Impact of Clinical Trial Design on Recruitment of Racial and Ethnic Minorities.

Knowledge related to how oncology treatment trial design influences enrollment of racial and ethnic minorities is limited. Rigorous identification of clinical trial design parameters that associate favorably with minority accrual provides educational opportunities for individuals interested in designing more representative treatment trials. We identified oncology trials with a minimum of 10 patients at an NCI-Designated Comprehensive Cancer Center from 2010 to 2021. We defined a study endpoint of racial and ethnic minority accrual greater than zero. Multivariable logistic regression was used to determine whether co-variables predicted our study endpoint. P-values of less than 0.05 were considered significant. A total of 352 cancer trials met eligibility criteria. These studies enrolled a total of 7981 patients with a total of 926 racial and ethnic minorities leading to a median enrollment of 10%. Trials open in community sites (yes versus no) were more likely to have a minority patient (OR, 2.21; 95% CI, 1.02-4.96) as well as pilot/phase I studies compared to phase II/III (OR, 3.19; 95% CI, 1.34-8.26). Trials incorporating immunotherapy (yes versus no) were less likely to have a minority patient (OR, 0.47; 95% CI, 0.23-0.94). Trials open in community sites as well as early phase treatment studies were more likely to accrue minority patients. However, studies including immunotherapy were less likely to accrue racial and ethnic minorities. Knowledge gained from our analysis may help individuals design oncology treatment trials that are representative of more diverse populations.

Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Abdominopelvic MR to CT registration using a synthetic CT intermediate.

Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.

Combined multiagent chemotherapy and radiotherapy is associated with prolonged overall survival in patients with non-operatively managed stage II-III pancreatic adenocarcinoma.

BACKGROUND: Most patients with pancreatic adenocarcinoma (PDAC) do not undergo surgical resection. The role of radiotherapy (RT) in non-operatively managed localized pancreatic adenocarcinoma is unclear. METHODS: The National Cancer Database (2010-2016) was queried for patients with clinical stage II-III PDAC treated with multiagent systemic chemotherapy (CT) +/- RT but not surgery. Factors associated with the receipt of RT and overall survival were compared after adjusting for patient demographics and clinical characteristics. RESULTS: A total of 14,921 patients were included, of whom 9279 received CT and 5382 received CT + RT. Patients treated with CT + RT were more likely to be younger (65vs66yrs), treated at non-academic facilities (48.8%vs46.7%), have private insurance (40.3%vs36.5%), and have clinical T4 tumors (53.6%vs48.7%). Most patients who were treated with RT received external beam radiotherapy (89.3%), and the median dose was 5,000 cGy. Median time to start of RT was 129 days. CT + RT was associated with longer overall survival (15.9vs11.8mos,p < 0.001), and remained associated with survival on multivariable analysis (HR 0.74, 95%CI 0.70-0.78). On a 4-month conditional survival analysis, combined CT + RT remained associated with improved survival compared to CT alone (16.0vs13.1mos,p < 0.001). CONCLUSIONS: In patients with non-operatively managed localized pancreatic adenocarcinoma, combined radiotherapy and multiagent systemic chemotherapy is associated with improved overall survival compared to chemotherapy alone.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Possible Bioenergetic Biomarker for Chronic Cancer-Related Fatigue.

BACKGROUND: Cancer-related fatigue (CRF) is a highly prevalent, debilitating, and persistent symptom experienced by patients receiving cancer treatments. Up to 71% of men with prostate cancer receiving radiation therapy experience acute and persistent CRF. There is neither an effective therapy nor a diagnostic biomarker for CRF. This pilot study aimed to discover potential biomarkers associated with chronic CRF in men with prostate cancer receiving radiation therapy. METHODS: We used a longitudinal repeated-measures research design. Twenty men with prostate cancer undergoing radiation therapy completed all study visits. CRF was evaluated by a well-established and validated questionnaire, the Patient-Reported Outcomes Measurement Information System for Fatigue (PROMIS-F) Short Form. In addition, peripheral blood mononuclear cells were harvested to quantify ribonucleic acid (RNA) gene expression of mitochondria-related genes. Data were collected before, during, on completion, and 24 months postradiation therapy and analyzed using paired t-tests and repeated-measures analysis of variance. RESULTS: The mean of the PROMIS-F T score was significantly increased over time in patients with prostate cancer, remaining elevated at 24 months postradiation therapy compared to baseline. A significant downregulated BC1 ubiquinol-cytochrome c reductase synthesis-like (BCS1L) was observed over time during radiation therapy and at 24 months postradiation therapy. An increased PROMIS-F score was trended with downregulated BCS1L in patients 24 months after completing radiation therapy. DISCUSSION: This is the first evidence to describe altered messenger RNA for BCS1L in chronic CRF using the PROMIS-F measure with men receiving radiation therapy for prostate cancer. CONCLUSION: Our results suggest that peripheral blood mononuclear cell messenger RNA for BCS1L is a potential biomarker and therapeutic target for radiation therapy-induced chronic CRF in this clinical population.

Higher Doses of Neoadjuvant Radiation for Esophageal Cancer Do Not Affect the Pathologic Complete Response Rate or Survival: A Propensity-Matched Analysis.

BACKGROUND: Traditional neoadjuvant therapy for esophageal cancer has used chemoradiation doses greater than 45 Gy. This study aimed to examine the dose of preoperative radiation in relation to the pathologic complete response (pCR) rate and overall survival (OS) for patients with resectable esophageal cancer. METHODS: The National Cancer Database was queried for all patients with esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy between 2006 and 2015. The radiation doses were divided into four ranges based on Grays (Gy) received: less than 39.6 Gy, 39.60-44.99 Gy, 45-49.99 Gy, and 50 Gy or more. RESULTS: The inclusion criteria were met by 10,293 patients. All patients received neoadjuvant CRT, with 689 patients (6.7%) receiving less than 39.6 Gy, 973 patients (9.5%) receiving 39.6-44.9 Gy, 3837 patients (37.3%) receiving 45-49.9 Gy, and 4794 patients (46.6%) receiving 50 Gy or more. The overall pCR rate was 17.2% (1769/10,293) and was significantly lower for those who received less than 39.6 Gy of radiation than for those who received 39.6 Gy or more (13.9% [96/689] vs. 17.4% [1673/9604]; p = 0.017). The median OS of 37.2 months was significantly better for those who received 39.6 Gy or more than for those who received less than 39.6 Gy (38 vs. 29.6 months (p < 0.0001). The pCR and OS did not differ between the three higher radiation doses (39.6-44.9 vs. 45-49.9 Gy vs. ≥ 50 Gy; pCR [p = 0.1] vs. OS [p = 0.097]). The patients who received 39.6-44.9 Gy were propensity matched with those who received 45 Gy or more of radiation. There remained no difference in pCR (p = 0.375) or OS (p = 0.957). CONCLUSIONS: In the United States, the heterogeneity in neoadjuvant CRT dosing is significant, with 84% of patients receiving more than 45 Gy. The benefit of neoadjuvant CRT in terms of pCR and overall  survival is seen with doses of 39.6 Gy or more, but not with doses higher than 45 Gy.

The role of neoadjuvant therapy in pancreatic cancer: a review.

Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting. Radiation and chemoradiation have also been incorporated into neoadjuvant strategies, and delivery of alternative fractionation regimens is being explored. This review provides an overview of neoadjuvant therapies for pancreatic cancer.

Adjuvant and neoadjuvant options in resectable gastric cancer: is there an optimal treatment approach?

Gastric cancer is one of the most prevalent and deadliest forms of cancer worldwide. Even though neoadjuvant, perioperative, and adjuvant chemotherapy and/or radiation therapy may improve outcomes compared with surgery alone, the optimal combination of treatment modalities remains controversial. While European and North American trials established perioperative chemotherapy and adjuvant chemoradiation regimens for gastric cancer, Asian countries have focused on the use of adjuvant chemotherapy. This review summarizes results from contemporary randomized controlled trials and meta-analyses to elucidate the relative merits of each treatment approach.

Patterns of recurrence after trimodality therapy for esophageal cancer.

BACKGROUND: Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined. METHODS: All patients in the current study were treated with trimodality therapy for nonmetastatic esophageal cancer from 1995 to 2009. Locoregional failure included lymph node failure (NF), anastomotic failure, or both. Abdominal paraaortic failure (PAF) was defined as disease recurrence at or below the superior mesenteric artery. RESULTS: Among 155 patients, the primary tumor location was the upper/middle esophagus in 18%, the lower esophagus in 32%, and the gastroesophageal junction in 50% (adenocarcinoma in 79% and squamous cell carcinoma in 21%) of patients. Staging methods included endoscopic ultrasound (73%), computed tomography (46%), and positron emission tomography/computed tomography (54%). Approximately 40% of patients had American Joint Committee on Cancer stage II disease and 60% had stage III disease. The median follow-up was 1.3 years. The 2-year locoregional control, event-free survival, and overall survival rates were 86%, 36%, and 48%, respectively. The 2-year NF rate was 14%, the isolated NF rate was 3%, and the anastomotic failure rate was 6%. The 2-year PAF rate was 9% and the isolated PAF rate was 5%. PAF was found to be increased among patients with gastroesophageal junction tumors (12% vs 6%), especially for the subset with ≥ 2 clinically involved lymph nodes at the time of diagnosis (19% vs 4%). CONCLUSIONS: Few patients experience isolated NF or PAF as their first disease recurrence. Therefore, it is unlikely that targeting additional regional lymph node basins with radiotherapy would significantly improve clinical outcomes.

Stereotactic body radiotherapy: an effective local treatment modality for hepatocellular carcinoma.

Although liver-directed therapies such as surgery or ablation can cure hepatocellular carcinoma, few patients are eligible due to advanced disease or medical comorbidities. In advanced disease, systemic therapies have yielded only incremental survival benefits. Historically, radiotherapy for liver cancer was dismissed due to concerns over unacceptable toxicities from even moderate doses. Although implementation requires more resources than standard radiotherapy, stereotactic body radiotherapy can deliver reproducible, highly conformal ablative radiotherapy to tumors while minimizing doses to nearby critical structures. Trials of stereotactic body radiotherapy for hepatocellular carcinoma have demonstrated promising local control and survival results with low levels of toxicity in Child-Pugh class A patients. We review the published literature and make recommendations for the future of this emerging modality.

Role of 18F-FDG PET/CT in the management of head and neck cancer patients with persistent cervical lymphadenopathy following chemoradiation.

BACKGROUND: We aim to describe the management and outcomes of patients with persistent lymphadenopathy (LAD) after primary chemoradiation for head and neck squamous cell carcinoma (HNSCC) based on post-treatment PET/CT results. METHODS: Retrospective chart review was conducted of all patients who underwent primary concurrent chemoradiation for HNSCC at a tertiary care center from 2010 to 2022 and had persistent post-treatment LAD. RESULTS: Nearly 62% of patients were managed conservatively, and 27.0% underwent neck dissection. PET-positive patients were more likely to undergo neck dissection than PET-negative patients (p = 0.042). Positive predictive value (PPV) and negative predictive values (NPV) of PET/CT in detecting residual disease in the neck were 48.0% and 73.7%, respectively. CONCLUSIONS: PPV and NPV of PET/CT for detecting residual neck disease in patients with post-treatment LAD was lower than those of HNSCC patients with and without persistent LAD reported in other studies.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

An Analysis of Cancer Center-Provided Rideshare Utilization for Radiation Therapy.

OBJECTIVES: The potential of rideshare services to facilitate timely radiation therapy (RT), especially for resource-limited patients, is understudied. METHODS: Patients (n = 63) who received 73 courses of RT (1,513 fractions) and utilized free hospital-provided rideshare service (537 rides) were included in this retrospective study. A multidimensional analysis was conducted including a comparison of demographic, disease characteristics, and treatment completion data; a revenue analysis to evaluate the financial impact of rideshare services; and a geospatial analysis to evaluate community-level characteristics of patients. RESULTS: Median age was 59; most were female (56%) and self-identified as Black or African American (56%), not working (91%), not partnered (83%), high school educated or less (78%), and insured with Medicaid (51%). Geospatial analysis revealed that patients lived in communities with significantly higher rates of resource deprivation. Median rideshare distance was 6.4 miles (interquartile range 3.4-11.2) with a median cost of $13.04 per rideshare (interquartile range 9-19). Of the rideshare-facilitated treatments, 100% were completed, with an overall course completion rate of 97.3% compared with 85.4% for those who did not use rideshare (P = .001); two patients discontinued RT for reasons unrelated to transportation. High rideshare utilization (n = 32), defined as utilization ≥ 45% of the treatment course, was associated with significantly shorter treatment courses and lower radiation doses compared with low rideshare utilization (P = .04). Total rideshare cost for high utilizers and whole cohort was $11,589 and $16,895, facilitating an estimated revenue of $401,952 and $1,175,119, respectively. CONCLUSIONS: Free hospital-provided rideshare service is economically feasible and associated with high RT completion rates. It may help enhance quality radiation care for those who come from resource-limited communities.

NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer.

The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.

Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma.

PURPOSE: Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown. METHODS: We conducted a multi-institutional prospective imaging substudy within NRG-GI002 (ClinicalTrials.gov identifier: NCT02921256) examining the ability of MR-based imaging to predict pathologic complete response (pCR) and correlate MR-TRG with the pathologic neoadjuvant response score (NAR). Serial MRIs were needed from 110 patients. Three radiologists independently, then collectively, reviewed each MRI for complete response (mriCR), which was tested for positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with pCR. MR-TRG was examined for association with the pathologic NAR score. All team members were blinded to pathologic data. RESULTS: A total of 121 patients from 71 institutions met criteria: 28% were female (n = 34), 84% White (n = 101), and median age was 55 (24-78 years). Kappa scores for T- and N-stage after TNT were 0.38 and 0.88, reflecting fair agreement and near-perfect agreement, respectively. Calling an mriCR resulted in a kappa score of 0.82 after chemotherapy and 0.56 after TNT reflected near-perfect agreement and moderate agreement, respectively. MR-TRG scores were associated with pCR (P < .01) and NAR (P < .0001), PPV for pCR was 40% (95% CI, 26 to 53), and NPV was 84% (95% CI, 75 to 94). CONCLUSION: MRI alone is a poor tool to distinguish pCR in rectal adenocarcinoma undergoing TNT. However, the MR-TRG score presents a now validated method, correlated with pathologic NAR, which can objectively measure regression magnitude during TNT.

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504.

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. RESULTS: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had >10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. CONCLUSIONS: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593).

Dehydration Reduction in Head and Neck Cancer (DRIHNC) Trial: Daily Oral Fluid and Electrolyte Maintenance to Prevent Acute Care Clinic and Emergency Department Visits for Patients Receiving Radiation for Head and Neck and Esophageal Cancer.

Purpose: Patients with head and neck (H&N) and esophageal cancer are at high risk for treatment-related symptomatic dehydration, often leading to interventions and hospital admissions. We tested the hypothesis that preemptive daily oral hydration during curative-intent radiation therapy would decrease dehydration as measured by intravenous fluid (IVF) delivery, acute care clinic (ACC) visits, and emergency department (ED) presentations. Methods and Materials: Patients with H&N or esophageal cancer undergoing definitive radiation therapy were enrolled in this prospective pilot study. Beyond standard nutritional counseling, patients were given one 20-oz bottle of an electrolyte-infused solution (EIS) daily throughout treatment. Compliance, presentations to the hospital ACC and/or ED for dehydration-related indications, and IVF infusions were documented and compared with a matched contemporary control cohort. The incidence and frequency of outcomes were compared with the Fisher exact test and Wilcoxon rank-sum test, respectively. Results: Thirty-one patients were compared during a 6-month period. Mean and median compliance rates were 87.4% and 100%, respectively. There were 0 unplanned dehydration-related ED presentations in the study group versus 3 (9.7%) among controls (P = .08). Of patients in the intervention cohort, 32.3% required presentation to the ACC, versus 64.5% in the control cohort (P = .02), with a total of 26 versus 117 visits, respectively (P = .002). On multivariable analysis, receipt of the EIS in the intervention cohort was the only significantly associated factor (P = .02). Among patients in the intervention cohort, 35.5% required IVF during treatment, versus 64.5% among controls (P = .004). The difference in ACC visits (P = .003) and IVF received (P = .008) was especially notable among patients with esophageal cancer. Patients with ≥60% EIS compliance had slightly fewer ACC visits versus those with <60% compliance (P = .067). Conclusions: Regimented oral hydration during radiation for H&N and esophageal cancer was associated with a significant decrease in ACC visits and IVF delivery during definitive radiation therapy. This noninvasive and inexpensive preventative program in a high-risk cohort warrants further study.

Impact of AJCC 8th edition staging system and definitive treatment choice on the prognosis of complete responders with p16+ and p16- oropharyngeal squamous cell carcinomas.

OBJECTIVES: To identify predictors of overall survival (OS) in oropharyngeal squamous cell carcinoma (OPSCC) patients who achieved complete response (CR). METHODS: We performed a retrospective study of OPSCC patients who achieved CR from a single academic medical center. Associations between OS, AJCC 8th edition staging system, definitive treatment choice, smoking history, and p16 status were assessed. RESULTS: p16+ status was associated with favorable prognosis for CR (p < 0.001) but not non-CR (p = 0.67) patients. For early stage, p16+ OPSCC patients who achieved CR, surgery + adjuvant radiation (RT) treatment was more durable compared to concurrent chemoradiation (CRT), particularly in smokers. CONCLUSIONS: Curative intent treatment choice and smoking history has an impact on the long-term OS of the CR p16+ OPSCC cohort. Prospective studies to define the optimal multi-modality treatment option to manage p16+ OPSCC patients is needed.