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Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non–small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment. Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib. In a second case, we identified a secondary acquired ALK G1202R, which also confers resistance to alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the solvent front of the ALK kinase domain and exhibits a high level of resistance to all other ALK inhibitors currently in clinical development in vitro. Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.

Background: North Dakota has substantially rural demographics with unique logistics, challenges, and other socio-economic complexities affecting timely intervention in stroke patients. The North Dakota Stroke System of Care (NDSSoC) Taskforce was legislatively created in 2009 and implemented, with authority to recommend system changes for state health officer implementation. The NDSSoC Task Force is composed of 11 appointed multidisciplinary members collaborating to provide recommendations in the development of a Stroke System of Care in North Dakota. Hypothesis: Implementation of the NDSSoC will result in improved timely interventions and increased quality of care. Methods: Quality of care was measured based on data input into the State Stroke Registry (SSR). The SSR utilizes the American Heart Association’s Get with the Guidelines®-Stroke (GWTG-S), an in hospital quality improvement program. The 2010 and 2013 data was compared. Results: The percent of acute ischemic stroke patients who arrived at the hospital within 2 hours of time last known well and for whom IV t-PA was initiated within 3 hours increased from 30.9% in 2010 to 80.9% in 2013. Cases receiving a brain CT scan within 25 minutes of arrival to the hospital increased from 16% of patients in 2010 to 25% in 2013. The structure has led to tertiary and state resource investment to support NDSSoC strategies, with a state annual investment of funding equivalent to 59 cents per capita and a state funded FTE coordinator. Conclusions: A collaborative statewide effort led by a multidisciplinary team can improve timely intervention and quality of care in stroke. The statewide task force with implementation authority can be successfully applied to areas with a rural demographic.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer. Since this time, however, few case reports outlining real-world usage have been published in the literature. Here, we detail the clinical history of an elderly woman with KRAS wild-type colon cancer who received regorafenib after prior treatment with other agents. We show that by employing dose modification strategies to address adverse events, this patient was able to remain on therapy for 11 months and achieve stable disease.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

A 32-year-old Chinese female never smoker presented with persistent cough in June 2009, and imaging studies revealed a right hilar mass. An endobronchial biopsy of the tumor revealed a moderately differentiated mucinous adenocarcinoma that was cytokeratin 7 (CK7) positive, CK20 negative, transcription tissue factor-1 (TTF-1) positive, and mucicarmine positive. Initial molecular analysis revealed the tumor to be both epidermal growth factor receptor and KRAS wild type. Her staging workup revealed metastasis to the liver and brain. She underwent stereotactic radiosurgery of her brain metastases that was followed by six cycles of cisplatin/pemetrexed/bevacizumab combination chemotherapy followed by bevacizumab maintenance therapy, with a partial response to treatment. In November 2009, she decided to undertake a treatment holiday for 3 months. By February 2010, however, her disease had progressed, and she commenced single-agent erlotinib treatment but had documented disease progression after 6 weeks. She was referred by her treating oncologist for possible enrollment into the phase I crizotinib trial because her clinical profile—young age, adenocarcinoma histology, never-smoking status, and most importantly her tumor is wild type for epidermal growth factor receptor and KRAS—fits the profile of an anaplastic lymphoma kinase (ALK)-positive patient with non-small cell lung cancer (NSCLC).