Description: Publication date: Available online 18 December 2017 Source: Radiotherapy and Oncology Author(s): Frank Verhaegen, Ludwig Dubois, Stefano Gianolini, Mark A. Hill, Christian P. Karger, Kirsten Lauber, Kevin M. Prise, David Sarrut, Daniela Thorwarth, Christian Vanhove, Boris Vojnovic, Robert Weersink, Jan J. Wilkens, Dietmar Georg Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies.

Description: Publication date: Available online 16 December 2017 Source: Radiotherapy and Oncology Author(s): Mai Lykkegaard Schmidt, Lone Hoffmann, Ditte S. Møller, Marianne Marquard Knap, Torben Riis Rasmussen, Birgitte Holst Folkersen, Per Rugaard Poulsen Background and purpose Internal target motion results in geometrical uncertainties in lung cancer radiotherapy. In this study, we determined the intrafraction motion and baseline shifts of mediastinal lymph node (LN) targets between setup imaging and treatment delivery. Material and methods Ten lung cancer patients with 2–4 fiducial markers implanted in LN targets received intensity-modulated radiotherapy with a daily setup cone-beam CT (CBCT) scan used for online soft-tissue match on the primary tumor. At a total of 122 fractions, 5 Hz fluoroscopic kV images were acquired orthogonal to the MV treatment beam during treatment delivery. Offline, the 3D trajectory of the markers was determined from their projected trajectory in the CBCT projections and in the intra-treatment kV images. Baseline shifts and changes in the respiratory motion amplitude between CBCT and treatment delivery were determined from the 3D trajectories. Results Systematic mean LN baseline shifts of 2.2 mm in the cranial direction (standard deviation (SD): 1.8 mm) and 1.0 mm in the posterior direction (SD: 1.2 mm) occurred between CBCT imaging and treatment delivery. The mean motion amplitudes during CBCT and treatment delivery agreed within 0.2 mm in all directions. Conclusions Systematic cranial and posterior intrafraction baseline shifts between CBCT and treatment delivery were observed for mediastinal LN targets. Intrafraction motion amplitudes were stable.

Description: Publication date: Available online 16 December 2017 Source: Radiotherapy and Oncology Author(s): Yuan Zhang, Wen-Fei Li, Xu Liu, Lei Chen, Rui Sun, Ying Sun, Qing Liu, Jun Ma Background and purpose Recent clinical trials and network meta-analysis have suggested that the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) could improve survival in locoregionally advanced NPC (LANPC). We aimed to develop a nomogram to estimate the benefit of IC for individual patients based on the data from a multicenter, randomized, phase III trial (NCT01245959) comparing IC plus CCRT with CCRT alone. Participants and methods This study analyzed all 480 patients enrolled in the original trial. A nomogram was developed to predict 3-year failure-free survival (FFS) with or without IC. Results With a median follow-up of 45 months, the 3-year FFS rates were 80.3% and 72.4% in the IC plus CCRT group and CCRT group, respectively ( P  = 0.034). In multivariate analysis, T category, N category and treatment group were predictive of FFS and were incorporated into the nomogram. Gender was also included due to its clinical importance. This nomogram predicted that the magnitude of benefit from IC could vary significantly. Conclusion We developed a convenient nomogram to estimate the benefit of IC for individual patients with LANPC. This tool can serve as a catalyst of individual treatment discussions and facilitator of informed decision-making.

Description: Publication date: Available online 15 December 2017 Source: Radiotherapy and Oncology Author(s): Stéphane Renaud, Joseph Seitlinger, Pierre Truntzer, Georges Noel, Gilbert Massard

Description: Publication date: Available online 13 December 2017 Source: Radiotherapy and Oncology Author(s): Ruta Zukauskaite, Christian R. Hansen, Cai Grau, Eva Samsøe, Jørgen Johansen, Jørgen B.B. Petersen, Elo Andersen, Carsten Brink, Jens Overgaard, Jesper G. Eriksen Introduction The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins. Materials and methods In total, 1576 patients completing radical primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0–2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point’s position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis. Results After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface ( p  = 0.4) or the dose to LRs ( p  = 0.2) was detected between the groups. A difference in LC was found univariate between the centers ( p  = 0.03), but not in multivariate analysis ( p  = 0.4). Conclusions No relation was found between the recurrences’ distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.

Description: Publication date: Available online 14 December 2017 Source: Radiotherapy and Oncology Author(s): Yutaka Shiraishi, Penny Fang, Cai Xu, Juhee Song, Sunil Krishnan, Eugene J. Koay, Reza J. Mehran, Wayne L. Hofstetter, Mariela Blum-Murphy, Jaffer A. Ajani, Ritsuko Komaki, Bruce Minsky, Radhe Mohan, Charles C. Hsu, Brian P. Hobbs, Steven H. Lin Background and purpose Circulating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). Material and methods EC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. Results Among the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P  〈 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16–0.52; P  〈 0.0001). Conclusion PBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

Description: Publication date: Available online 12 December 2017 Source: Radiotherapy and Oncology Author(s): Jean-Pierre Bissonnette, Mei Ling Yap, Katy Clarke, Andrea Shessel, Jane Higgins, Douglass Vines, Eshetu G. Atenafu, Nathan Becker, Claudia Leavens, Andrea Bezjak, David A. Jaffray, Alexander Sun Background and purpose A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power. Materials and methods Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan–Meier method. Results 32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p  〈 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival. Conclusions Several 4DPET/CT features and rates of change can reach significant association ( p  〈 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging.

Description: Publication date: Available online 12 December 2017 Source: Radiotherapy and Oncology Author(s): Marianne C. Aznar, Frances K. Duane, Sarah C. Darby, Zhe Wang, Carolyn W. Taylor Background and purpose We report a systematic review of lung radiation doses from breast cancer radiotherapy. Methods and materials Studies describing breast cancer radiotherapy regimens published during 2010–2015 and reporting lung dose were included. Doses were compared between different countries, anatomical regions irradiated, techniques and use of breathing adaptation. Results 471 regimens from 32 countries were identified. The average mean ipsilateral lung dose (MLD ipsi ) was 9.0 Gy. MLD ipsi for supine radiotherapy with no breathing adaption was 8.4 Gy for whole breast/chest wall (WB/CW) radiotherapy, 11.2 Gy when the axilla/supraclavicular fossa was irradiated, and 14.0 Gy with the addition of internal mammary chain irradiation; breathing adaptation reduced MLD ipsi by 1 Gy, 2 Gy and 3 Gy respectively ( p  〈 0.005). For WB/CW radiotherapy, MLD ipsi was lowest for tangents in prone (1.2 Gy) or lateral decubitus (0.8 Gy) positions. The highest MLD ipsi was for IMRT in supine position (9.4 Gy). The average mean contralateral lung dose (MLD cont ) for WB/CW radiotherapy was higher for IMRT (3.0 Gy) than for tangents (0.8 Gy). Conclusions Lung doses from breast cancer radiotherapy varied substantially worldwide, even between studies describing similar regimens. Lymph node inclusion and IMRT use increased exposure, while breathing adaptation and prone/lateral decubitus positioning reduced it.

Description: Publication date: Available online 9 December 2017 Source: Radiotherapy and Oncology Author(s): Chai Hong Rim, Chul Yong Kim, Dae Sik Yang, Won Sup Yoon Purpose We performed a meta-analysis and systematic review to compare the radiotherapy (RT) modalities for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT). Materials and methods We searched the PubMed, EMBASE, Medline, and Cochrane library databases. The primary endpoint was the 1-year overall survival (OS), and response rate (RR), local control (LC), 2-year OS, and grade ≥3 toxicity incidence were evaluated as secondary endpoints. Results Thirty-seven studies comprising 2513 patients were included. The pooled 1-year OS rates for the 3-dimensional conformal RT (3DCRT), selective internal RT (SIRT), and stereotactic body RT (SBRT) groups were 43.8% [95% confidence interval (CI): 37.6–50.2], 46.5% (95% CI: 37.7–55.6), and 48.5% (95% CI: 39.4–57.8). These inter-group differences were not statistically significant ( p  = 0.635). The pooled response rates were 51.3% (95% CI: 45.7–57.0), 33.3% (95% CI: 18.0–53.2), and 70.7 (95% CI: 63.7–76.8) for 3DCRT, SIRT, and SBRT groups, respectively; p  = 0.001 and 0.031 for 3DCRT vs. SBRT and SIRT, respectively. The most common grade ≥ 3 complications were lymphocytopenia and bilirubin abnormalities in the 3DCRT and SIRT groups, respectively. Grade ≥ 3 complication was rare in SBRT group. Conclusions OS did not differ among the modalities, although the response rates vary among modalities.

Description: Publication date: Available online 8 December 2017 Source: Radiotherapy and Oncology Author(s): T.P. Hanna, J. Shafiq, G.P. Delaney, S.K. Vinod, S.R. Thompson, M.B. Barton Background To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. Methods Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. Findings 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. Interpretation Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.