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Poster discussion: CL: Upper and Lower GI 1 PD-0421: Association of molecular profiles of pancreatic cancer with post-operative recurrence patterns X. Zhu, C. Yangsen, Y. Yusheng, J. Xiaoping, Z. Xianzhi, J. Lingong, G. Lei, S. Yuxin, Q. Shuiwang, C. Fei, J. Zhen, F. Fang, Z. Houjun. [Extracted from the article]

• IMPT resulted in less late xerostomia than IMRT for oropharyngeal cancer. • Oral cavity dosimetric variables were related to the occurrence of late xerostomia. • The dosimetric variables of parotids or submandibular were not associated with late xerostomia. To determine rates of xerostomia after intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) for oropharyngeal cancer (OPC) and identify dosimetric factors associated with xerostomia risk. Patients with OPC who received IMRT (n = 429) or IMPT (n = 103) from January 2011 through June 2015 at a single institution were studied retrospectively. Every 3 months after treatment, each patient completed an eight-item self-reported xerostomia-specific questionnaire (XQ; summary XQ score, 0–100). An XQ score of 50 was selected as the demarcation value for moderate-severe (XQs ≥ 50) and no-mild (XQs < 50) xerostomia. The mean doses and percent volumes of organs at risk receiving various doses (V5-V70) were extracted from the initial treatment plans. The dosimetric variables and xerostomia risk were compared using an independent-sample t -test or chi-square test. The median follow-up time was 36.2 months. The proportions of patients with moderate-severe xerostomia were similar in the two treatment groups up to 18 months after treatment. However, moderate-severe xerostomia was less common in the IMPT group than in the IMRT group at 18–24 months (6% vs. 20%; p = 0.025) and 24–36 months (6% vs. 20%; p = 0.01). During the late xerostomia period (24–36 months), high dose/volume exposures (V25-V70) in the oral cavity were associated with high proportions of patients with moderate-severe xerostomia (all p < 0.05), but dosimetric variables regarding the salivary glands were not associated with late xerostomia. IMPT was associated with less late xerostomia than was IMRT in OPC patients. Oral cavity dosimetric variables were related to the occurrence of late xerostomia. [ABSTRACT FROM AUTHOR]

• We studied patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC) from two clinical trials. • Rates of severe (grade ≥3) pulmonary and cardiac toxicity were low and similar between groups. • Adjuvant IO after CPBT led to a survival benefit with an acceptable toxicity profile in patients with LA-NSCLC. Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity. [ABSTRACT FROM AUTHOR]

• A cohort of 328 NSCLC patients receiving proton therapy were investigated. • The proton-derived model showed a smaller volume effect than did the photon model. • The model showed good predictive performance and robustness to future populations. To develop and test an Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP) model to predict radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving passive-scattering proton therapy (PSPT). We retrospectively reviewed 328 NSCLC patients receiving PSPT at our institution. Esophagitis severity was graded by physicians according to the Common Toxicity Criteria for Adverse Events version 3.0, and the primary endpoint was grade ≥2 RE within 6 months from the first treatment. LKB model parameters (n , m , and TD 50) were determined using maximum likelihood estimation. Overall performance of the model was quantified by Nagelkerke's R2 and the scaled Brier score. Discriminative ability was evaluated using the area under the receiver operating curve (AUC), and calibration was assessed with the Hosmer–Lemeshow goodness-of-fit test. Bootstrap internal validation was performed to assess the model uncertainty and generalizability. Grade 2–3 RE was observed in 136 (41.5%) patients, and no grade 4–5 RE was reported. The optimal LKB parameters were: n = 0.24, m = 0.51, and TD 50 = 44.83 Gy (relative biological effectiveness). The optimism-corrected AUC was 0.783, and the Hosmer–Lemeshow test showed significant agreement between predicted and observed morbidity. Bootstrap validation verified that the model was robust to similar future populations. Our LKB NTCP model to predict grade ≥2 RE in NSCLC patients who received PSPT showed good predictive performance and robustness to similar future populations, and a smaller volume effect than the previously observed in photon-treated populations. External validation of the model is warranted. [ABSTRACT FROM AUTHOR]

We aimed to determine whether multiple-CT (MCT) optimization of intensity-modulated proton therapy (IMPT) could improve plan robustness to anatomical changes and therefore reduce the additional need for adaptive planning. Ten patients with head and neck cancer who underwent IMPT were included in this retrospective study. Each patient had primary planning CT (PCT), a first adaptive planning CT (ACT1), and a second adaptive planning CT (ACT2). Selective robust IMPT plans were generated using each CT data set (PCT, ACT1, and ACT2). Moreover, a MCT optimized plan was generated using the PCT and ACT1 data sets together. Dose distributions optimized using each of the four plans (PCT, ACT1, ACT2, and MCT plans) were re-calculated on ACT2 data. The doses to the target and to organs at risk were compared between optimization strategies. MCT plans for all patients met all target dose and organs-at-risk criteria for all three CT data sets. Target dose and organs-at-risk dose for PCT and ACT1 plans re-calculated on ACT2 data set were compromised, indicating the need for adaptive planning on ACT2 if PCT or ACT1 plans were used. The D 98% of CTV1 and CTV3 of MCT plan re-calculated on ACT2 were both above the coverage criteria. The CTV2 coverage of the MCT plan re-calculated on ACT2 was worse than ACT2 plan. The MCT plan re-calculated on ACT2 data set had lower chiasm, esophagus, and larynx doses than did PCT, ACT1, or ACT2 plans re-calculated on ACT2 data set. MCT optimization can improve plan robustness toward anatomical change and may reduce the number of plan adaptation for head and neck cancers. [ABSTRACT FROM AUTHOR]

• This is the largest series of patients with localized prostate cancer treated with proton therapy (PT). • Long-term outcomes after PT ± ADT (androgen deprivation therapy) were excellent across all risk groups, particularly for patients with high-risk or very high-risk prostate cancer. • While the role of pelvic lymph node irradiation remains controversial, the clinical outcomes in this study were achieved with infrequent pelvic lymph node irradiation (1%). Proton therapy (PT) has emerged as a standard-of-care treatment option for localized prostate cancer at our comprehensive cancer center. However, there are few large-scale analyses examining the long-term clinical outcomes. Therefore, this article aims to evaluate the long-term effectiveness and toxicity of PT in patients with localized prostate cancer. Review of 2772 patients treated from May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 850]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 116]. Biochemical failure and toxicity were analyzed using Kaplan-Meier estimates and multivariate models. The median patient age was 66 years; the median follow-up time was 7.0 years. Pelvic lymph node irradiation was prescribed to 28 patients (1%) (2 [0.2%] U-IR, 11 [3.5%] HR, and 15 [12.9%] VHR). The median dose was 78 Gy in 1.8–2.0 Gy(RBE) fractions. Freedom from biochemical relapse (FFBR) rates at 5 years and 10 years were 98.2% and 96.8% for the LR group; 98.3% and 93.6%, F-IR; 94.2% and 90.2%, U-IR; 94.3% and 85.2%, HR; and 86.1% and 68.5%, VHR. Two patients died of prostate cancer. Overall rates of late grade ≥ 3 GU and GI toxicity were 0.87% and 1.01%. Proton therapy for localized prostate cancer demonstrated excellent clinical outcomes in this large cohort, even among higher-risk groups with historically poor outcomes despite aggressive therapy. [ABSTRACT FROM AUTHOR]

• Intensity modulated proton therapy is a highly conformal treatment option. • Treatment of inoperable NSCLC with IMPT offers excellent disease local control. • Treatment was well tolerated with no grade 4 or 5 toxicity. We report disease control, survival, and toxicity in patients with advanced inoperable non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy and intensity-modulated proton therapy (IMPT) at a single institution. All patients were treated with IMPT with concurrent chemotherapy. Endpoints assessed were local, regional, and distant control, disease-free survival (DFS), and overall survival (OS). Fifty-one patients were enrolled with a median follow-up time of 23.0 months; 39 (76%) were treated with a simultaneous integrated boost to the gross tumor volume (GTV). The median GTV dose was 67.3 CGE and the median CTV dose was 60.0 CGE. Median OS and DFS times were 33.9 months and 12.6 months. The 3-year local control rate was 78.3%. Treatment was well tolerated, with a grade 3 toxicity rate of 18% (9 events: 4 esophagitis, 3 dermatitis, 1 esophageal stricture, and 1 fatigue) and no grade 4 or 5 toxicity. The most common grade 2 toxic effects were esophagitis (22 [43%]), dermatitis (16 [31%]), pain (15 [29%]), and fatigue (14 [27%]). Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity. [ABSTRACT FROM AUTHOR]

Highlights • Demonstrate that IMPT with feedback guided breath hold and CT-on-rail guidance is a robust treatment approach for liver tumor cases. • Investigate the dosimetric impact of interactional anatomy change and breath hold uncertainties with breath hold for IMPT. • Investigate the treatment planning technique for liver patients with IMPT. Abstract Purpose To evaluate the effect of setup uncertainties including uncertainties between different breath holds (BH) and inter-fractional anatomical changes under CT-guided BH with intensity-modulated proton therapy (IMPT) in patients with liver cancer. Methods and materials This retrospective study considered 17 patients with liver tumors who underwent feedback-guided BH (FGBH) IMRT treatment with daily CT-on-rail imaging. Planning CT images were acquired at simulation using FGBH, and FGBH CT-on-rail images were also acquired prior to each treatment. Selective robust IMPT plans were generated using planning CT and re-calculated on each daily CT-on-rail image. Subsequently, the fractional doses were deformed and accumulated onto the planning CT according to the deformable image registration between daily and planning CTs. The doses to the target and organs at risk (OARs) were compared between IMRT, planned IMPT, and accumulated IMPT doses. Results For IMPT plans, the mean of D 98% of CTV for all 17 patients was slightly reduced from the planned dose of 68.90 ± 1.61 Gy to 66.48 ± 1.67 Gy for the accumulated dose. The target coverage could be further improved by adjusting planning techniques. The dose–volume histograms of both planned and accumulated IMPT doses showed better sparing of OARs than that of the IMRT. Conclusions IMPT with FGBH and CT-on-rail guidance is a robust treatment approach for liver tumor cases. [ABSTRACT FROM AUTHOR]

Purpose We compared mandibular doses and osteoradionecrosis in patients with oropharyngeal cancer after intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT). Methods and materials We identified 584 patients who received definitive radiotherapy for oropharyngeal cancer from January 2011 through June 2014 at MD Anderson Cancer Center (534 IMRT and 50 IMPT). The dosimetric variables and osteoradionecrosis were compared with Chi-square test or Fisher’s exact test. Results Median follow-up time for all patients (534 IMRT and IMPT) was 33.8 months (33.8 months IMRT vs. 34.6 months IMPT, P = 0.854), and median time to osteoradionecrosis was 11.4 months (range 6.74–16.1 months). Mandibular doses were lower for patients treated with IMPT (minimum 0.8 vs. 7.3 Gy; mean 25.6 vs. 41.2 Gy; P < 0.001), and osteoradionecrosis rates were lower as well: 2% IMPT (1 grade 1), 7.7% IMRT (12 grade 4, 5 grade 3, 1 grade 2 and 23 grade 1). Osteoradionecrosis location depended on the primary tumor site and high-dose field in the mandible. Conclusions Osteoradionecrosis events were significantly associated with higher dose irradiation to mandibular. Use of IMPT minimized excess irradiation of the mandible and consequently reduced the risk of osteoradionecrosis for oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Objective To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT). Methods This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve. Results 192 patients were included. The most prevalent tumor site was oropharynx ( n = 86, 45%), followed by sinonasal ( n = 28), nasopharyngeal ( n = 27) or parotid ( n = 27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6 months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6 months after PBT; 0.70 versus 0.68 for dry mouth 6 months after PBT; and 0.73 versus 0.85 for hypothyroidism 12 months after PBT. Conclusion Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC. [ABSTRACT FROM AUTHOR]

Background Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities. Methods We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010–2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis. Results Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32 months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8 years for IMRT patients and 61.1 years for IMPT patients, p -value = 0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR) = 0.55; 95% confidence interval (CI): 0.12–2.50, p -value = 0.44) or in progression-free survival (HR = 1.02; 95% CI: 0.41–2.54; p -value = 0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR = 0.53; 95% CI: 0.24–1.15; p -value = 0.11 and OR = 0.43; 95% CI: 0.16–1.17; p -value = 0.10 at 3 months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR = 0.44; 95% CI: 0.19–1.0; p -value = 0.05 at 3 months after treatment and OR = 0.23; 95% CI: 0.07–0.73; p -value = 0.01 at 1 year after treatment. Conclusion Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings. [ABSTRACT FROM AUTHOR]