Radiomic analysis has recently demonstrated versatile uses in improving diagnostic and prognostic prediction accuracy for lung cancer. However, since lung tumors are subject to substantial motion due to respiration, the stability of radiomic features over the respiratory cycle of the patient needs to be investigated to better evaluate the robustness of the inter-patient feature variability for clinical applications, and its impact in such applications needs to be assessed. A full panel of 841 radiomic features, including tumor intensity, shape, texture, and wavelet features, were extracted from individual phases of a four-dimensional (4D) computed tomography on 20 early-stage non-small-cell lung cancer (NSCLC) patients. The stability of each radiomic feature was assessed across different phase images of the same patient using the coefficient of variation (COV). The relationship between individual COVs and tumor motion magnitude was inspected. Population COVs, the mean COVs of all 20 patients, were used to evaluate feature motion stability and categorize the radiomic features into 4 different groups. The two extremes, the Very Small group (COV≤5%) and the Large group (COV>20%), each accounted for about a quarter of the features. Shape features were the most stable, with COV≤10% for all features. A clinical study was subsequently conducted using 140 early-stage NSCLC patients. Radiomic features were employed to predict the overall survival with a 500-round bootstrapping. Identical multiple regression model development process was applied, and the model performance was compared between models with and without a feature pre-selection step based on 4D COV to pre-exclude unstable features. Among the systematically tested cutoff values, feature pre-selection with 4D COV≤5% achieved the optimal model performance. The resulting 3-feature radiomic model significantly outperformed its counterpart with no 4D COV pre-selection, with P = 2.16x10 -27 in the one-tailed t-test comparing the prediction performances of the two models.

These data do not support the routine addition of chemotherapy to definitive RT for T1N0 NPC.

Background: The development of radiation pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT) is known to be associated with many different factors, although historical analyses of RP have commonly utilized heterogeneous fractionation schemes and methods of reporting. This study aims to correlate dosimetric values and their association with the development of Symptomatic RP according to recent reporting standards as recommended by the American Association of Physicists in Medicine. Methods: We performed a single-institution retrospective review for patients who received SBRT to the lung from 2010 to 2017. Inclusion criteria required near-homogeneous tumoricidal (α/β = 10 Gy) biological effective dose (BED10) of 100-105 Gy (e.g., 50/5, 48/4, 60/8), one or two synchronously treated lesions, and at least 6 months of follow up or documented evidence of pneumonitis. Symptomatic RP was determined clinically by treating radiation oncologists, requiring radiographic evidence and the administration of steroids. Dosimetric parameters and patient factors were recorded. Lung volumes subtracted gross tumor volume(s). Wilcoxon Rank Sums tests were used for nonparametric comparison of dosimetric data between patients with and without RP; p-values were Bonferroni adjusted when applicable. Logistic regressions were conducted to predict probabilities of symptomatic RP using univariable models for each radiation dosimetric parameter. Results: The final cohort included 103 treated lesions in 93 patients, eight of whom developed symptomatic RP (n = 8; 8.6%). The use of total mean lung dose (MLD) > 6 Gy alone captured five of the eight patients who developed symptomatic RP, while V20 > 10% captured two patients, both of whom demonstrated a MLD > 6 Gy. The remaining three patients who developed symptomatic RP without exceeding either metric were noted to have imaging evidence of moderate interstitial lung disease, inflammation of the lungs from recent concurrent chemoradiation therapy to the contralateral lung, or unique peri-tumoral inflammatory appearance at baseline before treatment. Conclusions: This study is the largest dosimetric analysis of symptomatic RP in the literature, of which we are aware, that utilizes near-homogenous tumoricidal BED fractionation schemes. Mean lung dose and V20 are the most consistently reported of the various dosimetric parameters associated with symptomatic RP. MLD should be considered alongside V20 in the treatment planning process. Trial registration: Retrospectively registered on IRB 398-17-EP.

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Objectives: To examine patterns of care associated with the administration of proton versus photon therapy for adult patients with primary brain tumors in a large national cohort from the United States. Methods: The National Cancer Database (NCDB) was queried for newly diagnosed primary brain tumors (2004-2014) in adult patients aged 18 and older receiving proton or photon radiotherapy. Clinical features, patient demographics and treatment parameters were extracted. Differences between groups were assessed using multivariable logistic regression analysis. Results: In total, 73,073 patients were analyzed (n = 72,635 [99.4%] photon therapy, n = 438 [0.6%] proton therapy). On multivariable analysis of photon versus proton therapy, several factors predicted for receipt of proton therapy, including younger age (p = .041), highest income quartile (p = .007), treatment at academic institutions (p < .001), in regional facilities outside the Midwest/South (p < .001), diagnosis in more recent years (p = .003), fewer comorbidities (p < .001) and non-glioblastoma histology (p < .001). Conclusions: There are several significant socioeconomic variables that influence receipt of proton therapy for primary brain tumors. Although not implying causation, the socioeconomic findings discovered herein should be taken into account when delivering cancer care to all patients.

not well-defined. We applied a quantitative method to evaluate radiologic lung fibrosis in patients who received lung SABR with a single-fraction (25Gy/1) or a multi-fraction (50Gy/4) regimen. We sought to characterize the relative contribution of these two regimens on the development of radiologic lung fibrosis after SABR. Materials/Methods: We evaluated 94 patients with non-small cell lung cancer treated with SABR to a single lung lesion using 50Gy/4 (60 patients) or 25Gy/1 (34 patients) between 2011-2018. Radiologic features (volume, mean and STD HU) of regions of interest (GTV, PTV) were extracted from pre-treatment CT scans. Lung fibrosis was evaluated on post-treatment 1st (1-4 months) and 2nd (4-10 months) follow-up scans. Lung fibrosis was quantified by delineating fibrotic regions (excluding GTV) and measuring the volume exceeding-135HU. Results: There were no significant differences in the median time to followup scans for patients receiving 25Gy/1 relative to patients receiving 50Gy/4 (1st: 3.07 vs. 3.07 months, pZ0.39; 2nd: 6.55 vs. 6.57 months, pZ0.73). Quantitative radiologic fibrosis increased from 1st to 2nd follow-up scan for patients receiving either 25Gy/1 fraction (1.96-fold, pZ0.0001) or 50Gy/4 (1.92-fold, p<0.0001). The volume of fibrosis was greater in patients receiving 50Gy/4 relative to patients receiving 25Gy/1 (1st: 4.11-fold, pZ0.0011; 2nd: 2.67-fold, pZ0.0021), but this difference was abrogated when normalized to PTV (1st: 1.65-fold, pZ0.69; 2nd: 1.06-fold, pZ0.96). PTV was positively correlated with the volume of fibrosis for patients receiving 25Gy/1 (1st: R 2 Z0.24, pZ0.0030; 2nd: R 2 Z0.034, pZ0.2975) or 50Gy/4 (1st: R 2 Z0.11, pZ0.0115; 2nd: R 2 Z0.19, pZ0.0010) and was also positively correlated in a combined analysis of all patients (1st: R 2 Z0.16, p<0.0001; 2nd: R 2 Z0.28, p<0.0001). On multi-variate analysis of all patients, PTV was significantly correlated with quantitative radiologic fibrosis (1st: pZ0.0014; 2nd: p<0.0001) but the SABR-regimen used (50Gy/4 or 25Gy/1) was not (1st: pZ0.89; 2nd: pZ0.29). Conclusion: PTV is positively correlated with radiologic lung fibrosis after lung SABR with either 25Gy/1 or 50Gy/4. When normalized to PTV, radiologic lung fibrosis after lung SABR is not significantly different in patients receiving 25Gy/1 relative to patients receiving 50Gy/4. These findings suggest that the volume of normal lung tissue receiving the prescription dose is a critical determinant in the volume of lung fibrosis after SABR across independent dose and fractionation regimens. Further studies will focus on identifying additional biologic and clinical factors that contribute to the development of radiologic lung fibrosis after SABR.

Introduction Radiation-induced lymphopenia (RIL) occurs during treatment with conventional radiation in multiple organ sites. Development of RIL portends poor prognosis. Stereotactic body radiation therapy (SBRT) spares RIL in pancreatic cancer, but has not been examined in other sites commonly treated with SBRT. This work examines if SBRT similarly spares RIL in patients with non-small cell lung cancer (NSCLC). Materials and methods Retrospective analysis was done at a single institution on 40 distinct cases of SBRT for early stage NSCLC from 2006–2017. Incidentally collected lymphocyte counts collected within 6 months of SBRT treatment were analyzed to determine if RIL occurred. The presence of RIL was correlated with location of initial failure and survival endpoints. Kaplan-Meier curves were constructed with significance defined at the level p < 0.05. Results RIL was observed in 35% of the analyzed patients. Patterns of failure and survival data were comparable to prior SBRT literature. There was no observed association in two year local, nodal, or distant failure, progression free survival, or overall survival based on the presence of RIL. Discussion SBRT spares RIL in NSCLC compared to historical rates observed with conventionally fractionated radiation. As understanding of the role of the immune system in cancer control continues to evolve, the importance of RIL sparing techniques take on increasing importance. This study represents further analysis of RIL sparing in SBRT in an early stage NSCLC cohort without the confounding influence of chemotherapy.

Highlights Stereotactic Radiotherapy (SRT) over 5–15 days is tolerable. Hypofractionated SRT for pancreatic adenocarcinoma should include regional nodes. SRT can be interdigitated earlier without delaying vital chemotherapy. Bridging chemotherapy after SRT may allow for extended intervals prior to surgery. Longer intervals to surgery may improve margin status and could influence survival.