Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.
BREAST CANCER
Whole-genome sequencing reveals breast cancers with mismatch repair deficiency
Mutational signature analysis found mismatch repair (MMR)-deficient breast cancer tumors, which could potentially be targeted with PD-1 immune checkpoint inhibitors, according to a recently published study (Can Res 2017; doi:10.1158/0008-5472.CAN-17-1083). Researchers used previously published whole genome sequencing data of breast cancer tumors from 640 patients and analyzed patterns of mutagenesis. They also looked for mutations in multiple genes known to be associated with MMR deficiency: MLH1, MSH2, MSH6, PMS2, PMS1, SETD2, MYH11, EPCAM, TGFBR2, MLH3, and MUTYH, in order to identify the defects responsible for the MMR deficiency. Findings showed that 11 of 640 tumors harbored the MMR deficiency in variable amounts. In addition to base substitution mutational signatures specific to MMR-deficient tumors, they also found an average of 20,870 small insertions/deletions in the 11 MMR-deficient breast cancer tumors compared to only a fraction, 270 on average, in the non-MMR-deficient tumors. Due to its high degree of sensitivity and specificity to classify tumors, mutational signature analysis might be a better biomarker for use in future clinical trials, according to study authors.
PANCREATIC CANCER
Association of alterations in main driver genes with outcomes of patients with resected pancreatic ductal adenocarcinoma
Alterations in four main genes are responsible for how long patients survive with pancreatic cancer, according to a new study (JAMA Oncol 2017; doi:10.1001/jamaoncol.2017.3420). The study included 356 patients with resected pancreatic adenocarcinoma. After the tumors were removed, scientists extracted DNA from the cancerous tissue and nearby normal tissue, and conducted next-generation DNA sequencing on the specimens. The analysis centered on the activity of the KRAS, CDKN2A, SMAD4, and TP53 genes. Results showed that patients who had three or four of the altered genes had worse disease-free survival and overall survival (OS) compared to patients with one or two altered genes. Five-year OS was 18.4 percent for patients with 0-2 gene alterations, 14.1 percent for individuals with three alterations, and 8.2 percent for those with four alterations, investigators reported. Pancreatic cancer is aggressive and generally has poor survival odds. Patients who can undergo surgery as part of treatment often survive longer, and some patients fare best when they can receive chemotherapy prior to surgery. "But having customized, molecular information will provide an even greater understanding of how the disease is likely to progress in each patient," researchers noted.
POST-ACUTE CARE
Predictors of posthospital transitions of care in patients with advanced cancer
Recent findings show patients with advanced cancer who are discharged to post-acute or hospice care demonstrated greater symptom burdens and impaired physical function, in addition to worse survival, than those discharged to the home (J Clin Oncol 2017; doi:10.1200/JCO.2017.74.0340). A prospective study was conducted among 932 patients with advanced cancer who had unplanned hospitalizations between September 2014 and March 2016. The primary outcome was discharge location and the secondary outcome was survival. Among the enrolled patients, the majority (77.9%; n=726) were discharged home without hospice, while 12.7 percent (n=118) were discharged to post-acute care, and 9.4 percent (n=88) were discharged to hospice. According to logistic regression, patients who went to hospice or post-acute care were older, lived alone, and had impaired mobility compared to patients who were discharged home. Additionally, they experienced longer hospital stays, as well as higher scores for physical outcomes and depression. Given these results, researchers concluded that "these patients may benefit from interventions to enhance their quality of life and care."
CAR T-CELL THERAPY
Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells
Researchers have discovered new potential biomarkers and a novel algorithm that could help identify patients at increased risk of suffering from severe neurotoxicity after receiving CD19 CAR T-cell therapy (Can Discov 2017; doi:10.1158/2159-8290.CD-17-0698). Researchers analyzed data from 133 adults with relapsed and/or refractory CD19 B-cell ALL, non-Hodgkin lymphoma, or chronic lymphocytic leukemia who were treated with lymphodepletion chemotherapy followed by infusion of JCAR014, a type of CD19 CAR T-cell therapy. Within 28 days of treatment, 53 patients (40%) developed grade 1 or higher neurologic adverse events and of these 28 (21%) had grade 3 or higher neurotoxicity; alterations in neurologic status completely resolved in a majority of cases. Four of the 133 patients (3%) developed fatal neurotoxicity. Investigators found that patients with an early onset of cytokine release syndrome were at increased risk of subsequently developing severe neurotoxicity. According to researchers, patients who experienced neurotoxicity were mostly younger and had B-cell ALL, higher tumor burden, and more CD19-positive cells in the bone marrow compared with those who did not develop this side effect. Researchers developed a predictive classification tree algorithm based on the side effects, including fever, and high serum IL-6 and MCP-1, to identify patients within the first 36 hours after CAR T-cell infusion, who are at increased risk for severe neurotoxicity.
DUCTAL CARCINOMA IN SITU
Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ
New findings suggest delaying radiotherapy by more than 12 weeks is associated with an increased risk for ipsilateral breast tumor recurrence among women who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) (Cancer 2017; doi:10.1002/cncr.30972). A prospectively maintained database was utilized to identify women (n=1,323) with DCIS who underwent breast-conserving surgery and radiotherapy between 1980 and 2010. Investigators compared recurrence rates among patients who began radiotherapy less than 8 weeks after surgery, 8-12 weeks after, and more than 12 weeks after surgery to evaluate the association between timing of radiotherapy and recurrence. Median follow-up was 6.6 years and 311 patients were followed for 10 or more years. Researchers categorized patients by radiotherapy timing with most patients (61%; n=806) receiving radiotherapy within 8 weeks of surgery. Twenty-nine percent (n=386) received radiotherapy at 8-12 weeks and 10 percent (n=131) at more than 12 weeks after surgery. The 5- and 10-year recurrence rates were 5.8 percent and 13.0 percent, respectively, for patients who started radiotherapy fewer than 8 weeks after surgery; 3.8 percent and 7.6 percent, respectively, for radiotherapy starting between 8-12 weeks after surgery; and 8.8 percent and 23.0 percent, respectively, for a radiotherapy delay of greater than 12 weeks after surgery (P = .004).
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