Faculty Bibliography

BACKGROUND:The use of treatment planning prostate MRI for Stereotactic Body Radiation Therapy (SBRT) is largely a standard, yet not all patients can receive MRI for a variety of clinical reasons. Thus, we aim to investigate the safety of patients who received CT alone based SBRT planning for the definitive treatment of localized prostate cancer. METHODS:Our study analyzed 3410 patients with localized prostate cancer who were treated with SBRT at a single academic institution between 2006 and 2020. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Expanded Prostate Cancer Index Composite (EPIC) questionnaires evaluated QOL and PSA nadir was evaluated to detect biochemical failures. RESULTS:A total of 162 patients (4.75%) received CT alone for treatment planning. The CT alone group was older relative to the MRI group (69.9 vs 67.2, p < 0.001) and had higher risk and grade disease (p < 0.001). Additionally, the CT group exhibited a trend in larger CTVs (82.56 cc vs 76.90 cc; p = 0.055), lower total radiation doses (p = 0.048), and more frequent pelvic nodal radiation versus the MRI group (p < 0.001). There were only two reported cases of Grade 3 + toxicity within the CT alone group. Quality of life data within the CT alone group revealed declines in urinary and bowel scores at one month with return to baseline at subsequent follow up. Early biochemical failure data at median time of 2.3 years revealed five failures by Phoenix definition. CONCLUSIONS:While clinical differences existed between the MRI and CT alone group, we observed tolerable toxicity profiles in the CT alone cohort, which was further supported by EPIC questionnaire data. The overall clinical outcomes appear comparable in patients unable to receive MRI for their SBRT treatment plan with early clinical follow up.

INTRODUCTION/BACKGROUND:Stereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores. METHODS:We retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis. RESULTS:With a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023). CONCLUSION/CONCLUSIONS:Stereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Purpose/UNASSIGNED:Stereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death. Methods/UNASSIGNED:Medically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Results/UNASSIGNED:=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%. Conclusions/UNASSIGNED:Central location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

Endometrial cancer is a common malignancy in elderly women that are more likely to suffer from limiting medical comorbidities. Given this narrower therapeutic ratio, we aimed to assess the oncologic outcomes and toxicity in the adjuvant setting. Out of a cohort of 975 women, seventy patients aged ≥ 80 years, treated with curative postoperative radiotherapy (RT) for endometrial cancer between 2005 and 2021, were identified. Outcomes were assessed using Kaplan-Meier-analysis and comorbidities using the Charlson Comorbidity Index and G8 geriatric score. The overall survival at 1-, 2- and 5-years was 94.4%, 82.6%, and 67.6%, respectively, with significant correlation to G8 score. At 1- and 5-years, the local control rates were 89.5% and 89.5% and distant control rates were 86.3% and 66.9%, respectively. Severe (≥grade 3) acute toxicity was rare with gastrointestinal (2.9%), genitourinary (1.4%), and vaginal disorders (1.4%). Univariate analysis significantly revealed inferior overall survival with lower RT dose, G8 score, hemoglobin levels and obesity, while higher grading, lymphangiosis, RT dose decrease and the omission of chemotherapy reduced distant control. Despite older age and additional comorbidities, elderly patients tolerated curative treatment well. The vast majority completed treatment as planned with very low rates of acute severe side-effects. RT offers durable local control; however, late distant failure remains an issue.

PURPOSE/OBJECTIVE(S): Definitive chemoradiation is standard-of-care treatment for locally advanced inoperable non-small cell lung cancer (NSCLC). However, some patients refuse radiation therapy (RT) and this information is captured in the National Cancer Database (NC

PURPOSE/OBJECTIVE(S): Historically, caution has been warranted when irradiating large target volumes particularly those in close proximity to organs at risk. Prior literature has demonstrated an increased incidence of GI and GU toxicity when men with large prostates were treated with conventionally fractionated radiation therapy. However, there is very limited data regarding the clinical outcomes when SBRT is used as a definitive treatment modality. We explore the long term oncologic, toxicity, and patient reported outcomes of men treated with definitive SBRT with ultra-large prostate glands (>= 100 cc.) MATERIALS/METHODS: From 2006 to 2020, a total of 3,393 patients with low and intermediate risk prostate cancer were treated with definitive robotic-SBRT. We performed a retrospective review to identify all patients in this cohort with pre-treatment prostate volumes >= 100 cc. Prostate volume was measured at the time of treatment regardless of ADT incorporation. All patients were treated to a total dose of 35-36.25 Gy in 5 fractions. All patients had a minimum of 2 years follow-up and were given pre- and post-treatment EPIC questionnaires at defined intervals. Biochemical control was assessed using the Phoenix definition. Late toxicity was defined using CTCAE version 5.0 and was characterized as occurring >= 6 months post treatment.
RESULT(S): A total of 67 patients were identified with >= 100 cc prostate glands. Of these, 18 patients received ADT prior to treatment. Overall, the median prostate volume was 139.37 cc (range 100.1 - 227 cc). The D'Amico risk classification was low (n=19) and intermediate (n=48). The median age was 70 years (range 54 - 87 years) and the median pretreatment PSA was 8.7 ng/ml. The mean pre-treatment EPIC bowel and urinary scores were 87.8 and 79.7, respectively. One-month following SBRT, mean EPIC bowel and urinary scores worsened to 83.6 and 76.5, respectively. Three months following SBRT, mean epic bowel and urinary scores continued to decline to 83.2 and 77.1, respectively. However, bowel and bladder symptomatology improved by 1 year to 86.16 and 77.19, and by 2 years improved above baseline to 90.00 and 85.78, respectively. There were no high grade (3+) GI toxicities observed, though one grade 3 urinary retention was identified. Excellent oncologic outcomes were observed with a 5-year median PSA nadir of 0.6 ng/mL and a biochemical relapse free survival (bRFS) of 100% at 5 years.
CONCLUSION(S): SBRT has been demonstrated to be oncologically effective with minimal toxicity, and has become a more ubiquitous radiation option in men with localized prostate cancer. Although there is a historical reticence for treatment of men with large glands, we report excellent clinical outcomes. Five-year bRFS was 100% and grade 3+ urinary toxicity was 2%. Although EPIC scores transiently dropped at 1 and 3 months following SBRT, resolution was seen by 1 year following treatment. The use of SBRT for the treatment of localized prostate cancer in men with ultra-large prostate gland is feasible with minimal toxicity.
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PURPOSE/OBJECTIVE(S): Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. MATERIALS/METHODS: Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.
RESULT(S): At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.
CONCLUSION(S): This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.
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PURPOSE/OBJECTIVE(S): Postoperative radiation (PORT) is recommended by consensus guidelines for incompletely resected stage II-III non-small cell lung cancer (NSCLC) to optimize local control. Prior data across disease sites has suggested disparities exist in receipt of beneficial adjuvant therapies based on sociodemographic barriers including geography. We sought to explore if receipt of PORT in margin positive locally advanced NSCLC was related to travel distance from the treating facility. MATERIALS/METHODS: We identified patients with pathologic stage II-III NSCLC within the National Cancer Data Base who underwent treatment with upfront surgery (lobectomy or pneumonectomy) found to have microscopic (R1) or macroscopic (R2) residual tumor. Only patients coded as receiving adjuvant external-beam PORT (50-74 Gy) or no radiation were included. Multivariable logistic regression was utilized to determine factors associated with PORT receipt. Cox regression was used to identify predictors of survival.
RESULT(S): We identified 7,270 pathologic stage II-III NSCLC patients who underwent R1/R2 resections from 2004-2015; of these, 36% received PORT. Median overall survival in these patients was significantly improved with the addition of PORT, from 22.3 months to 32.8 months and this persisted when stratified by distance traveled (see table 1). Of the patients who did not receive PORT, 43.4% did receive adjuvant chemotherapy and < 1% received immunotherapy. Reason for why PORT was not given was largely unknown, but stated reasons included: contraindicated due to risk factors (3.6%) and patient refusal (4.2%). In contrast, 79.1% of PORT patients also received chemotherapy. Half of PORT patients resided within 10 miles of treatment facility. Progressively father travel distance was associated with decreased likelihood of PORT (OR 0.89, P=0.002). Other factors associated with decreased PORT receipt included older age and decreased level of education. On Cox regression, higher co-morbidity score was predictive of death, while receipt of PORT was protective (HR 0.87, P < 0.001).
CONCLUSION(S): For NSCLC patients with margin positive disease after surgery, increasing distance was associated with decreased likelihood of receiving PORT, despite being routinely recommended in this setting and proven survival benefit irrespective of geography in our patient cohort. Decreased likelihood to receive PORT with increasing travel distance suggests location may play a role in the decision to undergo PORT for these patients with adverse pathology.
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BACKGROUND/UNASSIGNED:Vaginal cancer is a rare disease for which prospective randomized trials do not exist. We aimed to assess survival outcomes, patterns of recurrence, prognostic factors, and toxicity in the curative treatment using image-guided radiotherapy (RT). METHODS/UNASSIGNED:In this retrospective review, we identified 53 patients who were treated at a single center with external beam radiotherapy and brachytherapy with or without concomitant chemotherapy from 2000 to 2021. RESULTS/UNASSIGNED:= 0.027). Minimal toxicity was observed with no patients having documentation of high-grade toxicity (CTCAE grade 3+). CONCLUSION/UNASSIGNED:In treatment of vaginal cancer, high-dose RT in combination with brachytherapy is well tolerated and results in effective local control rates, which significantly improve with an EQD2(α/β=10) ⩾65 Gy. Multivariate analyses revealed concomitant chemotherapy was a positive prognostic factor for overall and progression-free survival.

The management of spine tumors is multimodal and personalized to each individual patient. Patients often require radiation therapy after surgical fixation. Although titanium implants are used most commonly, they produce significant artifact, leading to decreased confidence in target-volume coverage and normal tissue sparing. Carbon-based materials have been found to have minimal effects on dose perturbation in postoperative radiation therapy and have shown biostability and biocompatibility that are comparable to titanium implants. Using the PubMed and Web of Sciences databases, we conducted a systematic review of carbon-based screw and rod fixation systems in the treatment of spinal tumors. We reviewed clinical studies regarding safety of spine fixation with carbon fiber-reinforced (CFR) implants and biomechanical studies, as well as radiation and dosimetric studies. The radiolucency of CFR-polyether ether ketone implants has the potential to benefit patients with spine tumor. Clinical studies have shown no increase in complications with implementation of CFR-polyether ether ketone implants, and these devices seem to have sufficient stiffness and pullout strength. However, further trials are necessary to determine if there is a clinically significant impact on local tumor control.