Risk factors for symptomatic radiation pneumonitis after stereotactic body radiation therapy (SBRT) in patients with non-small cell lung cancer.

BACKGROUND AND PURPOSE: Radiation pneumonitis (RP) can be a potential fatal toxicity of stereotactic body radiation therapy (SBRT) for medically inoperable non-small cell lung cancer (NSCLC). This study aimed to examine the risk factors that predict RP and explore dosimetric tolerance for safe practice in a large institutional series of NSCLC patients. MATERIALS AND METHODS: Patients with early-stage and locally recurrent NSCLC who received lung SBRT between 2002 and 2015 formed the study population. The primary endpoint was grade 2 or above radiation pneumonitis (RP2). Lungs were re-contoured consistently by one radiation oncologist according to the RTOG atlas for organs at risk. Dosimetric factors were computed consistently with exclusion of gross tumor volume of either ipsilateral, contralateral, or total lungs. RESULTS: A total of 339 patients were eligible. With a median follow-up of 47 months, RP2 was recorded in 10% patients. History of respiratory comorbidity, previous thoracic radiation, right lung location, mean lung doses of total or ipsilateral lung, and total lung volume receiving 20 Gy were all significantly associated with the risk of RP2. The dosimetric parameters of contralateral lung, including mean dose and volume receiving more than 5, 10, and 20 Gy, were not significantly associated with RP2 (ps > 0.05). A model of combining significant clinical and dosimetric factors had a predictive accuracy AUC of 0.76. According to this model, RP2 can be limited to <10% should the patient have no previous lung radiation and the mean dose of total and ipsilateral lungs be kept less than 6 Gy and 20 Gy, respectively. CONCLUSION: Dosimetric factors of total or ipsilateral lung together with important clinical factors were significant risk factors for symptomatic radiation pneumonitis after SBRT. Constraining mean lung dose can limit clinically significant lung toxicity.

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

INTRODUCTION: The 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 METHODS: The 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). RESULTS: At 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. CONCLUSION: OLPF 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.

Predictors of Nodal and Metastatic Failure in Early Stage Non-small-cell Lung Cancer After Stereotactic Body Radiation Therapy.

INTRODUCTION/BACKGROUND: Many patients with early stage non-small-cell lung cancer (ES-NSCLC) undergoing stereotactic body radiation therapy (SBRT) develop metastases, which is associated with poor outcomes. We sought to identify factors predictive of metastases after lung SBRT and created a risk stratification tool. MATERIALS AND METHODS: We included 363 patients with ES-NSCLC who received SBRT; the median follow-up was 5.8 years. The following patient and tumor factors were retrospectively analyzed for their association with metastases (defined as nodal and/or distant failure): gender; age; lobe involved; centrality; previous NSCLC; smoking status; gross tumor volume (GTV); T-stage; histology; dose; minimum, maximum, and mean GTV dose; and parenchymal lung failure. A metastasis risk-score linear-model using beta coefficients from a multivariate Cox model was built. RESULTS: A total of 111 (27.3%) of 406 lesions metastasized. GTV and dose were significantly associated with metastases on univariate and multivariate Cox proportional hazards modeling (P < .001 and hazard ratio [HR], 1.02 per mL; P < .05 and HR, 0.99 per Gy, respectively). Histology, T-stage, centrality, lung parenchymal failures, and previous NSCLC were not associated with development of metastasis. A metastasis risk-score model using GTV and prescription dose was built: risk score = (0.01611 × GTV) - (0.00525 × dose [BED10]). Two risk-score cutoffs separating the cohort into low-, medium-, and high-risk subgroups were examined. The risk score identified significant differences in time to metastases between low-, medium-, and high-risk patients (P < .001), with 3-year estimates of 81.1%, 63.8%, and 38%, respectively. CONCLUSION: GTV and radiation dose are associated with time to metastasis and may be used to identify patients at higher risk of metastasis after lung SBRT.

Superior vena cava syndrome in a patient with locally advanced lung cancer with good response to definitive chemoradiation: a case report.

BACKGROUND: The incidence of superior vena cava syndrome within the United States is roughly 15,000 cases per year. Superior vena cava syndrome is a potentially life-threatening medical condition; however, superior vena cava syndrome is not fatal in the majority of cases. Superior vena cava syndrome encompasses a collection of signs and symptoms resulting from obstruction of the superior vena cava, including swelling of the upper body of the head, neck, arms, and/or breast. It is also associated with cyanosis, plethora, and distended subcutaneous vessels. Lung cancer, including both non-small cell lung cancer and small cell lung cancer, is the most common extrinsic cause of superior vena cava syndrome. Intrinsic disruption of superior vena cava flow can also precipitate superior vena cava syndrome. This case report describes an unusual presentation and potential etiology of superior vena cava syndrome. CASE PRESENTATION: Our patient was a 51-year-old black woman with locally advanced, stage IIIB non-small cell lung cancer who had no clinical symptoms of superior vena cava syndrome at the time of diagnosis. However, she did have radiographic evidence of superior vena cava stenosis caused by extrinsic compression from her large right hilar primary tumor. She was treated with definitive chemoradiation, receiving 60 Gy of external beam radiation therapy given concurrently with chemotherapy. Three months after completion of radiotherapy, she developed signs of superior vena cava syndrome, including breast and supraclavicular swelling. She had a chest computed tomography scan showing over 50% reduction in the size of a right hilar mass; however, she had continued radiographic stenosis of the superior vena cava. The distribution of stenosis appeared to be inferior to the caudal extent of pretreatment tumor volume. She had no other radiographic indications for superior vena cava syndrome. CONCLUSIONS: Generally, superior vena cava syndrome is the result of extrinsic compression of the superior vena cava by tumor. Our patient's case represents the development of superior vena cava syndrome after an excellent response of tumor with near-complete tumor response. We suspect chemoradiation therapy as a potential etiology for the precipitation of the superior vena cava syndrome, which is currently not well reported in the medical literature.

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy.

INTRODUCTION: It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. METHODS: The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. RESULTS: At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/ß = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005-1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). CONCLUSIONS: In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Undetected lymph node metastases in presumed early stage NSCLC SABR patients.

INTRODUCTION: Stereotactic body radiation therapy (SBRT, also called stereotactic ablative body radiation SABR) is the treatment of choice for many patients with early-stage non-small cell lung cancer (NSCLC), including those who are unfit for surgery or refuse surgery. AREAS COVERED: In an effort to develop optimal staging for the evaluation of SBRT candidates, we review the performance of available lymph node staging methods, as well as risk factors for lymph node involvement. Pubmed was searched to identify relevant literature. Current staging methods for NSCLC, including Positron Emission Tomography/Computed Tomography(PET/CT) and endobronchial ultra sound (EBUS), have limited sensitivities. Expert commentary: There are several factors, including primary tumor location, tumor size, and histology that are possibly associated with the sensitivity of PET/CT to detect mediastinal lymph node metastasis. Small lymph node metastases typically remain undetected by PET/CT. Therefore invasive nodal staging procedures are indicated for most presumed early-stage NSCLC patients, but these also have limited sensitivity. Occult lymph node metastasis is associated with adverse outcome in NSCLC. Moreover, there is overwhelming evidence that certain patients who have lymph node metastases detected at the time of surgery derive an overall survival benefit from adjuvant therapies. It remains to be determined if improved detection of lymph node metastases in SABR candidates can indeed improve prognosis.