Search Results (17)

In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. Full article

Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider–related. To date, there is a gap in the literature concerning a comprehensive understanding of factors related to medication adherence with anti-estrogen therapy in the adjuvant setting. The literature suggests that strategies for improving adherence should focus on education of patients, assessment of the ability of patients to understand their disease and related recurrence factors, and facilitation of adherence by patients by providing adequate support and strategies for good self-management. However, more research is needed to better understand how health care providers can support women with breast cancer on oral therapy in the adjuvant setting. Full article

There is growing evidence that follow-up for patients with early breast cancer (EBC) can be effectively carried out by the primary health care provider if a plan is in place. Here, we present data from a recent survey conducted in Ontario indicating that a shared-care model could work if communication between all health professionals involved in the care of ebc patients were to be improved. Patients and primary care providers benefit when the specialist provides written information about what their roles are and what to expect. Primary care providers need to have easy access to the specialist to discuss areas of concern. Patients also need to share responsibility for their care, ensuring that they attend follow-up visits on a regular basis and that they discuss areas of concern with their primary health care provider. A shared-care model has the potential to provide the best care for the least cost to the health system. Full article

This paper reports two cases of acrometastasis to the hands. The first case involved a 78-year-old woman with a permeative osteolytic lesion in her proximal second metacarpal. A biopsy of this lesion suggested a diagnosis of non-small-cell lung carcinoma with secondary osseous metastasis. This was the first presentation of the woman’s primary diagnosis. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient’s left hand. The treatment proved successful: the woman soon experienced pain relief and regained the use of her hand. The second case involved a 69- year-old woman with extensive lytic destruction involving the proximal two thirds of her third metacarpal. This patient had been diagnosed with carcinoma of the breast in 1990. She also received a single 8-Gy fraction of radiation, which improved both her pain and her hand mobility. An extensive review of the literature uncovered 257 previously reported cases of acrometastasis. Articles were analyzed based on age and sex of the patient, site of the primary carcinoma, metastatic locations within the hand and affected appendage or appendages, the treatment given, and the patient’s length of survival. Men were almost twice as likely to experience acrometastasis as women, and the median age of the patients overall was 58 years (range: 18 months–91 years). Lung, kidney, and breast carcinoma were the three most prevalent primary diagnoses reported in the literature. Cancers of the colon, stomach, liver, prostate, and rectum affected the remainder of the population. Overall, the right hand was more often host to the metastatic lesions. In addition, almost 10% of the patients experienced lesions in both hands. The third finger was the digit most affected by osseous metastases reported in the literature. Lesions of the thumb, fourth finger, second finger, and fifth finger were less commonly reported. The region of the digit most often affected within the patient population was the distal phalanx. The metacarpal bones, proximal phalanges, and middle phalanges comprised the remainder of the four most frequent acrometastatic sites. In the literature, single lesions were more prevalent than multiple bony lesions. Based on the reported cases, amputation appeared to be the preferred method of treatment. Radiation, excision, and systemic therapy were the next most frequently used treatments. Patient survival was not well documented within the literature. However, the median survival of patients in the reported cases was 6 months. Thus, our review suggested that a diagnosis of hand metastasis is an indication of poor prognosis. This report serves to emphasize the importance of properly diagnosing acrometastases. Identifying and effectively treating these metastases in a timely manner can lead to a dramatic improvement in a patient’s quality of life. Full article

“Radiation recall”—also called “radiation recall dermatitis”—has been defined as the “recalling” by skin of previous radiation exposure in response to the administration of certain response-inducing drugs. Although the phenomenon is relatively well known in the medical world, an exact cause has not been documented. Here, we report a rare occurrence of the radiation recall phenomenon in a breast cancer patient after palliative radiotherapy for bone, brain, and orbital metastases. Full article

Adjuvant therapy has made a significant contribution in reducing breast cancer–specific mortality. Standard chemotherapeutics and tamoxifen have been the mainstay treatment for years, but recent clinical evidence supports the use of novel small-molecule therapy and aromatase inhibitor therapy in selected settings, challenging not only the traditional paradigm of breast cancer treatment, but also provincial funding of oncologic care across Canada. The disparity in access to aromatase inhibitor therapy for postmenopausal women with early-stage hormone-sensitive breast cancer across Canada is highlighted as an example. Full article

Question: What is the safety and efficacy of interstitial chemotherapy with carmustine-loaded polymers (Gliadel wafers: MGI Pharma, Bloomington, MN, U.S.A.) in the treatment of newly diagnosed or recurrent malignant glioma (that is, glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligoastrocytoma, and anaplastic oligodendroglioma)? Perspectives: Malignant glioma is the most common type of primary brain tumour in adults. In general, efficacy of systemic therapy in this patient population has been disappointing, and novel treatment approaches are needed. Because several randomized controlled trials (rcts) investigating the safety and efficacy of Gliadel are available, the Neuro-oncology Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care decided that a systematic review of the evidence was necessary. Outcomes: The outcomes of interest for this review were overall survival, adverse events, and quality of life. Methodology: Systematic searches of the medline, embase, and Cochrane Library databases were conducted for relevant evidence. Fully-published reports of rcts comparing treatment with Gliadel wafers to placebo or alternative treatment were selected for inclusion. Prospective cohort studies were also included. Results: Two rcts that compared Gliadel to placebo in patients with newly diagnosed malignant glioma were obtained. Both rcts reported a significant survival benefit for patients who received Gliadel as compared with patients in the control group. One rct and one prospective cohort study were obtained that examined the role of Gliadel in patients with recurrent malignant glioma. The rct demonstrated a significant survival benefit for Gliadel only after adjustment for prognostic factors, and the prospective cohort study reported no survival benefit for Gliadel as compared with a historical control group. All three rcts reported similar rates of adverse events in the treatment and control groups. The most frequently reported adverse events were convulsions, confusion, brain edema, infection, hemiparesis, aphasia, and visual field defects. Conclusions: Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible. No evidence is available comparing Gliadel with systemic therapy, and a decision to combine Gliadel with systemic therapy should be made for patients individually. The patient population that would benefit from Gliadel (age, histology, and performance status) is unclear; further investigation is needed. Gliadel is also an option for patients with surgically resectable recurrent malignant glioma. Full article

Questions: Should patients with confirmed single brain metastasis undergo surgical resection? Should patients with single brain metastasis undergoing surgical resection receive adjuvant wholebrain radiation therapy (WBRT)? What is the role of stereotactic radiosurgery (SRS) in the management of patients with single brain metastasis? Perspectives: Approximately 15%–30% of patients with cancer will develop cerebral metastases over the course of their disease. Patients identified as having single brain metastasis generally undergo more aggressive treatment than do those with multiple metastases; however, in the province of Ontario, management of patients with single brain metastasis varies. Given that conflicting evidence has been reported, the Neuro-oncology Disease Site Group (DSG) of the Cancer Care Ontario Program in Evidence-based Care felt that a systematic review of the evidence and a practice guideline were warranted. Outcomes: Outcomes of interest were survival, local control of disease, quality of life, and adverse effects. Methodology: The MEDLINE, CANCERLIT, EMBASE, and Cochrane Library databases and abstracts published in the proceedings of the annual meetings of the American Society of Clinical Oncology (1997–2005) and American Society for Therapeutic Radiology and Oncology (1998–2004) were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (RCTS), nonrandomized prospective studies, and retrospective studies. The present systematic review and practice guideline has been reviewed and approved by the Neurooncology DSG, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. External review by Ontario practitioners was obtained through an electronic survey. Final approval of the guideline report was obtained from the Report Approval Panel and the Neuro-oncology DSG. Results: Quality of Evidence The literature search found three RCTS that compared surgical resection plus WBRT with WBRT alone. In addition, a Cochrane review, including a meta-analysis of published data from those three RCTS, was obtained. One RCT compared surgical resection plus WBRT with surgical resection alone. One RCT compared WBRT plus SRS with WBRT alone. Evidence comparing SRS with surgical resection or examining SRS with or without WBRT was limited to prospective case series and retrospective studies. Benefits Two of three RCTS reported a significant survival benefit for patients who underwent surgical resection as compared with those who received WBRT alone. Pooled results of the three RCTS indicated no significant difference in survival or likelihood of dying from neurologic causes; however, significant heterogeneity was detected between the trials. The RCT that compared surgical resection plus WBRT with surgical resection alone reported no significant difference in overall survival or length of functional independence; however, tumour recurrence at the site of the metastasis and anywhere in the brain was less frequent in patients who received WBRT as compared with patients in the observation group. In addition, patients who received WBRT were less likely to die from neurologic causes. Results of the RCT that compared WBRT plus SRS with WBRT alone indicated a significant improvement in median survival in patients who received SRS. No quality evidence compares the efficacy of SRS with surgical resection or examines the question of whether patients who receive SRS should also receive WBRT . Harms Pooled results of the three RCTS that examined surgical resection indicated no significant difference in adverse effects between groups. Postoperative complications included respiratory problems, intracerebral hemorrhage, and infection. One RCT reported no significant difference in adverse effects between patients who received WBRT plus SRS and those who received WBRT alone. Practice Guideline: Target Population The recommendations that follow apply to adults with confirmed cancer and a single brain metastasis. This practice guideline does not apply to patients with metastatic lymphoma, small-cell lung cancer, germ-cell tumour, leukemia, or sarcoma. Recommendations Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis amenable to complete excision. Because treatment in cases of single brain metastasis is considered palliative, invasive local treatments must be individualized. Patients with lesions requiring emergency decompression because of intracranial hypertension were excluded from the RCTS, but should be considered candidates for surgery. To reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis, postoperative WBRT should be considered. The optimal dose and fractionation schedule for WBRT is 3000 cGy in 10 fractions or 2000 cGy in 5 fractions. As an alternative to surgical resection, WBRT followed by SRS boost should be considered for patients with single brain metastasis. The evidence is insufficient to recommend SRS alone as a single-modality therapy. Qualifying Statements No high-quality data are available regarding the choice of surgery versus radiosurgery for single brain metastasis. In general, the size and location of the metastasis determine the optimal approach. The standard WBRT regimen for management of patients with single brain metastasis in the United States is 3000 cGy in 10 fractions, and this treatment is usually the standard arm in randomized studies of radiation in patients with brain metastases. Based solely on evidence, the understanding that no reason exists to choose 3000 cGy in 10 fractions over 2000 cGy in 5 fractions is correct; however, fraction size is believed to be important, and therefore 300 cGy daily (3000/10) is believed to be associated with fewer long-term neurocognitive effects than 400 cGy daily (2000/5) in the occasional long-term survivor. For that reason, many radiation oncologists in Ontario prefer 3000 cGy in 10 fractions. No data exist to either support or refute that preference; therefore, finding a resolution to this issue is not currently possible. The Neuro-oncology DSG will update the recommendations as new evidence becomes available. Full article

Prostate cancer is the most common non-skin malignancy in men. Almost all men who die from prostate cancer have hormone-refractory prostate cancer with metastasis to bone. Emerging supportive treatments—including chemotherapy, bisphosphonates, and surgery—require integration that is optimized in a multidisciplinary setting. A multidisciplinary clinic for bone metastases has been in place at Toronto–Sunnybrook Regional Cancer Centre since 1999, combining orthopedic surgery, radiation oncology, interventional radiology, and palliative medicine for all patients with bone metastases. The addition of a prostate-focused multidisciplinary clinic integrates these services for patients with advanced prostate cancer. Full article

Minimally invasive procedures such as percutaneous cementoplasty can provide immediate pain relief and can restore mechanical stability for patients with bone metastases who are not candidates for surgery or who show resistance to radiotherapy or analgesic treatment. Here, we examine a case of percutaneous cementoplasty to treat a lytic lesion of the acetabulum from breast cancer. Good filling was observed, and no complications occurred. A research assistant recorded the patient’s scores on the Karnofsky Performance Scale, Townsend Functional Assessment Scale, and Brief Pain Inventory before surgery and at days 1, 2, and 4 and weeks 1, 2, and 4 post-procedure. Improvement in pain and walking ability was demonstrated within the first 48 hours of treatment, and that improvement remained constant throughout follow-up. These findings echo the literature, in that percutaneous cementoplasty provides immediate and long-term pain relief with few complications. We recommend that percutaneous cementoplasty be used as an additional tool for palliative treatment of patients with bone metastases. Full article

Questions: Should patients with newly diagnosed brain tumours receive prophylactic anticonvulsants to reduce seizure risk? What is the best practice for patients with brain tumours who are taking anticonvulsant medications but who have never had a seizure? Perspectives: Patients with primary or metastatic brain tumours who have never had a seizure still have a 20% risk of experiencing a seizure over the course of their disease. Because considerable practice variation exists in regard to the management of patients with brain tumours who have never had a seizure, and because conflicting evidence has been reported, the Neuro-oncology Disease Site Group (DSG) of Cancer Care Ontario’s Program in Evidence-based Care felt that a systematic review of the evidence was warranted. Outcomes: Outcomes of interest were incidence of seizures and adverse effects of prophylactic anticonvulsant therapy. Methodology: The MEDLINE and Cochrane Library databases were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (RCTs), systematic reviews, meta-analyses, and practice guidelines. The present systematic review was reviewed and approved by the Neuro-oncology DSG, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. Results: Quality of Evidence: The literature search located one evidence-based practice guideline, one systematic review, and five RCTs that addressed prophylactic anticonvulsants for patients with brain tumours. Evidence for the best management of seizure-naïve patients who are already taking anticonvulsants was limited to one retrospective study and exploratory analyses within several RCTs. Benefits and Harms: Pooled results of the five RCTs suggest that the incidence of seizures in patients who receive prophylactic anticonvulsants is not significantly different from that in patients who do not receive anticonvulsants (relative risk: 1.04; 95% confidence interval: 0.70 to 1.54; p = 0.84). This analysis accords with results from a published meta-analysis. Evidence is insufficient to determine whether patients who are currently taking anticonvulsants but who have never had a seizure should taper the anticonvulsants. Patients who received anticonvulsants reported adverse effects, including rash, nausea, and hypotension, but whether these effects are a result of the anticonvulsants or of other treatments could not be determined. Conclusions: Based on the available evidence, the routine use of postoperative anticonvulsants is not recommended in seizure-naïve patients with newly diagnosed primary or secondary brain tumours, especially in light of a significant risk of serious adverse effects and problematic drug interactions. Because data are insufficient to recommend whether anticonvulsants should be tapered in patients who are already taking anticonvulsants but who have never had a seizure, treatment must be individualized. Full article