Systematic review of stereotactic body radiotherapy in stage III non-small cell lung cancer

Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85-90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20-24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario

Comparative analysis of thermoplastic masks versus vacuum cushions in stereotactic body radiotherapy

Background: To compare thermoplastic masks (TMP) and vacuum cushion system (VCS) to assess differences in interfraction set up accuracy in patients treated with stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to survey radiotherapy technologists to assess their satisfaction with the two systems. Methods: Retrospective study of patients treated with lung SBRT between 2008 to 2012 at our institution. Immobilization was performed for 73 treatment sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients considered ineligible for surgery with a life expectancy ≥6 months and performance status > 1 were included. Target lesion location was verified by cone beam computed tomography (CBCT) prior to each session, with displacements assessed by CBCT simulation prior to each treatment session. Couch shifts were registered prospectively in vertical, longitudinal, and latero-lateral directions to obtain Kernel coordinates (3D representation). Technologists were surveyed to assess their satisfaction with indexing, positioning, and learning curve of the two systems. Setup displacements were obtained in all patients for each treatment plan and for each session. To assess differences between the immobilization systems, a t-test (Welch) was performed. Results: Mean displacements for the TMP and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56 vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in all three treatment sessions. Technologists rated the learning curve, set up, and positioning more highly for TMP versus VCS. Conclusions: Due to the high doses and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up is essential. We found that thermoplastic masks offers better reproducibility with significantly less interfractional set up displacement than vacuum cushions. Moreover, radiotherapy technologists rated the TMP system higher. Taken together, these two findings suggest that TMP may be preferable to VCS. However, more research is needed to determine both inter- and intrafraction error to identify the optimal immobilisation system for use in lung SBRT

Comparative analysis of thermoplastic masks versus vacuum cushions in stereotactic body radiotherapy

Background: To compare thermoplastic masks (TMP) and vacuum cushion system (VCS) to assess differences in interfraction set up accuracy in patients treated with stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to survey radiotherapy technologists to assess their satisfaction with the two systems. Methods: Retrospective study of patients treated with lung SBRT between 2008 to 2012 at our institution. Immobilization was performed for 73 treatment sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients considered ineligible for surgery with a life expectancy ≥6 months and performance status > 1 were included. Target lesion location was verified by cone beam computed tomography (CBCT) prior to each session, with displacements assessed by CBCT simulation prior to each treatment session. Couch shifts were registered prospectively in vertical, longitudinal, and latero-lateral directions to obtain Kernel coordinates (3D representation). Technologists were surveyed to assess their satisfaction with indexing, positioning, and learning curve of the two systems. Setup displacements were obtained in all patients for each treatment plan and for each session. To assess differences between the immobilization systems, a t-test (Welch) was performed. Results: Mean displacements for the TMP and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56 vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in all three treatment sessions. Technologists rated the learning curve, set up, and positioning more highly for TMP versus VCS. Conclusions: Due to the high doses and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up is essential. We found that thermoplastic masks offers better reproducibility with significantly less interfractional set up displacement than vacuum cushions. Moreover, radiotherapy technologists rated the TMP system higher. Taken together, these two findings suggest that TMP may be preferable to VCS. However, more research is needed to determine both inter- and intrafraction error to identify the optimal immobilisation system for use in lung SBRT

Immune mechanisms mediating abscopal effects in radioimmunotherapy

Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immuno- therapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGFβ), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radio- therapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGFβ, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeu- tic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient