Cardiac Morbidity Following Chemoradiation in Stage III Non-small Cell Lung Cancer Patients: A Population-Based Cohort Study.

AIMS: To assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. MATERIALS AND METHODS: Patients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. RESULTS: In total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4-22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. CONCLUSION: The risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy.

A Canadian cancer trials group phase IB study of durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4) given concurrently or sequentially in patients with advanced, incurable solid malignancies.

Background The IND.226 study was a phase Ib study to determine the recommended phase II dose of durvalumab + tremelimumab in combination with standard platinum-doublet chemotherapy. Sequential administration of multiple agents increases total chair time adding costs overall and inconvenience for patients. This cohort of the IND.226 study evaluated the safety and tolerability of durvalumab + tremelimumab given either sequentially (SEQ) or concurrently (CON). Methods Patients with advanced solid tumours were enrolled and randomised to either SEQ tremelimumab 75 mg IV over 1 h followed by durvalumab 1500 mg IV over 1 h q4wks on the same day, or CON administration over 1 h. The serum pharmacokinetic profile of SEQ versus CON of durvalumab and tremelimumab administration was also evaluated. Results 14 patients either received SEQ (n = 7pts) or CON (n = 7 pts). There were no infusion related reactions. Drug related adverse events (AEs) were mainly low grade and manageable, and comparable in frequency between SEQ/CON- fatigue (43%/57%), rash (43%/43%), pruritus (43%/29%) and nausea (14%/29%). One patient in each cohort discontinued treatment due to toxicity. The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data. Conclusions Concurrent administration of durvalumab and tremelimumab over 1 h is safe with a comparable PK profile to sequential administration.

An evaluation of the safety of continuing trastuzumab despite overt left ventricular dysfunction.

Background: The major limitation in the use of trastuzumab therapy is cardiotoxicity. We evaluated the safety of a strategy of continuing trastuzumab in patients with breast cancer despite mild, asymptomatic left ventricular impairment. Methods: Charts of consecutive patients referred to a cardio-oncology clinic from January 2015 to March 2017 for decline in left ventricular ejection fraction (lvef), defined as a fall of 10 percentage points or more, or a value of less than 50% during trastuzumab therapy, were reviewed. The primary outcome of interest was change in lvef, measured before and during trastuzumab exposure and up to 3 times after initiation of cardiac medications during a median of 9 months. Results: All 18 patients referred for decline in lvef chose to remain on trastuzumab and were included. All patients were treated with angiotensin converting-enzyme inhibitors or beta-blockers, or both. After initiation of cardiac medications, lvef increased over time by 4.6 percentage points (95% confidence interval: 1.9 percentage points to 7.4 percentage points), approaching baseline values. Of the 18 patients, 17 (94%) were asymptomatic at all future visits. No deaths occurred in the group. Conclusions: Many patients with mildly reduced lvef and minimal heart failure symptoms might be able to continue trastuzumab without further decline in lvef, adverse cardiac events, or death when treated under the supervision of a cardiologist with close follow-up.

Resource use in the last three months of life by lung cancer patients in southern Ontario.

Background: End-of-life cancer care involves multidisciplinary teams working in various settings. Evaluating the quality of care and the feedback from such processes is an important aspect of health care quality improvement. Our retrospective cohort study reviewed health care use by lung cancer patients at end of life, their reasons for visiting the emergency department (ed), and feedback from regional health care professionals. Methods: We assessed 162 Ontario patients with small-cell and relapsed or advanced non-small-cell lung cancer. Demographics, disease characteristics, and resource use were collected, and the consenting caregivers for patients with ed visits were interviewed. Study results were disseminated, and feedback about barriers to care was sought. Results: Median patient age was 69 years; 73% of the group had non-small-cell lung cancer; and 39% and 69% had received chemotherapy and radiation therapy respectively. Median overall survival was 5.6 months. In the last 3 months of life, 93% of the study patients had visited an oncologist, 67% had telephoned their oncology team, 86% had received homecare, and 73% had visited the ed. Death occurred for 55% of the patients in hospital; 23%, at home; and 22%, in hospice. Goals of care had been documented for 68% of the patients. Homecare for longer than 3 months was associated with fewer ed visits (80.3% vs. 62.1%, p = 0.022). Key themes from stakeholders included the need for more resources and for effective communication between care teams. Conclusions: Use of acute-care services and rates of death in an acute-care facility are both high for lung cancer patients approaching end of life. In our study, interprofessional and patient-provider communication, earlier connection to homecare services, and improved access to community care were highlighted as having the potential to lower the need for acute-care resources.

Initial management of small-cell lung cancer (limited- and extensive-stage) and the role of thoracic radiotherapy and first-line chemotherapy: a systematic review.

Background: Patients with limited-stage (ls) or extensive-stage (es) small-cell lung cancer (sclc) are commonly given platinum-based chemotherapy as first-line treatment. Standard chemotherapy for patients with ls sclc includes a platinum agent such as cisplatin combined with the non-platinum agent etoposide. The objective of the present systematic review was to investigate the efficacy of adding radiotherapy to chemotherapy in patients with es sclc and to determine the appropriate timing, dose, and schedule of chemotherapy or radiation for patients with sclc. Methods: The medline and embase databases were searched for randomized controlled trials (rcts) comparing treatment with radiotherapy plus chemotherapy against treatment with chemotherapy alone in patients with es sclc. Identified rcts were also included if they compared various timings, doses, and schedules of treatment for patients with es sclc or ls sclc. Results: Sixty-four rcts were included. In patients with ls sclc, overall survival was greatest with platinum-etoposide compared with other chemotherapy regimens. In patients with es sclc, overall survival was greatest with chemotherapy containing platinum-irinotecan than with chemotherapy containing platinum-etoposide (hazard ratio: 0.84; 95% confidence interval: 0.74 to 0.95; p = 0.006). The addition of radiation to chemotherapy for patients with es sclc showed mixed results. There was no conclusive evidence that the timing, dose, or schedule of thoracic radiation affected treatment outcomes in sclc. Conclusions: In patients with ls sclc, cisplatin-etoposide plus radiotherapy should remain the standard therapy. In patients with es sclc, the evidence is insufficient to recommend the addition of radiotherapy to chemotherapy as standard practice to improve overall survival. However, on a case-by-case basis, radiotherapy might be added to reduce local recurrence. The most commonly used chemotherapy is platinum-etoposide; however, platinum-irinotecan can be considered.

Surgery after chemoradiotherapy in patients with stage III (N2 or N3, excluding T4) non-small-cell lung cancer: a systematic review.

Background: Chemoradiation with curative intent is considered the standard of care in patients with locally advanced, stage iii non-small-cell lung cancer (nsclc). However, some patients with stage iii (N2 or N3, excluding T4) nsclc might be eligible for surgery. The objective of the present systematic review was to investigate the efficacy of surgery after chemoradiotherapy compared with chemoradiotherapy alone in patients with potentially resectable locally advanced nsclc. Methods: A search of the medline, embase, and PubMed databases sought randomized controlled trials (rcts) comparing surgery after chemoradiotherapy with chemoradiotherapy alone in patients with stage iii (N2 or N3, excluding T4) nsclc. Results: Three included rcts consistently found no statistically significant difference in overall survival between patients with locally advanced nsclc who received surgery and chemoradiotherapy or chemoradiotherapy alone. Only one rct found that progression-free survival was significantly longer in patients treated with chemoradiation and surgery (hazard ratio: 0.77; 95% confidence interval: 0.62 to 0.96). In a post hoc analysis of the same trial, the overall survival rate was higher in the surgical group than in matched patients in a chemoradiation-only group if a lobectomy was performed (p = 0.002), but not if a pneumonectomy was performed. Furthermore, fewer treatment-related deaths occurred in patients who underwent lobectomy than in those who underwent pneumonectomy. Conclusions: For patients with locally advanced nsclc, the benefits of surgery after chemoradiation are uncertain. Surgery after chemoradiation for patients who do not require a pneumonectomy might be an option.

Guideline for the Initial Management of Small Cell Lung Cancer (Limited and Extensive Stage) and the Role of Thoracic Radiotherapy and First-line Chemotherapy.

AIMS: We investigated the efficacy of adding radiotherapy to chemotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) and the appropriate timing, dose and schedule of treatment for patients with ES-SCLC or limited stage SCLC (LS-SCLC). MATERIALS AND METHODS: The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of randomised controlled trials. KEY RECOMMENDATIONS: In patients with LS-SCLC (stage I, II and III), the addition of thoracic radiotherapy to standard chemotherapy is recommended. However, there is no clear evidence to inform definitive recommendations for optimal timing, sequential versus concurrent therapies and optimal dose or regimen. In patients with LS-SCLC, etoposide-cisplatin is the preferred regimen for adults who are being treated with combined modality therapy with curative intent. In patients with ES-SCLC (stage IV), there is insufficient evidence to recommend the addition of thoracic radiotherapy to standard chemotherapy as a standard practice for survival benefit; however, it could be considered on a case-by-case basis to reduce local recurrence. In patients with ES-SCLC, a platinum agent plus etoposide is the preferred regimen for adult patients who are being treated with combined modality therapy. Cisplatin and irinotecan represents an alternative treatment option to this, but is associated with increased rates of adverse events such as diarrhoea.

Antiangiogenic therapies in non-small-cell lung cancer.

Angiogenesis is frequent in non-small-cell lung cancer (nsclc) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with nsclc. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin-paclitaxel chemotherapy, has been shown to improve survival for patients with nsclc. However, bevacizumab-based therapy is not suitable for many nsclc patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders. Similar efficacy has also been seen with carboplatin-pemetrexed followed by maintenance pemetrexed chemotherapy. In the second-line setting, the addition of ramucirumab to docetaxel-or the addition of bevacizumab to paclitaxel-has resulted in a modest improvement in efficacy, although the clinical importance of those findings is questionable. Many trials in nsclc have also evaluated oral antiangiogenic compounds, both in the first line in combination with chemotherapy and upon disease progression either as combination or single-agent therapy. No clear improvements in overall survival have been observed, although a subgroup analysis of a trial evaluating the addition of nintedanib to docetaxel showed improved survival that was limited to patients with adenocarcinoma. Those findings require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with nsclc, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy.

Comparative survival in patients with brain metastases from non-small-cell lung cancer treated before and after implementation of radiosurgery.

INTRODUCTION: Survival after a diagnosis of brain metastasis in non-small-cell lung cancer (nsclc) is generally poor. We previously reported a median survival of approximately 4 months in a cohort of patients treated with whole-brain radiotherapy (wbrt). Since that time, we implemented a program of stereotactic radiosurgery (srs). In the present study, we examined survival and prognostic factors in a consecutive cohort of patients after the introduction of the srs program. METHODS: Data from a retrospective review of 167 nsclc patients with brain metastasis referred to a tertiary cancer centre during 2010-2012 were compared with data from a prior cohort of 91 patients treated during 2005-2007 ("pre-srs cohort"). RESULTS: Median overall survival from the date of diagnosis of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs cohort, p = 0.74) was not significantly different in the cohorts. The result was similar when the no-treatment group was excluded from the srs cohort. Within the srs cohort only, significant differences is overall survival were observed between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with improved survival being observed on univariate and multivariate analysis for patients receiving srs compared with patients receiving wbrt alone (p < 0.001). CONCLUSIONS: No improvement in survival was observed for nsclc patients with brain metastases after the implementation of srs. Selected patients (younger age, female sex, good performance status, fewer brain metastases) treated with srs appeared to demonstrate improved survival. However, those observations might also reflect better patient selection for srs or a greater tendency to offer those patients systemic therapy in addition to srs.

Guideline for radiotherapy with curative intent in patients with early-stage medically inoperable non-small-cell lung cancer.

OBJECTIVES: For this guideline, we investigated the effectiveness of radiotherapy with curative intent in medically inoperable patients with early-stage non-small-cell lung cancer (nsclc). METHODS: The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of mainly retrospective studies, expert consensus, and formal internal and external reviews. RECOMMENDATIONS: ■ Stereotactic body radiation therapy (sbrt) with curative intent is an option that should be considered for patients with early-stage, node-negative, medically inoperable nsclc. Qualifying Statements■ Because of the high dose per fraction, the planning process and treatment delivery for sbrt require the use of advanced technology to maintain an appropriate level of safety. Consistent patient positioning and 4-dimensional analysis of tumour and critical structure motion during simulation and treatment delivery are essential.■ Preliminary results for proton-beam therapy have been promising, but the technique requires further clinical study.■ Recommended fractionation schemes for sbrt should result in a biologically effective dose of 100 or greater by the linear quadric model, choosing an α/ß value of 10 [bed10(LQ) ≥ 100]. Qualifying Statements■ Because of the increased risk of treatment-related adverse events associated with centrally located tumours, consideration of tumour size and proximity to critical central structures is required when determining the dose and fractionation.■ Examples of dose-fractionation schemes used in the included studies have been provided.■ Based on the current evidence and the opinion of the authors, radiation doses at bed10(LQ) greater than 146 might significantly increase toxicity and should be avoided.■ Determination of the radiation bed by the linear quadratic model has limitations for the extreme hypofractionated schemes used in sbrt.

Approach to biomarker testing: perspectives from various specialties.

BACKGROUND: Despite its importance for patient outcomes, biomarker testing for lung cancer is not uniformly integrated into the Canadian health care system. To better understand current practice patterns for lung cancer biomarker testing, we assessed physician perspectives by specialty and region. METHODS: A national survey of Canadian lung cancer specialists was conducted to understand their perspectives on biomarker testing in lung cancer. The 11-item survey assessed the current practice and challenges of testing. The survey was sent to 375 specialists. RESULTS: The overall response rate for the survey was 36%. Nearly all specialists reported that knowing tumour genotyping results affects patient outcome and influences the treatment decision. Medical oncologists most commonly initiated molecular testing; however, most respondents suggested a shared model involving medical oncologists and pathologists. More than half of all responding specialists had the perception that fewer than 25% of test results are available for first-line treatment decisions. Identified barriers to routine testing for all lung cancer patients included cost, lack of funding, tissue availability, and sample quality. CONCLUSIONS: There was clear agreement that biomarker testing is important in determining appropriate treatment for patients. There is a need for general consensus on who should initiate molecular testing. Clear clinical guidance for pathologists has to be established for molecular testing, including defining the population to be tested, the timing of testing, and the tests to be performed. Testing could be facilitated by including more information on diagnostic sample requisitions, such as clinical suspicion of primary lung cancer, cancer history, and other samples already collected.

Diagnosing lung cancer in the 21st century: are we ready to meet the challenge of individualized care?

BACKGROUND: Histologic and molecular subtyping have become increasingly important as predictors of treatment benefit in lung cancer. The objective of the present study was to determine whether current diagnostic approaches provide adequate tissue to allow for individualized treatment decisions. METHODS: Our retrospective cohort study of new lung cancer patients seen at an academic centre between July 2007 and June 2008 collected baseline demographic and diagnostic information, including mode of diagnosis, type of diagnostic material, and pathology diagnosis. RESULTS: Of the 431 study patients, 20% had stage i or ii non-small-cell lung cancer (nsclc), 24% stage iii disease, and 39% stage iv nsclc. Three quarters of the small-cell lung cancer (sclc) cases were extensive stage. Diagnostically, 18% of patients had sclc; 30%, adenocarcinoma; 27%, squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma; 1%, mixed histology; 18%, nsclc not otherwise specified; 4%, other; and 2%, no pathology diagnosis. Surgical pathology material was available in 80% of cases, and cytology material alone in 20%. Surgical pathology material was more common in patients with early-stage than with advanced disease (89% for stages i and ii vs. 74% for stages iii and iv, p < 0.0001). The pathology report included ambiguous terms in 24% of cases: "consistent" (12%), "suspicious" (3%), "favour" (2%), "suggestive" (2%), "likely" (1%), "compatible" with malignancy (1%), "at least" (1%), "atypical" (0.5%), and "no pathology" (1.5%). CONCLUSIONS: Current diagnostic approaches in most lung cancer patients appear adequate, but complete histopathologic identification is missing in nearly 20% of cases, and some uncertainty as to the final diagnosis is expressed in 24% of pathology reports. Some improvement in diagnostic sampling and pathology reporting are required to allow for implementation of current treatment approaches.

Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review.

INTRODUCTION: This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients-unselected, selected, and molecularly selected-in three treatment settings: first line, second line, and maintenance. METHODS: Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review. RESULTS: In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfrtki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfrtkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfrtki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfrtki or second-line chemotherapy. The egfrtkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest. CONCLUSIONS: Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation-positive should be treated with an egfrtki as first-line therapy. An egfrtki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.

INTRODUCTION: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. METHODS: Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70. RESULTS: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. CONCLUSIONS: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.

Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases.

BACKGROUND: The prognosis of patients with brain metastases from non-small-cell lung cancer (nsclc) is poor. However, some reports suggest that patients with brain metastases at the time of initial diagnosis have a more favourable survival than do patients with advanced nsclc without brain metastases. METHODS: In a retrospective cohort of all new lung cancer patients seen at a Canadian tertiary centre between July 2005 and June 2007, we examined survival after a diagnosis of brain metastases for patients with brain metastases at initial diagnosis and patients who developed brain metastases later in their illness. RESULTS: During the 2-year period, 91 of 878 patients (10.4%) developed brain metastases. Median age in this cohort was 64 years. In 45, brain metastases were present at initial diagnosis, and in 46, brain metastases developed later in the course of the illness. Median survival in the entire cohort was 7.8 months. Survival after the diagnosis of brain metastases was similar for patients with brain metastases at diagnosis and later in the illness (4.8 months vs. 3.7 months, p = 0.53). As a result, patients who developed brain metastases later in their illness had a longer overall survival than did patients with brain metastases at diagnosis (9.8 months vs. 4.8 months). Among patients who received chemotherapy, the survival of patients with brain metastases at diagnosis was still poor (6.2 months). CONCLUSIONS: Our data show limited survival in patients with brain metastases from nsclc. Careful patient selection for more aggressive treatment approaches is necessary.

A comparison of patient knowledge of clinical trials and trialist priorities.

BACKGROUND: Recruitment to clinical trials remains poor, and patient knowledge of clinical trials is one barrier to recruitment. To identify knowledge deficits, we conducted and compared surveys measuring actual patient knowledge and clinical trialist priorities for patient knowledge. METHODS: Consenting patients at a tertiary cancer centre answered a survey that included 2 opinion questions about their own knowledge and willingness to join a trial, and22 knowledge questions. Clinical researchers at the centre were asked 13 questions about the importance of various trials factors. RESULTS: Of 126 patients surveyed, 16% had joined a clinical trial, and 42% had a secondary school education or less. The mean correct response rate on the knowledge questions was 58%. Higher rates of correct responses were associated with lower age (p = 0.05), greater education (p = 0.006), prior trial participation (p < 0.001), agreement or strong agreement with perceived understanding of trials (p < 0.001), and willingness to join a clinical trial (p = 0.002). Trialists valued an understanding of the rationale for clinical trials and of randomization, placebo, and patient protection, but those particular topics were poorly understood by patients. CONCLUSIONS: Patient knowledge about clinical trials is poor, including knowledge of several concepts ranked important by clinical trialists. The findings suggest that when developing education interventions, emphasis should be placed on the topics most directly related to patient care, and factors such as age and education level should be considered.

The importance of multidisciplinary team management of patients with non-small-cell lung cancer.

Historically, a simple approach to the treatment of non-small-cell lung cancer (nsclc) was applicable to nearly all patients. Recently, a more complex treatment algorithm has emerged, driven by both pathologic and molecular phenotype. This increasing complexity underscores the importance of a multidisciplinary team approach to the diagnosis, treatment, and supportive care of patients with nsclc. A team approach to management is important at all points: from diagnosis, through treatment, to end-of-life care. It also needs to be patient-centred and must involve the patient in decision-making concerning treatment. Multidisciplinary case conferencing is becoming an integral part of care. Early integration of palliative care into the team approach appears to contribute significantly to quality of life and potentially extends overall survival for these patients. Supportive approaches, including psychosocial and nutrition support, should be routinely incorporated into the team approach. Challenges to the implementation of multidisciplinary care require institutional commitment and support.

Role of pemetrexed in advanced non-small-cell lung cancer: meta-analysis of randomized controlled trials, with histology subgroup analysis.

PURPOSE: Platinum-based regimens represent the standard first-line treatment for non-small-cell lung cancer (nsclc). However, newer data have established a role for pemetrexed in the treatment of this disease. Such data suggest that histology represents a determining factor in the selection of treatment. METHODS: We undertook a systematic review of the literature for randomized controlled trials that compared the efficacy of pemetrexed with that of other treatments in advanced nsclc. Data and study quality were assessed according to published guidelines. RESULTS: We identified five trials that compared pemetrexed with other treatments or with placebo. Overall survival for patients treated with pemetrexed was superior to that with other treatments: hazard ratio (hr): 0.89; 95% confidence interval (ci): 0.80 to 0.99. The survival benefit was limited to patients with non-squamous histology: hr: 0.82; 95% ci: 0.73 to 0.91. Pemetrexed was inferior to other chemotherapy options in patients with squamous histology: hr: 1.19; 95% ci: 0.99 to 1.43. CONCLUSIONS: Compared with other chemotherapy agents, pemetrexed is more effective for the treatment of nsclc in patients with non-squamous histology.

Improving referral of patients for consideration of adjuvant chemotherapy after surgical resection of lung cancer.

BACKGROUND: Clinical trials demonstrate improved survival for patients with completely resected non-small-cell lung cancer (nsclc) who receive adjuvant chemotherapy. Concerns have been raised about the implementation of those data. The present study measured rates of referral for adjuvant chemotherapy and barriers to referral, and it also evaluated a knowledge translation strategy to change practice. METHODS: An audit and feedback approach was used. Using a retrospective cohort of patients undergoing thoracotomy at St. Joseph's Hospital in Hamilton, Ontario, during January-December 2008, anonymized data were presented to a group of thoracic surgeons for evaluation and feedback. RESULTS: Among 150 thoracotomies performed, 55 patients with nsclc were potentially eligible for adjuvant chemotherapy, but only 27 (49%) were referred for it. Significant variability in referral between surgeons (19%-100%) was observed. Reasons for non-referral were poorly documented in the medical record, but appeared to be primarily the surgeon's decision. The feedback session with surgeons produced a number of constructive suggestions to implement change in practice. CONCLUSIONS: Our findings suggest that surgeon choice was the most significant barrier to implementation of adjuvant chemotherapy for nsclc. Audit and feedback was a useful knowledge translation strategy. However, longer follow-up is needed to document change in practice.

Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24.

BACKGROUND: Hypertension (HTN), a recognized adverse effect of angiogenesis inhibitors, may be a potential biomarker of activity of these agents. We conducted a retrospective analysis to examine the incidence and predictors of the development of on-treatment HTN with the vascular endothelial growth factor receptor tyrosine kinase inhibitor cediranib, and the relationship of this adverse event with treatment outcomes. PATIENTS AND METHODS: BR24 was a double-blind placebo-controlled phase II trial of carboplatin/paclitaxel chemotherapy with either daily oral cediranib or placebo in patients (n = 296) with advanced non-small-cell lung cancer (NSCLC). Exploratory analyses characterized relationships between HTN, baseline variables, and efficacy outcomes. RESULTS: New onset or worsening of preexisting HTN (treatment-emergent HTN) was more frequent in patients receiving cediranib (68 versus 45%, P < 0.0001). Factors associated with HTN in all randomized patients were good performance status and treatment with cediranib. In both arms, treatment-emergent HTN was associated with improved efficacy outcomes, but there was no evidence of a differential treatment effect, with nonsignificant interaction P values. CONCLUSIONS: In advanced NSCLC, HTN is frequent in patients receiving chemotherapy, with or without cediranib. The development of HTN was favorably prognostic in these patients, but not predictive of a differential outcome with cediranib.