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Purpose/Objective(s) The investigators’ 2013 use it or lose it study suggested functional benefit of two pharyngeal activities during head and neck radiotherapy (RT) – maintenance of oral intake (EAT) and swallowing exercise. EAT and EXERCISE independently associated with better odds of resuming a regular diet in long term survivorship and shorter duration of gastrostomy (FT) dependence. The prior work is limited by the retrospective nature of the dataset and historically far higher FT utilization. Our aim was to validate the previous work in a contemporary cohort of oropharyngeal cancer (OPC) survivors treated with RT using prospectively acquired validated outcome measures. Materials/Methods Endpoints included subacute diet after RT per the performance status scale for head and neck cancer (PSS-HN; solid food diet coded as ≥60 and no FT) and length of FT-dependence in days. Primary independent variables included oral intake (PO) at the end of RT (nothing per oral/NPO; partial PO; full PO) and swallow exercise adherence. Multiple linear regression and logistic regression models were analyzed adjusting for tumor location, baseline diet, chemotherapy and N and T stage. Results Analysis included 595 patients treated with primary radiotherapy (RT; 19% 111) /chemoradiation (CRT; 73% 434) or primary TORS + CRT (8% 50) for OPC (base of tongue/glossopharyngeal sulcus [46% 276]; tonsil [44% 263]; other [9% 56]). At the end of RT 9% of patients were NPO (55), 19% partial PO (115), 71% full PO (425). Statistically significant (P Conclusion These prospective registry data validate prior work that indicate independent benefit of EAT and swallowing EXERCISE adherence during RT on subacute functional outcomes. Patients who maintained full PO and/or exercise were more likely to eat solid foods by 3-6 months after treatment, while patients who EAT during treatment expectedly have the shortest feeding tube dependence.

Purpose/Objective(s) Stereotactic body radiotherapy (SBRT) is an emerging modality for the reirradiation of head and neck cancers (HNC). The need to use smaller reirradiation volumes to limit severe toxicity concerns represents a challenge in determining optimal target coverage. Herein, we investigate the associated patterns of failure after SBRT using previously defined spatial and dosimetric analysis (Mohamed et al, Radiat Oncol. 2017). Materials/Methods SBRT reirradiation HNC cases treated between 2014-2019 and surveilled by CT, PET/CT, and/or MRI were reviewed retrospectively in this IRB approved study. Patients with radiographic evidence of recurrence within the head and neck region after SBRT were identified. Multifocal disease was defined as any non-contiguous FDG-avid or biopsy positive disease seen on imaging. Diagnostic scans were co-registered with planning CT scans (pCT) for manual segmentation of recurrent gross volumes (rGTV). rGTVs were then deformed to co-registered pCTs for failure classification. The classification followed a granular typology of 5 failure categories: central high-dose (type A or “in-field”), peripheral high-dose (type B), central low-dose (type C), peripheral low-dose (type D or “marginal”), and extraneous-dose (type E or “out of field”). Each type was determined based on the centroid location of rGTV relative to the planning target volumes plus the dose received by 95% of rGTV volume. Results A total of 106 SBRT cases were reviewed out of which 34 patients (32%) recurred after SBRT; 27 (79%) patients had squamous cell carcinomas, 7 (21%) received postoperative SBRT, and 24 (71%) received concurrent systemic therapy. Twenty-three (68%) patients received 42.5-45 Gy in 5 fractions (Fx) and 7 (21%) patients received 36 Gy in 6 Fx. Median time to failure was 5.5 months (range, 1-22 months). Twenty-two recurrences (65%) were out-of-field type E failures, 6 (18%) type A, 3 (9%) type C, and 3 (9%) type D. Fourteen of 16 (88%) multifocal SBRT reirradiation cases had Type E failures compared to 8 of 18 (44%) unifocal SBRT cases. Among the 6 in-field failures, 3 received 36 Gy in 6 Fx and 3 received 42.5-45 Gy in 5 Fx. Conclusion Post SBRT reirradiation recurrences were seen in one-third of cases with the majority of failures being Type E (outside the treatment field), particularly in patients who were treated for multifocal disease. The use of 42.5-45 Gy in 5 Fx appears to be an effective biological dose for local tumor control. Marginal (Type C and D) failures may be reduced with larger margins, but limit feasibility of SBRT. Therefore, future reirradiation strategies should aim to improve patient selection, multimodal therapy, and margin definition in the HNC SBRT reirradiation setting.

PURPOSE/OBJECTIVE(S) Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness of breath may empirically guide earlier detection of disease recurrence, their association with patient outcomes is less well studied, especially for HPV-positive disease. This study aimed to investigate the association between patient reported dysphagia and shortness of breath at 3-to-6 months following radiotherapy (RT) and overall survival (OS). MATERIALS/METHODS Data were collected from oropharyngeal cancer patients that received RT with curative intent from 2015-2019. Included patients had self-reported scores for shortness of breath, choking/coughing ("choke"), and difficulty swallowing/chewing ("swallow"), which were surveyed via the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaire at 3-to-6 months after RT. Symptom severity was scored from 0-10. Significant predictors of OS were analyzed via Cox regression. Symptom scores were also discretized for Kaplan-Meier (KM) analysis, with more severe symptoms being 6+ for "swallow" and "choke" and 2+ for shortness of breath. RESULTS Symptom scores were collected at 3-to-6 months from 470 patients. The majority (91.3%) were HPV-positive. Median follow-up time was 31.7 months (IQR: 21.9-42.1). Univariable Cox regression (Table 1) showed significant associations between OS and MDASI scores for shortness of breath, "choke," and "swallow." Furthermore, a composite variable integrating scores of all three symptoms had the best predictive value for OS (c-index = 0.748). Symptom severity stratified patients based on OS for all three symptoms, with more severe symptoms predicting worse OS on KM analysis (P < 0.001 for all symptoms). On subset analysis more severe symptoms remained significantly associated with worse OS among HPV-positive patients (P < 0.01 for all symptoms). CONCLUSION Quantitative early patient-reported measures of dysphagia and shortness of breath are significant predictors of OS in head and neck cancer, in particular for HPV-positive disease. Integrating quantitative symptom surveys into post-treatment surveillance may be beneficial for individualizing follow-up strategies.

Purpose/objective(s) Due to the differences in patients' lung conditions, radiation pneumonia (RP) sometimes occurs even if the lung's dose limitation is met. We are aiming to further predict the occurrence odd of radiation pneumonitis in NSCLC after receiving radiotherapy. Consider based on the dose-volume level to segment the lungs receiving radiation, use radiomic modeling, and evaluate its predictive effectiveness. Materials/methods The study retrospectively enrolled 306 CT scans from 102 NSCLC patients who received IMRT or VMAT from Oct 2015 to Aug 2016. A 0-5 grade RP occurred within 12 months after radiotherapy, considered as the endpoint event. The evaluation of radiation pneumonia in this study case was based on CTCAE 5.0. The whole cohort was divided into two groups, the RP and non-RP. The lung was segmented based on the dose-volume line as V5-10, V10-20, V20-30, V30-40, V40-50, and V50-60 as the region of interest (ROI). Then we register the ROI to the lung of the CT images in the middle and after the radiotherapy. We utilize open source software to extract the image features for each ROI to develop and validate the radiomics model to predict radiation pneumonitis. Two classifier models of random forest (Random forest, RF) and support vector machine (SVM) were used for classifying and learning samples' characteristics to distinguish between the pneumonia-occurring group and the non-occurring group effectively. We randomly divided the sample size into a training and validation group at a 4:1 ratio, and the five-fold cross-validation model (K fold cross-validation) was used for verification. The predictive performance was evaluated using overall accuracy for this triple classification task. Results The overall incidence of radiation pneumonia was 36%, and the incidence of severe radiation pneumonia (grade 3 and above) was 4%. The support vector machine (SVM) model has the best prediction performance compared to random forest, with an average accuracy rate of 0.72 and an average AUC value of 0.66. Under different dose line volume segmentation, the accuracy of the prediction models in pre-, mid-, and after treatment are 0.724, 0.744, 0.775 (V5-10), 0.736, 0.719, 0.737, (V10-20), 0.728, 0.696, 0.693 (V20-30), 0.671, 0.678, 0.684 (V30-40), 0.747, 0.724, 0.705 (v40-50), 0.799, 0.743, 0.726 (V50-60), respectively. The model constructed in the 50-60Gy area of CT before radiotherapy has the best performance in predicting radiation pneumonia. Conclusion Radiation pneumonia is a side effect that needs to be paid attention to in thoracic radiotherapy, and its incidence and severity directly affect patients' survival. Traditional radiation pneumonia prediction methods are relatively general. With the development of precise radiotherapy, further accurate radiation pneumonia prediction models are required. Radiomics can become a reliable prediction method for radiation pneumonia.

PURPOSE/OBJECTIVE(S) Xerostomia is a common sequela of radiation therapy (RT) and chemoradiotherapy (CRT). Head and neck cancer treatment can contribute to salivary glands injury with diminished salivary production and changes in consistency, volume, and pH of saliva. Previous studies examining xerostomia have investigated RT regimens, dosimetric predictors, and quality of life (QoL) associations but few have identified clinicodemographic risk factors for xerostomia and quantified their associations among oropharyngeal carcinoma (OPC) survivors. The objective of this study was to identify risk factors for xerostomia among long-term OPC survivors. MATERIALS/METHODS This was a cross-sectional study conducted at a comprehensive cancer center. Study participants included disease-free, adult OPC survivors who completed curative definitive radiotherapy treatment between January 2000 and December 2013, and responded to a survey administered from September 2015 to July 2016. This study included 881 OPC survivors with a median survival duration at time of survey of 7 years (range, 1-16 years) of which self-reported xerostomia scores were available for 853 participants. The primary outcome variable was patient-reported xerostomia measured using the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified using multivariable logistic regression. RESULTS Of 853 OPC survivors who responded to the xerostomia question, 337 (39.5%) reported moderate to severe xerostomia. Multivariable logistic regression identified current smoking at time of survey (OR:2.57, 95% CI: 1.20-5.53, P = 0.016) as a risk factor for moderate to severe xerostomia and concurrent cetuximab chemotherapy (OR:0.63; 95% CI: 0.41-0.97, P = 0.038) as a protective factor. Additionally, female sex (OR:1.81, 95% CI: 1.21-2.71, P = 0.004) and less than high school education (OR:1.68, 95% CI: 1.15-2.45, P = 0.008) were risk factors for moderate to severe xerostomia and bilateral intensity modulated radiotherapy (IMRT) combined with proton therapy (OR:0.34, 95% CI: 1.16-0.73, P = 0.005) and ipsilateral IMRT (OR:0.18, 95% CI: 0.07-0.46, P < 0.001) were protective. CONCLUSION In this large xerostomia study, about 4 out of 10 OPC survivors reported moderate to severe xerostomia over long-term follow-up. Continued smoking after cancer diagnosis, sex, and education were identified as important risk factors of moderate to severe xerostomia and concurrent cetuximab therapy and more modern RT regimens had a protective association. Sustained smoking post-diagnosis is a modifiable risk factor which can be addressed with continued smoking cessation efforts. Lastly, these results can inform future research and targeted patient-centered interventions to monitor and manage RT-associated xerostomia and preserve QoL among OPC patients.

Purpose/Objective(s) In the setting of head and neck (HN) re-irradiation (reRT), the goal is to adequately cover disease with as small a volume as appropriate to minimize normal tissue toxicity without compromising local control. However, it can be a challenge to gauge the extent microscopic disease beyond the gross tumor to be included in the reRT volume. Here, we aim to determine the patterns of failure after HN reRT. Materials/Methods Patients treated with curative intent intensity modulated radiation therapy (IMRT) or proton reRT from September 1999 – June 2015 were evaluated. A total of 148 patients with inoperable tumors received definitive reRT (intact) and 61 who underwent salvage surgery received post-operative reRT (postop). Those who had locoregional recurrence (LRR) and intact imaging data were analyzed. Using deformable imaging registration, diagnostic images at time of recurrence were overlaid on reRT treatment plans. The site of recurrence was delineated and evaluated by at least 2 radiation oncologists/radiologist with HN expertise. The patterns of failure were classified into five types based on spatial and dosimetric criteria: A (central high dose, or “in-field”), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose, or “out-of-field”). For patients who had multiple sites of recurrences, each site was classified independently. The kappa statistic was used to assess the inter-observer agreement on failure classification. Results Of the 209 patients treated, 67 developed LRR. This represented 44 of 148 (30%) intact patients (median dose 66 Gy) and 23 of 61 (38%) postop patients (median dose 60 Gy). Of these, 41 (61%) had imaging data for analysis, representing 47 sites of failures. Median time to failure was 21 weeks (range: 4 – 220 weeks). Patterns of failure among intact reRT were as follows: 13 Type A (39%), 6 Type B (18%), 1 Type C (3%), and 13 Type E (39%). The majority (79%) of failures were either in the high dose field or completely out of field. Interobserver agreement was 0.92. Patterns of failure among postop reRT were as follows: 4 type A (17%), 5 type B (22%), 5 type C (22%) and 5 type D (22%). The majority (56%) of recurrences were within 1 cm of the reconstructive flap bed, 40% recurred in the same primary subsite, and 17% recurred in the 1st echelon nodal level. Interobserver agreement was 0.68. Conclusion In patients who recurred after reRT, the majority was either within the central high-dose region, or completely outside the high-dose region suggesting poor disease biology. Biologic dose-escalation and or the addition of systemic therapies may offer improved disease control.

Purpose/Objective(s): Anatomical changes during radiation for head andneck cancer (HNC) induce differences between the planned and delivereddose. To account for this, an adapted treatment plan can be designed. Thedecision to do this is based on expert opinion after examination of inroomimages. The aims of this study were to 1. quantify the difference betweenplanned and delivered dose in HNC patients. 2. assess the consequentialdifference in normal tissue complication probability (DNTCP). 3. Assessthe positive predictive value (PPV) for the allocation of adaptive radiotherapy (ART) of clinical judgement vs. NTCP based on dose differencesat fraction 10 (F10) and 15 (F15).Materials/Methods: Daily CT scans in treatment position for 56 patientswere retrospectively analyzed. Delivered dose was calculated based on theanatomy of the day and subsequently mapped back to the planning CT toallow dose accumulation. The difference between planned and delivereddose was analyzed for CTVs and 9 organs at risk (OAR). DNTCP wascalculated for xerostomia, dysphagia, parotid gland dysfunction and tubefeeding dependency at 6 months post treatment (Tube6m) using previouslypublished NTCP models. ART was deemed necessary if DNTCP was>5%. To predict DNTCP at the end of treatment using the dose differenceat F10 or F15, the dose on that day was extrapolated to the full treatmentlength prior to the NTCP calculation. The PPV was calculated for identification of ART-patients by clinical judgement, DNTCP at F10 and F15. Elekta AB ; American Society for Radiation Oncology (ASTRO)