A new approach to combined proton-photon therapy for metastatic cancer patients.

Objective:Proton therapy is a limited resource and is typically not available to metastatic cancer patients. Combined proton-photon therapy (CPPT), where most fractions are delivered with photons and only few with protons, represents an approach to distribute proton resources over a larger patient population. In this study, we consider stereotactic radiotherapy of multiple brain or liver metastases, and develop an approach to optimally take advantage of a single proton fraction by optimizing the proton and photon dose contributions to each individual metastasis. Approach:CPPT treatments must balance two competing goals: 1) deliver a larger dose in the proton fractions to reduce integral dose, and 2) fractionate the dose in the normal tissue between metastases, which requires using the photon fractions. Such CPPT treatments are generated by simultaneously optimizing IMPT and IMRT plans based on their cumulative biologically effective dose (BEDα/ß). The dose contributions of the proton and photon fractions to each individual metastasis are handled as additional optimization variables in the optimization problem. The method is demonstrated for two patients with 29 and 30 brain metastases, and two patients with 4 and 3 liver metastases. Main results:Optimized CPPT plans increase the proton dose contribution to most of the metastases, while using photons to fractionate the dose around metastases which are large or located close to critical structures. On average, the optimized CPPT plans reduce the mean brain BED2by 29% and the mean liver BED4by 42% compared to IMRT-only plans. Thereby, the CPPT plans approach the dosimetric quality of IMPT-only plans, for which the mean brain BED2and mean liver BED4are reduced by 28% and 58%, respectively, compared to IMRT-only plans. Significance:CPPT with optimized proton and photon dose contributions to individual metastases may benefit selected metastatic cancer patients without tying up major proton resources. .

Combined proton-photon therapy for non-small cell lung cancer.

PURPOSE: Advanced non-small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton-photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. MATERIALS AND METHODS: A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning computed tomography scan (CT) and multiple repeated CTs from three different days and for different breath-holds on each day. Treatment plans for combined proton-photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non-adapted) as well as on each daily CT respectively (adapted). The impact of inter-fractional changes and/or breath-hold variability was then assessed on the repeat breath-hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. RESULTS: Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT-only plans. Inter-fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath-holds into account. CONCLUSIONS: Optimally combined proton-photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients.

Combined proton-photon treatment for breast cancer.

Objective.Proton therapy remains a limited resource due to gantry size and its cost. Recently, a new design without a gantry has been suggested. It may enable combined proton-photon therapy (CPPT) in conventional bunkers and allow the widespread use of protons. In this work, we explore this concept for breast cancer.Methods.The treatment room consists of a LINAC for intensity modulated radiation therapy (IMRT), a fixed proton beamline (FBL) with beam scanning and a motorized couch for treatments in lying positions with accurate patient setup. Thereby, proton and photon beams are delivered in the same fraction. Treatment planning is performed by simultaneously optimizing IMRT and IMPT plans based on the cumulative dose. The concept is investigated for three breast cancers where the goal is to minimize mean dose to the heart and lung while delivering 40.05 Gy in 15 fractions to the PTV with a SIB of 48 Gy to the tumor bed. The probabilistic approach is applied to mitigate the sensitivity to range uncertainties.Results. CPPT is particularly advantageous for irradiating concave target volumes that wrap around a curved chest wall. There, protons may deliver dose to the peripheral and medial parts of the target volume including lymph nodes. Thereby, the mean dose in normal tissues is reduced compared to single-modality IMRT. However, tangential photon beams may treat parts of the target volume near the interface to the lung. To ensure target coverage for range undershoot in an IMPT plan, proton beams have to deliberately overshoot into the lung tissue-a problem that can be mitigated via the photon component which ensures plan conformity and robustness.Conclusion.CPPT using an FBL may represent a realistic approach to make protons available to more patients. In addition, CPPT may generally improve treatment quality compared to both single-modality proton and photon treatments.

Cochlea sparing optimized radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: Definitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing. MATERIALS AND METHODS: Treatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2-2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant. RESULTS: The re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52-91.1%) for the original plans, compared to 4.60% (range 1.46-90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0-99.0%) to 0.00% (range 0-98.5%, p < 0.001). CONCLUSIONS: A significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.