Purpose: Radium-223 has been demonstrated in clinical trials to improve survival in castration-resistant prostate cancer (CRPC) patients with bone metastases. However, its performance in routine use remains to be fully characterized. This study aims to describe patient outcomes in the real world as well as identify factors associated with completion of the 6-dose regimen and alkaline phosphatase (ALP) response. Methods: Thirty-six patients who received at least one dose of radium-223 at the Jewish General Hospital in Montréal, Canada, were analysed in a retrospective manner. Using logistic regression, the primary analysis aimed to identify factors associated with treatment completion, and the secondary analysis aimed to identify factors associated with ALP response. Results: Twenty-one out of 36 patients received all 6 doses of radium-223. Fifteen patients had an ALP response, defined as a 30% decrease in ALP from baseline values. On primary analysis, baseline ALP > 120 U/L and prostate-specific antigen (PSA) > 50 μg/L were significantly associated with lower therapy completion rates (OR = 0.10, p = 0.004; OR = 0.18, p = 0.022 respectively). On adjustment for confounders, only ALP remained significant (OR = 0.14, p = 0.021). Clinical disease progression was the most common reason for treatment non-completion, and it was also associated with elevated baseline ALP (OR = 6.00, p = 0.044). On secondary analysis, previous chemotherapy for CRPC was a negative predictor of ALP response (OR = 0.15, p = 0.034). Conclusion Elevated baseline ALP and PSA were associated with a lower rate of radium-223 regimen completion; receiving chemotherapy for CRPC prior to radium-223 was associated with a lower rate of ALP response.

Purpose: Rectal cancer treatment has a wide range of possible approaches from radical extirpative surgery to nonoperative watchful waiting following chemoradiotherapy, with or without, additional chemotherapy. Our goal was to assess the personal opinion of active practicing surgeons on rectal cancer treatment if he/she was the patient. Methods: A panel of the International Society of University Colon and Rectal Surgeons (ISUCRS) selected 10 questions that were included in a questionnaire that included other items including demographics. The questionnaire was distributed electronically to ISUCRS fellows and other surgeons included in our database and remained open from April 16 to 28, 2020. Results: One hundred sixty-three specialists completed the survey. The majority of surgeons (n=65, 39.9%) chose the minimally invasive (laparoscopic) surgery for their personal treatment of rectal cancer. For low-lying rectal cancer T1 and T2, the treatment choice was standard chemoradiation+local excision (n=60, 36.8%) followed by local excision±chemoradiotherapy if needed (n=55, 33.7%). In regards to locally advanced low rectal cancer T3 or greater, the preference of the responders was for laparoscopic surgery (n=65, 39.9%). We found a statistically significant relationship between surgeons’ age and their preference for minimally invasive techniques demonstrating an age-based bias on senior surgeons’ inclination toward open approach. Conclusion Our survey reveals an age-based preference by surgeons for minimally invasive surgical techniques as well as organ-preserving techniques for personal treatment of treating rectal cancer. Only 1/4 of specialists do adhere to the international guidelines for treating early rectal cancer.

Objectives: The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. Method: Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. Results: Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. Conclusion This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.
Pharmacogenetics ; Cytochrome P-450 CYP2D6 ; Lung Neoplasms ; Biomarkers

Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.
Colorectal Neoplasms ; Polymorphism, Genetic