Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

BACKGROUND AND PURPOSE: Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. MATERIAL AND METHODS: Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. RESULTS: All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. INTERPRETATION: The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Bone versus soft-tissue setup in proton therapy for patients with oesophageal cancer.

BACKGROUND: The aim of this study was to investigate the effect of patient positioning based on either bone or soft-tissue matching for PT in oesophageal cancer and its impact on plan adaptation. MATERIALS AND METHODS: Two retrospective patient cohorts treated with radiotherapy were included in the study. Cohort A consisted of 26 consecutive patients with a planning 4DCT scan (CT1) and a surveillance 4DCT scan (CT2) at fraction ten. Cohort B consisted of 17 patients selected based on large anatomical changes identified during treatment resulting in a rescan (CT2). Mean dose to the iCTV (sum of the CTVs in all respiratory phases) was 50.4 Gy (RBE) in 28 fractions or 41.4 Gy (RBE) in 23 fractions. A nominal pencil beam scanning plan was created using two posterior beams and robust optimization (5 mm setup, 3.5% range). For each patient, two rigid registrations were made between average (avg) CT1 and CT2: a match on the vertebral column (bone match) and a match on the iCTV (soft-tissue match). Robustness towards setup (5 mm) and range (3.5%) errors was evaluated at CT2. Robustness towards respiration was evaluated by recalculation of the plan on all phases of the CT2 scan. Dose coverage <96% would trigger adaptation. The statistical significance (p-value <0.05) between dose coverage for the two registration methods was assessed using the Wilcoxon signed rank test. RESULTS: All plans fulfilled V95%iCTV>99% for the nominal plan and V95%iCTV>97% for all respiratory phases and robustness scenarios at CT1. In two (8%) and three (18%) patients, V95%iCTV<96% on CT2 for Cohort A and B, respectively when bone match was used. For soft-tissue match, V95%iCTV >96% for all patients. V95%iCTV was significantly higher (p-value = 0.0001) for soft-tissue match than bone match. CONCLUSION: Anatomical changes during the treatment course led to target dose deterioration and a need for plan adaptation when using a bone match.

Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer.

Purpose: This study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities. Materials and Methods: Twenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models. Results: The primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons. Conclusion: Proton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.

Spot-scanning proton therapy for targets with adjacent cardiac implantable electronic devices - Strategies for breast and head & neck cancer.

BACKGROUND AND PURPOSE: Cardiac implantable electronic device (CIED) malfunctions can be induced by secondary neutron dose from spot-scanning proton therapy. A recent in-vitro study investigating secondary neutron dose to CIEDs up to 7 mSv per fraction found that exposure of secondary neutrons in this range was clinically manageable. This study presents decision algorithms proposed by a national expert group for selection of patients with breast and head & neck (H&N) cancer with CIEDs adjacent to target for proton therapy based on the 7 mSv threshold. METHODS AND MATERIALS: Ten patients with breast cancer and five with H&N cancer were included in the study. Five patients with breast cancer received photon therapy with CIED and proton plans were retrospectively created. The remaining patients received proton therapy without CIED and a worst-case position of a virtual CIED was retrospectively delineated. Secondary neutron dose was estimated as ambient dose equivalent H*(10) using Monte Carlo simulations. RESULTS: For patients with breast cancer and with contralateral CIED, the secondary neutron dose to the CIED was below 7 mSv per fraction for CTV < 1500 cm3 in 2 Gy fractions and CTV < 1000 cm3 in 2.67 Gy fractions. The secondary neutron dose to the CIED was below 7 mSv per fraction for all patients with H&N cancer. CONCLUSIONS: Simulations of neutron exposure suggest that proton therapy is feasible for most patients with CIED adjacent to target. This forms the basis for decision algorithms for selection of patients with CIED for proton therapy.

Risk of Cardiac Implantable Electronic Device Malfunctioning During Pencil Beam Proton Scanning in an In Vitro Setting.

PURPOSE: Cardiac implantable electronic devices (CIED) are sensitive to scattered secondary neutrons from proton beam irradiation. This experimental in vitro study investigated risk of CIED errors during pencil beam proton therapy. METHODS AND MATERIALS: We used 62 explanted CIEDs from 4 manufacturers; 49 CIEDs were subjected to a simulated clinical protocol with daily 2 Gy relative biological effectiveness fractions prescribed to the phantom. Devices were located at 3 different lateral distances from the spread-out Bragg peak to investigate the risk of permanent or temporary device errors. Additionally, 13 devices with leads connected were monitored live during consecutive irradiations to investigate the risk of noise, over- or undersense, pace inhibition, and inappropriate shock therapy. RESULTS: We detected 61 reset errors in 1728 fractions, and all except 1 CIED were reprogrammed to normal function. All, except 1 reset, occurred in devices from the same manufacturer. These were successfully reprogrammed to normal function. The 1 remaining CIED was locked in permanent safety mode. Secondary neutron dose, as estimated by Monte Carlo simulations, was found to significantly increase the odds of CIED resets by 55% per mSv. Clinically significant battery depletion was observed in 5 devices. We observed no noise, over- or undersense, pace inhibition, or inappropriate shock therapy during 362 fractions of live monitoring. CONCLUSIONS: Reprogrammable CIED reset was the most commonly observed malfunction during proton therapy, and reset risk depended on secondary neutron exposure. The benefits of proton therapy are expected to outweigh the risk of CIED malfunctioning for most patients.

Treatment planning for proton therapy: what is needed in the next 10 years?

Treatment planning is the process where the prescription of the radiation oncologist is translated into a deliverable treatment. With the complexity of contemporary radiotherapy, treatment planning cannot be performed without a computerized treatment planning system. Proton therapy (PT) enables highly conformal treatment plans with a minimum of dose to tissues outside the target volume, but to obtain the most optimal plan for the treatment, there are a multitude of parameters that need to be addressed. In this review areas of ongoing improvements and research in the field of PT treatment planning are identified and discussed. The main focus is on issues of immediate clinical and practical relevance to the PT community highlighting the needs for the near future but also in a longer perspective. We anticipate that the manual tasks performed by treatment planners in the future will involve a high degree of computational thinking, as many issues can be solved much better by e.g. scripting. More accurate and faster dose calculation algorithms are needed, automation for contouring and planning is required and practical tools to handle the variable biological efficiency in PT is urgently demanded just to mention a few of the expected improvements over the coming 10 years.

Adaptation is mandatory for intensity modulated proton therapy of advanced lung cancer to ensure target coverage.

BACKGROUND AND PURPOSE: Large anatomical changes during radiotherapy are seen for a large proportion of lung cancer patients. We investigate the applicability of a decision support protocol for photon therapy in a proton therapy setting. MATERIAL AND METHODS: Twenty-three consecutive NSCLC patients treated with adaptive photon therapy were retrospectively planned using IMPT. The adaptive protocol was based on geometrical measures of target positioning and large anatomical changes as shown on daily CBCT scans. Two surveillance CT-scans were acquired during the treatment course. The consequences of anatomical changes were evaluated by recalculating the proton plans on the surveillance scans. The CTV receiving 95% of the prescribed dose was analysed. RESULTS: Fourteen (61%) patients needed adaptations when treated with protons, given that 95% of the CTV must be covered by 95% of the dose. In comparison, no patients needed adaptation when treated with photons using this criterion. The adaptive protocol was found to identify patients with large target under-dosage for proton therapy (six patients). Additionally, target under-dosage was observed for eight patients with non-rigid changes up to 15mm in the positioning of the bones. CONCLUSIONS: Proton therapy for loco-regional lung cancer demands daily imaging and therapy adaptation for a high proportion of patients.