Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results.

OBJECTIVES: To evaluate the safety and effectiveness of medical cannabis (MC) in reducing pain and concurrent medications in patients with cancer. METHODS: This study analysed data collected from patients with cancer who were part of the Quebec Cannabis Registry. Brief Pain Inventory (BPI), revised Edmonton Symptom Assessment System (ESAS-r) questionnaires, total medication burden (TMB) and morphine equivalent daily dose (MEDD) recorded at 3-month, 6-month, 9-month and 12-month follow-ups were compared with baseline values. Adverse events were also documented at each follow-up visit. RESULTS: This study included 358 patients with cancer. Thirteen out of 15 adverse events reported in 11 patients were not serious; 2 serious events (pneumonia and cardiovascular event) were considered unlikely related to MC. Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up for BPI worst pain (5.5±0.7 baseline, 3.6±0.7, 3.6±0.7, 3.6±0.8; p<0.01), average pain (4.1±0.6 baseline, 2.4±0.6, 2.3±0.6, 2.7±0.7; p<0.01), overall pain severity (3.7±0.5 baseline, 2.3±0.6, 2.3±0.6, 2.4±0.6; p<0.01) and pain interference (4.3±0.6 baseline, 2.4±0.6, 2.2±0.6, 2.4±0.7, p<0.01). ESAS-r pain scores decreased significantly at 3-month, 6-month and 9-month follow-up (3.7±0.6 baseline, 2.5±0.6, 2.2±0.6, 2.0±0.7, p<0.01). THC:CBD balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains. Decreases in TMB were observed at all follow-ups. Decreases in MEDD were observed at the first three follow-ups. CONCLUSIONS: Real-world data from this large, prospective, multicentre registry indicate that MC is a safe and effective complementary treatment for pain relief in patients with cancer. Our findings should be confirmed through randomised placebo-controlled trials.

Sex differences exist in the perceived relief of cancer symptoms with medical cannabis: results from the Quebec Cannabis Registry.

PURPOSE: This study explored whether symptom relief differs by sex in patients with cancer receiving medical cannabis (MC) therapy. METHODS: This is an analysis of data collected from patients with cancer enrolled in the Quebec Cannabis Registry. MC was initiated for the therapeutic management of cancer symptoms. Patients completed the revised Edmonton Symptom Assessment System (ESAS-r) questionnaire at baseline and 3-month follow-up. We examined the interaction between sex and time on each ESAS-r symptom and the interaction between time and tetrahydrocannabinol:cannabidiol (THC:CBD) ratios for each sex on total symptom burden. RESULTS: The analysis included 358 patients (M: 171). There were no sex differences in baseline ESAS-r scores. Three months of MC therapy led to significant improvements in pain (M: - 1.4 ± 0.3, p < 0.001; F: - 1.1 ± 0.3, p < 0.01), tiredness (M: - 1.7 ± 0.4, p < 0.001; F: - 1.2 ± 0.4, p < 0.05), anxiety (M: - 1.1 ± 0.4, p < 0.05; F: - 1.2 ± 0.4, p < 0.001), and well-being (M: - 1.2 ± 0.4, p < 0.05; F: - 1.4 ± 0.4, p < 0.01) in both sexes. Only F perceived improved drowsiness (- 1.1 ± 0.4, p < 0.05), nausea (- 0.9 ± 0.3, p < 0.05), lack of appetite (- 1.7 ± 0.4, p < 0.001), and shortness of breath (- 0.9 ± 0.3, p < 0.05). From baseline to 3-month follow-up, THC-dominant MC significantly reduced pain (- 1.52 ± 0.52, p < 0.05) in M, whereas in F it diminished nausea (- 2.52 ± 0.70, p < 0.01) and improved well-being (- 2.41 ± 0.79, p < 0.05). THC:CBD-balanced products significantly reduced pain (- 1.48 ± 0.49, p < 0.05), tiredness (- 1.82 ± 0.62, p < 0.05), anxiety (- 1.83 ± 0.54, p < 0.05), and improved well-being (- 2.01 ± 0.56, p < 0.01) in M. CBD-dominant products did not offer significant symptom relief in either sex. CONCLUSION: The perceived relief of cancer symptoms from MC differs between sexes. More randomized controlled trials are needed to confirm our findings.

Extracellular vesicles from genetically unstable, oncogene-driven cancer cells trigger micronuclei formation in endothelial cells.

Oncogenic transformation impacts cancer cell interactions with their stroma, including through formation of abnormal blood vessels. This influence is often attributed to angiogenic growth factors, either soluble, or associated with tumor cell-derived extracellular vesicles (EVs). Here we examine some of the cancer-specific components of EV-mediated tumor-vascular interactions, including the impact of genetic driver mutations and genetic instability. Cancer cells expressing mutant HRAS oncogene exhibit aberrations of chromatin architecture, aneuploidy, cytoplasmic chromatin deposition and formation of micronuclei with a non-random chromosome content. EVs released from such HRAS-driven cells carry genomic DNA, including oncogenic sequences, and transfer this material to endothelial cells while inducing abnormal formation of micronuclei, along with cell migration and proliferation. Micronuclei were also triggered following treatment with EVs derived from glioma cells (and stem cells) expressing EGFRvIII oncogene, and in both endothelial cells and astrocytes. EVs from HRAS and EGFRvIII-driven cancer cells carry 19 common proteins while EVs from indolent control cells exhibit more divergent proteomes. Immortalized endothelial cell lines with disrupted TP53 pathway were refractory to EV-mediated micronuclei induction. We suggest that oncogenic transformation and intercellular trafficking of cancer-derived EVs may contribute to pathological vascular responses in cancer due to intercellular transmission of genomic instability.

Metabolic networks of the human gut microbiota.

The human gut microbiota controls factors that relate to human metabolism with a reach far greater than originally expected. Microbial communities and human (or animal) hosts entertain reciprocal exchanges between various inputs that are largely controlled by the host via its genetic make-up, nutrition and lifestyle. The composition of these microbial communities is fundamental to supply metabolic capabilities beyond those encoded in the host genome, and contributes to hormone and cellular signalling that support the dynamic adaptation to changes in food availability, environment and organismal development. Poor functional exchange between the microbial communities and their human host is associated with dysbiosis, metabolic dysfunction and disease. This review examines the biology of the dynamic relationship between the reciprocal metabolic state of the microbiota-host entity in balance with its environment (i.e. in healthy states), the enzymatic and metabolic changes associated with its imbalance in three well-studied diseases states such as obesity, diabetes and atherosclerosis, and the effects of bariatric surgery and exercise.

Improving ultrasound-based prostate volume estimation.

BACKGROUND: To define a new coefficient to be used in the formula (Volume = L x H x W x Coefficient) that better estimates prostate volume using dimensions of fresh prostates from patients who had transrectal ultrasound (TRUS) imaging prior to prostatectomy. METHODS: The prostate was obtained from 153 patients, weighed and measured to obtain length (L), height (H), and width (W). The density was determined by water displacement to calculate volume. TRUS data were retrieved from patient charts. Linear regression analyses were performed to compare various prostate volume formulas, including the commonly used ellipsoid formula and newly introduced bullet-shaped formula. RESULTS: By relating measured prostate volumes from fresh prostates to TRUS-estimated prostate volumes, 0.66 was the best fitting coefficient in the (L x H x W x Coefficient) equation. This newfound coefficient combined with outlier removal yielded a linear equation with an R2 of 0.64, compared to 0.55 and 0.60, for the ellipsoid and bullet, respectively. By comparing each of the measured vs. estimated dimensions, we observed that the mean prostate height and length were overestimated by 11.1 and 10.8% using ultrasound (p < 0.05), respectively, while the mean width was similar (p > 0.05). Overall, the ellipsoid formula underestimates prostate volumes by 18%, compared to an overestimation of 4.6 and 5.7% for the bullet formula and the formula using our coefficient, respectively. CONCLUSIONS: This study defines, for the first time, a coefficient based on freshly resected prostates as a reference to estimate volumes by imaging. Our findings support a bullet rather than an ellipsoid prostate shape. Moreover, substituting the coefficient commonly used in the ellipsoid formula by our calculated coefficient in the equation estimating prostate volume by TRUS, provides a more accurate value of the true prostate volume.

Psychosocial adjustment to a prostate cancer diagnosis in a cohort of radical prostatectomy patients in Quebec, Canada.

OBJECTIVE: The psychosocial impact of a prostate cancer diagnosis significantly affects a patient's quality of life. We studied patient communication at the time of diagnosis and its impact on psychosocial adjustment of patients. METHODS: This is a cross-sectional data analysis from self-administered questionnaires in the PROCURE biobank study, consisting of a cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec (Canada), 2006 to 2013. Odds ratios (OR) and their respective 95% confidence intervals (95% CI) were calculated using binary or ordered logistic regression models. RESULTS: Data from 1841 patients were analyzed. The median age of patients was 62 years (range 41-80 years), the majority was French-Canadian (68.3%) and married (79.6%). Most patients (90.1%) considered conversations with their treating physician a useful information source. Patients were dissatisfied on the communication when receiving their diagnosis by telephone (OR = 0.19, 95% CI, 0.11-0.33). Younger patients were also more dissatisfied. Most patients preferred to receive information on prostate cancer (89.5%) and radical prostatectomy (88.0%) at the time of diagnosis, while only 58.8% and 52.4% of patients received this information at this stage. Patients who were dissatisfied with the communication of the diagnosis had more negative responses, such as increased worries and fear (P < 0.05). The five most useful coping mechanisms were physical activity (62.3%), breathing exercises (44.5%), music (32.8%), faith (30.3%), and muscle relaxation (30.1%), but varied by demographics. CONCLUSIONS: This study highlights the importance of physicians communicating a prostate cancer diagnosis well to their patients. Patients may benefit from individually tailored interventions to facilitate their overall coping.

Leukobiopsy - A Possible New Liquid Biopsy Platform for Detecting Oncogenic Mutations.

Detection of unique oncogenic alterations encoded by the sequence or biochemical modification in cancer-associated transforming macromolecules has revolutionized diagnosis, classification and management of human cancers. While these signatures were traditionally regarded as largely intracellular and confined to the tumor mass, oncogenic mutations and actionable cancer-related molecular alterations can also be accessed remotely through their recovery from biofluids of either rare circulating tumor cells (CTCs), or of more abundant non-cellular carriers, such as extracellular vesicles (EVs), protein complexes, or cell-free tumor DNA (ctDNA). Tumor-related macromolecules may also accumulate in circulating platelets. Collectively, these approaches are known as liquid biopsy and hold promise as non-invasive, real-time opportunities to access to the evolving molecular landscape of human malignancies. More recently, a possibility of recovering cancer-specific DNA sequences from circulating leukocytes has also been postulated using experimental models. While it is often assumed that these and other liquid biopsy approaches rely on material passively shed from the tumor mass or its debris, recent evidence suggests that several regulated processes contribute to the abundance, nature, half-life, and turnover of different circulating cancer-related molecular signals. Moreover, many of these signals possess biological activity and may elicit local and systemic regulatory responses. Thus, a better understanding of the biology of liquid biopsy platforms and analytes may enable achieving improved performance of this promising and emerging diagnostic strategy in cancer.

The relationship between body-mass index, physical activity, and pathologic and clinical outcomes after radical prostatectomy for prostate cancer.

PURPOSE: We evaluated whether an increased body-mass index (BMI) and decreased physical activity increase the risk of locally advanced or high-risk prostate cancer (PCa) at radical prostatectomy (RP), and treatment failure after surgery. METHODS: Data were collected from the PROCURE Biobank, a prospective cohort of patients with localized PCa undergoing RP in four academic centers in Québec between 2006 and 2013. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy, and analyzed using the Kaplan-Meier method, log-rank tests, and Cox proportional-hazards models. Uni- and multivariate (ordered) logistic regression was used for time-independent variables. RESULTS: 1813 patients were included. Median follow-up time was 69 months. Patients who reported a lower BMI were generally older, of Asian descent, and physically more active (p < 0.05). Younger, black, and overweight/obese patients reported less physical activity (p < 0.05). In multivariate analyses, a higher BMI increased the risk for locally advanced, high-risk PCa (defined as a pT3, N1 and/or Gleason 8-10 tumor; odds ratio 1.33, p < 0.001), but increased physical activity did not predict high-risk disease (odds ratio 0.84, p = 0.39). Patients with a higher BMI also had a larger prostate at surgery (odds ratio 1.13, p = 0.03). BMI and physical activity were not associated with positive surgical margins or time to treatment failure (p > 0.05). CONCLUSIONS: BMI was an independent predictor for locally advanced, high-risk disease in this cohort of PCa patients undergoing RP, but was unrelated to treatment failure. Physical activity was not related to locally advanced, high-risk PCa or treatment failure.

Optimization of the 2014 Gleason grade grouping in a Canadian cohort of patients with localized prostate cancer.

OBJECTIVES: To evaluate the five-tier Gleason grade group (GG) scoring of prostate cancers adopted by the International Society of Urology Pathology (ISUP) in 2014, and to propose modifications to optimize its performance. PATIENTS AND METHODS: Data were obtained from PROCURE, a prospective cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec, 2006-2013. Surgical specimens were evaluated by genitourinary pathologists using 2014 ISUP criteria. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy. Analyses were conducted using Kaplan-Meier methods, log-rank tests, Cox proportional hazards models and Harrell's concordance indices. RESULTS: A total of 1 917 patients were included, with a median follow-up of 69 months. The 5-year treatment failure rates were 9.6%, 23.5%, 43.1%, 52.6% and 84.3% in GG1-5, respectively (P < 0.001 when comparing GG2 with GG3). Treatment failure rates for patients in GG2 and GG3 with tertiary Gleason 5 pattern were higher than patients in the same group without a tertiary pattern (P < 0.001), but were similar to rates for patients in GGs 3 or 4 without a tertiary pattern (P > 0.3). Primary Gleason pattern (4/5) predicted treatment failure in GG5 (5-year failure rates 82.3% vs 97.1%, respectively; P = 0.001). The five-tier GG system had greater accuracy as a prognostic indicator compared with the four-tier system (Harrell's concordance index 0.716 vs 0.676). When upgrading patients in GG2/3 with tertiary Gleason 5 pattern to patients in GG3/4, and separating patients in GG5 by primary Gleason pattern, the Harrell's concordance index increased to 0.730. CONCLUSION: The five-tier GG system increased accuracy for predicting treatment failure compared with the previous grading systems, but can be further improved.