Garces, Yolanda I.

Importance Standard adjuvant therapy for human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is radiation therapy 60 Gy with or without cisplatin delivered in 30 fractions during 6 weeks. A phase 3 randomized clinical trial demonstrated decreased toxic effects and improved patient-reported outcomes with de-escalated adjuvant radiation therapy (DART) compared with standard therapy; however, outcomes for patients treated in the clinical practice setting following trial adoption remain unknown. Objective To compare characteristics and oncologic outcomes of patients treated with DART during clinical trials (on study) and in clinical practice settings (off study) and report progression-free survival (PFS) by risk category. Design, Setting, and Participants This retrospective cohort study included patients treated with DART in the MC1273 and MC1675 trials and in clinical practice after study completion at a multisite tertiary care center. Patients with surgically resectable HPV-OPSCC who underwent margin-negative resection between August 20, 2013, and March 21, 2023, and were treated with DART were included in the analysis. Those with prior head and neck cancer, pT0 or pT4 disease, unknown HPV status, metastatic disease at presentation, synchronous primary tumors, induction chemotherapy, or treatment at an outside institution were excluded. Data were analyzed from July 1, 2024, to July 18, 2025. Interventions DART consisting of 30 to 36 Gy in 1.5- to 1.8-Gy fractions twice daily with docetaxel 15 mg/m 2 on days 1 and 8. Main Outcomes and Measures Progression-free survival as measured via Kaplan-Meier analysis. Results A total of 282 patients were included in the analysis: 176 (62.4%) in the on-study group and 106 (37.6%) in the off-study group (252 [89.4%] male; mean [SD] age, 59.1 [9.3] years). Both groups were predominantly male (157 [89.2%] and 95 [89.6%], respectively) and consisted mostly of never smokers (118 [67.0%] and 62 [58.5%], respectively). Pathologic features were similar between groups except for nodal stage (pN1: 155 [88.1%] on study vs 102 [96.2%] off study; pN2: 21 [11.9%] on study vs 4 [3.8%] off study; P = .02). The median follow-up times were 5.2 years (95% CI, 5.2-5.8 years) in the on-study group and 2.2 years (95% CI, 1.9-2.4 years) in the off-study group. Two-year PFS was similar (93% [95% CI, 88%-97%] on study vs 93% [95% CI, 88%-99%] off study). For patients with pN1 and no extranodal extension (ENE), 2- and 5-year PFS were 97% (95% CI, 93%-100%) and 96% (95% CI, 92%-100%), respectively. Patients with pN1 and ENE had a 2- and 5-year PFS of 93% (95% CI, 89%-98%) and 87% (95% CI, 81%-94%), respectively. Conclusions and Relevance In this retrospective cohort study of patients receiving DART on and off study, oncologic outcomes were similar between the 2 groups. Fewer patients with pN2 received DART off study, given the interim results of MC1675. Patients with pN1 and no ENE treated with DART had excellent 2- and 5-year PFS, supporting DART as a compelling treatment option in well-selected patients. An additional study that is currently underway will evaluate biomarker risk-stratified treatment of patients with pN1 and ENE receiving DART.

ImportanceThe De-escalated Adjuvant Radiation Therapy (DART) phase 3 randomized clinical trial (RCT) showed that in patients with human papillomavirus (HPV)−associated oropharyngeal squamous cell carcinoma, postoperative minimal residual disease (MRD), detected through circulating tumor HPV DNA (ctHPVDNA), was associated with a higher risk of disease progression. When considered along with pathologic factors, postoperative ctHPVDNA assessment may improve patient selection for adjuvant treatment de-escalation; however, more data are needed to demonstrate how it may be used in personalizing treatment intensity.ObjectiveTo determine the association of postoperative MRD status with progression-free survival (PFS) after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Design, Setting, and ParticipantsThis was a secondary analysis of the DART RCT, which was conducted from October 2016 to August 2020 in multiple sites in the US. Participants from the de-escalated adjuvant radiation therapy group and the standard of care group with available blood specimen data were included. Reports from 3-month posttreatment surveillance visits were used to assess associations and outcomes. Data analyses were performed from March 2023 to March of 2025.InterventionsThe DART group received 30 to 36 Gy of radiation therapy in 1.5 to 1.8 Gy twice daily, plus docetaxel, 15 mg/m2, on days 1 and 8. The standard of care group received 60 Gy with or without weekly cisplatin, 40 mg/m2.Main Outcome and MeasurePFS.ResultsThe analysis included 140 patients (mean [SD] age, 59.1 [8.4] years; 12 [8.6%] females and 128 [91.4%] males; 97 [69.3%] with no smoking history); characteristics were similar to the overall DART RCT population. Of these, 17 patients (12.1%) had postoperative MRD (13 of 96 [13.5%] receiving DART and 4 of 44 [9.1%] receiving standard of care). For all patients, postoperative MRD positivity was strongly associated with worsened PFS at 24 months (MRD positivity, 69.5%; MRD negativity, 95.9%; hazard ratio [HR], 0.19; 95% CI, 0.06-0.59). MRD positivity was associated with PFS when evaluating only those patients in the DART group, where 24-month PFS was 68.4% compared to 92.6% for MRD-negative patients (HR, 0.28; 95% CI, 0.08-0.93). Three months after completion of all treatment, 8 of 117 patients (6.8%) had detectable ctHPVDNA, whereas 109 of 117 (93.2%) did not, and detection was highly associated with PFS (HR, 20.48; 95% CI, 6.91-60.67).Conclusions and RelevanceThis secondary analysis of the DART RCT found that patients with detectable ctHPVDNA after surgery had a higher risk of disease progression. When added to the pathologic factors considered, ctHPVDNA assessment may improve selection of patients for treatment de-escalation. In addition, the 3-month posttreatment time point, early in surveillance, may identify a sizable portion of patients with progression and may guide intervention and surveillance after surgery for HPV-associated oropharyngeal squamous cell carcinoma.Trial RegistrationClinicalTrials.gov Identifier: NCT02908477

PurposeDevelop an efficient, interactive, and instructive checklist document for the management of implanted electronic medical devices in a multimodality radiotherapy clinic.MethodsThe built‐in scripting and interactivity of a popular commercial word processor was used to develop an interactive document that changes the information presented to the user based on drop‐down selections. The interactivity and scripting were compatible with the radiation oncology information system (ROIS) which allows the document to be accessible by all team members and serve as a permanent record in a patient's electronic chart.ResultsThe final interactive document, which was clinically deployed after beta testing with a group consisting of nurses and medical physicists, presents information and action plans to the user based on multiple departmental medical device decision trees that are specific to the combination of device, treatment modality, rhythm‐pacing dependence for cardiac devices, and distance from the device to the treatment volume.ConclusionA script‐enabled interactive document was developed for a busy multimodality clinic, condensing multiple comprehensive departmental guidelines spanning multiple device types and treatment modalities into a single interactive checklist accessible within the ROIS. Given the wide accessibility of the commercial word processor, this approach could be adopted by other clinics to streamline their own respective workflows.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. Conclusions: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

Abstract Purpose: RTOG 0617 was a phase III randomized trial for patients with unresectable stage IIIA/IIIB non–small cell lung cancer comparing standard-dose (60 Gy) versus high-dose (74 Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617. Experimental Design: From RTOG 0617, 328 of 496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran—Mantel–Haenzel tests and multivariable logistic regression models were used. All statistical tests were two sided, and a P value <0.05 was considered significant. Results: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients—while the hazard of death was higher in cetuximab-treated patients within year 1 [HR = 3.37, 95% confidence interval (CI): 1.13–10.10, P = 0.030], death was lower from year 1 to 4 (HR = 0.33, 95% CI: 0.11–0.97, P = 0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR = 1.59, 95% CI: 1.11–2.28, P = 0.012). Conclusions/Discussion: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy. Significance: The KRAS-variant is the first functional, inherited miRNA-disrupting variant identified in cancer. Our findings support that cetuximab has a potentially beneficial impact on KRAS-variant patients treated with radiation. The work confirms prior evidence that KRAS-variant patients are a subgroup who are especially sensitive to radiation. These findings further support the potential of this class of variants to enable true treatment personalization, considering the equally important endpoints of response and toxicity.

e20554 Background: The paradigm for locally advanced non-small cell lung cancer has been markedly altered to include maintenance durvalumab (D) post completion of definitive chemoradiation (CRT) following the publication of the Pacific trial in 2018. The toxicity of this treatment has not been well evaluated in the real-world setting. Methods: We identified 42 patients (pts) with Stage IIB-IIIC NSCLC treated at Mayo Clinic Rochester between 6/1/2018 and 10/1/2020 who received definitive CRT followed by maintenance D. Data were abstracted by retrospective chart review under an IRB approved protocol. Results: Median age was 66 yrs (range 47-90) and 62% were women. Primary lung cancer histology included 19 adenocarcinoma, 20 squamous cell, and 3 adenosquamous. The distribution of stages was: IIB (4/42), IIIA (15/42), IIIB (19/42), IIIC (4/42). Approximately half of patients had PDL1 expression > 25% (20/42). With a median follow up of 12.2 months (calculated from first cycle of D; range 4.2-30.5 months), 14 had completed one year of maintenance D, 16 were receiving ongoing D, and 10 stopped D early with 6/12 discontinuing due to disease progression (4/6 local progression, 2/6 distant progression). Other reasons for discontinuation (5/10) included grade 3 colitis, grade 2 hepatitis, aspergillus lung infection, and flare of autoimmune disorders. One quarter of patients experienced grade 2 radiation pneumonitis (RP; 10/42) with median time to development of RP 78 days from end of CRT and 45 days from start of D. RP was determined by multidisciplinary review of imaging and treatment fields. 17/42 patients developed immune related adverse events (see Table for details). There was minimal overlap between the patients who experienced pneumonitis and immune related toxicity; 2/17 had both pneumonitis and immune related toxicity (hepatitis, thyroiditis). Conclusions: In our early experience with the Pacific regimen, 29% of patients did not complete D due to either toxicity or progression during D administration. Pneumonitis was common (10/42 patients) although there were no grade 3 events. Nearly half of the patients developed an immune-related adverse event. Further analysis is needed to evaluate the real-world toxicity of this treatment as well as oncologic outcomes.[Table: see text]

9599 Background: We have previously identified overall a single-item measure for baseline quality of life (QOL) as a strong prognostic factor for survival (Tan, ASCO 2008), and that fatigue was an important component of patient QOL (Sloan, 2007). To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 NCCTG and MCCC oncology clinical trials of the effect of baseline fatigue on OS. Methods: 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0–100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0–50, n=1,497) vs not clinically deficient fatigue (nCDF, score 51–100, n=2,418). Cox proportional hazards models adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Results: Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 mos vs >83.9 mos, p<0.0001). The effect sizes were consistent across different disease sites (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR=1.23, p=0.02). Conclusions: Fatigue is a strong prognostic factor for OS independent of overall QOL and PS in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. No significant financial relationships to disclose.

9563 Background: Fatigue is a prevalent and debilitating symptom reported by cancer patients (pts) which compromises a pt's quality of life (QOL). This study examined the relationship between PR fatigue and QOL as well as cancer-related symptoms (CRS) in 43 North Central Cancer Treatment Group and Mayo Clinic Cancer Center clinical trials. Methods: 3,915 pts from 43 oncology clinical trials provided baseline fatigue data on a single-item 0–100 point scale. Pts' QOL assessment included a single-item overall QOL and associated QOL domains measured by numerical analogues, the Profile of Mood States (POMS), and PR symptom assessment measures. Associations between fatigue and QOL domains were assessed by Spearman correlation coefficients. Wilcoxon rank sum test compared QOL scores between pts with clinically deficient fatigue(CDF, score ≤50) vs. no clinically deficient fatigue (nCDF, score>50). Changes from baseline in fatigue and QOL were compared by Wilcoxon rank sum test with a 20-point change defined as clinically meaningful. Results: 38% of pts reported CDF at baseline and 45% of pts reported CDF at last assessment. Fatigue was only moderately correlated at best with overall QOL, pain, POMS, social and physical function (Spearman rho's of .27,.40, .56, .38 and .38 respectively). Pts with CDF averaged over 10 points lower overall QOL, pain, POMS, social, and physical function (see table below, all p<.0001) as well as worsening CRS including sleepiness, nausea, headache, abnormal sweating, trouble sleeping, dry mouth, and sexual dysfunction (all p<.001). Pts with 20+ points worsening in fatigue declined in overall QOL, physical function, pain and POMS (all p<.0001). Conclusions: Patients with CDF suffer greater deficits in QOL and CRS. Patients report fatigue as distinctly different from overall QOL, pain, physical, social, mood status and CRS. Fatigue appears with a broad spectrum of CRS clusters. Routine measurement and management of fatigue could impact QOL and treatment-related symptoms. [Table: see text] No significant financial relationships to disclose.