Proton therapy: the current status of the clinical evidences – by Dongryul Oh

Precision and Future Medicine 2019

Proton Therapy Clinical Evidences – Dongryul Oh

The dosimetric advantages of proton therapy—compared with photon therapy—have been clearly defined in many comparison studies involving various tumor sites. There are now accumulating clinical data demonstrating that this dosimetric advantage can lead to better outcomes such as reduced RT toxicity and improved treatment outcomes. 

Pediatric Tumors

RT has an important role in treating pediatric tumors including central nervous system (CNS) tumors, extra-cranial sarcomas, neuroblastoma, and hematopoietic tumors. Long-term toxicities, including secondary malignancies, neurocognitive dysfunctions, growth and musculoskeletal problems, and cardiac problems, are major concerns in pediatric patients who undergo RT. There have been many efforts to reduce the RT dose and volume to avoid these RT-related toxicities.

Proton therapy is one of the best options to reduce unnecessary irradiation dose and volume in pediatric patients.

More than 30 pediatric tumor types were treated, mainly with curative intent: 48% were CNS, 25% extra-cranial sarcomas, 7% neuroblastoma, and 5% hematopoietic tumors

Head and Neck Tumors

Retrospective data have demonstrated better local control (LC) and overall survival (OS) with proton therapy than with photon therapy including IMRT and stereotactic body radiation therapy (SBRT).

Proton therapy has also demonstrated better survival rates in nasal cavity and paranasal sinus tumors.

In oropharyngeal cancers, proton therapy can reduce toxicity to normal tissues.

Proton therapy can also reduce toxicities in unilateral irradiation, such as in cases involving major salivary gland tumor and oral cavity cancers, because the exit dose of the proton beam is essentially negligible

CNS tumors

Cognitive impairment has been one of major concerns following RT for CNS tumors. Proton therapy has a potential benefit to reduce the irradiated dose to normal brain tissue to prevent cognitive dysfunction. In addition, a dose escalation could be possible in radioresistant brain tumors such as high-grade gliomas.

Gastrointestinal tumors

Proton therapy can spare the surrounding normal tissues when it is used to treat gastrointestinal tumors. In the management of hepatocellular carcinoma (HCC), it is very important to spare liver function. Because the liver is an organ with parallel functional subunit in the model of radiation response of normal tissues, liver toxicity is more sensitive to irradiated volume. Proton therapy has a major advantage in reducing the irradiated volume of remnant liver when irradiating the tumor. In many retrospective trials, proton therapy resulted in favorable outcomes.

Re-irradiation

Proton therapy has the advantage of irradiating the target while reducing the dose to the surrounding normal tissues; thus, it has a potential benefit in re-irradiation. Many retrospective studies investigating re-irradiation in various tumor sites have been reported.

Non-Small Cell Lung Cancer

Low-dose shower is a major risk for radiation pneumonitis (RP) when treating non-small cell lung cancer (NSCLC) with photon therapy. If the lateral beam placement is avoided to reduce the lung dose, the irradiated dose to heart is consequently increased and results in increased cardiac death in long-term follow-up. In many dosimetric studies, proton therapy demonstrated advantages in lung and heart dose compared with photon therapy. Several clinical studies have reported treatment outcomes and toxicities of proton therapy in early-stage disease, locally advanced disease, re-irradiation, and in postoperative settings 

Indications for Proton Therapy

American Society for Radiation Oncology (ASTRO)  has updated the recommendations for insurance coverage. The ASTRO recommendation is based on four selection criteria:

  1. a decrease in dose inhomogeneity in a large treatment volume is required to avoid an excessive dose “hotspot” within the treated volume to lessen the risk for excessive early or late normal tissue toxicity;
  2. the target volume is in close proximity to ≥1 critical structure(s), and a steep dose gradient outside the target must be achieved to avoid exceeding the tolerance dose to the critical structure(s);
  3. a photon-based technique would increase the probability of clinically meaningful normal tissue toxicity by exceeding an integral dose-based metric associated with toxicity;
  4. and, finally, the same or an immediately adjacent area has been previously irradiated, and the dose distribution in the patient must be carefully modelled to avoid exceeding the cumulative tolerance dose to nearby normal tissues.

Based on the above medical necessity requirements and published clinical data, group 1, which is recommended coverage is listed as follows:

  • ocular tumors, including intraocular melanomas;
  • skull base tumors, primary or metastatic tumors of the spine, where spinal cord tolerance may be exceeded with conventional treatment or where the spinal cord has previously been irradiated;
  • hepatocellular cancer;
  • pediatric tumors;
  • patients with genetic syndromes making total volume of radiation minimization crucial;
  • malignant and benign primary CNS tumors;
  • advanced and/or unresectable H&N cancers;
  • the paranasal sinuses and other accessory sinuses cancers;
  • non-metastatic retroperitoneal sarcomas;
  • and cases requiring re-irradiation.

Read the full study on Precision and Future Medicine 2019

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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.

https://medicalxpress.com/news/2019-05-proton-therapy-cancer-lowers-side.html

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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.

https://www.onclive.com/publications/oncology-live/2019/vol-20-no-11/montefiore-study-may-help-establish-patient-criteria-for-proton-therapy

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Patient outcome of pencil beam-scanning proton therapy in Head and Neck adenoid cystic carcinoma

M. Pelak, M. Walser, B. Bachtiary, A. Bolsi, J. Hrbacek, A. Lomax, U. Kliebsch1, A. Pica, D.C. Weber

“Proton beam therapy using PBS is an effective and safe way of delivering definitive and adjuvant irradiation in patients with Adenoid Cystic Carcinoma (ACC) of the head and neck region. Most ACC patients that progressed after treatment failed distantly.”

https://lnkd.in/dEA3_rm

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