Overcoming the Challenges of Rare Cancers

Rare cancers collectively represent as much as one-quarter of all new adult diagnoses and close to three-quarters of child and adolescent cases, but clinical care and the development of treatments for these malignancies involve myriad challenges, resulting in poor survival rates. But innovations in clinical trial design and a shift from classifying cancers based on histology and site of origin to more focus on their molecular and mutational profiles offers a more hopeful path forward, according to Nancy Houlihan, RN, MA, AOCN, former director of nursing, Evidence-based Practice, at Memorial Sloan Kettering Cancer Center in New York City. Her talk detailing rare cancers was held on the Oncology Nursing Society (ONS) Bridge live virtual conference.

“[There are] challenges related to screening, diagnosis, treatment, research, education, and funding,” Houlihan said. The low prevalence of these diseases leads to late or incorrect diagnoses, relatively little research funding, and consequently, fewer treatment options. Patients have limited access to expert care; frequently must travel long distances for that care, disrupting careers and upending family and social support systems; and thanks in part to inconsistent or lack of insurance coverage, financial toxicity.

“Disparities exist across our health care systems and access to care for patients with rare cancers is even more challenging,” Houlihan explained.

People with rare cancers collectively have lower survival rates and quality of life than people with more common malignancies.

The US National Cancer Institute defines rare cancers in the United States as those with incidence rates of fewer than 15 cases per 100,000 people per year, or less than 40,000 cases a year. There are 181 rare cancer types with fewer than 6 cases per 100,000 per year, and 119 of those (3% of all cancers) are considered very rare, with incidence rates of 0.5 or fewer cases per 100,000 each year.

Among others, rare malignancies include digestive system, head and neck, biliary tract and gallbladder, tracheal, some brain, male breast and genital cancers, approximately one-third of female genital cancers, large-cell and sarcoid lung cancers, endocrine tumors, 38% of hematopoietic malignancies (including T-cell malignancies, leukemias, and Hodgkin lymphoma), and many adenocarcinomas.

All pediatric cancers are rare, Houlihan noted.

Genetic sequencing is yielding a longer list of molecular subtypes and opening up some rare cancers to new targeted and immune therapies, she added. “The number of rare cancers will continue to increase as cancers are further defined by molecular markers,” she said.

Rare cancers with gene alternative mismatch repair (MMR) deficiencies that are treated with immune checkpoint inhibitor pembrolizumab [Keytruda] “achieve unprecedented response rates in patients with advanced, pretreated cancers,” Houlihan said. The FDA approved pembrolizumab for MMR deficient cancers in 2017.

“Rare subtypes have been identified in cancers that were recognized as a single disease, for example, the ALK and ROS1 subtype of lung adenocarcinoma,” Houlihan said. “A large number of rare cancer patients treated with immune checkpoint inhibitors as salvage therapy show a positive correlation between response rates and overall survival.”