Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Appropriate vitamin D loading regimen for patients with advanced lung cancer.

BACKGROUND: Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens. METHODS: In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy. RESULTS: Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol. CONCLUSION: Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

Real-World Evidence of the Impact of the COVID-19 Pandemic on Lung Cancer Survival: Canadian Perspective.

Background: The effect of COVID-19 on treatment outcomes in the literature remains limited and is mostly reported either as predictive survival using prioritization and modeling techniques. We aimed to quantify the effect of COVID-19 on lung cancer survival using real-world data collected at the Jewish General Hospital, Montreal. Methods: This is a retrospective chart review study of patients diagnosed between March 2019 and March 2022. We compared three cohorts: pre-COVID-19, and 1st and 2nd year of the pandemic. Results: 417 patients were diagnosed and treated with lung cancer at our centre: 130 in 2019, 103 in 2020 and 184 in 2021. Although the proportion of advanced/metastatic-stage lung cancer remained the same, there was a significant increase in the late-stage presentation during the pandemic. The proportion of M1c (multiple extrathoracic sites) cases in 2020 and 2021 was 57% and 51%, respectively, compared to 31% in 2019 (p < 0.05). Median survival for early stages of lung cancer was similar in the three cohorts. However, patients diagnosed in the M1c stage had a significantly increased risk of death. The 6-month mortality rate was 53% in 2021 compared to 47% in 2020 and 29% in 2019 (p = 0.004). The median survival in this subgroup of patients decreased significantly from 13 months in 2019 to 6 months in 2020 and 5 months in 2021 (p < 0.001). Conclusions: This study is, to our knowledge, the largest single-institution study in Canada looking at lung cancer survival during the COVID-19 pandemic. Our study looks at overall survival in the advanced/metastatic setting of NSCLC during the COVID-19 pandemic. We have previously reported on treatment pattern changes and increased wait times for NSCLC patients during the pandemic. In this study, we report that the advanced/metastatic subgroup had both an increase in the 6-month mortality rate and worsening overall survival during this same time period. Although there was no statistical difference in the proportion of patients with advanced disease, there was a concerning trend of increased M1c disease in cohorts 2 and 3. The higher M1c disease during the COVID-19 pandemic (cohorts 2 and 3) likely played a crucial role in increasing the 6-month mortality rate and leading to a reduced overall survival of lung cancer patients during the pandemic. These findings are more likely to be better identified with longer follow-up.

Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

Cell-Free Tumor DNA (ctDNA) Utility in Detection of Original Sensitizing and Resistant EGFR Mutations in Non-Small Cell Lung Cancer (NSCLC).

BACKGROUND: Recent studies have demonstrated the utility of cell-free tumor DNA (ctDNA) from plasma as an alternative source of genomic material for detection of sensitizing and resistance mutations in NSCLC. We hypothesized that the plasma level of ctDNA is an effective biomarker to provide a non-invasive and thus a less risky method to determine new resistance mutations and to monitor response to treatment and tumor progression in lung cancer patients. METHODS: This prospective cohort study was approved and conducted at the Peter Brojde Lung Cancer Centre, Montreal. Blood was collected in STRECK tubes at four time points. DNA was extracted from plasma, and ctDNA was analyzed for the presence of mutations in the EGFR gene using the COBAS® EGFR v2 qPCR (Roche) test. RESULTS: Overall, 75 pts were enrolled in the study. In total, 23 pts were TKI-naïve, and 52 were already receiving first-line TKI treatment. ctDNA detected the original mutations (OM) in 35/75 (48%) patients. Significantly higher detection rates were observed in TKI-naïve patients compared to the TKI-treated group, 70% versus 37%, respectively (p = 0.012). The detection of the original mutation at the study baseline was a negative predictor of progression-free survival (PFS) and overall survival (OS). The resistance mutation (T790M) was detected in 32/74 (43%) patients. In 27/32 (84%), the T790M was detected during treatment with TKI: in 25/27 patients, T790M was detected at the time of radiologic progression, in one patient, T790M was detected before radiologic progression, and in one patient, T790M was detected four weeks after starting systemic chemotherapy post progression on TKI. At the time of progression, the detection of T790M significantly correlates with the re-appearance of OM (p = 0.001). CONCLUSION: Plasma ctDNA is a noninvasive patient-friendly test that can be used to monitor response to treatment, early progression, and detection of acquired resistant mutations. Monitoring of clearance and re-emergence of driver mutations during TKI treatment effectively identifies progression of the disease. As larger NGS panels are available for ctDNA testing, these findings may also have implications for other biomarkers. The results from ongoing and prospective studies will further determine the utility of plasma testing to diagnose, monitor for disease progression, and guide treatment decisions in NSCLC.

The Impact of COVID-19 on the Diagnosis and Treatment of Lung Cancer over a 2-Year Period at a Canadian Academic Center.

BACKGROUND: We have recently reported a 35% drop in new lung cancer diagnoses and a 64% drop in lung cancer surgeries during the first year of the pandemic. METHODS: The target population was divided into three cohorts: pre-COVID-19 (2019), first year of COVID-19 (2020), and second year of COVID-19 (2021). RESULTS: The number of new lung cancer diagnoses during the second year of the pandemic increased by 75%, with more than 50% being in the advanced/metastatic stage. There was a significant increase in cases with multiple extrathoracic sites of metastases during the pandemic. During the first year of the pandemic, significantly more patients were treated with radiosurgery compared to the pre-COVID-19 year. During the second year, the number of radiosurgery and surgical cases returned to pre-COVID-19 levels. No significant changes were observed in systemic chemotherapy and targeted therapy. No statistical difference was identified in the mean wait time for diagnosis and treatment during the three years of observation. However, the wait time for surgery was prolonged compared to the pre-COVID-19 cohort. CONCLUSIONS: The significant drop in new diagnoses of lung cancer during the first year of the pandemic was followed by an almost two-fold increase in the second year, with the increased rate of metastatic disease with multiple extra-thoracic site metastases. Limited access to surgery resulted in the more frequent use of radiosurgery.

The Impact of COVID-19 on the Diagnosis and Treatment of Lung Cancer at a Canadian Academic Center: A Retrospective Chart Review.

The large burden of COVID-19 on health care systems worldwide has raised concerns among medical oncologists about the impact of COVID-19 on the diagnosis and treatment of lung cancer patients. In this retrospective cohort study, we investigated the impact of COVID-19 on lung cancer diagnosis and treatment before and during the COVID-19 era. New lung cancer diagnoses decreased by 34.7% during the pandemic with slightly more advanced stages of disease, there was a significant increase in the utilization of radiosurgery as the first definitive treatment, and a decrease in both systemic treatment as well as surgery compared to the pre-COVID-19 era. There was no significant delay in starting chemotherapy and radiation treatment during the pandemic compared to pre-COVID-19 time. However, we observed a delay to lung cancer surgery during the pandemic time. COVID-19 seems to have had a major impact at our lung cancer center on the diagnoses and treatment patterns of lung cancer patients. Many oncologists fear that they will see an increase in newly diagnosed lung cancer patients in the coming year. This study is still ongoing and further data will be collected and analyzed to better understand the total impact of the COVID-19 pandemic on our lung cancer patient population.

Real-World Pattern of Treatment and Clinical Outcomes of EGFR-Mutant Non-Small Cell Lung Cancer in a Single Academic Centre in Quebec.

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62-13.44) months for first-line treatment, and 4.4 (95% CI: 1.47-7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9-30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5-27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.

Prevalence of obstructive sleep apnea-hypopnea in severe versus moderate asthma.

BACKGROUND: Previous studies have suggested a link between obstructive sleep apnea and poor asthma control, which may be mediated through airway inflammation, obesity, and other mechanisms. OBJECTIVE: To test the hypothesis that the prevalence and severity of sleep apnea is greater among patients with severe compared with moderate asthma and controls without asthma. METHODS: Complete overnight home polysomnography was performed in 26 patients with severe asthma consecutively recruited to a difficult asthma program, 26 patients with moderate asthma, and 26 controls without asthma of similar age and body mass index. Flow rates and Juniper asthma control and quality of life questionnaires were also obtained. RESULTS: Obstructive sleep apnea-hypopnea, defined by an Apnea-Hypopnea Index > or = 15 events/h of sleep scored using Chicago criteria, was present in 23 of 26 (88%) patients with severe asthma, 15 of 26 (58%) patients with moderate asthma, and 8 of 26 (31%) controls without asthma (chi(2): P < .001). Using the more restrictive scoring criteria applied in the Wisconsin cohort study, Apnea-Hypopnea Index > or = 5/h was present in 50% (severe), 23% (moderate), and 12% (control) of subjects (P = .007). Mean nocturnal arterial oxygen saturation was significantly lower in patients with severe asthma versus controls, and apnea-hypopnea severity measures were significantly worse for both asthmatic groups compared with controls. Among subjects with asthma, no significant correlations were identified between the severity of sleep-disordered breathing and asthma severity or control measures (FEV(1), Juniper scores). CONCLUSIONS: Obstructive sleep apnea-hypopnea was significantly more prevalent among patients with severe compared with moderate asthma, and more prevalent for both asthma groups than controls without asthma. These observations suggest potential pathophysiologic interactions between obstructive sleep apnea-hypopnea and asthma severity and control.

The use of a standardized Chinese herbal formula in patients with advanced lung cancer: a feasibility study.

OBJECTIVE: Increasing numbers of cancer patients are using Chinese herbs (CHs). However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life. METHODS: A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer (NSCLC, Seventh American Joint Committee on Cancer TNM staging system). RESULTS: Patients with advanced lung cancer were interested in using the CH formula. Completion (93%) and adherence (98%) levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild (Grade 1 or 2) and only a small minority (8%) were potentially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness. CONCLUSION: This study provides preliminary evidence that short-term use of a carefully selected and prepared CH formula in patients with stage 4 NSCLC is acceptable and safe.

Comparison of the yield of different diagnostic procedures for cellular differentiation and genetic profiling of non-small-cell lung cancer.

INTRODUCTION: As treatments for non-small-cell lung cancer (NSCLC) become personalized, cellular and molecular differentiation of the tumor is becoming the standard of care. Our objective is to compare the yield of different diagnostic procedures for cellular differentiation of NSCLC and analysis of epidermal growth factor receptor (EGFR) mutation. METHODS: We evaluated all patients diagnosed with NSCLC from January 2004 to September 2010 at the Jewish General Hospital, Montreal. Diagnostic procedures included surgical biopsies, nonsurgical histologic biopsies (endobronchial and core needle), transbronchial needle aspirate (TBNA) and transthoracic needle aspirate (TTNA), bronchoalveolar lavage (BAL), and pleural fluid samples. RESULTS: We included 702 subjects investigated for histopathologic differentiation of NSCLC. Of these, 269 were also investigated for EGFR mutation. Failure to ascertain the cellular subtype and EGFR mutation status was least likely with surgical specimens (0% and 1.8%, respectively); followed by TTNA (14% and 10%, respectively) and histologic biopsy (18% for both); and was frequent with TBNA (39% and 30%, respectively). Although BAL and pleural fluid specimens provided reasonable yield for cellular differentiation (20 % and 11%, respectively), their results were not accurate in 6% of their samples when compared with concurrent or subsequent surgical specimens (reference standard) performed in a subgroup of patients. CONCLUSION: Radiologically guided TTNA and histologic biopsies provided high yield for both molecular and histologic analyses. The yield of unguided TBNA was relatively low. Further studies are needed to assess the adequacy of BAL and pleural fluid samples for EGFR mutation analysis and accurate characterization of cellular subtypes of NSCLC.

Are frailty markers useful for predicting treatment toxicity and mortality in older newly diagnosed cancer patients? Results from a prospective pilot study.

INTRODUCTION: The concept of frailty may be useful to characterize vulnerability. The aim of this pilot study was to explore the association between frailty/functional status and treatment toxicity at 3 months and mortality at 6 months. METHODS: Patients aged ≥65 years referred to the Jewish General Hospital, Montreal, with a new cancer diagnosis. Seven frailty markers and 4 functional status measures were examined. Logistic regression was used to examine the association between frailty/functional status and toxicity, and Cox models for time to death. RESULTS: 112 participated, median age 74.1, 31 had toxicity and 15 died. At baseline, 88% had ≥1 frailty marker. Low grip strength predicted toxicity (OR 8.47, 95%CI: 1.3-53.6), ECOG performance status and ADL disability predicted time to death. CONCLUSION: The majority had ≥1 frailty marker. Low grip strength predicted toxicity, none of the functional measures did. Further researcher investigating the usefulness of frailty markers is needed.

Prognostic value of the six-minute walk in advanced non-small cell lung cancer.

BACKGROUND: The 6 minute walk (6MW) is usually used to evaluate exercise capacity in a variety of patient populations. We hypothesized that the 6MW would decline after chemotherapy and assessed the prognostic value of this test. MATERIALS AND METHODS: The 6MW was conducted in newly diagnosed advanced non-small cell lung cancer patients on three different days: twice before (one initial and one prechemotherapy test) and once after two cycles of chemotherapy. RESULTS: Sixty-four patients were enrolled and 45 (70%) completed the study. For patients who dropped out the distance on initial 6MW was 361 m (SD 99) compared with 445 m (SD 85) for completers (p = 0.004).In the 45 completers, the mean 6MW decreased significantly after two cycles. There was a clinically significant (>54 m) decline in 6MW in 13 patients (29%), and an improved/unchanged 6MW in 32 patients (71%).For patients who walked <400 m on initial 6MW, rates of drop out were significantly higher (p = 0.02), progression of disease was statistically more frequent (p = 0.03), and median survival was significantly shorter: 6.7 months (95% confidence interval 2.6-10.8) compared with 13.9 months (95% confidence interval 10.0-17.8) in patients walking > or =400 m (p = 0.01).An initial 6MW of > or =400 m was the only variable with a significant effect on survival in a Cox regression after adjusting for all known covariates of interest. CONCLUSIONS: The 6MW declines significantly after two cycles of chemotherapy. This decline may have been even greater as patients with lower 6MW were more likely to drop out of the study. An initial 6MW > or =400 m might be a useful prognostic factor for survival in patients with advanced non-small cell lung cancer.

Should patient-rated performance status affect treatment decisions in advanced lung cancer?

INTRODUCTION: The Eastern Cooperative Oncology Group (ECOG) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials. The patient-rated performance status score (Pt-PS), section of the patient generated subjective global assessment scale, has identical criteria to the physician-rated ECOG scale (MD-PS). We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial. METHODS: Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated questionnaire, which was then correlated (kappa statistic) with the ECOG PS recorded at the same time. Patients were treated with standard chemotherapy. Survival was determined using Kaplan-Meier statistics. RESULTS: One hundred nine patients (M:F-54:55) were recruited. Pt-PS differed from MD-PS in 59 (54%) instances (p = 0.0001). When scores were not congruent, 41/59 (69%) patients evaluated themselves as having a worse PS than the physician's rating. Pt-PS was 0 to 1 in 60 (55%) patients whereas MD-PS was 0 to 1 in 78 (72%) patients. The functional status irrespective of evaluator was predictive of survival (p = 0.001 for MD-PS and p = 0.001 for Pt-PS). However, the median survival in those with MD-PS >/=2 was 3.3 (CI; 1.7-4.9) months whereas individuals with Pt-PS >/=2 had a median survival of 6.2 (CI; 5.4-6.9) months. CONCLUSIONS: Pt-PS and MD-PS were not congruent in over half of the cases, with Pt-PS scores usually poorer. Almost half the patients would have excluded themselves from a hypothetical clinical trial (Pt-PS >/=2). This requires prospective evaluation.

Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10.

PURPOSE: Recent trials have shown significant survival benefit from adjuvant chemotherapy for non-small-cell lung cancer (NSCLC). Whether elderly patients tolerate platinum-based adjuvant chemotherapy and derive the same survival advantage is unknown. This retrospective study evaluated the influence of age on survival, adjuvant chemotherapy delivery, and toxicity in National Cancer Institute of Canada (NCIC) Clinical Trials Group study JBR.10. PATIENTS AND METHODS: Pretreatment characteristics and survival were compared for 327 young (< or = 65 years) and 155 elderly (> 65 years) patients. Chemotherapy delivery and toxicity were compared for 213 treated patients (63 elderly, 150 young). RESULTS: Baseline demographics by age were similar with the exception of histology (adenocarcinoma: 58% young, 43% elderly; squamous: 32% young, 49% elderly; P = .001) and performance status (PS; PS 0: 53% young, 41% elderly; P = .01). Chemotherapy significantly prolonged overall survival for elderly patients (hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .04). This benefit is similar to the effect for all patients in JBR.10. Mean dose-intensities of vinorelbine and cisplatin were 13.2 and 18.0 mg/m2/wk in young, respectively, and 9.9 and 14.1 mg/m2/wk in elderly patients (vinorelbine, P = .0004; cisplatin, P = .001), respectively. The elderly received significantly fewer doses of vinorelbine (P = .014) and cisplatin (P = .006). Fewer elderly patients completed treatment and more refused treatment (P = .03). There were no significant differences in toxicities, hospitalization, or treatment-related death by age group. Fifteen (11.9%) of 126 deaths in the young resulted from nonmalignant causes, and 15 (21.1%) of 71 in the elderly (P = .13). CONCLUSION: Despite elderly patients' receiving less chemotherapy, adjuvant vinorelbine and cisplatin improves survival in patients older than 65 years with acceptable toxicity. Adjuvant chemotherapy should not be withheld from elderly patients.

Differences in airway remodeling between subjects with severe and moderate asthma.

BACKGROUND: Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. OBJECTIVE: We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. METHODS: Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle alpha-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. RESULTS: ASM area was greater in subjects with severe (0.24+/- 0.03 mm(2)) than in subjects with moderate (0.05+/- 0.01 mm(2)) asthma (P<.001). The distance between the epithelial and ASM layers was less in the severe group (0.12+/- 0.01 mm) than in the moderate group (0.24+/- 0.02, P<.001). A trend toward greater subepithelial fibrosis in subjects with severe asthma did not reach statistical significance. IL-8 and eotaxin expression, but not RANTES expression, were increased in the ASM of subjects with severe asthma compared with in subjects with moderate asthma. CONCLUSION: Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma.