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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.



Differential burden of rare and common variants on tumor characteristics, survival, and mode of detection in breast cancer

The presence of certain rare mutations was indicative of increased risk from interval breast cancers and death, according to recently published data (Cancer Res 2018; doi:10.1158/0008-5472.CAN-18-1018). Researchers analyzed data from over 5,000 breast cancer patients diagnosed between 2001 and 2008 through the Stockholm-Gotland Regional Breast Cancer Register. They studied associations with tumor characteristics and survival outcomes for patients with rare protein-truncating variants (PTVs) in 31 cancer predisposition genes, including BRCA1/2. In addition, a polygenic risk score was developed through the weighted sum of all known common breast cancer variants, which was also correlated with tumor characteristics and overall survival. Given that interval cancers are not identified through routine mammography screenings, the mode of detection was analyzed for cancers driven by rare PTVs or common variants. Since dense tissue is a key reason for masked tumors, researchers stratified women into risk categories based on percent breast density (low risk < 25%; high risk >= 25%). Of the 5,099 breast cancer patients analyzed, 597 carried PTVs. These patients were younger, had more aggressive tumor phenotypes, and had 1.65 times the risk of death from breast cancer compared to those who did not carry PTVs, according to the research team. "After excluding 92 women that carried mutations to BRCA1/2 from this cohort, women with PTVs had 1.76 times the risk of death from breast cancer compared to those without PTVs," investigators reported. They concluded that "these findings offer the potential to improve screening practices for breast cancer by providing a deeper understanding of how risk variants affect disease progression and mode of detection."



A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade

Researchers have identified a gene expression pattern that human melanoma cells use to resist immunotherapy, and demonstrated a combination therapy approach that could overcome this resistance (Cell 2018; Single-cell RNA sequencing data was utilized to analyze melanoma cells from more than 30 melanoma patients, half of which had exhibited resistance to immunotherapies. A distinct gene expression pattern was identified that correlated with reduced T-cell presence in the tumor and other features of immunotherapy resistance, according to the research team. "The program is expressed prior to immunotherapy, characterizes cold niches in situ, and predicts clinical responses to anti-PD-1 therapy in an independent cohort of 112 melanoma patients," researchers reported. Mining data across hundreds of human cell lines, the team predicted that CDK4/6 inhibitors could in part reverse the resistance program in cells. "CDK4/6-inhibition represses this program in individual malignant cells, induces senescence, and reduces melanoma tumor outgrowth in mouse models in vivo when given in combination with immunotherapy, according to the study authors, who concluded that the research "provides a high-resolution landscape of immune checkpoint inhibitor resistant cell states, identifies clinically predictive signatures, and suggests new therapeutic strategies to overcome immunotherapy resistance."



Extended-field chemoradiation therapy for definitive treatment of anal canal squamous cell carcinoma involving the para-aortic lymph nodes

Among patients with advanced-stage anal cancer whose disease has spread to the para-aortic lymph nodes, a combination of extended-field radiation therapy and chemotherapy could substantially improve overall survival and control the cancer without increasing serious side effects (Int J Radiat Oncol Biol Phys 2018;102(1):102-108). Researchers assessed long-term outcomes for 30 patients who were treated with curative-intent, extended-field chemoradiation between September 2002 and February 2016 at the University of Texas MD Anderson Cancer Center in Houston and the Mayo Clinic in Rochester, Minn. Due to the evolution of external beam radiation therapy techniques, some patients were treated with 3D conformal techniques during the early phase of the study and a few were treated with intensity modulated proton therapy during the later phases. The vast majority of patients, however, were treated with intensity modulated radiation therapy. For chemotherapy regimens, patients received either 6 weekly cycles of cisplatin with 5-fluorouracil/capecitabine (5-FU), two cycles of mitomycin-C with 5-FU, or daily capecitabine. After 3.1 years of follow-up, 18 of 30 patients remained alive and 17 showed no evidence of anal cancer, researchers reported. The overall survival rate was 67 percent (95% CI 49-89), with a disease-free survival rate of 42 percent (95% CI 25-69). Cancer recurred in 15 of the patients (50%), predominantly as distant metastases. No patients died from side effects related to the aggressive combination therapy. "Extended-field chemoradiation therapy is a potentially curative treatment option for patients presenting with squamous cell carcinoma of the anal canal with metastases limited to the para-aortic lymph nodes," the study authors wrote.



Minimally invasive versus abdominal radical hysterectomy for cervical cancer

Research shows that minimally invasive radical hysterectomy is associated with higher recurrence rates and worse overall survival (OS) compared to abdominal radical hysterectomy (N Engl J Med 2018; doi:10.1056/NEJMoa1806395). The international study was a multi-institutional collaboration with 33 centers worldwide. Opening in 2008, it was designed to randomize 740 women with early-stage (1A or 1B) cervical cancer to undergo either minimally invasive or open radical hysterectomy (1:1 ratio). Patients were equally stratified for risk factors, such as histologic subtypes, tumor size, stage, lymph node involvement, and adjuvant treatment. In 2017, the study was stopped because of a noted safety signal; 631 patients were enrolled. Women receiving minimally invasive radical hysterectomy were found to have higher rates of recurrences, worse progression-free survival (PFS), and worse OS. Key findings, according to researchers, included the following: minimally invasive radical hysterectomy was associated with a three-fold increase in disease progression, compared to open radical hysterectomy; the rate of disease-free survival at 4.5 years was 86 percent with a minimally invasive surgery and 96.5 percent with open surgery; and 3-year OS overall survival was 91.2 percent in the minimally invasive group compared to 97.1 percent in the open surgery arm.


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