Mesothelioma Treatment Combines Proton and Photodynamic Therapy

Intraoperative photodynamic therapy combined with novel proton radiation improved survival time significantly for recent patients with advanced-stage pleural mesothelioma.

The study — the first to measure the impact of this combination — involved 10 consecutive patients treated at the University of Pennsylvania’s Abramson Cancer Center.

The treatment regimen resulted in a 90 percent, two-year disease control rate and an impressive 30.3-month median overall survival from the time of diagnosis.

All 10 patients were diagnosed before treatment began with stage 3 or stage 4 disease, which typically results in a 10 to 14-month survival.

“The combination may have worked synergistically to better fight the cancer,” Dr. Charles Simone, senior study author, told The Mesothelioma Center at Asbestos.com. “Results were impressive…with better than expected clinical outcomes.”

Simone Bringing Proton Therapy to New York

Simone has pioneered the use of proton therapy for mesothelioma.

He was recently named chief medical officer at the New York Proton Center, which opens in May as the first facility in the state to offer this type of radiation therapy.

The journal Photochemistry and Photobiology published the study in January 2019.

Simone, previously the medical director at the University of Maryland School of Medicine, was joined by doctors from the Perelman School of Medicine at the University of Pennsylvania and The UCSF Helen Diller Family Comprehensive Cancer in the study.

All patients underwent aggressive pleurectomy and decortication surgery along with photodynamic therapy.

Seven also received neoadjuvant chemotherapy and eight received adjuvant chemotherapy and immunotherapy.

The proton therapy was used in an adjuvant setting in all 10 patients. The median survival from the end of proton therapy treatment was 19.5 months.

Survival exceeded the previous rate at the same institution without the photodynamic therapy, suggesting the synergistic effect.

Synergistic Effect Improves Both Therapies

Photodynamic therapy, which is used in the treatment of malignant and nonmalignant diseases, can lead to an inflammatory reaction that invokes an anti-tumor response and immunogenic cell death of cancer.

“The combination of priming the immune system with intraoperative photodynamic therapy and then delivering proton therapy may have worked synergistically to stimulate the patient’s immune system to better fight the cancer,” Simone said. “More research on a cellular level is needed.”

Proton therapy is a unique type of radiation therapy that can more precisely target tumors while better protecting nearby normal tissue from the harmful radiation effects.

Normal tissues beyond and before the tumor cells are better spared, leaving far fewer side effects for patients, which is especially important with lung-sparing pleurectomy and decortication surgery.

With a diffuse tumor such as pleural mesothelioma covering a large surface, Simone believes proton therapy is considerably more beneficial than traditional photon therapy, including the intensity-modulated radiation therapy that is often used.

“Given the ability of proton therapy to better protect normal tissues, no patient in the entire cohort experienced any notable acute or late toxicities,” he said. “It seems to be a safe and highly effective option for these patients with great potential to reduce side effects, and even improve clinical outcomes.”

All Patients Had Epithelial Subtype

The one-year and two-year survival rates from completion of proton therapy were 58 and 29 percent, respectively.

The prolonged survival may have been helped by the epithelial subtype of mesothelioma in all 10 patients.

Epithelial cells account for about 70 percent of mesothelioma cases and carry a better prognosis compared to other cell types.

“While studies with larger patient numbers would be helpful to confirm our findings, our study should serve as a baseline to encourage further studies,” the authors wrote.

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