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Objective: To evaluate the validity of the Utah statewide All-Payer Claims Database (APCD), we compared breast cancer-specific treatments and dosages with gold-standard abstraction of medical records., Study Design: In this pilot study, breast cancer treatments were abstracted by a certified tumor registrar at the Utah Cancer Registry (UCR) for patients diagnosed in 2013 with breast cancer. The abstraction of medical records was the gold standard for comparison with treatments identified in the APCD. The reliability and agreement between the treatment identified in the APCD and abstraction data were measured with sensitivity and specificity. Dose consistency was measured with the intraclass correlation coefficients (ICC)., Results: Compared with the 186 abstractions, the sensitivity of the APCD to identify chemotherapy agents was high: 89% for any agent, 91% for carboplatin, 83% for docetaxel, 82% for doxorubicin, or 94.7% for biologic therapy. The consistency between the chemotherapy dosage identified in the claims and the abstraction varied from 63% to 76%. For radiotherapy, the sensitivity of the claims to identify the completed radiotherapy regimen was 66%. The ICC between radiotherapy doses identified in the claims and the abstraction was 54% (95% confidence interval [CI], 48%, 67%)., Conclusions: Employing these novel methods, the claims were highly reliable in identifying cancer treatment agents overall, namely carboplatin, docetaxel, and trastuzumab. The claims were of moderate utility in capturing the treatment dose information. In addition to the APCD, the use of multiple data sources improved the completeness of cancer treatment information., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose/objectives: NRG/RTOG 0436 evaluated cetuximab added to chemoradiation (CRT) for non-operative esophageal cancer management. PRO objectives assessed improvement in the FACT-Esophageal cancer subscale (ECS), version 4, with cetuximab, and if improved ECS correlated with clinical complete response (cCR)., Materials/methods: Patients were randomized to cisplatin/paclitaxel/radiation ± cetuximab. Overall survival (OS) was the primary endpoint, with a 420 patient target, which also provided 82% power to detect ≥ 15 increase in the proportion of cetuximab patients with ECS improvement from baseline to 6-8 weeks post-CRT; α = 0.05, using a χ 2 test. Improvement in ECS and its Swallowing and Eating Indices (SI, EI) was defined as 5, 4 and 2 point increases, respectively, from baseline to 6-8 weeks post-CRT. Univariate logistic regression assessed if cCR was associated with improved ECS., Results: This study was stopped early for not meeting a pre-specified OS endpoint and did not show survival benefit. Of 420 planned patients, 344 enrolled and 281 consented to PROs. ECS was completed by 261 (93%) at baseline, 173 (66%) 6-8 weeks post-CRT, and 117 (64%) at 1 year. At 6-8 weeks, patients receiving CRT + Cetuximab didn't have improved ECS; they experienced a lower proportion of improvement compared to standard CRT (37% vs. 53%; P = 0.04). The proportion of CRT patients with improvement in SI was 9% higher than with cetuximab, but not statistically significant (39% vs. 30%, P = 0.22). There was no association between treatment and EI. When examining ECS scores at 1 year by cCR vs. residual disease, a higher proportion of cCR patients improved, but not statistically significant (48% vs. 45%, P = 0.74)., Conclusions: The addition of cetuximab to CRT for the nonoperative management of esophageal cancer did not improve PROs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Objective: Local intraprostatic radiorecurrence of prostate cancer (IPR-PC) can be associated with an aggressive natural history and impact long-term disease-specific survival. While appropriate local salvage intervention can be curative, best practices for workup and local salvage of intraprostatic recurrence are poorly defined. The American Radium Society (ARS) Genitourinary Appropriate Use Criteria Committee sought to develop evidence-based recommendations to address this gap., Methods: PubMed and Embase were searched to retrieve a comprehensive set of relevant peer-reviewed articles on four topics relevant to the workup and treatment of IPR-PC. The literature was evaluated and summarized by three investigators, and clinical variants were created for each of the four topics. The ARS Genitourinary AUC multidisciplinary expert panel voted on the most appropriate procedures for each variant, and a modified Delphi approach was used to summarize recommendations., Key Findings and Limitations: The panel concluded that radiographic staging via prostate-specific membrane antigen positron emission tomography (PSMA PET) and multiparametric magnetic resonance imaging should be performed to exclude patients with metastatic disease and identify the local extent of radiorecurrence. Biopsy is required before local salvage to avoid excessive toxicity in patients whose radiographic recurrence represents a treatment effect. Consideration of local salvage is preferred in lieu of noncurative hormonal manipulation alone, although shared decision-making is critical. Salvage reirradiation approaches are recommended to limit toxicity. Hormonal therapy may be beneficial for radiosensitization when radiotherapeutic salvage is pursued, but only of short duration, and classic androgen deprivation therapies are preferred over novel hormonal agents. Focal salvage should be pursued when confidence in focal recurrence can be confirmed via multiple radiographic and tissue sampling modalities, although the toxicity associated with whole-gland salvage appears to be very tolerable. Several radiotherapeutic salvage regimens exist, most of which can be carried out in six or fewer fractions. The data informing this guideline are limited to individuals initially treated with conventionally fractionated external beam radiotherapy and with workup for recurrence before the PSMA PET era., Conclusions and Clinical Implications: This consensus guideline provides evidence-based guidance on the appropriate procedures for workup and treatment of IPR-PC. Prospective evidence to enrich these guidelines is eagerly anticipated., Patient Summary: We summarize evidence for the best workup and treatment for patients with local recurrence of prostate cancer after radiotherapy. A panel of experts evaluated previous studies and voted on the procedures that should be performed and those that should be avoided. This guideline is a useful tool for helping doctors to discuss the best treatment options that maximize the chance of cure while minimizing side effects., (Published by Elsevier B.V.)

Background: Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer., Methods: Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided., Results: The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P < .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis., Conclusion: Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objective: Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer., Methods: The literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023., Key Content and Findings: Clinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers., Conclusions: According to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-843/coif). P.Z. reports funding supports from General Project of Key Research and Development Plan, Shaanxi Provincial Department of Science and Technology (No. 2021SF-374) and General Research Project of Xi'an Science and Technology Bureau (No. 23YXYJ0136). A.M. received payment/honoraria for being speaker and panelist at ASCO Advantage program upper GI cancer program in Virginia, USA for 2022 and 2023. S.L. reports consulting fees from Cancer Study Group and expert witness fees from Kipp and Christian. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Limited population-based studies have focused on breast cancer survivors in rural populations. We sought to evaluate the risk of adverse health outcomes among rural and urban breast cancer survivors and to evaluate potential predictors for the highest risk outcomes., Methods: A population-based cohort of rural and urban breast cancer survivors diagnosed between 1997 and 2017 was identified in the Utah Cancer Registry (UCR). Rural breast cancer survivors were matched on year (±1 year) and age at cancer diagnosis (±1 year) with up to 5 urban breast cancer survivors (2,359 rural breast cancer survivors; 11,748 urban breast cancer survivors). Cox proportional hazards models were used to calculate HRs with 99% confidence intervals (CI) for adverse health outcomes overall, within 5 years, and >5 years after cancer diagnosis., Results: Compared with urban breast cancer survivors, rural breast cancer survivors had a 39% (HR, 1.39; 95% CI, 1.02-1.65) higher risk of heart failure (HF) within the 5 years of follow-up. Overall, there was no increase in the risk of other evaluated adverse health outcomes. A higher baseline body mass index and Charlson Comorbidity Index, family history of cardiovascular diseases, family history of breast cancer, and advanced cancer stage were risk factors for HF for rural and urban breast cancer survivors, with similar levels of HF risk., Conclusions: Rural residence was associated with an increased risk of HF among breast cancer survivors., Impact: Our study highlights the need for primary preventive strategies for rural cancer survivors at risk of heart failure., (©2023 American Association for Cancer Research.)

Background: Randomized trials have shown that risk-adapted intraoperative radiation therapy (IORT) after breast-conserving surgery for low-risk breast cancer patients is a safe alternative to whole-breast radiation therapy (WBRT). The risk-adapted strategy allows additional WBRT for predefined high-risk pathologic characteristics discovered on final histopathology. The greater the percentage of patients receiving WBRT, the lower the recurrence rate. The risk-adapted strategy, although important and necessary, can make IORT appear better than it actually is., Methods: Risk-adapted IORT was used to treat 1600 breast cancers. They were analyzed by the intention-to-treat method and per protocol to better understand the contribution of IORT with and without additional whole-breast treatment. Any ipsilateral breast tumor event was considered a local recurrence., Results: During a median follow-up period of 63 months, local recurrence differed significantly between the patients who received local treatment and those who received whole-breast treatment. For 1393 patients the treatment was local treatment alone. These patients experienced 79 local recurrences and a 5-year local recurrence probability of 5.95 %. For 207 patients with high-risk final histopathology, additional whole-breast treatment was administered. They experienced two local recurrences and a 5-year local recurrence probability of 0.5 % (p = 0.0009)., Conclusions: Whole-breast treatment works well at reducing local recurrence, and it is a totally acceptable and necessary addition to IORT as part of a risk-adapted program. However, the more whole-breast treatment that is given, the more it dilutes the original plan of simplifying local treatment and the less we understand exactly what IORT contributes to local control as a stand-alone treatment., (© 2023. The Author(s).)

Purpose: Rural disparities in prostate cancer survivorship and cardiovascular disease remain. Prostate cancer treatment also contributes to worse cardiovascular disease outcomes. Our objective was to determine whether rural-urban differences in cardiovascular outcomes contribute to disparities in prostate cancer survivorship., Materials and Methods: Data were collected from the Utah Population Database. Rural and urban prostate cancer survivors were matched by diagnosis year and age. Cox proportional hazards models were used to estimate hazard ratios for cardiovascular disease (levels 1-3) based on rural-urban classification, while controlling for demographic and socioeconomic characteristics. We identified 3,379 rural and 16,253 urban prostate cancer survivors with a median follow-up of 9.3 years., Results: Results revealed that rural survivors had a lower risk of hypertension (HR 0.90), diseases of arteries (HR 0.92), and veins (HR 0.92) but a higher risk of congestive heart failure (HR 1.17). Interactions between level 2 cardiovascular diseases and rural/urban status, showed that diseases of the heart had a distinct between-group relationship for all-cause (P = 0.005) and cancer-specific mortality (P = 0.008)., Conclusions: This study revealed complex relationships between rural-urban status, cardiovascular disease, and prostate cancer. Rural survivors were less likely to be diagnosed with screen-detected cardiovascular disease but more likely to have heart failure. Further, the relationship between cardiovascular disease and survival was different between rural and urban survivors. It may be that our findings underscore differences in healthcare access where rural patients are less likely to be screened for preventable cardiovascular disease and have worse outcomes when they have a major cardiovascular event., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Rural cancer survivors experience considerable health disparities compared to urban cancer survivors for cancer treatment and survival. The objective of our study was to investigate the risk of developing diseases for rural compared to urban prostate cancer survivors in Utah., Methods: We identified a cohort of 3575 rural prostate cancer survivors and 17,778 urban prostate cancer survivors from the Utah Cancer Registry. The Fine-Gray subdistribution hazards model was used to estimate hazard ratios and 95 % confidence intervals for diseases in major body systems among rural compared to urban prostate cancer survivors at > 1-5 years and > 5 years after prostate cancer diagnosis., Results: Rural residence was associated with an increased risk of diseases of the respiratory system at > 5 years (HR: 1.16, 95 % CI: 1.01-1.32) after cancer diagnosis compared to urban residence among prostate cancer survivors in Utah. Decreased risks were observed in infectious and parasitic diseases, diseases of the blood and blood-forming organs, diseases of the nervous system and sense organs, and diseases of the skin and subcutaneous tissue for rural prostate cancer survivors between 1 and 5 years after cancer diagnosis., Conclusions: Rural prostate cancer survivors in Utah were somewhat healthier compared to urban prostate cancer survivors. Further studies are needed to confirm whether these associations are also supported for rural prostate cancer survivors in other regions of the U.S., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: In 2021, 59.6% of low-risk patients with prostate cancer were under active surveillance (AS) as their first course of treatment. However, few studies have investigated AS and watchful waiting (WW) separately. The objectives of this study were to develop and validate a population-level machine learning model for distinguishing AS and WW in the conservative treatment group, and to investigate initial cancer management trends from 2004 to 2017 and the risk of chronic diseases among patients with prostate cancer with different treatment modalities., Methods: In a cohort of 18,134 patients with prostate adenocarcinoma diagnosed between 2004 and 2017, 1,926 patients with available AS/WW information were analyzed using machine learning algorithms with 10-fold cross-validation. Models were evaluated using performance metrics and Brier score. Cox proportional hazard models were used to estimate hazard ratios for chronic disease risk., Results: Logistic regression models achieved a test area under the receiver operating curve of 0.73, F -score of 0.79, accuracy of 0.71, and Brier score of 0.29, demonstrating good calibration, precision, and recall values. We noted a sharp increase in AS use between 2004 and 2016 among patients with low-risk prostate cancer and a moderate increase among intermediate-risk patients between 2008 and 2017. Compared with the AS group, radical treatment was associated with a lower risk of prostate cancer-specific mortality but higher risks of Alzheimer disease, anemia, glaucoma, hyperlipidemia, and hypertension., Conclusion: A machine learning approach accurately distinguished AS and WW groups in conservative treatment in this decision analytical model study. Our results provide insight into the necessity to separate AS and WW in population-based studies.

Purpose There are several studies suggesting a correlation between image-guided radiotherapy (IGRT) setup errors and body mass index (BMI). However, abdominal fat content has visceral and subcutaneous components, which may affect setup errors differently. This study aims to analyze a potential workflow for characterizing adipose content and distribution in the region of the target that would allow a quickly calculated metric of abdominal fat content to stratify these patients. Methods IGRT shift data was retrospectively tabulated from daily fan-beam CT-on-rails pre-treatment alignment for 50 abdominal radiation therapy (RT) patients, and systematic and random errors in the daily setup were characterized by tabulating average and standard deviations of shift data for each patient and looking at differences for different distributions of adipose content. Visceral and subcutaneous fat content were defined by visceral fat area (VFA) and subcutaneous fat area (SFA) using a region-growing algorithm to contour adipose tissue on CT simulation scans. All contours were created for a single slice at the treatment isocenter, on which the VFA and SFA were calculated. A log-rank test was used to test trends in shifts over quartiles of adiposity. Results VFA ranged from 1.9-342.8c m 2 , and SFA from 11.8-756.0 cm 2 . The standard definition (SD) of random error (σ) in the lateral axis for Q1 vs. Q4 VFA was 0.10cm vs. 0.29cm, 0.12cm vs. 0.28cm for SFA, and 0.12cm vs. 0.31cm for BMI. The percentage of longitudinal shifts greater than 10mm for Q1 vs. Q4 VFA was 0% vs. 9%, 2% vs. 19% for SFA, and 0% vs. 20% for BMI. Statistically significant trends in shifts vs. the BMI quartile were seen for both pitch and the longitudinal direction, as well as for pitch corrections vs. the VFA quartile. Conclusion Within this dataset, abdominal cancer patients showed statistically significant trends in shift probability vs. BMI and VFA. Also, patients in the upper quartiles of all adiposity metrics showed an increased SD of σ in the lateral direction and increased shifts over 10 mm in the longitudinal direction. However, despite these relationships, neither VFA nor SFA offered discernible advantages in their relationship to shift uncertainty relative to BMI., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Price et al.)

Purpose: The purpose of this study is to understand factors associated with timing of adjuvant therapy for cholangiocarcinoma and the impact of delays on overall survival (OS)., Methods: Data from the National Cancer Database (NCDB) for patients with non-metastatic bile duct cancer from 2004 to 2015 were analyzed. Patients were included only if they underwent surgery and adjuvant chemotherapy and/or radiotherapy (RT). Patients who underwent neoadjuvant or palliative treatments were excluded. Pearson's chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity score matching with inverse probability of treatment weighting, OS was compared between patients initiating therapy past various time points using Kaplan Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling., Results: In total, 7,733 of 17,363 (45%) patients underwent adjuvant treatment. The median time to adjuvant therapy initiation was 59 days (interquartile range 45-78 days). Age over 65, black and Hispanic race, and treatment with RT alone were associated with later initiation of adjuvant treatment. Patients with larger tumors and high-grade disease were more likely to initiate treatment early. After propensity score weighting, there was an OS decrement to initiation of treatment beyond the median of 59 days after surgery., Conclusions: We identified characteristics that are related to the timing of adjuvant therapy in patients with biliary cancers. There was an OS decrement associated with delays beyond the median time point of 59 days. This finding may be especially relevant given the treatment delays seen as a result of COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes., Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT)., Design, Setting, and Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023., Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy., Main Outcomes and Measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable., Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07)., Conclusions and Relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Background: Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis., Methods: We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation., Results: A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%])., Conclusion: Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis., (© 2022 Wiley Periodicals LLC.)

Introduction: Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer., Patients and Methods: From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests., Results: The cohort included 631 patients (n = 428 RP, n = 203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm., Conclusion: Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality., (Copyright © 2022. Published by Elsevier Inc.)

Background: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified., Methods: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data., Results: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001)., Conclusions: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation., (© 2022 American Cancer Society.)

Purpose: Delays in initiation of radiotherapy may contribute to inferior oncologic outcomes that are more commonly observed in minoritized populations in the United States. We aimed to examine inequities associated with delayed initiation of intensity-modulated radiotherapy (IMRT)., Materials and Methods: The National Cancer Database was queried to identify the 10 cancer sites most commonly treated with IMRT. Interval to initiation of treatment (IIT) was broken into quartiles for each disease site, with the 4 th quartile classified as delayed. Multivariable logistic regression for delayed IIT was performed for each disease site using clinical and demographic covariates. Differences in magnitude of delay between subsets of patients stratified by race and insurance status were evaluated using two-sample t -tests., Results: Among patients (n = 350,425) treated with IMRT between 2004 and 2017, non-Hispanic Black (NHB), Hispanic, and Asian patients were significantly more likely to have delayed IIT with IMRT for nearly all disease sites compared with non-Hispanic White (NHW) patients. NHB, Hispanic, and Asian patients had significantly longer median IIT than NHW patients (NHB 87 days, P < .01; Hispanic 76 days, P < .01; Asian 74 days, P < .01; and NHW 67 days). NHW, Hispanic, and Asian patients with private insurance had shorter median IIT than those with Medicare ( P < .01); however, NHB patients with private insurance had longer IIT than those with Medicare ( P < .01)., Conclusion: Delays in initiation of IMRT in NHB, Hispanic, and Asian patients may contribute to the known differences in cancer outcomes and warrant further investigation, particularly to further clarify the role of different insurance policies in delays in advanced modality radiotherapy.

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC)., Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test., Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs . 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96)., Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy., Trial Registration: ClinicalTrials.gov NCT02448979., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3810/coif). YSM, SGG, YL, ALH, JFL, XFL, THR, JHF, JQM, MQX, RQZ, GMX, XNF, KNC, WMM, YYL, HXL, ZRZ, YF, DHF, XDW, LGY, SM, WQW, YBG, JH report that this work was supported by the grants from National Science and Technology Support Program (Study ID Number: NKTRDP-2015BAI12B08-01, YSM). The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Adjuvant guidelines in surgically resected p16+ oropharyngeal carcinoma (OPC) with positive surgical margins (PSM) or extranodal extension (ENE) are based on randomized controlled trials predating p16 status. It remains unclear if adjuvant chemotherapy is necessary in p16+ patients with these features., Methods: The National Cancer Database was used to identify cases of nonmetastatic p16+ OPC diagnosed from 2010 to 2017. Patients treated with surgical resection followed by adjuvant radiation (aRT) or adjuvant chemoradiation (aCRT) were eligible for analysis., Results: A total of 14 071 patients were eligible for analysis. Overall survival (OS) was not statistically different between aRT and aCRT in patients with PSM (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.56-1.28), ENE (HR 0.93, 95% CI 0.69-1.27) or both (HR 0.73, 95% CI 0.41-1.31)., Conclusions: In patients with p16+ OPC with ENE, PSM, or both, adding chemotherapy to aRT was not associated with improved OS., (© 2021 Wiley Periodicals LLC.)

Background: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer (PCa) outcomes. However, the impact of MTD in PCa treated with external beam radiotherapy and brachytherapy boost (EBRT+BB) remains unknown., Materials and Methods: Patients with PCa treated with EBRT+BB were identified from an institutional database. Clinical data including MTD, age, androgen deprivation therapy (ADT) use, prostate specific antigen (PSA), International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging were retrospectively collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced with MTD grouped by receiver operating characteristic (ROC) cut-point. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group., Results: Of 191 patients treated with EBRT+BB, 113 had MTD measurements available. Larger MTD was associated with increased ADT use and seminal vesicle involvement. ROC optimization identified MTD of 24 mm as the optimal cut-point for both BF and DM. MTD was independently associated with both BF (HR 8.61, P = .048, 95% CI 1.02-72.97) and DM (HR 8.55, P = .05, 95% CI 1.00-73.19). In patients with ISUP group 4 to 5 disease, MTD > 24 mm was independently associated with increased risk of DM (HR 10.13, P = .04, 95% CI 1.13-91.12)., Conclusions: This is the first study to evaluate MTD in the setting of EBRT+BB. These results demonstrate that MTD is independently associated with BF and metastasis. This suggests a possible role for MTD in risk assessment models and clinical decision-making for men receiving EBRT+BB., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The benefits of intensity modulated radiation therapy (IMRT) compared with standard 3-dimensional conformal radiation therapy have been demonstrated in many cancer sites and include decreased acute and late toxicity, improved quality of life, and opportunities for dose escalation. Limited literature suggests non-white patients may have lower utilization of IMRT. We hypothesized that as the use of IMRT has increased in recent years, racial inequities have persisted and disproportionately affect non-Hispanic Black (NHB) patients. We aim to evaluate temporal trends in IMRT utilization focusing on disparities among minoritized populations., Methods and Materials: The National Cancer Database was queried to identify the 10 disease sites with the highest total number of cancer patients treated with definitive intent IMRT in 2017, the most recent year for which data are available. Exclusions included stage IV, age <18 years, unknown insurance status, unknown race, and palliative intent radiation. Race and ethnicity variables were combined and classified as non-Hispanic White, Hispanic, NHB, Asian, Native American/Eskimo, and Hawaiian/Pacific Islander. Multivariable logistic regression for IMRT utilization was performed for each disease site for both early (2004-2010) and contemporary (2011-2017) cohorts, adjusting for clinical and demographic covariates., Results: Among the 10 selected disease sites, 1,010,292 patients received radiation therapy as part of definitive treatment between 2004 and 2017. Overall IMRT utilization rates increased from 22.0% in 2004 to 57.8% in 2017. After adjustment and compared with non-Hispanic White patients, NHB patients were significantly less likely to receive IMRT in 1 of 10 disease sites in the 2004 to 2010 cohort, and 5 of 10 disease sites in the 2011 to 2017 cohort., Conclusions: Despite greater awareness of racial disparities in cancer care and outcomes, this study demonstrates worsening disparities in the use of IMRT, particularly for NHB patients. These differences may exacerbate racial disparities in cancer outcomes; therefore, identification of underlying drivers of differential IMRT utilization is warranted., (© 2022 The Author(s).)

Introduction: Managing pathologically node positive (pN+) prostate cancer (PCa) is controversial. We describe temporal patterns and predictors of pN+ PCa in men with initially surgically managed clinically node negative (cN-) PCa., Materials and Methods: This observational retrospective analysis of nonmetastatic, cN- PCa uses the National Cancer Database. Multivariable logistic regression was used to identify covariates associated with pN+ disease. Cox proportional hazards modeling and Kaplan-Meier analysis were used to evaluate survival patients undergoing radical prostatectomy with or without pelvic lymph node dissection (PLND)., Results: The rates of radical prostatectomy in men with grade group (GG) 4 and GG5 increased from 47.6% to 53.1% and from 42.5% to 49.5%, respectively. The annual rate increased from 2.02% in 2010 to 5.12% in 2017 (P < .001). The annual rates of PLND increased from 54.3% to 71.7%. The most significant predictor of pN+ PCa was ISUP GG4 (odds ratio [OR] 12.5, P< .001) and GG 5 (OR 26.2, P < .001). Rates of pN+ identification increased from 5.5% to 9.4% in men with GG4 and from 13.4% to 19.5% in men with GG5 (P< .001). In GG4 and GG5, patients undergoing PLND had superior survival to those managed without PLND (P < .01)., Conclusion: Among patients with cN- PCa, the diagnosis of pN+ PCa has become more common over time. GG4 and GG5 are the strongest independent predictors of pN+ disease. Because incidental pN+ results in upstaging these data are useful for informing discussions before radical prostatectomy., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Radiation therapy (RT) and intrathecal drug delivery systems (IDDS) are often used concurrently to optimize pain management in patients with cancer. Concern remains among clinicians regarding the potential for IDDS malfunction in the setting of RT. Here we assessed the frequency of IDDS malfunction in a large cohort of patients treated with RT., Materials and Methods: Cancer patients with IDDS and subsequent RT at our institution from 2011 to 2019 were eligible for this study. Patients were excluded in the rare event that their IDDS was managed by an outside clinic and follow-up documentation was unavailable. Eighty-eight patients aged 22-88 years old (43% female, 57% male) representing 106 separate courses of RT were retrospectively identified. Patients received varying levels of radiation for treatment of cancer and cumulative dose to the IDDS was calculated. IDDS interrogation was subsequently performed by a pain specialist. Malfunction was recorded as deviation from the expected drug volume and/or device errors reported upon interrogation as defined by the manufacturer., Results: Total measured RT dose to the IDDS ranged from 0 to 18.0 Gy (median = 0.2 Gy) with median dose of 0.04 Gy/fraction (range, 0-3.2 Gy/fraction). Ten pumps received a total dose >2 Gy and three received ≥5 Gy. Eighty-two percentage of patients had follow-up with a pain specialist for IDDS interrogation and all patients underwent follow-up with a healthcare provider following RT. There were zero incidences of IDDS malfunction related to RT. No patient had clinical evidence of radiation related pump malfunction at subsequent encounters., Conclusions: We found no evidence that RT in patients with IDDS led to device failure or dysfunction. While radiation oncologists and pain specialists should coordinate patient care, it does not appear that RT dose impacts the function of the IDDS to warrant significant clinical concern., (© 2021 International Neuromodulation Society.)

Background: Surgical resection is an integral component of the curative-intent treatment for most patients with non-metastatic rectal cancer. However, some patients refuse surgery for a number of reasons. Utilizing the National Cancer Database (NCDB), we investigated the sociodemographic and clinical factors associated with patients who were coded as having been offered but refused surgery, and the factors affecting overall survival (OS) in these patients., Methods: Adult patients with adenocarcinoma of the rectum (excluding T1N0M0 and M1 disease) diagnosed from 2004 to 2015 were analyzed in this retrospective cohort study. Logistic regression was performed to identify factors associated with refusal of surgery. OS of patients refusing surgery was compared using Kaplan-Meier estimate, log-rank test, propensity score matching, and proportional hazards regression., Results: A total of 55,704 patients were identified: 54,266 received definitive surgery (97.4%) and 1,438 refused (2.6%). Of patients refusing surgery, 135 (9.4%) were stage I, 709 (49.3%) were stage II, and 594 (41.3%) were stage III. Patients were more likely to refuse surgery as the study period progressed (P<0.01). Factors associated with refusal of surgery on multivariate analysis include: age ≥70 years, Black race, non-private insurance, and tumor size greater than 2 cm (all values P≤0.01). The 5-year OS was 61.6% for the surgery cohort and 35.7% for the refusal cohort. In the propensity matched groups, median survival was 84.2 months in patients who received definitive surgery compared to 43.7 months in patients who refused surgery. As an index for comparison, patients who refused surgery but received both radiotherapy and chemotherapy had a median survival of 48.5 months. Among patients that refused surgery, those that received radiotherapy alone, chemotherapy alone, or radiotherapy and chemotherapy (compared to no treatment) experienced a survival benefit (all values P≤0.01)., Conclusions: In patients with non-metastatic adenocarcinoma of the rectum reported in the NCDB, age, race, and insurance status were associated with refusal of surgery. Refusal of surgery was more common in the later years of the study. Survival is poor in patients who refused surgical resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-20-437). RT reports personal fees from QED Therapeutics and personal fees from the Lynx Group, which are both outside of the submitted work. The other authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: The use of stereotactic body radiation therapy (SBRT) in pediatric patients has been underreported. We reviewed practice patterns, outcomes, and toxicity of SBRT in this population., Methods and Materials: In this multi-institutional study, 55 patients with 107 non-central nervous system lesions treated with SBRT between 2010 and 2016 were reviewed. Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST v1.1 criteria for soft-tissue and bone lesions, respectively. Patterns of local failure (LF) were assessed dosimetrically. The cumulative incidence of LF and toxicity were estimated accounting for the competing risk event of death. Predictors of LF were identified through joint frailty models for clustered competing risks., Results: The median (range) dose/fraction was 7 (4.5-25) Gy, the total (range) dose/site was 35 (12-45), and the median (range) number of fractions was 5 (1-9). The radiographic response rates of bone and soft-tissue lesions were 90.6% and 76.7%, respectively. Symptom improvement was observed for 62% of symptomatic sites. A total of 27 LFs were documented, with 14 in-field, 9 marginal, and 4 out-of-field LFs. The 1-year estimated cumulative LF rate, progression-free survival, and overall survival were 25.2% (95% confidence interval [CI], 17.2%-36.1%), 17.5% (95% CI, 9.0%-34.1%), and 61% (95% CI, 48.9%-76.1%), respectively. Lesion type (soft tissue vs bone) was the only significant predictor of LF on multivariable analysis (P = .04), with increased hazard for soft-tissue lesions. No acute or late toxicity of grade 4 or higher was observed; the estimated 1-year cumulative incidence of late toxicity of any grade was 7.5% (95% CI, 3.6%-12.1%)., Conclusions: The SBRT was well tolerated and resulted in radiographic response and symptom palliation in most pediatric patients with advanced disease. The 1-year cumulative LF rate of 25% will serve as a benchmark for further modifications to radiation therapy indications, parameters, and combination therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT., Methods and Materials: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework., Results: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent., Conclusions: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to understand factors associated with refusal of local therapy in esophageal cancer and compare the overall survival (OS) of patients who refuse therapies with those who undergo recommended treatment., Methods: National Cancer Database data for patients with non-metastatic esophageal cancer from 2006 to 2013 were pooled. T1N0M0 tumors were excluded. Pearson's Chi-square test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, OS was compared between patients who refused therapies and those who underwent recommended therapy, using Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling., Results: In total, 37,618 patients were recommended radiation therapy (RT) and/or esophagectomy; we found 1403 (3.7%) refused local therapies. Specifically, 890 of 18,942 (4.6%) patients refused surgery and 667 of 31,937 (2.1%) refused RT. Older patients, females, those with unknown lymphovascular space invasion, and those uninsured or on Medicare were more likely to refuse. Those with squamous cell carcinoma, N1 disease, higher incomes, living farther from care, and those who received chemotherapy were less likely to refuse. Five-year OS was decreased in patients who refused (18.1% vs. 27.6%). The survival decrement was present in adenocarcinoma but not squamous cell carcinoma. In patients who received surgery or ≥ 50.4 Gy RT, there was no OS decrement to refusing the other therapy., Conclusions: We identified characteristics that correlate with refusal of local therapy. Refusal of therapy was associated with decreased OS. Patients who received either surgery or ≥ 50.4 Gy RT had no survival decrement from refusing the opposite modality.

Primary squamous cell carcinoma is a rare, aggressive disease with historically poor outcomes and no established treatment guidelines. Case reports are limited but describe multiple treatment approaches. Seeking to identify practice patterns and treatment outcomes, we used the US National Cancer Data Base to identify 66 males with locoregional primary squamous cell carcinoma of the prostate treated with surgery, chemotherapy, and/or radiotherapy between 2004 and 2015. Patients were stratified into treatment groups consisting of local therapy alone ( n  = 40; 61%), local therapy and chemotherapy ( n  = 13; 20%), chemotherapy alone ( n  = 7; 11%), and observation ( n  = 6; 9%). Patients with clinical stage T3-T4 disease were significantly more likely to receive combined chemotherapy and local therapy on multivariable analysis. Median survival was 20 mo for patients treated with local therapy alone, 37 mo with local therapy and chemotherapy, and 11 mo with chemotherapy alone. Overall survival was not significantly different between treatment groups. Despite limitations in sample size, these data suggest that addition of chemotherapy to local therapy is a reasonable treatment approach for select patients., Patient Summary: Squamous cell carcinoma of the prostate is an extremely rare disease. Our review of patterns of care using data from the National Cancer Data Base shows inconsistent use of combined local and systemic therapy. The small sample size for this rare disease limits any conclusions regarding survival differences, but the data suggest that a combination approach using chemotherapy in addition to surgery or radiation is a reasonable treatment option for disease confined to the prostate., (© 2020 The Author(s).)

For patients treated with SBRT for spinal metastases in the cervical area, a thermoplastic mask is the usual immobilization technique. This project investigates the impact of shoulder position variability on target coverage for such cases. Eight HN patients treated in a suite equipped with a CT-on-rails system (CTOR) were randomly chosen. Of these, three were treated with shoulder depressors. For each patient, their planning CT was used to contour spine targets at the C5, C6 and C7 levels for which two VMAT plans were developed to deliver 18 Gy to each target per the RTOG 0631 protocol. One plan used full arcs while the other used avoidance sectors around the lateral positions. For each patient, IGRT CTOR images were used to recalculate doses that would have been delivered from these plans. Target coverage and dose to the spinal cord were compared for four scenarios: full and partial arcs, with or without depressors. A Dunn test showed significant differences between groups with and without shoulder depressors, but not between those with full versus partial arcs. For most of the investigated cases, the coverage ended up being higher than planned due to the shoulder position being inferior at treatment compared to simulation. In some cases, this led to higher spinal cord doses than allowed per protocol. The results of this study confirm that, when treating lower cervical spine lesions with SBRT, special care should be taken to ensure that the shoulders are positioned as they were during planning CT acquisition., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2021 Old City Publishing, Inc.)

Introduction: Ultrasound (US) guidance of the prostate has long been conducted using a transabdominal (TA) approach. More recently, a transperineal (TP) approach has been made available for image guidance. Our aim was to determine if both methods produced similar alignments within the same patients., Materials and Methods: We utilized two clinical US image guidance (IG) systems (Elekta Clarity and Best BAT). The B-mode Acquisition and Targeting USIG system is a bi-planar, so-called 2.5D USIG system, that is acquired TA. Clarity is a 3D US system that generates a volumetric 3D US data set and US-derived IG contours that are coregistered to the planning CT images. The probe is oriented in the sagittal plane against the perineum (TP). After positioning the patient for treatment using the TP USIG, we maintained the position defined by Clarity tracking and then acquired a TA-based USIG. The two US-based methods of localizing the prostate (TA vs TP) were compared via Bland-Altman (BA) statistical analysis to determine if there was alignment agreement between methods., Results: The BA test for all 101 patients, 2093 fractions resulted in 95% confidence intervals (upper and lower limits of the BA test) of 0.6 mm in LR, 0.9 mm in AP and 1.0 mm in SI. The bias between the two systems was calculated as 0.03, 0.02, and 0.03 mm in LR, AP, and SI., Conclusions: Both systems resulted in statistically equivalent targeting positions for the prostate. Because of the unique intrafraction, real-time motion tracking capability of the TP system, this solution represents a unique extension to the previously reported clinical benefits of a TA approach by providing assurance of the prostate remaining in the treatment field during beam-on., (© 2020 American Association of Physicists in Medicine.)

Background: Li-Fraumeni Syndrome (LFS) is a rare cancer-predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well-characterized. Here we describe the risk of subsequent malignancy and cancer-related death in LFS patients after undergoing RT for a first or second primary cancer., Methods: We reviewed a multi-institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non-RT group)., Results: Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow-up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative-intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non-RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy., Conclusion: We found that four of14 patients treated with RT developed in-field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT-induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT)., Patients and Methods: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey., Results: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains., Conclusion: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Using a large national registry, we investigated patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy or radiotherapy (RT), or with a multimodal approach., Patients and Methods: Adult patients with metastatic rectal cancer who did not undergo resection diagnosed from 2004 to 2014 were included. Kaplan-Meier, log-rank, and Cox regression analyses were performed., Results: We identified 2385 patients. Of these, 1020 patients (43%) received chemotherapy alone, 228 (10%) received RT alone, 850 (36%) received chemotherapy and RT, and 287 (12%) received no treatment. Receipt of chemotherapy alone increased over the study period, and receipt of chemoradiotherapy decreased (P < .01). The only factor predictive of receiving any RT on multivariate analysis was clinical stage T3 disease. Factors predictive of OS on multivariate analysis included receipt of chemotherapy, Hispanic race, income greater than $46,000, and presence of lung metastasis. The OS for patients treated with chemotherapy and RT was not significantly different than chemotherapy alone. Five-year OS with chemotherapy alone, RT alone, chemoradiotherapy, and no treatment were, respectively, 84%, 56%, 79%, and 46%., Conclusion: Metastatic rectal cancer patients with T3 tumors were more likely to receive RT. Local RT does not improve survival for patients with metastatic rectal cancer who do not also undergo surgery. The use of chemotherapy alone for metastatic rectal cancer is increasing, and chemotherapy is associated with higher OS compared to no treatment and RT alone. This remained true even in patients older than 80 years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia., Methods: From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model., Results: Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors., Conclusion: We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia., (© 2020 Wiley Periodicals, Inc.)

Background: The prognosis for nonmetastatic, primary pancreatic squamous cell carcinoma (SCC) is thought to be poor compared with adenocarcinoma (AC); however, this is based on limited data. Additionally, the optimal definitive treatment strategy for nonmetastatic pancreatic SCC is unknown., Methods: We analyzed patients with nonmetastatic pancreatic cancer using the National Cancer Database for patients diagnosed from 2006 to 2014. Patients were analyzed according to histology-only AC, adenosquamous carcinoma (A-SCC), and SCC were included. The primary endpoint was overall survival (OS) from the time of diagnosis., Results: A total of 94 928 cases were included; 94 016 AC, 757 A-SCC, and 155 SCC. Median OS was lower for SCC (8.67 months), compared to AC (13.93 months) and A-SCC (12.71 months, P < .001). SCC was resected less often (25.5% vs 46.7% and 74.5%). On subgroup analysis of patients with pancreatic SCC, factors on multivariate analysis associated with improved survival included surgery (HR 0.19, P < .001), and chemotherapy (HR 0.22, P = .01). In 38 patients with SCC undergoing surgical resection, median OS improved (MS = 6.8 months without surgery vs 21.3 months with surgery, P < .001)., Conclusions: Nonmetastatic pancreatic SCC presents with more advanced disease, which is less often surgically resected or treated with any definitive local therapy. In contrast, AC and A-SCC behave more similarly and have higher surgical resection rates and improved survival. In patients with nonmetastatic SCC of the pancreas, surgical resection provides the most significant survival benefit, with systemic chemotherapy providing a less significant benefit, and localized radiation providing no statistical benefit for any subgroup., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Urothelial cancer is the second most common cancer, and cause of cancer death, related to the genitourinary tract. The goals of surveillance imaging after the treatment of urothelial cancer of the urinary bladder are to detect new or previously undetected urothelial tumors, to identify metastatic disease, and to evaluate for complications of therapy. For surveillance, patients can be stratified into one of three groups: (1) nonmuscle invasive bladder cancer with no symptoms or additional risk factors; (2) nonmuscle invasive bladder cancer with symptoms or additional risk factors; and (3) muscle invasive bladder cancer. This article is a review of the current literature for urothelial cancer and resulting recommendations for surveillance imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate long-term prevalence of new dysphagia-related diagnoses in a large cohort of head and neck cancer survivors., Study Design: Retrospective cohort., Setting: Population based., Subjects and Methods: In total, 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow-up were compared with 7796 controls matched for age, sex, and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2 to 5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed., Results: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2 to 5 years, increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% confidence interval [CI], 5.08-17.87) and 12.57 (7.17-22.04), respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45-197.33) to 35.2 (7.81-158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50-4.42) to 2.12 (1.63-2.75). Treatment with radiation therapy and age older than 65 years were associated with increased hazard ratio for dysphagia-related diagnoses., Conclusion: Our data suggest that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

Background: Single-center studies in pancreatic adenocarcinoma have suggested that preoperative chemotherapy (PCT) is associated with higher lymph node ratio (LNR) than preoperative chemoradiation (PCRT). The association of postoperative chemotherapy with overall survival (OS) in patients treated with PCT and PCRT remains unclear. Our objectives were to investigate whether (1) PCT is associated with higher LNR than PCRT and (2) postoperative chemotherapy is associated with longer OS after PCT and PCRT in LNR-stratified cohorts., Methods: A retrospective cohort study was performed of patients with pancreatic adenocarcinoma treated with PCT or PCRT followed by resection between 2006 and 2014 in the National Cancer Database. Temporal trends were evaluated with Cuzick's test. OS was evaluated with multivariable Cox regression and inverse probability weighted (IPW) Cox regression., Results: Of 4187 patients, 1993 (47.6%) received PCT. PCT rates were stable at approximately 30% in 2006-2010 (p = 0.33) but increased to 64.9% by 2014 (p < 0.001). Node positivity rates were higher after PCT than PCRT (62.7 vs. 41.8%, P < 0.001) and mean LNR was higher (0.10 [95% CI 0.096, 0.11] vs. 0.058 [95% CI 0.052, 0.063], P < 0.001). Postoperative chemotherapy was associated with longer OS in patients with LNR 0.01-0.149 after PCT by univariate analysis (median OS 34.5 vs. 26.5 months, P = 0.002), multivariable Cox regression (HR 0.64, 95% CI 0.48, 0.84), and IPW Cox regression (HR 0.72, 95% CI 0.55, 0.94). Postoperative chemotherapy was not associated with longer OS for patients who were node-negative or who had LNR ≥ 0.15 after PCT or for any patient subgroups after PCRT., Conclusions: PCT is associated with a higher LNR and higher rates of node positivity than PCRT. Postoperative chemotherapy is associated with longer OS than observation in patients with a LNR of 0.01-0.149 after PCT.

Background: Adult head and neck (H&N) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes. This study uses the National Cancer Database (NCDB) to investigate whether PORT improves overall survival (OS) in adult H&N sarcomas with a positive margin and how utilization has changed., Methods: Patients (n = 1142) in the NCDB from 2004-2013 with adult H&N sarcomas who underwent resection and had a positive margin., Results: Factors significantly associated with increased utilization of PORT were: having insurance, salivary gland primary site, high-risk histology, poor differentiation, and a macroscopic positive margin. Treatment with PORT was associated with improved 5-year OS for all patients with a positive margin (57% vs 48%; P = .002), both microscopic (57% vs 49%; P = .010) and macroscopic (57% vs 41%; P = .036). Improved OS was significant after controlling for other known covariates on multivariate analysis (HR: 0.76; [0.64-0.90]; P = .002). Treatment at a community-based facility was an independent predictor for reduced OS (HR: 1.37; [1.15-1.64]; P < .001). The percentage utilization (53%) of PORT for these patients did not change significantly over time., Conclusion: PORT provides a significant survival benefit for adult H&N sarcoma patients with either a microscopic or macroscopic positive margin; however, PORT is underutilized. Treatment at academic/research cancer programs was associated with increased utilization of PORT and improved survival outcomes., (© 2019 Wiley Periodicals, Inc.)

Objectives: To determine the risk and risk factors for mental illness among colorectal cancer (CRC) survivors across short-term and long-term follow-up periods., Methods: We used the Utah Cancer Registry to identify CRC survivors diagnosed between 1997 and 2013. Mental health diagnoses were available in electronic medical records and statewide facilities data that were linked by the Utah Population Database. CRC survivors were matched to individuals from a general population cohort. The risk of developing a mental illness was compared between cohorts. The association between mental illness and mortality was also analyzed., Results: In total, 8961 CRC survivors and 35,897 individuals in a general population cohort were identified. CRC survivors were at increased risk for any mental health diagnosis at 0 to 2 years (hazard ratio [HR], 3.70; 95% confidence interval [CI], 3.47-3.95), >2 to 5 years (HR, 1.23; 95% CI, 1.09-1.38), and >5 years (HR, 1.20; 95% CI, 1.07-1.36) after cancer diagnosis. CRC survivors were also at increased risk of depressive disorders specifically during the same time periods. At >5 years, CRC survivors still had an increased risk of developing many mental health diagnoses. Factors associated with increased risk of any mental health disorder among CRC survivors included colostomy and Charlson Comorbidity Index of 1+. There was an increased risk of death for CRC survivors diagnosed with any mental health disorder (HR, 2.18; 95% CI, 2.02-2.35) and depression (HR, 2.10; 95% CI, 1.92-2.28)., Conclusions: CRC survivors are at increased risk for mental health disorders in the short-term and long-term. Survivors who develop mental health disorders also experience decreased survival.

Background and Purpose: A lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT)., Methods and Materials: We identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort., Results: 71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395-0.290, p < 0.001)., Conclusion: Peripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Surgical resection is the most important therapeutic intervention for eligible patients with pancreatic cancer; however, a majority of patients never receive surgery for a variety of reasons, including patient refusal. Utilizing the National Cancer Database, we investigated the associated sociodemographic and clinical factors for those patients who refused surgery, and the impact of this decision on overall survival (OS)., Methods and Materials: We analyzed adult patients with non-metastatic adenocarcinoma of the pancreas diagnosed from 2004 to 2013. Univariate and multivariate logistic regression modeling was used to identify factors predictive of refusing surgery, and Kaplan-Meier and log-rank analysis was performed to investigate the effect on OS., Results: A total of 48,902 patients were identified: 47,107 received surgery (96.3%) and 1795 were offered surgery but refused (3.7%). Factors associated with refusing surgery include both sociodemographic factors [age > 50 years, female sex, Black race, non-private insurance, treatment at a non-academic institution or non-metro facility, Carlson Comorbidity Index of 2 + (p ≤ 0.01)], and clinical factors [advanced clinical T (tumor) category and tumor size > 20 cm (p ≤ 0.01)]. Patients who refused surgery and received no treatment at all experienced a median survival of 5.1 months, while those who refused surgery but received chemoradiotherapy experienced a median survival of 11.2 months. As an index for comparison, those who received surgery had a median survival of 20.5 months., Conclusion: Refusing surgery is an understudied phenomenon associated with several sociodemographic and clinical factors. The expected prognosis for patients who refuse surgery is presented.

We sought to review published aggregate dataset studies on pancreatic cancer in the national and international settings, discuss the advantages and disadvantages these datasets possess, and possible future directions. A combination of Google Scholar, PubMed, and MEDLINE were used with search terms "pancreatic cancer" + "resectable" + "national cancer database", "pancreatic cancer" + "unresectable" + "national cancer database" and more broadly "borderline resectable pancreatic cancer", "locally advanced pancreatic cancer", "unresectable pancreatic cancer", and "resectable pancreatic cancer". Original articles and abstracts from this search were included, including data from the Surveillance, Epidemiology, and End Results (SEER) database, National Cancer Database (NCDB), and SEER-Medicare within the United States (US), as well as international database studies. Multiple database studies have been published regarding the role for radiotherapy in resected pancreatic cancer (n=6), the timing of additional therapy in resectable pancreatic cancer (n=4), and the role for radiotherapy and resection in locally advanced pancreatic cancer (LAPC) (n=4). Studies from both SEER and NCDB found a survival benefit to post-operative radiotherapy. In resectable pancreatic cancer, neoadjuvant treatment was found to be superior to adjuvant (NCDB). Chemoradiotherapy was found to be more beneficial than chemotherapy alone in LAPC, and patients who received highly-conformal or stereotactic body radiotherapy (SBRT) had improved survival compared to either conformal radiotherapy or chemotherapy alone. These studies also found that up to 10% of patients underwent resection, with a 90% margin-negative rate, and either one-half to one-third the risk of death of non-surgical patients. Criticism of large datasets includes lack of granularity of performance status, diagnosis, treatment, and outcomes-related data compared to properly administered prospective trials, as well as cross-over between treatment arms that cannot be accounted for, and concerns over quality of data represented. The US has witnessed a growing number of comparative effectiveness studies in pancreatic cancer. When taken together, certain themes emerge that are consistent with both single-institution data and clinical trials. These studies have also provided insight into questions not readily answerable by clinical trials. However, they require caution in interpretation., Competing Interests: Conflicts of Interest: S Lloyd has received funding from Sirtex Medical outside of the submitted work. The other authors have no conflicts of interest to declare.

Background: Stereotactic body radiation therapy (SBRT) treatments of pancreatic cancer typically employ relatively small margins. This study characterizes the motion of high visibility structures in close proximity to the pancreas to determine how much the motion envelope of such a structure changes due to respiratory variation between fractions., Methods: Fanbeam, four-dimensional computed tomography (4DCT) studies acquired initially for planning and again prior to each treatment for 6 patients were used to fully characterize the change in motion of high-contrast structures in close proximity to the pancreas., Results: Three of the six patients investigated had structures that showed a change in motion over the course of treatment that would not have been covered when using the typical 3 mm planning target volume (PTV) margins. For most of these large changes in motion envelope, a 4 mm uniform PTV margin would have allowed for coverage of the tumor., Conclusions: Half of the patients showed a change in motion envelope greater than would be covered by the commonly used PTV margins in pancreas SBRT. This shows that the impact of small margins must be very carefully considered during the planning process., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, with its mortality rate approaching its incidence rate every year. Accordingly, much interest has been generated in harnessing the immune system in order to improve survival outcomes for these patients. Pancreatic cancer is not thought to be as immunogenic as other cancers that have seen promising results with immune checkpoint inhibitors alone, therefore likely several targets within the cancer-immunity cycle will need to be employed for successful treatment. We sought to investigate both the current state of the field in immunotherapy in PDAC with a special emphasis on combined approaches with radiation therapy (RT). We also summarized ongoing clinical trials that are examining the use of radiotherapy with other immune-stimulating agents in the treatment of PDAC. A PubMed and clinicaltrials.gov search was conducted using the following search terms, either alone or in combination: "pancreatic cancer", "immunotherapy", and "abscopal effect". Open clinical trials were reviewed and included if they involved both RT and other immune-stimulating agents. Pancreatic cancers tend to reside within immune-suppressive tumor microenvironments (TME), express PD-L1, and secrete several immuno-suppressive agents, such as TGF-B, IL-10, indoleamine 2,3-dioxygenase, galectin-1. Whole-cell vaccine therapies, peptide and protein vaccines, dendritic cell vaccines, and vaccines with micro-organisms have been investigated by themselves with promising results. Open clinical trials are currently investigating the use of these vaccines, which increase antigen presentation, with treatments that stimulate release of tumor antigens including RT. There are currently at least 21 open clinical trials investigating the combination of RT with other immune-stimulating agents. The combination of RT and immunotherapy may be a promising avenue for PDAC treatment and deserves further research., Competing Interests: Conflicts of Interest: S Lloyd has received funding from Sirtex Medical outside of the submitted work. The other authors have no conflicts of interest to declare.

Survival for upper gastrointestinal tumors remains poor, likely in part due to treatment resistance associated with intratumoral hypoxia. In this review, we highlight advances in nuclear medicine imaging that allow for characterization of in vivo tumor hypoxia in esophageal, pancreatic, and liver cancers. Strategies for adaptive radiotherapy in upper gastrointestinal tumors are proposed that would apply information gained through hypoxia imaging to the creation of personalized radiotherapy treatment plans able to overcome hypoxia-induced treatment resistance, minimize treatment-related toxicities, and improve patient outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The safety and efficacy of FOLFIRINOX (FX) followed by consolidative chemoradiation (CRT) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has not been extensively studied. We sought to evaluate outcomes and toxicities of this regimen., Methods: A retrospective review was performed of 33 patients with BRPC or LAPC treated with FX followed by CRT. Radiotherapy was directed at the primary tumor and any involved nodes (84.8% received 50-50.4 Gy with standard fractionation and concurrent capecitabine, while 15.2% of patients received 36 Gy in 15 fractions with weekly gemcitabine). Toxicities of FX and CRT were graded using Common Terminology Criteria for Adverse Events (CTCAE v4.0), and radiographic response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS), distant metastasis-free survival (DMFS), and local control (LC) were calculated using Kaplan-Meier analyses, and a Cox proportional hazards model was used to assess the impact of clinicopathologic factors on OS., Results: Median follow-up was 19.9 months and patients received a median of 6.4 months of chemotherapy (range, 2.2-12.0 months). There were more T4 tumors than T3 tumors (70% vs. 30%). Grade ≥3 toxicities were low, including fatigue (9.1%), diarrhea (6.1%), neuropathy (6.1%), and dehydration (6.1%). R0 surgical resection was achieved in 5 patients (15.2%) after CRT. Median OS was 22.0 months (91% at 1 year and 45% at 2 years). Median DMFS was 17.8 months (69% at 1 year and 35% at 2 years). LC was 84% at 1 year and 55% at 2 years., Conclusions: OS is promising with the use of FX in BRPC and LAPC, and consolidative CRT was well tolerated in this cohort. Therefore, the role of radiation after multi-agent chemotherapy should be further evaluated in prospective trials., Competing Interests: Conflicts of Interest: This research was presented in part as a poster viewing presentation at the 55th Annual Meeting of the American Society for Radiation Oncology (ASTRO), September 22–25, 2013, Atlanta, GA.

Background: The available literature to guide treatment decision making in esthesioneuroblastoma (ENB) is limited., Objective: To define treatment patterns and outcomes in ENB according to treatment modality using a large national cancer registry., Methods: This study is a retrospective cohort analysis of 931 patients with a diagnosis of ENB who were treated with surgery, radiation therapy, and/or chemotherapy in the United States between the years of 2004 and 2012. Log-rank statistics were used to compare overall survival by primary treatment modality. Logistic regression modeling was used to identify predictors of receipt of postoperative radiotherapy (PORT). Cox proportional hazards modeling was used to determine the survival benefit of PORT. Subgroup analyses identified subgroups that derived the greatest benefit of PORT., Results: Primary surgery was the most common treatment modality (90%) and resulted in superior survival compared to radiation (P < .01) or chemotherapy (P < .01). On multivariate analysis, PORT was associated with decreased risk of death (hazard ratio [HR] 0.53, P < .01). PORT showed a survival benefit in Kadish stage C (HR 0.42, P < .01) and D (HR 0.09, P = .01), but not Kadish A (HR 1.17, P = .74) and B (HR 1.37, P = .80). Patients who received chemotherapy derived greater benefit from PORT (HR 0.22, P < .01) compared with those who did not (HR 0.68, P = .13). Predictors of PORT included stage, grade, extent of resection, and chemotherapy use., Conclusion: Best outcomes were obtained in patients undergoing primary surgery. The benefit of PORT was driven by patients with stages C and D disease, and by those also receiving chemotherapy.