The efficacy-associated biomarkers for immune checkpoint inhibitors in gastrointestinal cancer: a literature review.

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.

Mental health outcomes in a population-based cohort of patients with prostate cancer.

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.

Comparing Active Surveillance and Watchful Waiting With Radical Treatment Using Machine Learning Models Among Patients With Prostate Cancer.

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.

Adverse Health Outcomes among Rural and Urban Breast Cancer Survivors: A Population-Based Cohort Study.

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.

Adipose Tissue Distribution and Body Mass Index (BMI) Correlation With Daily Image-Guided Radiotherapy (IGRT) Shifts of Abdominal Radiation Therapy Patients.

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 m2, and SFA from 11.8-756.0 cm2. 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.

Determining the association of rurality and cardiovascular disease among prostate cancer survivors.

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.

Risk-Adapted Intraoperative Radiation Therapy (IORT) for Breast Cancer: A Novel Analysis.

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.

Adverse health outcomes among rural prostate cancer survivors: A population-based study.

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.

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials.

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.

Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation.

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.

The Implications of Treatment Delays in Adjuvant Therapy for Resected Cholangiocarcinoma Patients.

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.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

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.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

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.

Racial and Ethnic Health Disparities in Delay to Initiation of Intensity-Modulated Radiotherapy.

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 4th 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.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

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.

Worsening Racial Disparities in Utilization of Intensity Modulated Radiation Therapy.

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.

The Effect of Maximum Tumor Diameter by MRI on Disease Control in Intermediate and High-risk Prostate Cancer Patients Treated With Brachytherapy Boost.

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.

Comparing adjuvant radiation to adjuvant chemoradiation in postsurgical p16+ oropharyngeal carcinoma patients with extranodal extension or positive margins.

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.

Evaluation of the dosimetric impact of changes in shoulder position on target coverage for spine SBRT to metastases in the lower cervical spine region.

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.