Consolidative mediastinal irradiation of malignant lymphoma using active scanning proton beams: clinical outcome and dosimetric comparison.

PURPOSE: Current research approaches in lymphoma focus on reduction of therapy-associated long-term side effects. Especially in mediastinal lymphoma, proton beam radiotherapy (PT) may be a promising approach for reducing the dose to organs at risk (OAR). PATIENTS: In total, 20 patients were irradiated with active scanning PT at Heidelberg Ion Beam Therapy Center (HIT) between September 2014 and February 2017. For comparative analysis, additional photon irradiation plans with helical intensity-modulated radiotherapy (IMRT) were calculated and quantitative and qualitative dose evaluations were made for both treatment modalities. Toxicity and survival outcomes were evaluated. RESULTS: Clinical target volume coverage was comparable in both treatment modalities and did not significantly differ between IMRT and PT. Nevertheless, PT showed superiority regarding the homogeneity index (HIPT = 1.041 vs. HIIMRT = 1.075, p < 0.001). For all OAR, PT showed significantly higher dose reductions compared with IMRT. In particular, the dose to the heart was reduced in PT (absolute dose reduction of Dmean of 3.3 Gy [all patients] and 4.2 Gy [patients with pericardial involvement]). Likewise, the subgroup analysis of female patients, who were expected to receive higher doses to the breast, showed a higher dose reduction in Dmean of 1.2 Gy (right side) and 2.2 Gy (left side). After a median follow-up of 32 months (range 21-48 months), local and distant progression free survival (LPFS and DPFS) were 95.5% and 95.0%, respectively. Radiotherapy was tolerated well with only mild (grade 1-2) radiation-induced acute and chronic side effects. CONCLUSION: A significant reduction in the dose to the surrounding OAR was achieved with PT compared with photon irradiation, without compromising target volume coverage. Dosimetric advantages may have the potential to translate into a reduction of long-term radiation-induced toxicity in young patients with malignant lymphoma of the mediastinum.

Neoadjuvant versus definitive chemoradiotherapy for locally advanced esophageal cancer : Outcomes and patterns of failure.

PURPOSE: Randomized trials examining neoadjuvant chemoradiotherapy followed by surgical resection (nCRT-S) and definitive CRT (dCRT) for esophageal cancer (EC) patients are hampered by use of nonstandard treatment paradigms. Outcomes of nCRT-S versus dCRT in a more common patient population are lacking. We investigated local control and survival, evaluated clinical factors associated with endpoints, and assessed patterns of failure between these cohorts. METHODS: We retrospectively analyzed 130 patients with locally advanced EC receiving either dCRT or nCRT-S at our institution from 2000-2012. Inclusion criteria were curatively treated nonmetastatic EC, Karnofsky performance status ≥70%, and receipt of concomitant CRT. Patients were excluded if receiving <41 Gy neoadjuvantly or <50 Gy definitively. Kaplan-Meier analysis was used to evaluate local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Univariate and multivariate Cox proportional hazards modeling addressed factors associated with outcomes. Patterns of failure were enumerated as local, regional, or distant. RESULTS: Mean follow-up was 34.2 months. The 3­year LR was 10.8% in the nCRT-S group and 21.5% in the dCRT group (p = 0.266). Median PFS were 15.6 and 14.9 months, respectively (p = 0.549). Median OS were 20.6 and 25.9 months, respectively (p = 0.81). On univariate and multivariate analysis, none of the investigated factors was associated with outcomes, although node-positive disease showed a trend for worse OS and PFS. Most common failures in both groups were distant (dCRT 31.2% vs. nCRT-S 21.6%) followed by local in-field recurrences (dCRT 26.9% vs. nCRT-S 10.8%). CONCLUSIONS: In this institutional analysis, no significant differences regarding outcomes and patterns of failure were observed between nCRT-S and dCRT.

Dosimetric comparison of advanced radiotherapy approaches using photon techniques and particle therapy in the postoperative management of thymoma.

BACKGROUND: The purpose of this study was to compare dosimetric differences related to target volume and organs-at-risk (OAR) using 3D-conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), TomoTherapy (Tomo), proton radiotherapy (PRT), and carbon ion radiotherapy (CIRT) as part of postoperative thymoma irradiation. MATERIAL AND METHODS: This single-institutional analysis included 10 consecutive patients treated with adjuvant radiotherapy between December 2013 and September 2016. CT-datasets and respective RT-structures were anonymized and plans for all investigated RT modalities (3DCRT, VMAT, Tomo, PRT, CIRT) were optimized for a total dose of 50 Gy in 25 fractions. Comparisons between target volume and OAR dosimetric parameters were performed using the Wilcoxon rank-sum test. RESULTS: The best target volume coverage (mean PTV V95% for all patients) was observed for Tomo (97.9%), PRT (97.6%), and CIRT (96.6%) followed by VMAT (85.4%) and 3DCRT (74.7%). PRT and CIRT both significantly reduced mean doses to the lungs, breasts, heart, and esophagus, as well as the spinal cord maximum dose compared with photon modalities. Among photon-based techniques, VMAT showed improved OAR sparing over 3DCRT. Tomo was associated with considerable low-dose exposure to the lungs, breasts, and heart. CONCLUSIONS: Particle radiotherapy (PRT, CIRT) showed superior OAR sparing and optimal target volume coverage. The observed dosimetric advantages are expected to reduce toxicity rates. However, their clinical impact must be investigated prospectively.

Elective Node Irradiation With Integrated Boost to the Prostate Using Helical IMRT-Clinical Outcome of the Prospective PLATIN-1 Trial.

Introduction: This prospective, non-randomized phase II trial aimed to investigate the role of additional irradiation of the pelvic nodes for patients with prostate cancer and a high risk for nodal metastases using helical intensity-modulated radiotherapy with daily image guidance (IMRT/IGRT). Methods and materials: Between 2009 and 2012, 40 men with treatment-naïve prostate cancer and a risk of lymph node involvement of more than 20% were enrolled in the PLATIN-1 trial. All patients received definitive, helical IMRT of the pelvic nodes (total dose of 51.0 Gy) with a simultaneous integrated boost (SIB) to the prostate (total dose of 76.5 Gy) in 34 fractions. Antihormonal therapy (AHT) was administered for a minimum of 2 months before radiotherapy continuing for at least 24 months. Results: After a median follow-up of 71 months (range: 5-95 months), pelvic irradiation was associated with a 5-year overall survival (OS) and biochemical progression-free survival (bPFS) of 94.3% and 83.6%, respectively. For our cohort, no grade 4 gastrointestinal (GI) and genitourinary (GU) toxicity was observed. Quality of life (QoL) assessed by EORTC QLQ-C30 questionnaire was comparable to EORTC reference values without significant changes. Conclusion: The current trial demonstrates that elective IMRT/IGRT of the pelvic nodes with SIB to the prostate for patients with a high-risk of lymphatic spread is safe and shows an excellent clinical outcome without compromising the quality of life. The PLATIN-1 trial delivers eminent baseline data for future studies using modern irradiation techniques.

3D-Printed masks as a new approach for immobilization in radiotherapy - a study of positioning accuracy.

We developed a new approach to produce individual immobilization devices for the head based on MRI data and 3D printing technologies. The purpose of this study was to determine positioning accuracy with healthy volunteers. 3D MRI data of the head were acquired for 8 volunteers. In-house developed software processed the image data to generate a surface mesh model of the immobilization mask. After adding an interface for the couch, the fixation setup was materialized using a 3D printer with acrylonitrile butadiene styrene (ABS). Repeated MRI datasets (n=10) were acquired for all volunteers wearing their masks thus simulating a setup for multiple fractions. Using automatic image-to-image registration, displacements of the head were calculated relative to the first dataset (6 degrees of freedom). The production process has been described in detail. The absolute lateral (x), vertical (y) and longitudinal (z) translations ranged between -0.7 and 0.5 mm, -1.8 and 1.4 mm, and -1.6 and 2.4 mm, respectively. The absolute rotations for pitch (x), yaw (y) and roll (z) ranged between -0.9 and 0.8°, -0.5 and 1.1°, and -0.6 and 0.8°, respectively. The mean 3D displacement was 0.9 mm with a standard deviation (SD) of the systematic and random error of 0.2 mm and 0.5 mm, respectively. In conclusion, an almost entirely automated production process of 3D printed immobilization masks for the head derived from MRI data was established. A high level of setup accuracy was demonstrated in a volunteer cohort. Future research will have to focus on workflow optimization and clinical evaluation.

Intensity-modulated versus 3-dimensional conformal radiotherapy in the definitive treatment of esophageal cancer: comparison of outcomes and acute toxicity.

BACKGROUND: Though the vast majority of seminal trials for locally advanced esophageal cancer (EC) utilized three-dimensional conformal radiotherapy (3DCRT), the advanced and highly conformal technology known as intensity-modulated radiotherapy (IMRT) can decrease doses to critical cardiopulmonary organs. To date, there have been no studies comparing both modalities as part of definitive chemoradiation (dCRT) for EC. Herein, we investigated local control and survival and evaluated clinical factors associated with these endpoints between cohorts. METHODS: We retrospectively analyzed 93 patients (3DCRT n = 49, IMRT n = 44) who received dCRT at our institution between 2000 and 2012 with the histologic diagnosis of nonmetastatic EC, a Karnofsky performance status of ≥70, curative treatment intent, and receipt of concomitant CRT. Patients were excluded if receiving <50 Gy. Kaplan-Meier analysis was used to evaluate the endpoints of local relapse rate (LR), progression-free survival (PFS), and overall survival (OS). Cox proportional hazards modeling addressed factors associated with outcomes with univariate and multivariate approaches. Rates of acute toxicities and basic dosimetric parameters were compared between 3DCRT and IMRT patients. RESULTS: Mean follow-up was 34.7 months. The 3-year LR was 28.6% in the 3DCRT group and 22.7% in the IMRT group (p = 0.620). Median PFS were 13.8 and 16.6 months, respectively (p = 0.448). Median OS were 18.4 and 42.0 months, respectively (p = 0.198). On univariate analysis, only cumulative radiation dose was associated with superior LR (hazard ratio (HR) 0.736; 95% confidence interval (CI) 0.635 - 0.916, p = 0.004). Factors clearly affecting survival were not observed. CONCLUSIONS: When comparing 3DCRT- versus IMRT-based dCRT, no survival benefits were observed. However, we found a lower local recurrence rate in the IMRT group potentially owing to dose-escalation. Prospective data are needed to verify the presented results herein.