The abscopal effect in head-and-neck squamous cell carcinoma treated with radiotherapy and nivolumab: a case report and literature review.

Introduction: The abscopal effect is a rarely observed outcome of radiotherapy wherein there is a reduction in metastatic disease burden outside of the targeted treatment area. Likely due to an in situ vaccine effect of radiotherapy, the abscopal effect may be augmented by immunotherapy. This report is the first case of the abscopal effect observed in metastatic head-and-neck squamous cell carcinoma (hnscc) treated with concurrent radiotherapy and single-agent nivolumab. Case Description: An otherwise healthy 57-year-old man underwent craniofacial resection and adjuvant chemoradiotherapy for advanced sinonasal squamous cell carcinoma. Distant metastatic disease developed shortly after primary treatment, and immunotherapy in the form of nivolumab was initiated. Subsequent oligometastatic progression despite immunotherapy prompted palliative radiotherapy to a single metastasis due to pending symptomatology. Post-radiotherapy, the abscopal effect was observed with all distant sites of metastatic disease shrinking. Five months following treatment, a sustained reduction in disease burden has been demonstrated. Summary: We present the first case of the abscopal effect in a patient with metastatic hnscc treated with palliative radiotherapy concurrent with single-agent nivolumab immunotherapy, and only the third case of the abscopal effect in metastatic head-and-neck cancer. Dual treatment with immunotherapy and radiotherapy may be an important treatment option in the future, mediated through the abscopal effect.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.

Palliative care consultation and aggressive care at end of life in unresectable pancreatic cancer.

Background: Palliative care (pc) consultation has been associated with less aggressive care at end of life in a number of malignancies, but the effect of the consultation timing has not yet been fully characterized. For patients with unresectable pancreatic cancer (upcc), aggressive and resource-intensive treatment at the end of life can be costly, but not necessarily of better quality. In the present study, we investigated the association, if any, between the timing of specialist pc consultation and indicators of aggressive care at end of life in patients with upcc. Methods: This retrospective cohort study examined the potential effect of the timing of specialist pc consultation on key indicators of aggressive care at end of life in all patients diagnosed with upcc in Nova Scotia between 1 January 2010 and 31 December 2015. Statistical analysis included univariable and multivariable logistic regression. Results: In the 365 patients identified for inclusion in the study, specialist pc consultation was found to be associated with decreased odds of experiencing an indicator of aggressive care at end of life; however, the timing of the consultation was not significant. Residency in an urban area was associated with decreased odds of experiencing an indicator of aggressive care at end of life. We observed no association between experiencing an indicator of aggressive care at end of life and consultation with medical oncology or radiation oncology. Conclusions: Regardless of timing, specialist pc consultation was associated with decreased odds of experiencing an indicator of aggressive care at end of life. That finding provides further evidence to support the integral role of pc in managing patients with a life-limiting malignancy.

Adjuvant treatment in older patients with rectal cancer: a population-based review.

Background: Little is known about the benefits of adjuvant chemotherapy (adj) in the older population with locally advanced rectal cancer (larc). We evaluated use of adj, survival outcomes, and adj-related toxicity in older patients with larc. Methods: Our retrospective review included 286 patients with larc (stages ii and iii) diagnosed between January 2010 and December 2013 in Nova Scotia who underwent curative-intent surgery. Baseline patient, tumour, and treatment characteristics were collected. The survival analysis used the Kaplan-Meier method and Cox regression statistics. Results: Of 286 identified patients, 152 were 65 years of age or older, and 92 were 70 years of age or older. Median follow-up was 46 months, and 163 patients (57%) received neoadjuvant chemoradiation. Although adj was given to 81% of patients (n = 109) less than 65 years of age, only 29% patients (n = 27) 70 years of age and older received adj. Kaplan-Meier analysis suggested a potential survival advantage for adj regardless of age. In multivariate Cox regression analysis, Eastern Cooperative Oncology Group performance status, T stage, and adj were significant predictors of overall survival (p < 0.04); age was not. Similarly, N stage, neoadjuvant chemoradiation, and adj were significant predictors of disease-free survival (p < 0.01). Poor Eastern Cooperative Oncology Group performance status was the most common cause of adj omission. In patients 70 years of age and older, grade 1 or greater chemotherapy-related toxicities were experienced significantly more often by those treated with adj (85% vs. 68% for those not treated with adj, p < 0.05). Conclusions: Regardless of age, patients with larc seem to experience a survival benefit with adj. However, older patients are less likely to receive adj, and when they do, they experience more chemotherapy-related toxicities.

Orbital mass as first presentation of metastatic p16-positive oropharyngeal squamous cell carcinoma.

We describe a case in which a 67-year-old man was diagnosed with a metastatic recurrence of p16-positive oropharyngeal squamous cell carcinoma after presenting with a medial orbital mass in the region of the nasolacrimal apparatus. A review of the literature revealed that metastasis to the orbit from any malignancy is an uncommon occurrence, and no cases of p16-positive oropharyngeal squamous cell carcinoma have previously been reported. Our case highlights the importance of maintaining a high index of suspicion during surveillance visits with such patients.

Cost-utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels.

BACKGROUND: Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost-utility (cu) of this therapy could help to determine its role in clinical practice. METHODS: Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. RESULTS: Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained. CONCLUSIONS: Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.

Drug-induced subacute cutaneous lupus erythematosus associated with nab-paclitaxel therapy.

Drug-induced lupus erythematosus (dile) syndromes are documented complications of chemotherapeutic agents, including paclitaxel. Subacute cutaneous lupus erythematosus (scle) is a distinct dile syndrome presenting with characteristic annular or papulosquamous skin lesions in a photosensitive distribution with associated high anti-ssa titres. Previously, dile syndromes complicating paclitaxel therapy have been attributed to polyethoxylated castor oil (Kolliphor EL: BASF, Ludwigshafen, Germany), the biologic solvent included in the drug's original formulation (Taxol: Bristol-Myers Squibb, Montreal, QC), rather than the parent chemotherapy molecule. Here, we report a characteristic case of drug-induced scle complicating treatment with nanoparticle albumin bound (nab)-paclitaxel (Abraxane: Celgene, Summit, NJ, U.S.A.), a solvent-free taxane formulation. The pertinent English-language literature is also discussed. This case report is the first to link solvent-free paclitaxel with scle, and it suggests that the parent molecule is responsible for the reaction.

Changes in structural aspects of mood during 39-66 h of sleep loss using matched controls.

A number of studies have described mood change during sleep loss in the laboratory, however, an understanding of fluctuations in structural aspects of mood under such conditions is lacking. Sixty-two healthy young adults completed one of three possible conditions: one (n = 20) or two (n = 23) nights of sleep loss or the control condition which consisted of one (n = 9) or two (n = 10) nights of 9 h time in bed. The Mood Scale II was completed every two waking hours and data were analysed in terms of the frequency and intensity of mood reports. Overall, sleep loss conditions were associated with significantly less frequent happiness and activation and more frequent fatigue reports (p < 0.001). Intensity was also significantly reduced for activation and happiness, and increased for depression, anger and fatigue (p < 0.05). Interestingly, there were no significant differences in anger following two nights in the laboratory with or without sleep. Further, two nights in the lab with normal sleep was associated with significant increases in depression intensity (p < 0.05). Findings support the hypothesis of a mood regulatory function of sleep and highlight the relative independence of frequency and intensity and of positive and negative mood dimensions. Findings also suggest that the laboratory environment, in the absence of sleep loss, may have a significant negative impact on mood.

The impact of a week of simulated night work on sleep, circadian phase, and performance.

AIMS: To investigate factors that may contribute to performance adaptation during permanent night work. METHODS: Fifteen healthy subjects participated in an adaptation and baseline night sleep, directly followed by seven simulated eight-hour night shifts (2300 to 0700 hours). At the end of each shift they were taken outside and exposed to natural light for 20 minutes. They then slept from approximately 0800 hours until they naturally awoke. RESULTS: There was a significant increase in mean performance on a visual psychomotor vigilance task across the week. Daytime sleep quality and quantity were not negatively affected. Total sleep time (TST) for each of the daytime sleeps was reduced, resulting in an average cumulative sleep debt of 3.53 hours prior to the final night shift. TST for each of the daytime sleep periods did not significantly differ from the baseline night, nor did TST significantly vary across the week. There was a significant decrease in wake time after sleep onset and sleep onset latency across the week; sleep efficiency showed a trend towards greater efficiency across the consecutive daytime sleeps. Hours of wakefulness prior to each simulated night shift significantly varied across the week. The melatonin profile significantly shifted across the week. CONCLUSIONS: Results suggest that under optimal conditions, the sleep debt that accumulates during consecutive night shifts is relatively small and does not exacerbate decrements in night-time performance resulting from other factors. When sleep loss is minimised, adaptation of performance during consecutive night shifts can occur in conjunction with circadian adaptation.

Performance, sleep and circadian phase during a week of simulated night work.

The current study investigated changes in night-time performance, daytime sleep, and circadian phase during a week of simulated shift work. Fifteen young subjects participated in an adaptation and baseline night sleep, directly followed by seven night shifts. Subjects slept from approximately 0800 hr until they naturally awoke. Polysomnographic data was collected for each sleep period. Saliva samples were collected at half hourly intervals, from 2000 hr to bedtime. Each night, performance was tested at hourly intervals. Analysis indicated that there was a significant increase in mean performance across the week. In general, sleep was not negatively affected. Rather, sleep quality appeared to improve across the week. However, total sleep time (TST) for each day sleep was slightly reduced from baseline, resulting in a small cumulative sleep debt of 3.53 (SD = 5.62) hours. Finally, the melatonin profile shifted across the week, resulting in a mean phase delay of 5.5 hours. These findings indicate that when sleep loss is minimized and a circadian phase shift occurs, adaptation of performance can occur during several consecutive night shifts.

Daytime cardiac autonomic activity during one week of continuous night shift.

Shift workers encounter an increased risk of cardiovascular disease compared to their day working counterparts. To explore this phenomenon, the effects of one week of simulated night shift on cardiac sympathetic (SNS) and parasympathetic (PNS) activity were assessed. Ten (5m; 5f) healthy subjects aged 18-29 years attended an adaptation and baseline night before commencing one week of night shift (2300-0700 h). Sleep was recorded using a standard polysomnogram and circadian phase was tracked using salivary melatonin data. During sleep, heart rate (HR), cardiac PNS activity (RMSSD) and cardiac SNS activity (pre-ejection period) were recorded. Night shift did not influence seep quality, but reduced sleep duration by a mean of 52 +/- 29 min. One week of night shift evoked a small chronic sleep debt of 5 h 14 +/- 56 min and a cumulative circadian phase delay of 5 h +/- 14 min. Night shift had no significant effect on mean HR, but mean cardiac SNS activity during sleep was consistently higher and mean cardiac PNS activity during sleep declined gradually across the week. These results suggest that shiftwork has direct and unfavourable effects on cardiac autonomic activity and that this might be one mechanism via which shiftwork increases the risk of cardiovascular disease. It is postulated that sleep loss could be one mediator of the association between shiftwork and cardiovascular health.

A week of simulated night work delays salivary melatonin onset.

In most studies, the magnitude and rate of adaptation to various night work schedules is assessed using core body temperature as the marker of circadian phase. The aim of the current study was to assess adaptation to a simulated night work schedule using salivary dim light melatonin onset (DLMO) as an alternative circadian phase marker. It was hypothesised that the night work schedule would result in a phase delay, manifest in relatively later DLMO, but that this delay would be somewhat inhibited by exposure to natural light. Participants worked seven consecutive simulated 8-hour night shifts (23:00-07:00 h). By night 7, there was a mean cumulative phase delay of 5.5 hours, equivalent to an average delay of 0.8 hours per day. This indicates that partial circadian adaptation occurred in response to the simulated night work schedule. The radioimmunoassay used in the current study provides a sensitive assessment of melatonin concentration in saliva that can be used to determine DLMO, and thus provides an alternative phase marker to core body temperature, at least in laboratory studies.

The ability to self-monitor performance when fatigued.

The present study aimed to systematically investigate the effects of elevated fatigue levels on the ability to self-monitor performance. Eighteen participants, aged 19-26 y, remained awake for a period of 28 h. Neurobehavioural performance was measured at hourly intervals using four tests from a standardized computer test battery. From these four tests, six measures of performance were obtained: grammatical reasoning (accuracy and response latency); vigilance (accuracy and response latency); simple sensory comparison and tracking. In addition, before and after each test, participants completed visual analogue scales which required them to rate their alertness level and the speed and accuracy of their performance. Individual test results for both self-ratings and neurobehavioural performance were converted to z-scores. Planned comparison analysis indicated that scores on four of the six performance measures decreased significantly as hours of wakefulness increased. Similarly, predicted performance scores for all six measures of performance decreased significantly. Analysis revealed moderate correlations between predicted and actual performance for the four parameters affected by fatigue. Furthermore, moderate to high correlations were found between all six performance parameters and their respective post-test self-ratings. In addition, moderate to high correlations were found between predicted performance and alertness. Taken together, these findings suggest that as fatigue levels increase, subjects globally assess performance decrements. Results suggest that subjective alertness may in part mediate an individual's global assessment of performance.

Factors predicting sleep disruption in Type II diabetes.

This study investigated four correlates of diabetes as potential predictors of sleep disruption in people with Type II diabetes. A tentative causal model proposed obesity would lead to more severe diabetes, which would result in increased physical complications, which might in turn affect emotional adjustment, and all of these might combine to cause sleep disruption. It was found that within a diabetic sample, severity of diabetes was related to sleep disruption. Path analysis indicated that the relationship between Type II diabetes and sleep disruption was mediated by physical complications of the disease (pain and nocturia), and not by either obesity or emotional adjustment.

Quantifying the performance impairment associated with fatigue.

The present study systematically compared the effects of fatigue and alcohol intoxication on a range of neurobehavioural tasks. By doing so, it was possible to quantify the performance impairment associated with fatigue and express it as a blood alcohol impairment equivalent. Twenty-two healthy subjects aged 19-26 years participated in three counterbalanced conditions. In the sustained wakefulness condition, subjects were kept awake for 28 h. In the alcohol and placebo conditions, subjects consumed either an alcoholic or non-alcoholic beverage at 30 min intervals, until their blood alcohol concentration reached 0.10%. In each session, performance was measured at hourly intervals using four tasks from a standardised computer-based test battery. Analysis indicated that the placebo beverage did not significantly effect mean relative performance. In contrast, as blood alcohol concentration increased performance on all the tasks, except for one, significantly decreased. Similarly, as hours of wakefulness increased performance levels for four of the six parameters significantly decreased. More importantly, equating the performance impairment in the two conditions indicated that, depending on the task measured, approximately 20-25 h of wakefulness produced performance decrements equivalent to those observed at a blood alcohol concentration (BAC) of 0.10%. Overall, these results suggest that moderate levels of fatigue produce performance equivalent to or greater than those observed at levels of alcohol intoxication deemed unacceptable when driving, working and/or operating dangerous equipment.