Curr. Oncol., Volume 17, Issue 1 (February 2010) – 15 articles

Aromatase inhibitors (AIS) are commonly used as adjuvant treatment in postmenopausal women with hormone receptor–positive early breast cancer. With both steroidal and nonsteroidal AIS, AI-induced arthralgia is frequently observed. The mechanism of AI-induced arthralgia remains unknown, and the data available from clinical trails using AIS are limited. We review the pertinent information from a clinical perspective, including an algorithm to treat AI-induced arthralgia. Full article

Hormone-suppression therapies are used for the treatment of breast cancer in the adjuvant and metastatic settings alike. However, side effects—including hot flashes—are frequently reported by patients as a cause of therapy discontinuation. This paper presents an overview of hormonal therapies and the evidence-based management options for hot flashes, summarized in a treatment algorithm. Full article

In recent years, various rna-based technologies have been under evaluation as potential next-generation cancer therapeutics. MicroRNAS (miRNAS), known to regulate the cell cycle and development, are deregulated in various cancers. Thus, they might serve as good targets or candidates in an exploration of anticancer therapeutics. One attractive candidate for this purpose is let-7 (“lethal-7”). Let-7 is underexpressed in various cancers, and restoration of its normal expression is found to inhibit cancer growth by targeting various oncogenes and inhibiting key regulators of several mitogenic pathways. In vivo, let-7 administration was found effective against mouse-model lung and breast cancers, and our computational prediction supports the possible effectiveness of let-7 in estrogen receptor (ER)–positive metastatic breast cancer. Data also suggest that let-7 regulates apoptosis and cancer stem cell (CSC) differentiation and can therefore be tested as a potential therapeutic in cancer treatment. However, the exact role of let-7 in cancer is not yet fully understood. There is a need to understand the causative molecular basis of let-7 alterations in cancer and to develop proper delivery systems before proceeding to therapeutic applications. This article attempts to highlight certain critical aspects of let-7’s therapeutic potential in cancer. Full article

Here we report a case of primary epithelioid angiosarcoma (EAS) of the breast occurring in a 30-year-old woman. Following fine-needle asspiration cytology (FNAC) and tru-cut biopsy, the patient was initially diagnosed with mammary carcinoma and thereafter underwent modified radical mastectomy. Postoperative histopathologic examination and immunohistochemistry revealed a diagnosis of primary epithelioid angiosarcoma of the breast. The patient received postoperative radiotherapy to the chest wall and was started on adjuvant thalidomide. Preoperatively, EAS can be mistaken for carcinoma because it is difficult to appreciate the typical morphology on FNAC or tru-cut biopsy. Indeed, this is an area of potential diagnostic error because, nowadays, neoadjuvant therapy is often instituted after core biopsy of a breast mass. This case is being reported not only for its diagnostic difficulty, but also because of its rarity in English literature. Full article

Capecitabine, an oral prodrug of 5-fluorouracil (5FU), has been integrated into the management of multiple cancer types because of convenience of administration and efficacy comparable with 5FU. Cardiotoxicity induced by 5FU—in particular angina—has been well described in the literature, but reports of adverse cardiac events with capecitabine are also emerging. The mechanism underlying 5FU cardiotoxicity has long been thought to result from coronary vasospasm, but animal-model studies and patient echocardiographic findings both suggest a cardiomyopathic picture. Although 5FU cardiotoxicity is often reversible and can be managed supportively, presentations that are more severe—including arrhythmias, acute ischemic events, and cardiogenic shock—have been documented. In this report, we describe the case of a patient who ultimately required a pacemaker after developing symptomatic bradycardia and sinus arrest while receiving capecitabine for colon cancer. Full article

Lung cancer is rare disease in patients under 25 years of age. It typically occurs in older patients with a history of tobacco use. This case concerns a 20-year-old man with no history of tobacco use who complained of several months of cough and lower back pain and an 11.3-kg weight loss. He was treated for pneumonia after a chest radiograph showed total opacification of the right lung. Computed tomography imaging subsequently revealed a superior right hilar mass and mediastinal lymphadenopathy. Further imaging studies showed diffuse metastatic disease. Mediastinal biopsy showed poorly differentiated epithelioid tumour with desmoplastic stromal reaction, neutrophil infiltration, and squamous differentiation. Tissue immunostaining confirmed a non-small-cell lung cancer. Unfortunately, despite aggressive therapy, the patient’s disease progressed, and he died within 9 months. In this paper, we hope to illustrate the unique challenges in diagnosing and treating young patients with metastatic lung cancer. Full article

Background and Purpose: Palliative radiotherapy (PRT) is a routine part of oncology care in adult patients, but it is used much less frequently among children with incurable cancer. We surveyed Canadian pediatric oncologists to learn about their knowledge and use of PRT and to identify potential barriers to referral. Methods: A 13-item questionnaire assessing PRT knowledge and utilization was sent to 80 Canadian pediatric oncologists. Results: The survey completion rate was 80%, with most respondents being providers of palliative care for children and making referrals for PRT. Although 62% had received training in radiation oncology, only 28% had received formal palliative care training. Respondents with palliative care training were found to be significantly more knowledgeable about PRT and were more likely to refer children for PRT (p < 0.01). Only 59% of respondents thought that they had adequate knowledge about the indications for PRT. A positive correlation was found between knowledge about the indications for PRT and referral for treatment (p < 0.01). Among survey respondents, 51% believed that PRT was underutilized, and the perceived barriers to prt referral included patient or family reluctance, distance to the cancer centre, belief that PRT has little impact on quality of life, and concerns about toxicity. Conclusions: Palliative radiotherapy is considered to be underutilized among children. This situation appears to be related, in part, to inadequate knowledge and training among pediatric oncologists, suggesting that more emphasis needs to be placed on pediatric palliative care education. Full article

We applied a learning methodology framework to assist in the threshold-based segmentation of non-small-cell lung cancer (NSCLC) tumours in positron-emission tomography–computed tomography (PET–CT) imaging for use in radiotherapy planning. Gated and standard free-breathing studies of two patients were independently analysed (four studies in total). Each study had a PET–CT and a treatment-planning CT image. The reference gross tumour volume (GTV) was identified by two experienced radiation oncologists who also determined reference standardized uptake value (SUV) thresholds that most closely approximated the GTV contour on each slice. A set of uptake distribution-related attributes was calculated for each PET slice. A machine learning algorithm was trained on a subset of the PET slices to cope with slice-to-slice variation in the optimal SUV threshold: that is, to predict the most appropriate SUV threshold from the calculated attributes for each slice. The algorithm’s performance was evaluated using the remainder of the PET slices. A high degree of geometric similarity was achieved between the areas outlined by the predicted and the reference SUV thresholds (Jaccard index exceeding 0.82). No significant difference was found between the gated and the free-breathing results in the same patient. In this preliminary work, we demonstrated the potential applicability of a machine learning methodology as an auxiliary tool for radiation treatment planning in NSCLC. Full article

Aim: Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (NSCLC) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic NSCLC among Canadian radiation oncologists. Materials and Methods: An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate. The survey consisted of three scenarios focusing on areas of NSCLC treatment in which the radiotherapy (RT) regimen that provides the best therapeutic ratio is unclear. Results: Replies from 41 respondents were analyzed. For an asymptomatic patient with stage IIIB NSCLC unsuitable for radical treatment, 22% recommended immediate RT, and 78% recommended RT only if the patient were to become symptomatic. Those who believed that immediate rt prolongs survival were more likely to recommend it (p = 0.028). For a patient with a bulky stage IIIB tumour and good performance status, 39% recommended palliative treatment, and 61% recommended radical treatment (84% concurrent vs. 16% sequential chemoradiation at 60–66 Gy in 30–33 fractions). Those who believed that chemoradiation has a greater impact on survival were more likely to recommend it (p < 0.001). For a symptomatic patient with stage IV NSCLC, 54% recommended external-beam RT (EBRT) alone, 41% recommended other modalities (brachytherapy, endobronchial therapy, or chemotherapy) with or without EBRT, and 5% recommended best supportive care. A majority (76%) prescribed 20 Gy in 5 fractions for EBRT. Conclusions: Compared with previous surveys, more radiation oncologists now offer radical treatment for locally advanced NSCLC. Management of NSCLC in Canada may be evidence-based, but perception by radiation oncologists of the treatment’s impact on survival also influences treatment decisions. Full article

Background: Despite recommendations favouring review of cancer pathology specimens for patients being treated at an institution other than the one that produced the initial pathology report, data regarding discordance rates and their potential clinical impact remain limited, particularly for breast cancer. At the QEII Health Sciences Centre in Halifax, Nova Scotia, it was routine practice to review histopathology when patients referred for adjuvant therapy had undergone their breast cancer surgery and pathology reporting at another institution. The aim of the present study was to determine the rate and clinical impact of discordance in inter-institutional pathology consultations for breast cancer in Nova Scotia. Methods: We conducted a retrospective review of 100 randomly selected inter-institutional pathology consultations for breast cancer patients referred to the QEII in 2004. Cases were categorized as having either no discordance, discordance with no clinical impact, or discordance with potential for clinical impact. Cases with potential clinical impact were independently reviewed by 2 medical oncologists and 2 radiation oncologists, and the discordances were rated as having high, medium, or no clinical impact. Results: The study cohort consisted of 93 cases that met the inclusion criteria. Of these 93 cases, 6 had no discordance, 7 had discordance with no clinical impact, and 80 had discordance with potential for clinical impact. Overall, 10 cases (11%) were rated as having either high or medium clinical impact, with agreement on the clinical impact ratings by oncologist reviewers in the same specialty. The remaining cases had either no clinical impact or disagreement on the clinical impact rating. Conclusions: Inter-institutional pathology consultations for breast cancer in Nova Scotia identified discordant findings with potential clinical impact as determined by oncologist reviewers. Further evaluation of inter-institutional pathology consultations and the impact on clinical decision-making is warranted. Full article

Objective: The cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5FU/LV)—the FOLFOX regimen—was compared with that of 5FU/LV alone as adjuvant therapy for patients with stage III colon cancer, from the perspective of the Cancer Care Ontario New Drug Funding Program. In the MOSAIC (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) trial, the FOLFOX regimen significantly improved disease-free survival. The MOSAIC trial formed the basis of the present analysis. Methodology: Extrapolated patient-level data from the MOSAIC trial were used to model patient outcomes from treatment until death. Utilities were obtained from the literature. Resource utilization data were derived from the MOSAIC trial and supplemented with data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, the London Health Sciences Centre, and the literature. Results: Lifetime incremental cost-effectiveness ratios for FOLFOX compared with 5FU/LV were CA$14,266 per disease-free year, CA$23,598 per life-year saved, and CA$24,104 per quality adjusted life-year (QALY) gained, discounting costs and outcomes at 5% per annum. These results were stable for a wide range of inputs; only utility values associated with relapse seemed to influence the cost-effectiveness ratios observed. Conclusions: With an incremental cost of CA$24,104 per QALY gained, FOLFOX is a cost-effective adjuvant treatment for stage III colon cancer. Compared with 5FU/LV alone, this regimen offers better clinical outcomes and provides good value for money. Full article

Background: This economic analysis aimed to determine, from the perspective of a Canadian provincial government payer, the cost-effectiveness of docetaxel (Taxotere: Sanofi–Aventis, Laval, QC) in combination with doxorubicin and cyclophosphamide (TAC) compared with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) following primary surgery for breast cancer in women with operable, axillary lymph node–positive breast cancer. Methods: A Markov model looking at two time phases—5-year treatment and long-term follow-up—was constructed. Clinical events included clinical response (based on disease-free survival and overall survival) and rates of febrile neutropenia, stomatitis, diarrhea, and infections. Health states were “no recurrence,” “locoregional recurrence,” “distant recurrence,” and “death.” Costs were based on published sources and are presented in 2006 Canadian dollars. Model inputs included chemotherapy drug acquisition costs, chemotherapy administration costs, relapse and follow-up costs, costs for management of adverse events, and costs for granulocyte colony-stimulating factor (G-CSF) prophylaxis. A 5% discount rate was applied to costs and outcomes alike. Health utilities were obtained from published sources. Results: For TAC as compared with FAC, the incremental cost was $6921 per life-year (LY) gained and $6,848 per quality-adjusted life-year (QALY) gained. The model was robust to changes in input variables (for example, febrile neutropenia rate, utility). When G-CSF and antibiotics were given prophylactically before every cycle, the incremental ratios increased to $13,183 and $13,044 respectively. Conclusions: Compared with FAC, TAC offered improved response at a higher cost. The cost-effectiveness ratios were low, indicating good economic value in the adjuvant setting of node-positive breast cancer patients. Full article