Radiation-Induced Peripheral Neuropathy After Thoracic Stereotactic Ablative Radiotherapy: Case Report.

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for medically inoperable patients with early stage NSCLC. Because of its noninvasive nature and favorable toxicity profile, the use of SABR continues to expand for eligible patients. We present here two uncommon cases of peripheral neuropathy secondary to SABR-induced injury to recurrent laryngeal and phrenic nerves, resulting in unilateral vocal cord and diaphragmatic paralysis, respectively.

The Role of Thoracic Radiation Therapy Dosing in the Treatment of Limited-Stage Small Cell Lung Cancer: A Study Based on the National Cancer Database.

Purpose: Small cell lung cancer (SCLC) is a highly fatal disease, but its treatment has remained relatively unchanged for decades. Randomized clinical trials evaluating radiation therapy (RT) dosing and fractionation have yielded mixed results on overall survival (OS). Methods and Materials: We identified 2261 patients with limited-stage (LS) SCLC undergoing definitive RT at 1.5, 1.8, and 2.0 Gy dose per fraction, concurrently with chemotherapy, between 2004 and 2015 within the National Cancer Database. Overall survival (OS) was evaluated using the Kaplan-Meier method, and Cox proportional hazards regression was used to investigate whether there was any survival difference among patients who received hyperfractionated, twice-daily RT at 1.5 Gy per fraction (HF1.5) and once-daily, standard fractionation RT at 1.8 Gy (SF1.8) or 2.0 Gy (SF2.0) per fraction. Subgroup analyses by age, sex, race, time to RT, facility type, and Charlson comorbidity index were also performed. Results: All stage median OS rates for HF1.5, SF1.8, and SF2.0 Gy groups were 21.6, 18.9, and 19.4 months, respectively (log-rank P = .0079). Multivariate analyses adjusting for demographic factors, socioeconomic status, tumor characteristics, and year of diagnosis showed SF1.8 (hazard ratio [HR] = 1.30, 1.03-1.63) and SF2.0 (HR = 1.20, 1.00-1.45) was associated with worse 1-year survival compared with HF1.5. This association was more evident in stage IIb-stage III than stage I to stage IIa patients. Propensity score-weighted analysis showed similar results. Stratified analyses showed the significant associations were confined to male or black patients, those aged >65 years, with 1 comorbidity, who had waited >60 days to start RT or were treated at an academic medical center. Conclusions: Analyses of real-world treatment outcome data showed that receiving hyperfractionated, twice-daily RT was associated with improved survival among patients with LS-SCLC compared with standard, once-daily fractionation regimens at 1 year after diagnosis, particularly for subsets of patients. Some associations retained statistical significance 3 years postdiagnosis.

Estimating the Practice-Level and National Cost Burden of Treatment-Related Prior Authorization for Academic Radiation Oncology Practices.

PURPOSE: Prior authorization (PA) imposes significant time burdens on radiation oncology practices, but its financial impact has not been characterized. We used time-driven activity-based costing (TDABC) to assess the cost burden of treatment-related PA events at an academic radiation oncology practice. We then estimated annual costs for an academic practice and academic practices nationally. METHODS AND MATERIALS: Using internal analyses, we created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. Using published compensation data, internal workhour estimates, and supervisory requirements, we calculated the cost of each PA event and annual costs. Using data from the 2017 American Society for Radiation Oncology Workforce Survey and the 2018 American Society for Radiation Oncology Prior Authorization Survey, we estimated annual PA costs for academic medical centers nationally. RESULTS: We successfully created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. There were significant time and cost burdens for all events (range: 51-95 minutes, $28-$101 US dollars [USD]), with significant increases when peer-to-peer discussion was required (range: 92-95 minutes, $75-$101 USD). Annual treatment-related PA departmental costs were estimated to be $491,989 USD, with approved treatments accounting for the majority (94%; $463,027 USD). Nationally, annual treatment-related PA costs were estimated to be $40,125,848 USD, with approved treatments accounting for the majority (86%; $34,632,620 USD). CONCLUSION: TDABC can be used to estimate the cost burden of PA events. These burdens are significant and translate into massive organizational costs. Our national estimates highlight the tremendous cost of PA for academic radiation oncology practices, with the majority of costs related to approved treatments.

Practical demonstration of time bias with administration of adjuvant therapy in lung cancer.

PURPOSE/BACKGROUND: Immortal time bias (ITB) can hinder appropriate interpretations of studies administering adjuvant therapies. Given the increase in National Cancer Data Base (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to practically demonstrate the effects of ITB by performing a series of simulated NCDB analyses. METHODS: A simulated NCDB analysis was performed to examine how the reported benefit of PORT in stage III non-small cell lung cancer (NSCLC) may change with adjustment for ITB utilizing sequential land mark analysis (SLMA) and time dependent Cox (TDC) modeling. RESULTS: On the simulation analysis of 6440 NSCLC patients, we found that the omission of PORT without ITB adjustment was associated with an increased risk of death (HR 1.17, p < 0.0001). After performing a sequential LMA, the detrmient of omitting PORT continued to decrease until it was no longer significant at 8 months, HR 1.05 (p = 0.09). With the TDC model, although still significant, the relative benefit of PORT decreased, to a HR of 1.07 (p = 0.02). CONCLUSIONS: Immortal time bias can alter the results of survival analyses if not carefully accounted for. Adjusting for this bias is essential for accurate data interpretation and to better quantify the impact and effect size of adjuvant therapies such as PORT.

Monte Carlo study on dose distributions from total skin electron irradiation therapy (TSET).

Total skin electron therapy (TSET) has been used to treat mycosis fungoides since the 1950s. Practitioners of TSET rely on relatively crude, phantom-based point measurements for commissioning and treatment plan dosimetry. Using Monte Carlo simulation techniques, this study presents whole-body dosimetry for a patient receiving rotational, dual-field TSET. The Monte Carlo codes, BEAMnrc/DOSXYZnrc, were used to simulate 6 MeV electron beams to calculate skin dose from TSET. Simulations were validated with experimental measurements. The rotational dual-field technique uses extended source-to-surface distance with an acrylic beam degrader between the patient and incident beams. Simulations incorporated patient positioning: standing on a platform that rotates during radiation delivery. Resultant patient doses were analyzed as a function of skin depth-dose coverage and evaluated using dose-volume-histograms. Good agreement was obtained between simulations and measurements. For a cylinder with a 30 cm diameter, the depths that dose fell to 50% of the surface dose was 0.66 cm, 1.15 cm and 1.42 cm for thicknesses of 9 mm, 3 mm and without an acrylic scatter plate, respectively. The results are insensitive to cylinder diameter. Relatively uniform skin surface dose was obtained for skin in the torso area although large dose variations (>25%) were found in other areas resulting from partial beam shielding of the extremities. To achieve 95% mean dose to the first 5 mm of skin depth, the mean dose to skin depth of 5-10 mm and depth of 10-15 mm from the skin surface was 74% (57%) and 50% (25%) of the prescribed dose when using a 3 mm (9 mm) thickness scatter plate, respectively. As a result of this investigation on patient skin dose distributions we changed our patient treatments to use a 3 mm instead of a 9 mm thickness Acrylic scatter plate for clinically preferred skin depth dose coverage.

Prospective observational trial of low-dose skin electron beam therapy in mycosis fungoides using a rotational technique.

INTRODUCTION: Low-dose total skin electron beam therapy provides a durable treatment response for skin lesions caused by cutaneous T-cell lymphoma. We prospectively assessed the durability of response and quality of life for patients receiving low-dose total skin electron beam therapy using a novel rotational technique and dosing regimen. METHODS: Patients completed baseline Skindex-29 quality-of-life surveys and had baseline Modified Severity-Weighted Assessment Tool score recorded. Patients received 12 Gy in 12 fractions with a dual-field rotational technique. The primary outcome was overall response rate, with the secondary outcomes being time to treatment response, duration of clinical benefit, and quality-of-life change. RESULTS: We enrolled 20 patients and recorded an overall response rate of 90%. The median time to treatment response was 6.5 weeks. The baseline Modified Severity-Weighted Assessment Tool score was 55.6 and it declined to a median of 2.2 at last follow-up (P < .001). The median duration of clinical benefit was 21 months. There was a decline in the Skindex-29 total score and every subdomain when each follow-up visit was compared (P = .004). CONCLUSIONS: This prospective study demonstrated a very high overall response rate and improvement in skin-related quality of life. Low-dose rotational total skin electron beam therapy can be implemented routinely in clinical practice.

Radiation Therapy Adherence Among Patients Experiencing Homelessness.

PURPOSE: Radiation therapy is a valuable, yet time- and resource-intense therapy. Patients experiencing homelessness (PEH) face many barriers related to the timely receipt of radiation therapy. Owing to a paucity of data regarding cancer treatment and homelessness, clinicians have a limited evidence base when recommending therapy to PEH. This study was performed to evaluate adherence to radiation therapy treatment regimens in PEH with cancer. METHODS AND MATERIALS: The study cohort was primarily derived from the Vanderbilt University Medical Center Homeless Health Services program. Patients in the Homeless Health Services program with radiation oncology visits were identified by query of the electronic medical record. Manual chart review was performed to gather standard treatment parameters and data describing missed appointments. A comparison group of patients not experiencing homelessness (non-PEH) was generated by aggregating appointment data for all other patients receiving similar treatments at Vanderbilt University Medical Center during multiple, consecutive years. RESULTS: In the study, 3408 PEH were identified, of whom 48 underwent radiation oncology consultation. Thirty-two were prescribed at least 1 course of radiation therapy, for a total of 54 unique courses. Out of these courses, 34 (62.9%) were completed as prescribed without delay, 12 (22.2%) were completed with delay(s), and 8 (14.8%) were not fully completed. Although the PEH cohort had significantly higher rates of delayed and undelivered fractions, the proportion of delayed or incomplete courses was not significantly different from the comparison group of non-PEH, particularly for courses with 10 or fewer fractions. Reasons for missed appointments for PEH were variable. CONCLUSIONS: This is the first publication describing adherence to radiation therapy in PEH. Our data suggest that PEH are as likely as non-PEH to complete a course of radiation therapy, albeit with more treatment interruptions. When treatment courses of >10 fractions are expected, PEH may benefit from more hypofractionated regimens, provided they have equivalent clinical efficacy to longer regimens. Documenting reasons for missed appointments will be essential to further understanding the needs of PEH. This study serves as a foundation for further analysis regarding homelessness and radiation therapy.

Dosimetric analysis of lymphopenia during chemoradiotherapy for esophageal cancer.

BACKGROUND: Lymphopenia during chemoradiation (CRT) for esophageal cancer (EC) can adversely affect clinical outcomes. We sought to explore an association between lymphopenia and dosimetric parameters during CRT for EC. METHODS: After IRB approval, we retrospectively reviewed 54 patients treated with either definitive or neoadjuvant CRT for EC. Absolute lymphocyte count was recorded weekly during CRT up and graded according to the common terminology of adverse events (CTCAE) version 4.0. Dose volume histograms (DVH) parameters were collected based on vertebral body, body dose, dose to peripheral lymphocytes, and spleen. Logistic regression correlated Grade 4 toxicity with DVH parameters and linear regression analysis correlated absolute lymphocyte nadir counts with DVH parameters. Receiver operator curves (ROC) were constructed to define dosimetric thresholds. RESULTS: There were a total of 21 Grade 4 events (38.8%) of lymphopenia. Increasing vertebral volume receiving ≥10 Gy (OR 1.1, P=0.04), ≥20 Gy (OR 1.1, P=0.03), ≥30 Gy (OR 1.1, P=0.012), or mean body dose (OR 1.04, P=0.032) were correlated with Grade 4 lymphopenia on multivariable logistic regression. The dosimetric parameters most predictive of Grade 4 toxicity via a ROC analysis included absolute vertebral volume receiving 10 Gy >289 cc, 20 Gy ≥270 cc, and vertebral volumes receiving 30 Gy ≥197 cc. On multivariable linear regression increasing volume receiving 20 Gy (Beta -0.004, P=0.001), 30 Gy (Beta -0.005, P=0.0046), and mean body dose (Beta -0.002, P=0.001) all correlated with absolute lymphocyte nadir. CONCLUSIONS: Lymphopenia, a known negative prognostic factor in EC, is closely correlated with the volume of vertebral bodies receiving radiation during CRT for EC. Dosimetric sparing of the vertebral bodies may result in better outcomes.

Childhood cancer survivors: The integral role of the cardiologist and cardiovascular imaging.

IMPORTANCE: With 80% of childhood cancer survivors (CCS) alive 30 years after diagnosis, preventable causes of death, such as cardiovascular disease resulting from initial cancer therapy, becomes an important metric. This leads to a more pronounced role for cardiologists in the care of CCS. OBSERVATIONS: While routine cardiovascular screening has been traditionally performed by the hematologist/oncologist or primary care provider, our understanding of cardiovascular disease in CCS has advanced. The measurement of left ventricular ejection fraction (LVEF) can now be complemented with additional assessments of strain, LV mass, right ventricular function, diastolic function, valve function, the pericardium, coronary perfusion, and biomarkers. Risk factor modification, prophylaxis, and timing of treatment are also critical. CONCLUSIONS AND RELEVANCE: Early cardiovascular screening and treatment in asymptomatic CCS can be nuanced and complex. As a result, there is a renewed opportunity for the cardiologist to play an integral role in the care of CCS. KEY POINTS: Question/Purpose: Review cardiovascular disease and the role of the cardiologist in the care of asymptomatic childhood cancer survivors (CCS). FINDINGS: Cardiovascular care in CCS benefits from a multi-faceted approach that does not overly rely on LVEF. Meaning: Adequate screening and treatment of cardiovascular disease in asymptomatic CCS may often be optimized by the involvement of a cardiologist.

Mean cardiopulmonary dose and vertebral marrow dose differentially predict lineage-specific leukopenia kinetics during radiotherapy for esophageal cancer.

BACKGROUND AND PURPOSE: Lymphopenia is associated with poor outcomes in esophageal cancer (EC) patients undergoing chemoradiotherapy (CRT). We hypothesized that radiation dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) may have unique effects on WBC counts and clinical outcomes in EC. MATERIALS AND METHODS: Weekly and 90-day post-CRT blood cell counts were evaluated for 46 patients with stage II-III EC treated with CRT. Thoracic vertebral volume spared (TVS) radiation was extracted from dose volume histograms (DVH). Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels as a surrogate for circulating blood pool. Linear and logistic regression identified associations between dosimetric variables and hematologic toxicities (HT). Repeated measures ANOVA tested associations between cell count trends and clinical predictors. RESULTS: WBCs and platelets reached nadir at week 6 of CRT. On multivariate analysis, mCPD was associated with lower WBC and neutrophil nadirs (p < 0.05). TVS5-40 Gy were associated with higher lymphocyte nadirs (all p < 0.05). Repeated measures ANOVA revealed an interaction effect of sex on absolute lymphocyte trend as well as age (<67 vs. >67) and diabetes on normalized lymphocyte trend (all p < 0.015). CONCLUSIONS: mCPD and volume of thoracic marrow spared radiation differentially predict lineage-specific leukopenias during CRT for EC. mCPD is significantly associated with lower total WBC and neutrophil nadirs. In contrast, greater thoracic marrow spared radiation is associated with mitigation of lymphopenia during CRT. Clinical factors such as sex, age, and diabetes may be associated with a more rapid decline in hematologic counts during treatment.

Immortal Time Bias in National Cancer Database Studies.

PURPOSE: In studies evaluating the benefit of adjuvant therapies, immortal time bias (ITB) can affect the results by incorrectly reporting a survival advantage. It does so by including all deceased patients who may have been planned to receive adjuvant therapy within the observation cohort. Given the increase in National Cancer Database (NCDB) analyses evaluating postoperative radiation therapy (PORT) as an adjuvant therapy, we sought to examine how often such studies accounted and adjusted for ITB. METHODS AND MATERIALS: A systematic review was undertaken to search MEDLINE and EMBASE from January 2014 until May 2019 for NCDB studies evaluating PORT. After appropriate exclusion criteria were applied, 60 peer-reviewed manuscripts in which PORT was compared with postoperative observation or maintenance therapy were reviewed. The manuscripts were reviewed to evaluate whether ITB was accounted for, the method with which it was adjusted for, impact factor, year of publication, and whether PORT was beneficial. RESULTS: Of the 60 publications reviewed, 23 studies (38.3%) did not include an adjustment for ITB. Most studies that did adjust for ITB employed a single landmark (LM) time (n = 31), 4 used a sequential landmark analyses, and 2 used a time-dependent Cox model. In 23 of 31 studies (74.2%) that did adjust for ITB via a single LM time, the rationale behind why the specified LM time was chosen was not clearly explained. There was no relationship between adjusting for ITB and year of publication (P = .074) or whether the study was published in a high-impact journal (P = .55). CONCLUSIONS: Studies assessing adjuvant radiation therapy by analyzing the NCDB are susceptible to ITB, which overestimates the effect size of adjuvant therapies and can provide misleading results. Adjusting for this bias is essential for accurate data representation and to better quantify the impact of adjuvant therapies such as PORT.

Systemic inflammatory dynamics during chemoradiotherapy predict response, relapse, metastasis, and survival in esophageal carcinoma.

BACKGROUND AND OBJECTIVES: Lymphopenia associated with chemoradiotherapy predicts prognosis in esophageal carcinoma. The purpose of our study was to evaluate alterations in hematologic measures of inflammation during chemoradiation. METHODS: We performed an observational study evaluating adults treated with chemoradiation in the neoadjuvant or definitive setting for stage II-III esophageal carcinoma. Multivariable logistic regression evaluated predictors of pathologic response. Survival was analyzed by time-varying multivariable Cox proportional hazards regressions. RESULTS: A total of 94 patients were included with median follow-up of 1.6 years. Elevated neutrophil:lymphocyte ratio (NLR) was predictive of incomplete pathologic response to neoadjuvant chemoradiation (OR, 1.07; P = .0030) as well as shorter distant metastasis-free survival (HR, 1.01; P = .0369) and reduced overall survival (HR, 1.01; P = .0448). An NLR > 5.55 in week two of chemoradiation predicted shorter overall survival (P = .0070). Upon adjusted analysis, NLR was independently associated with reduced probability of complete pathologic response (OR, 0.80; P = .0291), as well as poor histologic response to neoadjuvant chemoradiation (OR, 1.05; P = .0303), shorter disease-free survival (HR, 1.02; P = .0077), and reduced overall survival (HR, 1.02; P = .0070). CONCLUSIONS: Dynamic time-dependent changes in NLR during chemoradiation predict response, relapse, metastasis, and survival in esophageal carcinoma. Prospective validation is warranted.

Stereotactic body radiotherapy versus conventional radiotherapy for early-stage small cell lung cancer.

PURPOSE: This study was designed to compare survival outcomes for non-surgically managed T1-T2N0M0 small cell lung cancer (SCLC) who received either stereotactic body radiation therapy (SBRT) or conventionally fractionated radiotherapy (CFRT) using the National Cancer Data Base (NCDB). METHODS: The was queried between 2004-2015 for patients with T1-T2N0M0 SCLC. Patients must have been treated with curative intent SBRT or CFRT (delivered daily or twice daily, 45-70 Gy) with or without chemotherapy. The primary outcome was overall survival (OS). A subset analysis of patient receiving chemotherapy was also performed. A propensity score matched (PSM) analysis was performed to compare OS among patients who received chemotherapy. RESULTS: We evaluated 1378 patients in the general cohort. Multivariable Cox regression analysis(MVA) in the general cohort revealed that SBRT was significantly associated with improved survival (HR 0.68, p<0.001) along with receipt of chemotherapy (HR 0.63, p <0.001). SBRT patients were less likely to receive chemotherapy compared to CFRT patients (p<0.01). In the chemotherapy subset, of 1096 patients, on MVA, there was a trend in favor of the SBRT group (HR 0.73; p=0.06). A 3:1 PSM analysis on the chemotherapy subset found similar results on MVA with a trend in favor of SBRT (p=0.06). CONCLUSION: Patients with T1-2N0M0 SCLC treated with SBRT regimens incorporating chemotherapy had comparable outcomes to concurrent chemoradiotherapy using standard fractionation. Treatment paradigms for T1-2N0M0 SCLC incorporating SBRT warrant further exploration and should incorporate chemotherapy.

Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer.

The treatment of patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) is one of the most challenging and controversial areas of thoracic oncology. This heterogeneous group is characterized by varying tumor size and location, the potential for involvement of surrounding structures, and ipsilateral mediastinal lymph node spread. Neoadjuvant chemotherapy, administered prior to definitive local therapy, has been found to improve survival in patients with stage IIIA (N2) NSCLC. Concurrent chemoradiation has also been evaluated in phase III studies in efforts to improve control of locoregional disease. In certain instances, a tri-modality approach involving concurrent chemoradiation followed by surgery, may offer patients the best chance for cure. In this article, we provide an overview of the trials evaluating neoadjuvant therapy in patients with stage IIIA (N2) NSCLC that have resulted in current practice strategies, and we highlight the areas of uncertainty in the management of this challenging disease. We also review the current ongoing research and future directions in the management of stage IIIA (N2) NSCLC.

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer.

PURPOSE: This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. RESULTS: A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/ß of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). CONCLUSIONS: ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival.

Central liver toxicity after SBRT: An expanded analysis and predictive nomogram.

PURPOSE: To further explore the correlation of central biliary tract (cHBT) radiation doses with hepatobiliary toxicity (HBT) after stereotactic body radiation therapy (SBRT) in a larger patient dataset. METHODS: We reviewed the treatment and outcomes of all patients who received SBRT for primary liver cancer (PLC) and metastatic liver tumors between July 2004 and November 2015 at our institution. The cHBT was defined as isotropic expansions (5, 10, 15, 20 and 25mm) from the portal vein (PV). Doses were converted to biologically effective doses by using the standard linear quadratic model with α/ß of 10 (BED10). HBT was graded according to the Common Terminology Criteria for Adverse Events v4.03. RESULTS: Median follow-up was 13months. Out of the 130 patients with complete follow-up records analyzed, 60 (46.1%) had liver metastases, 40 (30.8%) had hepatocellular carcinoma (HCC), 26 (20%) had cholangiocarcinoma (CCA) and 4 (3.1%) patients other PLC histologies. Thirty-three (25.4%) grade 2+ and 28 (21.5%) grade 3+ HBT were observed. Grade 3+ HBT was seen in 13 patients (50%) with CCA, 7 patients (17.5%) with HCC and 7 (11.7%) patients with liver metastases. SBRT doses to the cHBT were highly associated with HBT, but only for PLC patients when analyzed by histological subtype. The 15mm expansion from the PV (cHBT15) proved to be an appropriate surrogate for the cHBT. The strongest cHBT15 dose predictors for G3+ HBT for PLC were the VBED1040⩾37cc (p<0.0001) and the VBED1030⩾45cc (p<0.0001). CONCLUSION: SBRT doses to the cHBT are associated with occurrence of HBT only in PLC patients. Limiting the dose to the cHBT to VBED1040<37cc and VBED1030<45cc when treating PLC patients with SBRT may reduce the risk of HBT.