Yale Cancer Center research highlighted at ASTRO 2019
Yale Cancer Center (YCC) scientists presented research at the 61st annual American Society for Radiation Oncology (ASTRO) annual meeting in Chicago. The conference brought together clinicians and researchers from all oncology disciplines to exchange ideas and promote multidisciplinary care for cancer. Here are the research highlights from YCC scientists:
Results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer.
The results of a phase II clinical trial by YCC researchers show adding high-dose radiation after patients become resistant to immunotherapy increases survival time for patients with metastatic non-small-cell lung cancer (NSCLC).
“This study provides one more important piece of data that indicates the combination of immunotherapy and radiation is safe, and that for certain patients, may emerge as an important therapeutic option when immunotherapy alone stops working,” said Allison M. Campbell, M.D., Ph.D., a resident in the Department of Therapeutic Radiology at YCC and lead author on the study.
The clinical trial, performed at Smilow Cancer Hospital, enrolled 21 patients who progressed after receiving the immunotherapy drug pembrolizumab. Patients with high numbers of T cells in their tumors before radiation did best, with a median progression free survival of 6.7 months. In a few of the patients, the researchers saw responses in tumors through the whole body, not just the single site treated with radiation. Those responses lasted longer than one year.
External validation and radiologist comparison of a deep learning model to identify extranodal extension in head and neck squamous cell carcinoma with pretreatment computed tomography imaging.
Oncologists planning therapy for patients with head and neck squamous cell carcinoma (HNSCC) want to know if the tumor has expanded beyond the lymph nodes, because in that case, surgery often does not improve outcomes. However, it’s very difficult for radiologists to judge whether this “extranodal extension” (ENE) is present by analyzing computer tomography (CT) images of lymph nodes, therefore avoiding the side effects and costs of unnecessary surgery.
Benjamin Kann, M.D., lead author of the study and associates in the lab of Sanjay Aneja, M.D., senior author of the study, have developed a computer model based on a form of artificial intelligence (AI) called deep learning that outperformed standard checks for ENE among CT scans from 82 HNSCC patients. The deep learning software also delivered more accurate predictions than two diagnostic radiologists who examined the CT scans.
“These results are an indication that we can push this deep learning model forward into a first clinical trial,” said Kann, who is currently an instructor of radiation oncology at Dana-Farber Cancer Institute. “Deep learning in general has been shown to be a great way to tease out information within images that humans have difficulty in obtaining or can’t obtain. There is a huge opportunity to apply these techniques to better predict patient outcomes and help in clinical decision-making across many cancers.”
The Effect of Race and Decision Aids on Provider Recommendation for Prostate Cancer Treatment Planning: A Randomized Study
According to YCC researchers, African-American men are more likely to be diagnosed with prostate cancer and to succumb to the disease than Caucasian men, largely because of more limited access to healthcare. “In a randomized online survey of decision-making in prostate cancer we demonstrated that radiation oncologists take the race of the patient into account when recommending treatment,” said Amandeep Mahal, a medical student at Yale University and lead author of the study.
The survey began with a hypothetical clinical vignette of a 70-year-old man with prostate cancer who recently underwent prostatectomy. Survey respondents read identical clinical vignettes but were randomly assigned an African-American or Caucasian patient, with a photograph. They were then asked if they would treat with adjuvant radiotherapy or observation. Participants next received an American Society of Clinical Oncologists value framework decision-making aid that incorporated relevant data to compare the two treatment options, and asked again for a selection.
Overall, the radiation oncologists chose radiotherapy far more often for the African-American patient than the Caucasian patient. This group was even more likely to make that decision after viewing the value framework—recommending radiotherapy for 77% of African-American patients and 38% of Caucasian patients. However, urologists and medical students were more likely to recommend observation than radiotherapy for all patients. Neither race nor the value framework affected their choices.
One explanation for the different response by medical specialty, Mahal said, is that radiation oncologists may be most knowledgeable about radiotherapy and most familiar with the most recent evidence about its effectiveness. “For example, one recent study indicated that African-American men have comparatively higher cure rates than Caucasian men when treated with radiation therapy,” Mahal noted. “Radiation oncologists also may have formed strong opinions about the utility of adjuvant treatment, as well as the need for more aggressive therapy in African-American men. It is likely that some force other than physician bias is largely responsible for disparities in outcomes between African-American and Caucasian men. Socio-cultural inequalities such as access to healthcare and the pervasive effects of structural racism remain implicated.”
Whole Genome CRISPR-Cas9 Screen Identifies STING as a Determinant of Intrinsic Radio-sensitivity in Head and Neck Squamous Cell Carcinoma.
Findings in a new study by YCC researchers show head and neck squamous cell carcinoma (HNSCC) that is not associated with the human papillomavirus (HPV) has a poor prognosis compared to HPV-associated HNSCC tumors. Thomas Hayman, M.D., Ph.D., lead author of the study and a resident in the Department of Therapeutic Radiology at YCC and colleagues in the lab of Joseph Contessa, M.D., Ph.D., found that loss of a protein called STING causes increased survival after radiation – suggesting that activation of this pathway may aid in treating the condition.
YCC scientists aimed to identify new factors that regulate HNSCC tumor cell survival after treatment with radiation therapy, using a relatively new method of whole-genome screening based on CRISPR-Cas9 genetic engineering. This technique allowed them to create populations of cells in which each cell is missing expression of one human gene that codes for a protein. The researchers then irradiated these cells and examined which cells survived. “To the best of our knowledge, no one has completed this whole-genome CRISPR-Cas9 screening with radiation,” said Hayman. “Strikingly, we found that one gene significantly enhanced resistance to radiation when knocked out, and that gene was STING.” The researchers confirmed these findings in mice using tumors engineered to lose the STING protein. They also discovered that STING loss boosted resistance to cisplatin, a chemotherapy commonly used in HNSCC in combination with radiation.