ABSTRACT
BACKGROUND: Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. METHODS: One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. DISCUSSION: SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).
Subject(s)
Radiosurgery , Humans , Radiosurgery/methods , Neoplasm Metastasis , Female , Male , Neoplasms, Multiple Primary/radiotherapy , Aged , Clinical Trials, Phase III as Topic , Middle AgedABSTRACT
BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.
Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Pandemics , COVID-19/epidemiology , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Radiosurgery/methods , Treatment OutcomeABSTRACT
BACKGROUND: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD. METHODS: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR. DISCUSSION: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Diseases, Interstitial/radiotherapy , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Diseases, Interstitial/pathology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Radiosurgery/adverse effects , Radiotherapy Dosage , Tomography, X-Ray Computed/methods , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Response EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. METHODS AND MATERIALS: We reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54-60 Gy in 3-8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final 'gold-standard' assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. RESULTS: Eighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33-68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. CONCLUSION: Using RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.
Subject(s)
Lung Neoplasms , Radiosurgery , Humans , Response Evaluation Criteria in Solid Tumors , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Treatment Outcome , Positron Emission Tomography Computed Tomography/methods , Radiosurgery/methods , Lung/diagnostic imaging , Lung/pathologyABSTRACT
PURPOSE: Using diagnostic computed tomography (dCT) scans instead of CT simulation (CTsim) scans can increase departmental efficiency and reduce patient burden. The goal of the DART trial was to assess the efficacy and acceptability of dCT-based planning workflows with a focus on patient experiences, plan deliverability and adequacy of target coverage, and workflows. METHODS AND MATERIALS: Patients undergoing same-day CTsim and treatment for palliative radiation therapy to thoracic, abdominopelvic, or proximal limb targets with a recent dCT (within 28 days) in a reproducible position were eligible. After stratifying by target type (bone or soft tissue vs. visceral), participants were randomized (1:2 ratio) between CTsim-based (CTsim arm) vs. dCT-based planning (dCT arm). The primary endpoint was time in center (TIC), defined as total time spent in the cancer center on first day of treatment, from first radiation department appointment to first fraction completion. Secondary endpoints included plan deliverability, adequacy of target coverage, and stakeholder acceptability. RESULTS: Thirty-three patients (42 treatment sites) were enrolled between June 2022 and April 2023. The median age was 72 (interquartile range [IQR]: 67-78), 73% were male, and the most common primary cancers were lung (33%), prostate (24%), and breast (12%). The most common dose and fractionations were 8 Gy in 1 and 20 Gy in 5 fractions (50% and 43% of plans, respectively). TIC was 4.7 ± 1.1 hours (mean ± SD) in the CTsim arm vs. 0.41 ± 0.14 hours in the dCT arm (P < .001). All dCT plans were deliverable. All plans in both arms were rated as "acceptable" (80% CTsim; 81% dCT) or "acceptable with minor deviation" (20% CTsim; 19% dCT). Patient perception of acceptability was similar in both arms with the exception of time burden, which was rated as "acceptable" by 50% in the CTsim arm vs. 90% in the dCT arm (P = .025). CONCLUSION: dCT-based radiation planning substantially reduced TIC without detriment in plan deliverability or quality and had a tangible impact on patient experience with reduced patient-reported time burden.
Subject(s)
Palliative Care , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray Computed , Humans , Male , Palliative Care/methods , Female , Radiotherapy Planning, Computer-Assisted/methods , Aged , Middle Aged , Neoplasms/radiotherapy , Neoplasms/diagnostic imaging , Workflow , Aged, 80 and over , Time FactorsABSTRACT
PURPOSE: Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT. METHODS AND MATERIALS: NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/- memantine), performed longitudinal NCF testing, and included an optional blood draw for APOE analysis. NCF test results were compared at baseline and over time with mixed-effects models. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm and APOE carrier status. RESULTS: APOE results were available for 45% of patients (n = 227/508). NCF did not differ by APOE e4 carrier status at baseline. Mixed-effects modeling showed that APOE e4 carriers had worse memory after WBRT compared with APOE e4 noncarriers (Hopkins Verbal Learning Test-Revised total recall [least square mean difference, 0.63; P = .0074], delayed recognition [least square mean difference, 0.75; P = .023]). However, APOE e4 carrier status was not associated with time to NCF failure (hazard ratio, 0.86; 95% CI, 0.60-1.23; P = .40). Memantine delayed the time to NCF failure, regardless of carrier status (hazard ratio, 0.72; 95% CI, 0.52-1.01; P = .054). CONCLUSIONS: APOE e4 carriers with brain metastases exhibited greater decline in learning and memory, executive function, and the Clinical Trial Battery Composite score after treatment with WBRT (+/- memantine), without acceleration of onset of difference in time to NCF failure.
Subject(s)
Brain Neoplasms , Memantine , Adult , Aged , Female , Humans , Male , Middle Aged , Apolipoprotein E4/genetics , Apolipoproteins E/genetics , Brain Neoplasms/secondary , Brain Neoplasms/radiotherapy , Brain Neoplasms/genetics , Cognition/radiation effects , Cranial Irradiation/adverse effects , Genotype , Heterozygote , Memantine/therapeutic use , Proportional Hazards ModelsABSTRACT
Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Diseases, Interstitial , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Lung Diseases, Interstitial/etiology , Male , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Female , Radiosurgery/adverse effects , Radiosurgery/methods , Aged , Prospective Studies , Middle Aged , Aged, 80 and over , Quality of Life , CanadaABSTRACT
PURPOSE: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology. METHODS AND MATERIALS: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible. The maximally tolerated dose was defined as the dose of radiation therapy associated with a ≤30% rate of grade (G) 3 to 5 prespecified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume; tumors with endobronchial invasion were excluded. This primary analysis occurred 2 years after completion of accrual. RESULTS: Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range, 65-87) and 17 (57%) were female. Planning tumor volume was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%), and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range, 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia. The latter had computed tomography findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% CI, 52.3%-85.3%), progression-free survival 66.1% (95% CI, 46.1%-80.2%), local control 89.6% (95% CI, 71.2%-96.5%), regional control 96.4% (95% CI, 77.2%-99.5%), and distant control 85.9% (95% CI, 66.7%-94.5%). Quality-of-life scores declined numerically over time, but the decreases were not clinically or statistically significant. CONCLUSIONS: Sixty Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the prespecified acceptability criteria and results in excellent control for ultracentral tumors.
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Purpose: The goal of this study was to assess the potential real-world effect of the recently reported SC.24 trial on spine stereotactic body radiation therapy (SBRT) utilization. We estimated the proportion of patients treated with conventional radiation therapy (CRT) who would have been eligible for spine SBRT per trial inclusion criteria and analyzed the potential estimated increased costs to our institution. Methods and Materials: This was a retrospective review of patients who received spine CRT at our institution between August and October 2020. Data abstracted included demographics, SC.24 eligibility criteria, provider-reported pain response, and survival. A cost analysis and time survey was performed using institutional and provincial data. Results: Of 73 patients reviewed, 24 patients (33%) were eligible. The most common exclusion factors included irradiation of ≥3 consecutive spinal segments (n = 32, 44%), Eastern Cooperative Oncology Group performance status >2 (n = 17, 23%), and symptomatic spinal cord compression (n = 13, 18%). Of eligible patients, the mean age was 68.92 years, median spinal instability in neoplasia score was 8 (interquartile range, 7-9), and median Eastern Cooperative Oncology Group performance status was 2 (interquartile range, 1-2). The most common primary cancer types among eligible patients were lung (n = 10) and breast (n = 4). The median survival of eligible patients was 10 months (95% confidence interval, 4 months to not reached) with 58% surviving longer than 3 months. Of patients who had subjective pain documented after CRT, 54% had at least some response. The cost of spine SBRT was estimated at CA$4764.80 compared with $3589.10 for CRT, and tasks for spine SBRT took roughly 3 times as long as those for CRT. Conclusions: One-third of patients who received palliative spine CRT met eligibility criteria for SC.24. This possible expanded indication for spine SBRT can have a substantial effect on resource utilization. These data may be useful in guiding resource planning at institutions looking to commence a spine SBRT program.
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As the coronavirus disease 2019 (COVID-19) pandemic continues to disrupt nearly all facets of daily life, residency programs must ensure the safety and wellness of their residents while maintaining a commitment to their training and advancement. In addition to standard clinical training, radiation oncology residency programs integrate highly specialized elements specific to the delivery of radiation therapy. Few publications have addressed the significant effects of the pandemic on medical training and even fewer have addressed concerns specific to radiation oncology. We report our experience developing a resident-led adaptation of our training program in response to the COVID-19 pandemic with the aim of assisting other programs to meet this challenge.
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PURPOSE: We examined whether female authorship, traditionally underrepresented in the radiation oncology (RO) literature, has improved during the past decade, and whether the introduction of double-blind peer review (where reviewers are blinded to author names and vice-versa) improved female authorship rates. METHODS: We analyzed authorship lists during a 10-year period (2007-2016) from the 2 highest impact-factor RO journals: The International Journal of Radiation Oncology, Biology, Physics (IJROBP) and Radiotherapy and Oncology (R&O). From each journal, 20 articles per year were randomly selected. Gender trends of the first, second, last, and collaborating authors (defined as all other positions), were analyzed. A one-sample proportion test was used to compare US female senior authorship (2012-2016) with the 2015 benchmark for female US academic radiation oncologists (30.6%). RESULTS: Across 400 articles, the mean ± standard deviation percentage of female authors was 30.9% ± 22.0% with 34.8% of first, 36.7% of second, and 25.4% of last authors being female. The total percentage of female authors per year increased from 2007 to 2016 (P = .005), with no significant increase in the percentage of first (P = .250), second (P = .063), or last (P = .213) female authors. Double-blind peer review was associated with an increase in the mean percentage of female authors (2007-2011: 27.4% vs 2012-2016: 34.0%; P = .012). The proportion of US female senior authors in the latter period (27.6%) and the proportion of female US academic radiation oncologists (30.6%) were not significantly different (P = .570). CONCLUSIONS: Although the percentage of female authors in RO has increased during the past decade, this did not correspond to a higher representation of women in high-profile authorship positions. Introduction of double-blind peer review was associated with a rise in female authorship. The proportion of female US senior authors and academic radiation oncologists is similar, suggesting that senior authorship rates are approaching appropriate levels in the United States.
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(1) Background: Research productivity is a mandatory component of Canadian radiation oncology (RO) resident training. To our knowledge, Canadian RO resident research publication productivity has not previously been analysed. (2) Methods: We compiled a 12-year database of RO residents in Canadian training programs who completed residency between June 2005 and June 2016. Resident names and dates of training were abstracted from provincial databases and department websites and were used to abstract data from PubMed, including training program, publication year, journal, type of research, topic and authorship position. Residents were divided into four time periods and the linear trend test evaluated publication rates over time. Univariable and multivariable logistic regression analyses were performed to identify authorship predictors. (3) Results: 227 RO residents representing 363 publications were identified. The majority were first-author publications (56%) and original research (77%). Overall, 82% of first-author, and 80% of any-author articles were published in resident year 4 or higher. Mean number of publications for first-author and any-author positions increased significantly over time (p = 0.016 and p = 0.039, respectively). After adjusting for gender and time period, large institutions (> 3 residents per year) trended toward associations with more first-author publications (odds ratio (OR): 2.44; p = 0.066) and more any-author publications (OR: 2.49; p = 0.052). No significant differences were observed by gender. (4) Conclusions: Canadian RO resident publication productivity nearly doubled over a 12-year period. The majority of publications are released in the last 2 years of residency, and larger residency programs may be associated with more publications. These findings serve as a baseline as programs transition to Competency Based Medical Education (CBME).
Subject(s)
Internship and Residency , Radiation Oncology , Authorship , Canada , Efficiency , Humans , Radiation Oncology/educationABSTRACT
INTRODUCTION: The safety and effectiveness of stereotactic ablative radiotherapy (SABR) in patients with ultra-central lung tumors is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions. METHODS: We performed a systematic review based on the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines using the PubMed and Embase databases. The databases were queried from dates of inception until September 27, 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation, and studies with fewer than five patients were excluded. RESULTS: A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 ultra-central lung patients and all studies were retrospective in design. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically effective doses (BED10) ranging from 48 to 138 Gy10 (median, 78-103 Gy10). Median treatment-related grade 3 or greater toxicity was 10% (range, 0-50%). Median treatment-related mortality was 5% (range, 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree greater than or equal to 180 Gy3 (BED3, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range, 63%-100%) and 2-year local control rate was 92% (range, 57%-100%). CONCLUSIONS: SABR for ultra-central lung lesions appears feasible but there is a potential for severe toxicity in patients receiving high doses to the proximal bronchial tree, those with endobronchial disease, and those receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes, and normal tissue tolerances for SABR in this patient population.
Subject(s)
Lung Neoplasms/radiotherapy , Radiosurgery/methods , Dose Fractionation, Radiation , Female , Humans , Lung Neoplasms/pathology , Male , Retrospective StudiesABSTRACT
BACKGROUND: Lung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed 'ultra-central' tumors. As there is no consensus regarding the optimal radiotherapy treatment regimen for these tumors, we performed a modeling study to evaluate the trade-offs between predicted toxicity and local control for commonly used high-precision dose-fractionation regimens. METHODS: Ten patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for 3 different hypofractionated schemes: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each regimen, one plan was created that prioritized planning target volume (PTV) coverage, potentially at the expense of organ at risk (OAR) tolerance, and a second that compromised PTV coverage to respect OAR dose constraints. Published radiobiological models were employed to evaluate competing treatment plans based on estimates for local control and the likelihood for toxicity to OAR. RESULTS: The risk of esophageal or pulmonary toxicity was low (< 5%) in all scenarios. When PTV coverage was prioritized, tumor control probabilities were 92.9% for 50 Gy in 5 fractions, 92.4% for 60 Gy in 8 fractions, and 52.0% for 60 Gy in 15 fractions; however the estimated risk of grade ≥ 4 toxicity to the proximal bronchial tree was 68%, 44% and 2% respectively. When dose to OAR was prioritized, the risk of major pulmonary toxicity was reduced to < 1% in all schemes, but this compromise reduced tumor control probability to 60.3% for 50 Gy in 5 fractions, 65.7% for 60 Gy in 8 fractions and 47.8% for 60 Gy in 15 fractions. CONCLUSIONS: The tradeoff between local control and central airway toxicity are considerable in the use of 3 commonly used hypofractionated radiotherapy regimens for ultra-central lung cancer. The results of this planning study predict that the best balance may be achieved with 60 Gy in 8 fractions compromising PTV coverage as required to maintain acceptable doses to OAR. A prospective phase I trial (SUNSET) is planned to further evaluate this challenging clinical scenario.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Organs at Risk/radiation effects , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Carcinoma, Non-Small-Cell Lung/pathology , Computer Simulation , Dose Fractionation, Radiation , Humans , Lung Neoplasms/pathology , Radiobiology , Radiosurgery/adverse effects , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methodsABSTRACT
PURPOSE: As no completed randomized trials of surgery versus stereotactic ablative radiation therapy (SABR) in patients with early-stage non-small cell lung cancer are available, numerous propensity score studies have attempted to mimic the setting of clinical trials using nonrandomized data. We performed a meta-analysis of propensity score studies comparing SABR and surgery. METHODS AND MATERIALS: The MEDLINE and Embase databases were queried up to December 2016. Two authors independently reviewed the records for inclusion and extracted outcome measures. The study was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The primary meta-analysis and secondary analyses were carried out using R (version 3.3.2) at a significance level of .05. RESULTS: Sixteen studies were included in the meta-analysis. Overall survival favored surgery (hazard ratio for SABR vs surgery, 1.48 [95% confidence interval, 1.26-1.72]; I2 = 80.5%). Lung cancer-specific survival was not significantly different between SABR and surgery (hazard ratio, 1.17 [95% confidence interval, 0.92-1.50]; I2 = 18.6%). On stratification, overall survival favored both lobectomy and sublobar resection over SABR, although lung cancer-specific survival was again not significantly different. On secondary analysis, the lymph node upstaging rate was 15.6% following surgery, with 11.4% of patients receiving chemotherapy. The propensity score-matching caliper distance and first-author specialty were found to be associated with survival endpoints on regression. CONCLUSIONS: For patients with early-stage non-small cell lung cancer who are eligible for either treatment, better overall survival was seen after surgery compared with SABR. However, lung cancer-specific survival was similar for both treatments. Prospective clinical trials are preferred to propensity analyses in evaluating the nature of non-cancer-related death after SABR.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Propensity Score , Radiosurgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Confidence Intervals , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Pneumonectomy/mortality , Radiosurgery/mortalityABSTRACT
Chylothorax is a rare complication of advanced lymphoma. We present the case of an 80-year-old man diagnosed with B cell lymphoma presenting with a right chylothorax secondary to a large retroperitoneal mass. His disease was not responsive to initial treatment with chemotherapy. Fractionated radiotherapy to a dose of 2,000 cGy in five fractions was delivered to the retroperitoneal mass, and the chylothorax improved significantly within days of initiation of treatment.