhoods and rural areas to improve patient access to supportive care services and DFS. Citation Format: Jinbing Bai, Stephanie L. Pugh, Ronald Eldridge, Katherine Yeager, Qi Zhang, W Robert Lee, Amit B. Shah, Ian S. Dayes, David P. D'Souza, Jeff M. Michalski, Jason A. Efstathiou, John M. Longo, Thomas M. Pisansky, Jordan M. Maier, Sergio L. Faria, Anand B. Desai, Samantha A. Seaward, Howard M. Sandler, Mary E. Cooley, Deborah W. Bruner. Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2528.

Effects of Anticoagulants on Experimental Models of Established Chronic Liver Diseases: A Systematic Review and Meta-Analysis.

Objective The role of anticoagulants in chronic liver diseases is inconclusive. A meta-analysis was thus undertaken to evaluate treatment-related survival and antifibrotic effects in animal models of chronic liver diseases. Methods A systematic search of the literature took place (up to November 2020), screening for preclinical studies that evaluated anticoagulant effects in animal models of chronic liver diseases. We assessed the quality of methods and the certainty of evidence. Data on outcomes were extracted and pooled into random-effects models. Results Sixteen studies proved eligible, each assessing anticoagulant use in animals with chronic liver diseases. Generally, the pooled evidence demonstrated that the administration of anticoagulants is preventive against fibrogenesis, as indicated by METAVIR fibrosis scores (risk ratio = 0.66, 95% confidence interval: 0.47 to 0.94), portal pressure determinations (mean difference = −1.39, 95% confidence interval: −2.33 to −0.44), inflammatory activity (mean difference = −169.69, 95% confidence interval: −257.64 to −81.74), and indices of hepatic injury, specifically alanine aminotransferase (mean difference = −82.7, 95% confidence interval: −107.36 to −58.04), aspartate aminotransferase (mean difference = −186.12, 95% confidence interval: −254.90 to −117.33), albumin (mean difference = 0.59, 95% confidence interval: 0.16 to 1.01), and total bilirubin (mean difference = −0.96, 95% confidence interval: −1.46 to −0.46), and it had no impact on animal survival (risk ratio = 1.03, 95% confidence interval: 0.94 to 1.13). Conclusions Our assessments indicate that in animal models of chronic liver diseases, anticoagulants may alleviate the degree of fibrosis evaluated by the METAVIR score system, portal pressure, inflammatory activity, and serum indices of hepatocellular injury, without impacting survival. High-quality experimental studies are still required.

Overall health at diagnosis predicts the risk of complications within the first year after breast cancer diagnosis.

Breast cancer patients with overall poor health are at a greater risk of both complications during treatment and mortality from competing causes. We sought to determine the association of pre-existing comorbidities on treatment-related complications and overall survival. We identified women ages 40-90 years old from our institutional registry with stage I-II invasive breast cancer from 2005 to 2014. Recursive partitioning was used to stratify women based on pre-existing comorbidities as low, moderate, or high risk of treatment-associated complications. Cox proportional hazards model was constructed to estimate the association of risk with overall survival. 2077 women were studied. Mean age was 60 (IQR 51-68). Over half (54%) had ≥ 1 comorbid condition, and 29% experienced at least one adverse medical event within 1 year of diagnosis. Risk categories included low (no comorbidities or hypertension), moderate (combinations of comorbidities excluding congestive heart failure), and high (congestive heart failure in isolation or in combination with other conditions). High-risk women had a lower 10-year OS compared to moderate- or low-risk women (89% vs 90% vs 96%, log-rank p < 0.001). After adjustment, being at moderate (HR 2.20, 95% CI 1.30-3.72, p = 0.003) or high risk (HR 5.07, 95% CI 1.66-15.52, p = 0.004) of adverse sequelae was associated with reduced OS compared to those at low risk of these adverse medical events. Following breast cancer diagnosis, overall poor health was associated with a greater risk of mortality and complications within the first year of treatment, which was driven by a pre-existing diagnosis of congestive heart failure.

Abstract B5: Reversing epigenetic gene silencing to overcome immune evasion in CNS malignancies

Abstract Glioblastoma (GBM) is a lethal brain malignancy, and standard of care only offers a modest survival benefit. Emerging evidence of immune surveillance in the brain has prompted investigation of immunotherapy as a potential treatment strategy. However, preliminary studies have demonstrated impaired immune cell trafficking to the tumor, making GBMs immunologically “cold.” One mechanism of immune evasion by the tumor is to epigenetically silence the expression of chemoattractant cytokines. Previous studies in ovarian and prostate cancer have successfully established the ability of GSK126, a small-molecule inhibitor of histone methyl transferase EZH2, to promote tumor T-cell infiltration and subsequent antitumor response. Mechanistically, GSK126 was shown to promote expression of interferon gamma (IFN gamma)-induced chemokines CXCL9 and CXCL10. In the present study we evaluated the therapeutic efficacy of GSK126 in preclinical models of GBM. Our studies determined that treatment of murine and human glioblastoma cell lines with GSK126 increased IFN gamma-mediated gene expression of CXCL9 and CXCL10. Transwell migration assays performed using human T cells demonstrated increased T-cell migration when exposed to conditioned medium from tumor cells treated with GSK126 and IFN gamma. In vivo, efficacy of GSK126 was tested in combination with anti-PD-1 antibody in C57Bl/6 immunocompetent mice subcutaneously implanted with the syngeneic glioma cell line CT2A. Mice treated with the combination of GSK126 and anti-PD-1 antibody showed a significant decrease in tumor volume and improved overall survival. Tumors treated with combination therapy showed increased infiltration of CD8+ IFN gamma expressing T cells and increased CXCR3+ migratory T cells in the tumor-draining lymph node. Interestingly, treatment of mice with intracranial CT2A tumors with GSK126 alone resulted in small tumors with better prognosis. Treatment-related survival benefit was lost in immune-compromised mice, suggesting that efficacy depended upon drug-related increased lymphocyte trafficking and subsequent T cell-mediated antitumor response. Analysis of post-treatment tumor by LC-MS confirmed that GSK126 crosses the blood-brain barrier. Taken together, our data suggest a potential synergistic therapeutic role for GSK126 in glioblastoma by enhancing current immunotherapy regimens with reversing the epigenetic changes that enable immune cell evasion with resultant increases in immune cell trafficking to the tumor. Citation Format: Nivedita M. Ratnam, Heather M. Sonnemann, Mark R. Gilbert, Amber J. Giles. Reversing epigenetic gene silencing to overcome immune evasion in CNS malignancies [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B5.

Willingness to bear adversity and beliefs about the curability of advanced cancer.

20 Background: Older patients with advanced cancer who are certain that they could be cured pose unique challenges for physicians who wish to help them prepare for death. By estimating the prevalence of absolute certainty about curability (ACC) and examining its correlates we aim to inform the development of interventions to improve end of life care. We hypothesized that patients who report greater willingness to bear adversity in exchange for longevity will be more likely to demonstrate ACC. Methods: This is a cross-sectional analysis of a nationwide geriatric assessment trial. Patients were asked: “What are the chances the cancer will go away and never come back with treatment [100% (ACC), &gt; 50%, 50/50, &lt; 50%, 0%, or unclear].” We assessed willingness to bear adversity using two types of trade-off questions. For trade-offs between treatment-related adverse reactions and survival, five statements on specific adverse reactions (nausea/vomiting, assistance with activities, bedbound state, confusion, worsening memory) were administered. For trade-off preferences between quality of life (QoL) and survival, patients answered the following statement: “Maintaining my QoL is more important to me than living longer”. Logistic regression was used to assess the independent associations of patient trade-off preferences with ACC, after controlling for covariates. Results: 349 older patients were included; 8.0% had ACC. 7.4% of respondents disagreed/strongly disagreed with the statement “Maintaining my QoL is more important than living longer.” Patients who were willing to trade QoL for survival were more likely to demonstrate ACC (AOR 4.43, 95% CI 1.13-17.42). Trade-off preferences between adverse reactions and survival were not associated with ACC. Non-white race, &lt; high school education, lower household income, lack of social support, intact functional status, and no polypharmacy were associated with ACC (p &lt; 0.05). Conclusions: Patients with advanced cancer who are more willing to accept a decreased QoL for survival are more likely to be certain that they will be cured. Beyond sharing prognosis, clinicians might help patients improve prognostic understanding by helping them identify and articulate their values and beliefs.

PS02.109: CLINICAL SIGNIFICANCE OF NEOADJUVANT CHEMOTHERAPY IN ESOPHAGEAL CANCER PATIENTS WITH SEVERE DYSPHAGIA

Abstract Background Neoadjuvant chemotherapy (NAC) followed by curative resection is a standard treatment for resectable locally advanced esophageal cancer. However, clinical significance of NAC for patients with severe dysphasia due to esophageal stenosis was not fully validated. Methods Fifty patients with resectable locally advanced esophageal cancer who received cisplatin and 5-fluorouracil followed by curative resection between 2006 and 2005 in our institution were retrospectively reviewed. Twenty-one patients required nutritional support due to severe dysphasia before or during NAC (Group A) and the remaining 29 patients had no dysphagia (Group B). Clinicopathological characteristics, nutritional status, treatment-related adverse events, and survival were compared between the two groups. Results Seventeen patients received enteral feeding with transnasal tube and the remaining 4 patients (19%) received parenteral nutrition alone in group A. There were no significant differences in tumor characteristics between the two groups. Serum albumin levels of group A and B before NAC were 3.8 and 4.3 g/dL (P = 0.02), and those after NAC were 3.6 and 4.0 g/dL, respectively (P &lt; 0.01). NAC completion rates of group A and B were 86% and 83% (P = 0.78) and grade 3 or higher leukocytopenia developed in 33% and 10%, respectively (P = 0.07). Postoperative pneumonia of grade 2 or higher according to the Clavien-Dindo classification occurred in 48% and 28%, respectively (P = 0.23). Five-year overall survival rates of group A and B were 45% and 71%, respectively (P = 0.04). Conclusion NAC could be safely completed in patients with severe dysphagia; however, those were likely to have treatment-related adverse events and poorer survival. Disclosure All authors have declared no conflicts of interest.

Subgroup analysis based on prognostic and predictive gene signatures for adjuvant chemotherapy in early-stage non-small-cell lung cancer patients

ABSTRACTIn treating patients diagnosed with early Stage I non-small-cell lung cancer (NSCLC), doctors must choose surgery alone, Adjuvant Cisplatin-Based Chemotherapy (ACT) alone or both. For patients with resected stages IB to IIIA, clinical trials have shown a survival advantage from 4–15% with the adoption of ACT. However, due to the inherent toxicity of chemotherapy, it is necessary for doctors to identify patients whose chance of success with ACT is sufficient to justify the risks. This research seeks to use gene expression profiling in the development of a statistical decision-making algorithm to identify patients whose survival rates will improve from ACT treatment. Using the data from the National Cancer Institute, the lasso method in the Cox-Proportional-Hazards regression model is used as the main method to determine a feasible number of genes that are strongly associated with the treatment-related patient survival. Considering treatment groups separately, the patients are assigned a risk category based on the estimation of survival times. These risk categories are used to develop a Random Forests classification model to identify patients who are likely to benefit from chemotherapy treatment. This model allows the prediction of a new patient’s prognosis and the likelihood of survival benefit from ACT treatment based on a feasible number of genomic biomarkers. The proposed methods are evaluated using a simulation study.

Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer

Claudin-2 is a trans-membrane protein—component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU±irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.

Synchronous peritoneal metastases of small bowel adenocarcinoma: Insights into an underexposed clinical phenomenon

BackgroundThe aim of this population-based study was to provide insight into the incidence, risk factors and treatment-related survival of patients with peritoneal metastases (PM) of small bowel adenocarcinoma (SBA). MethodsData from the Netherlands Cancer Registry were used. All patients diagnosed with SBA between 2005 and 2014 were included. The influence of patient and tumour characteristics on the odds of developing PM was analysed. Subsequently, for all further analyses, patients without synchronous PM of SBA were excluded. The log-rank test and Kaplan-Meier analyses were conducted to estimate survival, and the Cox proportional hazards model was used to evaluate the risk of death. ResultsOf the 1428 included patients diagnosed with SBA, 181 (13%) presented with synchronous PM. Synchronous PM was found in 9% of the duodenal tumours and in 17% of the more distal tumours. Median overall survival of all patients with PM was 5.9 months, whereas survival of both 11 months was observed in patients treated with primary tumour resection or palliative chemotherapy and 32 months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC). Poor prognostic factors for survival were age ≥70 years (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.1–2.2), systemic metastases other than PM (HR 2.0, 95% CI 1.4–2.9) and an advanced (HR 1.9, 95% CI 1.3–3.0) or unknown T-stage (HR 2.1, 95% CI 1.2–3.5). ConclusionsSynchronous PM was frequently encountered in SBA. Without treatment, prognosis was extremely poor. Survival was higher after primary tumour resection, palliative chemotherapy and CRS+HIPEC, but selection bias probably played a significant role calling for further clinical research.