De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: Who, why, what, where, when, how, how much and what next?

The emergence of treatment de-escalation as a feasible option for patients with newly diagnosed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has generated considerable excitement among both providers and patients alike. Since HPV-positive oropharyngeal carcinoma has been shown to be a unique entity with distinct clinical and molecular characteristics, the rationale for customizing treatment for patients with this disease is compelling. Indeed, evidence has accumulated demonstrating that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus might possibly be targeted with de-escalated approaches. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the intensity of treatment and thus the incidence of both short- and long-term toxicity. Given the rapidly increasing incidence of this disease, particularly among younger patients who are generally healthy, the focus on quality of life seems germane. Although the exact reason for the improved sensitivity of HPV-positive oropharyngeal carcinoma to treatment is uncertain, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been fairly heterogeneous in design, and it remains questionable how to apply their findings to real-world practice. The potential of integrating translational approaches into clinical paradigms is also just starting to become recognized. Consequently, multiple uncertainties continue to exist with respect to de-escalation for HPV-positive oropharyngeal cancer, and these questions comprise the crux of this review.

Translational risk-adapted approaches to de-escalated radiation for human papillomavirus-positive oropharyngeal cancer: Past, present, and future.

Interest in the use of de-escalated radiation to treat patients with newly diagnosed human papillomavirus (HPV)-positive oropharyngeal cancer has grown dramatically with the publication of prospective trials demonstrating the efficacy of such an approach. While the rationale for de-escalation--- namely to decrease treatment-related toxicity while maintaining the excellent rates of disease control historically observed in patients with this disease-is inherently obvious, uncertainty exists regarding how to best select patients for de-escalation. Consequently, risk-adapted strategies using a variety of translational and clinical platforms have been increasingly popularized to better refine treatment. These have integrated contemporary methods of mid-treatment response assessment using advanced technologies and molecular assays to customize the radiation dose. By monitoring the response as patients actively proceed through treatment, risk-adapted protocols have the potential to provide insight into the biological behavior of tumors and make individualized therapy possible. The purpose of this review is to summarize the evidence to date on risk-adapted approaches to de-escalated radiation-- highlighting the clinical, radiological, and biological data which may ultimately help usher the principles of precision medicine into practice for patients with HPV-positive oropharyngeal cancer.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer.

PURPOSE: The optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. METHODS AND MATERIALS: A review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39-84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2-102 months). RESULTS: Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local-regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). CONCLUSION: Although re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Integrating Overall Survival and Tumor Control Probability Models to Predict Local Progression After Brain Metastasis Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma.

OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

Refining Target Volume Coverage After Parotidectomy for Cutaneous Squamous Cell Carcinoma: Omission of the Cervical Neck From the Radiation Field.

Purpose: For patients without pathologic evidence of cervical disease after neck dissection for cutaneous squamous cell carcinoma involving the parotid region, inclusion of the ipsilateral cervical neck in the postparotidectomy radiation volume is routinely performed. We report our experience with selective avoidance of the ipsilateral neck for patients undergoing postoperative radiation to the parotid bed. Methods and Materials: From January 2014 to December 2023, a total of 30 consecutive patients underwent postoperative radiation after parotidectomy for cutaneous squamous cell carcinoma involving the parotid area. All patients had previously had a neck dissection confirming pathologic N0 disease. Treatment was delivered using intensity modulated radiation therapy to a median dose of 60 Gy (range, 56-66 Gy). The radiation target volumes included the parotid bed only, with deliberate avoidance of the ipsilateral cervical neck. The median pathologic tumor size of the parotid tumor was 3.3 cm (range, 0.2-9.4 cm). Final pathologic evaluation showed positive microscopic margins in 8 patients (27%), perineural invasion in 17 patients (57%), and facial nerve involvement in 6 patients (20%). Results: There were no isolated nodal failures. One patient developed an ipsilateral neck recurrence approximately 8 months after completion of radiation therapy. This occurred 2 months subsequent to the development of local recurrence. The 5-year actuarial rates of local (parotid) control, neck control, and overall survival were 87%, 97%, and 76%, respectively. Conclusions: Omission of the ipsilateral neck from the parotid volume does not compromise disease control for pathologically N0 patients undergoing postoperative radiation for cutaneous squamous cell carcinoma involving the parotid region. Practical implications are discussed.

Effect of a Same-Day-Appointment Initiative on Access-Related Benchmarks in Radiation Oncology.

PURPOSE: The timely delivery of health care is an important quality indicator that has been shown to correlate with outcomes for cancer patients. We present our single-institution experience with the implementation of a same-day-access scheduling initiative in outpatient radiation oncology. METHODS AND MATERIALS: From March 2021 to March 2023, a total of 4301 consecutive new patients referred for radiation oncology consultation were offered same-day appointments as part of a prospective pilot initiative conducted at a tertiary-based academic medical center. Descriptive statistics were used to study the effect of this initiative on access-related benchmarks compared with historical control patients referred during a preceding 24-month period. RESULTS: Among the 3414 patients scheduled, 477 (14%) opted for same-day appointments. Black, Latino, and Asian patients were significantly more likely to use same-day access versus Caucasian patients (P < .001). The same-day-access initiative increased the proportion of patients seen within 5 days from referral from 22% to 61% (P < .001). The median time from referral to consult was 12 days (range, 0-149 days) before the implementation of the same-day-access initiative compared with 3 days (range, 0-101 days) after (P < .001). The no-show rate was reduced from 15% to 7% with the initiative (P < .001). All patients who requested a same-day appointment were successfully accommodated. CONCLUSIONS: The implementation of this same-day-access initiative enhanced operational efficiency and reduced barriers to care in the outpatient setting.

Socioeconomic and demographic factors predictive of missed appointments in outpatient radiation oncology: an evaluation of access.

Purpose: While missed patient appointments reduce clinic efficiency and limit effective resource allocation, factors predictive of "no shows" are poorly understood in radiation oncology. Methods and materials: A prospective data registry of consecutive patients referred for initial consultation from October 2,018 to April 2022 was reviewed. Demographic characteristics recorded included age, gender, race, language preference, living situation, and insurance status. Zip code data linked to a patient's residential address was used to determine socioeconomic status (SES) based on publicly available data on median household income. No show encounters were defined as all encounters where the patient failed to cancel their visit and did not sign-in to their scheduled appointment. Descriptive statistics were presented to identify factors predictive of missed appointments. Results: A total of 9,241 consecutive patients were referred and logged into the database during the 4-year period, of which 5,755 were successfully scheduled and registered. A total of 523 patients (9%) failed to show for their appointments. Missed appointments were associated with low-income status, homeless living situation, and Black or Latino race (p < 0.05, for all). The proportion of White, Latino, Asian, and Black patients who missed appointments was 6%, 14%, 9%, and 12%, respectively (p < 0.001). Patient characteristics independently associated with higher odds of appointment non-adherence included low-income status ((OR) = 2.90, 95% CI (1.44-5.89) and Black or Latino race [(OR) = 3.31, 95% CI: 1.22-7.65]. Conclusions: Our results highlight the influence of demographic, financial, and racial disparities on proper health care utilization among patients with cancer. Future interventions aimed at reducing appointment no shows could channel resources to the at risk-populations identified in this analysis, improving access to care, and optimize clinic efficiency.

Racial disparities in the timely receipt of adjuvant radiotherapy for head and neck cancer.

PURPOSE: To evaluate the influence of socioeconomic and demographic factors which might predict for excessive delays in the receipt of adjuvant radiotherapy for head and neck cancer. METHODS AND MATERIALS: The medical records of 430 consecutive patients referred for adjuvant radiation after surgical resection for squamous cell carcinoma of the head and neck were reviewed. The number of days from surgery to initiation of radiation was recorded. To study the variability in which adjuvant radiation was delivered, descriptive statistics were used to determine the percentage of patients who deviated from starting treatment beyond the recommended benchmark of 42 days. The chi-square statistic was used to compare differences in proportion among subsets. A Cox proportional hazards model was constructed to perform a multi-variate analysis to identify factors which independently influenced the likelihood for non-adherence. RESULTS: The interval between surgery and the start of radiation therapy ranged from 5 to 128 days (mean, 36 days). The mean number of days from surgery to radiation therapy was 31 days, 35 days, 40 days, and 42 days for Caucasians, Asians, Latino, and Black patients (p = 0.01). In all, 359 of 430 patients (83 %) started adjuvant radiation within 42 days. The proportion of patients who initiated radiation therapy within 42 days of surgery was 91 %, 86 %, 71 %, 65 %, and 80 % for Caucasians, Asians, Latinos, Blacks, and Native Hawaiian/Pacific Islanders, respectively (p < 0.001). Patient characteristics associated with higher odds of non-adherence to the timely receipt of adjuvant radiation therapy within then 42-day benchmark from surgery to radiation included race ([OR] = 4.23 95 % CI (1.30-7.97), non-English speaking status ([OR] = 2.38, 95 % CI: 0.61-4.50), and low socioeconomic status ([OR] = 1.21, 95 % CI: 1.01-1.86). CONCLUSION: Underrepresented minorities are more likely to experience delays in the receipt of adjuvant radiation for head and neck cancer. The potential underlying reasons are discussed.

Posttreatment Surveillance Imaging After Radiation for Head and Neck Cancer.

Importance: The role of surveillance imaging after treatment for head and neck cancer is controversial and evidence to support decision-making is limited. Objective: To determine the use of surveillance imaging in asymptomatic patients with head and neck cancer in remission after completion of chemoradiation. Design, Setting, and Participants: This was a retrospective, comparative effectiveness research review of adult patients who had achieved a complete metabolic response to initial treatment for head and neck cancer as defined by having an unequivocally negative positron emission tomography (PET) scan using the PET response criteria in solid tumors (PERCIST) scale within the first 6 months of completing therapy. The medical records of 501 consecutive patients who completed definitive radiation therapy (with or without chemotherapy) for newly diagnosed squamous cell carcinoma of the head and neck between January 2014 and June 2022 were reviewed. Exposure: Surveillance imaging was defined as the acquisition of a PET with computed tomography (CT), magnetic resonance imaging (MRI), or CT of the head and neck region in the absence of any clinically suspicious symptoms and/or examination findings. For remaining patients, subsequent surveillance after the achievement of a complete metabolic response to initial therapy was performed on an observational basis in the setting of routine follow-up using history-taking and physical examination, including endoscopy. This expectant approach led to imaging only in the presence of clinically suspicious symptoms and/or physical examination findings. Main Outcome and Measures: Local-regional control, overall survival, and progression-free survival based on assignment to either the surveillance imaging or expectant management cohort. Results: This study included 340 patients (mean [SD] age, 59 [10] years; 201 males [59%]; 88 Latino patients [26%]; 145 White patients [43%]) who achieved a complete metabolic response during this period. There was no difference in 3-year local-regional control, overall survival, progression-free survival, or freedom from distant metastasis between patients treated with surveillance imaging vs those treated expectantly. Conclusions and Relevance: In this comparative effectiveness research, imaging-based surveillance failed to improve outcomes compared with expectant management for patients who were seemingly in remission after completion of primary radiation therapy for head and neck cancer.

Management of unknown primary head and neck cancer with radiation therapy in the era of human papillomavirus (HPV): No longer cutting down the tree to get an apple.

PURPOSE: Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era. METHODS AND MATERIALS: This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed. RESULTS: While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist. CONCLUSIONS: Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.

Effect of a same day appointment initiative on racial disparities in access for radiation oncology.

PURPOSE: We present our single-institution experience with the development of a same day access scheduling initiative for an outpatient radiation oncology unit, focusing on its potential influence on ameliorating racial disparities. METHODS AND MATERIALS: From March 2021 to August 2022, a pilot initiative was conducted such that all new patients referred to a tertiary care-based radiation oncology department were offered the ability to be seen as a same day consultation. The timespan of this analysis was categorized into 2 distinct successive periods over 36 months-a 18-month pre-initiative period (September 2019 to February 2021) and another subsequent one (March 2021 to August 2022). Descriptive statistics were used to study the impact of this initiative on access-related benchmarks. RESULTS: A total of 2897 patients were referred. Among the 2107 patients scheduled, three hundred and sixteen (15 %) opted for same day appointments. Black, Latino, and Asian patients were significantly more likely to use the same day access initiative versus Caucasian patients (p = 0.01). The same day access initiative increased the proportion of patients seen within 5 days from referral from 8 % to 34 % for Blacks, 12-57 % for Latinos, and 18-67 % for Asians, compared to 39-55 % for Caucasians (p < 0.001). The no-show rate was reduced from 20 % to 7 % and 14-5 %, for Black and Latino patients, respectively (p < 0.001). CONCLUSIONS: The implementation of a same day access initiative narrowed disparities with respect to access-related benchmarks.

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: evolving paradigms and future strategies.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has increased dramatically in recent years reaching epidemic-like proportions. Data has emerged not only showing that these cancers are a unique entity with distinct molecular characteristics but that they also have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts. This, it has been increasingly suggested that these tumors can be targeted with de-escalated approaches using reduced doses of radiation. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. As the data continues to mature on de-escalation, it is unquestionable that treatment paradigms for this disease will evolve. The ongoing quest to define a standard regimen comprises the subject of this review.

Timing of chemotherapy and radiation delivery for patients receiving chemoradiation for head and neck cancer: When does "concurrent" mean concurrent?

PURPOSE: To analyze practice patterns focusing on variations in the timing of chemotherapy relative to radiation in patients treated with concurrent chemoradiation for head and neck cancer. METHODS AND MATERIALS: The medical records of 302 consecutive adult patients treated with concurrent chemoradiation for head and neck cancer between April 2014 and February 2022 were reviewed. After excluding 38 patients who received non-platinum-based regimens, induction chemotherapy, and/or had non-squamous cell histology, a total of 264 patients formed the primary population. To study the variability in which concurrent chemoradiation was delivered, descriptive statistics were used to determine the percentage of patients who deviated from starting chemotherapy and radiation on the same day. The chi-square statistic was used to compare differences in proportion among various subsets. A Cox proportional hazards model was then used to perform a multi-variate analysis to identify factors which independently influenced the likelihood for non-adeherence. RESULTS: Among the 264 patients, a total of 187 patients (70.8%) had chemotherapy and radiation started on the same day with 171 of these (91.4%) receiving chemotherapy prior to radiation delivery. On multivariate analysis, both non-Caucasian ethnicity (OR: 1.13, 95% C.I. 1.01-1.20) and being non-English speaking (OR: 1.39; 95% C.I. 1.18--1.51) was significantly associated with greater likelihood of the receipt of radiation and chemotherapy on different days. CONCLUSION: Significant variation exists in the timing of chemotherapy relative to radiation for concurrent chemoradiation in the clinical setting. The potential repercussions on outcome warrante further invesigtation and are discussed.

De-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a specific entity with distinct clinical and molecular characteristics. It is now firmly established that patients with HPV-positive oropharyngeal SCC have a significantly improved prognosis because this variant has exquisite radiosensitivity compared with HPV-negative oropharyngeal SCC; thus, it can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain high rates of cure and preserve the quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. How treatment paradigms will evolve, particularly in the era of precision medicine, is a provocative question and is the subject of this review.

Incidence and Predictors of Persistent Opioid Use in Survivors of Head and Neck Cancer Treated With Curative Radiation.

PURPOSE: We sought to characterize the incidence of chronic opioid dependence among head and neck cancer survivors treated by radiation, as well as to identify patient and treatment factors associated with persistent use. MATERIALS AND METHODS: The medical records of patients with head and neck cancer who received radiation therapy from January 2012 to July 2016 were reviewed. All patients received 60 to 70 Gy with curative intent. Patients who progressed or died within 1 year were intentionally excluded. Opioid doses were calculated in morphine equivalent daily doses in milligrams (mg). Univariate and multivariate regression models were used to identify associations between demographic, medical, disease, and persistent opioid use. RESULTS: Two hundred and sixty-one patients were included. The median follow-up was 39 months (range: 12 to 83 mo). Two hundred and eleven patients (80%) received opioids for pain control during radiation. The median morphine equivalent daily dose during treatment was 73.8 mg (range: 5 to 561 mg). Rates of persistent opioid use at 6 months, 1 year, and 2 years from completion of radiation were 41.8%, 30.1%, and 26.0%, respectively. On multivariate analysis, only preradiation opioid use correlated with persistent opioid use at all 3 time points (P<0.05). Smoking history and a Charlson comorbidity index ≥2 predicted for persistent opioid use at some time points, but not all. CONCLUSIONS: High rates of persistent opioid use exist in patients with head and neck cancer after radiation therapy. Early interventions to appropriately wean patients should be further investigated.

Stereotactic Body Radiation Therapy for Apical Lung Tumors: Dosimetric Analysis of the Brachial Plexus and Preliminary Clinical Outcomes.

PURPOSE: Dosimetric constraints of the brachial plexus have not yet been well-established for patients undergoing stereotactic body radiation therapy (SBRT). This study evaluated long-term experience with the treatment of early-stage apical lung tumors with SBRT and reports on dosimetric correlates of outcome. METHODS AND MATERIALS: Between 2009 and 2018, a total of 78 consecutive patients with 81 apical lung tumors underwent SBRT for T1-3N0 non-small cell lung cancer. Apical tumors were those with tumor epicenter superior to the aortic arch. The brachial plexus (BP) was anatomically contoured according to the Radiation Therapy Oncology Group atlas. Patient medical records were reviewed retrospectively to determine incidence of brachial plexus injury (BPI) and a normal tissue complication probability model was applied to the dosimetric data. RESULTS: Five patients (6.4%) reported neuropathic symptoms consistent with BPI and occurred a median 11.9 months after treatment (range, 5.2-28.1 months). Most common dose and fractionation in those developing BPI were 50 Gy in 5 fractions (4 patients). Symptoms consisted of pain in 2 patients (40.0%), numbness in the hand or axilla in 4 patients (80.0%), and ipsilateral hand weakness in 1 patient (20.0%). In the overall cohort the median BP Dmax (EQD23 Gy) was 5.13 Gy (range, 0.18-217.2 Gy) and in patients with BPI the median BP Dmax (EQD23 Gy) was 32.14 Gy (range, 13.4-99.9 Gy). The normal tissue complication probability model gave good fit with an area under the curve of 0.75 (odds ratio, 7.3; 95% confidence interval, 0.8-68.3) for BP Dmax (EQD23 Gy) threshold of 20 Gy. CONCLUSIONS: Significant variation exists in the dose delivered to the brachial plexus for patients treated by SBRT for apical lung tumors. The incidence of neuropathic symptoms in the post-SBRT setting was appreciable and prospective clinical correlation with dosimetric information should be used to develop evidence-based dose constraints.