Purpose/Objective(s) Lymph node metastases (LNMs) reflect the interplay between cancer cells and immune cells in the lymph node microenvironment. Given that the immune microenvironment likely reflects common host responses against cancer, we hypothesized that molecular classification of immune expression profiles in LNMs provides biological markers that are shared across different subtypes of head and neck squamous cell cancers (HNSCCs). Materials/Methods We performed exomic capture mRNAseq in 69 LNMs from 59 patients with Human Papillomavirus (HPV)-positive HNSCCs. Unsupervised clustering was performed using immunology-related genes from the InnateDB. 33 non-overlapping genes reflecting immune rejection and tolerance clusters were used to generate a Lymph Node Immune Score (LNIS). LNIS was calculated as the difference between clusters from average total gene expression in an individual lymph node. Gene set enrichment analysis was performed using QuSAGE. Immune cell abundance was calculated using MCPcounter. Associations of LNIS with relapse free survival, extranodal extension (ENE) and existing prognostic gene signatures were tested using univariate Cox proportional hazard models or the Mann-Whitney test, respectively. The LNIS was validated using two previously published datasets of HPV-negative HNSCC LNMs (EGAS00001003233) or non-small cell lung cancer (NSCLC) LNMs (GSE197929). Results Unsupervised clustering identified two immune gene clusters in HPV-positive HNSCCs representing Immune Rejection and Immune Tolerance subtypes. Confirming these phenotypes, the Immune Rejection subtype was enriched for several HLA genes while the Immune Tolerance subtype was enriched for checkpoint genes, including CTLA4 and PDCD1 (PD-1). A LNIS was generated that quantified the relative dominance between the Immune Rejection subtype, which had a positive LNIS, and the Immune Tolerance subtype, which had a negative LNIS. A positive LNIS was associated with increase in T cell and B cell populations (P<0.0001), the absence of ENE (P=0.03) and correlated with favorable prognostic gene signatures (P< 0.0001). By contrast, a negative LNIS was associated with neutrophil (P=0.04) and fibroblast (P=0.02) populations In HPV-negative HNSCC patients, the LNIS correlated with a similar immune cell infiltrates, prognostic gene signatures (P<0.0001), locoregional control (P=0.01) and trended to an association with ENE (P=0.09). Finally, in a NSCLC cohort, a positive LNIS was associated with significantly improved relapse free survival (P=0.01). Conclusion Differences in immune phenotypes in metastatic lymph nodes were associated with distinct biological features and outcomes in HNSCCs and NSCLCs. Identification of immune microenvironments in LNMs can elucidate cancers with a propensity for immune evasion that benefit from treatment intensification.

Purpose/Objective(s) Treatment de-escalation is an effective strategy to mitigate treatment toxicities in human papillomavirus (HPV) related OPSCC. To avoid compromise of tumor control, reliable biomarkers to identify patients with high risk of treatment failure (TF) are critical. We evaluated the clearance of circulating tumor tissue modified viral (TTMV)-HPV DNA and its reverting positive (RP) score in predicting TF in patients with HPV+ OPSCC who received CRT. Materials/Methods Patients were enrolled from a single institution in a multicenter Phase III randomized trial comparing IMRT vs IMPT (CRT) in OPSCC. RT dose was 70 Gy, followed by restaging, with or without lymph node dissection (ND). Blood samples were collected in EDTA tubes from 10/23/2013 – 6/5/2023 prior to RT (baseline), during RT (at 2, 4, and 6 weeks), and post RT (at 3, 6, 9, 12, 16, 20, 24, 30 months). Isolated plasma (0.5 ml) was used for analysis of TTMV-HPV DNA (droplet digital PCR assay). Kaplan-Meier was used for the comparisons of TTMV-HPV DNA clearance post IMPT vs IMRT, and TF prediction by RP-TTMV-HPV DNA vs imaging. The association of RP-TTMV-HPV DNA score and TF was analyzed. Results A total of 1,352 plasma samples were analyzed (155 patients, median age: 59 [range = 33-84], 92.3% males). Clinical stages (AJCC 7) were: III 6.5%, IVA 92.9%, and IVB 0.7%. TTMV-HPV DNA resolved to undetectable in 11/17 patients (64.7%) post induction chemotherapy (IC). The data of 130 evaluable patients with detectable TTMV-HPV DNA at baseline (IMRT N = 71; IMPT N = 59) were further analyzed. In 20 patients with ND, TTMV-HPV DNA cleared in 3/7 patients (42.9%) post ND. Post CRT and ND, the TTMV-HPV DNA score in 128 patients (98.5%) resolved to undetectable (the mean and median time [months]: IMRT were 2.1 ± 0.4 and 1.0 [range = 0.5 – 24]; IMPT were 1.4 ± 0.2 and 1.0 [range = 0.5 – 6]). In patients with RP-TTMV-HPV DNA score at certain time points, 14/19 of them (73.7%) experienced TF; while 14 /18 patients (77.8%) with TF had a RP-TTMV-HPV DNA score. The presence of a RP-TTMV-HPV DNA score was significantly correlated with TF (p < 0.01) (Table). In patients with TF, the mean and median time (months) of appearing RP-TTMV-HPV DNA score (9.6 ± 1.6 and 6.0 [range = 0 – 20]) was shorter than that of the appearing of positive imaging (21.3 ± 5.6 and 12.0 [range = 3 – 96]). Conclusion RP-TTMV-HPV DNA score is a potential robust biomarker for TF in OPSCC. The clearance of TTMV-HPV DNA is similar in IMPT vs IMRT. RP-TTMV-HPV DNA score may predict the potential of TF earlier than imaging in OPSCC.

Purpose/Objective(s) Stereotactic body radiation therapy (SBRT) is an emerging approach for treating recurrent head and neck cancers (HNCs) and uses various fractionation schemes. However, limited data exists comparing the biologically effective doses (BEDs) of SBRT fractionation schemes and patient outcomes. Here, we hypothesized that higher BED was associated with improved survival in HNC patients treated with SBRT. Materials/Methods Utilizing the National Cancer Database, we identified 455 M0 patients with HNC treated with SBRT. SBRT was defined as a total dose of 20-50 Gy delivered in ≤ 6 fractions ranging from 5-10 Gy per fraction. BEDs were calculated using an α/β ratio of 10. Factors associated with BED were analyzed using logistic regression, and patients were stratified into BED < 50 Gy (BED50; n = 181), 50-80 Gy (BED50-80; n = 196), and > 80 Gy (BED80; n = 78). Overall survival was analyzed using Kaplan–Meier and Cox regression models. Results The most commonly treated sites included oropharynx (38.2%), oral cavity (22.0%), and larynx (14.7%), with the remainder of sites being hypopharynx, nasopharynx, paranasal sinus, and salivary. There was no difference in sex, HPV-status, performance status, T-stage, N-stage, or use of surgery or chemotherapy across groups. Of note, 110 patients (24.2%) underwent surgery prior to radiation. Median follow-up duration was 11.1 months (m). Multivariate analysis revealed survival associations with BED50-80 (HR = 0.70, p = 0.007), surgery (HR = 0.56, p = 0.001), age > 70y (HR = 1.74, p = 0.049), N-stage 2-3 (HR = 1.41, p = 0.022) and performance status (Charlson–Deyo 2 vs 0–1: HR = 2.19, p = 0.003). In patients not undergoing surgery, higher BEDs correlated with improved median survival (BED50 = 7.8m vs. BED50-80 = 14.6m vs. BED80 = 10.1m; P = 0.0001). Conversely, patients treated with initial surgery showed no survival improvement with increasing BED (p = 0.4503). Conclusion In HNC patients, higher BEDs in SBRT regimens were associated with enhanced survival among those with intact disease, in contrast to the absence of a survival advantage in surgically resected patients. These findings suggest that higher-dose SBRT regimens are critical for intact disease, while adjuvant SBRT regimens do not require dose escalation.

Intraoperative HAM BT resulted in favorable rates of IRC with acceptable toxicity in the reirradiation setting for HNSCC.

An approach to generate clinically acceptable automated contours for cervical lymph node levels in the head and neck was demonstrated. Furthermore, for nodal levels I-V, there was no significant difference in clinical acceptability in manual vs AI contours. Because we were able to generate and validate a model for each lymph node level individually, the output is applicable to a complete range of disease in which cervical lymph nodes are treated.

AC is a rare skin cancer with a primarily locoregional recurrence pattern. In our experience, adjuvant RT was associated with improved LC which, depending on the tumor location, may help prevent morbid or cosmetically-impactful salvage surgery. Patients with AC would benefit from radiation oncology referral to discuss adjuvant treatment.

Purpose/Objective(s) MCC is a rare cutaneous malignancy. This study evaluates patterns of care and outcomes for head and neck (HN) vs. non-HN (NHN) MCC at a large referral center. Materials/Methods We identified 144 locoregionally-confined MCC patients (pts) who received curative intent radiation therapy (RT) between 2003-2021. Clinicopathologic variables were described and time to relapse events were assessed by the Kaplan-Meier method. Results Of 144 pts, 80 (56%) had HN and 64 (44%) had NHN MCC. HN pts were older (median 70; IQR 66-76 vs. 65; IQR 57-73, p<0.001) and more likely male (63; 79% HN vs. 39; 61% NHN, p=0.03). Stage (I-II 42; 53% HN vs. 27; 42% NHN, p=0.24) and unknown primary presentation were similar (16; 20% HN vs. 7; 11% NHN, p=0.17). For pts with known primary tumor, wide local excision (WLE) after biopsy was less common in HN pts (46; 72% HN vs. 57; 100% NHN, p<0.001). Including 5 HN pts with excisional biopsies, R1 margin status was more common in the HN (15; 31% vs. 7; 13%, p=0.03), while all 13 definitive RT pts had HN disease. Most patients in this overall cohort received RT to the primary site (62; 96% HN vs. 55; 96% NHN) with a higher median dose for HN pts overall (60 Gy HN; IQR 56-60 Gy vs. 50 Gy NHN; IQR 56-60 Gy, p<0.001) as well as for pts having WLE (56 Gy HN; IQR 50-60 Gy vs. 50 Gy NHN; IQR 50-60). Similar rates of clinically LN+ disease were observed between cohorts (cLN+, 24; 30% HN vs. 18; 28% NHN, p=0.86), but HN pts had fewer LN dissections (LND, 14; 58% HN vs. 16; 89% NHN, p=0.024). Adjuvant nodal RT was delivered to most cLN+ pts (14; 100% HN vs. 14; 88% NHN, p=0.49) but this dose was higher for HN pts (med 59 Gy, IQR 52-60 Gy vs. med 50 Gy, IQR 50-54 Gy, p=0.013). For cLN- pts, fewer HN pts had sentinel lymph node biopsy (SLNB, 30; 54% HN vs. 42; 91% NHN, p<0.001). Of those SLN+ (11; 37% HN vs. 14, 33% NHN; p=0.81), only 1 HN pt and 2 NHN pts had completion LND. More HN pts received nodal RT for SLN+ disease (11; 100% HN vs. 9; 64% NHN, P=0.009) and elective nodal RT following N0 disease (4; 21% HN, med 46 Gy [IQR 46-53 Gy] vs 0% NHN, p=0.02). Nodal RT dose for cLN- pts trended higher in HN pts (med 52.5 Gy, IQR 46-60 Gy vs. 50 Gy, IQR 50-50.4 Gy, p=0.059). Median follow up was 40 months (IQR 22-58 mo) with similar outcomes for HN and NHN pts (3-yr LC 92% vs. 94%, p=0.85; 3-yr NC 83% vs. 79%, p=0.32; 3-yr DFS 64% vs. 60%, p=0.39). Conclusion Different treatment approaches exist for MCC pts at our institution based on tumor location. HN management historically relied more on comprehensive RT with higher doses whereas NHN management involves more comprehensive surgery and less RT. Anatomic limitations likely contributed to variation in practice. Despite differences in management tumor control outcomes are similar. Further study into the optimal approach to maximize disease control while limiting toxicity is warranted.

Purpose/Objective(s) Per the National Comprehensive Cancer Network (NCCN) guidelines, patients with locoregional recurrence or second primary with prior radiation therapy have a "dealer's choice" array of options following salvage resection for head and neck cancer (HNC). One option is stereotactic radiation therapy (SBRT). The aim of this retrospective study was to evaluate this shorter course of postoperative radiation therapy for patients in a previously irradiated area of the head and neck. Materials/Methods We analyzed the outcomes of patients treated with SBRT following resection of a recurrent or second primary head and neck cancer between 2015-2021 at our institution. Outcomes of interest included local control (LC), regional control (RC), distant metastatic control (DMC), overall survival (OS) and toxicity. Cox proportional hazards were used to identify predictors of OS. Follow up interval was defined as from the end of SBRT to last follow up or death. Results Sixty-seven patients with 71 resected lesions formed the cohort. Fifty-five percent of cases (n=39) were squamous cell carcinoma (SCC). The median initial radiation to reirradiation (XRT- reXRT) interval was 37 months (range 4-285), and the median interval from surgery to SBRT was 6.9 weeks (range 3.9-13.9). Twenty-eight percent (n=20) of patients received induction systemic therapy, 27% (n=19) received concurrent and 17% (n=12) received adjuvant therapy. The median SBRT dose was 35Gy (range 10-45Gy) delivered in 5 fractions (range 1-6) at median BED of 59.5Gy (range 20-84.8Gy) to a median target volume of 21cc (range 1-266cc). Median follow up was 11 months (range 0-50). Median LC was 38 months with 14 in-field failures and 5 marginal failures. The 1-year LC was 73%, 1-year RC was 70%, 1-year DMC was 80% and 1-year OS was 81%. On multivariate analysis, SCC histology was associated with worse OS (HR 4.48, 95% CI 1.33-15.12, p=0.02) and longer XRT- reXRT interval was associated with improved OS (HR 0.99, 95% CI 0.97-0.99, p=0.03). There was 1 grade 3 acute toxicity requiring feeding tube placement and no grade 4+ acute toxicities. With respect to late toxicities, there were 12 grade 3 (2 xerostomia, 1 pain, 3 soft tissue infection/necrosis, 1 trismus, 1 hearing loss, 1 osteoradionecrosis (ORN), 3 dysphagia requiring feeding tube), 2 grade 4 (1 ORN, 1 temporal lobe necrosis) and 1 grade 5 toxicity associated with complications from temporal lobe necrosis. Conclusion Oncologic and toxicity outcomes suggest that surgery and SBRT re-irradiation may be an appropriate option for well selected patients in this setting. The role and sequence of systemic therapy requires further investigation and reduced exposure to normal structures may further decrease late toxicities. Per the National Comprehensive Cancer Network (NCCN) guidelines, patients with locoregional recurrence or second primary with prior radiation therapy have a "dealer's choice" array of options following salvage resection for head and neck cancer (HNC). One option is stereotactic radiation therapy (SBRT). The aim of this retrospective study was to evaluate this shorter course of postoperative radiation therapy for patients in a previously irradiated area of the head and neck. We analyzed the outcomes of patients treated with SBRT following resection of a recurrent or second primary head and neck cancer between 2015-2021 at our institution. Outcomes of interest included local control (LC), regional control (RC), distant metastatic control (DMC), overall survival (OS) and toxicity. Cox proportional hazards were used to identify predictors of OS. Follow up interval was defined as from the end of SBRT to last follow up or death. Sixty-seven patients with 71 resected lesions formed the cohort. Fifty-five percent of cases (n=39) were squamous cell carcinoma (SCC). The median initial radiation to reirradiation (XRT- reXRT) interval was 37 months (range 4-285), and the median interval from surgery to SBRT was 6.9 weeks (range 3.9-13.9). Twenty-eight percent (n=20) of patients received induction systemic therapy, 27% (n=19) received concurrent and 17% (n=12) received adjuvant therapy. The median SBRT dose was 35Gy (range 10-45Gy) delivered in 5 fractions (range 1-6) at median BED of 59.5Gy (range 20-84.8Gy) to a median target volume of 21cc (range 1-266cc). Median follow up was 11 months (range 0-50). Median LC was 38 months with 14 in-field failures and 5 marginal failures. The 1-year LC was 73%, 1-year RC was 70%, 1-year DMC was 80% and 1-year OS was 81%. On multivariate analysis, SCC histology was associated with worse OS (HR 4.48, 95% CI 1.33-15.12, p=0.02) and longer XRT- reXRT interval was associated with improved OS (HR 0.99, 95% CI 0.97-0.99, p=0.03). There was 1 grade 3 acute toxicity requiring feeding tube placement and no grade 4+ acute toxicities. With respect to late toxicities, there were 12 grade 3 (2 xerostomia, 1 pain, 3 soft tissue infection/necrosis, 1 trismus, 1 hearing loss, 1 osteoradionecrosis (ORN), 3 dysphagia requiring feeding tube), 2 grade 4 (1 ORN, 1 temporal lobe necrosis) and 1 grade 5 toxicity associated with complications from temporal lobe necrosis. Oncologic and toxicity outcomes suggest that surgery and SBRT re-irradiation may be an appropriate option for well selected patients in this setting. The role and sequence of systemic therapy requires further investigation and reduced exposure to normal structures may further decrease late toxicities.

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.

NRG/RTOG 0022 was the first trial testing the feasibility of IMRT in a multi-institutional setting. In addition to meeting the criteria for acceptable local-regional control and reduction in acute xerostomia, long-term outcomes were very good with few deaths attributed to the studied cancer, 2/3 of patients alive at 10 years, and few grade 3-4 toxicities. Since conduct of this study, further improvements in IMRT have been accomplished both with regards to technical advancements in treatment delivery as well as attention to additional avoidance structures beyond the parotid glands. IMRT has transitioned from an optional form of radiation to the expected radiation technique to be delivered in RTOG/NRG Oncology trials of HN cancer.

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.

Tongue-depressing stents improve positional reproducibility and the use of a lateralizing oral stent diverts the mobile tongue to the contralateral side in order to minimize dose-dependent oral toxicities. However, data on long-term clinical outcome is still lacking. Since dosimetric studies already showed a benefit of stent use during photon RT, our hypothesis is that these stents decrease late oral toxicities and should routinely be applied. The aim of this study was therefore to evaluate the use of these stents regarding the association with late symptom burden in a large IRB-approved prospective longitudinal toxicity survey of oropharyngeal cancer (OPC) patients.

Complex oral treatment devices (COTD) used during radiation therapy (RT) for head and neck cancers (HNC) reduce the volume of normal tissue exposure to RT. Although a reduction in normal tissue exposure is associated with decreased incidence and severity of acute RT induced toxicities, COTDs are not a standard fixture in HNC RT. The objective of this study was to identify factors from epidemiological data obtained from Surveillance, Epidemiology, and End Results Medicare (SEER)-Medicare that serve as predictive factors of patient utilization of COTDs. A 1992-2013 retrospective cohort study using SEER-Medicare data was done to analyze the usage of COTDs during intensity-modulated radiation therapy (IMRT) for Medicare patients diagnosed with one of five subtypes (tongue, floor of mouth, nasopharynx, tonsil, oropharynx) of HNC. Medicare billing codes served as surrogate measures for identifying patients who used a COTD during IMRT. Patients with a radiation simulation code and complex treatment device code within 4 weeks of the first IMRT claim met COTD usage criteria. Demographic, tumor, and treatment data were collected. Multivariate logistic regression analysis was conducted to infer correlation between covariates and outcome variables. Of the 4511 patients that met eligibility criteria for the SEER-Medicare cohort, 1932 (42.8%) met COTD usage criteria. Patients aged 86+ were less likely to receive a COTD for treatment of HNC compared to those aged 66-70. (OR = 0.713, 95% CI: 0.528 – 0.962). Male patients were less likely to receive a COTD (OR = 0.817, 95% CI: 0.710 – 0.941). Non-Hispanic Black patients were significantly less likely to receive a COTD compared to non-Hispanic White patients (OR = 0.750, 95% CI: 0.582 – 0.966). Residents in Connecticut, Louisiana, and New Jersey were significantly less likely to receive a COTD. Socioeconomic status, HNC site, grade, stage, or function of IMRT did not have significant predictive effect of COTD usage. This study serves as the first known SEER-Medicare review of COTD utilization. Less than half of all HNC cancer patients receive a COTD. The main drivers of reduced utilization were age, gender, race and region. Cancer-related and economic factors were not associated with device usage. This suggests that the observed utilization rates are a function of a lack of availability as opposed to a lack of access. Further investigation into the availability of oral oncology support to make these devices for specific patient populations may help increase utilization.

To assess the outcomes and toxicities for squamous cell carcinoma (SCC) of the larynx treated with proton therapy.

We evaluated the patterns of loco-regional failure (LRF) and patient outcomes after intensity modulated radiation therapy (IMRT) in patients with unresectable anaplastic thyroid cancer (ATC) to inform target volume delineation and treatment strategies. We reviewed patients with unresectable ATC treated from 2010-2019 who received therapeutic dose IMRT (≥ 45Gy) and had at least 1 post-treatment neck CT. LRF after IMRT was defined as increase in size of treated disease or development of new disease in the neck. Recurrent gross tumor volumes (rGTV) were contoured on diagnostic CTs and co-registered with initial planning CTs using deformable image registration (Velocity AI). LRFs were classified based on established spatial and dosimetric criteria: Type A- central high dose; B- peripheral high dose; C- central elective dose; D- peripheral elective dose; and E- extraneous dose. Survival was estimated using the Kaplan-Meier method and groups were compared using Wilcoxon or log-rank analysis. 30 patients formed the cohort; 17 were stage IVA/B and 13 IVC. Median follow up after IMRT was 6.2m (1d-63m). Median prescribed dose was 66Gy (45-68Gy). 24 patients (80%) were treated with multi-dose levels and 6 patients (20%) were treated with a single dose level. 27 patients (90%) received concurrent chemotherapy. 17 patients (57%) developed LRF. 35 rGTVs were identified. Median LRF free survival (LRFFS) was 8.4m. Fractionation (daily, twice daily, or 6x/week) did not predict LRFFS (p = 0.7). No difference in LRFFS was seen in patients treated to 1 dose level vs. multi-dose levels (p = 0.7). A majority of failures occurred in the high dose volume- Type A (n = 25, 71%) and Type B (n = 2, 5.7%). 3 recurrences in 3 patients (2 Type C, 1 Type D) occurred in elective dose volumes, while the remaining 5 recurrences in 4 patients were in extraneous dose regions (Type E). Mean high dose target volume in those with vs. those without LRF was 217 cc vs. 192 cc, respectively (p = 0.6). Median OS was 6.7m from end of IMRT (11.8m for stage IVA/B, 3.1m for IVC, p = 0.02). For those with stage IVA/B, median OS was 11m for those with LRF and 15m for those without (p = 0.7). Overall, 24 patients (80%) developed distant failure (13 with new sites, 11 with progressive DM). Only 4 patients (13%) required tracheostomy or tracheal stent during or after IMRT. 15 (50%) required a feeding tube. Despite an aggressive chemoRT schedule, central high dose failures predominated. These findings are consistent with a classic radio-resistant disease profile. Given the high competing risk for distant failure, no survival difference was detected between those with vs. those without local regional control. However, the low rate of airway interventions required suggests a palliative benefit. Strategies to maximize both local and distant control including neoadjuvant targeted therapy in those with actionable mutations, followed by surgical resection and post-operative chemoRT are under current investigation.

Purpose: We evaluated the geometric and dosimetric-based distribution of mucosal and nodal recurrences in patients with metastatic head and neck squamous cell carcinoma to cervical lymph nodes of unknown primary after intensity modulated radiation therapy using validated typology-indicative taxonomy. Methods and Materials: We reviewed the data of 260 patients who were irradiated between 2000 and 2015 and had a median follow-up time for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on computed tomography images demonstrating the recurrences. The images were overlaid on the treatment plan using deformable image registration. The locations of the recurrences were determined relative to the original planning target volumes and doses using centroid-based approaches. Subsequently, the pattern of failures were classified into 5 types based on combined spatial and dosimetric criteria: A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose). For patients with type A failure with simultaneous nontype A lesions, the overall pattern of failures was defined as type A. Results: Thirty-two patients had mucosal or nodal recurrences. The most common clinical nodal stage was N2b (66%). Preradiation therapy neck dissections were performed in 6 patients. The median dose delivered to clinical tumor volume 1 was 66 Gy. The majority (84%) had total/partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences, and 1 had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure, and 7 of the mucosal failures (89%) were type C. Conclusions: The majority of nodal recurrences occurred within the high-dose area, demanding the need for identification of radioresistant areas within malignant nodes. Future studies should focus on either dose escalation of high-risk volumes or novel radiosensitizers.

The purpose of this study was to analyze locoregional control and survival in patients with recurrent oropharyngeal cancerfollowing reirradiation with intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and proton beam therapy (PBT).

Only few studies have addressed dysgeusia dose-toxicity relationship in head and neck cancer patients treated with definitive RT, all without ROI-specific analysis. To this end, we aim to assess the impact of different delineation methods of taste bud-bearing tongue mucosa on the dosimetric parameters and toxicity outcomes. A total of 42 T1-3 NX-2 oropharyngeal cancer patients treated with IMRT alone were prospectively enrolled under an IRB-approved protocol. All patients were disease-free and without cancer-directed therapy for the last 6 months prior to enrollment. Three ROIs were manually delineated on the planning CT: A) the whole tongue (extrinsic and intrinsic muscles), B) the dorsal mucosa of the oral tongue using a highly reproducible approach by adapting the whole tongue structure in a defined way and C) the dorsal mucosa using a much faster method with axial adaption of a midsagittal contour. Both, B and C, consisted of a 5mm layer reaching from the apex along the upper tongue surface to the base of tongue. Dosimetric parameters were calculated from the original RT plan. The single item Taste assessment of the MD Anderson Symptom Inventory – Head and Neck module (MDASI-HN), rating taste changes between 0 ("not at all") and 10 ("the worst you can imagine"), was collected after a median of 5 years following IMRT (range 2-10). Wilcoxon signed rank test has been used to test for differences between the contouring methods. TD50 of dysgeusia (scores of 1+) was calculated using logistic regression. Multivariate analysis was done to assess for correlation with clinical parameters. A p-value of <0.05 was considered significant. The mean volume of the contours differed significantly between the three methods, with highest volume for the whole tongue (method A, 122.2cc, SD 26.0), followed by the mucosa contoured according to method B (20.0cc, SD 5.8) and C (18.8cc, SD 4.9). Dose difference was statistically significant between method A / B and method A / C regarding min, max, mean doses as well as V30, 40, 50 (all p<0.001). The difference between the mean dose in method A (49.3 Gy) and B (46.6 Gy) accounted on average +2.6 Gy (SD 4.5, range -6.3 – 19.7). There was also a difference for V20 (p<0.06) and V60 (p<0.05), but in a lesser extent. No significant difference in any of the dose parameters was found between method B and C. Mean MDASI Taste score was 2.3 (SD 3.1, range 0-10) with 57% of patients having dysgeusia. Patients with higher mean doses in the ROIs were more likely to exhibit dysgeusia. TD50 for mean dose was 30.8 Gy with method A, and much higher with method B (40.4 Gy) and C (39.8 Gy). No significant correlation was found between dysgeusia and age, smoking status or T stage. Dosimetric results differed significantly for nearly all tested parameters with the different delineation methods contouring the whole tongue or the dorsal mucosa only. This is highly relevant and should be considered in the evaluation of any normal tissue complication probability of dysgeusia.

Locoregional recurrence remains the most common pattern of failure in head and neck cancers (HNC). Despite emerging retrospective data showing durable local control and improved survival with highly conformal reirradiation (reRT) techniques, prospective data of large patient cohorts is lacking. Here we present preliminary clinical outcomes of our prospective reRT registry protocol. 167 patients with history of prior HN radiation were prospectively enrolled and treated with curative-intent IMRT, proton therapy (PBT), or stereotactic radiotherapy (SABR) between 2015 and 2018 for recurrent or second primary HNC. Outcomes were evaluated using Kaplan-Meier and stratified by treatment modality. Toxicity was evaluated using CTCAE v4.03. UVA and MVA was performed via Cox proportional hazards and logistic regression modeling. A total of 69 IMRT, 54 SABR, and 44 PBT reRT courses were assessed. Overall median follow-up was 18.2 months (0.4-45.7). There were no significant differences in age, gender, performance status, smoking status, or previous RT dose among treatment groups. The mean reRT BED (α/β 10) was 76.6±8.7 Gy. Overall, 55% received upfront surgery (SABR 28% vs. 55% PBT vs 77% IMRT, p<0.0001), and 66% received chemotherapy. 1- and 2-year OS rates were 83% and 70%, with no differences by radiation modality (p=0.584). Median time to LRF and PFS were 23.2 months (95% CI: 13.3-33.1) and 13.6 months (95% CI: 9.2-18.0), respectively, with no significant differences noted. Table 1 provides a summary of stratified clinical outcomes stratified. 11% of patients developed DM. In the 8 patients with DM before reRT, there was a 14.9 month median OS with only one death and one LRF. On MVA, SCC histology was associated with greater mortality (HR 4.1, 95% CI 1.6-10.2; p=0.003), whereas ECE was adverse for LRC (HR 2.0, 95% CI 1.1-3.7; p=0.025) and PFS (HR 2.5, 95% CI 1.4-4.4; p=0.002). Acute G3-4 toxicity rates were 19% overall (28% IMRT, 2% SABR, 38% PBT; p<0.001), with dermatitis (11%) and dysphagia (8%) most common. Late G3-4 toxicity occurred in 9% of patients. Acute and late feeding tube rates were each 3%. Smoking history (any) was significantly associated with late toxicity (OR 9.0, 95% CI 1.8-45.0; p=0.007). Aggressive reRT, even in the setting of limited metastatic disease, should be considered for recurrent HNC given favorable clinical outcomes and low toxicity rates. This large, prospective cohort showed comparable results for protons, IMRT, and SABR. Future analyses may seek to further define patient selection for each modality.Abstract 2868; Table 1Actuarial clinical outcome ratesIMRTProtonSABROverallMedian1-yr2-yr1-yr2-yr1-yr2-yr1-yr2-yrOS84%71%81%63%84%72%83%70%NRLC68%61%66%63%67%50%67%56%29.8 (23.2-36.4)LRC59%52%59%41%56%40%58%48%23.2 (13.3-33.1)PFS56%45%54%52%48%27%53%40%13.6 (9.2-18.0) Open table in a new tab

Oropharyngeal cancer (OPC) patients undergoing chemoradiation (CRT) are at high risk for "financial toxicity" from missed or lost work during and after treatment, as patients undergo intensive multimodality therapy impacting acute and long-term daily activities/function. Despite growing appreciation for the need to identify optimal CRT approaches that enable preserving work, productivity, and economic burden, no randomized studies have compared how treatments impact work outcomes in OPC. We compared the effect of intensity-modulated proton therapy (IMPT) vs intensity-modulated photon therapy (IMRT) on work and productivity outcomes in OPC patients receiving CRT on a randomized trial. From 2014-2018, 188 patients were randomized to IMPT vs. IMRT for stage II-IVB (7th ed) squamous cell carcinoma of the oropharynx, stratified by induction chemotherapy, HPV/p16 and smoking. A pre-specified aim compared patient-reported work outcomes using the validated Work Productivity and Activity Impairment (WPAI) questionnaire at baseline, end of CRT, 6 months, 1 year, and 2 years. Patients reported whether they were working, and working patients scored (0-100) levels of absenteeism, impairment while working, and productivity losses over the prior 7 days. Cochran-Armitage test analyzed differences in the proportion of patients working during follow-up. WPAI scores were compared using the Wilcoxon rank sum test. Mixed effects models tested longitudinal predictors. In 96 patients receiving IMPT and 92 IMRT, median age was 59. Baseline demographics, stage, employment, and insurance were balanced. 78% (n=147) participated in patient-reported outcomes aims, with evaluable responses in 79% of patients at 6 months, 67% at 1 year and 44% at 2 years. At baseline, there was no difference in the proportion of working IMPT patients (61%) vs. IMRT patients (58%) (P=0.71). However, among IMPT patients, the proportion who returned to/maintained work after treatment significantly increased over time, from 63%-78% (P=0.02). In contrast, among IMRT patients, the proportion working was unchanged over time, from 48%-55% (P=0.58). Among working patients, absenteeism, impaired work, and productivity loss ascribed to cancer did not differ by treatment arms, approaching baseline scores by 2 years (P= 0.17 to 0.80 for IMPT vs. IMRT scores at end of CRT, 6 months, 1 year, and 2 years). Adjusted scores were comparable in multivariate models. After CRT for OPC, patients undergoing IMPT were more frequently able to return to work with comparable productivity vs. those undergoing IMRT, demonstrating an absolute benefit of 26% at 2 years. Results provide Level 1 evidence in a randomized setting, using novel outcomes measures to demonstrate favorable societal- and patient-level economic impacts of IMPT for patients with OPC.Abstract 2977; Table 1Proportion of patients working (%)RandomizationPre-CRTEnd of CRT6 Months1 Year2 YearsPPBT61%63%71%71%78%0.02IMRT58%48%55%54%52%0.58 Open table in a new tab