Benjamin Goldenberg - Academia.edu (original) (raw)

Papers by Benjamin Goldenberg

Canadian Journal of Surgery

Supportive Care in Cancer, Feb 23, 2020

Purpose Many patients with cancer are interested in complementary therapies, including strategies... more Purpose Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. Method A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. Results Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. Conclusion The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

Current Oncology

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care ... more The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015. Rates of ED visits were also stratified by ED location, severity, and cancer type. We found a 6% (95% CI 1.00–1.13, p-value = 0.0389) increase in PCC visits, a 7% (95% CI 0.99–1.15, p-value = 0.0737) increase in hospitalizations, a 4% (95% CI 0.86–1.08, p-value = 0.5053) decrease in the rate of ED visits, and a 3% (95% CI 0.92–1.17, p-value = 0.5778) increase in the rate of ED visits during the UCC clinic hours after the UCC clinic opened...

Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased ris... more Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer-Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median (range) age, 56.1 (36.0-76.4 years)]. Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed. Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.

Supportive Care in Cancer

Purpose Pancreatic cancer is a lethaldisease. Many patients experience a heavy burden of cancer-a... more Purpose Pancreatic cancer is a lethaldisease. Many patients experience a heavy burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care alongside standard oncologic care results in improved QOL and survival in some cancer types. The benefit in advanced pancreatic cancer (APC) is not fully quantified. Methods In this prospective case-crossover study, patients ≥ 18 years old with APC were recruited from ambulatory clinics at a tertiary cancer center. Patients underwent a palliative care consultation within 2 weeks of registration, with follow up visits every 2 weeks for the first month, then every 4 weeks until week 16, then as needed. The primary outcome was change in QOL between baseline (BL) and week 16, measured by Functional Assessment of Cancer Therapy-hepatobiliary (FACT-Hep). Secondary outcomes included symptom control (ESAS-r), depression, and anxiety (HADS, PHQ-9) at week 16. Results Of 40 patients, 25 (63%) were male, 28 (70%) had metastatic disease, 31 (78%) had ECOG performance status 0-1, 31 (78%) received chemotherapy. Median age was 70. Mean FACT-hep score at BL was 118.8, compared to 125.7 at week 16 (mean change 6.89, [95%CI (-1.69-15.6); p = 0.11]). On multivariable analysis, metastatic disease (mean change 15.3 [95%CI (5.3-25.2); p = 0.004]) and age < 70 (mean change 12.9 [95%CI (0.5-25.4); p = 0.04]) were associated with improved QOL. Patients with metastatic disease had significant improvement in symptom burden (mean change-7.4 [95%CI (-13.4 to-1.4); p = 0.02]). There was no difference in depression or anxiety from BL to week 16. Conclusion Palliative care should be integrated early in the journey for patients with APC, as it can improve QOL and symptom burden. Trial registration Clinicaltrials.gov identifier: NCT03837132.

European Heart Journal - Case Reports

BackgroundCapecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is c... more BackgroundCapecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is commonly used in the treatment of colorectal cancer. Adverse cardiac side effects are reported in 1–18% of patients receiving Capecitabine. The most commonly proposed mechanism of cardiotoxicity in the setting of Capecitabine use is vasospasm of the coronary arteries. However, cardiotoxicity can also present as an acute coronary syndrome, arrhythmia, hypertension, and/or sudden cardiac death. Profound non-vasospastic cardiotoxicity is rare.Case summaryWe describe two cases of acute heart failure leading to cardiogenic shock in patients shortly after exposure to Capecitabine. Both patients did not demonstrate the characteristic transient ST elevation seen in patients with coronary artery vasospasms secondary to Capecitabine. Both patients required admission to the Acute Cardiac Care Unit requiring vasopressor and inotropic support. Thorough diagnostic investigations including echocardiogra...

Cancer Research

Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast canc... more Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast cancer (BC) risk by 50-65%. Despite this significant reduction, a small proportion of high risk women take ET, due to attitudes toward medications, inaccurate risk perception and drug side-effects. The addition of a polygenic risk score (PRS), comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)), to the standard risk calculator estimates, can be used to improve BC risk estimation. We previously reported on the influence of the PRS-adjusted BC risk estimates on the intent to use ET (Abstract, SABCS, 2019). Here we report on the influence of PRS-adjusted BC risk estimates on ET adherence at 1 and 2 year follow –up. We also report on ET side effects over this same time period. Methods: Women older than age 35 were eligible if they were deemed at high risk for BC by either a 5 year Gail Model risk of ≥3% or 10 year Tyrer-Cuzick risk (IBIS) of ≥5%. We excluded wo...

Cancer Research

Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine ... more Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine therapy (ET) and yet drug uptake and adherence in this setting is suboptimal even among high risk women. A Polygenic Risk Score (PRS) comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)) can provide a personalized risk assessment and potentially influence ET adherence. We assessed ET adherence at 1 year comparing women whose risk estimate increased due to PRS versus women whose risk estimate decreased due to PRS. The effect of ET use on quality of life (hot flashes, night sweats, vaginal dryness, weight gain, joint pain) was evaluated. Methods: Eligible women required either a 5 year Gail Model risk of ≥3% or 10 year IBIS ( International Breast Intervention Study or Tyrer-Cuzick model) of ≥5%. Women with a history of breast cancer (BC) or hereditary BC syndrome were excluded. High risk women were counseled at baseline using their Gail and IBIS risk score...

Cancer Prevention Research, 2020

Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased ris... more Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer–Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median ...

Current Oncology, 2021

In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs... more In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs of individuals diagnosed with cancer experiencing acute complications of cancer or its treatment. This retrospective cohort study compared the characteristics of individuals diagnosed with cancer that visited the UCC to those who visited an emergency department (ED) and determined predictors of use. Multivariable logistic mixed models were run to predict an individual’s likelihood of visiting the UCC or an ED. Scaled Brier scores were calculated to determine how greatly each predictor impacted UCC or ED use. We found that UCC visits increased up to 4 months after eligibility to visit and then decreased. ED visits were highest immediately after eligibility and then decreased. The median number of hours between triage and discharge was 2 h for UCC visits and 9 h for ED visits. Chemotherapy had the strongest association with UCC visits, whereas ED visits prior to diagnosis had the stronges...

Journal of Clinical Oncology, 2020

TPS777 Background: Pancreatic cancer is lethal. Chemotherapy can improve survival by months; howe... more TPS777 Background: Pancreatic cancer is lethal. Chemotherapy can improve survival by months; however, many patients experience an overwhelming burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care (EPC) alongside standard oncologic care results in improved QOL and survival in patients with lung cancer. Although international guidelines recommend EPC for patients with advanced pancreatic cancer (PANC), the benefit is not known. Objectives: The primary objective is to test for change in QOL between baseline (BL) and 16 weeks (wk). Secondary objectives are to test for change between BL and 16 wk in (a) symptom control; and (b) depression and anxiety. Methods: This prospective case-crossover study of patients with PANC provides EPC plus standard oncologic care. Primary oncology clinics refer patients to an EPC team led by a palliative care physician and a clinical nurse specialist. BL questionnaires are completed prior to initial EPC assessment, then...

Supportive Care in Cancer, 2020

Purpose Many patients with cancer are interested in complementary therapies, including strategies... more Purpose Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. Method A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. Results Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. Conclusion The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

Journal of Clinical Oncology, 2016

e18220Title: Intervention Programs to Improve Oral Chemotherapy Safety and Quality Background: Wi... more e18220Title: Intervention Programs to Improve Oral Chemotherapy Safety and Quality Background: With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective syste...

Journal of Clinical Oncology, 2019

1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very f... more 1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very few at-risk women choose to take them. A woman’s perceived BC risk correlates with uptake of ET. A PRS comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP) improves the accuracy of risk prediction for BC. We examined the impact of the addition of individualized PRS BC risk prediction to standard risk calculator estimates on intent to take BC prevention medication. Methods: Eligible women had ≥5% 10 yr BC Tyrer-Cuzick risk (IBIS) or 5 year Gail score ≥3%, with no history of BC or hereditary BC syndrome. Standard BC risk estimates (IBIS or Gail) were incorporated into the counselling on BC preventive ET. A self-reported questionnaire at baseline quantified intention to take ET and explored factors associated with this decision. Blood samples were obtained and genotyped for 77 SNPs, individualized PRS were calculated then incorporated into IBIS and Gail predi...

The American journal of gastroenterology, Jan 16, 2018

The rectum has distinctive anatomic and physiologic features, which increase the risk of local sp... more The rectum has distinctive anatomic and physiologic features, which increase the risk of local spread and recurrence among rectal cancers as compared to colon cancers. Essential to the management of rectal cancers is accurate endoscopic localization as well as preoperative imaging assessment of local and distant disease. Successful oncologic care is multidisciplinary including input from Gastroenterologists, Surgeons, Medical and Radiation Oncologists, Radiologists, and Pathologists. Extensive planning of curative intent is mandatory as failures of upfront treatment present great long-term difficulty for patients and caregivers. Local recurrences are frequently associated with major morbidity including bowel and urinary obstruction, severe pain, and significantly diminished quality of life. Distant recurrence is associated with lower survival. Over the last two decades, there have been many advances in diagnostic imaging techniques as well as surgical techniques including transanal ...

JAMA oncology, 2017

With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective ... more With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective systems to administer and manage these agents. A comprehensive synthesis of literature on oral chemotherapy care delivery programs to which clinicians can look for best practices is lacking. To summarize the peer-reviewed and gray literature on interventions to improve oral chemotherapy care delivery toward describing best practices and identifying current gaps. Using search terms pertaining to the concepts of oral chemotherapy, cancer, and interventions and outcomes, we performed a systematic review of PubMed, EMBASE, and CINAHL from January 1995 to May 24, 2016, to identify oral chemotherapy intervention programs. We searched the gray literature from January 1995 through February 2016 and contacted gray literature authors for further information. Four physician abstractors reviewed the titles, abstracts, and articles. Quality of the articles was assessed using SQUIRE2 guidelines. Inter...

The American journal of gastroenterology, 2013

We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflam... more We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflammatory bowel disease (IBD). We assessed iron deficiency and anemia in 280 participants from the population-based Manitoba IBD Cohort Study. Iron deficiency was identified in 20% with Crohn's disease and 27% with ulcerative colitis. Anemia was identified overall in 50 (18%), with 230 who were nonanemic. In the nonanemic subgroup, there were no significant differences between iron-deficient and -sufficient groups in mean fatigue levels or proportions with problematic fatigue. There was no unique contribution of iron deficiency to problematic fatigue after adjustment for active disease and anemia. There was no evidence of an association between iron deficiency and fatigue in the absence of anemia, suggesting that iron deficiency is not a clinically relevant contributor to fatigue in IBD.

The American Journal of Gastroenterology, 2004

We aimed at determining the utility of measuring 6-thioguanine (6-TG) and 6-methylmercaptopurine ... more We aimed at determining the utility of measuring 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in inflammatory bowel disease (IBD) patients on azathioprine (AZA) or 6-mercaptopurine (6-MP), whether the described therapeutic range for 6-TG (235-400 pmol/8 x 10(8) red blood cells, RBC) correlated with clinical remission or leukopenia, and if 6-MMP level was a marker for hepatotoxicity (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5,700 pmol/8 x 10(8) RBC). Study eligibility included an IBD diagnosis of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 months and either active disease or disease remission of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 months and the use of AZA/6-MP for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 wk consecutively. Metabolite levels were evaluated against clinical status, CBC, and hepatic parameters. Seventy-four of 166 AZA/6-MP users were eligible. 6-TG levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;235 pmol/8 x 10(8) RBC were found in 22/59 (38%) with active disease and in 7/15 with remission (47%, p= 0.16). There was a trend of higher 6-TG levels among those in remission versus those with active disease (mean 325 +/- 284 vs 223 +/- 159 pmol/8 x 10(8) RBC, p= 0.2). No hepatotoxicity was observed, although 12.2% had 6-MMP levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 5,700 pmol/8 x 10(8) RBC. The correlation between 6-MP dose and 6-TG levels was weak (r = 0.22, p= 0.08). The 6-TG level did not correlate with WBC. There were five instances, each of markedly low levels of both 6-TG and 6-MMP, suggesting noncompliance and of marked 6-MMP levels versus 6-TG. There was a poor correlation between 6-TG levels and remission. Nonetheless, the measurements of these levels are helpful when patients are on high doses but not achieving remission since noncompliance or metabolism favoring 6-MMP can be established.

The American journal of gastroenterology, 2013

We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflam... more We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflammatory bowel disease (IBD). We assessed iron deficiency and anemia in 280 participants from the population-based Manitoba IBD Cohort Study. Iron deficiency was identified in 20% with Crohn's disease and 27% with ulcerative colitis. Anemia was identified overall in 50 (18%), with 230 who were nonanemic. In the nonanemic subgroup, there were no significant differences between iron-deficient and -sufficient groups in mean fatigue levels or proportions with problematic fatigue. There was no unique contribution of iron deficiency to problematic fatigue after adjustment for active disease and anemia. There was no evidence of an association between iron deficiency and fatigue in the absence of anemia, suggesting that iron deficiency is not a clinically relevant contributor to fatigue in IBD.

Canadian Journal of Surgery

Supportive Care in Cancer, Feb 23, 2020

Purpose Many patients with cancer are interested in complementary therapies, including strategies... more Purpose Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. Method A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. Results Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. Conclusion The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

Current Oncology

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care ... more The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015. Rates of ED visits were also stratified by ED location, severity, and cancer type. We found a 6% (95% CI 1.00–1.13, p-value = 0.0389) increase in PCC visits, a 7% (95% CI 0.99–1.15, p-value = 0.0737) increase in hospitalizations, a 4% (95% CI 0.86–1.08, p-value = 0.5053) decrease in the rate of ED visits, and a 3% (95% CI 0.92–1.17, p-value = 0.5778) increase in the rate of ED visits during the UCC clinic hours after the UCC clinic opened...

Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased ris... more Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer-Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median (range) age, 56.1 (36.0-76.4 years)]. Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed. Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.

Supportive Care in Cancer

Purpose Pancreatic cancer is a lethaldisease. Many patients experience a heavy burden of cancer-a... more Purpose Pancreatic cancer is a lethaldisease. Many patients experience a heavy burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care alongside standard oncologic care results in improved QOL and survival in some cancer types. The benefit in advanced pancreatic cancer (APC) is not fully quantified. Methods In this prospective case-crossover study, patients ≥ 18 years old with APC were recruited from ambulatory clinics at a tertiary cancer center. Patients underwent a palliative care consultation within 2 weeks of registration, with follow up visits every 2 weeks for the first month, then every 4 weeks until week 16, then as needed. The primary outcome was change in QOL between baseline (BL) and week 16, measured by Functional Assessment of Cancer Therapy-hepatobiliary (FACT-Hep). Secondary outcomes included symptom control (ESAS-r), depression, and anxiety (HADS, PHQ-9) at week 16. Results Of 40 patients, 25 (63%) were male, 28 (70%) had metastatic disease, 31 (78%) had ECOG performance status 0-1, 31 (78%) received chemotherapy. Median age was 70. Mean FACT-hep score at BL was 118.8, compared to 125.7 at week 16 (mean change 6.89, [95%CI (-1.69-15.6); p = 0.11]). On multivariable analysis, metastatic disease (mean change 15.3 [95%CI (5.3-25.2); p = 0.004]) and age < 70 (mean change 12.9 [95%CI (0.5-25.4); p = 0.04]) were associated with improved QOL. Patients with metastatic disease had significant improvement in symptom burden (mean change-7.4 [95%CI (-13.4 to-1.4); p = 0.02]). There was no difference in depression or anxiety from BL to week 16. Conclusion Palliative care should be integrated early in the journey for patients with APC, as it can improve QOL and symptom burden. Trial registration Clinicaltrials.gov identifier: NCT03837132.

European Heart Journal - Case Reports

BackgroundCapecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is c... more BackgroundCapecitabine is a pyrimidine antimetabolite that inhibits thymidylate synthase and is commonly used in the treatment of colorectal cancer. Adverse cardiac side effects are reported in 1–18% of patients receiving Capecitabine. The most commonly proposed mechanism of cardiotoxicity in the setting of Capecitabine use is vasospasm of the coronary arteries. However, cardiotoxicity can also present as an acute coronary syndrome, arrhythmia, hypertension, and/or sudden cardiac death. Profound non-vasospastic cardiotoxicity is rare.Case summaryWe describe two cases of acute heart failure leading to cardiogenic shock in patients shortly after exposure to Capecitabine. Both patients did not demonstrate the characteristic transient ST elevation seen in patients with coronary artery vasospasms secondary to Capecitabine. Both patients required admission to the Acute Cardiac Care Unit requiring vasopressor and inotropic support. Thorough diagnostic investigations including echocardiogra...

Cancer Research

Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast canc... more Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast cancer (BC) risk by 50-65%. Despite this significant reduction, a small proportion of high risk women take ET, due to attitudes toward medications, inaccurate risk perception and drug side-effects. The addition of a polygenic risk score (PRS), comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)), to the standard risk calculator estimates, can be used to improve BC risk estimation. We previously reported on the influence of the PRS-adjusted BC risk estimates on the intent to use ET (Abstract, SABCS, 2019). Here we report on the influence of PRS-adjusted BC risk estimates on ET adherence at 1 and 2 year follow –up. We also report on ET side effects over this same time period. Methods: Women older than age 35 were eligible if they were deemed at high risk for BC by either a 5 year Gail Model risk of ≥3% or 10 year Tyrer-Cuzick risk (IBIS) of ≥5%. We excluded wo...

Cancer Research

Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine ... more Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine therapy (ET) and yet drug uptake and adherence in this setting is suboptimal even among high risk women. A Polygenic Risk Score (PRS) comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)) can provide a personalized risk assessment and potentially influence ET adherence. We assessed ET adherence at 1 year comparing women whose risk estimate increased due to PRS versus women whose risk estimate decreased due to PRS. The effect of ET use on quality of life (hot flashes, night sweats, vaginal dryness, weight gain, joint pain) was evaluated. Methods: Eligible women required either a 5 year Gail Model risk of ≥3% or 10 year IBIS ( International Breast Intervention Study or Tyrer-Cuzick model) of ≥5%. Women with a history of breast cancer (BC) or hereditary BC syndrome were excluded. High risk women were counseled at baseline using their Gail and IBIS risk score...

Cancer Prevention Research, 2020

Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased ris... more Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer–Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median ...

Current Oncology, 2021

In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs... more In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs of individuals diagnosed with cancer experiencing acute complications of cancer or its treatment. This retrospective cohort study compared the characteristics of individuals diagnosed with cancer that visited the UCC to those who visited an emergency department (ED) and determined predictors of use. Multivariable logistic mixed models were run to predict an individual’s likelihood of visiting the UCC or an ED. Scaled Brier scores were calculated to determine how greatly each predictor impacted UCC or ED use. We found that UCC visits increased up to 4 months after eligibility to visit and then decreased. ED visits were highest immediately after eligibility and then decreased. The median number of hours between triage and discharge was 2 h for UCC visits and 9 h for ED visits. Chemotherapy had the strongest association with UCC visits, whereas ED visits prior to diagnosis had the stronges...

Journal of Clinical Oncology, 2020

TPS777 Background: Pancreatic cancer is lethal. Chemotherapy can improve survival by months; howe... more TPS777 Background: Pancreatic cancer is lethal. Chemotherapy can improve survival by months; however, many patients experience an overwhelming burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care (EPC) alongside standard oncologic care results in improved QOL and survival in patients with lung cancer. Although international guidelines recommend EPC for patients with advanced pancreatic cancer (PANC), the benefit is not known. Objectives: The primary objective is to test for change in QOL between baseline (BL) and 16 weeks (wk). Secondary objectives are to test for change between BL and 16 wk in (a) symptom control; and (b) depression and anxiety. Methods: This prospective case-crossover study of patients with PANC provides EPC plus standard oncologic care. Primary oncology clinics refer patients to an EPC team led by a palliative care physician and a clinical nurse specialist. BL questionnaires are completed prior to initial EPC assessment, then...

Supportive Care in Cancer, 2020

Purpose Many patients with cancer are interested in complementary therapies, including strategies... more Purpose Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. Method A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. Results Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. Conclusion The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.

Journal of Clinical Oncology, 2016

e18220Title: Intervention Programs to Improve Oral Chemotherapy Safety and Quality Background: Wi... more e18220Title: Intervention Programs to Improve Oral Chemotherapy Safety and Quality Background: With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective syste...

Journal of Clinical Oncology, 2019

1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very f... more 1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very few at-risk women choose to take them. A woman’s perceived BC risk correlates with uptake of ET. A PRS comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP) improves the accuracy of risk prediction for BC. We examined the impact of the addition of individualized PRS BC risk prediction to standard risk calculator estimates on intent to take BC prevention medication. Methods: Eligible women had ≥5% 10 yr BC Tyrer-Cuzick risk (IBIS) or 5 year Gail score ≥3%, with no history of BC or hereditary BC syndrome. Standard BC risk estimates (IBIS or Gail) were incorporated into the counselling on BC preventive ET. A self-reported questionnaire at baseline quantified intention to take ET and explored factors associated with this decision. Blood samples were obtained and genotyped for 77 SNPs, individualized PRS were calculated then incorporated into IBIS and Gail predi...

The American journal of gastroenterology, Jan 16, 2018

The rectum has distinctive anatomic and physiologic features, which increase the risk of local sp... more The rectum has distinctive anatomic and physiologic features, which increase the risk of local spread and recurrence among rectal cancers as compared to colon cancers. Essential to the management of rectal cancers is accurate endoscopic localization as well as preoperative imaging assessment of local and distant disease. Successful oncologic care is multidisciplinary including input from Gastroenterologists, Surgeons, Medical and Radiation Oncologists, Radiologists, and Pathologists. Extensive planning of curative intent is mandatory as failures of upfront treatment present great long-term difficulty for patients and caregivers. Local recurrences are frequently associated with major morbidity including bowel and urinary obstruction, severe pain, and significantly diminished quality of life. Distant recurrence is associated with lower survival. Over the last two decades, there have been many advances in diagnostic imaging techniques as well as surgical techniques including transanal ...

JAMA oncology, 2017

With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective ... more With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective systems to administer and manage these agents. A comprehensive synthesis of literature on oral chemotherapy care delivery programs to which clinicians can look for best practices is lacking. To summarize the peer-reviewed and gray literature on interventions to improve oral chemotherapy care delivery toward describing best practices and identifying current gaps. Using search terms pertaining to the concepts of oral chemotherapy, cancer, and interventions and outcomes, we performed a systematic review of PubMed, EMBASE, and CINAHL from January 1995 to May 24, 2016, to identify oral chemotherapy intervention programs. We searched the gray literature from January 1995 through February 2016 and contacted gray literature authors for further information. Four physician abstractors reviewed the titles, abstracts, and articles. Quality of the articles was assessed using SQUIRE2 guidelines. Inter...

The American journal of gastroenterology, 2013

We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflam... more We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflammatory bowel disease (IBD). We assessed iron deficiency and anemia in 280 participants from the population-based Manitoba IBD Cohort Study. Iron deficiency was identified in 20% with Crohn's disease and 27% with ulcerative colitis. Anemia was identified overall in 50 (18%), with 230 who were nonanemic. In the nonanemic subgroup, there were no significant differences between iron-deficient and -sufficient groups in mean fatigue levels or proportions with problematic fatigue. There was no unique contribution of iron deficiency to problematic fatigue after adjustment for active disease and anemia. There was no evidence of an association between iron deficiency and fatigue in the absence of anemia, suggesting that iron deficiency is not a clinically relevant contributor to fatigue in IBD.

The American Journal of Gastroenterology, 2004

We aimed at determining the utility of measuring 6-thioguanine (6-TG) and 6-methylmercaptopurine ... more We aimed at determining the utility of measuring 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in inflammatory bowel disease (IBD) patients on azathioprine (AZA) or 6-mercaptopurine (6-MP), whether the described therapeutic range for 6-TG (235-400 pmol/8 x 10(8) red blood cells, RBC) correlated with clinical remission or leukopenia, and if 6-MMP level was a marker for hepatotoxicity (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5,700 pmol/8 x 10(8) RBC). Study eligibility included an IBD diagnosis of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 months and either active disease or disease remission of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6 months and the use of AZA/6-MP for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 wk consecutively. Metabolite levels were evaluated against clinical status, CBC, and hepatic parameters. Seventy-four of 166 AZA/6-MP users were eligible. 6-TG levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;235 pmol/8 x 10(8) RBC were found in 22/59 (38%) with active disease and in 7/15 with remission (47%, p= 0.16). There was a trend of higher 6-TG levels among those in remission versus those with active disease (mean 325 +/- 284 vs 223 +/- 159 pmol/8 x 10(8) RBC, p= 0.2). No hepatotoxicity was observed, although 12.2% had 6-MMP levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 5,700 pmol/8 x 10(8) RBC. The correlation between 6-MP dose and 6-TG levels was weak (r = 0.22, p= 0.08). The 6-TG level did not correlate with WBC. There were five instances, each of markedly low levels of both 6-TG and 6-MMP, suggesting noncompliance and of marked 6-MMP levels versus 6-TG. There was a poor correlation between 6-TG levels and remission. Nonetheless, the measurements of these levels are helpful when patients are on high doses but not achieving remission since noncompliance or metabolism favoring 6-MMP can be established.

The American journal of gastroenterology, 2013

We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflam... more We explored whether iron deficiency in the absence of anemia is associated with fatigue in inflammatory bowel disease (IBD). We assessed iron deficiency and anemia in 280 participants from the population-based Manitoba IBD Cohort Study. Iron deficiency was identified in 20% with Crohn's disease and 27% with ulcerative colitis. Anemia was identified overall in 50 (18%), with 230 who were nonanemic. In the nonanemic subgroup, there were no significant differences between iron-deficient and -sufficient groups in mean fatigue levels or proportions with problematic fatigue. There was no unique contribution of iron deficiency to problematic fatigue after adjustment for active disease and anemia. There was no evidence of an association between iron deficiency and fatigue in the absence of anemia, suggesting that iron deficiency is not a clinically relevant contributor to fatigue in IBD.