Description: Publication date: Available online 29 December 2017 Source: Radiotherapy and Oncology Author(s): Pierina Navarria, Federico Pessina, Ciro Franzese, Stefano Tomatis, Matteo Perrino, Luca Cozzi, Matteo Simonelli, Lorenzo Bello, Elena Clerici, Marco Riva, Armando Santoro, Marta Scorsetti Background The current treatment for newly diagnosed glioblastoma consists of surgery followed by conventional radiotherapy (CRT) with concomitant and adjuvant chemotherapy. Hypofractionated radiation therapy (HFRT) has been investigated and it resulted feasible and safe. The aim of this study was to evaluate whether HFRT can be comparable to CRT. Materials and methods The analysis included newly diagnosed glioblastoma patients treated with CRT 60 Gy/30 fractions or HFRT 60 Gy/15 fractions. A propensity score matching analysis (PSM) was performed using a logistic regression that considered age, KPS, extent of surgery, MGMT and IDH status. Results A total of 267 patients were included; before PSM 169 were in CRT-group and 98 in HRFT-group. After 1:1 matching, 82 patients resulted in each group. The median OS time was 17.9 months for the CRT-group and 16.7 months for the HFRT-group; the 1, 2, 3-year OS rates were 75.6%, 32.7%, and 15.5% for the CRT-group, and 75.6%, 33.3%, and 18.9% for the HFRT-group ( p value = 0.8). No statistically significant differences were recorded between the two radiation therapy treatments performed. Conclusions A short course of radiation therapy would seem comparable to CRT in terms of outcome and less burdensome for these poor prognosis patients.

Description: Publication date: Available online 28 December 2017 Source: Radiotherapy and Oncology Author(s): Enid M. Eslick, John Kipritidis, Denis Gradinscak, Mark J. Stevens, Dale L. Bailey, Benjamin Harris, Jeremy T. Booth, Paul J. Keall Background and purpose CT ventilation imaging (CTVI) derived from four dimensional CT (4DCT) has shown only moderate spatial accuracy in humans due to 4DCT image artefacts. Here we assess the accuracy of an improved CTVI using high quality exhale/inhale breath-hold CT (BHCT). Materials and methods Eighteen lung cancer patients underwent exhale/inhale BHCT, 4DCT and Galligas PET ventilation scans in a single imaging session. For each BHCT and 4DCT scan, we performed deformable image registration (DIR) between the inhale and exhale phase images to quantify ventilation using three published metrics: (i) breathing induced lung density change, CTVI DIR - HU (ii) breathing induced volume change CTVI DIR - Jac and (iii) the regional air-tissue product, CTVI HU Spatial accuracy was reported as the voxel-wise Spearman correlation r between CTVI and Galligas PET. Results For BHCT-based CTVIs ( N  = 16), the CTVI DIR - HU , CTVI DIR - Jac and CTVI HU methods yielded mean (range) r values of 0.67 (0.52–0.87), 0.57 (0.18–0.77) and 0.49 (0.14–0.75) respectively. By comparison the 4DCT-based CTVIs ( n  = 14) had values of 0.32 (−0.04 to 0.51), 0.16 (−0.31 to 44) and 0.49 (0.20–0.77) respectively. Conclusions High quality CT imaging is a key requirement for accurate CT ventilation imaging. The use of exhale/inhale BHCT can improve the accuracy of CTVI for human subjects.

Description: Publication date: Available online 26 December 2017 Source: Radiotherapy and Oncology Author(s): Wen-Chi Yang, Jin-Yuan Shih, Chao-Chi Ho, Feng-Ming Hsu

Description: Publication date: Available online 23 December 2017 Source: Radiotherapy and Oncology Author(s): Lorenzo Preda, Davide Stoppa, Maria Rosaria Fiore, Giulia Fontana, Sofia Camisa, Roberto Sacchi, Michele Ghitti, Gisela Viselner, Piero Fossati, Francesca Valvo, Viviana Vitolo, Maria Bonora, Alberto Iannalfi, Barbara Vischioni, Alessandro Vai, Edoardo Mastella, Guido Baroni, Roberto Orecchia Background and purpose To compare RECIST 1.1 with volume modifications in patients with sacral chordoma not suitable for surgery treated with carbon ions radiotherapy (CIRT) alone. To evaluate patients pain before and after CIRT. To detect if baseline Apparent Diffusion Coefficient values (ADC) from Diffusion Weighted sequences could predict response to treatment. Material and methods Patients included had one cycle of CIRT and underwent MRI before and after treatment. For each MRI, lesion maximum diameter and volume were obtained, and ADC values were analyzed within the whole lesion volume. Patients pain was evaluated with Numerical Rating Scale (NRS), considering the upper tumor level at baseline MRIs. Results 39 patients were studied (mean follow-up 18 months). Considering RECIST 1.1 there was not a significant reduction in tumor diameters ( p  = 0.19), instead there was a significant reduction in tumor volume ( p  〈 0.001), with a significant reduction in pain ( p  = 0.021) if the tumors were above vertebrae S2–S3 at baseline MRIs. The assessment of baseline ADC maps demonstrated higher median values and more negative skewness values in progressive disease (PD) patients versus both partial response (PR) and stable disease (SD). Conclusions Lesion volume measurement is more accurate than maximum diameter to better stratify the response of sacral chordoma treated with CIRT. Preliminary results suggest that baseline ADC values could be predictive of response to CIRT.

Description: Publication date: Available online 23 December 2017 Source: Radiotherapy and Oncology Author(s): Lauren Henke, Rojano Kashani, Clifford Robinson, Austen Curcuru, Todd DeWees, Jeffrey Bradley, Olga Green, Jeff Michalski, Sasa Mutic, Parag Parikh, Jeffrey Olsen Purpose/objectives SBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT’s therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies. Materials/methods Twenty patients with oligometastatic or unresectable primary liver ( n  = 10) and non-liver ( n  = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR “anatomy-of-the-day” to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded. Results Online adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (〈6 months) treatment-related toxicities were observed. Discussion SMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT.

Description: Publication date: Available online 22 December 2017 Source: Radiotherapy and Oncology Author(s): Tsung-Ming Chen, Kuan-Chou Lin, Kevin Sheng-Po Yuan, Chia-Lun Chang, Jyh-Ming Chow, Szu-Yuan Wu Background No large-scale, head-to-head, phase III, randomized, controlled trial with an adequate sample size has investigated the effect of concurrent low-dose (LD) or high-dose (HD) cisplatin with radiotherapy on nasopharyngeal cancer (NPC). Thus, we conducted a propensity-score-matched, nationwide, population-based cohort study in Taiwan to investigate the outcomes of LD-concurrent chemoradiotherapy (CCRT) or HD-CCRT with intensity-modulated radiotherapy (IMRT) in patients with advanced NPC. Methods In this study, patients were categorized into 2 groups according to their chemotherapy regimen: HD-CCRT and LD-CCRT groups. Results We enrolled 1968 patients (328 and 1640 in the LD-CCRT and HD-CCRT groups, respectively) who had received CCRT with IMRT. According to both univariate and multivariate Cox regression analyses, a hazard ratio (95% confidence interval) of 0.75 (0.54–1.06, P  = .103) was derived for the HD-CCRT group. Conclusion LD-CCRT or HD-CCRT with IMRT can be a standard treatment that can prolong the survival of patients with advanced NPC.

Description: Publication date: Available online 19 December 2017 Source: Radiotherapy and Oncology Author(s): Mireia Crispin-Ortuzar, Aditya Apte, Milan Grkovski, Jung Hun Oh, Nancy Y. Lee, Heiko Schöder, John L. Humm, Joseph O. Deasy Background and purpose Hypoxia is a known prognostic factor in head and neck cancer. Hypoxia imaging PET radiotracers such as 18 F-FMISO are promising but not widely available. The aim of this study was therefore to design a surrogate for 18 F-FMISO TBR max based on 18 F-FDG PET and contrast-enhanced CT radiomics features, and to study its performance in the context of hypoxia-based patient stratification. Methods 121 lesions from 75 head and neck cancer patients were used in the analysis. Patients received pre-treatment 18 F-FDG and 18 F-FMISO PET/CT scans. 79 lesions were used to train a cross-validated LASSO regression model based on radiomics features, while the remaining 42 were held out as an internal test subset. Results In the training subset, the highest AUC ( 0.873 ± 0.008 ) was obtained from a signature combining CT and 18 F-FDG PET features. The best performance on the unseen test subset was also obtained from the combined signature, with an AUC of 0.833, while the model based on the 90th percentile of 18 F-FDG uptake had a test AUC of 0.756. Conclusion A radiomics signature built from 18 F-FDG PET and contrast-enhanced CT features correlates with 18 F-FMISO TBR max in head and neck cancer patients, providing significantly better performance with respect to models based on 18 F-FDG PET only. Such a biomarker could potentially be useful to personalize head and neck cancer treatment at centers for which dedicated hypoxia imaging PET radiotracers are unavailable.

Description: Publication date: Available online 19 December 2017 Source: Radiotherapy and Oncology Author(s): Ji Zhu, Xinxiang Li, Yunzhu Shen, Yun Guan, Weilie Gu, Peng Lian, Weiqi Sheng, Sanjun Cai, Zhen Zhang Purpose We aimed to identify the maximum tolerated dose (MTD) of weekly irinotecan in combination with capecitabine-based neoadjuvant chemoradiation according to the UGT1A1∗28 genotype in patients with locally advanced rectal cancer. Patients and methods Patients with clinical stage T3-4, N0-2 who were eligible for preoperative chemoradiotherapy were screened for the UGT1A1∗28 genotype. Twenty-six patients with either the ∗1∗1 or ∗1∗28 genotype were eligible for dose escalation of irinotecan, and patients with a ∗28∗28 genotype were excluded. The starting dose of weekly irinotecan was 50 mg/m 2 for the two genotype groups, whereas the dose of capecitabine was fixed at 625 mg/m 2 . Intensity-modulated radiation therapy (IMRT) was applied to the whole pelvis (total dose of 50 Gy in 25 fractions). Results The dose of weekly irinotecan was escalated to 95 mg/m 2 in patients with the ∗1∗1 genotype and to 80 mg/m 2 in those with the ∗1∗28 genotype. Dose-limiting toxicities (DLTs) were observed in 2/2 ∗1∗1 patients at 95 mg/m 2 and 2/3 ∗1∗28 patients at 80 mg/m 2 . No DLT cases were observed among the three ∗1∗1 patients at 80 mg/m 2 , and one DLT case was observed among the six patients with ∗1∗28 at 65 mg/m 2 . Hence, 80 mg/m 2 and 65 mg/m 2 were the MTDs for the two groups. The most common grade 3 to 4 toxicities were neutropenia and diarrhea. Conclusion A higher dose of weekly irinotecan in combination with capecitabine-based CRT is feasible under the guidance of the UGT1A1∗28 genotype. Further clinical trials at these dose levels are warranted.

Description: Publication date: Available online 18 December 2017 Source: Radiotherapy and Oncology Author(s): Jian-Hua Zhu, Jing Wang, Yong-Gui Wang, Meng Li, Xiao-Jing Liu, Chuan-Bin Guo Background and purpose To investigate the feasibility and accuracy of robot-assisted brachytherapy for skull base tumours. Material and methods A custom robot system was tested on both phantom and cadaveric specimen. Cone beam CT (CBCT) images were transferred to the graphical user interface (GUI) for planning trajectories and the data were sent to the robot control unit. Following registration, the puncture needle was inserted into the target by the robot under navigation guidance, and seeds were implanted. Placement error was instantly displayed on the GUI; the result was verified after postoperative image scanning. Results A total of 150 seeds (100 for phantom experiments, 50 for cadaveric studies) were deposited by the robot system. In phantom experiments the mean placement error was 0.57 ± 0.21 mm (measured by the navigation system) vs. 1.41 ± 0.38 mm (measured by image fusion) ( p  〈 0.001); in cadaveric studies the corresponding figures were 0.60 ± 0.30 mm vs. 2.48 ± 0.32 mm ( p  〈 0.001). There was no significant difference for comparison of accuracy test in phantom experiments ( p  = 0.173) as well as in cadaveric studies ( p  = 0.354). Accuracy was better in the phantom experiment than in cadaveric studies ( p  〈 0.001). Conclusions The performance of robot-assisted skull base brachytherapy is feasible and accurate. Dosimetric coverage will need to be demonstrated in further studies.

Description: Publication date: Available online 19 December 2017 Source: Radiotherapy and Oncology Author(s): Marlene Hechtner, Mechthild Krause, Jochem König, Steffen Appold, Beate Hornemann, Susanne Singer, Michael Baumann Background and purpose To evaluate the quality of life (QoL) of patients with inoperable non-small cell lung cancer treated with conventionally fractionated radiotherapy (CF) vs. continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL). Material and methods The largest monocentric subgroup of the phase III CHARTWEL trial was analyzed up to three years after randomization. QoL was assessed with the European Organization for Research and Treatment of Cancer QoL Core Questionnaire (QLQ-C30) and lung cancer module (QLQ-LC13) and compared using linear mixed models. QoL interrelations with recurrence, metastasis, and death were explored by multi-state modeling. Results 160 patients (98%) provided at least one QoL assessment. Average treatment differences of CF vs. CHARTWEL over three years were −5.4 points (95%CI [−13.6,2.8], p  = 0.19) in global QoL, 11.9 ([2.8,21.0], p  = 0.01) in fatigue, 13.4 ([3.5,23.3], p  = 0.009) in pain, 10.5 ([1.3,19.6], p  = 0.03) in dyspnea, and 5.2 ([−2.7,13.0], p  = 0.19) in dysphagia. At 12 months, the probabilities of being disease-free with good, good or moderate, any global QoL, or alive were 5.1%, 20.3%, 34.2%, 54.4% under CF and 10.4%, 21.0%, 37.5%, 65.3% under CHARTWEL. Conclusions Over three years, QoL was similar or more favorable under CHARTWEL compared to CF. Modeling QoL together with disease states provided additional insight into treatment comparisons.