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.

CANCER COSTS

Financial burden in survivors of childhood cancer: a report from the childhood cancer survivor study

A recent study has found that adult survivors of childhood cancer spent significant portions of their income on out-of-pocket medical costs compared to their siblings without a history of cancer (J Clin Oncol 2017; doi:10.1200/JCO.2016.71.7066). Between May 2011 and April 2012, an age-stratified, random sample of survivors of childhood cancer and a sibling comparison group were surveyed by researchers. Enrolled patients completed a survey on household income, out-of-pocket medical costs, and financial burdens. Based on study findings, childhood cancer survivors were more likely than siblings to experience out-of-pocket medical costs of 10 percent or more of their annual income (10% vs. 2.9%; P < .01). Researchers found that survivors with greater out-of-pocket costs also reported lower incomes. Data supported an association between higher out-of-pocket costs and hospitalization within the past year for childhood cancer survivors (OR = 2.3; 95% CI, 1.1-4.9). Investigators concluded that these findings "highlight the need to address financial burden in this population with long-term health care needs."

CARCINOMA OF UNKNOWN PRIMARY

Utility of genomic analysis in circulating tumor DNA from patients with carcinoma of unknown primary

New research, utilizing next-generation sequencing of circulating tumor DNA (ctDNA), identified distinct genomic profiles with potentially-targetable alterations in 99.7 percent of patients with carcinoma of unknown primary (CUP) who have detectable alterations (Cancer Res 2017; doi:10.1158/0008-5472.CAN-17-0628). Liquid biopsies from 442 patients with CUP were utilized to interrogate 54-70 genes in ctDNA. Investigators found that a total of 66 percent of patients had at least one characterized genetic mutation and 43.9 percent harbored two or more. According to study results, the most prevalent variants were found in the genes TP53, KRAS, PIK3CA, BRAF, and MYC. Researchers conducted two case studies to demonstrate the clinical relevance of their findings. The first case study analyzed a series of five liquid biopsies from a woman with metastatic CUP and identified dynamic changes in ctDNA that corresponded to therapeutic interventions. The second case matched a patient with adenocarcinoma of unknown primary with liver and abdominal lymph node metastases harboring KRAS and MLH1 mutations to combination treatment with trametinib and nivolumab. Within 8 weeks, researchers reported that the patient had a partial response (36.4% tumor reduction) and a rapid decline in tumor marker CA-19-9. "Our results demonstrate that ctDNA evaluation is feasible in CUP and that most patients harbor a unique somatic profile with pharmacologically-actionable alterations, justifying the inclusion of noninvasive liquid biopsies in next-generation clinical trials," study authors concluded.

BREAST CANCER

Functional IGF1R variant predicts breast cancer risk in women with preeclampsia in California teachers study

Recently published data suggest women with a history of preeclampsia are at lower risk for breast cancer if they carry a specific common gene variant (Cancer Causes Control 2017; doi:10.1007/s10552-017-0942-7). The California Teachers Study cohort includes over 130,000 female educators. "DNA was available from a nested case-control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls," according to investigators. This study included all participants from the case-control group with a self-reported history of preeclampsia. Researchers found that women with preeclampsia have a 74 percent lower risk of HR-positive breast cancer if they carried two T alleles of a variant of the insulin-like growth factor receptor gene when compared to women carrying no T alleles. This decrease in risk increased to 90 percent if the pregnancy with preeclampsia occurred before the age of 30, according to study results. These findings confirm that the "T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with age of first birth < 30."

IMMUNOTHERAPY

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade

Cancer immunotherapies that block two different checkpoints on T cells launch immune attacks on cancer by expanding distinct types of T cells that infiltrate tumors, according to new data (Cell 2017; http://dx.doi.org/10.1016/j.cell.2017.07.024). Investigators analyzed infiltrating immune cells from mouse tumor models and human melanomas treated with either anti-CTLA-4 or anti PD-1 checkpoint inhibitors. Utilizing mass cytometry, 33 surface markers and 10 intracellular markers were analyzed to characterize infiltrating cells. Researchers found anti-CTLA-4 treatment expanded the presence of CD4 effector T cells that are positive for the immune-stimulating protein, ICOS. Additionally, these cells were strongly associated with smaller tumors in the mice. According to study findings, both anti-PD-1 and anti-CTLA-4 treatment significantly expanded the presence of CD8 T cells. Investigators concluded that the results "indicate that anti-CTLA-4 and anti-PD-1 checkpoint-blockade-induced immune responses are driven by distinct cellular mechanisms."

LUNG CANCER

Radiotherapy prolongs the survival of advanced non-small-cell-lung-cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev)

Researchers evaluating combination therapies for unresectable lung cancer have recently discovered improved survival rates by up to 1 year when patients treated with a newly-formulated chemotherapy regimen are also given radiation therapy (Oncotarget 2017; https://doi.org/10.18632/oncotarget.20411). A cohort of patients with metastatic non-small cell lung cancer (NSCLC), who had already been enrolled in a clinical trial, underwent radiation therapy in addition to their treatment with a novel chemotherapy formulation, mPEBev. Researchers identified candidates for this combination therapy in a retrospective analysis of a subset of 69 patients who received the mPEBev regimen in a recent clinical trial. Forty-five of these patients were also given palliative radiotherapy treatments to one or more metastatic sites. According to study results, survival increased among patients who received radiotherapy by an average of 10 months, with the longest survival of over 2 years [chemotherapy vs. chemotherapy + radiotherapy: 12.1 +/-2.5 (95%CI 3.35-8.6) vs. 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015]. Study authors wrote, "these results suggest that tumor irradiation may prolong the survival of NSCLC patients undergone mPEBev regimen presumably by eliciting an immune-mediated effect and provide the rationale for further perspective clinical studies."

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