Evidence-based guidance on venous thromboembolism in patients with solid tumours

Venous thromboembolism (vte) is a serious, life-threatening complication of cancer. Anticoagulation therapy such as low molecular weight heparin (lmwh) has been shown to treat and prevent vte. Cancer therapy is often complex and ongoing, making the management of vte less straightforward in patients with cancer. There are no published Canadian guidelines available to suggest appropriate strategies for the management of vte in patients with solid tumours. We therefore aimed to develop a clear, evidence-based guideline on this topic.A systematic review of clinical trials and meta-analyses published between 2002 and 2013 in PubMed was conducted. Reference lists were hand-searched for additional publications. The National Guidelines Clearinghouse was searched for relevant guidelines. Recommendations were developed based on the best available evidence.In patients with solid tumours, lmwh is recommended for those with established vte and for those without established vte but with a high risk for developing vte. Options for lmwh include dalteparin, enoxaparin, and tinzaparin. No one agent can be recommended over another, but in the setting of renal insufficiency, tinzaparin is preferred. Unfractionated heparin can be used under select circumstances only (that is, when rapid clearance of the anticoagulant is desired). The most common adverse event is bleeding, but major events are rare, and with appropriate follow-up care, bleeding can be monitored and appropriately managed.     

Learning experiences with sunitinib continuous daily dosing in patients with pancreatic neuroendocrine tumours

Molecular strategies to improve outcomes for patients with pancreatic neuroendocrine tumours (nets) have focused on targeting vascular endothelial growth factor, platelet-derived growth factor, and mtor (the mammalian target of rapamycin). This approach has led to the regulatory approval of two molecularly targeted agents for advanced pancreatic nets: sunitinib, a multi-targeted tyrosine kinase inhibitor, and everolimus, an mtor inhibitor.Initial experience with sunitinib in advanced pancreatic net was gained from the phase iii registration trial, which used a continuous daily dosing (cdd) schedule instead of daily drug administration for 4 consecutive weeks every 6 weeks (schedule 4/2), the approved schedule for advanced renal cell carcinoma (rcc) and gastrointestinal stromal tumour (gist). Clinical experience gained with schedule 4/2 in rcc and gist shows that, using a therapy management approach, patients can start and be maintained on the recommended dose and schedule, thus optimizing treatment outcomes. Here, we discuss challenges that can potentially be faced by physicians who use sunitinib on the cdd schedule, and we use clinical data and real-life clinical experience to present therapy management approaches that support cdd in advanced pancreatic net.     

Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec

Background

Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies.

Methods

Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk.

Results

The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases.

Conclusions

Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.     

A systematic review of active treatment options in patients with desmoid tumours

Introduction

We conducted a systematic review to determine the optimal treatment options in patients with desmoid tumours who have declined observational management.

Methods

A search was conducted of the medline and embase databases (1990 to September 2012), the Cochrane Library, and relevant guideline Web sites and conference materials.

Results

One systematic review and forty-six studies met the preplanned study selection criteria; data from twenty-eight articles were extracted and analyzed. For local control, three studies reported a statistically significant difference in favour of surgery plus radiotherapy (rt) compared with surgery alone, and one study did not; two studies reported the lack of a statistical difference between surgery plus rt and rt alone in maintaining local control. Multivariate risk factors for local recurrence included positive surgical margins and young patient age. Single-agent imatinib led to a progression-free survival rate of 55% at 2 years and 58% at 3 years. Methotrexate plus vinblastine led to a progression-free survival rate of 67% at 10 years. Significant toxicities were reported for all treatment modalities, including surgical morbidity, and rt- and chemotherapy-related toxicities.

Conclusions

In patients who have declined observational management, the local control rate was higher with surgery plus rt than with surgery alone. However, the additional rt-related complications should be considered in treatment decision-making. Surgery, rt, and systemic therapy are all reasonable treatment options for patients with desmoid tumours.     

Cost-effectiveness of systemic therapies for metastatic pancreatic cancer

PurposeGemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem-e), and folfirinox (5-fluorouracil–leucovorin–irinotecan–oxaliplatin) are new treatment options for metastatic pancreatic cancer, but they are also more expensive and potentially more toxic than gemcitabine alone (gem). We conducted a cost-effectiveness analysis of these treatment options compared with gem.MethodsA Markov model was constructed to examine costs and outcomes of gem-cap, gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the perspective of a government health care plan. Ontario health economic and costing data (2010 Canadian dollars) were used. Efficacy data for the treatments were obtained from the published literature. Resource utilization data were derived from a chart review of consecutive metastatic patients treated for pancreatic cancer at Princess Margaret Hospital, Toronto, Ontario, 2008–2009, and supplemented with data from the literature. Utilities were obtained by surveying medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness ratios (icers) were calculated.ResultsThe icers for gem-cap, gem-e, and folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The gem-e option was dominated by the other treatments.ConclusionsThe most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective.     

Treatment and follow-up strategies in desmoid tumours: a practice guideline

Objectives

We set out to

• determine the optimal treatment options—surgery, radiation therapy (rt), systemic therapy, or any combinations thereof—for patients with desmoid tumours once the decision to undergo active treatment has been made (that is, monitoring and observation have been determined to be inadequate).
• provide clinical-expert consensus opinions on follow-up strategies in patients with desmoid tumours after primary interventional management.

Methods

This guideline was developed by Cancer Care Ontario’s Program in Evidence-Based Care and the Sarcoma Disease Site Group. The medline, embase, and Cochrane Library databases, main guideline Web sites, and abstracts of relevant annual meetings (1990 to September 2012) were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Sarcoma Disease Site Group.

Recommendations

Treatments

• Surgery with or without rt can be a reasonable treatment option for patients with desmoid tumours whose surgical morbidity is deemed to be low.
• The decision about whether rt should be offered in conjunction with surgery should be made by clinicians and patients after weighing the potential benefit of improved local control against the potential harms and toxicity associated with rt.
• Depending on individual patient preferences, systemic therapy alone or rt alone might also be reasonable treatment options, regardless of whether the desmoid umours are deemed to be resectable.

Follow-Up Strategies

• Undergo evaluation for rehabilitation (occupational therapy or physical therapy, or both).
• Continue with rehabilitation until maximal function is achieved.
• Undergo history and physical examinations with appropriate imaging every 3–6 months for 2–3 years, and then annually.

     

fdg-pet in two cases of neurofibromatosis type 1 and atypical malignancies

Patients with neurofibromatosis type 1 (nf1) are at increased risk for both benign and malignant tumours, and distinguishing the malignant potential of an individual tumour is a common clinical problem in these patients. Here, we review two cases of uncommon malignancies (Hodgkin lymphoma and mediastinal germ-cell tumour) in patients with nf1. Although ¹⁸F-fluorodeoxyglucose positron-emission tomography (fdg-pet) has been used to differentiate benign neurofibromas from malignant peripheral nerve sheath tumours, fdg-pet characteristics for more rare tumours have been poorly described in children with nf1. Here, we report the role of pet imaging in clinical decision-making in each case. In nf1, fdg-pet might be useful in the clinical management of unusual tumour presentations and might help to provide information about the malignant potential of uncommon tumours.     

Impact of a single-day multidisciplinary clinic on the management of patients with liver tumours

Purpose

Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (mdlc) affected care recommendations for patients compared with the recommendations provided before presentation to the mdlc.

Methods

We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (osp) and the mdlc.

Results

Most patients were white (n = 259, 76%); median age was 60 years; and 146 were women (43%). Outside providers referred 182 patients (53%); the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7–247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the osp, and a formal management plan had been formulated for about half (n = 168, 49%).Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the mdlc resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued.

Conclusions

Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The mdlc is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours.     

Cost-effectiveness of folfirinox for first-line treatment of metastatic pancreatic cancer

Background

The accord 11/0402 trial demonstrated that folfirinox (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is significantly more efficacious than gemcitabine monotherapy in the first-line treatment of metastatic pancreatic cancer (mpc). The present study assessed the cost-effectiveness of first-line folfirinox compared with first-line gemcitabine for public payers in Canada.

Methods

A Markov model simulated the movement of mpc patients from first-line treatment until death. Overall survival (os) and progression-free survival (pfs) data were derived from accord. Published utility data and Canadian costs were applied based on time in each health state and on treatment-related adverse event (ae) rates. Costs included first- and second-line therapy, monitoring, and costs to treat aes. Two separate analyses were performed. Analysis 1 was based on trial data [first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by second-line platinum-based chemotherapy, with use of granulocyte colony–stimulating factor (g-csf) allowed], and analysis 2 used Ontario treatment patterns before folfirinox funding (first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by best supportive care, no use of g-csf).

Results

Compared with first-line gemcitabine, first-line folfirinox resulted in more life-years and quality adjusted life-years (qalys). Probabilistic sensitivity analysis results showed that, for analyses 1 and 2 respectively, folfirinox has a greater than 85% probability and an approximately 80% probability of being cost-effective at the $100,000 threshold.

Conclusions

Compared with gemcitabine, first-line folfirinox significantly prolongs median os. Given the favourable cost per qaly, the improvement in clinical efficacy, and the limited available treatment options, folfirinox represents an attractive cost-effective treatment for mpc.     

The use and effectiveness of temozolomide in children with central nervous system tumours: a survey from the Canadian Paediatric Brain Tumour Consortium

Objective

To describe the use of temozolomide (tmz) in Canadian children treated for brain tumours and to evaluate survival and predictors of survival for children treated with this agent.

Methods

A survey was conducted within the Canadian Paediatric Brain Tumour Consortium (cpbtc), a group of tertiary care centres in pediatric neuro-oncology (n = 16) in Canada that are involved in the treatment of children with central nervous system tumours.

Results

In 10 of the 16 participating pediatric oncology centres of the cpbtc, 137 children with brain tumours were treated with tmz between January 2000 and March 2006. Although 33% of the children were enrolled into a clinical trial, 67% were treated outside open studies. Most patients (72%) received tmz treatment on recurrence of their brain tumour (first or subsequent). The most commonly administered regimen was single-agent tmz 150–200 mg/m² administered on 5 consecutive days every 28 days. The median duration of tmz treatment was 141 days (range: 4–1102 days). Response data were provided for 127 of the 137 patients, of whom 6 showed a complete response. Sixteen patients experienced a minor or partial response, 53 had stable disease, and 52 had progressive disease. Of 32 patients alive at last follow-up, 19 had a diagnosis of low-grade glioma.

Conclusions

Temozolomide is used in a variety of pediatric brain tumours, often at the time of recurrence. The lack of insight into clear indications for this agent in pediatric brain tumours—used either alone or in combination therapy—may be a result of suboptimal design of phase i and ii studies and a lack of phase iii trials in the pediatric brain tumour population.     

Dosimetric and clinical toxicity comparison of critical organ preservation with three-dimensional conformal radiotherapy,intensity-modulated radiotherapy,and RapidArc for the treatment of locally advanced cancer of the pancreatic head

PurposeWe compared dosimetry and clinical toxicity for 3-dimensional conformal radiotherapy (3D-crt), intensity-modulated radiotherapy (imrt), and RapidArc (Varian Medical Systems, Palo Alto, CA, U.S.A.) in locally advanced pancreatic cancer (lapcc). We hypothesized that the technique with better sparing of organs at risk (oars) and better target dose distributions could lead to decreased clinical toxicity.MethodsThe study analyzed 280 patients with lapcc who had undergone radiotherapy. The dosimetry comparison was performed using 20 of those patients. Dose–volume histograms for the target volume and the oars were compared. The clinical toxicity comparison used the 280 patients who received radiation with 3D-crt, imrt, or RapidArc.ResultsCompared with 3D-crt, RapidArc and imrt both achieved a better conformal index, homogeneity index, V_95%, and V_110%. Compared with 3D-crt or imrt, RapidArc reduced the V₁₀, V₂₀, and mean dose to duodenum, the V₂₀ of the right kidney, and the liver mean dose. Compared with 3D-crt, RapidArc reduced the V₃₅, and V₄₅ of duodenum, the mean dose to small bowel, and the V₁₅ of right kidney. The incidences of grades 3 and 4 diarrhea (p = 0.037) and anorexia (p = 0.042) were lower with RapidArc than with 3D-crt, and the incidences of grades 3 and 4 diarrhea (p = 0.027) were lower with RapidArc than with imrt.ConclusionsCompared with 3D-crt or imrt, RapidArc showed better sparing of oars, especially duodenum, small bowel, and right kidney. Also, fewer acute grades 3 and 4 gastrointestinal toxicities were seen with RapidArc than with 3D-crt or imrt. A technique with better sparing of oars and better target dose distributions could result in decreased clinical toxicities during radiation treatment for lapcc.     

Axillary lymph node status,adjusted for pathologic complete response in breast and axilla after neoadjuvant chemotherapy,predicts differential disease-free survival in breast cancer

Background

Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pcr) information into axillary lymph node restaging after neoadjuvant chemotherapy (nac) adds significance to its prognostic values.

Methods

Patients included in the analysis had stage ii or iii disease, with post-nac axillary lymph node dissection (alnd), without sentinel lymph node biopsy before completion of nac, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pcr in both breast and axilla into ypN0(pcr) and ypN0(non-pcr). Univariate and multivariate survival analyses were performed.

Results

Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (hr+) and negative for the human epidermal growth factor receptor (her2–), 101 had tumours that were positive for her2 (her2+), and 55 had tumours that were triple-negative. The rate of pcr in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pcr patients, the pcr patients had better disease-free survival (dfs) and overall survival (os): p = 0.002 for dfs and p = 0.011 for os. In non-pcr patients, dfs and os were similar in the ypN0(non-pcr) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pcr) (n = 75), ypN0– 1(non-pcr) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year dfs was 98%, 91%, and 56%, and the 3-year os was 100%, 91%, and 82% respectively. The differences in dfs and os between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pcr were the only two independent factors predicting dfs.

Conclusions

Axillary lymph node status after nac, adjusted for pcr in breast and axilla, predicts differential dfs in patients without prior sentinel lymph node biopsy.     

Negative predictive value of preoperative computed tomography in determining pathologic local invasion,nodal disease,and abdominal metastases in gastric cancer

BackgroundBefore undergoing curative-intent resection of gastric adenocarcinoma (ga), most patients undergo abdominal computed tomography (ct) imaging to determine contraindications to resection (local invasion, distant metastases). However, the ability to detect contraindications is variable, and the literature is limited to single-institution studies. We sought to assess, on a population level, the clinical relevance of preoperative ct in evaluating the resectability of ga tumours in patients undergoing surgery.MethodsIn a provincial cancer registry, 2414 patients with ga diagnosed during 2005–2008 at 116 institutions were identified, and a primary chart review of radiology, operative, and pathology reports was performed for all patients. Preoperative abdominal ct reports were compared with intraoperative findings and final pathology reports (reference standard) to determine the negative predictive value (npv) of ct in assessing local invasion, nodal involvement, and intra-abdominal metastases.ResultsAmong patients undergoing gastrectomy, the npv of ct imaging in detecting local invasion was 86.9% (n = 536). For nodal metastasis, the npv of ct was 43.3% (n = 450). Among patients undergoing surgical exploration, the npv of ct for intra-abdominal metastases was 52.3% (n = 407).ConclusionsPreoperative abdominal ct imaging reported as negative is most accurate in determining local invasion and least accurate in nodal assessment. The poor npv of ct should be taken into account when selecting patients for staging laparoscopy.     

Population-based home care services in breast cancer: utilization and costs

Objective

To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc).

Methods

Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005–2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis.

Results

Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient–year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient–year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased.

Interpretation

Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population.     

Consensus recommendations for the diagnosis and management of well-differentiated gastroenterohepatic neuroendocrine tumours: a revised statement from a Canadian National Expert Group

Well-differentiated neuroendocrine tumours (nets—previously called “carcinoid tumours”) are relatively rare tumours originating from the diffuse neuroendocrine system; they are found most often in the bronchial or gastrointestinal systems. In Canada, gastroenterohepatic nets represent less than 0.25% of oncology cases. Because of the relative rarity of these tumours, diagnostic and therapeutic approaches vary and are often based on individual physician experience. A number of European and North American groups have developed consensus guidelines for the diagnosis and management of well-differentiated gastroenterohepatic nets, and in 2006, Canadian consensus guidelines were published by a Canadian expert group. The updated and expanded current Canadian guidelines are based on a consensus meeting held in Paris, France, in 2008 and are based on the most current literature.     

Concurrent chemoradiotherapy for locally advanced breast cancer—time for a new paradigm?

Background

In cases of locally advanced breast cancer (labc), preoperative (“neoadjuvant”) therapy was traditionally reserved to render the patient operable. More recently, neoadjuvant therapy, particularly chemotherapy, is being used in patients with operable disease to increase the opportunity for breast conservation. Despite the increasing use of preoperative chemotherapy, rates of pathologic complete response, a surrogate marker for disease-free survival, remain modest in patients with locally advanced disease and particularly so when the tumour is estrogen or progesterone receptor–positive and her2-negative. A new paradigm for labc patients is needed. In other solid tumours (for example, rectal, esophageal, and lung cancers), concurrent chemoradiotherapy (ccrt) is routinely used in neoadjuvant and adjuvant treatment protocols alike.

Results

The literature suggests that ccrt in labc patients with inoperable disease is associated with response rates higher than would be anticipated with systemic therapy alone.

Conclusions

Ongoing trials in this field are eagerly awaited to determine if ccrt should become the new paradigm.     

A single-centre chart review exploring the adjusted association between breast cancer phenotype and prognosis

Purpose and Methods

Using a retrospective chart review, we investigated the differences in survival and prognostic factors between patients with triple-negative breast cancer (tnbc) and those with non-tnbc. The review included 1018 breast cancer patients who were diagnosed between 2000 and 2005 in Essex, Kent, and Lambton counties in Ontario, Canada.

Results

Our findings indicate that, although the unadjusted results suggested that patients with tnbc were more likely than patients with non-tnbc to die [hazard ratio (hr): 2.29; 95% confidence interval (ci): 1.33 to 2.93], an adjusted survival analysis revealed no significant difference in overall survival between the groups (hr: 1.22; 95% ci: 0.63 to 2.39). The significant predictors of survival in the adjusted analysis were age, stage of cancer, and size of cancer.

Conclusions

Our findings support those of earlier reports, which suggest that presenting tumour size is the most important prognostic factor in tnbc. Investigations into unique screening methods to identify these tumours at an earlier stage and to prevent advanced-stage cancer in this patient subpopulation are necessary.     

Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients

Breast cancer is heterogenous, with variable expression of the estrogen receptor (er), progesterone receptor (pr), and human epidermal growth factor receptor 2 (her2). Overexpression of her2 is generally considered a negative prognostic feature, but whether outcomes for her2-positive early breast cancer remain different from those for other subtypes in the era of trastuzumab-based adjuvant therapy is unknown.

Methods

Using a retrospective chart review, we compared overall survival (os) and relapse-free survival (rfs) in 3 groups of patients with early-stage breast cancer: er-positive or pr-positive (or both) and her2-negative [“hormone receptor–positive” (hr+)]; her2-positive (her2+); and er-negative, pr-negative, and her2-negative [“triple-negative” (tn)].

Results

In the 503 charts analyzed (332 hr+, 94 her2+, 77 tn), the 5-year os and rfs were, respectively, 94.2% and 87.2% for hr+ patients, 88.6% and 74.9% for her2+ patients, and 85.4% and 76.2% for tn patients. On multivariate analysis, the os for the her2+ subtype was similar to that for the hr+ subtype (hazard ratio:1.07; 95% confidence interval: 0.31 to 3.67 with hr+ as reference), but os was significantly worse for tn patients than for hr+ patients (hazard ratio: 4.37; 95% confidence interval: 1.56 to 12.24). In her2+ patients, the 5-year os and rfs trended better for patients with er+ or pr+ disease than for patients with er-negative and pr-negative disease (5-year os: 92.1% vs. 86.9%; 5-year rfs: 79.8% vs. 71.4%). Of her2+ patients, just 80.9% received trastuzumab, including 33.3% of her2+ patients with sub-centimetre tumours.

Conclusions

In the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort.     

The use of prophylactic anticonvulsants in patients with brain tumours-a systematic review

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.