By Laura Williamson, Science Writer
The Cancer Breakthroughs session is a collaborative effort among medical societies to share the latest cutting-edge cancer research, showcasing studies from the 2023 annual meetings of the American Society of Clinical Oncology (ASCO) and American Association of Physicists in Medicine (AAPM). The session was moderated by ASTRO President Howard Sandler, MD, FASTRO, Cedars-Sinai Medical Center, Los Angeles.
The first discussant was Kimmie Ng, MD, MPH, Dana-Farber Cancer Institute/Harvard Medical School, Boston, who shared two abstracts from ASCO’s 2023 annual meeting that she called “practice changing.” Dr. Ng noted that both ASCO and ASTRO had chosen to focus their meetings on the importance of partnering with patients.
Dr. Ng began with a presentation of “INDIGO: A Phase 3, Global, Randomized, Double-blinded Study of Vorasidenib versus Placebo in Patients with Residual or Recurrent Grade 2 Glioma with an IDH1/2 Mutation.” The study showed that in patients who had prior surgery, vorasidenib, an oral inhibitor of IDH1 and IDH2 mutations, was superior to placebo for progression free survival and showed significant improvement in time to next treatment intervention.
Dr. Ng explained that IDH1/2 mutations occur in the vast majority of low-grade diffuse gliomas, affecting predominantly young adults. “They are incurable tumors that can infiltrate the brain, leading to severe disability and death. New treatment approaches are desperately needed.”
Varasidenib showed a benefit across all subgroups of patients and was very well tolerated, she said. “This is what oncologists really dream of for their patients. Varasidenib represents a new standard of care for patients with grade 2 glioma, with evidence of measurable non-enhancing disease, but without immediate need for radiation plus chemotherapy.”
Dr. Ng then presented “Preoperative Chemotherapy with Selective Chemoradiation versus Chemoradiation for Locally Advanced Rectal Cancer: The PROSPECT Trial.” She noted that in keeping with the theme of partnering with patients, investigators worked directly with patient advocates when designing the study and included patient-reported adverse events, with an emphasis on quality of life.
This de-escalation trial found “neoadjuvant FOLFOX, with only selective use of chemoradiation, was a safe and effective treatment option for patients with cT2N+, cT3N-, or cT3N+ rectal cancer who are candidates for sphincter-sparing surgery,” she said. “Overall health-related quality of life was not significantly different between the two arms.”
While there was significantly more toxicity among those treated with FOLFOX compared to chemoradiotherapy, by 12 months there were very low rates of severe side effects in both arms, she said, adding that “patient preferences need to be taken into account when making treatment decisions.”
When the PROSPECT study was originally reported in June, ASTRO’s Gastrointestinal (GI) Resource Panel issued a patient-focused statement to clarify that the trial did not explicitly conclude that radiation therapy should be omitted, contrary to many news reports, but rather that select patients now have an additional treatment option to consider in discussions with their care team. The PROSPECT approach was recently adopted by the National Comprehensive Cancer Network (NCCN) in its clinical practice guidelines.
Discussant Kristy K. Brock, PhD, FASTRO, MD Anderson Cancer Center, Houston, who is vice chair of the AAPM Science Council, next presented three studies from AAPM’s 2023 annual meeting. Dr. Brock highlighted, “some of the work that the medical physics field is doing in leveraging deep learning to classify cancer subtypes from histological images using transformers and to investigate the use of deep learning and transformer models to aggregate large amounts of data from electronic health records to be able to predict overall survival,” as well as "a study on the prompt gamma rays spectroscopy for proton range verification.”
The first abstract she presented, “Cancer Subtype Classification from Histologic Images Using Transformers,” tested a hierarchical model using a transformer encoder and decoder for cancer subtype classification, with histopathology whole slide images. The model outperformed majority voting and multiple-instance, learning-based classifiers in three cancer subtype classification tasks.
The findings “demonstrate the significant benefit of transformer models and the importance of large, publicly available datasets to compare algorithms,” she concluded.
She next presented findings from “Investigating Aggregation Methods of Contextualized Transformer Embeddings of Long Electronic Health Record Notes for Glioma Overall Survival Prediction.” This study looked at aggregating unstructured data from clinical notes for use in predicting outcomes. “The goal was to be able to predict 14-month survival of glioma patients,” Dr. Brock said.
The study showed a sequential aggregation encoder effectively aggregated long electronic health record notes for outcome prediction tasks. “Large language models can help us to investigate at a scale not previously possible,” she concluded.
Finally, Dr. Brock described an ongoing study, “Clinical Study of Prompt y-ray Spectroscopy for Proton Range Verification,” which has been enrolling patients with brain tumors since 2022. The trial is investigating ways to fine-tune proton radiation treatment by better measuring proton range. To date, the clinical prototype has been successfully used to deliver 30 treatment fractions to six patients.
Initial findings suggest “prompt y-ray spectroscopy provides a non-invasive in vivo measurement of the proton range,” she said. “The first results show mainly systemic range errors.” Patient recruitment is ongoing and investigators are considering expansion to other treatment sites.
“This has very exciting potential for clinical impact,” said Dr. Brock. Benefits include the ability to spare normal tissue, enable patient-specific measurements and learn across patient populations.
Registered participants can view the Cancer Breakthroughs session via the Annual Meeting Portal.
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