Proton Therapy News and Research

Although radiation therapy is a key treatment for patients with breast cancer, the proximity of the heart to the treatment area – especially in patients with left-sided breast cancer – increases the risk of radiation-induced cardiac disease (RIC). Reducing this risk is an important area of continued study for researchers. While mean heart dose remains a key metric used to indicate the risk of a cardiac event following RT, the authors of this article point to several studies to advocate for further research aimed at better understanding which substructures in the heart may be more specifically correlated to RIC (like the left anterior descending artery) and then further studying the threshold for RT on those substructures. Empirical evidence linking the heart’s substructures to RT thresholds and RIC risk – paired with proton therapy technology like pencil-beam scanning – could pave the way for delivering even more precise RT, while reducing the potential risk of RIC in breast cancer patients.

There is growing interest among the medical community in using irradiation – or radiosurgery – as a pre-operative treatment for brain tumors. A webinar held by The Radiosurgery Society covers the latest research, clinical evidence, and rationale for using pre- operative radiosurgery to treat brain tumors. Dr. Victor Mangona of Texas Center for Proton Therapy noted that it is not uncommon for patients with brain tumors to have a dominant mass, as well as smaller lesions, and pre-operative radiosurgery has the potential to simultaneously treat presenting symptoms like these, while gathering a pathology report of the patient’s tumor. Additionally, patients may also benefit from faster time to treatment because they would not have to wait on post-operative recovery, before undergoing irradiation treatment.

Interim analysis of a Phase II study of patients with metastatic lung and breast cancers indicates that proton craniospinal irradiation therapy can mitigate disease progression in the central nervous system and improve overall survival when used to treat patients whose disease has metastasized into the leptomeningeal space surrounding the brain and spinal cord. Survival for patients with this disease is four to six months with standard irradiation treatments, such as whole-brain radiotherapy (WBRT) or focal spine radiotherapy. While these therapies relieve symptoms, they do not stop progression in the leptomeningeal space or prolong survival. Whereas analysis of the study indicated proton craniospinal irradiation therapy increased survival from six months to 9.9 months. Additionally, results showed that 92 percent of patients receiving standard photon involved-field radiotherapy (IFRT) saw disease progression in the central nervous system at six months – compared to only 22 percent of patients who received proton craniospinal irradiation.

This article outlines the results of a phase III clinical trial, originally reported in the Journal of Clinical Oncology, which demonstrated an increase in neurocognitive impairment outcomes in pediatric patients undergoing radiation therapy for medulloblastoma, specifically when increasing radiotherapy doses to the cerebral cortex or frontal white matter and hippocampus. The implications of the study are significant, underscoring the need for targeted proton-beam therapy to potentially mitigate or eliminate cognitive declines in pediatric patients with medulloblastoma by implementing brain substructure- informed radiotherapy planning techniques.

A follow-up study published in the International Journal of Radiation Oncology, Biology, Physics on Nov. 1, 2021, demonstrated that childhood cancer survivors, who received intensity-modulated radiation therapy, had an increased risk of developing second malignant neoplasms (SMNs). The study findings suggest that alternatives to IMRT, including proton beam therapy (PBT) should be considered. As an alternative modality for radiation treatment, proton therapy delivers radiation to a tumor in a precisely planned dose, thereby minimizing potential damage to surrounding normal tissue and reducing the cumulative incidence of malignant recurrence.

On Nov. 1, 2021, the International Journal of Radiation Oncology, Biology, Physics published the results of an assessment that examines optimal radiation therapy – comparing craniospinal irradiation (CSI) or focal field – used to treat atypical teratoid rhabdoid tumors (ATRTs). The study evaluated treatment in 65 pediatric patients across 19 institutions chronicled in the Pediatric Proton/Photon Consortium Registry (PPCR). Tumor, treatment, and outcome data were compiled to assess the impact of radiation therapy dose and volume, and an overall survival analysis was performed using the Kaplan Meier method, with the reverse Kaplan Meier method implemented for median follow-up. The findings showed that practice patterns strongly favored focal RT and 54Gy improved local control. Further studies are warranted and in progress.

This study examined the feasibility of reducing general anesthesia use among pediatric patients undergoing radiation therapy to mitigate associated short-and long-term risks. The team of researchers reviewed prospectively-collected data on pediatric patients treated with proton therapy from the Pediatric Proton/Photon Consortium Registry (PPCR), representing a cohort of more than 3,000 patients – who range in age from 0 – 21 years old and were treated at 17 proton therapy centers across the United States from 2001-2021. The study determined that age and receipt of craniospinal irradiation (CSI) were the most important predictors of anesthesia use with proton therapy.

A study published in the International Journal of Radiation Oncology, Biology, Physics on Nov. 1, 2021, follows a scientific team’s efforts to characterize proton craniospinal irradiation (CSI) practice patterns by carefully examining CSI plans included in the Pediatric Proton/Photon Consortium Registry (PPCR). The study findings indicate significant variability in current proton CSI practices, and the research team recommends the development of clear guidelines to optimize and standardize target delineation and planning of CSI is recommended as evidence evolves.

This article explores the results of a randomized controlled trial in patients with esophageal cancer. Authors of the study, published in the Journal of Clinical Oncology on July 25, 2020, report that proton therapy significantly reduced toxicity in patients who participated in the trial. The article includes commentary of independent peers within the industry.

A randomized trial of patients with esophageal cancer compared total toxicity burden and progression-free survival between two modalities: intensity-modulated radiation therapy (IMRT) and proton beam therapy. Total toxicity burden rates were lower for patients treated with proton beam therapy versus IMRT, concluding that for locally advanced esophageal cancer, proton beam therapy reduced the risk and severity of adverse events compared with IMRT.

Research continues to demonstrate the crucial role of radiation therapy in cancer care.  New research demonstrates that even in patients with the most advanced nasopharyngeal carcinomas who have isolated metastasis, there is a benefit for adding local radiation therapy.  In this recent study they use the most advanced radiation technique available to them, IMRT, however patients in Texas have an even more advanced radiation technique to reduce toxicity and extend life by using proton therapy, a specialized form of radiation therapy that excels at the treatment of nasopharyngeal carcinoma.  Prior studies have demonstrated that proton therapy has superior dosimetry and should allow these most advanced patients to get their treatment with as little toxicity as possible so they can continue their lives with minimal residual side effects.

The relatively higher cardiac dose exposure for esophageal cancer may result in the earlier onset of cardiac diseases, according to a study of 479 patients with esophageal cancer. The study examined incidence, onset, and long-term survival outcomes of high-grade cardiac events following radiotherapy, the results of which conclude severe cardiac events were relatively common in patients with early onset esophageal cancer after radiotherapy, especially those with preexisting cardiac disease and higher radiation doses to the heart.

In a study of 450,373 pediatric and adult patients with a first cancer diagnoses between 2004 and 2015 who received 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy (IMRT), or proton beam therapy, overall, the incidence of a second cancer diagnosis was less likely to occur in patients whose primary cancer was treated with proton beam therapy. There was no overall difference in the risk of second cancer in patients who received 3-dimensional conformal radiotherapy versus IMRT.

Pediatric patients with medulloblastoma responded more favorably in this first known study to compare intellectual trajectories between those treated with proton radiotherapy versus those treated with photon radiotherapy. Proton radiotherapy may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy.

In this analysis, the authors evaluated 1,483 adults with nonmetastatic cancer for the risk of severe adverse events associated with unplanned hospitalizations with concurrent proton-based chemoradiotherapy for patients undergoing conventional photon radiotherapy. The findings suggest that proton-based chemoradiotherapy was associated with significantly reduced adverse events that caused unplanned hospitalizations, with similar disease-free and overall survival.