Hypofractionated Proton Therapy Research Articles

Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design

BackgroundOncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma.MethodsOur study titled “PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)” is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2–12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response.DiscussionPRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting.Trial registration: NCT05917301 (registered 23/6/2023).

Balancing Innovation and Patient Care in Breast Cancer: Integrating Hypofractionated Proton Therapy With Breast Reconstruction Outcomes.

This review aims to assess the application of hypofractionated proton therapy in breast cancer reconstruction, analyzing its advantages, challenges, and broader implications for patient care. The goal is to comprehensively understand how this innovative approach can be integrated into breast cancer treatment. Proton therapy exhibits superior target coverage and safety, reducing radiation-induced complications and sparing critical organs, but skin toxicity outcomes differ from photon therapy. Tissue expanders are vital in breast reconstruction, employing innovative planning for positive long-term outcomes and highlighting the importance of balancing cancer treatment effectiveness with cosmetic outcomes. Hypofractionated proton therapy and breast cancer reconstruction present promising innovations with notable advantages in target coverage and organ sparing. However, variations in skin toxicity outcomes and the need for a careful balance between treatment effectiveness and cosmetic outcomes underscore ongoing challenges. Future directions should focus on refining treatment protocols, optimizing patient selection criteria, and integrating emerging technologies to enhance therapeutic outcomes while minimizing adverse effects.

Five-Fraction Proton Therapy for the Treatment of Skull Base Chordomas and Chondrosarcomas: Early Results of a Prospective Series and Description of a Clinical Trial

(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9–15 months) with 100% local control. Acute grade I–II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.

Optimal Bladder Volume for Hypofractionated Proton Therapy in Each Localized Prostate Cancer Risk Group

Optimal Bladder Volume for Hypofractionated Proton Therapy in Each Localized Prostate Cancer Risk Group

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

EP07.02-07 Prospective Study of Hypofractionated Proton Therapy for Inoperable Early Stage Non-small Cell Lung Cancer

Phase II Clinical Trial of Hypofractionated Image-Guided Proton Therapy with 12 Fractions for Prostate Cancer.

Towards hypofractionated proton therapy for prostate cancer for improving convenience for patients to receive treatment and improving therapeutic efficacy, image-guided technique with hydrogel spacer solved the late gastrointestinal toxicity, but it is unclear whether acute genitourinary (GU) toxicity is acceptable. The aim of this phase II study was to evaluate the safety and efficacy of hypofractionated image-guided proton therapy (IGPT) with 12 fractions for prostate cancer. Eligibility criteria were as follows: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by (UICC TNM8th); (3) ECOG-PS ≤ 2; (4) age ≥ 20 years; (5) no serious underlying disease or other cancers; (6) technically capable of proton therapy, and (7) written informed consent. Primary endpoint was the ratio of grade 2 or more acute genitourinary toxicity. We used the modified CTCAE grading of grade 2 GU toxicities, in which prescribing two and more types of drugs for dysuria within 3 months of the start of radiation was considered to indicate grade 2 GU toxicity. A phase II trial was planned based on the minimax Simon's two-stage design with a significance level of 0.05 and a power of 90%. The acceptable incidence is considered to be less than 5%, and the unacceptable incidence is considered to be more than 15%. A total of 83 patients is required for completion of the trial (7 patients or fewer). After evaluating the primary endpoint in 83 patients, 217 additional patients were registered and a total of 300 patients were registered in order to further examine the safety and efficacy. The prescribed dose to the isocenter was 51.6 GyRBE in 12 fractions (4 days a week). From January 2020 to March 2021, 30, 53, and 217 patients (total 300) were enrolled. The patient characteristics were as follows: median age, 70 (48-83) years; low/intermediate/high risk, 44/132/124. Forty-nine and 38 patients had benign prostatic hyperplasia and diabetes mellitus, respectively. Grade 2 acute GU toxicities were observed in 1, 5 and 13 patients, respectively (total 6.3%). No grade 3 or higher acute GU toxicities were observed. However, urinary retention during IGPT, which was not previously observed, was observed in 3 cases, and temporary urethral catheterization was performed (Grade 2). Most of the acute GU toxicity tended to improve at 1 month after IGPT, and almost improved at 3 months. Mean score deteriorations beyond the minimum clinically important difference threshold (1/2 SD) were observed only at 1 month in the following scales: summary (-6.0), bother (-7.0), and irritative/obstructive (-6.3). Hypofractionated IGPT with 12 fractions for prostate cancer is well tolerated in acute GU toxicities. Longer follow-up is necessary to evaluate the efficacy and late toxicities. Further investigation of hypofractionated IGPT with 12 fractions for prostate cancer is warranted. Since April 2021, an additional 1000 cases of prospective registration study have been conducted.

Five-Fraction Proton Therapy for Chordomas and Chondrosarcomas of the Skull Base: Preliminary Results of a Prospective Series

To describe the first series of patients with clival chordomas and chondrosarcomas treated with extremely hypofractionated proton therapy in a single institution with focus on acute tolerance and dosimetric parameters. A total of 11 consecutive patients with biopsy proven chordomas and chondrosarcomas were prospectively included in a five-fraction proton therapy protocol between June 2022 and January 2023. The inclusion criteria for this protocol were: Age > 18 yo., Karnofsky Performance Status (KPS) ≥ 70%, absence of metastases, no previous radiation courses, clinical target volume (CTV) up to 50 cc and CTV location relative to organs at risk that allowed compliance with the necessary dose restrictions for hypofractionated treatments in 5 fractions, according to the international guidelines. Treatment was delivered with a Proteus®ONE cyclotron using Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT). Patient setup was performed with CBCT imaging at isocenter and X-Ray obliques, allowing a robust planning with 1 mm setup uncertainty and 3.5% range uncertainty. IMPT plans were obtained with RayStation employing 4 to 6 non-coplanar beams. In 7 patients' apertures were used in 2 of the beams, to reduce lateral penumbra and to optimize dose gradient. A total of 11 patients (7 males and 5 females) with an age range between 29 and 79 yo, were included. 6 patients with classic chordomas and 5 patients with grade I-II chondrosarcomas were treated with a total dose of 37.5 GyRBE and 35 GyRBE, respectively, in 5 daily fractions. All the patients had received previous surgery with complete resection in 2 patients, subtotal resection in 7 patients and partial resection in 2 patients. Most common symptoms at diagnosis were diplopia and headache and baseline median KPS after surgery was 90% (70 - 100%). Median CTV was 30.62 cc (10.56 - 47.47 cc). Median CTV coverage was V95% = D95.5%. Median maximal dose for the brainstem was 26.5 GyRBE (30 - 24.7 GyRBE) and for the optic pathway was 20.7 GyRBE (8.9 - 23.6 GyRBE). Median follow-up was 3 months (8 - 1 months). Acute toxicity during follow-up was mild, with grade I - II headache (64%), grade I asthenia (45%), grade I nausea (27%), grade I dysphagia (18%) and reversible alopecia (45%). Only one patient showed nystagmus and mild loss of strength in left lower limb related with an ischemic brainstem lesion, in a low dose region, not clearly radiation related. 8 patients had a 3-month follow-up MRI with no signs of progression. Five-fraction proton therapy for the treatment of clival chordomas and chondrosarcomas is dosimetrically feasible and well tolerated for selected patients. Proton therapy remains a limited resource, consequently, reducing treatment time can have significant financial and psychosocial implications. Longer follow up is needed to validate these results.

Single-Masked Randomized Phase 2 Study Assessing 2 Forms of Hypofractionated Proton Therapy in Patients With Large Choroidal Melanomas

Patients with large uveal melanomas are at major risk of liver metastases. Some patients are reluctant to undergo the standard treatment (ie, immediate enucleation). Proton therapy yields 5-year local control rates and eyeball retention of >85% and ≈20% in large uveal melanomas. Patients with T3/T4 uveal melanomas refusing enucleation were randomized between standard 4 to 13 Gy-fraction or moderately hypofractionated 8 to 6.5 Gy-fraction proton therapy. The main endpoint was the 2-year local recurrence-free survival without enucleation. A single-masked 1:2 randomized phase 2 trial was conducted between 2015 and 2017 with planned endoresection and distance to the posterior pole as strata. Local events were defined as local relapse, or enucleation due to complications or relapse. The 32 patients, with a mean age of 64 years, had T3/4 (N=17/15), M1 (N=2) uveal melanomas, of mean tumor diameter and thickness of 16.5 mm and 9.1 mm, and of posterior location in 56.5%. Median follow-up was 56.7 months. The 2-year local recurrence-free survival rate without enucleation was 79% (95% confidence interval, 65%-96%), similar in both arms. There were 9 enucleations, 3 at relapse and 6 for toxicities. Twelve patients had distant metastases. The 2-year-overall survival was 72% (95% confidence interval, 58%-89%). At baseline, visual acuity by average logarithm value of the minimum angle of resolution was 0.68 and 0.70 in the standard and experimental arms, and at last follow-up 2 and 1.7, with mean differences of 1.44 and 1.01, respectively (P=.39). An 8-times 6.5 Gy scheme is feasible without deteriorating local control and with similar toxicity rates in patients with large uveal melanomas. Larger studies incorporating adjuvant treatments are warranted.

PO-1482 Moderately hypofractionated proton therapy with implantable spacer in patients with prostate cancer

PO-1482 Moderately hypofractionated proton therapy with implantable spacer in patients with prostate cancer

Long-term Outcomes After Moderate Hypofractionated Proton Therapy for Centrally Located Non-small Cell Lung Cancer.

To investigate the outcomes of patients with centrally located non-small-cell lung cancer (NSCLC) treated with proton beam therapy (PBT) using moderate hypofractionation. Between 2006 and 2019, 34 patients with centrally located T1-T4N0M0 NSCLC who received moderate hypofractionated PBT were retrospectively reviewed. The median follow-up was 50.8 months (range=5.8-100.4 months). The 3-year overall survival, progression-free survival (PFS), and local control rates were 70.4%, 55.5% and 80.5%, respectively. Grade 2 or 3 lung adverse events (AEs) after PBT were observed in five (14.7%) patients; however, grade 3 radiation pneumonitis was observed in one (2.9%) patient. Notably, no grade 4 or higher AEs were observed. Regarding the correlation between the lung dose and proximal bronchial tree maximum dose and grade 2 or higher lung AEs, a weak correlation was observed between the mean lung dose and AEs (p=0.035). Although the clinical target volume (CTV) was a risk factor for poor PFS, no significant correlation was found between the CTV and lung AEs after PBT. Moderate hypofractionated PBT may be a useful radiotherapy method for centrally located cT1-T4N0M0 NSCLC.

A retrospective study of adjuvant proton radiotherapy for breast cancer after lumpectomy: a comparison of conventional-dose and hypofractionated dose

PurposeThis study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer.Materials and methodsBreast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively.ResultFrom January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy. According to the AJCC 8th Edition standard, there were stage I in 26 patients, stage II in 22 patients, and stage III in 2 patients. A total of 14 patients received intensity-modulated proton therapy at a dose of 50 Gy in 25 fractions, followed by a 10 Gy 4 fractionated boost to the lumpectomy cavity, while 36 received 40.05 Gy in 15 fractions, simultaneous integrated boost (SIB) 48 Gy to the lumpectomy cavity. Median follow-up time for 40.05 Gy group was 35.6 months (15–43 months). Median follow-up time for 50 Gy group was 46.8 months (36–68 months). For acute toxicity, the grade 1 and 2 radiodermatitis in conventional-dose group were 35.7% and 57.1%, respectively. In hypofractionated dose group, the grade 1 and 2 radiodermatitis were 91.7% and 8.3%, respectively. The radiodermatitis is hypofractionneted dose better than conventional-dose significantly. Grade 1 radiation-induced esophagitis in conventional-dose group and hypofractionated dose group were 85.71% and 60%, respectively. For late toxicity, no patients developed radiation-induced pneumonitis and rib fracture in conventional-dose group. Three patients presented grade 1 pneumonitis; one patient presented graded 2 pneumonitides and two patients presented rib fracture in hypofractionated dose group. One presented hypothyroidism in hypofractionated dose group. All patients were satisfied with breast shape. The one- and two-year OS and DFS for conventional-dose group were 100 and 100; 100 and 92.9%, respectively. The one- and two-year OS and DFS for hypofractionated dose group were 100 and 100; 100 and 100%, respectively.ConclusionProton radiation therapy can significantly reduce the normal tissue dose in breast cancer patients' hearts, lungs, and other organs. Hypofractionated proton therapy shortens the treatment course with mild radiation-related adverse effects, and has a better effect on addressing the acute adverse reactions than conventional proton radiotherapy.

Acute genitourinary toxicity of pencil beam scanning proton therapy for localized prostate cancer: utility of the transition zone index and average urinary flow rate in predicting acute urinary retention.

The purpose of this study was to evaluate the incidence of acute genitourinary toxicities in patients undergoing pencil beam scanning proton therapy for prostate cancer and investigate predictive factors associated with acute urinary retention. A total of 227 patients treated between 2018 and 2021 were divided into the normo-fractionated proton therapy group (n=107) and the moderately hypo-fractionated proton therapy group (n=120), with prescribed doses of 76-78Gy relative biological effectiveness in 38-39 fractions and 60-63Gy relative biological effectiveness in 20-21 fractions, respectively. Uroflowmetry parameters and the transition zone index were prospectively evaluated. Forty-five patients (42%) in the normo-fractionated proton therapy and 33 (28%) in the moderately hypo-fractionated proton therapy developed acute grade 2 genitourinary toxicities (P=0.02). The most common acute genitourinary toxicity was acute urinary retention. Thirty-nine patients (36%) treated with normo-fractionated proton therapy and 27 (23%) treated with moderately hypo-fractionated proton therapy developed grade 2 acute urinary retention (P=0.02). No patients developed grade≥3 toxicity. Univariate analysis showed the transition zone index, prostate volume, international prostate symptom score, voided volume, maximum flow rate and average flow rate were associated with grade 2 acute urinary retention. Multivariate analysis in both groups revealed the transition zone index (P=0.025 and 0.029) and average flow rate (P=0.039 and 0.044) were predictors of grade 2 acute urinary retention. The incidence of acute genitourinary toxicities was lower in the moderately hypo-fractionated proton therapy compared with the normo-fractionated proton therapy. Lower pretreatment average flow rate and a higher transition zone index were useful predictors of grade 2 acute urinary retention.

Normofractionated and moderately hypofractionated proton therapy: comparison of acute toxicity and early quality of life outcomes

AimData on the safety of moderately hypofractionated proton beam therapy (PBT) are limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT).Material and methodsWe prospectively compared acute toxicity and QoL between patients treated with nPBT (dose per fraction 1.8–2.3 Gy, n = 90) and hPBT (dose per fraction 2.5–3.1 Gy, n = 49) in following locations: head and neck (H&N, n = 85), abdomen and pelvis (A&P, n = 43), and other soft tissue (ST, n = 11). The toxicities were grouped into categories—mucosal, skin, and other sites—and evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at baseline, treatment completion, and 3 months after PBT completion. QoL was evaluated with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 scale for all locations and additionally with EORTC QLQ-HN35 for H&N patients.ResultsOverall, the highest toxicity grades of G0, G1, G2, and G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%), and 15 (10.8%) patients, respectively. According to organ and site, no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile as compared to nPBT with a higher frequency of G0 and G1 and a lower frequency of G2 and G3 events (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023), and full resolution of toxicities (87% vs 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except for loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (−8.33 vs −25, p = 0.016).ConclusionHypofractionated proton therapy offers non-inferior early safety and QoL as compared to normofractionated irradiation and warrants further clinical investigation.

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.

Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer

Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer. A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel. From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n=2), 56.25 Gy (n=4), and 60 Gy (n=14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively. Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted.

Patient-Reported Quality of Life Outcomes after Moderately Hypofractionated and Normofractionated Proton Therapy for Localized Prostate Cancer.

Simple SummaryFor patients with localized prostate cancer (PCa), information on the quality of life (QOL) after treatment is important when determining their preferred treatment option. In external beam radiation therapy, moderate hypofractionation (MH) is becoming an alternative standard for PCa treatment and MH is increasingly used in proton therapy (PT). Although MHPT is a promising strategy, there is little evidence regarding the data of long-term QOL after MHPT. This study evaluated patient-reported QOL over three years after MHPT and compared the data with that after normofractionated PT (NFPT) using the Expanded Prostate Cancer Index Composite-50. We revealed urinary QOL was temporarily decreased with clinically meaningful changes at 1 month, but did not observe clinically meaningful QOL deterioration in other assessment points in the urinary, bowel, and sexual domains over three years after MHPT. In addition, the QOL after MHPT and NFPT was similar overall.We retrospectively evaluated the three-year patient-reported quality of life (QOL) after moderately hypofractionated proton therapy (MHPT) for localized prostate cancer in comparison with that after normofractionated PT (NFPT) using the Expanded Prostate Cancer Index Composite-50. Patients who received MHPT (60–63 Gy (relative biological effectiveness equivalents; RBE)/20–21 fractions) (n = 343) or NFPT (74–78 Gy (RBE)/37–39 fractions) (n = 296) between 2013 and 2016 were analyzed. The minimum clinically important difference (MCID) threshold was defined as one-half of a standard deviation of the baseline value. The median follow-up was 56 months and 83% completed questionnaires at 36 months. Clinically meaningful score deterioration was observed in the urinary domain at 1 month in both groups and in the sexual domain at 6–36 months in the NFPT group, but not observed in the bowel domain. At 36 months, the mean score change for urinary summary was −0.3 (MHPT) and −1.6 points (NFPT), and that for bowel summary was +0.1 and −2.0 points; the proportion of patients with MCID was 21% and 24% for urinary summary and 18% and 29% for bowel summary. Overall, MHPT had small negative impacts on QOL over three years, and the QOL after MHPT and NFPT was similar.

Hypofractionated proton therapy in breast cancer: where are we? A critical review of the literature.

To critically review available literature on hypofractionated (≥ 3Gy/fraction) proton therapy (PT) for breast cancer (BCa). A systematic screening of the literature was performed in April 2021 in compliance with the preferred reporting items for systematic reviews and meta-analyses recommendations. All full-text publication written in English were considered eligible. Acute and late toxicities, oncological outcomes and dosimetric features were considered for the analysis. Twelve publications met the inclusion criteria; all studies but one focused on accelerated partial breast irradiation (APBI). Eleven works considered post-operative patients, one referred to ABPI as a curative-intent modality. The dosimetric profile of PT compared favorably with both photon-based 3D conformal and intensity-modulated techniques, while a more extended follow-up is warranted to fully assess both the long-term toxicities and the non-inferiority of oncological outcomes. Our work shows that results on PT for BCa are currently only available for APBI applications, with dosimetric analyses demonstrating a clear advantage over both 3D conformal and intensity modulated X-rays techniques, especially when ≥ 2 treatment fields were used. However, further evidence is needed to define whether suchtheoretical benefit translates into clinical improvements, especially in the long-term.

Hypofractionated Proton Therapy for Non-Small Cell Lung Cancer: Ready for Prime Time? A Systematic Review and Meta-Analysis

Hypofractionated Proton Therapy for Non-Small Cell Lung Cancer: Ready for Prime Time? A Systematic Review and Meta-Analysis

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer

Background To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. Material and methods We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. Results Median follow-up was 8.0 years (0.9–12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. Conclusion Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Updated Toxicity and Quality-of-Life Outcomes From a Randomized Phase III Trial of Extreme Hypofractionated vs. Standard Fractionated Proton Therapy for Low-Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> We present an interim analysis of toxicity and quality-of-life (QOL) from a randomized phase III trial of extreme hypofractionated versus standard hypofractionated proton therapy for low-risk prostate cancer. <h3>Materials/Methods</h3> From 2011-2020, low-risk prostate cancer patients were randomized in a 1:2 fashion to standard fractionation (79.2 Gy [RBE] in 44 fractions, Arm A) versus extreme hypofractionation (38 Gy [RBE] in 5 fractions, Arm B) proton therapy. Patients were excluded if they had an American Urological Association Symptom Index (AUASI) > 17. Toxicity was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and adjusted for pre-treatment toxicities. Patients completed Expanded Prostate Cancer Index Composite + (EPIC), Short Form 12 (SF) and AUASI surveys at baseline and 3, 6, 12, 18, 24 and 36 months. <h3>Results</h3> Forty-six patients were included in Arm A and 84 patients in Arm B. Median follow-up was 50 months. The majority of patients were clinical T1c (89% Arm A, 84.5% Arm B, <i>P</i> = 0.86) and a PSA > 4-10 (80.4% Arm A, 78.6% Arm B, <i>P</i> = 1.00). For both groups, median AUASI was 5 (range 0-14). Four patients (1 Arm A, 3 Arm B) had died at the time of last follow-up, none related to their prostate cancer or treatment. Between the two arms, no significant differences were noted in acute treatment-related genitourinary (GU) or gastrointestinal (GI) toxicities: acute GU grade ≥ 2 (0% Arm A, 5% Arm B), GU grade ≥ 3 (0% each arm), GI grade ≥ 2 (0% Arm A, 2% Arm B), grade ≥ 3 (0% each arm). Similarly, no significant differences were noted in late treatment-related GU or GI toxicities: late GU grade ≥ 2 (26% Arm A, 33% Arm B), GU grade ≥ 3 (2% Arm A, 1% Arm B), GI grade ≥ 2 (13% Arm A, 19% Arm B), GI grade ≥ 3 (0% each arm). When analyzing QOL by arm and timepoints, only EPIC Overall scores at 36 months were clinically significantly different (> MID) between the two arms with Arm B having improved scores (+29.62 points, <i>P</i> = 0.02). Other QOL domains (EPIC Urinary, EPIC Bowel, AUASI) were not clinically significantly different between the two arms across timepoints. <h3>Conclusion</h3> In a phase III randomized controlled trial comparing extreme hypofractionation to standard fractionation for the treatment of prostate cancer, no significant differences for treatment-related acute or late, grade ≥ 2 or ≥ 3, toxicity were found for GU or GI toxicities. Additionally, improved EPIC Overall scores at 36 months were found in patients treated with extreme hypofractionation. This trial was registered with Western IRB 20101536, and NCT01230866.