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Background: Breast cancer is the second most commonly diagnosed cancer in North American women. The administration of neoadjuvant chemotherapy (NAC) is the mainstay of treatment for individuals with high risk disease in an effort to reduce the extent of surgery, evaluate the role of additional adjuvant therapies (based on pathologic response to NAC), and improve disease-free and overall survival (OS). Anthracyclines have been shown to increase response rates leading to a greater likelihood of pathologic complete response compared to non-anthracycline regimens. However, for some individuals anthracyclines are omitted from the NAC regimen due to toxicities including greater immunosuppression, cardiac toxicity and risk of acute leukemia. We established a population-based cohort of individuals treated with NAC for breast cancer. We report the outcomes of women selected for treatment with non-anthracycline NAC compared to those treated with anthracyclines. Methods: This is a retrospective population-based cohort study using linked health administrative data held at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. We identified adult women diagnosed with stage I-III breast cancer (ICD-10 C50^) between 2012 and 2020 who received NAC. Administration of at least 50% of the planned chemotherapy regimen was required. We excluded patients with bilateral breast cancer, previous malignancy and male sex. NAC regimens were classified as anthracycline and non-anthracycline-containing regimens. To address confounding between those receiving anthracycline and other regimens, we built a propensity score model including patient and disease characteristics. The association with OS was calculated using Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using cause-specific Cox proportional hazards models. Models were adjusted for the propensity score, radiation treatment as a time-varying covariate, age, socioeconomic status, breast cancer stage and receptor sub-type, as well as Charlson comorbidity index. Results: A total of 4,180 women were identified with a median follow up of 62 months (IQR 44 – 85). Of these, 279 (6.7%) were treated with non-anthracycline regimens compared to 3,901 treated with anthracycline. Patients who received non-anthracyclines were older (median 62 years vs. 50 years; p < 0.001), and less likely to have stage III disease (33.0% vs. 48.7%; p < 0.001), and harbor triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p < 0.001). They were more likely to have no recorded comorbidities (89.2% vs. 96.5%; p < 0.001), undergo mastectomy (82.1% vs. 71.9%; p < 0.001), and sentinel lymph node biopsy (44.4% vs. 32.3%; p < 0.001). After propensity score and multivariable adjustment, women selected for treatment with non-anthracycline regimens had similar OS (HR 0.85, 95% CI 0.60-1.21) and BCSS (cause-specific HR 0.76, 95% CI 0.46-1.25) compared to those treated with anthracyclines. When stratified by stage, women treated with non-anthracycline regimens did not have significantly higher incidences of breast cancer death or death from any cause (stages I, II, and III Gray’s Test p-value all > 0.1). The mean OS was 7.2 years for women who received non-anthracycline regimens (95% CI 7.0 – 7.4) compared to 7.9 years for those who received anthracycline (95% CI 7.9 – 8.0) (log-rank p = 0.100). Conclusions: Women with stage I-III breast cancer treated with non-anthracycline NAC regimens are a highly selected population. These patients were older and healthier, with earlier stage disease and more favorable subtype (i.e. non-TNBC) when compared to those treated with anthracycline NAC. Our results demonstrate that women were well selected to omit anthracyclines and did not have worse survival outcomes. Further research is needed to better understand in whom anthracycline can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Matthew Castelo, Rinku Sutradhar, Lena Nguyen, Neil Faught, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-10.

IMPORTANCE: Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making. OBJECTIVE: To develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018. INTERVENTIONS: All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines. MAIN OUTCOMES AND MEASURES: Main outcomes were LRF, DM, and overall survival (OS). Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups. RESULTS: Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS. CONCLUSIONS: In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival.

The objective of this study was to describe the clinical presentation and outcomes of human papillomavirus (HPV)-positive nasopharyngeal cancer (NPC) versus Epstein-Barr virus (EBV)-positive NPC and HPV-positive oropharyngeal cancer (OPC).Clinical characteristics and presenting signs/symptoms were compared between patients who had viral-related NPC versus viral-related OPC treated with intensity-modulated radiotherapy from 2005 to 2020 and who were matched 1:1 (by tumor and lymph node categories, smoking, age, sex, histology, and year of diagnosis). Locoregional control (LRC), distant control (DC), and overall survival (OS) were compared using the 2005-2018 cohort to maintain 2 years of minimum follow-up. Multivariable analysis was used to evaluate the cohort effect.Similar to HPV-positive OPC (n = 1531), HPV-positive NPC (n = 29) occurred mostly in White patients compared with EBV-positive NPC (n = 422; 86% vs. 15%; p.001). Primary tumor volumes were larger in HPV-positive NPC versus EBV-positive NPC (median volume, 51 vs. 23 cmHPV-positive NPC and EBV-positive NPC seem to be mutually exclusive diseases. Patients who have HPV-positive NPC have greater local symptom burden and larger primary tumors but have similar outcomes compared with patients who have EBV-positive NPC or HPV-positive OPC.

Extranodal extension (ENE) represents a spectrum of tumor invasion beyond the nodal capsule. The earliest stages of ENE can only be detected under the microscope (pathologic-ENE, pENE). As ENE progresses, it can eventually become visible on imaging (radiologic-ENE, rENE). When ENE further advances to invade skin and/or underlining structures causing fixation and neurovascular impairment, it becomes clinically evident (clinical-ENE, cENE). pENE is the most objective and sensitive way of identifying ENE while subjectivity exists for rENE and cENE detection. Hence, pENE often serves as a gold standard for assessing the accuracy of rENE and cENE. The sensitivity and specificity of rENE for pENE depends on the level of certainty that a radiologist has adopted for declaration. If unequivocal radiologic signs are used for declaration, the specificity of rENE for pENE is very high. Unequivocal rENE carries prognostic significance beyond traditional cN classification for both viral-related and unrelated head and neck cancer, and can serve an important role for clinical care and risk stratification. For clinical care, such as triaging HPV-positive oropharyngeal cancer to surgery vs radiotherapy, a relatively modest level of certainty (>50%) may be used for rENE declaration before treatment assignment to achieve high sensitivity and avoid potential triple-modality treatment. For staging, a high level of certainty (>90%) should be used for rENE declaration to preserve its prognostic importance and avoid dilution due to equivocal cases, or the inclusion of minimal ENE lacking importance due to mitigation by contemporary treatments. Standardization of definitions and radiology reporting templates should facilitate the adoption of rENE into clinical care and staging.

PURPOSE To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution. METHODS AND MATERIALS NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) and rENE-negative (rENE-) patients. Multivariable analysis (MVA) confirmed the prognostic importance of rENE and its grade. Staging schemas including rENE in N-classification were proposed and their performance evaluated. RESULTS A total of 274 patients were eligible (43 cN0; 231 cN-positive). rENE was identified in 83/231 (36%) cN-positive, including grade 1/2/3 rENE in 14/58/11 cases. Compared to rENE-, rENE+ patients had a lower OS (68% vs 89%, p

Purpose: Breast cancer (BC) patients (pts) who are not surgical candidates or decline surgical resection are usually managed with palliative systemic therapy alone or palliative radiotherapy if clinically appropriate. Stereotactic body radiotherapy (SBRT) has shown excellent results for different primary malignancies, and we hypothesized it could improve outcomes in this context with acceptable toxicity. This study aims to assess the local control (LC) and toxicity rates of breast SBRT in pts unsuitable for surgical resection. Methods and Materials: We performed a retrospective analysis using an institutional registry of all BC pts unsuitable for resection who underwent breast and/or regional lymph node (LN) SBRT to a dose of 35-40 Gy in 5 fractions from 2014 to 2021. Patients were deemed unsuitable for resection if they were medically inoperable, declined surgery, had unresectable tumors, or where surgery was not appropriate, such as due to metastatic disease. The primary endpoint was LC (defined as no evidence of progression of the treated lesion as per RECIST 1.1 criteria) and toxicity grade ≥ 3 (as per CTCAE v5.0). Secondary endpoints included radiological response (RR) of the target tumor at the last follow-up, progression-free survival (PFS), and overall survival (OS). All endpoints were assessed per course of treatment, with death as a competing factor for LC. Results: This study included 61 treatment courses in 57 pts. The median age was 81 years (range 38-99), 74% being older than 70 years of age. Eighteen percent had stage I-II, 44% stage III, and 38% stage IV disease. Unresectable tumor (10%), patient refusal (18%), medically inoperability (34%), and metastatic disease (38%) were the main causes of not having surgery. The molecular subtypes were HER-2 in 3%, basal-like 23%, and luminal disease 74%. Previous systemic treatment consisted of endocrine therapy (ET) alone (49%), chemotherapy (CT) or target therapy (TT) alone (11%), both ET and CT/TT (18%), or none (21%). Seventy-two percent of tumors were progressing on ET (44%) or CT/TT (28%) at the time of SBRT. The median interval from cancer diagnosis to SBRT was 14.6 (range 0.5-180) months (mos). Fifty-four percent had breast SBRT, 15% LN SBRT, and 31% both. For LN treatment, axillary, internal mammary, and supraclavicular nodes were the target in 43%, 3%, and 2% of treatments, respectively. The median clinical and radiological follow-up was 16.8 (range 0.2-87) and 13.4 mos (range 1-81), respectively. The worst acute and late grade ≥ 3 toxicity was 16% and 4%, respectively, and all cases consisted of radiation dermatitis. No patient was unable to complete treatment due to acute toxicity. There was one case of grade 4 skin necrosis 6.3 mos after 35 Gy in 5 fractions to an axillary LN. The LC rate at 1 year was 100% and 2 years 88.6% (95% CI = 79-99%). The median time to local progression among those who progressed was 18.2 mos (95% CI = 12-not reached). At last FU, the RR of treated tumors was: complete response = 8%, partial response = 46%, stable disease = 38%, and progressive disease = 8%. The PFS and OS rates at 1 year was 69.8 % (95% CI = 58-82) and 74.6% (95% IC = 63-86), 2 years 39.1% (95% CI = 26—52) and 50.6% (95% IC = 36-65), 3 years 26.7 % (95% CI =14-39) and 38.7% (95% IC = 24-54), and 4 years 18.5 % (95% CI = 8-29) and 29.2% (95% CI = 14-44), respectively. The median PFS was 21.7 mos (95% CI = 17-28) and OS 31.1 mos (95% CI = 21- 38). Ongoing analysis intends to identify clinical and pathological predictors of LC, PFS, and OS. Conclusion: Our initial data suggest that breast SBRT safely provides excellent LC rates in non-operable BC pts. This approach may be a treatment option in pts who are not good surgical candidates, particularly in elderly pts with multiple comorbidities, which comprised 74% of our cohort. A clinical trial is underway to determine the optimal dose and side effect profile for primary breast SBRT with curative intent in pts not undergoing definitive surgery. Citation Format: Daniel Palhares, Hanbo Chen, Benazir Khan, Claire McCann, Sandi Bosnic, Ezra Hahn, Hany Soliman, Eileen Rakovitch, Justin Lee, Danny Vesprini. Locoregional Stereotactic Body Radiotherapy in Breast Cancer Patients Unsuitable for Surgical Resection [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-04.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

Purpose Mitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. Methods and Materials A state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. Results After the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. Conclusions A significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.

Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach.HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup.A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n = 189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS.Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.

ImportanceWhile several studies have documented a link between socioeconomic status and survival in head and neck cancer, nearly all have used ecologic, community-based measures. Studies using more granular patient-level data are lacking.ObjectiveTo determine the association of baseline annual household income with financial toxicity, health utility, and survival.Design, Setting, and ParticipantsThis was a prospective cohort of adult patients with head and neck cancer treated at a tertiary cancer center in Toronto, Ontario, between September 17, 2015, and December 19, 2019. Data analysis was performed from April to December 2021.ExposuresAnnual household income at time of diagnosis.Main Outcome and MeasuresThe primary outcome of interest was disease-free survival. Secondary outcomes included subjective financial toxicity, measured using the Financial Index of Toxicity (FIT) tool, and health utility, measured using the Health Utilities Index Mark 3. Cox proportional hazards models were used to estimate the association between household income and survival. Income was regressed onto log-transformed FIT scores using linear models. The association between income and health utility was explored using generalized linear models. Generalized estimating equations were used to account for patient-level clustering.ResultsThere were 555 patients (mean [SD] age, 62.7 [10.7] years; 109 [20%] women and 446 [80%] men) included in this cohort. Two-year disease-free survival was worse for patients in the bottom income quartile (Conclusions and RelevanceIn this cohort study, patients with head and neck cancer with a household income less than CAD$30 000 experienced worse financial toxicity, health status, and disease-free survival. Significant disparities exist for Ontario’s patients with head and neck cancer.

The paucity of data on women with large (≥ 40 mm) DCIS tumors lead to uncertainty on the safety of breast-conserving surgery (BCS) for these patients. We evaluated the impact of large tumor size on local recurrence (LR) among women with DCIS treated with BCS ± radiotherapy (RT).Treatment and outcomes were ascertained through administrative databases for all women with DCIS in Ontario from 1994 to 2003 treated with BCS ± RT with negative margins; 82% had pathology review. Cox proportional hazards model was used to evaluate the impact of tumor size on LR. 10- and 15-year LR-free survival (LRFS) were calculated using Kaplan-Meier method.The cohort includes 2049 women treated by BCS (N = 1073 with RT). Median follow-up is 14 years (IQR 9-17 years). Referenced to tumors ≤ 10 mm, the risk of LR following BCS was significantly higher for larger tumors: HR ≥ 40 mm = 3.67 (95% CI 2.13, 6.33; p 0.001), HR 26-39 mm = 2.27 (95% CI 1.47, 3.50, p 0.001), and HR 11-25 mm = 1.42 (95% CI 1.06, 1.92, p = 0.02). However, for individuals with BCS + RT, large tumor size was not associated with a significantly increased risk of LR (HR ≥ 40 mm = 1.92 (95% CI 0.97, 3.79); HR 26-39 mm = 1.81 (95% CI 1.09-2.99)). For women with tumors ≥ 40 mm, 10-year LRFS risk for those treated by BCS alone, BCS + RT without boost, and BCS + RT with boost was 58.9%, 82.8%, and 83.9%.Large DCIS lesions ≥ 40 mm are associated with higher risks of LR following BCS, but high long-term LRFS rates can be achieved with the addition of breast RT.

Highlights • For 40 years, all soft tissue sarcoma (STS) used the same TNM where T1 was 5 cm. • Despite smaller size, local recurrence is higher in STSHN compared to other STS. • A new T classification with 2 and 4 cm cut-offs for STSHN was introduced in TNM-8. • Future requirements for STSHN Stage Group development are mentioned., The tumor, node, metastases (TNM) anatomic staging system plays a pivotal role in cancer care, research, and cancer control activities. Since the first edition of the American Joint Committee on Cancer TNM staging classification published in 1977, soft tissue sarcomas have been staged in an anatomic site agnostic fashion whereby the primary tumor size (T) was categorized as T1 if 5 cm; this remained unchanged through the 7th edition of the TNM. However, soft tissue sarcomas of the head and neck (STSHN) usually present smaller than sarcomas of other sites, but carry a disproportionate risk of local recurrence. Up to 70% of tumors are less than 5 cm at presentation, and therefore classified together as T1. Given the rarity of STSHN, there is a paucity of data to guide progress in their classification. Moreover, the majority of publications only report tumor size as less than or greater than 5 cm, presumably based on conventions of the TNM system that remained unchanged for 40 years, thereby affecting progress of STSHN classification. This formed the impetus for change in the 8th edition in 2 key ways: 1) several soft tissue sarcoma site based changes occurred including STSHN now having its own system, and 2) primary tumor size cut-offs of 2 cm and 4 cm used in STSHN now reflect sizes that head and neck specialists commonly encounter in their practice. This update was pragmatic in modifying the TNM from a system with a T category not serving STSHN and which was originally based on sarcoma data from non-head and neck anatomic sites. The background to this change is outlined which provides a framework in which data can be reported to generate evidence for future staging modifications.

e18057 Background: We aimed to identify the incidence and risk factors for osteoradionecrosis (ORN) in head and neck cancer (HNC) patients. We also compared frequency of severity scores across different ORN grading systems. Methods: Retrospective review was conducted for HNC patients who were managed at our institution (2011-2018) with curative-intent definitive, pre- or post-operative intensity-modulated radiation therapy (IMRT) with 45Gy, and underwent pre-IMRT dental evaluation. Jaw ORN was defined based on: 1) clinical signs (exposed bone, bone spicules, sequestra, infection and fistula), 2) radiological finding (abnormal bone pattern, radiographic sequestra and pathological fracture), and 3) treatment required and response to therapy, either conservative (chlorhexidine rinse, antibiotics, PENTOCLO, and hyperbaric oxygen) or surgical (sequestrectomy, debridement, and jaw resection). ORN events were retrospectively graded using 6 different grading systems. Pre-IMRT periodontal condition (PC) was classified by universal multi-dimensional staging system based on number of teeth and bone loss (stages 0 to IV). Multivariable analysis (MVA) using logistic regression was applied to identify risk factors of ORN. Results: A total of 2735 HNC patients were included; median age 61 years, 30% (n = 807) current/ex-smokers, 72% (n = 1914) had moderate to severe PC (stage II-IV), 53% (n = 1459) oral cavity/oropharynx (OC/OP) primary tumor. The median IMRT dose was 70Gy/35 fractions, 43% (n = 1170) received concurrent chemotherapy, and 37% (n = 1006) underwent surgery. A total of 227 patients (8.3%) developed ORN. There was discrepancy in different grading system for capturing and reporting the degree of severity (i.e. grade) of ORN (table). On MVA, risk factors for ORN were: current/ex-smoker (OR 1.5, 95% CI: 1.12-2, p< 0.01), stage II-IV PC (OR 1.7, 95% CI: 1.17-2.36, p< 0.01), primary OC/OP tumor (OR 4.4, 95% CI: 3.08-6.29, p< 0.001], and IMRT dose prescription ≥60Gy (OR 3.5, 95%CI: 1.11-11.33, p< 0.01). Conclusions: ORN is relatively uncommon in HNC patients, however it can be under-reported by different grading systems. Risk factors for ORN were: smoking history, pre-IMRT poor PC condition, OC/OP primary tumor, and higher dose (≥60Gy) IMRT.[Table: see text]

577 Background: The Choosing Wisely guidelines recommend against surgical axillary staging (AS) in women ≥70 years with ER+/HER2- early stage breast cancer (BC). However, there has been little change in practice patterns, which may be influenced by observational studies reporting worse survival among women not receiving AS. Previous analyses did not take into account comorbidities, specific adjuvant treatments and HER2 status which may confound the association between AS omission and survival. This study examined the impact of AS omission on survival in older patients with Stage I/II BC, and secondarily emulated the Choosing Wisely population in a subgroup of those ≥70 years undergoing sentinel node biopsy (SLNB) vs. no AS for ER+/HER2- tumors. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women aged 65-95 years who underwent surgery for Stage I/II BC between 2010 and 2016. We excluded women who received neoadjuvant chemotherapy. To address confounding between those who did and did not receive AS, we built a propensity score model including patient and disease characteristics. Patients were weighted by propensity scores using overlap weights. Association with overall survival (OS) was calculated using weighted Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using weighted Fine and Gray models, adjusting for biomarkers and adjuvant treatments. Adjuvant treatment receipt was modelled with weighted log-binomial models. Results: Among 17,546 older women, 1,807 (10.3%) did not undergo AS, who were older, more comorbid, less likely to undergo mastectomy, and more likely to have tumors ≥ 2 cm. After propensity score weighting, baseline characteristics including comorbidity were balanced between the two groups. Women who did not undergo AS were less likely to receive adjuvant chemotherapy (adjusted RR 0.70. 95% CI 0.58-0.84), endocrine therapy (adjusted RR 0.85, 95% CI 0.82-0.89) and radiotherapy (adjusted RR 0.69, 95% CI 0.65-0.73). Unadjusted 5-year survival was lower for women who did not undergo AS (68.1%, 95% CI 65.8-70.2 vs. 87.6%, 95% CI 87.0-88.1; p< 0.001), and there was a higher 5-year incidence of BC deaths (7.6%, 95% CI 6.2-9.2 vs. 4.3%, 95% CI 3.9-4.7; p< 0.001). After weighting and adjustment, women who did not undergo AS continued to have worse OS (adjusted HR 1.13, 95% CI 1.03-1.24), however, there was no significant difference in BCSS (adjusted HR 1.00, 95% CI 0.78-1.26). The results among 6,286 ER+/HER2- women ≥70 years undergoing SLNB vs. no AS were similar for OS (adjusted HR 1.22, 95% CI 1.05-1.42) and BCSS (adjusted HR 1.08, 95% CI 0.67-1.76). Conclusions: The omission of AS in older women with early stage BC was associated with worse OS, reflecting selection bias, but no significant difference in BCSS.

6092 Background: Sinonasal cancers (SC) are heterogeneous diseases. Despite multimodality treatment, overall survival (OS) remains unsatisfactory. We aimed to identify prognostic factors (PFs) associated with patterns of failure and OS in non-metastatic SC (nmSC). Methods: We retrospectively reviewed a pooled dataset of nmSC from Princess Margaret (Canada) and Catalan Institute of Oncology (Spain) treated with definitive surgery ± postop radiotherapy (RT) or RT ± chemo according to institutional protocols between 2010-2019. In squamous cell carcinoma (SCC), HPV status was tested by p16 staining, and HPV DNA (ISH or PCR) if equivocal. The primary goal was to assess the association of tumor histology, stage (by 7th edition TNM), and other clinicopathological variables on locoregional control (LRC), distant control (DC) and OS. Actuarial rates were calculated with Kaplan–Meier (KM) method. Multivariable analysis (MVA) calculated hazard ratios (aHR) adjusted for histology type, T-/N-categories, and primary treatment. Results: Out of 342 pts, median age was 62 years (y) (range 21-96), Male:Female = 212:130, 95% had ECOG 0-1. Tumor histology types were: 192 (56%) SCC (p16+: 35; p16-/untested: 157), 40 (12%) adenocarcinoma (AD), 33 (10%) sinonasal undifferentiated carcinoma or sinonasal neuroendocrine tumors (SNUC/SNEC), 28 (8%) malignant melanoma (MM), 27 (8%) esthesioneuroblastoma (ES) and 22 (6%) adenoid cystic carcinoma (ACC). Median follow up was 3.6 y (range 0.1-11.3). Three-year actuarial rates for each endpoint are included in table. The PFs for LRC by MVA were: SNUC/SNEC (vs SCC) histology, T3-4 (vs T1-2: aHR 2.4, p = < 0.01) and N+ (vs N-: aHR 1.7, p = 0.02) diseases. The PFs for DC were: MM (vs SCC) and SNUC/SNEC (vs SCC) histology, and T3-4 (vs T1-2: aHR 6.0, p = 0.01) disease. The PFs for OS were: MM (vs SCC) histology, older age (aHR 1.0, p < 0.01), T3-4 (vs T1-2: aHR 5.6, p < 0.01), and N+ (vs N-: aHR 2.5, p < 0.01) disease. There was no difference in primary surgery vs RT in any outcome endpoint (all p > 0.05). p16+ SCC had a marginally higher LRC but similar DC and OS vs p16-/untested SCC (table). Conclusions: This large multicentre cohort of nmSC shows different patterns of relapse and survival with different tumor histologies. Our results suggest that individualization of treatment and follow-up strategies by histologic type is recommended to optimize outcomes in these orphan diseases. [Table: see text]

We compare clinical behaviour of East-Indians and White-Canadians with oral cavity squamous cell carcinoma (OSCC) treated at a Western institution within a uniform health care system.Newly diagnosed OSCC patients who underwent postoperative (chemo-)radiotherapy (PORT/POCRT) between 2005 and 2017 were included. Data on ethnicity and other variables were extracted from patient-questionnaires, a prospective database and supplemented by chart review. Baseline characteristics were compared between East-Indian versus White-Canadian groups. A propensity-matched (1:1 ratio) of East-Indian versus White-Canadian cohorts was generated to compare locoregional control (LRC), distant control (DC), overall survival (OS), and acute and late toxicities.A total of 53 East-Indian and 467 White-Canadian OSCC patients were identified. Compared to White-Canadians, East-Indian patients were younger, had less exposure to smoking and alcohol (p 0.001), but more chewed betel (areca) nut /tobacco (43% vs 0.2%, p 0.001). Buccal/retromolar-trigone/lower gingiva primaries were more common in East-Indians (49% vs 25%, p 0.001). Median follow-up was 5.0 years. Propensity-score paired analysis revealed inferior 3-year LRC (68% vs 81%, p = 0.030), non-significantly lower OS (61% vs 75%, p = 0.257), but similar DC (81% vs 87%, p = 0.428) in East-Indian versus White-Canadian patients. Actuarial rate of toxicities was higher in East-Indians vs White-Canadians: acute toxicity at 6 weeks: 47% vs 30%, p = 0.012; chronic trismus at 5-years: 16% vs 2%, p = 0.013.East-Indian OSCC patients have a greater betel nut/ chewable tobacco exposure compared to White-Canadians and a different distribution of OSCC sites. Propensity-matched cohort analysis showed lower LRC and higher toxicities in East-Indian OSCC patients, suggesting a complicated interaction between genetic/biological and life-style factors.

Purpose/objective(s) Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/methods A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for Conclusion HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Purpose/Objective(s) Only 9% of adult Rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS), often as a paranasal mass with proptosis, orbital and skull base invasion, and a prodigious risk of regional node involvement and distant metastatic dissemination to unusual locations in the young adult with the embryonal/alveolar (E/A) subtype. E/A-RMS respond rapidly to chemotherapy and radiotherapy (RT) and management is extrapolated from the pediatric experience where prognosis is better but treatment imperatives differ. We report on adults with HNRMS treated over 3 decades. Materials/Methods We reviewed adult patients treated from 1984 – 2017 via chart review and a prospectively maintained database from 1989 onward. RMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-RMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. Chemotherapy regimens included VAC and VAC/IE, with VC given concurrently with RT. P-RMS were treated with surgery +/- RT. IMRT was adopted from 2005 onward. Results Fifty-eight patients met inclusion criteria; median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were > 5cm. Of 45 patients with M0 disease treated with curative intent, 33 (73%) had E/A-RMS and 12 (27%) had P-RMS. All E/A-RMS patients received definitive RT with either 66 Gy or 70 Gy in 2 Gy per fraction, except 2 who had surgery for diagnostic purposes. Involved nodal regions were treated with radical dose RT and elective nodal RT was routinely delivered. In the IMRT-era, patients with primary disease in the nasopharynx or paranasal sinuses were treated with bilateral neck RT, while patients with well lateralized primary disease were generally treated with ipsilateral neck RT. Pre-IMRT, out of 23 patients with initial M0 E/A-RMS, 12 (52%) had a loco-regional recurrence. Post-IMRT, out of 10 patients with initial MO disease, only 1 (10%) had a local recurrence; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy due to local toxicity, but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was statistically superior in the IMRT era as compared to pre-IMRT (Fisher's exact test, P = 0.049). Overall, distant metastasis was the predominant mode of treatment failure (n = 17/33, 52%). Conclusion In our experience, the rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT is excellent. As such CRT should be considered the treatment of choice in this population to avoid extensive surgery including craniofacial resection and orbital exenteration, which would be needed for many of these patients but has functional and cosmetic consequence; it would also interrupt ongoing maintenance chemotherapy which has proven survival benefit. In contrast P-RMS is distinct and requires surgery +/- RT.

PURPOSE/OBJECTIVE(S) Patient-derived xenografts (PDX) can help identify oral cavity squamous cell carcinoma (OSCC) patients at risk for disease recurrence and optimize clinical decision-making. In this study, we develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. MATERIALS/METHODS PDX models were generated from OSCC patients. Patients were scored as a ''non-engrafter" if PDX formation did not occur within 6 months. Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups using a 10-fold cross-validation approach. RESULTS Overall 288 OSCC patients were analyzed. MVA identified pT3-4, pENE, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (HR 1.98, 95% CI: 1.24-3.18, P < 0.01), and DM (HR 2.64, 95% CI 1.21-5.75, P < 0.01) compared to non-engrafters. A prediction score based on the aforementioned variables identified patients at high-risk (defined as having at least two of the three high risk features i.e., engraftment, pT3-4, pENE) and low-risk for LRF (43.5% vs 26.5% at 5-years, P < 0.001), DM (38.2% vs 8.4% at 5-years, P < 0.001), and poorer 5-year OS (34% vs 66%, P < 0.001). The prediction model that included engraftment had the highest discriminatory capacity in the cross-validation analysis (AUC: 67.8 [63.5-72.9]), while removal of engraftment as a predictor resulted in a lower c-index (AUC: 62.7 [57.0-68.4]). In patients classified based on a clinical score only (i.e., presence or absence of pT3-4 and pENE), engraftment remained useful in identifying those with worse outcomes. Compared to non-engrafters, engraftment was associated with higher rates of DM (15.8% vs. 5.4%, P < 0.05) in clinically "high risk" patients as well as higher rates of LRF (31.9% vs. 13.8%, P < 0.05) in clinically "low risk" patients at 5-years. Finally, engraftment was associated with poorer 5-year OS in both clinically "high risk" (36% vs. 65%, P < 0.05), and "low risk" patients (57% vs. 78%, P < 0.01). CONCLUSION A prediction score utilizing OSCC PDX engraftment, in conjunction with pT3-4 and pENE, improves the prognostic utility of existing clinical models and predicts patients at risk for LRF, DM and poor survival.

Purpose/Objective(s) Nasopharyngeal cancer (NPC) is traditionally EBV related. However, HPV-positive (HPV+) NPC seems to be increasing in the Western world recently. We describe the clinical behavior and outcomes of HPV+ NPC compared to EBV-positive (EBV+) NPC and HPV+ oropharyngeal cancer (OPC). Materials/Methods All newly diagnosed non-metastatic viral-related NPC and OPC treated with IMRT from 2005-2020 were reviewed. Viral etiology was confirmed by p16 staining, supplemented by real-time polymerase chain reaction of DNA for high-risk HPV, and EBER in-situ hybridization for EBV. Clinical characteristics of HPV+ and EBV+ NPC were compared using the 2005-2020 NPC cohort, while locoregional control (LRC), distant control (DC) and overall survival (OS) were compared using the 2005-2018 cohort to allow sufficient follow-up among HPV+ NPC, EBV+ NPC and HPV+ OPC patients. Presenting signs/symptoms of HPV+ NPC and EBV+ NPC were compared by 1:1 matched pair analysis (matched to T category, N category, smoking, age, gender, WHO type IIA vs IIB, and diagnosed year). Multivariable analysis (MVA) evaluated the cohort effect adjusting for confounders. Results A total of 29 HPV+ NPC (25 Caucasians and 4 Asians), 422 EBV+ NPC, and 1310 HPV+ OPC were eligible. HPV genotype was available in 20/29 HPV+ NPC patients: 14 (70%) HPV-16; 6 (30%) non-HPV-16. Compared to EBV+ NPC overall, HPV+ NPC patients were older (median age: 58 vs 52 years, P = 0.006), were predominantly Caucasian (86% vs 15%, P 0.05). Median follow-up for HPV+ NPC, EBV+ NPC and HPV+ OPC was 3.1, 6.0, and 5.2 years respectively. Compared to EBV+ NPC (n = 374), HPV+ NPC (n = 20) had similar 3-year LRC (95% vs 90%, P = 0.416) and OS (84% vs 89%, P = 0.137), but non-significantly lower DC (75% vs 88%, P = 0.13). Compared to HPV+ OPC (n = 1310), HPV+ NPC also had similar 3-year LRC (95% vs 94%, P = 0.74) and OS (84% vs 87%, P = 0.307), but lower DC (75% vs 90%, P = 0.036). The difference in DC became non-significant in MVA [HR 1.83 (0.73-4.58), P = 0.19] after adjusting for T category, N category, smoking pack-years, and chemotherapy. Conclusion HPV+ NPC is an emerging entity, of which about one-third are caused by non-HPV-16 genotype. Compared with the more common EBV+ NPC cases, HPV+ NPC presents with more local pain and advanced T categories but has similar outcomes. HPV+ NPC also has similar outcomes to HPV+ OPC except that DC is lower in univariable analysis, possibly attributable to higher T category and non-HPV-16 genotypes. There may be a role for modification of systemic therapy in HPV+ NPC to address distant failure risk.

Transoral surgery (TOS) and IMRT represent two primary local ablative treatment modalities for oropharyngeal cancer (OPC). The choice of one over the other represents an interplay between the chance of cure vs risk of late sequelae. HPV-mediated (HPV+) OPC patients generally have excellent outcomes, especially in TNM-8 stage I disease. Controversies exist over which treatment has a more favorable toxicity profile and equal efficacy in the management of this population. Non-randomized retrospective data show comparable oncological and functional outcomes between TOS-based vs IMRT-based treatment for this disease. Several de-intensification concepts have been explored in this subset in both primary surgery-based vs primary radiotherapy-based trials. However, no robust mature trial data are available to convincingly guide treatment selection. TOS is often presented as one of the de-intensification options although the majority of series also describe the use of adjuvant treatments which inevitably result in non-negligible toxicities. Patient selection and surgeons' training are paramount. Understanding tumor biology and the prognostic value of traditional 'adverse' features will further guide trial design for refinement of risk tailored approach. In conclusion, comparative data suggests TOS and IMRT are both effective treatment for TNM-8 stage I HPV+ OPC with similar oncological and functional outcomes. TOS as a single modality has potential advantages in mitigating radiation included toxicities. TOS should be avoided in the presence of clinically overt extranodal extension or when negative margins are unlikely to be achieved. TOS is also less ideal for cases with radiological features predicting a high risk of distant metastasis.

Purpose/Objective(s) To evaluate the association of contralateral nodal involvement (CNI) with automatically defined midline proximity in patients (pts) with head and neck cancer based on treatment planning (TP) real world data (RWD). Materials/Methods All available TPs for head and neck cancer pts between 2010 and 2017 were analyzed in an automated data analysis pipeline where the pt's midline was determined objectively using their external contour and discounting distortion due to neck lymphadenopathy via linear modeling. Primary gross tumor volumes (GTVp) and nodal volumes (GTVn) were contoured by treating radiation oncologists. Objective tumor laterality (OTL) was calculated as the difference between the GTVp center of mass and the midline in the R/L direction. OTL accuracy compared to the clinically assigned laterality (when available) was assessed. Midline proximity (MP) was the difference between the medial edge of the GTVp bounding box to the patient midline with positive values representing progressively lateralized tumors and negative values representing tumors crossing midline. Nodal involvement (ipsilateral and contralateral levels 1-5 and retropharyngeal) was determined using the TP nodal target contours labeled by neck level as is standard practice at our institution during treatment planning. The primary endpoint, CNI, was defined based on these TP contours. Volumes of GTVp were calculated from the TP. Clinical variables including HPV status, age, smoking, disease site and subsite were used for model development. The factors predictive of CNI were assessed using logistic regression (LR). Results Of 2458 pts available for analysis, 2031 had a clinically assigned laterality. The accuracy of automatically assigned laterality was 0.91 when compared with the clinically assigned laterality. Using the automatically assigned laterality (n = 2458), the overall rate of CNI was 45% and varied by disease site and nodal level involved: oropharynx (55.1%, n = 629/1142), larynx (17.6%, n = 124/703), nasopharynx (79.7%, n = 231/290). Multivariable logistic regression (LR) including subsite, HPV status, GTVp, GTVp center of mass relative to midline, GTVp midline proximity, and ipsilateral nodal involvement was performed. In the oropharynx, multivariable LR demonstrated GTVp volume (P Conclusion Automated TP analysis can be used to generate RWD-based predictions of CNI. CNI risk remains a critical radiotherapy endpoint and RWD may help determine CLI risk using combinations of anatomic and clinical features.

PURPOSE/OBJECTIVE(S) In response to the COVID-19 pandemic, radiotherapy (RT) departments around the world created new policies as a means of reducing risk of exposure for patients and staff, while attempting to maintain high-quality RT. We aim to describe the impact of the pandemic on changes in breast cancer RT patterns of practice for new patient referrals at a tertiary cancer center. MATERIALS/METHODS Newly diagnosed breast cancer patients referred to our department from March 17-June 30, 2020 were included. Referrals for palliative RT were excluded. Demographic characteristics, COVID-19 status (if available) and RT treatment information, including deviations from usual practice because of the pandemic, were extracted from medical records by independent reviewers, and validated by the treating radiation oncologist. Descriptive statistics were used to summarize the data. The results were compared to breast cancer patients treated from March 17-June 30, 2019. RESULTS A total of 271 and 306 patients met selection criteria for the 2020 and 2019 cohorts, respectively. The majority of consultations in 2020 were virtual (96%), conducted via telephone or videoconference, whereas in 2019 all were conducted in-person. Median age of the cohorts was similar: 58 years (range: 24-86) in 2020 and 59 years (range: 26-88) in 2019. Of those treated with adjuvant RT (n = 209), 56% of patients received whole breast (WB), 36% regional nodal irradiation (RNI) and 8% partial breast (PB) RT in 2020, whereas in 2019 (n = 284), 60% received WB, 31% RNI and 9% PB (Chi-squared test P = 0.43). As a result of the pandemic, 78% of cases (n = 211) received one or more deviations in RT practice compared to pre-pandemic institutional policies. The most common was an "altered dose/fractionation protocol" (n = 197; 93%), such as use of hypofractionated RNI (2020: 97%, 74/76 cases vs. 2019: 3%, 3/87 cases) or the FAST Forward regimen (2020: 43%, 57/134 WB/PB cases vs. 2019: 0/197 cases). Other deviations included a delay in RT start (defined as > 12 weeks post-op) noted in 11% (n = 29) and omission of RT in only 8% (n = 17), both were recommended when the risks associated with COVID-19 were felt to outweigh the benefit of RT. One patient had a deviation in RT as a result of testing positive for COVID-19. CONCLUSION In order to minimize hospital visits in response to the COVID-19 pandemic, a substantial proportion of breast cancer patients were seen virtually and treated with newer hypofractionated dose schedules, while total omission of adjuvant RT was infrequently observed. Continuously tracking patterns of practice provides an opportunity to evaluate the impact of the pandemic on clinical outcomes and help inform post-pandemic value-enhancing practices.

Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry.A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries.There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, P.001), volume of left anterior descending artery receiving 5 Gy (HR 0.98, P=.003), and volume of left circumflex artery receiving 20 Gy (HR 1.03, P.001).In addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior.

Squamous cell carcinoma of oral cavity (OSCC) is predominantly managed with surgery. Post-operative radiotherapy (PORT) and chemoradiotherapy (POCRT) enhance disease control in OSCC patients with adverse anatomic and pathologic primary and nodal features. Knowledge about disease behavior, surgery and radiotherapy advances, and the emergence of new systemic agents prompt refinement of PORT volumes and POCRT regimens. Traditional and emerging prognostic models that include adverse histopathological features underpin such approaches. This review summarizes research over recent decades with emphasis on the 2015 to Feb 2019 period describing: (1) Indications for PORT and/or POCRT, addressing surgical "margin status" including the definition of a "clear" margin to permit withholding PORT/POCRT; these concepts include characterizing the specimen yielding these measurements, the optimal time point to assess these findings, and the putative value of a "revised margin" performed during the same operative procedure, (2) Emerging prognostic factors including nodal burden (total number of involved lymph nodes) and perineural invasion, (3) PORT volume design, dose/fractionation and optimal surgery-to-PORT interval, (4) Chemotherapy dose, schedule, and agents, and (5) On-going clinical trials involving systemic agents and combinations of chemotherapy with immunotherapy.

Introduction Accurate prediction of local recurrence (LR) after breast conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS) is crucial to personalize recommendations for adjuvant radiotherapy (RT). The 21-gene recurrence score (RS) predicts for distant metastases for woman with invasive breast cancer. We hypothesised that the RS could improve prediction of LR after BCS for DCIS. Methods We performed a population-based analysis of 1226 woman aged ≤74 treated with BCS ± RT for pure DCIS. Expert pathology review was obtained for all cases, as was the RS. Treatment and outcomes were obtained by deterministic linkage to administrative databases and chart review. Clinico-pathologic features obtained included: age, tumor size, nuclear grade, presence of comedonecrosis, multifocality, margins, and adjuvant radiation. The outcome assessed was local recurrence by 10 years from diagnosis of DCIS. The LR prediction model was developed using multivariable Cox regression, where a non-parametric approach was implemented to estimate the baseline hazard function. The proportional hazards assumption was assessed and time-interaction terms were included with each covariate in the model. Models were ranked based on c-statistic, log-likelihood estimate, and Akaike information criterion (AIC). Backward selection was used to obtain the final reduced model with time-interaction terms. Calibration for the best model was examined by grouping predicted 10-year risk of LR into deciles and plotting against observed 10-year risk of LR based on mean Kaplan-Meier estimates. Internal validation was performed by bootstrapping. Results Of the 1226 woman included, 514 were treated with BCS alone and 712 received adjuvant RT. Median follow up from time of treatment was 16 years (interquartile range (IQR): 14-18). The median age was 56 years (IQR: 49-64). Margins were negative in 90.5% of cases. Tumor size was ≤1cm in 430 (35.1%), 1-2.5cm in 633 (51.6%), and >2.5cm in 163 (13.3%). The median RS was 15 (IQR: 8-30) and the mean RS was 21.37 (SD 18.93). The best predictive model included the RS and had a c-statistic of 0.68 as well as the lowest AIC. This model included the following variables: RS, age, tumor size, nuclear grade, margin status, comedonecrosis (≤30% vs higher), multifocality, and treatment (BCS vs BCS+RT); it also included the following interaction terms: treatment and time, RS and time, comedonecrosis and time, and treatment and tumor size. Due to the non-linear relationship between certain characteristics and the risk of LR, quadratic terms for RS and age were also included. This model was well calibrated overall, especially in the lower risk range around the 10% risk threshold. It was also well calibrated in this risk range in the subset of woman who were treated with BCS alone. Conclusion The best performing model generated to predict LR after BCS for DCIS includes the RS. Work is ongoing to compare RS and the 12-gene DCIS score in terms of prediction of LR, as well as prediction of invasive LR specifically. This work can help guide future clinical de-escalation trials by better identifying woman with truly low risk of LR after BCS for DCIS. Citation Format: Ezra Hahn, Rinku Sutradhar, Sumei Gu, Lawrence Paszat, Danielle Rodin, Sharon Nofech-Mozes, Cindy Fong, Eileen Rakovitch. Including a 21-gene assay recurrence score in multivariable predictive model generation improves prediction of local recurrence after breast conserving surgery for ductal carcinoma-in-situ [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-05.

396 Background: Most guidelines recommend active surveillance (AS) as initial management for stage I testis cancer (TC). AS entails blood work and imaging at regular intervals requiring multiple clinic visits spanning 5 years. This can be time-consuming, difficult to adhere to, dissatisfying and costly for patients and health care systems. We innovated a secure online platform, WATChmAN (Web-based virtuAl Testicular CANcer clinic) allowing asynchronous communication between patients, results, and physician team. Methods: We are conducting an RCT (NCT03360994) where patients with stage I TC on AS are randomized to virtual care (WATChmAN), or standard in-person care. Primary endpoint is safety: examining loss-to-follow-up and compliance with AS schedules, incidence of relapse, delays in detection of relapse, and burden of relapse. Non-compliance represents a) patient-derived delay in visit; or b) follow-up visit with incomplete testing. Secondary endpoints include: patient/physician satisfaction and cost savings. Results: At present, 102 of a planned 144 patients are enrolled: 51 to virtual care, and 51 to standard in-person care. More patients in the virtual arm have been compliant with AS schedules (89% vs 73%) with shorter median compliance delays (12 vs. 14 days). To date, 10 patients have relapsed: 6 virtual (11.8%) and 4 standard (7.8%). Median time to relapse was shorter for the virtual arm (8 vs. 9.5 months), with no difference in burden of disease at relapse. Response rates to 6-month surveys were 90% and 59% for virtual and standard arms respectively. When asked if satisfied with their care, on the virtual arm 67% reported “extremely satisfied”, and 33% “satisfied” compared to 50% and 45% for the standard arm. When WATChmAN patients were asked if the application is able to provide the same excellence of care as in-person appointments, 82% reported “strongly agree” or “agree”. Conclusions: Interim results suggest virtual care in stage I TC is feasible and safe with improvements in patient satisfaction. Through semi-structured interviews and cost-effectiveness analyses, we anticipate more insight into virtual care. This may serve as a potential model for virtual care for other cancers. Clinical trial information: NCT03360994.

Purpose External beam radiation therapy (RT) is an effective palliative treatment for patients with choroidal metastases and is aimed at preserving vision and obtaining local tumor control. Delivery of 30 to 40 Gy in 2-Gy daily fractions is a standard approach at many centers. This study reports the outcomes of a hypofractionated schedule of 20 Gy in 5 fractions in this palliative setting. Methods and materials We conducted a retrospective review of patients who were treated with RT (20 Gy in 5 fractions) for choroidal metastases between January 1999 and November 2012. The primary outcome measures were change in visual acuity and tumor response. Secondary outcomes included toxicities of RT, tumor control, and overall survival (OS) from diagnosis of choroidal metastases. Univariate and multivariable Cox regression modeling was used to investigate the predictors for OS. Results Fifty-five patients with 71 affected eyes were included. Decreased vision was the presenting symptom in 43 eyes (61%). Visual acuity improved from a median of 20/70 at baseline to 20/40 at last follow-up and remained stable or improved in 56 eyes (80%). Tumor regression was observed in 64 eyes (91%) with complete response in 47 eyes (67%). Local progression occurred in 4 eyes (6%). The median survival after diagnosis of choroidal metastases was 13 months. No acute complications were observed in 49 patients (89%). Mild acute toxicities included transitory dryness in 5 patients and episcleritis in 1 patient. Cataracts, retinopathy, optic neuropathy, pigmentary maculopathy, and neovascular glaucoma developed in 4 eyes (6%), 1 eye, 7 eyes (10%), 5 eyes (7%), and 1 eye, respectively. No variables were statistically significantly associated with OS. Conclusions A short fractionation schedule of 20 Gy in 5 fractions is a well-tolerated treatment that effectively preserves vision and gains local tumor control for many patients with choroidal metastases. This hypofractionated approach would help reduce the burden of a longer treatment course in this palliative patient population.

Purpose Graves' ophthalmopathy (GO) is an autoimmune condition primarily managed with prolonged courses of glucocorticoids, which can be associated with significant side effects. Orbital radiation therapy (RT) is an alternative treatment that has shown variable efficacy in improving orbital and visual symptoms. In this study, the therapeutic benefit of RT was evaluated in terms of patient's ability to taper their corticosteroid requirements, which may better reflect the proposed mechanism of RT and provide a clinically relevant response endpoint. Methods and materials This is a retrospective review of consecutive patients treated with orbital RT for GO between 2000 and 2010 at a single tertiary hospital with a dedicated ocular radiation therapy clinic. The primary measure of treatment response was defined as the ability to taper glucocorticoids following RT without any further exacerbation of orbitopathy symptoms. Additional endpoints including ocular symptoms (diplopia, proptosis, visual acuity, extraocular movement) and need for surgical intervention were reported. Results Of 86 eligible patients, with a mean follow-up of 9.3 months, 81 (94%) patients responded to RT. Of patients taking corticosteroids at baseline, 91% were able to taper off corticosteroids completely and the remaining patients had decreased their doses by 83%. Diplopia, visual acuity, and extraocular movements improved in 29%, 81%, and 58% of patients, respectively. The median reduction in proptosis was 2.5 mm and 2 mm in the left and right eyes, respectively (range, −18 mm to 23 mm). Conclusions Orbital RT is a generally well-tolerated treatment that helps minimize the dose and duration of corticosteroid therapy for patients with GO while improving ocular symptoms, including proptosis and diplopia. Prospective research should consider using corticosteroid requirement as a measure of response to orbital RT for GO.

Chemoprevention of colorectal cancer is a promising science that has particular importance due to the limited success of current treatments for most advanced common malignancies. Many chemopreventive agents have been studied including cyclooxygenase (COX) inhibitors. Two isoforms of the COX enzymes are COX-1 and COX-2. COX-1 is constitutively expressed in normal tissue, serving an important role in tissue homeostasis, whereas COX-2 is an inducible enzyme, which is markedly overexpressed at sites of inflammation and colorectal neoplasms. The preventive efficacy of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit COX-1 and/or COX-2, has considerable support from animal and epidemiological studies; however, there are well-documented toxicities associated with NSAID use. These adverse effects are attributed to NSAIDs’ inhibition of COX-1. The development of COX-2 specific inhibitors gave hopes of bypassing the associated traditional NSAID toxicities while better targeting tissues sustaining inflammation and neoplasia. The PrsSAP, APC and APPROVe trials demonstrated the efficacy of COX-2 specific inhibitors in preventing the recurrence of sporadic colorectal polyps. However, the trials were terminated early due to discovery of significant cardiovascular toxicity, although the exact extent of this toxicity remains unclear. The exact mechanisms through which NSAIDs exert their cancer preventing effects are currently unknown; inhibition of COX-2 is of great importance, but COX-2 independent pathways exist as well. In addition, the efficacy of NSAID use for cancer prevention can differ significantly between individuals. Personalized medicine in this field is also greatly anticipated. Combination therapy is under extensive research in order to improve efficacy while reducing toxicity profiles. Chemoprevention of colorectal cancer is largely possible, but the ultimate drug and proper patient selection, among other elements of the cancer prevention equation, are still needed.