Curative-Intent Therapies in Localized Hepatocellular Carcinoma.

PURPOSE OF REVIEW: The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvants preparing patients for curative treatment. RECENT FINDINGS: For HCC < 3 cm, percutaneous thermal ablation provides oncologic outcomes similar to surgical resection and is now a recommended first-line therapy in the EASL guidelines. Both ablation and embolization are recommended as bridging therapies for HCC patients awaiting liver transplantation. T3 HCC can be downstaged by embolization to T2, allowing liver transplantation with similar outcomes to patients transplanted within Milan criteria. New and evolving techniques such as SBRT, radiation segmentectomy and lobectomy, and combination therapies show promise but require further prospective data before they can be integrated into treatment algorithms. Combinations of embolic, ablative, and extirpative therapies can increase access to curative-intent treatment of HCC. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location, and underlying liver cirrhosis.

Patterns, perceptions and their association with changes in alcohol consumption in cancer survivors.

Continued consumption of alcohol after a cancer diagnosis is associated with poorer outcomes. We evaluated whether perceptions of the effects of continued alcohol use and receiving information on moderating alcohol reduced alcohol consumption in adult cancer survivors. A total of 509 cancer survivors were cross-sectionally surveyed at follow-up for their alcohol use before and after cancer diagnosis and perceptions of continued drinking. Multivariable logistic regression models evaluated factors associated with changes in alcohol consumption after diagnosis. Among 299 patients who were drinking alcohol at diagnosis (13% exceeding gender-specific guidelines), 52% reduced/ceased alcohol consumption 1 year after diagnosis. Patients perceiving that alcohol worsened their own (a) quality of life, (b) cancer-related fatigue or (c) overall survival were more likely (aORs = 2.43-3.35, p < 0.002) to reduce (moderating or quitting) their alcohol use 1 year after diagnosis. Only 14% of individuals currently drinking regularly recalled receiving information/counselling from healthcare providers on alcohol consumption (7% from oncologists). However, there was a significant fourfold to sixfold increase in cessation with such information/counselling (p < 0.01). Similar trends were observed in patients exceeding gender-specific guidelines. Perception of negative effects of alcohol use on their health by cancer survivors was associated with reducing harmful alcohol consumption. Counselling, especially from the oncologist, may play a significant role for reducing consumption.

Patterns, perceptions, and perceived barriers to physical activity in adult cancer survivors.

PURPOSE: Physical activity (PA) during and after cancer treatment is associated with improved cancer- and non-cancer-related outcomes. We assessed for predictors of change in PA levels among cancer survivors. METHODS: Adult cancer survivors from a comprehensive cancer center completed a one-time questionnaire retrospectively assessing PA levels before, during, and after cancer treatment along with their perceptions of PA. Multivariable logistic regression models evaluated the association of clinico-demographics variables and perceptions of PA with changes in whether patients were meeting PA guidelines after cancer diagnosis. RESULTS: Among the 1003 patients, 319 (32%) met moderate to vigorous PA (MVPA) guidelines before diagnosis. Among those meeting guidelines before diagnosis, 50% still met guidelines after treatment; 12% not meeting MVPA guidelines initially met them after treatment/at follow-up. Among patients meeting guidelines before diagnosis, better ECOG performance status at follow-up, receiving curative therapy, and spending a longer time on PA initially were each associated with meeting guidelines at follow-up. After controlling for other variables, perceiving that PA improves quality of life (adjusted odds ratio, aOR = 11.09, 95%CI [1.42-86.64], P = 0.02) and overall survival (aOR = 8.52, 95%CI [1.12-64.71], P = 0.04) was each associated with meeting MVPA guidelines during/after treatment, in patients who did not meet guidelines initially. Only 13% reported receiving counseling, which was not associated with PA levels. Common reported barriers to PA included fatigue, lacking motivation, and being too busy. CONCLUSIONS: Patient perceptions of PA benefits are strongly associated with improving PA levels after a cancer diagnosis. Clinician counseling should focus on patient education and changing patient perceptions.

The role of second-hand smoke exposure on smoking cessation in non-tobacco-related cancers.

BACKGROUND: Second-hand smoke (SHS) is a significant barrier to smoking cessation after a diagnosis of cancer in patients with lung as well as head and neck cancers. In the current study, the authors evaluated the effect of SHS on smoking cessation among patients with those cancers not traditionally perceived to be strongly associated with smoking. METHODS: Patients recruited from a single tertiary care center completed a self-administered questionnaire. Multivariate logistic regression and Cox proportional hazards models evaluated the association of sociodemographics, clinicopathological variables, and exposure to SHS with either smoking cessation or time to quitting. RESULTS: In all, 926 patients with diverse cancer subtypes completed the questionnaire. Of the 161 who were current smokers at the time of their cancer diagnosis, 48% quit after diagnosis. Lack of exposure to SHS at home was found to be associated with smoking cessation at any time after diagnosis (adjusted odd ratio, 4.28; 95% confidence interval, 1.56-11.78 [P =.005]), with similar trends noted 1 year after diagnosis (adjusted odds ratio, 2.56; 95% confidence interval, 0.91-7.22 [P =.08]). There was a significant inverse dose-response relationship between hours of SHS exposure at home and smoking cessation. Spousal and peer smoking were not found to be significantly associated with smoking cessation on multivariate analysis (P>.05). Kaplan-Meier analysis found that of patients who did quit smoking, 61% quit within 6 months of their cancer diagnosis. CONCLUSIONS: Exposure to SHS at home is a significant barrier to smoking cessation in patients whose cancers are not traditionally perceived as being related to tobacco. SHS should be a key consideration in the development of survivorship programs geared toward smoking cessation for all patients with cancer.

Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. METHODS: This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. RESULTS: A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P = .003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P = .01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P = .001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P = .006] were each independently associated with increased odds of ototoxicity. CONCLUSIONS: Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity.

UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castration-sensitive prostate cancer.

OBJECTIVE: To assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response. PATIENTS AND METHODS: Retrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated. RESULTS: Fifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1-4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9-41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12-0.81; P=0.02). CONCLUSIONS: DR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.

Liver-directed therapy for hepatocellular carcinoma.

The high mortality rate for hepatocellular carcinoma (HCC) relative to its prevalence underscores the need for curative-intent therapies. Multidisciplinary treatment decisions are required to craft optimal treatment strategies considering tumor size, location and underlying liver cirrhosis. Surgical resection of anatomically limited tumors with adequate hepatic reserve provides long-term survival in more than half of patients and remains a standard first-line therapy. Eligibility for resection among newly diagnosed patients is low and recurrences in the remaining cirrhotic liver are common. Transplantation offers a higher chance of cure. Long wait times for the limited door pool require neoadjuvant loco-regional therapies to maintain transplant eligibility. Image-guided therapies such as ablation and embolization have an established role as primary or neoadjuvant preparing patients for curative treatment. Percutaneous ablation in appropriately selected patients offers long-term survival similar to resection. New and evolving techniques such as stereotactic body radiotherapy (SBRT), radiation segmentectomy and lobectomy, and combination therapies employing both trans-arterial and ablative approaches show promise for curative-intent treatment but require further prospective data before they can be integrated into treatment algorithms. For palliativeintent therapy, conventional trans-arterial chemoembolization with lipiodol-based emulsions remains the only technique supported by clinical trials. Newer platforms such as drug-eluting embolics failed to improve survival over bland embolization in randomized trials and showed increased hepatobiliary toxicity. Transarterial radioembolization offers similar overall survival (OS) to transarterial chemoembolization (TACE) and non-inferiority to sorafenib in meta-analyses. The more favorable clinical toxicity profile makes it an appealing technique for patients willing to accept the longer time to response.

Impact of immigration status on health behaviors and perceptions in cancer survivors.

BACKGROUND: Health behaviors including smoking cessation, physical activity (PA), and alcohol moderation are key aspects of cancer survivorship. Immigrants may have unique survivorship needs. We evaluated whether immigrant cancer survivors had health behaviors and perceptions that were distinct from native-born cancer survivors. METHODS: Adult cancer patients from Princess Margaret Cancer Centre were surveyed on their smoking, PA, and alcohol habits and perceptions of the effects of these behaviors on quality of life (QoL), 5-year survival, and fatigue. Multivariable models evaluated the association of immigration status and region-of-origin on behaviors and perceptions. RESULTS: Of the 784 patients, 39% self-identified as immigrants. Median time of survey was 24 months after histological diagnosis. At baseline, immigrants had trends toward not meeting Canadian PA guidelines or being ever-drinkers; patients from non-Western countries were less likely to smoke (aORcurrent  = 0.46, aORex-smoker  = 0.47, P = 0.02), drink alcohol (aORcurrent  = 0.22, aORex-drinker  = 0.52, P < 0.001), or meet PA guidelines (aOR = 0.44, P = 0.006). Among immigrants, remote immigrants (migrated ≥40 years ago) were more likely to be consuming alcohol at diagnosis (aOR = 5.70, P < 0.001) compared to recent immigrants. Compared to nonimmigrants, immigrants were less likely to perceive smoking as harmful on QoL (aOR = 0.58, P = 0.008) and survival (aOR = 0.56, P = 0.002), and less likely to perceive that PA improved fatigue (aOR = 0.62, P = 0.04) and survival (aOR = 0.64, P = 0.08). CONCLUSIONS: Immigrants had different patterns of health behaviors than nonimmigrants. Immigrants were less likely to perceive continued smoking as harmful and were less likely to be aware of PA benefits. Culturally tailored counselling may be required for immigrants who smoke or are physically sedentary at diagnosis.

EQ-5D Health Utility Scores: Data from a Comprehensive Canadian Cancer Centre.

BACKGROUND: To improve the precision of health economics analyses in oncology, reference datasets of health utility (HU) scores are needed from cancer survivors across different disease sites. These data are particularly sparse amongst Canadian survivors. METHODS: A survey was completed by 1759 ambulatory cancer survivors at the Princess Margaret Cancer Centre which contained demographic questions and the EuroQol-5D (EQ-5D) instrument. Clinical information was abstracted from electronic records and HU scores were calculated using Canadian health state valuations. Construct validity was assessed through correlation of HU and visual analog scale (VAS) scores (Spearman) and by comparing HU scores between performance status groups (effect size). The influence of socio-demographic clinical variables on HU was analyzed by non-parametric between-group comparisons and multiple linear regression. RESULTS: Mean EQ-5D HU scores were derived for 26 cancers. Among all survivors, the mean ± standard error of the mean EQ-5D utility score was 0.81 ± 0.004. Scores varied significantly by performance status (p < 0.0001) and correlated with VAS (Spearman r = 0.61). The cancer sites with the lowest mean HU scores were acute lymphoblastic leukemia (0.70 ± 0.03) and pancreatic cancer (0.76 ± 0.03); testicular cancer (0.89 ± 0.02) and chronic lymphocytic leukemia (0.90 ± 0.05) had the highest mean scores. A multiple regression model showed that scores were influenced by disease site (p < 0.001), education level (p < 0.001), partner status (p < 0.001), disease extent (p = 0.0029), and type of most recent treatment (p = 0.0061). CONCLUSIONS: This work represents the first set of HU scores for numerous cancer sites derived using Canadian preference weights. The dataset demonstrated construct validity and HU scores varied by general socio-demographic and clinical parameters.

Cancer Patients? Willingness to Routinely Complete the EQ-5D Instrument at Clinic Visits.

BACKGROUND: Health utility (HU) scores play an essential role in pharmacoeconomic analyses. Routine clinical administration of the EuroQol-5 Dimensions (EQ-5D) can allow for HU and health related quality of life (HRQOL) assessments in the real-world setting. OBJECTIVES: The primary goals of this study were to evaluate whether patients were willing to complete the EQ-5D instrument on a routine basis and which clinical or demographic factors influence this willingness. METHODS: 618 adult cancer survivors across multiple cancer disease sites at the Princess Margaret Cancer Centre completed an acceptability survey after completing the EQ-5D instrument. RESULTS: The mean (SD) EQ-5D score was 0.81 (0.15). Among those surveyed, 88% reported that the EQ-5D was easy to complete. 91% took under 5 minutes and 88% were satisfied with its length. 85% were satisfied with the types of questions asked on the EQ-5D. Importantly, 92% reported that they would complete the EQ-5D, even if it were used solely for research purposes; 73% agreed with the notion of completing it regularly at their clinic visits. Patients with lower EQ-5D scores (p=0.0006), and non-Caucasians (p=0.0024; 60% willing) were less willing to complete the instrument on a regular basis. Curability of tumour, disease site, age, and gender did not influence willingness. CONCLUSIONS: The majority of cancer patients across disease sites are willing to complete the EQ-5D instrument regularly, even if it were solely for research purposes, but up to 39% declined participation in the first place.

Lifestyle Behaviors in Elderly Cancer Survivors: A Comparison With Middle-Age Cancer Survivors.

PURPOSE: Improved cancer screening and treatment have led to a greater focus on cancer survivorship care. Older cancer survivors may be a unique population. We evaluated whether older cancer survivors (age ≥ 65 years) had lifestyle behaviors, attitudes, and knowledge distinct from younger survivors. PATIENTS AND METHODS: Adult cancer survivors with diverse cancer subtypes were recruited from Princess Margaret Cancer Centre (Toronto, Ontario, Canada). Multivariable models evaluated the effect of age on smoking, alcohol, and physical activity habits, attitudes toward and knowledge of these habits on cancer outcomes, and lifestyle information and recommendations received from health care providers, adjusted for sociodemographic and clinicopathologic covariates. RESULTS: Among the 616 survivors recruited, 23% (n = 139) were older. Median follow-up since diagnosis was 24 months. Older survivors were more likely ex-smokers and less likely current smokers than younger survivors, but they were less likely to know that smoking could affect cancer treatment (adjusted odds ratio [OR], 0.53; P = .007) or prognosis (adjusted OR, 0.53; P = .008). Older survivors were more likely to perceive alcohol as improving overall survival (adjusted OR, 2.39; P = .02). Rates of meeting moderate-to-vigorous physical activity guidelines 1 year before diagnosis (adjusted OR, 0.55; P = .02) and maintaining and improving their exercise levels to meet these guidelines after diagnosis (adjusted OR, 0.48; P = .02) were lower in older survivors. Older and younger cancer survivors reported similar rates of receiving lifestyle behavior information from health care providers (P = .36 to .98). CONCLUSION: Older cancer survivors reported being less aware of the impact of smoking on their overall health, more likely perceived alcohol as beneficial to survival, and were less likely to meet exercise goals compared with younger survivors. Survivorship programs need to consider age when counseling on lifestyle behaviors.