Curr. Oncol., Volume 15, Issue 2 (April 2008) – 10 articles

Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy. Full article

Background: Surgical margin status is an important predictor of risk of relapse among patients with rectal cancer. Methods: Patients referred to the British Columbia Cancer Agency for consideration of adjuvant therapy for rectal adenocarcinoma were included. Predictors of margin positivity were determined from uni- and multivariate analysis. Results: Among 340 patients, 83% had negative resection margins. In 268 patients with resectable tumours, a significantly higher rate of margin positivity was observed in low rectal tumours (32.2%) as compared with midrectal (3.9%) and high rectal (14.3%) tumours. Among 59 patients with locally advanced rectal cancer treated with preoperative radiation (with or without chemotherapy), 32% with low tumours had margin positivity. Of patients with T4 tumours, 50% (11/22) had a positive resection margin. Conclusions: In a population cohort, distal-third rectal location, locally advanced presentation, and T4 cancer represent subgroups for whom further improvement in therapy is required. Full article

Chronic myeloid leukemia (CML) is a myeloproliferative disorder whose therapy has changed dramatically since the late 1990s. With the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate, the treatment outcomes for patients with CML have improved markedly, and hematopoietic stem-cell transplantation is no longer routinely offered as first-line therapy for most patients in chronic phase. However, resistance to TKI therapy is increasingly being recognized, and alternative therapy is needed for this group of patients. In addition, the development of models predicting response to TKI therapy is desired, so that appropriate treatment strategies can be used for individual patients. The present report serves to outline the approach to the treatment of CML in British Columbia and to highlight areas of ongoing research. Full article

Questions: (1) In patients with inoperable locally advanced or metastatic soft tissue sarcoma, does first-line doseintensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation improve response rate, time to disease progression, or survival as compared with standarddose chemotherapy? (2) What are the effects of first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation on toxicity and quality of life? Perspectives: Because therapeutic options for adult patients with advanced or metastatic soft tissue sarcoma are scarce and the possibility of cure for these patients is extremely limited, the Sarcoma Disease Site Group (DSG) felt that a review of the available literature on doseintensive chemotherapy for adult patients with locally advanced or metastatic soft tissue sarcoma and subsequent development of a clinical practice guideline based on the evidence were important. Methodology: A systematic review was developed and clinical recommendations relevant to patients in Ontario were drafted. The practice guideline report was reviewed and approved by the Sarcoma DSG, which comprises medical oncologists, radiation oncologists, surgeons, a pathologist, a methodologist, and community representatives. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final review and approval of the practice guideline was obtained from the Report Approval Panel. Practice Guideline: Based on the systematic review, consensus, and external review, the Sarcoma DSG makes these recommendations: (1) Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma. (2) The data are insufficient to support the use of highdose chemotherapy with autologous bone marrow or stem-cell transplantation as first-line treatment in this group of patients. (3) Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds. Qualifying Statements: High-dose chemotherapy with growth factor or autologous bone marrow or stem-cell transplantation has adverse effects similar to those seen with standard-dose chemotherapy. With high-dose regimens, the incidence of grades 3 and 4 thrombocytopenia is significantly higher, and neutropenic fever and febrile neutropenia occur more frequently. Compared with standard treatment, the rate of treatment-related death is also higher with highdose regimens. Full article

The use of complementary and alternative medicine is gaining popularity worldwide. Cancer patients are major consumers of natural health products for a variety of reasons; the most common is to build the body’s defense by augmenting the immune system. Various species of mushrooms have been studied for decades because of their alleged immuno-stimulating properties. Active substances from more than fifty species of mushrooms have been isolated and found to have such properties. Of these, polysaccharide-K and polysaccharide-peptide, extracted from the mushroom Coriolus versicolor (CV), have been more systematically investigated in human cancer research. CV extracts are extremely popular in certain ethnic communities with a long tradition of employing healing practices that are unconventional in nature compared with western medicine approaches. Cancer patients are using CV extracts as part of their adjunctive cancer therapy. Cancer specialists and allied health care professionals may not be fully aware of such a choice especially when patients do not disclose the information. As communities in North America are becoming more culturally diverse, the rise in the use of natural health products is most likely inevitable. Better understanding of some popular natural health products and the reasons behind their use may foster communication between patient and health care provider and is crucial in helping patients address their needs and concerns in the hope of optimizing cancer care. Exploring the mechanism of CV extracts, their safety, risks and possible benefits is one step toward these goals. Full article

Traditional Chinese Medicine (TCM) is a whole system containing therapeutic interventions that individually induce biomodulation at the physiologic, chemical, and molecular levels. The theory of TCM proposes a synergy between specific interventions selected as part of a care plan based on TCM diagnostic theory. Combining TCM with the modern practice of oncology seems, in conjunction with biomedical interventions (surgery, radiotherapy, chemotherapy, and pharmaceuticals), to have potential advantages through the synergy of biomodulation. Biomodulation approaches are broadly categorized as modification of tumour response and reduction of adverse effects; modulation of immunity; prevention of cancer progression; and enhancement of symptom control. Although the database of preclinical studies is rapidly expanding, good-quality clinical trials are notably scarce. Laboratory studies suggest that some herbs increase the effectiveness of conventional chemotherapy without increasing toxicity. A healthy immune system is necessary for control of malignant disease, and the immune suppression associated with cancer contributes to its progression. Many Chinese herbs contain glycoproteins and polysaccharides (among them, constituents of Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Astragalus membranaceus, Panax ginseng, and various other medicinal mushrooms) that can modulate metastatic potential and the innate immune system. Phytochemicals such as specific polysaccharides have been shown to boost the innate immune system, especially through interaction with Toll-like receptors in mucosa-associated lymphoid tissue. This intervention can potentially improve the effectiveness of new anticancer vaccines. An increase in virus-associated cancers presents a major public health problem that requires novel therapeutic strategies. A number of herbal therapies have both antiviral activity and the ability to promote immunity, possibly inhibiting the initiation and promotion of virus-associated cancers. The mechanisms learned from basic science should be applied to clinical trials both of specific interventions and of whole-system care plans that safely combine the TCM approach with the conventional biomedical model. In Western medicine, the combination of TCM herbs with drug therapies is controversial, given lack of knowledge concerning whether a drug is favourably enhanced or whether adverse effects occur. Using initial data from the preclinical studies, future clinical research needs to evaluate the combinations, some of which are showing favourable synergy. Full article

Methylation of DNA is known to be an important mechanism of gene regulation. A hallmark of cancer is the deregulation of the DNA methylation machinery and aberrant DNA methylation patterns ¹. In vertebrate genomes, a large fraction of the CG dinucleotide sequence is modified by methylation in gene- and tissuespecific patterns ². Methylation of critical regulatory regions silences gene expression; loss of methylation is associated with gene activation ³. Because cancer progression requires many changes in the normal program of gene expression, it stands to reason that aberrations in DNA methylation play a critical role in the changes in gene expression involved in cancer progression and metastasis. Methylation changes in DNA play a role very similar to that of genetic mutations in cancer; however, unlike a genetic alteration, DNA methylation is potentially reversible with pharmacologic intervention. The DNA methylation machinery was therefore proposed—almost a decade and a half ago—to be an attractive anticancer target ⁴. Full article