A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

Our plain-English summary of A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma, by S.R. Rice, Y.R. Li, T.M. Busch, et al (Photochemistry and Photobiology, 2019).

The study

• Authors: S.R. Rice, Y.R. Li, T.M. Busch, M.M. Kim, S. McNulty, A. Dimofte, T.C. Zhu, K.A. Cengel, C.B. Simone
• Journal: Photochemistry and Photobiology
• Published: 2019;95(1):411-418
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy (PT) and photodynamic therapy (PDT) and the largest-ever mesothelioma PT experience (n = 10). PDT photosensitizers included porfimer sodium (2 mg·kg-1 ; 24 h drug-light interval) or 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) (4 mg·m-2 ;48 h) with wavelengths of 630 nm to 60J·cm-2 and 665 nm to 15-45J·cm-2 , respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III-IV disease (100%). PT was delivered to a median of 55.0 CGE/1.8-2.0 CGE (range 50-75 CGE) adjuvantly (n = 8) or as salvage therapy (n = 2) following extended pleurectomy/decortication (ePD)/PDT. Two-year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation (n = 3), pneumonia (n = 2), and deep vein thrombosis (n = 2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1- and 2-year survival rates were 58% and 29%. No patient experienced CTCAEv4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced-stage patients compares favorably to survival for PT without PDT and photon therapy with PDT, suggesting possible spatial or systemic cooperativity and immune effect.

© 2018 The American Society of Photobiology.

In plain English

This small prospective study followed 10 consecutive patients with malignant pleural mesothelioma treated at the Hospital of the University of Pennsylvania between 2011 and 2015. All had the epithelioid subtype and stage III to IV disease, and 8 of the 10 had known asbestos exposure. Each had lung-sparing surgery (extended pleurectomy/decortication) with photodynamic therapy, a light-activated drug treatment given during the operation. Proton radiation therapy followed, either as planned follow-up treatment (8 patients) or after the disease came back (2 patients). Local control at 1 and 2 years was 90%. Three patients had regional (lymph node) recurrences and five had spread to distant sites. Median survival was 19.5 months after proton therapy ended and 30.3 months from diagnosis. One-year and 2-year survival rates were 58% and 29%. No patient had grade 3 or higher side effects, though some had grade 2 effects, including one case of grade 2 radiation pneumonitis. The authors concluded the combination was well tolerated, called the work hypothesis generating, and said larger studies would help confirm the findings.

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: Prospective study of a single group of patients, all of whom received the combined treatment, enrolled on one of two trials. There was no comparison group within the study.
• Who was studied: 10 consecutive patients with malignant pleural mesothelioma at the Hospital of the University of Pennsylvania, 2011 to 2015. Median age at diagnosis was 69 years (range 51 to 80). 90% were male and all were Caucasian. All had the epithelial (epithelioid) subtype and AJCC 7th Edition stage III to IV disease.
• Exposure: The study examined treatment, not asbestos. All patients had extended pleurectomy/decortication with intraoperative photodynamic therapy using porfimer sodium (Photofrin, 7 patients) or HPPH (3 patients). This was followed by proton therapy to a median dose of 5500 cCGE in 180 to 200 cCGE daily fractions, given as adjuvant therapy in 8 patients and as salvage therapy in 2. Table 1 lists known asbestos exposure in 8 of the 10 patients (80%).
• Main results:
  • Local control at 1 and 2 years was 90% in the 10 patients. One patient had a local recurrence 3.2 months after proton therapy ended.
  • 3 of the 10 patients had regional recurrences, at a median of 2.5 months (range 1.8 to 6.3 months) after proton therapy.
  • 5 of the 10 patients had distant failure. The first sites were the liver (2), peritoneum (1), contralateral lung (1) and bone (1).
  • Median survival from the end of proton therapy was 19.5 months. One-year and 2-year survival rates were 58% and 29%. Median follow-up was 7.1 months (range 2.0 to 33.2) from completion of proton therapy.
  • Median survival measured from diagnosis was 30.3 months.
  • Surgical complications: 3 patients had transient atrial fibrillation, 2 had deep vein thrombosis and 2 had pneumonia. No external phototoxicities from photodynamic therapy were seen.
  • No patient had grade 3 or higher acute or late toxicity. Grade 2 effects did occur:
• radiation pneumonitis in 1 patient (10%)
• radiation dermatitis in 5 patients (50%)
• cough in 1 patient
• dyspnea in 2 patients
• dysphagia in 2 patients
• The authors' conclusion: The authors concluded that the sequential combination was well tolerated and that proton therapy may reduce the toxicities of radiotherapy when given after surgery with photodynamic therapy. They said the survival results compared favorably with earlier reports and may suggest cooperative or immune effects of the two therapies.
• Limitations the authors state:
  • The authors said larger studies would be helpful to confirm the findings.
  • The authors noted that the epithelial subtype of all patients may have contributed, in part, to the longer survival.
  • The authors described the work as hypothesis generating.
  • The authors said outcomes might have been different if more patients had received immunotherapy.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Proton Therapy, Mesothelioma, Epithelioid, Histology, Pleurectomy/Decortication (P/D), Chemotherapy, Immunotherapy.

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