Proton therapy for thoracic malignancies: a review of oncologic outcomes

Our plain-English summary of Proton therapy for thoracic malignancies: a review of oncologic outcomes, by N.V. Patel, N.Y. Yu, A. Koroulakis, et al (Expert Review of Anticancer Therapy, 2021).

The study

• Authors: N.V. Patel, N.Y. Yu, A. Koroulakis, T. Diwanji, A. Sawant, T.T. Sio, P. Mohindra
• Journal: Expert Review of Anticancer Therapy
• Published: 2021;21(2):177-191
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Radiotherapy is an integral component in the treatment of the majority of thoracic malignancies. By taking advantage of the steep dose fall-off characteristic of protons combined with modern optimization and delivery techniques, proton beam therapy (PBT) has emerged as a potential tool to improve oncologic outcomes while reducing toxicities from treatment.Areas covered: We review the physical properties and treatment techniques that form the basis of PBT as applicable for thoracic malignancies, including a brief discussion on the recent advances that show promise to enhance treatment planning and delivery. The dosimetric advantages and clinical outcomes of PBT are critically reviewed for each of the major thoracic malignancies, including lung cancer, esophageal cancer, mesothelioma, thymic cancer, and primary mediastinal lymphoma.Expert opinion: Despite clear dosimetric benefits with PBT in thoracic radiotherapy, the improvement in clinical outcomes remains to be seen. Nevertheless, with the incorporation of newer techniques, PBT remains a promising modality and ongoing randomized studies will clarify its role to determine which patients with thoracic malignancies receive the most benefit. Re-irradiation, advanced disease requiring high cardio-pulmonary irradiation volume and younger patients will likely derive maximum benefit with modern PBT.

In plain English

This article was a review, not a new study. The authors summarized research on proton beam therapy, a type of radiation treatment, for cancers in the chest: lung cancer, esophageal cancer, malignant pleural mesothelioma, thymic cancers and mediastinal lymphoma. It did not study asbestos exposure. For mesothelioma, the authors reported that several treatment-planning studies found proton therapy delivered less radiation to nearby organs than photon-based IMRT, but that clinical outcome data were scarce. One University of Pennsylvania prospective study they described included 10 patients with nonmetastatic stage III to IV mesothelioma, given proton therapy after pleurectomy and decortication surgery plus photodynamic therapy. It reported two-year local control of 90% and 1- and 2-year survival of 58% and 29%. For esophageal cancer, they described a randomized trial of 145 patients that found similar survival but less total toxicity with protons than with IMRT. The authors concluded that, despite clear dosimetric benefit, improvement in clinical outcomes remains to be seen, and that proton therapy for mesothelioma is still investigational. They noted that randomized evidence was limited to a few lung and esophageal cancer studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies on proton beam therapy for thoracic cancers
• Who was studied: Patients in previously published studies with thoracic cancers: lung cancer (mainly non-small cell lung cancer), esophageal cancer, malignant pleural mesothelioma, thymic malignancies and mediastinal lymphomas. The review gives no search method, dates or total numbers.
• Exposure: No asbestos exposure was studied. The review covered treatment with proton beam therapy (passive scattering, pencil beam scanning and intensity-modulated proton therapy), usually compared with photon radiotherapy such as IMRT.
• Main results:
  • Malignant pleural mesothelioma, planning studies: the review reported that multiple studies found dosimetric benefits of proton therapy over IMRT. In a Swiss study, 8 patients treated with IMRT after extrapleural pneumonectomy were replanned for proton therapy. With proton therapy, doses to the kidneys, contralateral lung, liver, heart and spinal cord were significantly reduced.
  • Malignant pleural mesothelioma: the authors stated that clinical outcome data for proton therapy are scarce.
  • Malignant pleural mesothelioma, University of Pennsylvania series (8 patients after lung-sparing radical pleurectomy, 8 after progression on systemic therapy, 1 upfront definitive treatment; median dose 51.75 GyE): median overall survival had not been reached and there were no reports of grade 3 or higher toxicity.
  • Malignant pleural mesothelioma, University of Pennsylvania prospective study of proton therapy with photodynamic therapy in 10 patients with Stage III to IV nonmetastatic disease. Proton therapy was given after pleurectomy and decortication, as adjuvant treatment in 8 patients and as salvage in 2. Two-year local control was 90%, distant failure 50% and regional failure 30%. Median survival was 19.5 months from completion of radiotherapy, and 1- and 2-year survival were 58% and 29%. There were no grade 2 or higher acute or late toxicities.
  • Malignant pleural mesothelioma, University of Washington series of 3 patients treated with IMPT after extrapleural pneumonectomy: no radiation pneumonitis was seen.
  • Locally advanced non-small cell lung cancer, randomized trial of IMRT versus passive scattering proton therapy: there was no benefit in grade 3 or higher pneumonitis (10.5% with protons, 6.5% with IMRT) or in local failure (about 11% in both groups).
  • Locally advanced esophageal cancer, randomized phase IIB trial of 145 patients (proton therapy versus IMRT): 3-year progression-free and overall survival were similar. Total toxicity burden and postoperative complication rates were improved with proton therapy.
• The authors' conclusion: The authors concluded that, despite clear dosimetric benefit with proton therapy in thoracic radiotherapy, improvement in clinical outcomes remains to be seen. They stated that ongoing randomized studies will clarify its role, and that for malignant pleural mesothelioma the use of proton therapy is still investigational.
• Limitations the authors state:
  • The authors stated that randomized data comparing proton and photon radiation are limited to a small number of lung and esophageal cancer studies. They added that most evidence comes from retrospective analyses or single-arm prospective trials.
  • For mesothelioma, the authors stated that additional studies are needed to determine the benefit of proton therapy.

Topics

Medical terms in this study, explained in our Lexicon: Proton Therapy, Lung Cancer, Esophageal Cancer, Mesothelioma.

Related studies

• A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma — S.R. Rice, Y.R. Li, et al. (2019)
• Is there a single spot size and grid for intensity modulated proton therapy? Simulation of head and neck, prostate and mesothelioma cases — L. Widesott, A.J. Lomax, et al. (2012)
• Proton Beam Therapy and Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma — M.G. McCusker, K.A. Scilla, et al. (2019)
• Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies — S. Kiesgen, L. Chicaybam, et al. (2018)
• Repositioning PARP inhibitors in the treatment of thoracic malignancies — F. Passiglia, M.L. Reale, et al. (2021)
• COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study — M.C. Garassino, J.G. Whisenant, et al. (2020)

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