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Evaluation of First-Line Radiosurgery vs. Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study

The international First-line Radiosurgery for Small-Cell Lung Cancer (FIRE-SCLC) analysis led by University of Colorado Cancer Center researchers details clinical outcomes for 710 patients with brain metastases from small cell lung cancer treated with first-line stereotactic radiosurgery (SRS), without prior treatment with whole-brain radiation (WBRT) or prophylactic cranial irradiation (JAMA Oncol 2020; doi:10.1001/jamaoncol.2020.1271). Following first-line SRS, the outcomes were encouraging overall with a median time to brain progression of 8.1 months and a median overall survival of 8.5 months. The investigators also compared these SRS results with a control group of 219 patients treated with first-line WBRT for brain metastases, which is the current standard of care for small cell lung cancer. Importantly, no overall survival benefit was observed with WBRT compared to SRS. In fact, the survival outcomes were slightly better with SRS even after matching for baseline characteristics. The authors were careful to note, however, that the observed differences in survival in favor of SRS could be related to uncontrolled treatment selection factors in the setting of a retrospective analysis. The study also provided detailed analyses of outcomes with SRS by the number of brain lesions treated. Patients treated with SRS for a single brain metastasis experienced the best brain control and overall survival outcomes. After that, the clinical outcomes for patients with 2-4 versus 5-10 brain metastases were very similar, whereas patients with 11 or more metastases were seen to have the shortest time to brain progression and overall survival. The authors note that prospective trials evaluating the role of first-line SRS for small cell lung cancer patients are needed to confirm the encouraging results observed in this retrospective study. In the meantime, this large international analysis provides important descriptive and comparative data on first-line SRS as a potential emerging treatment option for brain metastases in carefully selected small cell lung cancer patients.



Glutamine Depletion Regulates Slug to Promote EMT & Metastasis in Pancreatic Cancer

Scientists have shown that pancreatic cancer metastasis can be suppressed by inhibiting a protein called Slug that regulates cell movement. The study also revealed two druggable targets that interact with Slug and hold promise as treatments that may stop the spread of pancreatic cancer (J Exp Med 2020; Pancreatic cancer cells, like all cancer cells, grow rapidly and quickly deplete the nutrients in their surrounding environment. To meet their energy needs, tumor cells boost metabolic pathways that normal cells don't use. The researchers aimed to understand how pancreatic cancer cells respond to nutrient deprivation-focusing on the most commonly depleted nutrient, glutamine-with the goal of finding treatments that stop the growth of cancer cells without harming healthy cells. In the study, the scientists used a mouse model of pancreatic cancer to show that, in response to glutamine deficiency, a protein called Slug drives metastasis by activating the epithelial-mesenchymal transition, or EMT-the process cells use to free themselves from tightly packed tissue. Inhibiting Slug reduced the cancer's ability to spread-demonstrated by a reduction in the number and size of secondary lung tumors. The scientists also established that patient samples with higher levels of Slug were linked to a poor prognosis-further indicating that blocking the protein may be beneficial. Because Slug is considered "undruggable" due to inherent biological properties, the scientists continued to search for proteins that interact with Slug and could be targeted with a drug. Their research identified two promising targets: ERK and eIF2 alpha. ERK inhibitors are currently under evaluation in clinical trials for pancreatic and other cancers; and an eIF2 alpha inhibitor has completed animal testing.



Medical Costs Associated With Metastatic Breast Cancer in Younger, Midlife & Older Women

New research shows much higher costs for treating metastatic breast cancer patients than for earlier-stage cancer patients or those without cancer (Breast Cancer Res Treat 2020; The findings revealed the largest expected costs were among women ages 18-44. Breast cancer in younger women is typically diagnosed at more advanced stages, and is more aggressive and less responsive to treatment. Among women ages 18-44, the incremental average monthly costs of treating metastatic breast cancer were $4,463 compared to monthly costs of $2,418 for treating stage I cancer. Among other age groups, the treatment costs for advanced cancer were not statistically different. Women living in North Carolina and treated for breast cancer between 2003 and 2014 were included in the study that was funded by the U.S. Centers for Disease Control and Prevention. In the study group, 4,806 had metastatic breast cancer and 21,772 had non-metastatic cancer. The patient data was collected in a cancer registry coordinated by the Lineberger Comprehensive Cancer Center. Using statistical modeling based on insurance claims data, researchers estimated medical costs for patients with metastatic breast cancer. For comparison, they also estimated costs for patients with earlier-stage breast cancer and 109,631 women with no cancer who were in the same age group, from the same county of residence, and who had the same type of health insurance. For women with metastatic breast cancer where the 5-year survival rate is only 26.3 percent compared to 98.8 percent for localized cancer, treatment continues for longer and it includes end-of-life care. The finding that medical costs are higher for younger and middle age women may reflect their desire for more aggressive treatment and willingness to pay for additional months of life, researchers said, or it may reflect breakdowns in shared decision-making between patients and practitioners, leading to treatments with minimal financial and health benefits for patients.



BRCA1 Promoter Methylation & Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis

Scientists have found that a specific type of ovarian cancer could possibly benefit from existing platinum-based chemotherapy and new DNA repairing treatments, following better testing (JNCI 2020; Ovarian cancer patients with a mutated BRCA1 gene live longer with platinum chemotherapy and new DNA repairing treatments than patients who don't have the mutation. This led the researchers to investigate whether these treatments could also benefit other ovarian cancer patients whose BRCA1 gene has been modified in a different way. Instead of having an inherited mutated BRCA1 gene, some patients have this gene modified in a way that is thought to silence it. The researchers analyzed 2,636 patients with ovarian cancer from 15 international studies to see if those with this silenced BRCA1 gene had similar outcomes to those with the mutated gene. They found that both the mutated and silenced BRCA1 gene were found in serous ovarian cancers and arise at a younger age compared to cancer patients without a mutated or silenced gene. They also found that the patients with the silenced gene display faulty DNA repair more than the patients with the mutated gene. However, unlike those with the mutated BRCA1 gene, patients with the silenced gene did not respond any better to platinum chemotherapy or have a better prognosis than those with the normal functioning BRCA1 gene. The researchers believe this difference was the case due to the different methods used in each study to detect the silenced gene. The studies that used a specific test found that patients with a BRCA1 silenced gene lived longer on the platinum chemotherapy treatments compared to those patients whose did not have a silenced or mutated gene.