Optimal allocation of proton therapy slots in combined proton-photon radiotherapy

Abstract Purpose Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review. Materials and Methods We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients. Results A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; < 30 Gy, 86%; P = .82). Likewise, there was no difference in 2-year PFS among patients who received either proton or photon radiotherapy (proton, 94%; photon, 83%; P = .07). Conclusion Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality.

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Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.0720 ◽

2018 ◽

Vol 36 (18) ◽

pp. 1813-1822 ◽

Cited By ~ 89

Author(s):

Zhongxing Liao ◽

J. Jack Lee ◽

Ritsuko Komaki ◽

Daniel R. Gomez ◽

Michael S. O’Reilly ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tissue ◽

Proton Therapy ◽

Small Cell ◽

Small Cell Lung ◽

Intensity Modulated ◽

Dose Volume ◽

Grade 3 ◽

Photon Radiotherapy ◽

Passive Scattering

Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non–small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF). Patients and Methods Eligible patients had stage IIB to IIIB NSCLC (or stage IV NSCLC with a single brain metastasis or recurrent lung or mediastinal disease after surgery) who were candidates for concurrent chemoradiation therapy. Pairs of treatment plans for IMRT and PSPT were created for each patient. Patients were eligible for random assignment only if both plans satisfied the same prespecified dose-volume constraints for at-risk organs at the same tumor dose. Results Compared with IMRT (n = 92), PSPT (n = 57) exposed less lung tissue to doses of 5 to 10 Gy(RBE), which is the absorbed Gy dose multiplied by the relative biologic effectiveness (RBE) factor for protons; exposed more lung tissue to ≥ 20 Gy(RBE), but exposed less heart tissue at all dose levels between 5 and 80 Gy(RBE). The grade ≥ 3 RP rate for all patients was 8.1% (IMRT, 6.5%; PSPT, 10.5%); corresponding LF rates were 10.7% (all), 10.9% (IMRT), and 10.5% (PSPT). The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that the RP and LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% (before) versus 18.2% (after) for the IMRT group (P = .047) and 31.0% (before) versus 13.1% (after) for the PSPT group (P = .027). Conclusion PSPT did not improve dose-volume indices for lung but did for heart. No benefit was noted in RP or LF after PSPT. Improvements in both end points were observed over the course of the trial.

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Comparison of proton therapy and intensity modulated photon radiotherapy for locally advanced non-small cell lung cancer: considerations for optimal trial design

Journal of Thoracic Disease ◽

10.21037/jtd.2018.04.59 ◽

2018 ◽

Vol 10 (S9) ◽

pp. S988-S990 ◽

Cited By ~ 2

Author(s):

Taylor R. Cushman ◽

Vivek Verma ◽

Jean-Claude M. Rwigema

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Proton Therapy ◽

Trial Design ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung ◽

Intensity Modulated ◽

Photon Radiotherapy

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Impact of proton therapy on antitumor immune response

Scientific Reports ◽

10.1038/s41598-021-92942-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Céline Mirjolet ◽

Anaïs Nicol ◽

Emeric Limagne ◽

Carole Mura ◽

Corentin Richard ◽

...

Keyword(s):

Immune Response ◽

Proton Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Sequencing Analysis ◽

Rna Seq ◽

Interferon Signaling ◽

Functional Profiling ◽

Photon Radiotherapy

AbstractRadiotherapy delivered using photons induces an immune response that leads to modulation of the tumor microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors in association with photon radiotherapy. At present, there is no publication on the radio-induced immune response after proton therapy. Balb/c mice bearing subcutaneous CT26 colon tumors were irradiated by a single fraction of 16.4 Gy using a proton beam extracted from a TR24 cyclotron. RNA sequencing analysis was assessed at 3 days post-treatment. Proton therapy immune response was monitored by flow cytometry using several panels (lymphoid, myeloid cells, lymphoid cytokines) at 7 and 14 days post-irradiation. RNA-Seq functional profiling identified a large number of GO categories linked to “immune response” and “interferon signaling”. Immunomonitoring evaluation showed induced tumor infiltration by immune cells. This is the first study showing the effect of proton therapy on immune response. These interesting results provide a sound basis to assess the efficacy of a combination of proton therapy and immune checkpoint inhibitors.

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Impact of proton therapy on antitumor immune response

10.21203/rs.3.rs-199402/v1 ◽

2021 ◽

Author(s):

Céline Mirjolet ◽

Anaïs Nicol ◽

Emeric Limange ◽

Carole Mura ◽

Corentin Richard ◽

...

Keyword(s):

Immune Response ◽

Proton Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Sequencing Analysis ◽

Rna Seq ◽

Interferon Signaling ◽

Functional Profiling ◽

Photon Radiotherapy

Abstract Radiotherapy delivered using photons induces an immune response that leads to modulation of the tumor microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors in association with photon radiotherapy. At present, there is no publication on the radio-induced immune response after proton therapy. Balb/c mice bearing subcutaneous CT26 colon tumors were irradiated by a single fraction of 16.4 Gy using a proton beam extracted from a TR24 cyclotron. RNA sequencing analysis was assessed at 3 days post-treatment. Proton therapy immune response was monitored by flow cytometry using several panels (lymphoid, myeloid cells, lymphoid cytokines) at 7 and 14 days post-irradiation. RNA-Seq functional profiling identified a large number of GO categories linked to “immune system” and “interferon signaling”. Immunomonitoring evaluation showed induced tumor infiltration by immune cells. This is the first study showing the effect of proton therapy on immune response. These interesting results provide a sound basis to assess the efficacy of a combination of proton therapy and immune checkpoint inhibitors.

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Proton therapy for prostate cancer: current state and future perspectives

British Journal of Radiology ◽

10.1259/bjr.20210670 ◽

2021 ◽

pp. 20210670

Author(s):

Yao-Yu Wu ◽

Kang-Hsing Fan

Keyword(s):

Prostate Cancer ◽

Proton Therapy ◽

Cancer Control ◽

Cost Effective ◽

Current Data ◽

Extensive Literature ◽

Normal Tissues ◽

Radiation Delivery ◽

Clinical Benefits ◽

Photon Radiotherapy

Objective: Localized prostate cancer can be treated with several radiotherapeutic approaches. Proton therapy (PT) can precisely target tumors, thus sparing normal tissues and reducing side-effects without sacrificing cancer control. However, PT is a costly treatment compared with conventional photon radiotherapy, which may undermine its overall efficacy. In this review, we summarize current data on the dosimetric rationale, clinical benefits, and cost of PT for prostate cancer. Methods: An extensive literature review of PT for prostate cancer was performed with emphasis on studies investigating dosimetric advantage, clinical outcomes, cost-effective strategies, and novel technology trends. Results: PT is safe, and its efficacy is comparable to that of standard photon-based therapy or brachytherapy. Data on gastrointestinal, genitourinary, and sexual function toxicity profiles are conflicting; however, PT is associated with a low risk of second cancer and has no effects on testosterone levels. Regarding cost-effectiveness, PT is suboptimal, although evolving trends in radiation delivery and construction of PT centers may help reduce the cost. Conclusion: PT has several advantages over conventional photon radiotherapy, and novel approaches may increase its efficacy and safety. Large prospective randomized trials comparing photon therapy with proton-based treatments are ongoing and may provide data on the differences in efficacy, toxicity profile, and quality of life between proton- and photon-based treatments for prostate cancer in the modern era. Advances in knowledge: PT provides excellent physical advantages and has a superior dose profile compared with X-ray radiotherapy. Further evidence from clinical trials and research studies will clarify the role of PT in the treatment of prostate cancer, and facilitate the implementation of PT in a more accessible, affordable, efficient, and safe way.

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