Publications by authors named "Christina A Kim"

21 Publications

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Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference.

Curr Oncol 2022 03 8;29(3):1796-1807. Epub 2022 Mar 8.

Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada.

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.
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http://dx.doi.org/10.3390/curroncol29030147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947455PMC
March 2022

Report from the Western Canadian Gastrointestinal Consensus Cancer Conference-Management of Total Neoadjuvant Therapy in Rectal Cancer.

Curr Oncol 2022 02 8;29(2):924-927. Epub 2022 Feb 8.

Saskatoon Cancer Center, Saskatchewan Cancer Agency, Saskatoon, SK S7N 4H4, Canada.

An educational session related to the Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held virtually on 14 October 2020. The WCGCCC is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba), who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists, radiologists, and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of total neoadjuvant therapy in rectal cancer.
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http://dx.doi.org/10.3390/curroncol29020078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871158PMC
February 2022

Treatment Patterns, Toxicity, and Outcomes of Older Adults With Advanced Pancreatic Cancer Receiving First-line Palliative Chemotherapy.

Am J Clin Oncol 2022 02;45(2):55-60

Departments of Internal Medicine.

Objectives: Advanced pancreatic cancer (APC) disproportionately impacts older adults. Randomized trials demonstrate improved overall survival (OS) with combination chemotherapy including 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine compared with gemcitabine alone, but with increased toxicity. Older adults are at increased risk of side effects from chemotherapy. The aim of this study was to assess the efficacy and toxicity of chemotherapy in older adults with APC.

Methods: Patients diagnosed with APC from 2011 to 2016 were identified using the Manitoba Cancer Registry. Patient and treatment characteristics, toxicity, and outcomes of patients 65 years of age and above treated with palliative chemotherapy were compared by treatment regimen. OS was assessed using the Kaplan-Meier method. A Cox regression was used to identify independent predictors of OS.

Results: A total of 87 patients aged 65 years and above received palliative chemotherapy: 52 (59.7%) FOLFIRINOX, 21 (24.1%) nab-paclitaxel and gemcitabine, and 14 (16.1%) gemcitabine, with a median age of 69 (65 to 84), 75 (65 to 88), and 73 (67 to 82), Eastern Cooperative Oncology Group (ECOG) performance status difference in hematologic toxicity between regimens (P=0.807). An increase in nonhematologic toxicity was seen with FOLFIRINOX (P<0.001), specifically neuropathy (P=0.008), fatigue (P<0.001), and nausea/vomiting (P=0.008). FOLFIRINOX was associated with improved radiologic response (P=0.05) and OS (P=0.035). PS, baseline carbohydrate antigen 19-9 level, and chemotherapy regimen were independent predictors of survival.

Conclusions: FOLFIRINOX is associated with improved response and OS in older adults with APC. FOLFIRINOX has a manageable safety profile in this population and should be considered in fit older adults with APC.
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http://dx.doi.org/10.1097/COC.0000000000000882DOI Listing
February 2022

Report from the 21st Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; 20-21 September 2019.

Curr Oncol 2021 09 21;28(5):3629-3648. Epub 2021 Sep 21.

Tom Baker Cancer Center, Alberta Health Service, Calgary, AB T2N 4N2, Canada.

The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20-21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.
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http://dx.doi.org/10.3390/curroncol28050310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482207PMC
September 2021

Symptom Burden of Patients with Advanced Pancreas Cancer (APC): A Provincial Cancer Institute Observational Study.

Curr Oncol 2021 07 22;28(4):2789-2800. Epub 2021 Jul 22.

CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.

Patients with advanced pancreatic cancer (APC) experience many disease-related symptoms. ESAS-r measures the severity of 9 symptom domains and has been validated for use in the ambulatory oncology setting. We aimed to describe symptom burden at baseline for patients with APC treated with modern chemotherapy (CT), and to determine whether symptom burden at baseline is prognostic. Patients diagnosed with APC between 2012-2016, treated with ≥1 cycle of CT, who completed ≥1 ESAS-r were identified. Descriptive statistics were used to report symptom burden and common moderate-to-severe symptoms. A joint model was used to describe the trajectory of ESAS-r during follow-up while controlling for death. Multivariable Cox regression was used to identify independent predictors of death. Of 123 patients identified, the median age was 65 and 61% had metastatic disease. The median baseline ESAS-r total symptom distress score (TSDS) was 24. A total of 86% of patients had at least one symptom score of ≥4 at baseline, with the most common being: fatigue, nausea, anxiety, and shortness of breath. Median overall survival was 10.2 months. Baseline TSDS was not predictive for worse survival in the era of modern CT. Patients with APC have a high burden of cancer-associated symptoms and a high prevalence of moderate-to-severe symptoms. Early intervention has the potential to improve quality of life in this group of patients and should be investigated.
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http://dx.doi.org/10.3390/curroncol28040244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395517PMC
July 2021

Capecitabine-mediated heart failure in colorectal cancer: a case series.

Eur Heart J Case Rep 2021 Mar 2;5(3):ytab079. Epub 2021 Mar 2.

Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Capecitabine 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 Summary: We 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 echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography did not identify infarction, myocarditis, or any infiltrative process to explain their symptoms. Both patients had complete resolution of cardiac function, with no long-term sequalae.

Discussion: In patients receiving Capecitabine, reversible heart failure leading to cardiogenic shock should be considered as a potential cardiotoxic side effect.
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http://dx.doi.org/10.1093/ehjcr/ytab079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936921PMC
March 2021

Immune Checkpoint Inhibition as Primary Adjuvant Therapy for an -Mutant Anaplastic Astrocytoma in a Patient with CMMRD: A Case Report-Usage of Immune Checkpoint Inhibition in CMMRD.

Curr Oncol 2021 02 1;28(1):757-766. Epub 2021 Feb 1.

Section of Hematology/Oncology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive hereditary cancer syndrome due to biallelic germline mutation involving one of the four DNA mismatch repair genes. Here we present a case of a young female with CMMRD, homozygous for the c.2002A>G mutation in the gene. She developed an early stage adenocarcinoma of the colon at the age of 14. Surveillance MRI of the brain at age 18 resulted in the detection of an asymptomatic brain cancer. On resection, this was diagnosed as an anaplastic astrocytoma. Due to emerging literature suggesting benefit of immunotherapy in this patient population, she was treated with adjuvant dual immune checkpoint inhibition, avoiding radiation. The patient remains stable with no evidence of progression 20 months after resection. The patient's clinical course, as well as the rational for considering adjuvant immunotherapy in patients with CMMRD are discussed in this report.
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http://dx.doi.org/10.3390/curroncol28010074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985791PMC
February 2021

Impact of Personalized Genetic Breast Cancer Risk Estimation With Polygenic Risk Scores on Preventive Endocrine Therapy Intention and Uptake.

Cancer Prev Res (Phila) 2021 02 23;14(2):175-184. Epub 2020 Oct 23.

Breast Diagnostic Clinic, Mayo Clinic, Rochester, Minnesota.

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 ( < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy ( < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed. 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.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0154DOI Listing
February 2021

Utility of the modified frailty index in predicting toxicity and cancer outcomes for older adults with advanced pancreatic cancer receiving first-line palliative chemotherapy.

J Geriatr Oncol 2021 01 11;12(1):112-117. Epub 2020 Aug 11.

Department of Internal Medicine, University of Manitoba, 820 Sherbrook St, R3A 1R9 Winnipeg, MB, Canada; CancerCare Manitoba, Department of Hematology and Medical Oncology, 675 McDermot Ave, R3E 0V9 Winnipeg, MB, Canada; Research Institute in Oncology and Hematology, CancerCare Manitoba, 675 McDermot Ave, R3E 0V9 Winnipeg, MB, Canada. Electronic address:

Background: Pancreatic cancer primarily affects older adults and is associated with a high morbidity and mortality. Identifying frail patients with advanced pancreatic cancer (APC) helps to mitigate the risks of chemotherapy (CT). The modified Frailty Index (mFI) is an 11-point deficit measure used to identify frail patients. Although validated in surgical fields, it has not been assessed in an APC population.

Methods: A retrospective cohort study evaluated consecutive patients, aged ≥65 years, diagnosed with APC from 2011 to 2016 and treated with first line palliative-intent CT. mFI was categorized as: 0, 1, 2 and ≥ 3. Descriptive analysis was completed comparing patient characteristics, CT toxicity, response to treatment, and overall survival (OS) by mFI score.

Results: 87 patients with APC received palliative CT. Median age was 71 (65-88), 54% male. A mFI score of 0, 1, 2, and ≥ 3 occurred for 20 (23%), 28 (32.2%), 25 (28.7%) and 14 (16.1%) patients respectively. Patients with mFI scores of 0-1 were more likely to receive: 5-fluorouracil, irinotecan and oxaliplatin. CT toxicity, emergency room (ED) and urgent cancer clinic (UCC) presentation, and hospitalization length did not differ by mFI. Longer OS was associated with better ECOG and receipt of combination CT.

Conclusion: This is the first assessment of the mFI in an APC population receiving CT. The mFI score did not correlate with toxicity, ED/UCC visits, hospitalization length or OS. Ongoing assessment of tools that accurately identify frailty in patients with APC is critical to help better select candidates for aggressive CT.
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http://dx.doi.org/10.1016/j.jgo.2020.07.004DOI Listing
January 2021

Osseous sarcoidosis mimicking metastatic breast cancer.

CMAJ 2020 Jul;192(28):E799-E802

Max Rady College of Medicine (Li) and Department of Internal Medicine (Kim), Rady Faculty of Health Sciences, University of Manitoba; Sections of Adult Radiology (Stillwater) and Nuclear Medicine (Bryanton), Department of Radiology, University of Manitoba; Research Institute in Oncology and Hematology (Kim), Cancer-Care Manitoba, Winnipeg, Man.

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http://dx.doi.org/10.1503/cmaj.191661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828862PMC
July 2020

Ketogenic and low-sugar diets for patients with cancer: perceptions and practices of medical oncologists in Canada.

Support Care Cancer 2020 Nov 23;28(11):5243-5249. Epub 2020 Feb 23.

Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, Canada.

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.
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http://dx.doi.org/10.1007/s00520-020-05361-9DOI Listing
November 2020

Real-world Outcomes Among Patients Treated With Gemcitabine-based Therapy Post-FOLFIRINOX Failure in Advanced Pancreatic Cancer.

Am J Clin Oncol 2019 12;42(12):903-908

BC Cancer, Vancouver, BC.

Objectives: Limited evidence exists for chemotherapy selection in advanced pancreatic cancer (APC) after first-line FOLFIRINOX. Second-line gemcitabine/nab-paclitaxel (GEMNAB) is publicly funded in the Canadian provinces of Alberta (AB) and Manitoba (MB), but not in British Columbia (BC). We compared population-based outcomes by region to examine the utility of second-line GEMNAB versus gemcitabine (GEM) alone.

Methods: We identified patients treated with first-line FOLFIRINOX between 2013 and 2015 across BC, AB, and MB. Baseline characteristics and treatment regimens were compared between AB/MB and BC. Survival outcomes were assessed by the Kaplan-Meier method and compared with log-rank test.

Results: A total of 368 patients were treated with first-line FOLFIRINOX (143 AB/MB, 225 BC): median age 61 (interquartile range: 55 to 68) years, 42% comprising female individuals, and 67% with metastatic disease. Receipt of second-line therapy was 48% in AB/MB versus 44% in BC (P=0.35), and time from diagnosis to second-line therapy was 7.7 (AB/MB) versus 9.4 months (BC; P=0.1). Distribution of second-line GEM use: 73% GEMNAB, 23% GEM (AB/MB) versus 27% GEMNAB, 66% GEM (BC; P<0.001). Median overall survival (OS) from diagnosis was similar: 12.4 (AB/MB) versus 11.5 months (BC; P=0.91). On Cox regression analysis, region was not significant. Secondary survival analysis by second-line regimen demonstrated a median OS of 18.0 months with GEMNAB versus 14.3 months with GEM (P<0.01).

Conclusions: In this population-based comparison of APC patients treated with first-line FOLFIRINOX, survival outcomes were comparable regardless of funded access to second-line GEMNAB. OS by regimen favored second-line GEMNAB, but patient selection may be largely responsible for this difference.
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http://dx.doi.org/10.1097/COC.0000000000000625DOI Listing
December 2019

Durable complete response in a patient with metastatic left-sided colon cancer treated with 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) and panitumumab: A case report.

Clin Case Rep 2019 Jul 20;7(7):1302-1305. Epub 2019 May 20.

Department of Medicine, Saint-Boniface Hospital University of Manitoba Winnipeg Manitoba Canada.

There are rare patients with metastatic colon cancer who experience dramatic and durable responses. Primary tumor location is a prognostic and potentially predictive factor and should be taken into consideration when deciding on the optimal first-line therapy to be used in combination with chemotherapy.
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http://dx.doi.org/10.1002/ccr3.2210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637324PMC
July 2019

Abscopal Resolution of a Hepatic Metastasis in a Patient with Metastatic Cholangiocarcinoma Following Radical Stereotactic Body Radiotherapy to a Synchronous Early Stage Non-small Cell Lung Cancer.

Cureus 2019 Feb 16;11(2):e4082. Epub 2019 Feb 16.

Oncology and Hematology, CancerCare Manitoba, University of Manitoba, Winnipeg, CAN.

This case report describes the abscopal resolution of a liver metastasis in a patient with two separate primary malignancies. A 70-year-old male with an unresectable cholangiocarcinoma with an associated 5 cm liver metastasis was found during his staging investigations to have a 1.8 cm right upper lobe lung tumor. A CT-guided biopsy of the lung tumor revealed a primary adenocarcinoma of lung origin. Given the expected worse prognosis of the metastatic cholangiocarcinoma, after review of his case in provincial gastrointestinal and lung tumor boards, he was treated with eight cycles of palliative gemcitabine and cisplatin chemotherapy. Post eight cycles, the disease in the liver and the lung was stable. After completion of first line palliative systemic therapy, radical stereotactic body radiotherapy (SBRT), consisting of 48 Gy in four fractions, was delivered to the right upper lobe non-small cell lung cancer (NSCLC) primary. Three months post-completion of the SBRT, restaging CT scans were performed which revealed the intriguing spontaneous and complete resolution of his liver metastasis. These findings were confirmed on subsequent MRI imaging of his liver. As his liver metastasis was well outside of the SBRT fields, the spontaneous resolution of his liver metastasis presents clinical evidence of the abscopal effect of cholangiocarcinoma in response to SBRT to his lung tumor.
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http://dx.doi.org/10.7759/cureus.4082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467432PMC
February 2019

Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience.

Clin Colorectal Cancer 2018 09 8;17(3):e451-e456. Epub 2018 Mar 8.

Section of Haematology/Oncology, University of Manitoba, Winnipeg, MB, Canada.

Background: Advanced pancreatic cancer (APC) has a poor prognosis. Current first-line chemotherapy options include FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin), NG (nab-paclitaxel, gemcitabine), and GEM (gemcitabine) alone. The optimal second-line regimen is unclear. For patients with disease progression with FOLFIRINOX who have a good performance status, NG might be a reasonable second-line option.

Patients And Methods: Patients in whom APC was diagnosed from 2012 to 2016 who underwent chemotherapy at CancerCare Manitoba were identified from the Manitoba Cancer Registry. Pharmacy records were used to identified those patients who had received first-line FOLFIRINOX, followed by second-line NG, GEM alone, or best supportive care. A retrospective analysis was performed to identify the patient and treatment characteristics, toxicity, radiologic response, and survival. Edmonton Symptom Assessment System, revised, scores were analyzed to assess symptom control.

Results: A total of 146 patients had received first-line FOLFIRINOX. Of those with disease progression who were offered second-line therapy, 30 received NG, 8 GEM alone, and 22 best supportive care. NG was more toxic than GEM alone; however, the dose intensity was similar between the 2 groups. The median progression-free survival was 3.61 months in the NG group and 2.51 months in the GEM-alone group. The median overall survival was 5.69 months in the NG group and 3.82 months in the GEM-alone group. No significant differences were found in the Edmonton Symptom Assessment System, revised, scores when stratified by the treatment received.

Conclusion: For select patients with APC in whom first-line FOLFIRINOX fails, a role might exist for second-line NG. In our institution, second-line NG was associated with improvement in survival compared with second-line GEM alone, with a manageable toxicity profile.
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http://dx.doi.org/10.1016/j.clcc.2018.03.003DOI Listing
September 2018

Predictive Impact of Clinical Benefit in Chemotherapy-treated Advanced Pancreatic Cancer Patients in Northern Alberta.

Am J Clin Oncol 2018 09;41(9):867-873

Department of Medical Oncology.

Objectives: Patients with advanced pancreatic cancer (APC) have a poor prognosis and experience a large burden of disease-related symptoms. Despite advancements in the treatment of APC, survival is dismal and controlling disease-related symptoms and maintaining quality of life is paramount. We hypothesize that an improvement in disease-related symptoms, and therefore, a clinical benefit, while on chemotherapy is a predictive marker in APC.

Materials And Methods: Patients 18 and older with APC diagnosed between January 1, 2005 and December 31, 2010 and treated at the Cross Cancer Institute were identified using the provincial cancer registry. Disease symptoms were assessed at baseline and clinical benefit while on chemotherapy was defined using a composite endpoint of improvement in patient-reported pain, opioid consumption, Eastern Cooperative Oncology Group performance status, and/or weight. Best radiologic response, progression-free survival (PFS), and overall survival (OS) were recorded.

Results: Of 103 patients, the median age was 64, 58% were male and 66% had metastatic disease. At baseline, the majority of patients reported pain (80%), opioid use (61%), or weight loss (71%). In total, 35 (34%) patients received a clinical benefit with treatment but only 6 (17%) of these patients experienced a radiologic response. The median PFS and OS were improved in patients who experienced a clinical benefit (6.6 vs. 4.6 mo; P=0.03 and 11.7 vs. 6.1 mo; P<0.0001, respectively).

Conclusions: In patients with APC treated with chemotherapy, experiencing a clinical benefit was associated with improved PFS and OS. However, it did not appear to correlate with radiologic response to chemotherapy. Prospective studies are warranted to further investigate the prognostic and predictive value of clinical benefit and improvement in quality of life as measured by standardized tools, in APC.
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http://dx.doi.org/10.1097/COC.0000000000000385DOI Listing
September 2018

Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients.

Clin Colorectal Cancer 2016 09 28;15(3):257-63. Epub 2015 Dec 28.

Department of Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, Canada. Electronic address:

Background: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS.

Methods: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes.

Results: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005).

Conclusions: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses.
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http://dx.doi.org/10.1016/j.clcc.2015.12.008DOI Listing
September 2016

Effects of gender on capecitabine toxicity in colorectal cancer.

J Oncol Pharm Pract 2016 Jun 22;22(3):454-60. Epub 2015 May 22.

Cross Cancer Institute, Edmonton, Alberta, Canada

Background: Capecitabine is a highly water soluble prodrug of 5-fluorouracil that is dosed by patient body surface area. Body surface area dosing makes no allowances for differences in body composition. There is mounting evidence that lean body mass is a better predictor of toxicity than body surface area for drugs which distribute into the lean compartment. Because women, on average, have lower lean body mass than men, we expect that women would experience a higher incidence of toxicity than men when body surface area dosing is used.

Objective: To determine whether female colorectal cancer patients experienced a higher incidence of dose-limiting toxicity than men when treated with adjuvant capecitabine.

Methods: We conducted a retrospective chart review of colorectal cancer patients treated with adjuvant capecitabine at our institute between 2008 and 2012. Patients receiving capecitabine were identified from the pharmacy dispensing database and then screened for inclusion. Dosing and toxicity information were gathered and dose-limiting toxicity incidence (defined as a composite endpoint of dose delay, dose reduction, or discontinuation of therapy) was compared between males and females using the chi-square test. Binary logistic regression analysis was then performed to account for differences between male and female populations.

Results: A total of 299 patients (163 males, 136 females) met inclusion criteria. Females had a significantly higher dose-limiting toxicity incidence than males (67.7 vs. 52.2%, p = 0.007). Relationships between gender and dose-limiting toxicity incidence remained significant after logistic regression analysis (OR: 2.04; 95% CI: 1.23-3.36).

Conclusion: Female colorectal cancer patients experience a higher dose-limiting toxicity incidence than male patients when given adjuvant capecitabine dosed according to body surface area.
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http://dx.doi.org/10.1177/1078155215587345DOI Listing
June 2016

Efficacy and safety of single agent or combination adjuvant chemotherapy in elderly patients with colon cancer: a Canadian cancer institute experience.

Clin Colorectal Cancer 2014 Sep 26;13(3):199-206. Epub 2014 Jun 26.

Cross Cancer Institute, Edmonton, Alberta, Canada.

Background: The pattern of adjuvant chemotherapy (AC) use, toxicity profile, and survival benefit in elderly patients with colon cancer (CC) is unclear. We sought to (1) determine whether patients ≥ 65 years with stage III CC were offered single-agent or combination AC, (2) evaluate the reason for selecting single-agent versus combination AC, (3) evaluate the toxicity profile of single-agent and combination AC in the elderly, and (4) determine whether a survival benefit exists for elderly patients receiving combination AC.

Patients And Methods: A retrospective analysis of records of patients ≥ 65 years diagnosed with stage III CC from 2004 to 2010 was performed to identify baseline characteristics, AC protocols, toxicity, dose intensity, and survival.

Results: Two hundred sixty-eight patients ≥ 65 years were diagnosed and treated with AC from 2004 to 2010. Of these patients, 178 were treated with single-agent AC and 90 were treated with combination AC. The most common reasons for choosing single-agent AC were patient preference, comorbidities, and lack of drug coverage. For each year over 65 years, the odds of receiving combination over single-agent AC decreased by 22%. There were more dose delays, dose reductions, and early chemotherapy discontinuation in the combination AC group because of hematologic toxicity. The 5-year overall survival (OS) was 73% in patients who received single-agent AC compared with 84% in those who received combination AC. There was no difference in cancer-related deaths between the groups.

Conclusion: In elderly patients treated with AC for stage III CC, single-agent AC is used more frequently than combination AC, based on age, comorbidities, and patient choice. Toxicity with combination AC in elderly patients is high. No survival benefit was seen with combination AC over single-agent AC.
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http://dx.doi.org/10.1016/j.clcc.2014.06.002DOI Listing
September 2014

Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by cediranib in a patient with metastatic rectal cancer.

Invest New Drugs 2014 Oct 23;32(5):1036-45. Epub 2014 May 23.

Cross Cancer Institute, 11560 University Avenue NW, Edmonton, AB, T6G 1Z2, Canada,

Background: Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare clinicoradiologic syndrome characterized by neurologic symptoms such as seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of posterior white matter seen on neuroimaging. It has been reported in association with many anti-angiogenic therapies, including bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a potent, orally available small molecule tyrosine kinase inhibitor with anti-angiogenic activity, which has been shown to have activity against various solid tumors.

Case Report: We present a case of a 65 year old male with metastatic adenocarcinoma of the rectum who received cediranib as part of a phase I clinical trial. He developed confusion and fluctuations in his level of consciousness. MRI of the brain revealed diffuse low level T2 signal abnormality in the cerebral peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent with RPLS. With conservative management, including tight blood pressure control, his symptoms improved and MRI findings resolved.

Conclusion: RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled.
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http://dx.doi.org/10.1007/s10637-014-0113-6DOI Listing
October 2014

Effect of maternal birthplace on gestational diabetes prevalence in Colorado Hispanics.

J Immigr Minor Health 2011 Jun;13(3):426-33

Department of Pediatrics, University of Colorado Denver-School of Medicine, Denver Health and Hospitals, 501 28th St., Denver, CO 80205, USA.

(1) Describe gestational diabetes mellitus (GDM) prevalence time trends in USborn (USWH) and Mexico-born (MWH), white Hispanic Colorado women and (2) Determine effect of maternal birthplace on GDM prevalence. Retrospective population-based study of 1995-2004 Colorado birth certificate data for live, singleton births to white, Hispanic mothers estimated prevalence, trends, and association of GDM and maternal birthplace. Univariate, bivariate and logistic regression analyses were conducted. GDM prevalence in 154,957 births increased in both USWH (1.77-2.53%, P < 0.0001) and MWH (2.38-3.08%, P < 0.0001). Over study years, MWH had higher crude odds (OR = 1.30; 95% CI = 1.22-1.38) for developing GDM than USWH. Adjustment for maternal age and maternal education reduced GDM risk by birth country (OR = 1.05; 95% CI = 0.98-1.13, P = ns). GDM prevalence increased in both US-born and Mexico-born, white, Hispanic Colorado women. Mexico-born immigrant women may have increased risk for GDM compared with their USborn counterparts. Lower education attainment may be determinant of disease risk.
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http://dx.doi.org/10.1007/s10903-010-9370-4DOI Listing
June 2011
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