Curr. Oncol., Volume 21, Issue 5 (October 2014) – 23 articles

Hyperammonemic encephalopathy (HE) is a rare complication of malignancy and chemotherapy. Although the cause of HE is unclear, a functional arginine deficiency secondary to increased catabolism has been suggested as a possible mechanism. Either that deficiency or an undetermined metabolite could lead to inhibition of N-acetylglutamate synthase (NAGS), a urea cycle enzyme, resulting in hyperammonemia. We present a case of chemotherapy-induced HE in a patient with no underlying primary urea cycle disorder. The patient had a successful trial of carglumic acid (a synthetic analog of the product of NAGS), which suggests that, at least in some cases, HE can be treated by overcoming proximal inhibition of the urea cycle. Further, our case is the first in the literature to exclude genetic defects and disorders of the proximal urea cycle, suggesting that hyperammonemia in these patients is probably secondary to chemotherapy. Full article

The introduction of targeted agents has improved survival for patients with a number of types of cancer, including several breast cancer subtypes. However, these agents are not without toxicities, and the fact that many patients are now on targeted therapy for extended periods of time has presented new challenges for the management of adverse effects. Everolimus is an inhibitor of mTOR (the mammalian target of rapamycin) that is used as targeted therapy for advanced, hormone receptor–positive, HER2-negative breast cancer in postmenopausal women in combination with exemestane, after treatment failure with letrozole or anastrozole. Minor hemorrhagic events are relatively common with targeted agents, but life-threatening hemorrhages, although uncommon, can also occur. We report a case of life-threatening gastrointestinal bleeding in a 48-year-old woman being treated with everolimus for advanced infiltrating ductal carcinoma of the breast. The bleeding was successfully treated with 13 sessions of endoscopic hemostasis using argon plasma coagulation. Full article

Primary sarcomas of the aorta are extremely uncommon. Depending on histomorphology and immunohistochemical pattern, intimal sarcomas can show angiosarcomatous differentiation. Here, we describe the case of a 60-year-old woman with a primary intimal sarcoma of the aortic arch and signs of cerebral metastatic disease as the initial manifestation. After the patient experienced the onset of severe headaches, ataxia, and left-sided weakness, magnetic resonance imaging showed several brain lesions. Histologic assessment of a brain biopsy specimen revealed a malignant tumour composed of large pleomorphic cells that were positive for pancytokeratin and CD10. Radiation to the brain did not significantly improve the patient’s symptoms, and cranial computed tomography (ct) imaging revealed several metastases, indicating lack of response. Because of the patient’s smoking history, the presence of central nervous system and skeletal metastases on combined positron-emission tomography and ct imaging, and the focal pan-cytokeratin positivity of the tumour, carcinoma of the lung was favoured as the primary tumour. Despite chemotherapy with cisplatin and etoposide, the patient’s neurologic symptoms and general condition deteriorated rapidly, and she died within a few days. At autopsy, an undifferentiated intimal sarcoma of the aortic arch was diagnosed. The primary tumour in the aorta consisted of large pleomorphic cells. Immunohistochemical analysis of the aortic tumour and brain metastases demonstrated diffuse positivity for vimentin and p53 and focal S-100 staining. In summary, we report a challenging case of advanced intimal sarcoma of the aortic arch with brain and bone metastases at initial presentation. Our report demonstrates the difficulties in diagnosing and treating this disease, and the need for multicentre studies to accrue more patients for investigations of optimal therapy. Full article

Background: Anthracyclines and taxanes have historically constituted the backbone of chemotherapy regimens for patients with breast cancer positive for the human epidermal growth factor receptor 2 (HER2). For a subset of patients who categorically refuse alopecia, or for those with a contraindication to those drugs, there is an urgent need to define alternative regimens. Here, we report our institutional experience with trastuzumab and vinorelbine (TV), a combination with good clinical activity and a good side effect profile for patients with HER2-positive breast cancer. Methods: In a retrospective analysis, outcomes data were extracted for patients receiving TV as their only chemotherapy in the non-metastatic setting at the Jewish General Hospital. For the most part, TV was administered weekly for 6 months, followed by trastuzumab for 6 months. Results: The analysis identified 46 patients (mean age: 64 years) who received TV between 2003 and 2012 (n = 36 adjuvant, n = 10 neoadjuvant). Of the patients in the adjuvant group, 81% had stage i disease. In the neoadjuvant group, 3 patients experienced a complete pathologic response. Only 1 patient experienced local recurrence after a short course (3 months) of adjuvant TV. Overall survival and breast cancer–specific survival were 94% and 98% respectively at a median 5 years of follow-up. Febrile neutropenia–induced sepsis resulted in the death of 1 patient with significant medical comorbidities; 2 other patients died of comorbidities unrelated to their cancer or treatment. Grades 3 or 4 adverse events included neutropenia (23%), febrile neutropenia (10%), fatigue (2%), and anemia (2%). Conclusions: For patients with non-metastatic breast cancer refusing alopecia, or for patients who are not candidates for standard chemotherapy, TV is a reasonable alternative to standard adjuvant chemotherapy. Full article

Lung cancer patients report the highest distress levels of all cancer groups. In addition to poor prognosis, the self-blame and stigma associated with smoking might partially account for that distress and prevent patients from requesting help and communicating with their partners. The present study used innovative methods to investigate potential links of shame and guilt in lung cancer recovery with distress and marital adjustment. A specific emphasis was an examination of the impact of shame on partner communication. Lung cancer patients (n = 8) and their partners (n = 8) completed questionnaires and interviews that were videotaped. We report descriptive statistics and Spearman correlations between shame and guilt, relationship talk, marital satisfaction, distress, and smoking status. We coded the interviews for nonverbal expressions of shame. Greater self-reported shame was associated with decreased relationship-talk frequency and marital satisfaction, and with increased depression and smoking behaviour. Nonverbal shame behaviour also correlated with higher depression and increased smoking behaviour. Guilt results were more mixed. More recent smoking behaviour also correlated with higher depression. At a time when lung cancer patients often do not request help for distress, possibly because of shame, our preliminary study suggests that shame can also disrupt important partner relationships and might prevent patients from disclosing to physicians their need for psychosocial intervention and might increase their social isolation. Even if patients cannot verbally disclose their distress, nonverbal cues could potentially give clinicians an opportunity to intervene. Full article

We examined trends in radiation therapy (RT) utilization by a population-based breast cancer cohort in Ontario. The provincial cancer registry provided a breast cancer cohort based on diagnosis dates from April 1, 2005, to March 31, 2010. Staging information was also available. The cohort was then linked, by encrypted health card number, to linkable administrative datasets, including RT utilization. The average age in the identified female breast cancer cohort (n = 39,656) was 61.6 ± 14.0 years. Almost two thirds of the patients (n = 25,225) received RT, and staging information was available for 22,988 patients (9541 stage I, 8516 stage II, 4050 stage III, and 881 stage IV). The average number of RT courses received by the patients was 1.4 ± 0.7 for stage I, 1.8 ± 1.1 for stage II, 2.5 ± 1.3 for stage III, and 2.8 ± 2.4 for stage IV. The ratio of conventional RT to intensity-modulated RT was 70.9%:16.6% for stage I, 71.6%:11.3% for stage II, 74.6%:4.6% for stage III, and 89.6%:2.2% for stage IV. From 2005 to 2010, almost two thirds of a Canadian female breast cancer cohort received RT, and the average number of courses increased with disease severity. A similar trend was observed with the type of RT (use of conventional RT increased with disease severity). The next step is to apply unit costs to the number of fractions and to obtain RT planning and radiation therapist times. Full article

(1) Background: The treatment of head-and-neck cancer is complex and requires the involvement of various health care professionals with a wide range of expertise. We describe the process of developing a practice guideline with recommendations about the organization and delivery of health care services for head-and-neck cancer patients in Alberta. (2) Methods: Outcomes of interest included composition of the health care team, qualification requirements for team members, cancer centre and team member volumes, infrastructure needs, and wait times. A search for existing practice guidelines and a systematic review of the literature addressing the organization and delivery of health care services for head-and-neck cancer patients were conducted. The search included the Standards and Guidelines Evidence (sage) directory of cancer guidelines and PubMed. (3) Results: One practice guideline was identified for adaptation. Three additional practice guidelines provided supplementary evidence to inform guideline recommendations. Members of the Alberta Provincial Head and Neck Tumour Team (consisting of various health professionals from across the province) provided expert feedback on the adapted recommendations through an online and in-person review process. Selected experts in head-and-neck cancer from outside the province participated in an external online review. (4) Summary: The recommendations outlined in this practice guideline are based on existing guidelines that have been modified to fit the Alberta context. Although specific to Alberta, the recommendations lend credence to similar published guidelines and could be considered for use by groups lacking the resources of appointed guideline panels. The recommendations are meant to be a guide rather than a fixed protocol. The implementation of this practice guideline will depend on many factors, including but not limited to availability of trained personnel, adequate funding of infrastructure, and collaboration with other associations of health care professionals in the province. Full article

Based on demonstrated favourable risk–benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel–carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc. Full article

Backgroud: We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt). Methods: Medical records (1998–2007) were retrospectively reviewed for the population of interest. The Kaplan–Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr. Results: The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis–free survival (dmfs), and breast cancer–specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001). Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs. Conclusions: In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs. Full article

(1) Objective: High-dose methotrexate (hdmtx) is a common therapeutic agent in the treatment of osteosarcoma. However, hdmtx is highly toxic and requires complex pharmacokinetic monitoring and leucovorin rescue. Thus, alternative therapeutic strategies are necessary. Here, we analyzed the clinical efficacy of a dia regimen (cisplatin–ifosfamide–doxorubicin) to evaluate its potential as an alternative to hdmtx–based therapy. (2) Methods: Patients received 12 cycles of chemotherapy administered over 2 years (2 preoperative cycles and 10 postoperative cycles). Cumulative dose was the same in all cycles: cisplatin 120 mg/m² on day 1 of week 1, followed by ifosfamide 2.0 g/m² days 1–5 of week 2, and doxorubicin 20 mg/m² days 1–3 of week 2. (3) Results: Between January 2004 and October 2008, 39 eligible patients (median age: 16 years) were enrolled, with 36 being evaluable for the study. Of those 36 patients, 20 (55.6%) had a good histologic response to preoperative chemotherapy (>90% tumour necrosis). The estimated 5-year rates of event-free survival (efs) and overall survival were 54.8% and 61.5% respectively. (4) Conclusions: The results of our study suggest that, in osteosarcoma patients, the dia regimen produces an efs rate and survival outcomes comparable to those attained with hdmtx–containing regimens, with fewer adverse reactions. The dia regimen is well tolerated, and we observed a high level of patient compliance. Our results demonstrate that hdmtx-free osteosarcoma treatment regimens can be effective, warranting further investigation. Full article

Purpose: We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors. Methods: Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen. Results: Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (CI): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% CI: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% CI: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% CI: 4.58 to 10.16). Conclusions: Many colorectal cancer survivors within generalpopulation screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening. Full article

The Canadian Lung Cancer Conference 2014, held in Vancouver, British Columbia, was an opportunity for Canadian lung cancer researchers and treatment experts to meet and discuss current breakthroughs and paradigm shifts in the field. The full-day program featured lectures, discussion, and debates, with ample time for informal networking. We are already looking forward to next year’s meeting (scheduled for February 6, 2015), where we expect to discuss and reflect on some of the latest results and breakthroughs from both the American Society of Clinical Oncology and the European Society for Medical Oncology. Full article

Research has indicated that exercise is critical in the recovery process for breast cancer patients, and yet this evidence has infrequently been translated into sustainable community programming. The present article describes the processes and operations of BEAUTY (the Breast Cancer Patients Engaging in Activity and Undergoing Treatment program). This evidencebased 12-week exercise program, with an optional 12-week maintenance component, is supported by the Wings of Hope Foundation, allowing the program to be delivered at no cost to participants. The program was designed to restore and improve the physical well-being of women living with breast cancer as they undergo chemotherapy or radiation treatments. Evaluations measure safety and adherence to the program and the effects of the program on physiologic and psychological outcomes and quality of life. The BEAUTY program addresses the gap between the level of evidence for the benefits of exercise after a cancer diagnosis and translation of that evidence into community programming by providing an accessible, individualized, and safe physical activity program for women during treatment for breast cancer. Full article

In this interview with the patient representatives on the Expert Review Committee (pERC) of the Pan-Canadian Oncology Drug Review (pCODR), those representatives offer their views about how to be a valuable contributing member of Canada’s national cancer drug funding recommendation committee. The article seeks to inform readers, and especially clinicians, about pCODR from the perspective of the patient representatives. Full article

Background: Compared with photon therapy, proton-beam therapy (PBT) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access PBT, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from PBT and suggests an out-ofcountry referral process. Methods: The MEDLINE, EMBASE, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after PBT. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Results: Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (RT). In uncontrolled and retrospective studies, local control rates with PBT appear similar to, or in some cases higher than, photon RT. Randomized trials comparing equivalent doses of PBT and photon RT are not available. Summary: Referral for PBT is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases. Full article

The use of all-trans-retinoic acid (ATRA) and anthracyclines (with or without cytarabine) in the treatment of acute promyelocytic leukemia (APL) has dramatically changed the management and outcome of the disease over the past few decades. The addition of arsenic trioxide (ATO) in the relapsed setting—and, more recently, in reduced-chemotherapy or chemotherapy-free approaches in the first-line setting—continues to improve treatment outcomes by reducing some of the toxicities associated with anthracycline-based approaches. Despite those successes, a high rate of early death from complications of coagulopathy remains the primary cause of treatment failure before treatment begins. In addition to that pressing issue, clarity is needed about the use of ATO in the first-line setting and the role of hematopoietic stem-cell transplantation (HSCT) in the relapsed setting. The aim for the present consensus was to provide guidance to health care professionals about strategies to reduce the early death rate, information on the indications for HSCT and on the use of ATO in induction and consolidation in low-to-intermediate–risk and high-risk APL patients. Full article

(1) Rationale: Paper-based medical record systems are known to have major problems of inaccuracy, incomplete data, poor accessibility, and challenges to patient confidentiality. They are also an inefficient mechanism of record-sharing for interdisciplinary patient assessment and management, and represent a major problem for keeping current and monitoring quality control to facilitate improvement. To address those concerns, national, regional, and local health care authorities have increased the pressure on oncology practices to upgrade from paper-based systems to electronic health records. (2) Objectives: Here, we describe and discuss the challenges to implementing a region-wide oncology information system across four independent health care organizations, and we describe the lessons learned from the initial phases that are now being applied in subsequent activities of this complex project. (3) Results: The need for change must be shared across centres to increase buy-in, adoption, and implementation. It is essential to establish physician leadership, commitment, and engagement in the process. Work processes had to be revised to optimize use of the new system. Culture change must be included in the change management strategy. Furthermore, training and resource requirements must be thoroughly planned, implemented, monitored, and modified as required for effective adoption of new work processes and technology. Interfaces must be established with multiple existing electronic systems across the region to ensure appropriate patient flow. Periodic assessment of the existing project structure is necessary, and adjustments are often required to ensure that the project meets its objectives. (4) Conclusions: The implementation of region-wide oncology information systems across different health practice locations has many challenges. Leadership is essential. A strong, collaborative information-sharing strategy across the region and with the supplier is essential to identify, discuss, and resolve implementation problems. A structure that supports project management and accountability contributes to success. Full article

Background: Whether screening mammography programs should include women in their 40s is controversial. In Canada, screening of women aged 40–49 years has not been shown to reduce mortality from breast cancer. Given that screening mammography reduces mean tumour size and that tumour size is inversely associated with survival, the lack of benefit seen with screening is puzzling and suggests a possible adverse effect on mortality of mammography or subsequent treatment (or both) that counterbalances the expected benefit derived from downstaging. Methods: We followed 50,436 women 40–49 years of age until age 60 for mortality from breast cancer. Of those women, one half had been randomly assigned to annual mammography and one half to no mammography. The impact of mammography on breast cancer mortality was estimated using a left-censored Cox proportional hazards model. Results: Of 256 deaths from breast cancer recorded in the study cohort, 134 occurred in women allocated to mammography, and 122 occurred in those receiving usual care and not allocated to mammography. The cumulative risk of death from breast cancer to age 60 was 0.53% for women assigned to mammography and 0.48% for women not so assigned. The hazard ratio for breast cancer–specific death associated with 1 or more screening mammograms before age 50 was 1.10 (95% confidence interval: 0.86 to 1.40). Conclusions: Mammography in women 40–49 years of age is associated with a small but nonsignificant increase in the risk of dying of breast cancer before age 60. Caution should be exercised when recommending mammographic screening to women before age 50. Full article