Evaluation of Radiation Dose Effect on Lung Function Using Iodine Maps Derived From Dual-Energy Computed Tomography.

PURPOSE: There is interest in using dual-energy computed tomography (DECT) to evaluate organ function before and after radiation therapy (RT). The purpose of this study (trial identifier: NCT04863027) is to assess longitudinal changes in lung perfusion using iodine maps derived from DECT in patients with lung cancer treated with conventional or stereotactic RT. METHODS AND MATERIALS: For 48 prospectively enrolled patients with lung cancer, a contrast-enhanced DECT using a dual-source CT simulator was acquired pretreatment and at 6 and 12 months posttreatment. Pulmonary functions tests (PFT) were obtained at baseline and at 6 and 12 months posttreatment. Iodine maps were extracted from the DECT images using a previously described 2-material decomposition framework. Longitudinal iodine maps were normalized using a reference region defined as all voxels with perfusion in the top 10% outside of the 5 Gy isodose volume. Normalized functional responses (NFR) were calculated for 3 dose ranges: <5, 5 to 20, and >20 Gy. Mixed model analysis was used to assess the correlation between dose metrics and NFR. Pearson correlation was used to assess if NFRs were correlated with PFT changes. RESULTS: Out of the 48 patients, 21 (44%) were treated with stereotactic body RT and 27 (56%) were treated with conventionally fractionated intensity-modulated RT. Thirty-one out of these 48 patients were ultimately included in data analysis. It was found that NFR is linearly correlated with dose (P < .001) for both groups. The number of months elapsed post-RT was also found to correlate with NFR (P = .029), although this correlation was not observed for the stereotactic body RT subgroup. The NFR was not found to correlate with PFT changes. CONCLUSIONS: DECT-derived iodine maps are a promising method for detailed anatomic evaluation of radiation effect on lung function, including potentially subclinical changes.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

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.

Stereotactic Radiation Therapy in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease: A Nonrandomized Clinical Trial.

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.

A competing risk analysis of the patterns and risk factors of recurrence in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

INTRODUCTION: To assess patterns of recurrence after stereotactic ablative radiotherapy (SABR) in patient ineligible to surgery with early-stage non-small cell lung cancer (ES-NSCLC), report survival and treatment after first recurrence. METHODS: We performed a retrospective analysis on 1068 patients with ES-NSCLC and 1143 lesions. Between group differences were estimated using competing risk analysis and cause-specific hazard ratios were calculated. Overall survival (OS) after first recurrence was calculated. RESULTS: Median follow-up was 37.6 months. Univariate analysis demonstrated that ultra-central location was associated with higher risk of regional recurrence (RR) and distant metastasis (DM) (p = 0.004 and 0.01). Central lesions were associated with higher risk of local recurrence (LR) and RR (p < 0.001). Ultra-central lesions were associated with shorter OS (p = 0.002) compared to peripheral lesions. In multivariate analysis, central location was the only factor associated with increased LR and RR risks (p = 0.016 and 0.005). Median OS after first recurrence was 14.8 months. There was no difference in OS after first recurrence between ultra-central, central, and peripheral lesions (p = 0.83). Patients who received a second SABR course had an OS of 51.3 months, compared to 19.5 months with systemic therapy and 8.1 months with supportive care (p < 0.0001). DISCUSSION: The main prognostic factor for LR and RR risks was central location. Ultra-central and central tumors might benefit from treatment intensification strategies such as dose escalation and/or addition of systemic therapy to improve radiotherapy outcomes. After a first recurrence post SABR, patients with contralateral lung recurrences and those who were eligible to receive a second course of SABR had improved OS.

Prognostic Assessment of Interim F18-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer Treated With Chemoradiation With or Without Surgery.

Purpose This study aimed to evaluate if the F18-fluorodeoxyglucose positron emission tomography (F18-FDG PET) response after two weeks of chemoradiation for locoregionally advanced esophageal cancer (staged Tumor (T) 3 and/or Nodes (N)+ Metastases (M) 0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Materials and Methods Between March 2006 and September 2017, 40 patients were prospectively enrolled in our study, gave written consent, and had PET scans performed before treatment and after two weeks of chemoradiation. One patient did not undergo his two-week PET without informing study coordinators and was excluded from analyses. Results The median age at diagnosis was 62 years. Seventy-two percent of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, minor PET response, or good PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the positive predictive value (PPV) of the PET response relative to the pathologic response was 75% and the negative predictive value (NPV) was 62%. In study patients, the crude recurrence rate was 68% and there was no correlation between PET response and DFS. Conclusion In our study, interim PET response after two weeks of chemoradiation for locoregionally advanced esophageal cancer was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery).

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC).

BACKGROUND: Management of Non-Small Cell Lung Cancer (NSCLC) patients with oligoprogression remains controversial. There is limited data to support the strategy of Stereotactic Ablative Radiotherapy (SABR) targeting the oligoprogressive disease in combination with ongoing systemic treatment. We aim to assess the benefit of this approach compared to standard of care in the treatment of oligoprogressive NSCLC. METHODS: This phase II study will enroll 68 patients with oligoprogressive NSCLC, defined as 1-5 progressive extracranial lesions ≤5 cm involving ≤3 organs. Patients on active systemic therapy (chemotherapy, immunotherapy, targeted therapy or a combination) will be randomized 1:1 to either continue their current systemic therapy in combination with SABR to all lesions or the standard of care (switch to the next line of treatment, continue same treatment or observation). The co-primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include time to next systemic treatment, patient-reported quality of life, cost effectiveness as well as translational analysis to characterize both adaptive immunity and immunogenic cell death markers in the peripheral blood. DISCUSSION: There is an unmet need to carefully examine the efficacy, safety and quality of life impact of SABR in the context of oligoprogressive disease. The present study will provide higher level randomized evidence on the role of SABR in oligoprogressive NSCLC.

High-grade neuroendocrine small-cell carcinoma of the anal canal: Long-term remission with chemoradiotherapy.

Primary small-cell carcinoma of the anal canal is an exceedingly rare tumor with a poor prognosis even when aggressive therapy is initiated. We present the case of a 53-year-old male patient who presented with chronic anal pain. Examination under general anesthesia revealed the presence of a mass in the anal canal. A biopsy was performed, and histopathological examination showed a high-grade neuroendocrine small-cell carcinoma. Assessment with endoscopic ultrasound showed an invasion of the internal anal sphincter. The patient was treated with a chemoradiotherapy (CRT) regimen consisting of cisplatin and etoposide, combined to radiotherapy. The patient achieved long-term remission with CRT. This is one of the first reports in the literature of a case of a high-grade neuroendocrine small-cell carcinoma of the anal canal where long-term remission was achieved with non-surgical management of a tumor invading the anal sphincter. This favorable evolution with CRT suggests that remission could still be achieved with anal small-cell carcinomas. More cases are however required to validate this approach. RELEVANCE FOR PATIENTS: This case presentation suggests that long-term remission can still be achieved using CRT and without an extensive surgical resection in patients with small-cell carcinoma of the anal canal.

To Biopsy or Not to Biopsy?: A Matched Cohort Analysis of Early-Stage Lung Cancer Treated with Stereotactic Radiation with or Without Histologic Confirmation.

PURPOSE: For nonoperable stage I non-small cell lung cancer, stereotactic body radiation therapy (SBRT) has emerged as a standard treatment option. We aimed to compare the clinical outcomes of lung SBRT between patients with versus without pathologic cancer diagnosis. METHODS AND MATERIALS: We included patients treated by SBRT for a single pulmonary lesion between July 2009 and July 2017. Patients in the clinical diagnosis group had a positron emission tomography/computed tomography scan showing hypermetabolism, growth of the mass on sequential computed tomography, and were not eligible for biopsy, refused biopsy, or had an inconclusive biopsy. For each of those patients, a matched pair in the pathologic diagnosis group was identified by matching for patient, treatment, and tumoral characteristics. We performed a power calculation to estimate the sample size required to detect a difference arising from a 5% or 15% rate of benign processes in the group without pathology. RESULTS: A total of 924 lung SBRT treatments were performed among 878 patients from 2009 to 2017. Within this population, 131 patients were treated based on clinical findings. They were matched with 131 patients with a pathologic diagnosis who received treatment. At 3 years, no significant differences were observed in overall survival (hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.7-2.1), local control (HR, 0.9; 95% CI, 0.4-2), or regional (HR, 0.5; 95% CI, 0.2-1.4) or distant recurrence (HR, 0.6; 95% CI, 0.3-1.1). CONCLUSIONS: In our population, we found no clinically significant difference in patterns of recurrence or survival after lung SBRT for patients who had received clinical versus pathological diagnoses. There was, however, a trend toward more distant recurrences in the pathologic diagnosis group. Our power calculation suggests that data from multiple institutions would be required to rule out a difference in outcomes due to 5% to 15% of clinically diagnosed cases being treated for benign processes.

Risk-adapted stereotactic ablative radiotherapy for central and ultra-central lung tumours.

BACKGROUND: SABR is a widely accepted treatment for early-stage lung cancer but there are safety concerns for central and ultra-central tumours. Herein we report our experience using risk-adapted fractionation (prescribed doses: 40-60 Gy in 3-8 fractions) with prioritization of dose to organs at risk. METHODS: Patient declining or unsuitable for surgery with primitive or recurrent lung cancer were included. Tumours inside a 2 cm area around proximal bronchial tree (PBT) were classified as central while tumours with PTV overlapping PBT, oesophagus, great vessels and pericardial pleura were classified as ultra-central. We assessed overall survival (OS), disease-free survival (DFS), local control (LC) and toxicities. RESULTS: From 2009 to 2016, 137 patients were treated (median age: 75 years), with 60 central and 77 ultra-central tumours. Median follow-up was 36 months. Median tumour size, GTV and PTV were 2.5 cm (0.9-7), 7.8 cm3 (0.7-94.2) and 30.6 cm3 (6.5-274.3), respectively. For the whole population, median OS and DFS were 46 months and 33 months. One- and 2-years LC rates were 95% and 81%. Median OS between central and ultra-central tumours was statistically different with 57 vs 37 months (HR 0.48, p = 0.017), but LC was not different among them. We observed 4 Grade 3 and 6 Grade 5 toxicities (no grade 4). CONCLUSIONS: SABR for central and ultra-central tumours is associated with good OS, DFS and LC rates, with 7.3% grade 3-5 toxicities. Central tumours had a better prognosis in our cohort.

Central3D: A Computer Tool to Help Clinicians Differentiate Central and Peripheral Lung Tumors.

PURPOSE: We present a concise description of an in-house decision aid software called "Central3D" that allows a quick and robust lung tumor classification between central and peripheral as defined by the Radiation Therapy Oncology Group (RTOG) 0813. METHODS AND MATERIALS: Twenty cases of lung tumors were selected for this study and four radiation oncologists blindly classified them as peripheral versus central without assistance of our software. All discordant cases were reviewed using Central3D and prompt consensus was obtained. RESULTS: Many authors have stressed the importance of adopting risk adaptive fractionation schedule with lower biological equivalent dose when treating centrally-located high risks lesions. Central3D addresses the limitation of current treatment planning systems to represent image data in fixed planes and can help radiation oncologists to fully characterize these pulmonary lesions.

Stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer: A single center experience.

INTRODUCTION: Despite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution. METHODS: We reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30-35 Gy), delivered in 5-6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan-Meier method. RESULTS: Between October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1-28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I-II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT. CONCLUSION: In PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.

Management of stage III non-small cell lung cancer.

Optimal management of patients with locally advanced non-small cell lung cancer remains challenging in the context of this heterogeneous disease. Despite aggressive therapeutic approaches, survival benefits are still unsatisfactory for what might be viewed as a localized malignancy. A combined modality approach offers patients superior outcomes, especially because technological advances and refined surgical procedures now provide better results with fewer complications. Nevertheless, several features of therapy remain controversial and lack formal prospective data. Traditional cytotoxic chemoradiation therapy may have reached a plateau and future perspectives opting to integrate molecularly targeted agents and immunotherapy might be the way to improve outcomes in this disease subset.

Phase 1-2 Study of Dual-Energy Computed Tomography for Assessment of Pulmonary Function in Radiation Therapy Planning.

PURPOSE: To quantify lung function according to a dual-energy computed tomography (DECT)-derived iodine map in patients treated with radiation therapy for lung cancer, and to assess the dosimetric impact of its integration in radiation therapy planning. METHODS AND MATERIALS: Patients treated with stereotactic ablative radiation therapy for early-stage or intensity modulated radiation therapy for locally advanced lung cancer were prospectively enrolled in this study. A DECT in treatment position was obtained at time of treatment planning. The relative contribution of each voxel to the total lung function was based on iodine distribution. The composition of each voxel was determined on the basis of a 2-material decomposition. The DECT-derived lobar function was compared with single photon emission computed tomography/computed tomography (SPECT/CT). A functional map was integrated in the treatment planning system using 6 subvolumes of increasing iodine distribution levels. Percent lung volume receiving 5 Gy (V5), V20, and mean dose (MLD) to whole lungs (anatomic) versus functional lungs were compared. RESULTS: Twenty-five patients with lung cancer, including 18 patients treated with stereotactic ablative radiation therapy and 7 patients with intensity modulated radiation therapy (locally advanced), were included. Eighty-four percent had chronic obstructive pulmonary disease. Median (range) forced expiratory volume in 1 second was 62% of predicted (29%-113%), and median diffusing capacity of the lung for carbon monoxide was 56% (39%-91%). There was a strong linear correlation between DECT- and SPECT/CT-derived lobar function (Pearson coefficient correlation r=0.89, P<.00001). Mean (range) differences in V5, V20, and MLD between anatomic and functional lung volumes were 16% (0%-48%, P=.03), 5% (1%-15%, P=.12), and 15% (1%-43%, P=.047), respectively. CONCLUSIONS: Lobar function derived from a DECT iodine map correlates well with SPECT/CT, and its integration in lung treatment planning is associated with significant differences in V5 and MLD to functional lungs. Future work will involve integration of the weighted functional volume in the treatment planning system, along with integration of an iodine map for functional lung-sparing IMRT.

A dosimetric parameter to limit chest wall toxicity in SABR of NSCLC.

OBJECTIVE: Chest wall (CW) toxicity (rib fracture and/or pain) is a recognized complication of stereotactic ablative radiotherapy (SABR) for non-small-cell lung cancer. The aim of this study was to evaluate the frequency of CW toxicity following SABR and to propose a new dosimetric parameter. METHODS: We reviewed the charts and SABR plans from patients treated for T1-T2N0 peripheral non-small-cell lung cancer between 2009 and 2015. The CW structure was created through a 3-cm expansion of the lung. The median dose delivered to the planning target volume was 60 Gy. SABR was delivered in three fractions for patients with CW V30 < 30 cm3. If the CW V30 exceeded 30 cm3, five fractions were used, and the plan was optimized based on CW V37 (biologically equivalent to the V30 of three-fraction plans). RESULTS: In 6 years, 361 lesions from 356 patients were treated (3 fractions: 297; 5 fractions: 64). The median follow-up was 16 months. 23 patients (6.5%) developed CW toxicity after a median time of 10 months following treatment. The mean CW V30/V37 was 21 cm3 for patients with CW toxicity and 17 cm3 for patients without toxicity (p < 0.05). The 2-year local control and the CW toxicity rates were similar, whether patients received three or five fractions (97% vs 96% and 7% vs 5%). CONCLUSION: When the CW V30 is >30 cm3, altered fractionation combined with V37 optimization can limit CW toxicity. Advances in knowledge: The CW V37 is a suggested dosimetric parameter adapted to fractionation that may potentially limit CW toxicity after lung SABR.

The impacts of mid-treatment CBCT-guided patient repositioning on target coverage during lung VMAT.

INTRODUCTION: The purpose of this study is quantify intrafraction motion (IFM) during lung volumetric-modulated arc therapy (VMAT) and evaluate the impact of mid-treatment cone beam computed tomography (CBCT)-guided patient repositioning on target coverage. METHOD: This analysis included lung tumours treated with VMAT to 50-60 Gy in 3-5 fractions. Treatment planning was based on four-dimensional CT scans from which internal tumour volumes (ITV) were derived. An isotropic 5 mm margin was added to obtain the final planning target volume (PTV). Patients were treated supine with a customized dual vacuum immobilization device (BodyFIX, Elekta, Sweden). All patients underwent pre and mid-treatment CBCTs. Following each CBCT, a rigid registration was performed by a radiation oncologist. IFM was defined as the target displacement from pre to mid-treatment CBCT. For patients with an IFM vector ≥5 mm, a post hoc dose calculation analysis was performed to assess the dosimetric impact of CBCT-guided repositioning. RESULTS: Ninety-seven patients (367 fractions) were included. Mean (±SD) overall treatment time was 53:02 ± 13:08 min. Mean time for mid-treatment CBCT scan acquisition and patient repositioning was 15:49 ± 4:14 min. Mean IFM vector was 1.5 ± 1.4 mm (max = 8.1 mm) and was <5 mm in 354/367 (96%) of fractions. For all 13 fractions with an IFM vector ≥5 mm, dose calculation analysis of worst-case scenario indicates that ITV coverage would have remained ≥95% without mid-treatment repositioning. CONCLUSION: For 96% of fractions, the IFM vector was within the 5 mm PTV margin. Mid-treatment CBCT-guided couch repositioning did not significantly impact ITV coverage and prolonged treatment duration.

Single-center comparison of multiple chemotherapy regimens for concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer.

PURPOSE: To date, the best chemotherapy regimen to combine with concurrent radiotherapy in stage III non-small-cell lung cancer remains undetermined. We compared the survival outcomes and toxicities in patients who were treated with etoposide-cisplatin (EP), paclitaxel-carboplatin (PC), or vinblastine-cisplatin (VP) in one large cancer referral center. METHODS: We enrolled patients who received concurrent chemoradiotherapy at our university-affiliated hospital between January 1, 2009 and December 31, 2013. Demographic and clinical characteristics were identified. Progression-free survival (PFS) and overall survival (OS) between the different treatment groups were compared using Kaplan-Meier and Cox proportional hazards regression models. Treatment-related toxicities were also compared. RESULTS: A total of 107 patients were treated with EP (31.8%), PC (32.7%) or VP (35.5%). Treatment with VP was significantly superior to PC, both in terms of median PFS [29.2 vs. 10.5 months; hazard ratio (HR) 0.43; 95% CI 0.21-0.85; p = 0.01] and in terms of median OS [40.7 vs. 17.8 months; (HR) 0.42; (0.21-0.84); p = 0.01]. However, there was no survival difference between EP and either one of the other regimens, but there was significantly more toxicities reported with the use of EP (73.5%) compared to PC (44.7%) or VP (37.1%); (p = 0.001). The most frequent non-hematologic toxicities for the entire cohort were esophagitis (28%), fatigue (22.4%), pneumonitis (14%), and nephrotoxicity (9.3%). CONCLUSION: Although the present study is limited by its small cohort and its retrospective nature, the results suggest that VP might be superior to PC and is less toxic than EP.

Severe radiation pneumonitis after lung stereotactic ablative radiation therapy in patients with interstitial lung disease.

PURPOSE: To investigate the incidence and predictive factors of severe radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) in early-stage lung cancer patients with preexisting radiological interstitial lung disease (ILD). METHODS AND MATERIALS: A retrospective analysis of patients with stage I lung cancer treated with SABR from 2009 to 2014 was conducted. Interstitial lung disease diagnosis and grading was based on pretreatment high-resolution computed tomography imaging. A central review of pretreatment computed tomography by a single experienced thoracic radiologist was conducted. Univariate and multivariate analyses were conducted to determine potential predictors of severe RP in patients with ILD. RESULTS: Among 504 patients treated with SABR in this period, 6% were identified as having preexisting ILD. There was a 4% rate of ≥ grade 3 RP in the entire cohort. Interstitial lung disease was associated with increased risk of ≥ grade 3 RP (32% in ILD+ vs 2% in ILD-, P < .001). Five patients (21%) with ILD developed grade 5 RP. Lower forced expiratory volume in 1 second and forced vital capacity, higher V5Gy and mean lung dose, presence of severe radiological ILD, and combined emphysema were significant predictors of ≥ grade 3 RP on univariate analysis; only forced expiratory volume in 1 second remained on multivariate analysis. CONCLUSION: Interstitial lung disease is associated with an increased risk of severe RP after SABR. Chest imaging should be reviewed for ILD before SABR, and the risk of fatal RP should be carefully weighed against the benefits of SABR in this subgroup.

Assessing the Need for Adjuvant Chemotherapy After Stereotactic Body Radiation Therapy in Early-stage Non-small Cell Lung Carcinoma.

PURPOSE: Surgery remains the standard treatment for medically operable patients with early-stage non-small cell lung carcinoma (NSCLC). Following surgical resection, adjuvant chemotherapy is recommended for large tumors >4 cm. For unfit patients, stereotactic body radiation therapy (SBRT) has emerged as an excellent alternative to surgery. This study aims to assess patterns of recurrence and discuss the role of chemotherapy after SBRT for NSCLC. METHODS: We reviewed patients treated with SBRT for primary early-stage NSCLC between 2009 and 2015. Total target doses were between 50 and 60 Gy administered in three to eight fractions. All patients had a staging fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) scan, and histologic confirmation was obtained whenever possible. Mediastinal staging was performed if lymph node involvement was suspected on CT or PET/CT. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: Among the 559 early-stage NSCLC patients treated with SBRT, 121 patients were stage T2N0. The one-year and three-year overall survival rates were 88% and 70%, respectively, for patients with T2 disease, compared to 95% and 81%, respectively, for the T1 patients (p<0.05). The one-year and three-year local control rates were equal in both groups (98% and 91%, respectively). In T2 patients, 25 (21%) presented a relapse, among which 21 (84%) were nodal or distant. The median survival of T2N0 patients following a relapse was 11 months. CONCLUSION: Lung SBRT provides high local control rates, even for larger tumors. When patients relapse, the majority of them do so at regional or distant sites. These results raise the question as to whether adjuvant treatment should be considered following SBRT for larger tumors.

Stereotactic Body Radiotherapy for Inoperable Liver Tumors: Results of a Single Institutional Experience.

OBJECTIVES: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors unsuitable for ablation or surgery. We report our experience with SBRT in the treatment of liver tumors. MATERIALS AND METHODS: Patients with primary or secondary liver cancer were identified in our local SBRT database. Patients were included irrespective of prior liver-directed therapies. The primary endpoint of our review was in-field local control (LC). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From 2009 to 2015, a total of 71 liver lesions in 68 patients were treated with SBRT (three patients had two liver lesions treated). The median age was 71 years (27-89 years). Hepatocellular carcinoma (HCC) was the diagnosis in 23 patients (34%), with the grade of Child-Pugh A (52%), B (39%), or C (nine percent) cirrhosis. Six patients (nine percent) had intrahepatic cholangiocarcinoma (IHC). The remaining 39 patients (57%) had metastatic liver lesions. Colorectal adenocarcinoma was the most common primary tumor type (81%). The median size for HCC, IHC, and metastatic lesions was 5 cm (2-9 cm), 3.6 cm (2-4.9 cm), and 4 cm (1-8 cm), respectively. The median prescribed dose was 45 Gy (16-50 Gy). Median follow-up was 11.5 months (1-45 months). Actuarial one-year in-field LC for HCC and metastatic lesions was 85% and 64% respectively (p= 0.66). At one year, the actuarial rate of new liver lesions was 40% and 26%, respectively, (p=0.58) for HCC and metastases. Only six patients with IHC were treated with SBRT in this study - in these patients, one-year LC was 78% with new liver lesions in 53%. The SBRT treatments were well tolerated. The side effects included common criteria for adverse events (CTCAE) v4 grade 1 acute gastrointestinal toxicity in three patients, grade 3 nausea in one patient, and grade 3 acute dermatitis in another patient. Two patients had grade 5 toxicity. Radiation pneumonitis was observed in one patient two months post-SBRT treatment, and another patient was suspected to have had radio-induced liver disease (RILD) two months after SBRT. No late toxicity was seen. CONCLUSION: SBRT is a well-tolerated and effective alternative treatment option for selected patients with primary and metastatic liver tumors.

Long-term quality of life in early-stage non-small cell lung cancer patients treated with robotic stereotactic ablative radiation therapy.

PURPOSE: The purpose of this study was to prospectively evaluate the quality of life (QoL) and pulmonary function of patients with early-stage non-small cell lung cancer treated with robotic stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: Eligible patients all had histologically confirmed stage I non-small cell lung cancer and were not surgical candidates because of poor pulmonary function, comorbidities, or refusal of surgery. SABR was delivered at a median dose of 60 Gy in 3 fractions for peripheral tumors and 50 Gy in 4 or 5 fractions for central tumors. QoL was scored using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and Lung Cancer-13 questionnaires. Pulmonary function tests (PFTs) included forced expiratory volume in 1 second (FEV1) and lung diffusion capacity. Changes over time in QoL scores and PFTs were tested with nonparametric tests for longitudinal data. Local control, survival, and toxicities are also presented. RESULTS: From January 2010 to May 2013, 45 patients were enrolled. Median follow-up was 41 months. QLQ-C30 mean baseline scores for global QoL and physical functioning were 66 ± 20% and 73 ± 22%. Multilevel analyses showed no statistically and clinically significant (10-point change) deterioration in any of the QoL scores after SABR. Mean baseline FEV1 was 1.39 ± 0.51 L, and mean lung diffusion capacity was 63 ± 25% of predicted. We saw no significant change in PFTs at any time point. At 3 years, local control, disease-free survival, and overall survival were, respectively, 94%, 67%, and 75%. CONCLUSIONS: In nonsurgical patients with multiple comorbidities, lung SABR achieves long-term local control while maintaining QoL and pulmonary function.