Investigators from Children's Hospital Los Angeles and 37 other Children's Oncology Group hospitals in the U.S. and Canada have determined that sodium thiosulfate prevents cisplatin-induced hearing loss in children and adolescents with cancer. Results of this randomized, controlled, phase 3 study, called ACCL0431, have been published in the early online edition of Lancet Oncology.

"This federally-funded, cooperative group study is the first to show that cisplatin-induced hearing loss can be reduced by about half in children and adolescents being treated for cancer," said David R. Freyer, DO, MS, director of the Survivorship & Supportive Care Program in the Children's Center for Cancer and Blood Diseases at Children's Hospital Los Angeles, who was lead author and chair of the study. "It is an important step toward developing a safe and effective strategy that will greatly improve quality of life for cancer survivors." Freyer is also professor of Clinical Pediatrics and Medicine at the Keck School of Medicine of USC.

Cisplatin is a chemotherapy medication widely used to treat a variety of cancers in both adults and children. Although effective, cisplatin frequently causes permanent hearing loss and tinnitus (ringing in the ears), resulting in functional disability for patients who receive it. For young children in particular, hearing loss is especially serious because it results in impaired language development, learning and social interactions. Preventing ototoxicity, while preserving chemotherapeutic efficacy, has been a long-standing goal of physicians, scientists, parents and survivors. Historically, there have been no proven treatments for preventing cisplatin-induced hearing loss tested under the rigorous conditions of ACCL0431. Without otoprotection, the only way to prevent hearing loss is to delete or decrease cisplatin doses, which could render the cancer treatment less effective.

Breast cancer patients in one of the United States' largest and fastest-growing ethnic minority groups are likely to experience numerous gaps in care following their primary treatment, research from Oregon State University suggests.

Seventy-four Latina women who had breast cancer participated in the "survivorship" care research, recruited through support groups and health fairs. The subjects, ages 30 to 75, took part in semi-structured focus groups that used a question guide crafted by a task force of academic researchers and community partners such as the American Cancer Society. Approximately half of the women were low-income, uninsured or publicly insured.

"Results indicate numerous gaps and unmet needs in Latinas' survivorship care experiences, including problems with finances, continuity of care, unmet needs for information, and symptom management," said Carolyn Mendez-Luck, an assistant professor in OSU's College of Public Health and Human Sciences and one of the authors of the study.

The California Breast Cancer Research Program provided primary funding for the research. Results were recently published in Public Health Nursing. Optimal survivorship care, according to the Institute of Medicine, includes the prevention of recurrence, new cancer and late effects of cancer treatment; the monitoring or surveillance for cancer and medical, mood and social issues; interventions for the effects of cancer and its treatment; and coordination among specialists and primary care providers to ensure all health needs are met.

"Many survivors experience persisting symptoms including fatigue, pain, depression and sleep disturbance, but until recent years, survivorship has been relatively neglected in education, clinical practice and research," Mendez-Luck said.

People of Mexican, Cuban, Puerto Rican, and Central and South American descent comprise 17.6 percent of the U.S. population, and about 10 percent of the women in the Hispanic/Latino population will develop breast cancer at some point in their lifetime.

An existing drug known as a JAK inhibitor may help patients who don't respond to the so-called checkpoint inhibitor immunotherapy drugs overcome that resistance, suggests a new preclinical study published online in Cell by Penn Medicine researchers. Importantly, the results demonstrate that shutting down the interferon pathway, shown here to be critical to a tumor's resistance to immunotherapy, with a JAK inhibitor may improve checkpoint inhibitor drugs and even bypass the need for combinations of these drugs, which often come with serious side effects.

Today's checkpoint inhibitor drugs target receptors such as PD1 and CTLA-4, which act as a type of "off switch" on a T cell to prevent it from attacking other cells. Inhibiting these pathways with one or a more of the drugs releases these "brakes" so the immune system can fight the disease. However, over half of patients on the drugs relapse or their cancer progresses.

"The proposed approach has some elegance to it - rather than try to figure out all inhibitory pathways that the tumor has enabled, find a critical pathway that regulates many of the inhibitory signals and cripple that instead," said senior author Andy J. Minn, MD, PhD, an assistant professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania. "Interferon signaling is like a critical node in a network. Disable it and a large part of that network collapses."

Using breast cancer and melanoma mouse models, Minn, first-author Joseph L. Benci, a graduate student in Penn's Cell and Molecular Biology Graduate Group, and their colleagues from the departments of Radiation Oncology, Abramson Family Cancer Research Institute and Penn's Parker Institute for Cancer Immunotherapy showed that prolonged interferon signaling in tumor cells increased resistance to checkpoint inhibitors through multiple inhibitory pathways, and that blocking this response resulted in improved survival and powerful tumor responses.

Authors on the paper also include Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research, Amit Maity, MD, PhD, a professor of Radiation Oncology, and E. John Wherry, PhD, a professor of Microbiology and director of the Institute for Immunology at Penn.
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Studies have shown that combining checkpoint inhibitors, ipilimumab and pembrolizumab, for instance, as well as adding radiation therapy, as described in a Penn paper from the same researchers in Nature in 2015, elicits promising tumor responses in patients. But many still do not respond because of additional unidentified "brakes."