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.

Proton therapy significantly decreased the dose to critical structures (heart, lungs, esophagus, thyroid, and non-target body), specifically in patients with mediastinal lymphomas.

Everett AS, Hoppe BS, Louis D, McDonald AM, Morris CM, Mendenhall NP, Li Z, Flampouri S,

Comparison of Techniques for Involved-Site Radiation Therapy in Patients with Lower Mediastinal Lymphoma, Practical Radiation Oncology (2019), doi: j.prro.2019.05.009.

In this study, various radiation techniques and doses to Organs At Risk (OARs) are compared to determine the optimal treatment technique in patients with lower mediastinal lymphoma involvement.

In patients with lower mediastinal lymphoma, radiation delivery is particularly challenging because of the proximity of the target to critical structures, such as the heart and its substructures, lungs, breast, and esophagus. Therefore, PT has been increasingly used in patients with mediastinal lymphoma given its ability to improve dose conformity and decrease radiation to normal tissues while providing equivalent target coverage

Patients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity-modulated radiotherapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML.

Proton therapy significantly decreased the dose to critical structures (heart, lungs, esophagus, thyroid, and non-target body), specifically in patients with mediastinal lymphomas. Therefore, when PT is available and the patient has lower mediastinal involvement, PT should be considered to maximally reduce the dose to nearby normal structures and decrease the risk of late toxicity associated with LM lymphoma radiation treatment.

Among patients with lower mediastinal lymphoma involvement, PT significantly reduces radiation to the lung, heart, esophagus, thyroid, and non-target body compared with IMRT.

PT can provide a significant benefit over IMRT techniques and should be considered in patients with lower mediastinal lymphoma involvement.

Figure 2. Colorwash dose distribution for a representative patient showing (A) free-breathing intensity-modulated radiation therapy, (B) free-breathing proton therapy, (C) deep inspiration breath-hold intensity-modulated radiation therapy, and (D) deep-inspiration breath-hold proton therapy. Image borrowed with permission from Hoppe BS, Mendenhall NP, Louis D, et al. Comparing Breath Hold and Free Breathing during Intensity-Modulated Radiation Therapy and Proton Therapy in Patients with Mediastinal Hodgkin Lymphoma. International Journal of Particle Therapy. 2017;3(4):492-496. 10.14338/ijpt-17-000

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.

Montefiore Study May Help Establish Patient Criteria for Proton Therapy

N. Patrik Brodin, PhD

Data supporting the efficacy of proton therapy are robust for pediatric cancers, brain and base-of-skull tumors, and complex-shaped tumors near critical structures (…)

Proton therapy has emerged as an attractive option for patients with head and neck cancer. This is due to proton therapy beam technology, which precisely destroys cancers with an unmatched ability to stop at precise locations within the body.

Protons also have significantly fewer adverse effects (AEs) and toxicities than most other cancer therapies, because of the protons’ unique ability to sculpt radiation doses according to the shapes and sizes of tumors. This is particularly important for head and neck cancers, which frequently are close to or impeding on vocal cords, air passageways, swallowing muscles, salivary glands, and the oral mucosa. The opportunity to preserve healthy tissue is considerable.

AEs estimated to be significantly less prominent include swallowing difficulties, inflammation of the esophagus, and reduced saliva production. For people suffering from head and neck cancer and their families, the ability to avoid these types of complications makes an overwhelmingly important difference in QoL.

Younger patients, non-smokers, and patients with HPV p16- positive tumors will most likely benefit from proton therapy (…)

The highest expense in cancer therapy involves the regrowth of cancer—large sums are required to prolong survival and maintain QoL. By increasing cure rates and improving patients’ QoL, we can increase cost-effectiveness.

It is important for healthcare providers not only to educate our patients and their families about each treatment’s ability to destroy cancers, but also to manage expectations about different treatments and what life may look like “post cancer.”

Proton therapy is one of the most modern therapies available, and its ability to minimize AEs such as trouble swallowing, reduced ability to eat, dental problems, and difficulty digesting food can’t be understated for some of our patients (…) By increasing cure rates and improving patients’ Quality of Life, we can increase cost-effectiveness.

Hydrogel Spacer Reduces Rectal Dose during Proton Therapy for Prostate Cancer: A Dosimetric Analysis

Praveen Polamraju, BS; Alexander F. Bagley, MD, PhD; Tyler Williamson, BS, CMD; X. Ronald Zhu, PhD; Steven J. Frank, MD

Patients receiving radiation therapy for prostate cancer are at risk of developing treatment-related rectal toxicity, particularly as hypofractionated and stereotactic ablative approaches have become more prominent. Toxicity can manifest as rectal bleeding or bowel urgency, and the risk correlates with dosimetric parameters such as overall dose and the volume of rectum receiving at least 70 Gy (rectal V70). The increase in fractional doses raises concerns regarding greater rectal toxicity, but longer-term results are needed to clarify this issue. Approaches to minimize rectal radiation doses and thereby reduce treatment-related morbidity have become increasingly important in the management of prostate cancer.

Proton therapy has been used as a strategy to minimize radiation dose to adjacent structures including the rectum. Prior reports indicate that rectal volumes receiving 10 to 80 Gy are significantly lower with proton therapy (eg, V70 = 7.9%) than with intensity-modulated (photon) radiation therapy (IMRT) (eg, V70 = 14%), although others have questioned whether proton therapy alone is sufficient to reduce the rectal volume receiving high radiation doses. The 2 primary proton modalities, passive scattering proton therapy (PSPT) and intensity-modulated proton therapy (IMPT), have been compared for their relative ability to spare the rectum. An emerging approach aimed at further rectal sparing involves the use of biodegradable hydrogel spacers that physically displace the prostate from the rectal wall during treatment. In one randomized trial, use of such a spacer led to a relative reduction in mean rectal V70 of 74%. These studies suggest that significant dosimetric benefit requires at least 7- to 15-mm separation between the prostate and rectal wall.

The purpose of this study is to determine the effect of a biodegradable, injectable hydrogel spacer on rectal dose in treatment plans for PSPT and IMPT for prostate cancer. We analyzed a variety of clinically relevant dosimetric parameters for both modalities in the presence and absence of these spacers, and we correlated the extent of displacement between the prostate and rectal wall (with the spacer in place) with rectal V70 to determine the optimal amount of displacement in terms of reducing rectal dose in both modalities.

(A) : Dose-volume histogram for prostate, rectum, and seminal vesicles for representative patient ; (B) : isodose lines for PSPT without spacer (C) : PSPT with spacer (D) : IMPT without spacer (E) : IMPT with spacer . Normal tissues depicted with colorwash include prostate (blue), seminal vesicles (orange), and rectum (green). Abbreviations: IMPT, intensity-modulated proton therapy; PSPT, passive scattering proton therapy.

Conclusion: Use of biodegradable hydrogel spacers for prostate cancer treatment provides a significant reduction of radiation dose to the rectum with proton therapy. Significant reductions in rectal dose occurred in both PSPT and IMPT plans, with the greatest reduction for IMPT-with-spacer relative to PSPT alone. Prospective studies are ongoing to assess the clinical impact of reducing rectal dose with hydrogel spacers.

International Journal of Particle Therapy: Spring 2019, Vol. 5, No. 4, pp. 23-31.

Consider Proton Therapy to limit those side effects and to improve Quality of Life

Proton therapy can provide a better quality of life for cancer patients. It can spare them the grueling post-treatment complications described in article below that are common with conventional Radiation Therapy..

Understanding the Management of Chronic AEs After Radiation Therapy

“Treatment techniques and comorbidities have a significant impact on the severity of chronic side effects,” said Haynes-Lewis, a nurse practitioner at Montefiore Einstein Center for Cancer Care. “Nurses should work with the patients to develop a plan to manage chronic side effects that optimize quality of life.”

To start, she added, knowing the difference between late AEs (those that occur or begin after therapy is completed and may occur months to year post-treatment) and long-term AEs (prolonged effects that begin during treatment and continue beyond the end of treatment) is important.

In her presentation, Haynes-Lewis focused on the management of chronic late side effects among patients with cancer.

Central Nervous System

Disease sites under this category can include the brain and spinal cord, from which the tissue are late reacting. Therefore, these changes are found, not in the clinic, but through imaging.

AEs of the central nervous system include increased atherosclerosis of the blood vessels in the brain, increased incidence of secondary brain tumors, radiation necrosis, cognitive decline, hormonal deficits, vision changes, hearing loss, and radiation myopathy.

“This is where nurses come in because we really need to educate, educate, educate the patients and their families,” Haynes-Lewis said. “We need to talk to them about the symptoms of stroke, incidents of what it looked like if you had a tumor – headaches, changes in vision, changes in gait, changes in mental status – those are all things that we need to talk to the patient about. A lot of times I tell them, maybe you just don’t feel right because there aren’t any words. And if they don’t feel right, I tell them to call their provider. Sometimes that is what happens.”

AEs associated with the central nervous system are often treated with steroids, bevacizumab (Avastin), hyperbaric oxygen therapy, surgical resection, memantine, donepezil (Aricept), cognitive rehabilitation, cochlear implants, hormonal replacement, and pentoxifylline.

Head and Neck

These AEs can occur in the nasopharynx, oral cavity, salivary glands, or neck. They include xerostomia, dysgeusia, fibrosis, lymphedema, dysphagia, dental caries, osteoradionecrosis, hearing loss, neuropathy, and changes in voice quality.

“These side effects affect every part of your life and your quality of life,” Haynes-Lewis said.

Management of these AEs can include acupuncture and massage, therapy (physical therapy, decongestive therapy, swallowing rehabilitation), and medications such as pentoxifylline, vitamin E, analgesics, saliva substitutes and stimulants, conservative debridement, hyperbaric oxygen, surgical resection and reconstruction, hearing aids, tympanostomy and aspiration, myringotomy and grommet insertion, voice therapy, and injection larynoplasty.

“You need to help (the patients) by just putting 2 and 2 together,” Haynes-Lewis said. “If you have a dry mouth, what does that do? It can affect your teeth, so we need to make sure (the patient) is seeing the dentist, that they are doing good oral hygiene and that they understand what that is and how to do it.”


AEs of the chest can occur in the breast, lung, mediastinal or axillary adenopathy, or esophagus. In this area of the body, risk factors for chronic AEs include age, gender, treatment techniques, concurrent chemotherapy, lung disease, history of smoking, and poor performance status.

Chest AEs from radiation include exacerbation or worsening of underlying comorbid lung disease, lung fibrosis, chest wall fibrosis, esophageal stricture, telangiectasias, pain, lymphedema, brachial plexopathy, and cardiotoxicity. These can be managed with dietary and behavioral modifications, pulmonary rehabilitation and physical therapy, esophageal dilation, and medications such as steroids, anti-inflammatories, gabapentin, pentoxifylline, vitamin E, prokinetic agents, and oxygen therapy.


In disease sites of the abdomen (gastric, liver, pancreas, colon, stomach, and small bowel), radiation therapy is commonly used in neoadjuvant and adjuvant treatment, as well as effective palliation for pain, bleeding, and obstruction.

AEs include dysmotility, stricture, fistula, obstruction, ulceration or perforation, and bleeding. To manage these, Haynes-Lewis recommended for dietary modifications; medications like analgesics, enzyme supplementation, anti-diarrheal, antiemetics, and proton pump inhibitors; endoscopic dilation; percutaneous endoscopic gastrostomy tube; and surgical intervention.


Sites for these AEs can include the prostate, bladder, cervix, ovaries, and colon, for which chronic toxicity can be correlated with the volume of radiation received.

These AEs–including diarrhea, hemorrhoids, proctitis, leakage of fecal incontinence, fistula or stricture, and obstruction–can be managed with dietary modifications; bowel rest; medications such as anti-diarrheal, sucralfate enemas, steroid suppositories and creams, and topical lidocaine; endoscopic interventions; hyperbaric oxygen therapy; and surgical resection.

Skin and Extremities

These AEs can include telangiectasia, chronic dermatitis, pigmentation changes, atrophy, fibrosis, ulceration, bone fractures, alopecia, and edema. In addition, they are often managed with antihistamines, colloidal oatmeal treatments, aloe, massages, physical therapy, and wound care.

In addition, Haynes-Lewis noted that global chronic AEs, such as fatigue, depression, insomnia, pain, anxiety, and post-traumatic stress disorder, exist across all cancer types, adding that these can be managed with medications, exercise, energy conservation, mind-body techniques, therapy, and referral to a survivorship program.

“Nurses should be at the forefront of chronic side effect management as part of survivorship care as the number of cancer survivors continue to increase,” she concluded.