Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck.

PURPOSE: Surgery often represents the best chance for disease control in locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We investigated dual immune-checkpoint inhibition [anti-PD-1, nivolumab (N), and anti-KIR, lirilumab (L)] before and after salvage surgery to improve disease-free survival (DFS). PATIENTS AND METHODS: In this phase II study, patients received N (240 mg) + L (240 mg) 7 to 21 days before surgery, followed by six cycles of adjuvant N + L. Primary endpoint was 1-year DFS; secondary endpoints were safety, pre-op radiologic response, and overall survival (OS). Correlatives included tumor sequencing, PD-L1 scoring, and immunoprofiling. RESULTS: Among 28 patients, the median age was 66, 86% were smokers; primary site: 9 oral cavity, 9 oropharynx, and 10 larynx/hypopharynx; 96% had prior radiation. There were no delays to surgery. Grade 3+ adverse events: 11%. At the time of surgery, 96% had stable disease radiologically, one had progression. Pathologic response to N + L was observed in 43% (12/28): 4/28 (14%) major (tumor viability, TV ≤ 10%) and 8/28 (29%) partial (TV ≤ 50%). PD-L1 combined positive score (CPS) at surgery was similar regardless of pathologic response (P = 0.71). Thirteen (46%) recurred (loco-regional = 10, distant = 3). Five of 28 (18%) had positive margins, 4 later recurred. At median follow-up of 22.8 months, 1-year DFS was 55.2% (95% CI, 34.8-71.7) and 1-year OS was 85.7% (95% CI, 66.3-94.4). Two-year DFS and OS were 64% and 80% among pathologic responders. CONCLUSIONS: (Neo)adjuvant N + L was well tolerated, with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted.See related commentary by Sacco and Cohen, p. 435.

A summary of surveillance, morbidity and microbiology of laboratory-confirmed cases of infant botulism in Canada, 1979-2019.

BACKGROUND: Infant botulism is a rare toxicoinfectious disease caused by colonization of the infant's intestine with botulinum neurotoxin-producing clostridia (i.e. Clostridium botulinum or neurotoxigenic strains of C. butyricum or C. baratii). Our goal was to examine data from laboratory-confirmed cases of infant botulism reported in Canada to summarize incidence over time, over geographic distribution by province or territory, and by sex, and to compare these parameters with data from the Canadian Notifiable Disease Surveillance System (CNDSS). The average age of onset, serotype of botulinum neurotoxin (BoNT), case outcomes, length of hospitalization and suitability of clinical specimens for laboratory confirmation were also determined. METHODS: We examined laboratory records from the Health Canada Botulism Reference Service and the British Columbia Centre for Disease Control (BCCDC) Public Health Laboratory. The Discharge Abstract Database (DAD) and the Hospital Morbidity Database (HMDB) of the Canadian Institute of Health Information (CIHI) were queried for data on hospitalization of infant botulism cases. The CNDSS was queried for data on reported cases of infant botulism. RESULTS: From 1979 to 2019, 63 laboratory-confirmed cases of infant botulism were confirmed by the Health Canada Botulism Reference Service and the BCCDC Public Health Laboratory for an annual rate of 4.30 cases per million live births. From 1983 to 2018, 57 cases of infant botulism were reported to the CNDSS. Of the 63 cases confirmed by the reference laboratories, the median age of onset was 16 weeks with a range of 2 to 52 weeks. The majority of cases were type A (76%) and B (21%), with single cases of type F and type AB. Of the 23 laboratory-confirmed cases with matched hospital records, 13 were transferred to special care and eight needed ventilator support; no deaths were reported. CONCLUSION: Spores of C. botulinum are present naturally in the environment, thus diagnosis of infant botulism does not require a history of exposure to high-risk foods such as honey. Stool samples are the most useful diagnostic specimen.

A phase II trial of all-trans retinoic acid (ATRA) in advanced adenoid cystic carcinoma.

BACKGROUND: Effective therapies are lacking for recurrent, metastatic adenoid cystic carcinoma (R/M ACC) and preclinical models suggest retinoic acid agonists inhibit ACC growth. This phase II trial evaluated all-trans retinoic acid (ATRA) as a novel therapy for ACC. METHODS: Patients with R/M ACC (any site) with clinical and/or radiographic progression ≤12 months prior to study entry were eligible. Cohort 1 (CH1) received ATRA 45 mg/m2 split oral daily dosing on days 1-14 of a 28-day cycle; Cohort 2 (CH2) received the same dosing continuously. Primary endpoint was best overall response rate (CR + PR) (RECIST v1.1). Secondary endpoints: safety and progression-free survival (PFS). Exploratory analyses: ATRA impact on MYB expression and genomic predictors of response. RESULTS: Eighteen patients enrolled. There were no responses, but 61% (11/18) had stable disease (SD) and 28% (5/18) progression as best response; 11% (2/18) unevaluable. Median duration of stability: 3.7 months (95%CI, 1.9-3.9). One patient (CH1) remains on drug with SD approaching 1 year. Half of those who received prior VEGFR therapy achieved SD (4/8). At median follow up of 7.9 months, median PFS was 3.2 months (95%CI, 1.8-3.9). N = 1 required dose adjustment; N = 1 came off drug for toxicity. There were no grade 3-4 adverse events. NOTCH1 and PI3K pathway alterations were most frequent. Low MYB protein expression was associated with longer duration of stability on ATRA (P < 0.01). CONCLUSION(S): While the trial did not meet its prespecified response endpoint, ATRA alone or in combination may be a low toxicity treatment for disease growth stabilization in R/M ACC.

Country food consumption in Yukon, Northwest Territories and Nunavut, Foodbook study 2014-2015.

BACKGROUND: This article presents a descriptive summary of the consumption of various country food (i.e. locally harvested plant and animal foods) products by residents of Yukon (YT), Northwest Territories (NT) and Nunavut (NU). Data were collected as part of the Foodbook study in 2014-2015. METHODS: The Foodbook study was conducted by telephone over a one-year period. Respondents were asked about consumption of a wide range of food products over the previous seven days. Residents of the territories were also asked about consumption of regionally-specific country food. Data were weighted to develop territorial estimates of consumption. Data on age, gender, location, income and education were also collected. RESULTS: The national response rate for the Foodbook survey was 19.9%. In total, 1,235 residents of the territories participated in the study (YT, n=402; NT, n=458; NU, n=375). Consumption of any country food during the previous seven days was reported by 77.5%, 60.7%, and 66.4% of participants in NU, NT and YT, respectively. CONCLUSION: Responses to country food questions asked alongside the main Foodbook questionnaire provide insight on country food consumption in YT, NT and NU.

Outbreak of Escherichia coli O157:H7 Infections Linked to Mechanically Tenderized Beef and the Largest Beef Recall in Canada, 2012.

Contaminated beef is a known vehicle of Escherichia coli O157:H7 infection, although more attention is given to the control of E. coli O157:H7 in ground, rather than whole-cut, beef products. In September 2012, an investigation was initiated at an Alberta, Canada, beef plant after the detection of E. coli O157:H7 in two samples of trim cut from beef originating from this plant. Later in September 2012, Alberta Health Services identified five laboratory-confirmed infections of E. coli O157:H7, and case patients reported eating needle-tenderized beef steaks purchased at a store in Edmonton, Alberta, produced with beef from the Alberta plant. In total, 18 laboratory-confirmed illnesses in Canada in September and October 2012 were linked to beef from the Alberta plant, including the five individuals who ate needle-tenderized steaks purchased at the Edmonton store. A unique strain of E. coli O157:H7, defined by molecular subtyping and whole genome sequencing, was detected in clinical isolates, four samples of leftover beef from case patient homes, and eight samples of Alberta plant beef tested by industry and food safety partners. Investigators identified several deficiencies in the control of E. coli O157:H7 at the plant; in particular, the evaluation of, and response to, the detection of E. coli O157 in beef samples during routine testing were inadequate. To control the outbreak, 4,000 tons of beef products were recalled, making it the largest beef recall in Canadian history. This outbreak, in combination with similar outbreaks in the United States and research demonstrating that mechanical tenderization can transfer foodborne pathogens present on the surface into the interior of beef cuts, prompted amendments to Canada's Food and Drug Regulations requiring mechanically tenderized beef to be labeled as such and to provide safe cooking instructions to consumers. A detailed review of this event also led to recommendations and action to improve the safety of Canada's beef supply.

Investigation of the first cases of human-to-human infection with the new swine-origin influenza A (H1N1) virus in Canada.

The outbreak of human infection due to the novel swine-origin influenza A (H1N1) virus began in Mexico in March 2009. As of July 6, 2009, more than 94,000 laboratory-confirmed cases were reported in over 100 countries, including 7983 cases in Canada. In this report, we describe the epidemiologic and clinical characteristics of the first cluster of reported cases of human-to-human transmission of the new influenza virus in Canada.