Impact of Lung Parenchymal-Only Failure on Overall Survival in Early-Stage Lung Cancer Patients Treated With Stereotactic Ablative Radiotherapy

IntroductionThe impact of lung parenchymal-only failure on patient survival after stereotactic ablative body radiotherapy (SABR) for early-stage non–small-cell lung cancer (NSCLC) remains unclear.Patients and MethodsThe study population included 481 patients with early-stage NSCLC who were treated with 3- to 5-fraction SABR between 2000 and 2016. The primary study objective was to assess the impact of out-of-field lung parenchymal-only failure (OLPF) on overall survival (OS).ResultsAt a median follow-up of 5.9 years, the median OS was 2.7 years for all patients. Patients with OLPF did not have a significantly different OS compared to patients without failure (P = .0952, median OS 4.1 years with failure vs. 2.6 years never failure). Analysis in a 1:1 propensity score–matched cohort for Karnofsky performance status, comorbidity score, and smoking status showed no differences in OS between patients without failure and those with OLPF (P = .8). In subgroup analyses exploring the impact of time of failure on OS, patients with OLPF 6 months or more after diagnosis did not have significantly different OS compared to those without failure, when accounting for immortal time bias (P = .3, median OS 4.3 years vs. 3.5 years never failure). Only 7 patients in our data set experienced failure within 6 months of treatment, of which only 4 were confirmed to be true failures; therefore, limited data are available in our cohort on the impact of OLPF for ≤ 6 months on OS.ConclusionOLPF after SABR for early-stage NSCLC does not appear to adversely affect OS, especially if occurring at least 6 months after SABR. More studies are needed to understand if OLPF within 6 months of SABR is associated with adverse OS. These data are useful when discussing prognosis of lung parenchymal failures after initial SABR.     

Stereotactic Ablative Body Radiotherapy Versus Radical Radiotherapy: Comparing Real-World Outcomes in Stage I Lung Cancer

AimsStereotactic ablative body radiotherapy (SABR) is now considered the standard of care for medically inoperable stage I non-small cell lung cancer (NSCLC). The English National Cancer Registration and Analysis Service (NCRAS) collects data on all patients diagnosed with lung cancer, including information on treatment. We wanted to compare outcomes for patients with stage I NSCLC treated with radical radiotherapy with either SABR or fractionated radiotherapy.Materials and methodsAll patients diagnosed with stage I NSCLC in 2015 and 2016 were identified from the NCRAS dataset, validated by the National Lung Cancer Audit, and their treatment data were collated. For patients who received radiotherapy, those receiving radical dose fractionations, including SABR, were identified through linkage to the national Radiotherapy Dataset. Clinical outcomes for those receiving SABR or more fractionated radical radiotherapy were compared using univariate and fully adjusted Cox proportional hazards models.ResultsIn total, 12 384 patients with stage I NSCLC were identified during the study period; 53.5% underwent surgical resection, 24.3% received no documented treatment, 18.6% received radical radiotherapy and 3.5% received other non-curative-intent treatments. For those receiving radical radiotherapy, 69% received SABR and 31% received fractionated treatment. The hazard ratio of death for the 1587 patients who received SABR was 0.69 (95% confidence interval 0.61–0.79) compared with 717 patients who received radical fractionated radiotherapy; this benefit was seen for both stage Ia and stage Ib disease. The median overall survival was also longer for SABR versus radical radiotherapy (715 days versus 648 days). Exploratory travel time analysis shows that compared with stage I NSCLC patients receiving SABR, those receiving fractionated radiotherapy and those receiving no active treatment would have to travel longer and further to reach their nearest radiotherapy SABR centre.ConclusionThis study adds to the data that SABR has a survival benefit when compared with fractionated radical radiotherapy. Although the use of SABR increased in England over this study period, it has still not reached levels of use seen in other countries. This study also highlights that one quarter of stage I NSCLC patients overall received no active treatment.     

Biologically Effective Dose in Stereotactic Body Radiotherapy and Survival for Patients With Early-Stage NSCLC

IntroductionStereotactic body radiotherapy (SBRT) results in excellent local control of stage I NSCLC. Radiobiology models predict greater tumor response when higher biologically effective doses (BED₁₀) are given. Prior studies support a BED₁₀ greater than or equal to 100 Gy with SBRT; however, data are limited comparing outcomes after various SBRT regimens. We therefore sought to evaluate national trends and the effect of using “low” versus “high” BED₁₀ SBRT courses on overall survival (OS).MethodsThis retrospective study used the National Cancer Data Base to identify patients diagnosed with clinical stage I (cT1-2aN0M0) NSCLC from 2004 to 2014 treated with SBRT. Patients were categorized into LowBED (100-129 Gy) or HighBED (≥130 Gy) groups. A 1:1 matched analysis based on patient and tumor characteristics was used to compare OS by BED₁₀ group. Tumor centrality was not assessed.ResultsO 25,039 patients treated with LowBED (n = 14,756; 59%) or HighBED (n = 10,283; 41%) SBRT, 20,542 were matched. Shifts in HighBED to LowBED SBRT regimen use correlated with key publications in the literature. In the matched cohort, 5-year OS rates were 26% for LowBED and 34% for HighBED groups (p = 0.039). On multivariate analysis, receipt of LowBED was associated with significantly worse survival (hazard ratio = 1.046, 95% confidence interval: 1.004–1.090, p = 0.032).ConclusionsLowBED SBRT for treating stage I NSCLC is becoming more common. However, our findings suggest SBRT regimens with BED₁₀ greater than or equal to 130 Gy may confer an additional survival benefit. Additional studies are required to evaluate the dose-response relationship and toxicities associated with modern HighBED SBRT.     

Skin Toxicity in Early Breast Cancer Patients Treated with Field-In-Field Breast Intensity-Modulated Radiotherapy versus Helical Inverse Breast Intensity-Modulated Radiotherapy: Results of a Phase III Randomised Controlled Trial

AimsSkin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer.Materials and methodsThis phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms.ResultsIn total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT.ConclusionsOur study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.     

Pulmonary Hemorrhage in Patients Treated With Thoracic Stereotactic Ablative Radiotherapy and Antiangiogenic Agents

IntroductionSevere pulmonary hemorrhage can occur in patients treated with thoracic stereotactic ablative radiotherapy (SABR) and vascular endothelial growth factor inhibitors (VEGFis). There is limited understanding of which patients are at risk for toxicity with the combination of thoracic SABR and VEGFis or how the risk differs over either therapy alone.MethodsWe evaluated a prospectively maintained cohort of 690 patients with 818 pulmonary tumors treated with highly conformal SABR. Rates of any-grade and grade 3 plus (G3+) pulmonary hemorrhage were compared between patients treated with or without VEGFi therapy across tumor locations. Outcomes were compared between patients treated with SABR plus VEGFi and a propensity-matched cohort of those treated with VEGFi therapy alone.ResultsTreatment with VEGFi plus SABR was associated with higher rates of G3+ pulmonary hemorrhage compared with those treated with SABR alone for the overall cohort (3-y incidence: 7.9% versus 0.6%, p < 0.01) and those with central tumors (19.1% versus 3.3%, p = 0.04). When further subdivided, there were significantly higher toxicity rates with VEGFi for the ultracentral (9.0% versus 45.0%, p = 0.044), but not central nonabutting tumors (0.0% versus 1.3%, p = 0.69). There was an increased incidence of G3+ hemorrhage in patients treated with VEGFi plus SABR compared with VEGFi alone (9.6% versus 1.3%, p = 0.04).ConclusionsThe combination of VEGFi and SABR was associated with an increased risk of high-grade pulmonary hemorrhage over either therapy alone. Low rates of toxicity were observed when excluding patients with SABR to ultracentral tumors and applying highly conformal SABR techniques.     

Toxicity and Efficacy of Stereotactic Ablative Body Radiotherapy for Moderately Central Non-small Cell Lung Cancers Using 50 Gy in Five Fractions

AimsStereotactic ablative body radiotherapy doses for peripheral lung lesions caused high toxicity when used for central non-small cell lung cancer (NSCLC). To determine a safe stereotactic ablative body radiotherapy dose for central tumours, the phase I/II Radiation Therapy Oncology Group RTOG 0813 trial used 50 Gy/five fractions as a baseline. From 2013, 50 Gy/five fractions was adopted at the Beatson West of Scotland Cancer Centre for inoperable early stage central NSCLC. We report our prospectively collected toxicity and efficacy data.Materials and methodsPatient and treatment characteristics were obtained from electronic medical records. Tumours were classed as moderately central or ultra-central tumours using published definitions. Toxicity was assessed in a centralised follow-up clinic at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years after treatment.ResultsFifty patients (31 women, 19 men, median age 75.1 years) were identified with T1-2N0M0 moderately central NSCLC; one patient had both an ultra-central and a moderately central tumour. Eighty-four per cent were medically unfit for surgery. Forty per cent had biopsy-proven NSCLC and 60% were diagnosed radiologically using 18-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Fifty-six per cent of patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse. All patients received 50 Gy/five fractions on alternate days on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. There was one episode of early grade 3 oesophagitis and one grade 3 late dyspnoea. There was no grade 4 toxicity. Over a median follow-up of 25.2 months (range 1–70 months), there were 34 deaths: 18 unrelated to cancer and 16 due to cancer recurrence. The median overall survival was 27.0 months (95% confidence interval 20.6–35.9) and cancer-specific survival was 39.8 months (95% confidence interval 28.6, not reached).ConclusionThis study has shown that 50 Gy/five fractions is a safe dose and fractionation for early stage inoperable moderately central NSCLC, with outcomes comparable with other series, even with patients with a poor performance status.     

Local Control With Single-Fraction Lung Stereotactic Body Radiotherapy is not influenced by Non-Small Cell Lung Cancer Histologic Subtype

Introduction/BackgroundFor early stage medically inoperable lung cancer treated with fractionated stereotactic body radiotherapy (SBRT), higher local failure is associated with squamous carcinoma (SqC) compared to adenocarcinoma (AC). This study explored whether histology influences single-fraction SBRT local control.Materials and MethodsWe surveyed our prospective data registry from 12/2009 to 12/2019 for SF-SBRT cases with biopsy-proven AC or SqC only. Outcomes of interest included local (LF), nodal (NF), distant (DF) failure rates and overall survival (OS), as well as treatment-related toxicity.ResultsFor the 10-year interval surveyed, 113 patients met study criteria. There was no association between histology and dose received (34 Gy or 30 Gy). Median follow up was 22.9 months. Patient characteristics were balanced between histologic cohorts. Median tumor size was 1.9 cm. Comparing total AC vs. SqC cohorts, 2-year LF rates (%) were 7.3 vs. 9.6, respectively (P = .9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.8 vs. 6.4; 10.5 vs. 16.2; 15.8 vs. 13.0; 77.9 vs.71.2 (all P = non-significant). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.8 vs. 8.1; 5.9 vs. 18.0; 23.5 vs. 9.7; 70.6 vs. 77.1 (all P = non-significant). When considering toxicities, there were no grade 4/5 toxicities and no significant differences in any other toxicity rate by histology or dose.ConclusionSF-SBRT local control was not associated with histology, unlike fractionated schedules. This novel finding adds to the evolving understanding of this treatment schedule.     

Long-term Overall Survival Outcomes in Patients with Early Stage,Peripherally Located,Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiotherapy in a Non-academic Cancer Centre

AimsTo report long-term outcomes of patients treated with stereotactic ablative radiotherapy (SABR) for early stage, peripherally located non-small cell lung cancer.Materials and methodsData were collected retrospectively between September 2009 and May 2019. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. All patients were treated according to local protocol based on the national UK SABR Consortium guidelines. Risk-adapted treatment schedules were used depending on the size and the location of the tumour (54 Gy in three fractions, 55 Gy in five fractions, 60 Gy in eight fractions or 50 Gy in 10 fractions). Overall survival outcomes were evaluated using the Kaplan–Meier method.ResultsIn total, 412 patients were included in the analysis. The median age was 76 years (range 48–93 years). Histological confirmation was obtained in 233 cases (56.6%). The median overall survival for all patients was 42.3 months (95% confidence interval 37.3–47.3 months), with 3- and 5-year overall survival of 52.8% and 37.3%, respectively. For biopsy-proven patients (56.6%), 3- and 5-year overall survival was 57.3% and 40.1%, respectively. With respect to overall survival, univariate and multivariate analysis revealed no significant difference in survival by technique (volume-modulated arc therapy versus conformal; three-dimensional computed tomography versus four-dimensional computed tomography), tumour location, smoking status at first contact, pre-treatment tumour stage or pre-treatment standardised uptake value. Survival was poorer for patients who received the 50 Gy in 10 fractions schedule. Treatment was very well tolerated with very low rates of grade 3–4 toxicity (1%).ConclusionsSABR for peripherally located, medically inoperable non-small cell lung cancer can be safely and effectively implemented in a non-academic institution with appropriate equipment and training. Overall survival outcomes and toxicity rates are comparable with internationally published studies. Patients treated with 50 Gy in 10 fractions had a poorer survival outcome.     

Lung Metastases Treated With Stereotactic Ablative Radiation Therapy in Oligometastatic Colorectal Cancer Patients: Outcomes and Prognostic Factors After Long-Term Follow-Up

Background

We evaluated a series of oligometastatic colorectal cancer (CRC) patients treated with stereotactic ablative body radiotherapy (SABR) delivered in all active lung metastases.

Incidental Mediastinal Dose Does Not Explain Low Mediastinal Node Recurrence Rates in Patients With Early-Stage NSCLC Treated With Stereotactic Body Radiotherapy

BackgroundPatients with stage I non–small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) do not undergo a staging mediastinoscopy, yet reported mediastinal recurrence rates appear lower than in patients undergoing surgical resection. We determined incidental SBRT doses to assess whether this could account for the low rates of recurrence.Patients and MethodsBetween March 2009 and September 2012, we reviewed cases of patients with inoperable lung tumors (n = 136) treated with SBRT at our institution. The SBRT regimen was 54 Gy in 3 fractions with positron emission tomography/computed tomography (PET/CT) staging. Incidental doses to the mediastinal lymph node stations (MLNSs), primary tumor control, locoregional (LR), distant control (DC), and overall survival (OS) rates were determined.ResultsForty-six patients with stage I NSCLC met the inclusion criteria. The calculated median incidental SBRT dose to all MLNSs was < 5 Gy for the majority of patients (75%). At a median follow-up of 16.8 months (0.6-38.9 months), the 1- and 2-year primary tumor control, LR, OS, and DC rates were 100% and 95.5%, 97.4% and 81.7%, 88.1% and 81%, and 96.9% and 86.9%, respectively. Only 2 patients (4.9%) had mediastinal recurrence, with incidental SBRT doses to MLNSs that were similar to the rest of patients (P > .05).ConclusionLow mediastinal recurrence rates in stage I NSCLC treated with SBRT validates the omission of staging mediastinoscopy. The low incidental dose to MLNSs does not seem to explain the low mediastinal recurrence in the majority of patients. Our findings also confirm that prophylactic radiation to the mediastinum is not necessary and support the hypothesis that local ablation of the primary lesion could indirectly affect subclinical nodal disease through unknown mechanisms.     

Impact of Pretreatment Interstitial Lung Disease on Radiation Pneumonitis and Survival in Patients Treated With Lung Stereotactic Body Radiation Therapy (SBRT)

Introduction

The purpose of this study was to determine the impact of interstitial lung disease (ILD) on radiation pneumonitis (RP) and overall survival (OS) in lung stereotactic body radiation therapy (SBRT).

An Investigation of Dosimetric Correlates of Acute Toxicity in Prostate Stereotactic Body Radiotherapy: Dose to Urinary Trigone is Associated with Acute Urinary Toxicity

Aims

There are limited data on dosimetric correlates of toxicity in stereotactic body radiotherapy (SBRT) for prostate cancer. We aimed to identify potential relationships between dose and toxicity using conventional dose–volume histograms (DVHs) and dose–surface maps (DSMs).