Histologic transformation from adenocarcinoma to squamous cell carcinoma in lung cancer has not been reported as a mechanism of resistance to ALK inhibition. This report describes the clinical course of a female former light smoker with metastatic lung adenocarcinoma whose tumor underwent histologic transformation from a well-differentiated lung adenocarcinoma to a well-differentiated lung squamous cell carcinoma in the same location at the left mainstem bronchus while maintaining the ALK fusion oncogene without any resistance mutations. After experiencing disease progression while on crizotinib, the patient participated in clinical trials that provided early access to the novel ALK inhibitors ceritinib and alectinib before they were commercially available. Tumor recurrence occurred at the primary and metastatic central nervous system sites (ie, brain and spine). At tumor progression, liquid biopsy and tumor genomic profiling of plasma cell-free DNA next-generation sequencing (NGS) provided an accurate diagnosis with a short turnaround time compared with the tissue-based targeted capture NGS. The patient received several courses of radiation primarily to the brain and spine during her disease course. Her disease did not respond to the immune checkpoint inhibitor nivolumab, and she died on home hospice approximately 4 years after diagnosis. This case supports the importance of both histopathologic assessment and comprehensive genomic profiling in selecting appropriate treatment for patients with refractory, metastatic, ALK oncogene–driven non–small cell lung cancer. Use of symptom-directed radiation in tandem with ALK inhibitors contributed to the disease and symptomatic control and prolonged survival in this patient.
Jay Gong, Jeffrey P. Gregg, Weijie Ma, Ken Yoneda, Elizabeth H. Moore, Megan E. Daly, Yanhong Zhang, Melissa J. Williams and Tianhong Li
Supriya G. Mohile, Allison Magnuson, Chintan Pandya, Carla Velarde, Paul Duberstein, Arti Hurria, Kah Poh Loh, Megan Wells, Sandy Plumb, Nikesha Gilmore, Marie Flannery, Marsha Wittink, Ronald Epstein, Charles E. Heckler, Michelle Janelsins, Karen Mustian, Judith O. Hopkins, Jane Liu, Srihari Peri and William Dale
Background: This study's objectives were to describe community oncologists' beliefs about and confidence with geriatric care and to determine whether geriatric-relevant information influences cancer treatment decisions. Methods: Community oncologists were recruited to participate in 2 multisite geriatric oncology trials. Participants shared their beliefs about and confidence in caring for older adults. They were also asked to make a first-line chemotherapy recommendation (combination vs single-agent vs no chemotherapy) for a hypothetical vignette of an older patient with advanced pancreatic cancer. Each oncologist received one randomly chosen vignette that varied on 3 variables: age (72/84 years), impaired function (yes/no), and cognitive impairment (yes/no). Other patient characteristics were held constant. Logistic regression models were used to identify associations between oncologist/vignette-patient characteristics and treatment decisions. Results: Oncologist response rate was 61% (n=305/498). Most oncologists agreed that “the care of older adults with cancer needs to be improved” (89%) and that “geriatrics training is essential” (72%). However, <25% were “very confident” in recognizing dementia or conducting a fall risk or functional assessment, and only 23% reported using the geriatric assessment in clinic. Each randomly varied patient characteristic was independently associated with the decision to treat: younger age (adjusted odds ratio [aOR], 5.01; 95% CI, 2.73–9.20), normal cognition (aOR, 5.42; 95% CI, 3.01–9.76), and being functionally intact (aOR, 3.85; 95% CI, 2.12–7.00). Accounting for all vignettes across all scenarios, 161 oncologists (52%) said they would offer chemotherapy. All variables were independently associated with prescribing single-agent over combination chemotherapy (older age: aOR, 3.22; 95% CI 1.43–7.25, impaired cognition: aOR, 3.13; 95% CI, 1.36–7.20, impaired function: aOR, 2.48; 95% CI, 1.12–5.72). Oncologists' characteristics were not associated with decisions about providing chemotherapy. Conclusion: Geriatric-relevant information, when available, strongly influences community oncologists' treatment decisions.