Proton therapy has the potential to reduce cardiac toxicities compared to photon therapy

Photon vs proton therapy for reduction of cardiac toxicities in locally advanced lung cancer

S. Teoh,F. Fiorini,B. George,K.A. Vallis,F. Van den Heuvel

Proton therapy has the potential to reduce cardiac toxicities compared to photon therapy. This analysis suggests that patients with tumour extension to and below T7 vertebrae would benefit most from proton therapy over photon therapy. The absolute benefit is higher in patients with underlying cardiac disease.

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Proton therapy for cancer lowers risk of side effects

by Julia Evangelou Strait, Washington University School of Medicine

Proton therapy results in fewer side effects than traditional X-ray radiation therapy for many cancer patients, according to a new study led by Washington University School of Medicine in St. Louis and the Perelman School of Medicine at University of Pennsylvania. Even with reduced side effects, proton therapy resulted in cure rates similar to those of X-ray radiation therapy.

Proton therapy for cancer lowers risk of side effects
A new study led by Brian Baumann, M.D., of Washington University School of Medicine in St. Louis, found that proton therapy (bottom) is associated with fewer severe side effects than conventional X-ray radiation therapy (top) for many cancer patients. Credit: Brian Baumann/Mike Worful

The study is the first major side-by-side comparison of side effects related to proton therapy and X-ray radiation therapy. It included almost 1,500 patients receiving combined chemotherapy and radiation therapy for lung, brain, head and neck, gastrointestinal and gynecologic cancers that had not yet spread to other parts of the body. Such patients receive both radiation and chemotherapy, a treatment regimen that often cures nonmetastatic cancer. But it also causes severe side effects—such as difficulty swallowing, nausea and diarrhea—that reduce quality of life and can, in some cases, require hospitalization.

After controlling for differences between the groups, such as age and additional medical problems, the researchers found that patients receiving proton therapy experienced a two-thirds reduction in the relative risk of severe side effects within 90 days of treatment, compared with patients receiving X-ray radiation therapy. Forty-five of 391 patients receiving proton therapy experienced a severe side effect in the 90-day time frame (11.5 percent). In the X-ray radiation therapy group, 301 of 1,092 patients experienced a severe side effect in the same period (27.6 percent). Patient data on side effects were gathered as the trial was ongoing, rather than after the fact.

“Proton therapy was associated with a substantial reduction in the rates of severe acute side effects—those that cause unplanned hospitalizations or trips to the emergency room—compared with conventional photon, or X-ray, radiation for patients treated with concurrent radiation and chemotherapy,” said Baumann, an assistant professor of radiation oncology at Washington University and an adjunct assistant professor of radiation oncology at Penn. “The opportunity to reduce the risk of severe side effects for patients and thereby improve their quality of life is very exciting to me. While there have been other studies suggesting that proton therapy may have fewer side effects, we were somewhat surprised by the large magnitude of the benefit.”

The researchers focused their study on what are called grade 3 adverse events, which are severe enough to require hospitalization. These can include pain, difficulty swallowing that might result in weight loss, difficulty breathing, and nausea and diarrhea severe enough to cause dehydration.

The researchers also found no differences between the two groups in survival, suggesting that proton therapy was just as effective in treating the cancer even as it caused fewer side effects. Overall survival at one year for the proton therapy group was 83 percent of patients versus 81 percent for the X-ray radiation therapy group. This difference was not statistically significant.

This study is the first large review of data across several cancer types to show a reduced side-effect profile for proton therapy compared with X-ray radiation therapy for patients receiving combined chemotherapy and radiation. Both types of radiation therapy are approved by the Food and Drug Administration for cancer treatment. Protons are relatively heavy, positively charged particles that hit their target and stop. X-ray beams consist of photons, which are much smaller particles that have almost no mass, allowing them to travel all the way through the body, passing through healthy tissue on the way out.

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Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity.

Clinical outcomes after intensity-modulated proton therapy with concurrent chemotherapy for inoperable non-small cell lung cancer

Adnan Elhammali, Pierre Blanchard, Alison Yoder, Zhongxing Liao, Xiadong Zhang, X. Ronald Zhu, Pamela K. Allen, Melenda Jeter, James Welsh, Quynh-Nhu Nguyen


Intensity modulated proton therapy is a highly conformal treatment option.•

Treatment of inoperable NSCLC with IMPT offers excellent disease local control.•

Treatment was well tolerated with no grade 4 or 5 toxicity.


Background & purpose

We report disease control, survival, and toxicity in patients with advanced inoperable non-small cell lung cancer (NSCLC) receiving concurrent chemotherapy and intensity-modulated proton therapy (IMPT) at a single institution.

Material and methods

All patients were treated with IMPT with concurrent chemotherapy. Endpoints assessed were local, regional, and distant control, disease-free survival (DFS), and overall survival (OS).


Fifty-one patients were enrolled with a median follow-up time of 23.0 months; 39 (76%) were treated with a simultaneous integrated boost to the gross tumor volume (GTV). The median GTV dose was 67.3 CGE and the median CTV dose was 60.0 CGE. Median OS and DFS times were 33.9 months and 12.6 months. The 3-year local control rate was 78.3%. Treatment was well tolerated, with a grade 3 toxicity rate of 18% (9 events: 4 esophagitis, 3 dermatitis, 1 esophageal stricture, and 1 fatigue) and no grade 4 or 5 toxicity. The most common grade 2 toxic effects were esophagitis (22 [43%]), dermatitis (16 [31%]), pain (15 [29%]), and fatigue (14 [27%]).


Treatment of inoperable NSCLC with IMPT and concurrent chemotherapy achieves excellent disease control with tolerable toxicity.

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

“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.”

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

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Clinical Outcomes of Patients with Recurrent Lung Cancer Reirradiated with Proton Therapy on the Proton Collaborative Group and University of Florida Proton Therapy Institute Prospective Registry Studies

Badiyan, Shahed N. et al. Practical Radiation Oncology

This is the largest series to date of Proton Beam Therapy reirradiation for recurrent lung cancer, showing that reirradiation with Proton Beam Therapy is well tolerated with acceptable toxicity and encouraging efficacy.

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