Photon Therapy Research Articles

Experimental Validation of an Analytical Program and a Monte Carlo Simulation for the Computation of the Far Out-of-Field Dose in External Beam Photon Therapy Applied to Pediatric Patients.

BackgroundThe out-of-the-field absorbed dose affects the probability of primary second radiation-induced cancers. This is particularly relevant in the case of pediatric treatments. There are currently no methods employed in the clinical routine for the computation of dose distributions from stray radiation in radiotherapy. To overcome this limitation in the framework of conventional teletherapy with photon beams, two computational tools have been developed—one based on an analytical approach and another depending on a fast Monte Carlo algorithm. The purpose of this work is to evaluate the accuracy of these approaches by comparison with experimental data obtained from anthropomorphic phantom irradiations.Materials and MethodsAn anthropomorphic phantom representing a 5-year-old child (ATOM, CIRS) was irradiated considering a brain tumor using a Varian TrueBeam linac. Two treatments for the same planned target volume (PTV) were considered, namely, intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). In all cases, the irradiation was conducted with a 6-MV energy beam using the flattening filter for a prescribed dose of 3.6 Gy to the PTV. The phantom had natLiF : Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs) in its 180 holes. The uncertainty of the experimental data was around 20%, which was mostly attributed to the MCP-N energy dependence. To calculate the out-of-field dose, an analytical algorithm was implemented to be run from a Varian Eclipse TPS. This algorithm considers that all anatomical structures are filled with water, with the exception of the lungs which are made of air. The fast Monte Carlo code dose planning method was also used for computing the out-of-field dose. It was executed from the dose verification system PRIMO using a phase-space file containing 3x109 histories, reaching an average standard statistical uncertainty of less than 0.2% (coverage factor k = 1 ) on all voxels scoring more than 50% of the maximum dose. The standard statistical uncertainty of out-of-field voxels in the Monte Carlo simulation did not exceed 5%. For the Monte Carlo simulation the actual chemical composition of the materials used in ATOM, as provided by the manufacturer, was employed.ResultsIn the out-of-the-field region, the absorbed dose was on average four orders of magnitude lower than the dose at the PTV. For the two modalities employed, the discrepancy between the central values of the TLDs located in the out-of-the-field region and the corresponding positions in the analytic model were in general less than 40%. The discrepancy in the lung doses was more pronounced for IMRT. The same comparison between the experimental and the Monte Carlo data yielded differences which are, in general, smaller than 20%. It was observed that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT.ConclusionsThe proposed computational methods for the routine calculation of the out-of-the-field dose produce results that are similar, in most cases, with the experimental data. It has been experimentally found that the VMAT irradiation produces the smallest out-of-the-field dose when compared to IMRT for a given PTV.

Redefine the Role of Proton Beam Therapy for the Locally-Advanced Non-Small Cell Lung Cancer Assisting the Reduction of Acute Hematologic Toxicity.

PurposeTo investigate the potential clinical benefit of utilizing intensity-modulated proton therapy (IMPT) to reduce acute hematologic toxicity for locally advanced non-small cell lung cancer (LA-NSCLC) patients and explore the feasibility of a model-based patient selection approach via the normal tissue complication probability (NTCP).MethodsTwenty patients with LA-NSCLC were retrospectively selected. Volumetric modulated arc photon therapy (VMAT) and IMPT plans were generated with a prescription dose of 60 Gy in 30 fractions. A wide range of cases with varied tumor size, location, stations of metastatic lymph nodes were selected to represent the general cancer group. Contouring and treatment planning followed RTOG-1308 protocol. Doses to thoracic vertebral bodies (TVB) and other organ at risks were compared. Risk of grade ≥ 3 acute hematologic toxicity (HT3+) were calculated based on the NTCP model, and patients with a reduction on NTCP of HT3+ from VMAT to IMPT (△NTCP_HT3+) ≥ 10% were considered to ‘significantly benefit from proton therapy.’ResultsCompared to VMAT, IMPT significantly reduced the dose to the TVB, the lung, the heart, the esophagus and the spinal cord. Tumor distance to TVB was significantly associated with △NTCP _HT3+ ≥ 10%. For the patients with tumor distance ≤ 0.7 cm to TVB, the absolute reduction of dose (mean, V30 and V40) to TVB was significantly lower than that in patients with tumor distance > 0.7 cm.ConclusionIMPT decreased the probability of HT3+ compared to VMAT by reducing the dose to the TVB in LA-NSCLC patients. Patients with tumor distance to TVB less than 0.7 cm are likely to benefit most from proton over photon therapy.

Possibilities and challenges when using synthetic computed tomography in an adaptive carbon-ion treatment workflow

Background and purposeAnatomical surveillance during ion-beam therapy is the basis for an effective tumor treatment and optimal organ at risk (OAR) sparing. Synthetic computed tomography (sCT) based on magnetic resonance imaging (MRI) can replace the X-ray based planning CT (X-rayCT) in photon radiotherapy and improve the workflow efficiency without additional imaging dose. The extension to carbon-ion radiotherapy is highly challenging; complex patient positioning, unique anatomical situations, distinct horizontal and vertical beam incidence directions, and limited training data are only few problems. This study gives insight into the possibilities and challenges of using sCTs in carbon-ion therapy. Materials and methodsFor head and neck patients immobilised with thermoplastic masks 30 clinically applied actively scanned carbon-ion treatment plans on 15 CTs comprising 60 beams were analyzed. Those treatment plans were re-calculated on MRI based sCTs which were created employing a 3D U-Net. Dose differences and carbon-ion spot displacements between sCT and X-rayCT were evaluated on a patient specific basis. ResultsSpot displacement analysis showed a peak displacement by 0.2 cm caused by the immobilisation mask not measurable with the MRI. 95.7% of all spot displacements were located within 1 cm. For the clinical target volume (CTV) the median D50% agreed within −0.2% (−1.3 to 1.4%), while the median D0.01cc differed up to 4.2% (−1.3 to 25.3%) comparing the dose distribution on the X-rayCT and the sCT. OAR deviations depended strongly on the position and the dose gradient. For three patients no deterioration of the OAR parameters was observed. Other patients showed large deteriorations, e.g. for one patient D2% of the chiasm differed by 28.1%. ConclusionThe usage of sCTs opens several new questions, concluding that we are not ready yet for an MR-only workflow in carbon-ion therapy, as envisaged in photon therapy. Although omitting the X-rayCT seems unfavourable in the case of carbon-ion therapy, an sCT could be advantageous for monitoring, re-planning, and adaptation.

Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO2, TiO2, WO3 and HfO2), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO2 nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO2, leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy.

Brainstem Toxicity in Pediatric Patients Treated with Protons Using a Single-vault Synchrocyclotron System

PurposeCranial radiation therapy remains an integral component of curative treatment for pediatric patients with brain tumors. Proton beam radiation therapy (PBT) can limit collateral radiation dose to surrounding normal tissue, thus reducing off-target exposure while maintaining appropriate tumor coverage. While PBT offers significant advantages over photon therapy for pediatric patients with intracranial malignancies, cases of brainstem necrosis after PBT have raised concerns that PBT may pose an increased risk of necrosis over photon therapy. We investigated the incidence of brainstem necrosis at our institution in children treated with PBT for intracranial malignancies.Patients and MethodsPatients with pediatric brain tumor treated with passively scattered PBT, using a gantry-mounted, synchrocyclotron single-vault system between 2013 and 2018, were retrospectively reviewed. Inclusion criteria included patients 21 years of age or younger who received a minimum 0.1 cm3 maximum brainstem dose of 50 Gray relative biological effectiveness (GyRBE). Patients were assessed for “central nervous system necrosis” in the brainstem per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Cancer Institute, Bethesda, Maryland) criteria.ResultsFifty-eight patients were included for analysis. The median age was 10.3 years. Twenty-one (36.2%) patients received craniospinal irradiation. Thirty-four (58.6%) patients received chemotherapy. The median prescription radiation dose was 54 GyRBE. Regarding published dosimetric constraints used at 3 separate proton centers, the goal brainstem D50% <52 GyRBE was exceeded in 23 (40%) patients, but the brainstem Dmax <58 GyRBE was not exceeded in any patients. No patient experienced grade ≥2 brainstem injury. One patient demonstrated radiographic changes consistent with grade 1 toxicity. This patient had myeloablative chemotherapy with tandem stem cell rescue before PBT.ConclusionOur data demonstrates a low risk of any brainstem injury in children treated with passively scattered PBT using a single-vault synchrocyclotron.

Determining Out-of-Field Doses and Second Cancer Risk From Proton Therapy in Young Patients-An Overview.

Proton therapy has the potential to provide survival and tumor control outcomes comparable and frequently superior to photon therapy. This has led to a significant concern in the medical physics community on the risk for the induction of second cancers in all patients and especially in younger patients, as they are considered more radiosensitive than adults and have an even longer expected lifetime after treatment. Thus, our purpose is to present an overview of the research carried out on the evaluation of out-of-field doses linked to second cancer induction and the prediction of this risk. Most investigations consisted of Monte Carlo simulations in passive beam facilities for clinical scenarios. These works established that equivalent doses in organs could be up to 200 mSv or 900 mSv for a brain or a craniospinal treatment, respectively. The major contribution to this dose comes from the secondary neutrons produced in the beam line elements. Few works focused on scanned-beam facilities, but available data show that, for these facilities, equivalent doses could be between 2 and 50 times lower. Patient age is a relevant factor in the dose level, especially for younger patients (by means of the size of the body) and, in addition, in the predicted risk by models (due to the age dependence of the radiosensitivity). For risks, the sex of the patient also plays an important role, as female patients show higher sensitivity to radiation. Thus, predicted risks of craniospinal irradiation can range from 8% for a 15-year-old male patient to 58% for a 2-year-old female patient, using a risk model from a radiological protection field. These values must be taken with caution due to uncertainties in risk models, and then dosimetric evaluation of stray radiation becomes mandatory in order to complement epidemiological studies and be able to model appropriate dose–response functions for this dose range. In this sense, analytical models represent a useful tool and some models have been implemented to be used for young patients. Research carried out so far confirmed that proton beam therapy reduces the out-of-field doses and second cancer risk. However, further investigations may be required in scanned-beam delivery systems.

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

PurposeAdvanced 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 methodsA 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.ResultsCombined 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.ConclusionsOptimally 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.

A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy – including photon and proton therapy – for the treatment of radioresistant tumors: the ETOILE trial

BackgroundSome cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy.MethodsThe ETOILE study is a multicenter prospective randomized phase III trial comparing carbon ion therapy to either advanced photon or proton radiotherapy for inoperable or macroscopically incompletely resected (R2) radioresistant cancers including sarcomas and adenoid cystic carcinomas.In the experimental arm, carbon ion therapy will be performed at the National Center for Oncological Hadrontherapy (CNAO) in Pavia, Italy. In the control arm, photon or proton radiotherapy will be carried out in referent centers in France.The primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival and local control, toxicity profile, and quality of life. In addition, a prospective health-economic study and a radiobiological analysis will be conducted.To demonstrate an absolute improvement in the 5-year PFS rate of 20% in favor of carbon ion therapy, 250 patients have to be included in the study.DiscussionSo far, no clinical study of phase III has demonstrated the superiority of carbon ion therapy compared to conventional radiotherapy, including proton therapy, for the treatment of radioresistant tumors.Trial registrationClinicalTrials.gov identifier: NCT02838602. Date of registration: July 20, 2016. The posted information will be updated as needed to reflect protocol amendments and study progress.

Feasibility and Safety of Intraoperative Radiotherapy with Low Energy X-ray Photon Therapy for Recurrent Gynecological Cancer: A Case Series.

Objectives: To evaluate the feasibility and safety of low energy X-ray photon intraoperative radiotherapy (IORT) as an adjuvant therapy for recurrent gynecological cancer.Methods: Medical records of all recurrence gynecological cancer patients who underwent IORT were reviewed. Results: Between January 2018 and December 2021, five women (including cervical cancer (n = 2), endometrial cancer (n = 2), and uterine leiomyosarcoma (n = 1)), who underwent IORT and surgical resection for recurrent gynecologic cancer were reviewed. A median dose of 15.62 Gy (range, 12 to 20 Gy) was used for IORT. Repeated IORT and surgical resection was performed in two women. Three women experienced local recurrence, and three women died during follow-up. The 1-year local control rate was 60%. The 2-year overall survival rate was 30%. There was no Clavien–Dindo classification grade III–V complication. Conclusion: IORT using low energy X-ray photon therapy seems to be feasible and safe as an adjuvant therapy in women who underwent salvage surgery for recurrent gynecologic cancer. However, large-scale prospective studies are needed to confirm our findings and evaluate its efficacy.

Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer: Results from eight European centres

PurposeTo compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer. Materials and methodsAll centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions. Target volume receiving 95% of prescribed dose (V95%iCTVtotal) should be >99%. Robustness towards setup, range, and respiration was evaluated. The plans were recalculated on a surveillance 4DCT (sCT) acquired at fraction ten and robustness evaluation was performed to evaluate the effect of respiration and inter-fractional anatomical changes. ResultsAll PT and XT plans complied with V95%iCTVtotal >99% for the nominal plan and V95%iCTVtotal >97% for all respiratory and robustness scenarios. Lung and heart dose varied considerably between centres for both modalities. The difference in mean lung dose and mean heart dose between each pair of XT and PT plans was in median [range] 4.8 Gy [1.1;7.6] and 8.4 Gy [1.9;24.5], respectively. Patients B and C showed large inter-fractional anatomical changes on sCT. For patient B, the minimum V95%iCTVtotal in the worst-case robustness scenario was 45% and 94% for XT and PT, respectively. For patient C, the minimum V95%iCTVtotal was 57% and 72% for XT and PT, respectively. Patient A and D showed minor inter-fractional changes and the minimum V95%iCTVtotal was >85%. ConclusionLarge variability in dose to the lungs and heart was observed for both modalities. Inter-fractional anatomical changes led to larger target dose deterioration for XT than PT plans.

OC-0091 Brainstem toxicity after proton or photon therapy in children with localized intracranial ependymoma

OC-0091 Brainstem toxicity after proton or photon therapy in children with localized intracranial ependymoma

A Review of Proton Therapy - Current Status and Future Directions.

The original rationale for proton therapy was the highly conformal depth-dose distributions that protons are able to produce, compared to photons, which allow greater sparing of normal tissues and escalation of tumor doses, thus potentially improving outcomes. Additionally, recent research, which is still ongoing, has revealed previously unrecognized advantages of proton therapy. For instance, the higher relative biological effectiveness (RBE) near the end of the proton range can be exploited to increase the difference in biologically effective dose in tumors vs. normal tissues. Moreover, the smaller "dose bath", i.e., the compact nature of proton dose distributions has been found to reduce exposure of circulating lymphocytes and the immune organs at risk. There is emerging evidence that the resulting sparing of the immune system has the potential to improve outcomes. Protons, accelerated to therapeutic energies ranging from 70 to 250 MeV, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initially narrow beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanically for "passively-scattered proton therapy' (PSPT); or using magnetic scanning of thin "beamlets" of protons of a sequence of initial energies. The latter technique is used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton therapy modality, which is rapidly supplanting PSPT. Treatment planning and plan evaluation for proton therapy require different techniques compared to photon therapy due, in part, to the greater vulnerability of protons to uncertainties, especially those introduced by inter- and intra-fractional variations in anatomy. In addition to anatomic variations, other sources of uncertainty in the treatments delivered include the approximations and assumptions of models used for computing dose distributions and the current practice of proton therapy of assuming the RBE to have a constant value of 1.1. In reality, the RBE is variable and a complex function of proton energy, dose per fraction, tissue and cell type, end point, etc. Despite the high theoretical potential of proton therapy, the clinical evidence supporting its broad use has so far been mixed. The uncertainties and approximations mentioned above, and the technological limitations of proton therapy may have diminished its true clinical potential. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Promising results have been and continue to be reported for many other types of cancers as well; however, they are based on small studies. At the same time, there have been reports of unforeseen toxicities. Furthermore, because of the high cost of establishing and operating proton therapy centers, questions are often raised about the value of proton therapy. The general consensus is that there is a need for continued improvement in the state of the art of proton therapy. There is also a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to generate high level evidence of the advantages of protons. Fortuitously, such efforts are taking currently place. Ongoing research is aimed at better understanding the biological and immunomodulatory effects of proton therapy and the consequences of the physical uncertainties on proton therapy and reducing them through image-guidance and adaptive radiotherapy. Since residual uncertainties will remain despite our best efforts, in order to increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented and continue to be perfected. Such research and continuing technological advancements in planning and delivery methods are likely to help demonstrate the superiority of protons.

A Dosimetric Comparison of Lattice, Brass, and Proton Grid Therapy Treatment Plans

PurposeOur purpose was to dosimetrically compare volumetric modulated arc therapy (VMAT) lattice radiation therapy (LRT), brass, and proton grid therapy planning techniques and suggest potential clinical applications for each. Methods and MaterialsFour plans delivering 20 Gy in 1 fraction were created for each of 22 patients. Brass and proton grid plans used a single static field and the same beam angle. Proton grid plans used the same beam size and spacing as the brass block. Two VMAT LRT plans were generated for each patient: one with 1-cm diameter lattice points spaced 2-cm center-to-center (2-cm VMAT) and another with 1.5-cm diameter lattice points spaced 3-cm center-to-center (3- cm VMAT). Maximum, minimum, mean, and equivalent uniform dose and the dose to 90%, 50%, 20%, 10%, and 5% (D90%[%], D50%[%], etc) of gross tumor volume (GTV) were reported. D10%/D90% characterized dose heterogeneity. Normal tissue dose was generalized by the maximum dose and volume in cubic centimeters of tissue outside the GTV receiving 30% and 50% of prescription (body-GTV V30%[cm3]; body-GTV V50%[cm3]). ResultsVMAT LRT plans delivered the highest maximum GTV doses while brass and proton plans delivered higher D5%(%), D10%(%), and D20%(%) values. D50%(%), D90%(%), and minimum dose varied little between plan types. Proton and brass plans had the highest dose heterogeneity. Two-centimeter VMAT and brass grid plans had the highest mean GTV doses. Two-centimeter VMAT plans had the highest equivalent uniform dose, followed by 3-cm VMAT, brass, and proton plans. VMAT LRT plans exhibited the lowest normal tissue maximum and body GTV V30%(cm3) and body GTV V50%(cm3) values. ConclusionsAn in-depth comparison of target and normal tissue dosimetric parameters for common photon and proton grid therapy planning techniques was made. Strengths of each plan type were noted leading to general recommendations on usage.

Outcome after Radiotherapy for Vestibular Schwannomas (VS)-Differences in Tumor Control, Symptoms and Quality of Life after Radiotherapy with Photon versus Proton Therapy.

Simple SummaryThe standard of care for radiotherapy of symptomatic or progressive vestibular schwannomas (VS) is photon beam single-dose radiosurgery (applying 1 × 12 Gy) or (hypo)fractionated radiotherapy (applying 3 × 6 Gy up to 32 × 1.8 Gy). Only few centers also enable irradiation with protons. Proton therapy offers unique physical properties whereby healthy tissue around the tumor can be protected although a very high dose is applied to the target lesion. In patients with benign brain tumors such as vestibular schwannomas reduction of treatment-related side effects is very important. Few data comparing photon vs. proton beam radiotherapy for patients with VS are available. Thus, a detailed evaluation of differences in tumor control, symptoms and quality of life in patients with VS after photon beam vs. proton beam radiotherapy is needed.Background: To evaluate differences in local tumor control (LC), symptoms and quality of life (QOL) of 261 patients with VS after stereotactic radiosurgery/hypofractionated stereotactic radiotherapy (SRS/HFSRT) vs. fractionated radiotherapy (FRT) vs. fractionated proton therapy (FPT) were studied. Methods: For SRS/HFSRT (n = 149), the median fraction dose applied was 12 Gy. For FRT (n = 87) and FPT (n = 25), the median cumulative doses applied were 57.6 Gy and 54 Gy (RBE), respectively. FRT and FPT used single median doses of 1.8 Gy/Gy (RBE). Median follow-up was 38 months. We investigated dosimetry for organs at risk and analyzed toxicity and QOL by sending out a questionnaire. Results: LC was 99.5% at 12 months after RT with no statistical difference between treatment groups (p = 0.19). LC was significantly lower in NF2 patients (p = 0.004) and in patients with higher tumor extension grade (p = 0.039). The hearing preservation rate was 97% at 12 months after RT with no statistical difference between treatment groups (p = 0.31). Facial and trigeminal nerve affection after RT occurred as mild symptoms with highest toxicity rate in FPT patients. Conclusion: SRS/HFSRT, FRT and FPT for VS show similar overall clinical and functional outcomes. Cranial nerve impairment rates vary, potentially due to selection bias with larger VS in the FRT and FPT group.

Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

113P Proton-therapy and concurrent chemotherapy in stage III NSCLC: Effects on durvalumab eligibility and safety profile

Concurrent chemo-radiotherapy (CCRT) followed by adjuvant Durvalumab (D) represents standard of care for patients (pts) with unresectable stage III NSCLC. The RT can be delivered with both protons and photons. An earlier start of adjuvant D after CCRT may lead to better outcome. Little is known about the effects of protons on adjuvant D efficacy and safety. We assessed whether intensity modulated proton therapy (IMPT), compared to intensity modulated photon therapy (IMRT) affects eligibility for D (primary endpoint) and immune related adverse events (IRAEs) (secondary endpoint) in pts with stage III NSCLC treated with CCRT and adjuvant D. Retrospective data completion and analysis of a 2-center prospectively collected series of pts with stage III NSCLC, receiving CCRT between 06.16 and 02.21, staged with FDG-PET and brain imaging. Main exclusion criteria were previous cancer diagnosis-within 2 years- and thoracic RT. A list of 226 pts was collected, 67 pts received adjuvant D and were included (IMPT: n=28, IMRT: n=39). Median age was 66 years, 52% were male, 33% had a squamous NSCLC and 42% had a WHO Performance Status (PS) of 0 before CCRT. All pts received 60-64 Gy of RT. Programmed death-ligand 1 (PDL-1) level was available for 76% of pts and 39% had a PDL-1 ≥ 50% (no significant differences between IMPT and IMRT). At day 21 after CCRT, 93% (IMPT) vs 72% (IMRT) treated pts had a PS≤1 (Odds Ratio 0.8, 95% CI: 0.67-0.95, p=0.03). The median time from the end of CCRT and start of D was 32 vs 38 days respectively (Not Significant (NS)). IRAEs of any grade were reported in 21% versus 31% of pts treated with IMPT versus IMRT, respectively (NS). Hypothyroidism accounted for 44% of IRAEs. Any grade (grade 3) pneumonitis during D was reported in 25% (7%) of IMPT and 23% (5%) of IMRT (NS). Median follow-up was 19.5 months and 9.5 months for IMRT and IMPT, respectively. 90% of pts were still alive and 73% were disease free. IMPT vs IMRT treated pts received a significantly lower RT dose to bone marrow, heart and lungs. PS at day 21 after CCRT was better in IMPT treated pts, potentially increasing eligibility for adjuvant D. The lower RT dose delivered with IMPT might explain our findings. IMPT appears to be as safe as IMRT regarding IRAEs during D.

Comparison of 3D Conformal Proton Therapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Photon Therapy for Retroperitoneal Sarcoma.

Background External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). Intensity-modulated radiation therapy has been shown to improve target coverage and reduce doses to OAR. Objectives To compare target coverage and dose to OAR with 3D conformal proton therapy (3D CPT), intensity-modulated proton therapy (IMPT), and intensity-modulated photon therapy (IMXT). Methods We performed a comparative study of treatment plans with 3D CPT, IMPT, and IMXT for ten patients with retroperitoneal sarcomas. RT was delivered to 50.4 Gy to the clinical target volume (CTV), the structures considered at risk for microscopic disease. Results CTVs ranged from 74 to 357 cc (mean 188 cc). Dose conformity was improved with IMPT, while 3D CPT provided better dose homogeneity. Mean dose to the liver, small bowel, and stomach was reduced with IMPT compared with 3D CPT or IMXT. Conclusions IMPT, 3D CPT, and IMXT provide excellent target coverage for retroperitoneal sarcomas. OAR dose is lower with IMPT and 3D CPT, and IMPT achieves the closest conformity. These techniques offer the opportunity for further dose escalation to areas with positive margins.

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial

Hypofractionated radiation therapy has been safely implemented in the treatment of early-stage non-small cell lung cancer (NSCLC) but not locally advanced NSCLC owing to prohibitive toxicities with photon therapy. Proton therapy, however, may allow for safe delivery of hypofractionated radiation therapy. We sought to determine whether hypofractionated proton therapy with concurrent chemotherapy improves overall survival. The Proton Collaborative Group conducted a phase 1/2 single-arm nonrandomized prospective multicenter trial from 2013 through 2018. We received consent from 32 patients, of whom 28 were eligible for on-study treatment. Patients had stage II or III unresectable NSCLC (based on the 7th edition of the American Joint Committee on Cancer's staging manual) and received hypofractionated proton therapy at 2.5 to 4 Gy per fraction to a total 60 Gy with concurrent platin-based doublet chemotherapy. The primary outcome was 1-year overall survival comparable to the 62% reported for the Radiation Therapy Oncology Group (RTOG) 9410 trial. The trial closed early owing to slow accrual, in part, from a competing trial, RTOG 1308. Median patient age was 70 years (range, 50-86 years). Patients were predominantly male (n=20), White (n=23), and prior smokers (n=27). Most had stage III NSCLC (n=22), 50% of whom had adenocarcinoma. After a median follow-up of 31 months, the 1- and 3-year overall survival rates were 89% and 49%, respectively, and progression-free survival rates were 58% and 32%, respectively. No acute grade ≥3 esophagitis occurred. Only 14% developed a grade ≥3 radiation-related pulmonary toxic effect. Hypofractionated proton therapy delivered at 2.5 to 3.53 Gy per fraction to a total 60 Gy with concurrent chemotherapy provides promising survival, and additional examination through larger studies may be warranted.

Cognitive predictors of social adjustment in pediatric brain tumor survivors treated with photon versus proton radiation therapy.

Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. Survivors who underwent PRT (n=38) or XRT (n=20) participated in a neurocognitive evaluation >1year post radiotherapy. Group differences in cognitive and social functioning were assessed using analysis of covariance (ANCOVA). Regression analyses examined predictors of peer relations and social skills. Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p>.05). XRT participants were younger at diagnosis (XRT M=5.0years, PRT M=7.6years) and further out from radiotherapy (XRT M=8.7years, PRT M=4.6years). The XRT group performed worse than the PRT group on measures of processing speed (p=.01) and verbal memory (p<.01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation; χ2 (1)=38.67, p<.001; χ2 (1)=5.63, p<.05. Household poverty predicted peer relation difficulties (t=2.18, p<.05), and verbal memory approached significance (t=-1.99, p=.05). Tumor diameter predicted social skills (t=-2.07, p<.05). Regardless of radiation modality, survivors are at risk for social challenges. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship, as well as consideration of sociodemographic risk factors.

Retrofitting LINAC Vaults for Compact Proton Systems—Experiences Learned

We describe the installation of the Gordon Browne Proton Therapy Center within the Lunder Building at Massachusetts General Hospital. Advances in compact proton units with modular design brought to life the vision of allocating a space in a tight corner of a fully functioning high-rise building and installing equipment via pathways typical in a hospital setting. While the assembled equipment is larger than a conventional photon therapy linear accelerator, LINAC, the proton therapy equipment was designed to be modular to make installation easier. This allowed the largest components to be lowered down an elevator shaft and transported past areas used for patient care. Issues that complicated the installation process include the sharing of the loading dock with other activities in the hospital, elevator inspections, after-hours deliveries, infection control, lay-down space, and shielding requirements. This work is important in the identification of future sites for proton therapy.