N. Kopek

Comparison of survival and prognostic factors in patients treated with stereotactic body radiotherapy for oligometastases or oligoprogression

BACKGROUND AND PURPOSE Clinical challenges arise in the oligoprogressive (OP) state with little evidence to support the use of ablative strategies. Our aim is to report on outcomes and prognostic variables following stereotactic body radiotherapy (SBRT) for OP and oligometastases (OM). MATERIAL AND METHODS Overall (OS) and progression-free survivals (PFS) were calculated for 163 patients for 209 lesions (106 OM and 57 OP) treated with SBRT over 9 years. OS and PFS comparisons were calculated using the Kaplan-Meier actuarial survival and log rank methods. Uni, multi-variate analyses and cumulative incidences of local failure were performed using the Cox modelling and Grays test respectively. RESULTS The median OS and PFS was 37 and 15 months versus 21.7 and 6.4 months in the OM and OP groups respectively (P = 0.02 and P = 0.01). Performance status (⩾2 HR 2.95) and number of metastases (1/2 vs ⩾3 HR 1.88) were independent prognosticators for survival. The 1/2-year PFS were 55%/25% versus 22%/6% in the OM and OP cohorts. Patterns of first relapse were four times higher outside the irradiated field and OP status (p = 0.03), ⩾3 metastasis (p = 0.002) and concurrent systemic therapy (p = 0.001) conferred a greater risk. Time to second-line treatment was 20 vs 11 months in the OM and OP groups (P = 0.001). CONCLUSION Survival and distant relapse following SBRT to OM/OP is determined by the extent of metastatic disease and performance status. Future research should address the benefit of integrating SBRT with systemic therapies to allow deferral or continuation of therapeutic agents.

Stereotactic radiation therapy for residual chemorefractory primary mediastinal non-seminomatous germ cell tumor after surgical thoracotomy

Among germ cell tumors (GCTs), postpubertal primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have the worse prognosis, with a 5-year survival rate of 45% to 50% in the most recent and largest series.1,2 This rare tumor represents only 1% of all primary mediastinal tumors, whereas only 1% to 5% of all GCTs are extragonadal, with the mediastinum being the most frequent location.2 As a result, dedicated literature on this specific subgroup of GCT is limited. The initial management of postpubertal PMNSGCT is similar to metastatic testicular nonseminomatous GCT (NSGCT) and includes cisplatin-based chemotherapy and surgery.2 Rates of chemotherapy refractory cases and early progressions seem to be more elevated in PMNSGCT and lead to a worse prognosis.3 Use of ablative radiation therapy (RT) in that context is not well described in the literature.

Thoracic irradiation in 3 weeks for limited-stage small cell lung cancer: Is twice a day fractionation really needed?

PURPOSE Many Canadian institutions treat limited-disease small cell lung cancer with 40Gy in 15 fractions delivered once-a-day in 3weeks concomitantly with chemotherapy. This regimen is convenient and seems to be effective. Here, we report and compare with a literature review the outcomes of patients with limited-stage small cell lung cancer treated in our institution with this hypofractionated regimen. PATIENTS AND METHODS From January 2004 to December 2012, patients with limited-stage small cell lung cancer treated curatively with platinum-based chemotherapy and concurrent thoracic radiotherapy at a dose of 40Gy in 16 fractions once-a-day were eligible for this review. RESULTS Sixty-eight patients fit the analysis criteria, including ten patients with small pleural effusion. The median age was 66years old. After a median follow-up of 77months for those alive, the median survival was 28months. At 3 and 5years respectively, the locoregional control rates were 67 and 64%, while the overall survival rates were 40 and 35%. Prophylaxis cranial irradiation was delivered to 68% of the patients. Grade 2 and 3 acute esophagitis occurred in respectively 49 and 9% of the patients. There was no grade 4 radiation-induced toxicity. All patients, except for one, completed their thoracic irradiation course without interruption. CONCLUSION Once-a-day hypofractionated radiation with concurrent chemotherapy followed by prophylactic cranial irradiation is a practical regimen. Based on our experience and the published literature, it appears to be similarly effective as regimens using twice-daily fractionation in 3weeks, or once-daily in 6 to 7weeks with higher radiotherapy doses. Further prospective comparisons of hypofractionation with the current recommendations are needed.

WE-E-BRE-05: Ensemble of Graphical Models for Predicting Radiation Pneumontis Risk.

PURPOSE We propose a prior knowledge-based approach to construct an interaction graph of biological and dosimetric radiation pneumontis (RP) covariates for the purpose of developing a RP risk classifier. METHODS We recruited 59 NSCLC patients who received curative radiotherapy with minimum 6 month follow-up. 16 RP events was observed (CTCAE grade ≥2). Blood serum was collected from every patient before (pre-RT) and during RT (mid-RT). From each sample the concentration of the following five candidate biomarkers were taken as covariates: alpha-2-macroglobulin (α2M), angiotensin converting enzyme (ACE), transforming growth factor β (TGF-β), interleukin-6 (IL-6), and osteopontin (OPN). Dose-volumetric parameters were also included as covariates. The number of biological and dosimetric covariates was reduced by a variable selection scheme implemented by L1-regularized logistic regression (LASSO). Posterior probability distribution of interaction graphs between the selected variables was estimated from the data under the literature-based prior knowledge to weight more heavily the graphs that contain the expected associations. A graph ensemble was formed by averaging the most probable graphs weighted by their posterior, creating a Bayesian Network (BN)-based RP risk classifier. RESULTS The LASSO selected the following 7 RP covariates: (1) pre-RT concentration level of α2M, (2) α2M level mid- RT/pre-RT, (3) pre-RT IL6 level, (4) IL6 level mid-RT/pre-RT, (5) ACE mid-RT/pre-RT, (6) PTV volume, and (7) mean lung dose (MLD). The ensemble BN model achieved the maximum sensitivity/specificity of 81%/84% and outperformed univariate dosimetric predictors as shown by larger AUC values (0.78∼0.81) compared with MLD (0.61), V20 (0.65) and V30 (0.70). The ensembles obtained by incorporating the prior knowledge improved classification performance for the ensemble size 5∼50. CONCLUSION We demonstrated a probabilistic ensemble method to detect robust associations between RP covariates and its potential to improve RP prediction accuracy. Our Bayesian approach to incorporate prior knowledge can enhance efficiency in searching of such associations from data. The authors acknowledge partial support by: 1) CREATE Medical Physics Research Training Network grant of the Natural Sciences and Engineering Research Council (Grant number: 432290) and 2) The Terry Fox Foundation Strategic Training Initiative for Excellence in Radiation Research for the 21st Century (EIRR21).