Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review.

PURPOSE: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. METHODS AND MATERIALS: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. RESULTS: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. CONCLUSIONS: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Enhancing Nutrition Support for Esophageal Cancer Patients: Understanding Factors Influencing Feeding Tube Utilization.

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.

Unanticipated Radiation Replanning for Stage III Non-small Cell Lung Cancer.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Risk-adjusted chemoradiation according to human papilloma viral status for anal cancer: a pilot study.

Background and purpose: HPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV-) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status. Materials and methods: HPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV- received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category. Results: In the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV- patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients. Conclusion: De-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.

Predicting Pathological Fractures at Metastatic Humeral Lesions.

The humerus is the second most common site of metastatic disease involving long bones, yet it is still unclear which patients are at high risk for a fracture and may require prophylactic surgical fixation. The goal of this study was to assess the validity of the Mirels score to predict fractures of metastatic lesions in the humerus. Methods: We performed a retrospective electronic chart review of patients with humeral metastases at our institution (2005 to 2021), with 188 patients meeting the inclusion criteria. Sixty-one of the patients developed a fracture during follow-up. The metastatic humeral lesions were scored according to the Mirels rating system and additional radiographic criteria (cortical breach, location within the humerus, number of lesions). The predictive value of each Mirels score cutoff for fracture was assessed using sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and multivariate logistic regression. Survivorship until fracture was analyzed for each Mirels score cutoff using Kaplan-Meier curves and the log-rank test. Significance was set at p < 0.01. Results: There were no significant differences in age, sex, side of the lesion, type of malignancy, and radiation dose between the groups with and without fracture (all p > 0.01). A Mirels score of ≥8 points had the best predictive profile, with sensitivity of 83.6%, specificity of 79.5%, and AUC of 0.82 (95% confidence interval [CI], 0.75 to 0.88, p < 0.01). A logistic regression model also demonstrated that a Mirels score of ≥8 (odds ratio = 5.8, 95% CI = 1.9 to 18.2, p < 0.01) and a cortical breach (odds ratio = 21.0, 95% CI = 5.7 to 77.2, p < 0.01) were significant predictors of pathological fracture. No other radiographic characteristics were found to be significant predictors of fracture. Conclusions: This study indicated that a Mirels score of ≥8 points had the best predictive profile for anticipating fractures at a metastasis in the humerus. This is in contrast to the traditional Mirels definition of an impending pathological fracture that is used for the lower extremity, a score of ≥9. Additionally, the presence of a cortical breach was a significant predictor of fracture risk. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Detection of solid and subsolid pulmonary nodules with lung MRI: performance of UTE, T1 gradient-echo, and single-shot T2 fast spin echo.

BACKGROUND: Although MRI is a radiation-free imaging modality, it has historically been limited in lung imaging due to inherent technical restrictions. The aim of this study is to explore the performance of lung MRI in detecting solid and subsolid pulmonary nodules using T1 gradient-echo (GRE) (VIBE, Volumetric interpolated breath-hold examination), ultrashort time echo (UTE) and T2 Fast Spin Echo (HASTE, Half fourier Single-shot Turbo spin-Echo). METHODS: Patients underwent a lung MRI in a 3 T scanner as part of a prospective research project. A baseline Chest CT was obtained as part of their standard of care. Nodules were identified and measured on the baseline CT and categorized according to their density (solid and subsolid) and size (> 4 mm/ ≤ 4 mm). Nodules seen on the baseline CT were classified as present or absent on the different MRI sequences by two thoracic radiologists independently. Interobserver agreement was determined using the simple Kappa coefficient. Paired differences were compared using nonparametric Mann-Whitney U tests. The McNemar test was used to evaluate paired differences in nodule detection between MRI sequences. RESULTS: Thirty-six patients were prospectively enrolled. One hundred forty-nine nodules (100 solid/49 subsolid) with mean size 10.8 mm (SD = 9.4) were included in the analysis. There was substantial interobserver agreement (k = 0.7, p = 0.05). Detection for all nodules, solid and subsolid nodules was respectively; UTE: 71.8%/71.0%/73.5%; VIBE: 61.6%/65%/55.1%; HASTE 72.4%/72.2%/72.7%. Detection rate was higher for nodules > 4 mm in all groups: UTE 90.2%/93.4%/85.4%, VIBE 78.4%/88.5%/63.4%, HASTE 89.4%/93.8%/83.8%. Detection of lesions ≤4 mm was low for all sequences. UTE and HASTE performed significantly better than VIBE for detection of all nodules and subsolid nodules (diff = 18.4 and 17.6%, p = < 0.01 and p = 0.03, respectively). There was no significant difference between UTE and HASTE. There were no significant differences amongst MRI sequences for solid nodules. CONCLUSIONS: Lung MRI shows adequate performance for the detection of solid and subsolid pulmonary nodules larger than 4 mm and can serve as a promising radiation-free alternative to CT.

Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Systematic Review.

INTRODUCTION: Thymic epithelial tumors are rare and are classified as thymoma, thymic carcinoma, and thymic neuroendocrine tumors. The objective of this systematic review was to evaluate the treatment options for patients with thymic epithelial tumors. METHODS: This systematic review was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing surgical, radiotherapy, or systemic treatments against any combination of these treatments in patients with thymic epithelial tumors. Meta-analyses were conducted with clinically homogenous studies. RESULTS: A total of 106 studies were included, mainly from observational studies. There was an overall survival benefit with postoperative radiotherapy for patients with thymic carcinoma (hazard ratio = 0.65, 95% confidence interval: 0.47-0.89) and for patients with thymoma (hazard ratio = 0.70, 95% confidence interval: 0.59-0.82), especially for those with a high risk for mortality. Patients with thymic carcinoma or thymoma had a response to chemotherapy. Selection bias affected the results for studies that evaluated neoadjuvant chemotherapy or minimally invasive surgical techniques. Furthermore, the overall survival benefit found for adjuvant chemotherapy may have been confounded by the administration of postoperative radiotherapy. CONCLUSIONS: For patients with thymoma or thymic carcinoma, the literature is of low quality and subject to bias. There were overall survival benefits with postoperative radiotherapy. The results of this systematic review were used to inform treatment recommendations in a clinical practice guideline. Future large-scale prospective studies that control for confounders are needed.

Toxicity and Efficacy of Multitarget Thoracic Stereotactic Body Radiation Therapy.

PURPOSE: With the increasing use of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multitarget thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data, we report the experience of this strategy from a large academic center. METHODS AND MATERIALS: Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets separated by ≤1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival, and overall survival. Competing risk analysis was used to evaluate the cumulative incidence of CSRP, LF, and ICST. Univariate and multivariable analyses were performed to look for clinical and dosimetric predictive factors of CSRP and LF. RESULTS: One hundred ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Indications for SBRT were oligometastases (n = 70; 36.8%), oligoprogression (n = 62; 32.6%), curative intent in patients with primary lung cancer (n = 37; 19.5%), and control of dominant areas of metastatic progression (n = 21; 11.0%). The number of irradiated tumors ranged from 2 to 7 and the majority of SBRT courses were delivered simultaneously (88.2%). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The cumulative incidence of CSRP at 6 and 12 months was 5.3% and 7.6%, respectively. The cumulative incidence of LF at 2 years was 10.5%. The cumulative incidence of ICST at 2 years was 41.1%. Median progression-free survival was 11.8 months and median overall survival was 51.3 months. On multivariable analysis, a higher lung V35Gy (hazard ratio, 2.59; P = .02) was a statistically significant predictor of CSRP and colorectal histology predicted for higher LF (hazard ratio, 2.12; P = .02). CONCLUSIONS: In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Optimizing plans to lower the lung V35Gy may decrease the risk of CSRP.

Surgical, Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Clinical Practice Guideline.

INTRODUCTION: The aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors. METHODS: The guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews. RESULTS: Evidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline. CONCLUSIONS: This guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.

Safety Related to the Timing of Radiotherapy and Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer: A Single Institutional Experience.

BACKGROUND: The safety impact of radiotherapy (RT) timing relative to immune checkpoint inhibitors (ICIs) for advanced non-small-cell lung cancer (NSCLC) is unclear. We investigated if RT within 14 days (Interval 1) and 90 days (Interval 2) of ICI use is associated with toxicities compared to RT outside these intervals. METHODS: Advanced NSCLC patients treated with both RT and ICIs were reviewed. Toxicities were graded as per CTCAE v4.0 and attributed to either ICIs or RT by clinicians. Associations between RT timing and Grade ≥2 toxicities were analyzed using logistic regression models adjusted for patient, disease, and treatment factors (α = 0.05). RESULTS: Sixty-four patients were identified. Twenty received RT within Interval 1 and 40 within Interval 2. There were 20 Grade ≥2 toxicities in 18 (28%) patients; pneumonitis (6) and nausea (2) were most prevalent. One treatment-related death (immune encephalitis) was observed. Rates of patients with Grade ≥2 toxicities were 35%/25% in the group with/without RT within Interval 1 and 30%/25% in the group with/without RT within Interval 2. No significant association between RT timing relative to ICI use period and Grade ≥2 toxicities was observed. CONCLUSION: Albeit limited by the small sample size, the result suggested that pausing ICIs around RT use may not be necessary.

Survival analysis in lung cancer patients with interstitial lung disease.

OBJECTIVE: Lung cancer patients with interstitial lung disease (ILD) are prone for higher morbidity and mortality and their treatment is challenging. The purpose of this study is to investigate whether the survival of lung cancer patients is affected by the presence of ILD documented on CT. MATERIALS AND METHODS: 146 patients with ILD at initial chest CT were retrospectively included in the study. 146 lung cancer controls without ILD were selected. Chest CTs were evaluated for the presence of pulmonary fibrosis which was classified in 4 categories. Presence and type of emphysema, extent of ILD and emphysema, location and histologic type of cancer, clinical staging and treatment were evaluated. Kaplan-Meier estimates and Cox regression models were used to assess survival probability and hazard of death of different groups. P value < 0.05 was considered significant. RESULTS: 5-year survival for the study group was 41% versus 48% for the control group (log-rank test p = 0.0092). No significant difference in survival rate was found between the four different categories of ILD (log-rank test, p = 0.195) and the different histologic types (log-rank test, p = 0.4005). A cox proportional hazard model was used including presence of ILD, clinical stage and age. The hazard of death among patients with ILD was 1.522 times that among patients without ILD (95%CI, p = 0.029). CONCLUSION: Patients with lung cancer and CT evidence of ILD have a significantly shorter survival compared to patients with lung cancer only. Documenting the type and grading the severity of ILD in lung cancer patients will significantly contribute to their challenging management.

Salvage surgery for locally recurrent anal cancer after intensity modulated radiation therapy with concurrent chemotherapy.

INTRODUCTION: Chemoradiation (CRT) with intensity modulated radiation treatment (IMRT) has become the standard for anal cancer. In patients who fail this treatment modality, salvage surgery with abdominal perineal resection can result in long term cancer control. We aimed to evaluate a single centre's experience of salvage surgery for local recurrence since the introduction of IMRT. MATERIALS AND METHODS: A retrospective chart review was performed of all patients who underwent definitive CRT for anal carcinoma at a single tertiary referral center since IMRT became standard in 2009. Patients with recurrent or persistent disease after treatment who underwent salvage surgery were included. Details of CRT, salvage surgery and surgical complications, patterns of recurrence after surgery, and survival data were collected and described. RESULTS: Between 2009-2018, 181 patients underwent definitive treatment using IMRT for anal carcinoma. Of 26 patients who had locoregional recurrent or persistent disease, 14 underwent salvage surgery. Nine had multi-visceral resection and 8 required autologous flap reconstruction. Twelve patients had resections with clear margins and 2 had microscopic positive margins. Twelve patients (86%) experienced post-operative complications, and eight (57%) had perineal wound complications. After salvage, four patients (29%) recurred locally. None of the 8 patients with rpT2 disease recurred. After salvage surgery, 5-year disease free survival was 68.4% and 5-year overall survival was 75%. CONCLUSION: Following IMRT based chemoradiation, salvage surgery has high rates of surgical complications; however disease free and overall survival results are excellent particularly for small recurrences.

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center. METHODS AND MATERIALS: Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5). CONCLUSIONS: In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.

Stereotactic Radiotherapy for Pancreatic Cancer: A Single-Institution Experience.

Introduction Despite treatment advances, the prognosis of locally advanced pancreatic cancer is poor. Treatment remains varied and includes systemic and radiotherapy (RT). Stereotactic body radiotherapy (SBRT), highly conformal high-dose RT per fraction, is an emerging treatment option. Materials and methods We performed a single-institution retrospective review of patients with pancreatic adenocarcinoma treated with SBRT from 2015-2017. The median dose was 27 Gy (range: 21-36 Gy) in three fractions. Endpoints included local progression (RECIST 1.1; Response Evaluation Criteria in Solid Tumors 1.1), distant metastasis, overall survival, and toxicity. Results Forty-one patients were treated, with a median follow-up of eight months. Patients who received SBRT had unresectable (49%), metastatic (17%), or borderline resectable (7%) disease, declined surgery (17%), medically inoperable (7%), or developed local recurrence following the Whipple procedure (2%). The six-month and one-year rates of local progression-free survival, distant metastasis-free survival, and overall survival were 62% and 55%, 44% and 32%, and 70% and 49%, respectively. Five patients (12%) experienced seven late gastrointestinal (GI) grade 3 events. Conclusion  SBRT may be considered a treatment option to achieve local control of pancreatic cancer and is associated with a modest risk of severe late GI toxicities. Systemic therapies remain important, given the proportion of patients who develop distant metastases.

Stereotactic ablative radiotherapy for malignant mediastinal and hilar lymphadenopathy: a systematic review.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) safety and efficacy for mediastinal and hilar lymphadenopathy (MHL) is not yet established, given its potential for toxicity due to the proximity to esophagus and proximal bronchial tree (PBT). This review summarized current reported outcomes of MHL SABR. METHODS: This systematic review, based on the PRISMA guidelines, was performed using MEDLINE® (PubMed®), EMBASE and Cochrane Library databases from inception until December 2018. Studies reporting outcomes from SABR specifically for MHL from all primary malignancies were included. Non- English studies, guidelines, reviews, non-peer reviewed correspondences were excluded. Only the most recent publication and/or largest cohort from a single institution would be included for analysis. RESULTS: From the 222 studies identified, 4 retrospective studies totaling 196 patients were included in the analysis. One study included a small number of patients receiving non-ablative doses of stereotactic radiotherapy (RT). Non-small cell lung cancer (NSCLC) was the most common primary (65%), followed by breast (8%). Median follow-up ranged between 12 and 32 months. Reported dose and fractionation ranged from 21 to 60 Gy in 3-11 fractions, with median BED10 ranged from 46-106 Gy10. Three studies reported local control (LC) rates: study 1, 97% (1-year) and 77% (5-year); study 4, 88% (2-year); and study 2, 69% (6-month) and 66% (16-month). Pooled grade 3-5 toxicity rate according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 was 6% (n=11). Pooled SABR-related mortality (grade 5 toxicity) rate was 2% (n=4). Three SABR-related deaths from esophageal fistulae (2 to trachea, 1 to mediastinum) were reported, with all 3 having prior RT to the subcarinal nodes. CONCLUSIONS: Our review suggested SABR for MHL to be feasible and effective, though there is a potential for serious toxicity especially in the re-irradiation scenario. Multi-institutional and/or prospective studies will help determine the therapeutic benefit of SABR in this high-risk treatment scenario.

Intensity Modulated Radiation Therapy Plus Etoposide/Cisplatin for Patients With Limited Advanced Unresectable Thymic Epithelial Tumors: A Prospective Phase 2 Study.

PURPOSE: This prospective phase 2 study evaluated the efficacy and safety of intensity modulated radiation therapy plus etoposide/cisplatin (EP) for patients with unresectable thymic epithelial tumors (TETs). METHODS AND MATERIALS: Patients with limited advanced unresectable TETs whose lesions could be encompassed within radiation fields were enrolled in this study. Two cycles of EP (75 mg/m2 etoposide and 25 mg/m2 cisplatin on days 1-3 and days 29-31) were administered concurrently with radiation therapy, followed by 2 cycles after radiation therapy. The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival rate, overall survival rate, and incidence of adverse events. RESULTS: Fifty-six patients were enrolled between June 2011 and May 2018. Twenty-two and 34 patients had thymomas and thymic carcinomas, respectively. The median age was 52 (range, 21-76) years, and 30 patients (53.6%) were men. Eight patients (14.3%) had stage III tumors, 6 (10.7%) had stage IVA tumors, and 42 (75.0%) had stage IVB tumors. The objective response rate was 85.7% (95% confidence interval, 76.3%-95.2%). With a median follow-up of 46 (range, 7-101) months, the 1-, 2-, and 5-year progression-free survival rates were 66.1%, 48.0%, and 29.5%, and the 1-, 2-, and 5-year overall survival rates were 91.0%, 76.2%, and 56.2%, respectively. The most common grade 3 to 4 adverse event was leukopenia (42.9%). Pulmonary fibrosis was also observed (5.3%). CONCLUSIONS: Because intensity modulated radiation therapy with EP is effective and safe for limited advanced unresectable TETs, it could be a suitable treatment option for such patients.

Stereotactic Body Radiation Therapy for Extracranial Oligometastatic Non-small-cell Lung Cancer: A Systematic Review.

Stereotactic body radiation therapy (SBRT) has emerged as a treatment modality for selected patients with oligometastatic non-small-cell lung cancer (NSCLC). The objectives of this systematic review were to explore the benefits and risks of SBRT for extracranial oligometastatic NSCLC. The MEDLINE, Embase, PubMed, and CENTRAL databases were searched for relevant articles from January 1, 2000 to July 23, 2019. Fully published phase III or phase II trials of any sample size were included. Retrospective series published in manuscript form with at least 50 patients were also included. Four prospective phase II randomized trials (total, 188 participants), 4 prospective non-randomized studies (total, 140 participants), and eleven retrospective studies (total, 1288 participants) were included in this systematic review. A variety of dose fractionation schemes were used. The median overall survival (OS) ranged from 13.5 to 55 months. Progression-free survival (PFS) ranged from 4.4 to 14.7 months. Quality of life outcomes were reported in 2 studies. None of the studies reported symptom control outcomes. There are no fully completed phase III randomized trials that clarify the risks and benefits of SBRT for oligometastatic NSCLC. Higher PFS and OS with SBRT were reported in 4 phase II randomized studies. The results from mature phase III randomized data regarding whether SBRT for oligometastatic NSCLC benefits patients in terms of OS, PFS, quality of life, and symptom control are needed.

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic colorectal cancer: Dose and site of metastases matter.

BACKGROUND AND PURPOSE: To review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic colorectal cancer (mCRC) from a large academic institution. MATERIALS AND METHODS: Patients with mCRC treated with extracranial SBRT between 2008 and 2016 were identified from an institutional database. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. Endpoints included local progression (LP), overall survival (OS), progression-free survival (PFS), and cumulative incidence of starting or changing systemic therapy (SCST). Univariate and multivariable analyses (MVA) were performed to identify predictive factors. RESULTS: One hundred and sixty-five patients (262 lesions treated) were included. The 2-year cumulative incidence of LP was 23.8%. Lower SBRT doses and tumor location in the liver were significant predictors of LP on MVA. Median OS was 49.3 months, 19.3 months, and 9.0 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. Primary tumor not in situ, smaller tumors, fewer lines of previous systemic therapy, lower CEA, and oligometastases treatment indications were significant predictors of higher OS on MVA. For the entire cohort, median PFS was 9.9 months, while oligometastatic patients had a median PFS of 12.4 months. 2-year cumulative incidence of SCST was 41.7%. CONCLUSIONS: Survival outcomes are favorable after SBRT for mCRC patients. A significant proportion of patients did not have a change in systemic therapy after SBRT. Higher doses are required to obtain the best local control. Efforts should be made to better optimize SBRT delivery for liver metastases given their higher local failure rate.

Multisite stereotactic body radiotherapy for metastatic non-small-cell lung cancer: Delaying the need to start or change systemic therapy?

OBJECTIVES: The purpose of this study was to review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic non-small-cell lung cancer (NSCLC) from a large academic institution. MATERIALS AND METHODS: Metastatic NSCLC patients treated with extracranial SBRT were identified from an institutional database. Treatment indications were: (1) oligometastases, (2) oligoprogression, and (3) local control of dominant tumors. Endpoints included overall survival (OS), progression-free survival (PFS), time to starting/changing systemic therapy (SCST), and local failure (LF). Univariate and multivariable analyses were performed to look for predictive factors. RESULTS: 108 patients with 165 tumors were treated. SBRT was delivered for oligometastases in 66 patents, for oligoprogression in 20 patients, and for local control in 22 patients. Median OS and PFS for all patients were 27.3 months and 4.4 months, respectively, with treatment indication being the only predictive factor on multivariable analysis (patients with oligometastases having the highest median OS and PFS of 39.3 months and 7.6 months respectively). Cumulative incidence of SCST was only 21.5% at 1 year after SBRT, with larger tumor size and positivity for EGFR/ALK mutation being predictive of higher rates of SCST on multivariable analysis. LF was 15.6% at 1 year, with larger tumor size and exposure to previous systemic therapy being predictive of higher rates of LF on multivariable analysis. CONCLUSION: Patients treated with SBRT for oligometastases have better OS and PFS than those treated for oligoprogression or for local control of dominant tumors. Use of SBRT may delay the need for SCST. Larger tumors and previous exposure to systemic therapy were predictive of higher rates of LF.

Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected Non-Small-Cell Lung Cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice Guideline Update.

Purpose The panel updated the American Society of Clinical Oncology (ASCO) adjuvant therapy guideline for resected non-small-cell lung cancers. Methods ASCO convened an update panel and conducted a systematic review of the literature, investigating adjuvant therapy in resected non-small-cell lung cancers. Results The updated evidence base covered questions related to adjuvant systemic therapy and included a systematic review conducted by Cancer Care Ontario current to January 2016. A recent American Society for Radiation Oncology guideline and systematic review, previously endorsed by ASCO, was used as the basis for recommendations for adjuvant radiation therapy. An update of these systematic reviews and a search for studies related to radiation therapy found no additional randomized controlled trials. Recommendations Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stage IIA, IIB, or IIIA disease who have undergone complete surgical resections. For individuals with stage IB, adjuvant cisplatin-based chemotherapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a medical oncologist, is recommended to assess benefits and risks of adjuvant chemotherapy for each patient. The guideline provides information on factors other than stage to consider when making a recommendation for adjuvant chemotherapy, including tumor size, histopathologic features, and genetic alterations. Adjuvant chemotherapy is not recommended for patients with stage IA disease. Adjuvant radiation therapy is not recommended for patients with resected stage I or II disease. In patients with stage IIIA N2 disease, adjuvant radiation therapy is not recommended for routine use. However, a postoperative multimodality evaluation, including a consultation with a radiation oncologist, is recommended to assess benefits and risks of adjuvant radiation therapy for each patient with N2 disease. Additional information is available at www.asco.org/lung-cancer-guidelines and www.asco.org/guidelineswiki .