Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

The cost burden of trastuzumab and bevacizumab therapy for solid tumours in Canada.

OBJECTIVE: Monoclonal antibodies (MAbs) such as trastuzumab and bevacizumab have become important yet expensive components of systemic cancer therapy across a variety of disease sites. We assessed the potential cost implications of adopting trastuzumab and bevacizumab therapy in the context of their potential utilization in breast, lung, and colorectal cancers. DESIGN: We first estimated MAb costs per patient and treatment indication and then included the MAb acquisition cost and the costs of medical resource utilizations required for therapy delivery. Drug costs were based on 2005 average Canadian wholesale prices, assuming full drug delivery and uncomplicated cycles. A direct-payer perspective was undertaken, and results are reported in Canadian dollars. Potential lifetime costs were then derived according to constructed schema, which account for absolute numbers of target patients and systemic therapy utilization. We subsequently estimated costs of MAb therapy relative to total costs of conventional management without MAb therapy. RESULTS: Trastuzumab costs $49,915 and $28,350 per patient treated in the adjuvant and metastatic breast cancer settings, respectively; bevacizumab costs $48,490 and $39,614 per patient treated in the metastatic lung and colorectal cancer settings, respectively. Potential lifetime absolute costs to Canada's health care system were approximately $127 million and $299 million for trastuzumab and bevacizumab respectively, corresponding to an average increase in health care expenditure of approximately 19% for breast cancer and 21% for lung and colorectal cancer over conventional management without MAbs. CONCLUSIONS: Novel Mab-based therapies such as trastuzumab and bevacizumab will likely add a significant cost burden to Canada's publicly funded health care system.

Malignant by name or malignant by nature: a case of Wegener's granulomatosis diagnosed as adenocarcinoma of unknown primary.

Most malignancies are characterised by malignant behaviour at some point in the disease trajectory. However, non-malignant diseases may exhibit malignant behaviour. A diagnosis of malignancy based on fine needle aspiration cytology (FNAC) can be misleading. We report a case of Wegener's granulomatosis initially diagnosed by FNAC as adenocarcinoma of unknown primary. The limitations of FNAC, the disparate prognoses of the two diagnoses despite a compatible clinical picture and the need for clinical vigilance in monitoring a disease course are highlighted.

Independent prospective validation of the PaP score in terminally ill patients referred to a hospital-based palliative medicine consultation service.

The aim of this prospective study was to validate the Palliative Prognostic (PaP) Score in a population of hospitalized patients in Australia in order to determine its applicability in a different setting to that in which it was originally developed. Individual PaP scores were calculated for 100 terminally-ill patients consecutively referred to a palliative medicine consultation service based in a university teaching hospital. The PaP score was able to subdivide this heterogeneous patient population into three groups, the differences being highly statistically significant. Median survivals for the three groups were, respectively, 60 days (95% confidence interval 41-89 days), 34 days (25-40), and 8 days (2-11). The percentage survival at 30 days for the three groups was 66%, 54%, and 5% respectively. These data suggest that the PaP scoring system is a reasonably robust method for prognostication in advanced cancer that appears to be independent of the setting. The short survival of the third group in this study, which is consistent with the presence of a subset of gravely ill patients within the hospital setting who are referred to specialist palliative care services very late in the course of their illness, raises important issues for the care and treatment of these individuals.

Avascular necrosis of bone: the hidden risk of glucocorticoids used as antiemetics in cancer chemotherapy.

The role of antiemetics is invaluable in allowing cancer patients to complete otherwise potentially intolerable chemotherapy. Corticosteroids have an established place in the prevention and treatment of nausea and vomiting due to emetogenic cytotoxic agents. Avascular necrosis of bone is a recognised complication of glucocorticoid treatment--the risk of this increasing with higher doses and longer duration of use. This report details a case of bilateral avascular necrosis of the femoral heads in a patient receiving 'standard' doses of dexamethasone as part of the antiemetic regimen used in cisplatin-based combination chemotherapy.

Epirubicin, cisplatin, and prolonged or brief infusional 5-fluorouracil in the treatment of carcinoma of unknown primary site.

The cytotoxic regimen of epirubicin, cisplatin, and continuous infusional 5-fluorouracil (ECF) has demonstrated activity in a range of malignancies, including gastroesophageal, breast, and pancreatic cancers. Prolonged infusional central venous catheter (CVC) mediated therapy is not always feasible and modifications of the 5-fluorouracil (5FU) schedule have been reported. We reviewed our experience of both the standard and a modified ECF regimen in patients diagnosed with carcinoma of unknown primary site (CUPS). A retrospective analysis of all patients diagnosed with CUPS (31 adenocarcinoma and 5 poorly differentiated carcinoma) and treated with ECF between June 1994 and June 1998 was undertaken. Thirty-six patients, median age 56 (range: 24-74), were treated thrice-weekly with 50 mg/m2 epirubicin, 60 mg/m2 cisplatin, and 5-FU administered either by continuous infusion 200 mg/m2/d via a CVC (standard ECF) or as a 6-h infusion 600 mg/m2 through a peripheral venous catheter (modified ECF). Thirteen patients were treated with standard ECF and 23 received modified ECF. The median number of cycles administered was 4 (range: 1-10). Thirty-two patients had evaluable disease, seven (22%; 95% confidence interval: 8-36%) demonstrated a partial response, including three patients that received standard ECF and four treated with modified ECF. There were no complete responses. The median survival for all 36 patients was 9.0 mo. Median survival for patients treated with standard ECF was 11.7 mo as compared to 5.1 mo for the modified ECF schedule (p = 0.052). Liver involvement and elevation of serum CA19.9 were identified as possible adverse prognostic factors. Both regimens were well tolerated, with the only grade 3/4 toxicity recorded being leukopenia (four patients), nausea/vomiting (seven patients), and diarrhea (one patient). CVC complications in the standard ECF group were thrombosis (one patient) and infection (three patients). There were no treatment-related deaths. We conclude that ECF, whether modified or standard, has modest activity in the setting of CUPS. Patient survival is comparable to survival documented in previous reports of CUPS treatment. The apparent survival difference between the two ECF schedules may be the result of patient selection factors. The optimal treatment of CUPS remains unknown and can only be determined through randomized controlled trials.

Can we do better in end-of-life care? The mixed management model and palliative care.

The increasing duration of life from disease diagnosis to death in cancer and chronic non-malignant illnesses argues for a revised approach to end-of-life care that incorporates the principles of palliative care from an earlier stage (ie, a stage at which curative and/or life-prolonging treatments are still being provided). The provision of active treatment and comfort measures/death preparation in parallel has been called the "mixed management model" of end-of life care.

Pain management in palliative care. Reviewing the issues.

BACKGROUND: Cancer pain remains significantly undertreated despite being one of the most prevalent and feared symptoms associated with cancer. Approximately 90% of patients can have their cancer pain controlled through relatively simple measures. OBJECTIVE: The aim of this review is to facilitate the current optimal approach to the assessment and management of cancer pain within the context of the multidimensional nature of the pain experience. DISCUSSION: Each component of the pain experience is addressed using a four point approach to pain and involves pharmacological and nonpharmacological measures. The general practitioner's role is pivotal in optimal cancer pain management. This is the first of two articles by Kiran Virik and Paul Clare on pain management in palliative care. The second, outlining treatment options, will appear in the December issue of Australian Family Physician.

Pain management in palliative care. Morphine and the 'new' opioids in 2000.

BACKGROUND: Although morphine is the mainstay of pharmacological therapy in cancer pain, it remains feared and suboptimally used. Different formulations and the advent of 'new' opioids facilitate the attainment of pain control. OBJECTIVE: To clarify the current role of various opioids including morphine in the management of cancer pain. To provide a practical framework to guide 'best practice' opioid use in a general practice setting. DISCUSSION: The optimal application of opioids is governed by their clinical pharmacology and hindered by unfounded fears and misunderstanding. Different formulations within different types of opioids augment a favourable balance in the pain relief versus adverse effects equation and used within a four point approach, should serve to deliver optimal pain control.

Malignant transformation of craniopharyngioma.

Craniopharyngioma is a well recognised intracranial tumour; malignant transformation has been rarely described. In that case, malignant change occurred following irradiation for local recurrence and information is not provided on the biological behaviour of the tumour or the response to management. We report a further case of malignant transformation in recurrent craniopharyngioma following radiotherapy. The biological behaviour of malignant change in craniopharyngioma is uncertain so the treatment modalities require consideration of toxicity and other adverse sequelae balanced against anticipated outcome and comorbidities from previous treatments. The pathophysiology and therapeutic strategies are discussed. We review the possible pathogenic link between radiation therapy and malignant transformation.