Adjuvant Chemotherapy For Non-small Cell Lung Cancer Research Articles

Treatment of non-small cell lung cancer with Yiqi Buxue prescriptions combined with adjuvant chemotherapy on the cancer therapy-related cardiovascular toxicity: A systematic review and meta-analysis

Ethnopharmacological relevanceThe treatment and prognosis of patients with non-small cell lung cancer (NSCLC) was affected by the occurrence of cancer therapy-related cardiovascular toxicity (CTR-CVT). Yiqi Buxue prescriptions were a class of traditional single or compounded formulations that have become a consensus for NSCLC. There was no clear information and or summary available for Yiqi Buxue prescriptions combined with adjuvant chemotherapy for NSCLC in reducing CTR-CVT. Aim of the studyTo systematically evaluate the Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC. Materials and methodsSearch strategies were developed to identify relevant randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure (CNKI), SinoMed and WanFang Data from database inception date to October 2022. The methodological quality of evidence was assessed using the Cochrane risk of bias (ROBs) assessment tool, and the meta-analysis was analyzed using RevMan 5.3. ResultsA total of 9 studies were included. Compared with the adjuvant chemotherapy group, Yiqi Buxue prescriptions combined with adjuvant chemotherapy group showed no statistically significant in reducing CTR-CVT (RR 0.67, 95%CI 0.11 to 3.93, P = 0.65) and in CD4+/CD8+(MR 0.32, 95%CI -0.13 to 0.77, P = 0.16). However, it significantly improved the objective response rate (ORR) (RR 1.57, 95%CI 1.32 to 1.87, P < 0.00001), disease control rate (DCR) (RR 1.25, 95%CI 1.15 to 1.35, P < 0.00001), Karnofsky performance status (KPS) improvement rate (RR 1.34, 95%CI 1.16 to 1.55, P < 0.0001), CD3+ (MR 4.17, 95%CI 3.68 to 4.66, P < 0.00001), CD4+ (MR 4.87, 95%CI 4.28 to 5.46, P < 0.00001), and CD8+ (MR 3.12, 95%CI 2.57 to 3.67, P < 0.00001). ConclusionsThe current RCTs are hampered by small sample sizes and poor methodological quality. More rigorously designed and large sample RCTs with primary outcome of CTR-CVT are needed to investigate the effectiveness of Yiqi Buxue prescriptions combined with adjuvant chemotherapy in reducing CTR-CVT for patients with NSCLC.

Prediction of disease-free survival of N1/2 non-small cell lung cancer after adjuvant chemotherapy by the biomarker RPMB

No molecular biomarkers have been proven applicable in clinical practice to identify patients who can benefit from adjuvant chemotherapy in non-small cell lung cancer (NSCLC). In this study, we established a biomarker, RPMB, short for promotor methylation burden of DNA repair genes (DRGs), to identify the subgroup of patients who might benefit from adjuvant chemotherapy in NSCLC. Methylation profiles of 828 NSCLC primary tumors and their clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The RPMB for each patient after radical resection was calculated and its correlation with the prognosis of NSCLC was extensively investigated. DRGs of NSCLC were much more hypomethylated than the other genes (all p＜0.001). RPMB was defined as the ratio of methylated DRGs to the total number of all the DRGs. Patients with higher RPMB values tended to be nonsmokers, had adenocarcinoma, were female and had peripheral tumors. Subgroup analysis of forest plot among different clinical factors showed that high RPMB was significantly correlated to better disease-free survival (DFS) in pathologic N-positive patients after adjuvant chemotherapy (HR = 0.404, n = 62, p = 0.034). Notably, more superior DFS was exhibited in high RPMB NSCLCs with N1 nodal stage compared with those with low RPMB values (HR = 0.348, n = 47, p = 0.043). High RPMB might be used as a potential predictor to identify suitable N-positive NSCLC patients who can benefit from adjuvant chemotherapy after radical surgery.

Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability.

Simple SummaryThe establishment of biomarkers that can identify individuals at high risk of early recurrence after surgery will be an important issue in decision-making for perioperative therapy. In this review, we describe potential biomarkers for predicting the likelihood of recurrence in patients who undergo surgery for stage I NSCLC. ACTN4 is a possible biomarker for identifying patients at high risk of postoperative recurrence, and patients with gene amplification of ACTN4 might thus benefit the most from adjuvant chemotherapy.Surgical treatment is the best curative treatment option for patients with non-small cell lung cancer (NSCLC), but some patients have recurrence beyond the surgical margin even after receiving curative surgery. Therefore, therapies with anti-cancer agents also play an important role perioperatively. In this paper, we review the current status of adjuvant chemotherapy in NSCLC and describe promising perioperative therapies, including molecularly targeted therapies and immune checkpoint inhibitors. Previously reported biomarkers of adjuvant chemotherapy for NSCLC are discussed along with their limitations. Adjuvant chemotherapy after resective surgery was most effective in patients with metastatic lesions located just outside the surgical margin; in addition, these metastatic lesions were the most sensitive to adjuvant chemotherapy. Thus, the first step in predicting patients who have sensitivity to adjuvant therapies is to perform a qualified evaluation of metastatic ability using markers such as actinin-4 (ACTN4). In this review, we discuss the potential use of biomarkers in patient stratification for effective adjuvant chemotherapy and, in particular, the use of ACTN4 as a possible biomarker for NSCLC.

LACE-Bio: Validation of Predictive and/or Prognostic Immunohistochemistry/Histochemistry-based Biomarkers in Resected Non–small-cell Lung Cancer

BackgroundComplete resection of non–small-cell lung cancer (NSCLC) offers the potential for cure after surgery and adjuvant chemotherapy. Patients may not benefit and may experience severe toxicity. There are no validated molecular tools to allow better patient selection. Materials and MethodsThe LACE-Bio (LACE [Lung Adjuvant Cisplatin Evaluation]) project includes 4 trials (International Adjuvant Lung Cancer Trial [IALT], Adjuvant Navelbine International Trialist Association [ANITA], JBR10, and Cancer and Leukemia Group B (CALGB)-9633). Immunohistochemistry biomarkers shown in one trial to have a prognostic/predictive effect on overall survival were tested. ResultsThe majority of the promising biomarkers could not be validated; the prognostic effect of tumor infiltrating lymphocytes and β-tubulin was confirmed. Potential causes include tissue fixation, storage, the use of tissue microarrays, and varying reagent/antibody batches. ConclusionsImmunohistochemistry assays from single trials may be misleading and require validation before being used for patient selection. LACE-Bio-2 is evaluating potential genomic biomarkers that may allow more precise selection of patients with NSCLC for adjuvant chemotherapy in NSCLC.

EORTC-ETOP randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab versus placebo for patients with early stage non-small cell lung cancer (NSCLC) after resection and standard adjuvant chemotherapy: PEARLS (NCT02504372).

TPS8571Background: The benefit of adjuvant chemotherapy in NSCLC has plateaued at around 5.4% improvement in 5 year overall survival and is hampered by toxicities having a major impact on treatment...

Patients’ preferred and perceived roles in making decisions about adjuvant chemotherapy for non-small-cell lung cancer

BackgroundPeople with cancer have varying preferences for involvement in decision-making between active, collaborative and passive roles. We sought the preferred and perceived involvement in decision-making among patients considering adjuvant chemotherapy (ACT) after resection of early non-small cell lung cancer (NSCLC). MethodsPatients considering ACT for NSCLC were asked to complete a self-administered questionnaire at baseline and 6 months. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale (CPS). We examined differences between preferred and perceived roles, differences in preferred roles over time, determinants of preferences, and differences in treatment preferences between patients preferring active and less active roles. Results98 patients completed the baseline questionnaire; 75 completed the 6 month questionnaire. Most patients were male (55%) with a median age of 64 years (range, 43–79 years). Preferred role in decision-making at baseline (n=98) was active in 27%, collaborative in 47%, and passive in 27%. Perceived decision-making roles matched the preferred role in 79% of patients. Individuals’ role preferences often varied between baseline and 6 months, but there was no consistent direction to the change (25% changed preference to more active involvement, 22% to less active). Preferring a more active role was associated with university education (OR 2.9, p=0.02), deciding not to have ACT (OR 5.0, p<0.01), and worse health-related quality of life (HRQL) during ACT: physical well-being (OR 4.4, p=0.05), overall well-being (OR 5.5, p=0.02), sleep (OR 8.4, p<0.01) and shortness of breath (OR 7.6, p=0.01). Patients who preferred an active decision-making role judged larger survival benefits necessary to make ACT worthwhile than those preferring a passive role. ConclusionMost patients with resected NSCLC preferred and perceived a collaborative role in decision-making about ACT. Clinicians should elicit and consider patients’ preferences for involvement in decision-making when discussing ACT for NSCLC.

Final follow-up (f/u) results from RADIANT: A randomized double blind phase 3 trial of adjuvant erlotinib (E) versus placebo (P) following complete tumor resection in patients (pts) with stage IB–IIIA EGFR positive (IHC/FISH) non-small cell lung cancer (NSCLC).

7540 Background: Adjuvant chemotherapy for NSCLC has reached a plateau. The use of the tyrosine kinase inhibitor (TKI), E, was explored in the adjuvant setting given success in advanced setting.We ...

Abstract 3855: Adjuvant chemotherapy in the elderly with non-small cell lung cancer

Abstract Introduction: Clinical trials have shown improved survival with adjuvant chemotherapy (AC) for resected stages I-III non-small cell lung cancer (NSCLC). However, data regarding its use in older patients are limited. The objectives of this retrospective analysis were: (i) to assess the change in the frequency of AC use over the period 2000-2010, in both elderly and younger patients; (ii) to study the corresponding survival outcomes in each age group; and (iii) to identify the reasons for not receiving AC among patients in whom AC is recommended based on the current NCCN guidelines. Methods: After IRB approval, data were collected from the cancer registry at the Syracuse VA Medical Center for retrospective analysis of patients who were diagnosed with NSCLC and underwent surgical resection from 2000 to 2010. Patients were divided based on age groups into younger patients, aged &amp;lt;65 years or the elderly, aged &amp;gt; 65 years. Patients were also divided based on the period of diagnosis: a) 2000 - 2004 and b) 2005 -2010. Pearson Chi-square tests were used to examine patterns of AC use based on age groups and the period of diagnosis. The Kaplan-Meier procedure was used to estimate the survival probabilities. Log rank tests were used to test the equality of survival distributions between groups. Wald tests were used to test the equality of survival probabilities at 5 years, with the standard error estimated by Greenwood's formula. Reasons for non-receipt of AC when indicated but not administered were collected from the medical record. Results: We identified 154 patients from the tumor registry and 148 patients were included in data analysis after excluding 6 patients who died within 30 days of surgery. Of the 148 patients, AC was indicated in 66 patients but administered in 34 (52%) patients. Of 66 patients 32 (48%) were elderly. There was no difference in baseline characteristics (gender, histology and stage) between the two age groups. AC use was less frequent in the elderly patients (38% vs. 65%, p=0.03). The 5-year survival rate with and without AC was 61% vs. 38% (p=0.23) in elderly and 76% vs. 25% (p=0.001) in younger patients. For all 66 patients combined, there was a trend for more frequent use of AC after 2005, (41% vs. 63%, p=0.08). The proportion of elderly patients receiving AC prior to 2005 increased from 25% to 58% after 2005 (p=0.06). Cisplatin compared with carboplatin was used infrequently in the elderly (8% vs. 32%, p=0.210). Elderly patients were more likely to not receive AC even when indicated due to patient refusal or the oncology provider not offering AC (38% vs. 12%, p=0.015) Conclusion: Elderly patients with resected NSCLC are treated with AC less often than younger patients. There is a trend towards increased utilization of AC since 2005. The rate of refusing or not being offered AC was higher among elderly patients as compared to younger patients. Provider and patient education may enhance utilization of AC in NSCLC to improve outcomes in the elderly. Citation Format: Mijung Lee, Dongliang Wang, Ian G. Pinto, Stephen Graziano, Ajeet Gajra. Adjuvant chemotherapy in the elderly with non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3855. doi:10.1158/1538-7445.AM2014-3855

[Advance of postoperative adjuvant therapy in non-small cell lung cancer].

肺癌可分为非小细胞肺癌（non-small cell lung cancer, NSCLC）和小细胞肺癌，其发病率和死亡率均高居恶性肿瘤首位。本文主要就NSCLC术后辅助化疗的地位确立、辅助化疗的合适人群和化疗方案选择以及相关生物标志物研究进展作一综述。

P0153 Toxicity of vinorelbine with platinum as adjuvant chemotherapy for non-small-cell lung cancer: A single institution experience

<h3>Background</h3> Vinorelbine with platinum is a standard adjuvant treatment for patients with resectable non-small-cell lung cancer (NSCLC). The pivotal phase 3 studies using a weekly intravenous vinorelbine schedule report high levels of toxicity. In our centre we use vinorelbine on a day 1 and 8 schedule to reduce the incidence of neutropenia. We audited our adjuvant use of vinorelbine with platinum to assess toxicity. <h3>Methods</h3> We did a retrospective case note review of all patients receiving vinorelbine with either cisplatin or carboplatin between 2008 and 2013. <h3>Findings</h3> Thirty-one patients received either cisplatin 80mg/m² day 1 with vinorelbine intravenously 30mg/m² on day 1 and 8 or carboplatin AUC5 with vinorelbine intravenously 25mg/m² on day 1 and day 8 for a maximum of four cycles. Choice of platinum was based on the patient's renal function. Chemotherapy toxicity was generally manageable. Two patients discontinued treatment early due to toxicity, both after cycle 2 and dose adjustment was used to continue treatment in others. Fifteen patients (45%) experienced grade 2/3 neutropenia; there were two cases of grade 3 mucostitis, two cases of grade 3 fatigue and three cases of gastrointestinal toxicity (paralytic ileus). In addition, seven patients (21%) developed grade 3 thrombophlebitis and were switched to the oral formulation of vinorelbine to complete treatment. <h3>Interpretation</h3> Vinorelbine with platinum as adjuvant chemotherapy for NSCLC had manageable toxicity. Only two patients had to discontinue treatment due to toxicity. However, over a fifth of patients experienced serious intravenous complications and were switched to oral vinorelbine to complete treatment. We recommend using the oral formulation in this setting, which will help ease capacity constraints and is more comfortable for the patient.

A retrospective comparison of adjuvant chemotherapeutic regimens for non-small cell lung cancer (NSCLC): Paclitaxel plus carboplatin versus vinorelbine plus cisplatin

BackgroundAdjuvant chemotherapy with vinorelbine plus cisplatin (NP) has been demonstrated to increase overall survival in patients with stage II or IIIA non-small cell lung cancer (NSCLC). Although paclitaxel plus carboplatin (PC) failed to demonstrate efficacy in patients with stage IB NSCLC, an exploratory analysis suggested that patients with large tumors can benefit from adjuvant PC therapy. MethodsClinical outcomes of patients who received adjuvant NP or PC regimens after complete resection for their NSCLC were retrospectively compared. ResultsOf the 438 patients with completely resected NSCLC, 207 received PC and 231 patients received NP. The median relapse-free survival (RFS) was not significantly different, with 63.6 months for the PC group and 54.8 months for the NP group (P=.68). Overall survival also did not differ significantly between the two groups. The five-year overall survival rates were 73% (95% confidence interval (CI), 66–80%) in PC group and 71% (95% CI, 64–78%) in NP group (P=.71). In the subgroup analysis, RFS was comparable between the two groups across all variables. Analysis of the adverse events indicated that sensory neuropathy, alopecia, and myalgia are more frequent in the PC, while anemia, neutropenia, fatigue, anorexia, and vomiting are more common in the NP. ConclusionAlthough the adverse event profiles were different, the efficacy was comparable between the PC and NP regimens as adjuvant chemotherapy for NSCLC. While there is lack of prospective data, our retrospective data suggest that PC regimen can be considered as adjuvant chemotherapy for resected NSCLC.

The role of lymphatic vascular invasion in the prognosis and determination of therapy in surgically resected non-small cell carcinoma of the lung.

7554 Background: Lymphatic-vascular invasion (LVI) is not currently considered in staging of non-small cell lung cancer (NSCLC). We assessed the impact of LVI on overall survival (OS), local/distant recurrence (LR/DR) and patterns of recurrence. Methods: 869 consecutive patients who underwent a definitive surgical resection ± adjuvant chemotherapy for NSCLC from 2000–2008 were qualified for analysis if they did not receive any adjuvant/neo-adjuvant radiotherapy, had at least three months of follow-up, and did not have a history of other cancers within 5 years. Tumors with LVI (N = 160) were compared to tumors without LVI (N = 705). LR/DR rates at 2,3, and 5 years were calculated by the methods of Kaplan-Meier. Association between LVI and OS and LR/DR were compared in the total population and in a propensity matched population (PS) by factors affecting OS and LR/DR (n=160 matched pairs). Results: OS, LR, and DR were significantly worse in patients with LVI in the total population and in the subset of patients matched by propensity score (Table). In the PS-matched pairs, LVI was associated with a greater number of N1 nodes involved, a longer length of stay, higher histologic grade, and higher T-stage. Patterns of local failure (P&lt;.001) but not distant failure (P=.11) differed between patients with and without LVI. Tumors with LVI were 3-fold more likely to recur in ipsilateral mediastinal nodes. In a subset analysis of tumors &lt; 4cm (n=121 PS matched pairs), LVI was also associated with higher LR, DR, a lower OS and a 4-fold risk of mediastinal nodal recurrence. Conclusions: Detection of LVI in resected NSCLC predicts aggressive biologic behavior and provides important prognostic information. LVI may help identify high-risk cohorts within discreet TNM stages who could benefit from adjuvant therapies. [Table: see text]

Utilization and impact of adjuvant chemotherapy (AC) in surgically resected stages I-III non-small cell lung cancer (NSCLC).

7538 Background: Clinical trials demonstrating improved survival with AC for stages I-III NSCLC are limited in their applicability to broader populations. We sought to describe the pattern of AC use and its correlation with survival in the population-based VA system. Methods: We conducted a retrospective analysis of pts with stages I-III NSCLC in the VA Central Cancer Registry. Descriptive statistics were used to examine patterns of AC use over an 8 yr period and to obtain survival rates associated with use of AC. Chi-square was used to compare distributions. Results: Among 28,173 pts with stages I-III NSCLC in 2001-2008, 10,043 had surgical resection. The proportion receiving AC was 9% (stage I), 34% (II), and 40% (III). Receipt of AC increased for each stage, with the greatest increase observed in stage II (2001-03: 12%; 2004-05: 41%; 2006-08: 50%). About 90% received a platinum agent; among these carboplatin was most common (77%) but by 2008 43% received cisplatin. For stages II and III in 2001-2003, the 3-year survival rate was similar irrespective of AC use. In latter time periods, survival rates were significantly higher for stage II AC pts (2004-2005: 53 vs 43%, p=0.03; 2006-2008: 58 vs 46%, p=0.001). Stage III AC pt diagnosed in 2006-2008 had a higher 3-yr survival (52 vs 36%, p&lt;0.001). For all stages and years combined, use of cisplatin yielded a better 3-yr survival rate compared to carboplatin (62% vs 55%; p=0.01). 3-yr survival for stage I, II, and III, regardless of AC, increased over time (stage I: 60, 64, and 69%; stage II: 44, 47, 52%; stage III: 33, 40, and 44%). The fraction of lung cancer pts diagnosed at each stage during the 3 time periods was not significantly different. Conclusions: This retrospective study suggests a significant increase in use of AC for NSCLC in the VA, though half of surgically treated pts with stage II and III did not receive AC in 2006-2008. By univariate analysis, AC use is associated with a significantly better 3-yr survival for resected stage II and III NSCLC and the stage-specific 3-year survival for all pts improved over time in association with increasing use of AC. Cisplatin is associated with better survival compared to carboplatin. Multivariate analysis is planned.

A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non–Small Cell Lung Cancer Patients

Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non-small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC. An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC. Using a cohort of 442 stage I to III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set that robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, and RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (n = 90 and 176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: HR = 0.34, P = 0.017; JBR.10 clinical trial data: HR = 0.36, P = 0.038), whereas the predicted nonbenefit group showed no survival benefit for 2 datasets (HR = 0.80, P = 0.70; HR = 0.91, P = 0.82). This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non-small cell lung cancer will have a survival benefit with ACT.

High Serum CEA and CYFRA21-1 Levels after a Two-Cycle Adjuvant Chemotherapy for NSCLC: Possible Poor Prognostic Factors.

ObjectiveThe aim of this study was to test whether carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA21-1) can be used as a prognostic factor for non-small-cell lung cancer (NSCLC) after two cycles of adjuvant chemotherapy in NSCLC patients.MethodsA total of 169 patients underwent at least two cycles of adjuvant chemotherapy. The serum levels of CEA and CYFRA21-1 were recorded after the second cycle of chemotherapy, and the patient follow-up was conducted. Overall survival (OS) and disease-free survival (DFS) were used as the primary endpoint and the secondary endpoint, respectively.ResultsThe high levels of CEA and CYFRA21-1 after two cycles of adjuvant chemotherapy were poor prognostic factors for OS, with risk ratios (RR) of 2.003 and 1.702, respectively. A high CEA level was a poor prognostic factor (RR 1.152) for DFS. The median survival time (MST) of the high CEA level group was 26 months, whereas that of the normal group was 61 months (P<0.0001). The median DFS time of the high CEA group and the normal group was 34 and 53 months, respectively (P<0.0001). The MST of the high CYFRA21-1 group and the normal group was 43 and 56 months, respectively (P<0.0001).ConclusionsThe high serum levels of CEA or CYFRA21-1 after two cycles of adjuvant chemotherapy are poor prognostic factors for NSCLC patients.

Role of adjuvant chemotherapy after pneumonectomy for non-small cell lung cancer

Adjuvant chemotherapy is used as an alternative treatment for non-small cell lung cancer (NSCLC); however, the efficiency of post-pneumonectomy adjuvant chemotherapy in NSCLC has not been clarified. In the present study, patients who benefited from adjuvant chemotherapy with TP/NP/GP were identified. A total of 217 patients who underwent pneumonectomy were identified in this study. Of these, 87 underwent pneumonectomy combined with adjuvant chemotherapy (TP/NP/GP regimen) and 130 underwent pneumonectomy only in the initial management. The primary endpoint of the present study was overall survival. Actuarial survival analysis was conducted using the Kaplan-Meier method. Postoperative adjuvant chemotherapy significantly improved the survival rate of patients who underwent left pneumonectomy and in patients with a preoperative forced expiratory volume in 1 sec (FEV1) greater than or equal to 21. Age had no effect on the survival rate of patients with or without postoperative adjuvant therapy. Post-pneumonectomy adjuvant chemotherapy is an efficient therapy in NSCLC for patients with preoperative FEV1 greater than or equal to 21 or who received left pneumonectomy.

Factors associated with referral to medical oncology (MO) and subsequent use of adjuvant chemotherapy (ACT) among patients with resected non-small cell lung cancer (NSCLC): A population-based study.

1583 Background: ACT for NSCLC is associated with improved survival in the general population but may be underutilized. Underutilization may relate to lack of referral from surgeon to MO, MO not offering ACT, or patient declining ACT. Here we explore factors associated with referral to MO and use of ACT among patients with resected NSCLC in Ontario Canada. Methods: The Ontario Cancer Registry was used to identify all incident cases of NSCLC diagnosed in Ontario 2004-2006. We linked electronic records of treatment to identify surgery, ACT, and MO consultation. Co-morbidity was classified using the Charlson Comorbidity Index modified for administrative data. A multivariate logistic regression model was used to evaluate factors associated with referral to MO and use of ACT. Results: 3354 cases of NSCLC were resected in Ontario 2004-2006, 1830 (55%) were seen post-operatively by MO and 1032 (31%) were treated with ACT. Cases younger than 70 were more likely to have MO consultation (age 60-69 OR 1.6; 50-59 OR 2.3; 20-49 OR 2.2, p&lt;0.001) as were cases with stage II/III (ORs 2.7 and 2.0, p&lt;0.01) compared to stage I disease. There was substantial geographic variation in the proportion of surgical cases referred to MO (range 32-88%, p&lt;0.001). Among cases seen by MO, patients younger than 70 were more likely to have ACT (age 60-69 OR 3.1; 50-59 OR 4.7; 20-49 OR 6.7, p&lt;0.001) as were cases with stage II/III (ORs 2.7 and 3.0, p&lt;0.001) compared to stage I disease. Less co-morbidity (OR 2.1, p=0.02) and shorter post-operative stay (OR 1.4, p=0.001) were also associated with use of ACT. Among cases seen by MO, there was some geographic variation (range 46-63%, p&lt;0.001) in rates of ACT utilization. Conclusions: The upstream decision to refer to MO is associated with age and stage of disease and these factors have an even greater effect on ACT utilization once patients are seen by MO. While co-morbidity and post-operative length of stay are not associated with referral to MO, they are associated with use of ACT among cases seen by MO. There is substantial geographic variation in referral patterns to MO and less variation in ACT utilization once patients are seen by MO.

Impact of increased use of adjuvant chemotherapy in non-small cell lung cancer: A population and economic assessment.

e16630 Background: Lung cancer confers a substantial burden on patients and healthcare systems. Among patients with resectable non-small cell lung cancer (NSCLC), adjuvant chemotherapy (AC) has improved survival, but uptake has been incomplete. To determine the impact of increased use of AC, microsimulations were undertaken using the Cancer Risk Management (CRM) model developed by Statistics Canada and the Canadian Partnership Against Cancer. Methods: The CRM model uses inputs from Canadian demographics, risk factors, direct healthcare costs, and clinical practice data to assess incremental life expectancy (LE), health-adjusted life expectancy (HALE), and cost from the perspective of the Canadian healthcare system. Sensitivity analysis examined rates of use of AC over a range of 0-100% in 10% increments. The baseline regimen tested was 4 cycles of cisplatin and vinorelbine (PV) assuming a 50% uptake with a hazard ratio (HR) of 0.68 for overall mortality. Sensitivity analysis with HR=0.74 was performed. Alternate regimens included cisplatin and etoposide (given for 3 or 4 cycles (PE3, PE4) and assessing a HR range of 0.95 to 0.68), gemcitabine with cisplatin (PG) or carboplatin (CG) (HR=0.68) and baseline PV plus bevacizumab q3 weeks to 1 year (EPB). Results: In the PV baseline scenario, LE was 76.2 years, HALE was 66.2 years and the lifetime cost per patient was $32,290. Adjuvant chemotherapy remained cost-effective under the sensitivity analysis (HR=0.74). Each 10% increase in the use of AC resulted in an average increase of 3.7 months in LE and 2.7 months in HALE, and a lifetime cost savings of up to $360 per patient. Compared with baseline PV, the PE regimen was not cost-effective, with the exception of PE3 assuming HR = 0.68. PG and CG were less cost-effective than PV, at an additional lifetime cost of $589 and $1023 per patient, respectively. The EPB scenario would be cost-effective at $100,000 per QALY compared to baseline PV if the survival HR=0.55. Conclusions: The CRM model suggests greater use of PV AC in NSCLC would improve LE and net healthcare costs, with other drug pairs being less cost-effective. The HR required for bevacizumab to be cost-effective will be difficult to achieve in current trials.

Adoption of Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer: A Population-Based Outcomes Study

Since 2004, several clinical trials have demonstrated that adjuvant chemotherapy (ACT) improves survival in patients with early-stage non-small-cell lung cancer (NSCLC). Here, we evaluate the uptake of ACT and its impact on outcomes in the general population of Ontario, Canada. All patients diagnosed with NSCLC in Ontario from 2001 to 2006 who underwent surgical resection (n = 6,304) were identified using the Ontario Cancer Registry. We linked electronic records of treatment to the registry. We described uptake of ACT and compared survival of all patients with surgically resected NSCLC diagnosed from 2001 to 2003 with patients diagnosed from 2004 to 2006. As a proxy measure of ACT-related toxicity, we evaluated hospitalizations within 6 months of surgery. Demographic, disease, and treatment-related characteristics did not differ between the 2001 to 2003 and 2004 to 2006 study cohorts. Over the study period, the proportion of patients receiving ACT increased from 7% (192 of 2,950 patients) to 31% (1,032 of 3,354 patients; P < .001). The proportion of patients admitted to hospital within 6 months of surgery remained stable and (36% in the 2001 to 2003 cohort and 37% in the 2004 to 2006 cohort). However, within 2 years of surgery, there was a 33% reduction in the proportion of patients admitted to hospital with metastatic disease (P < .001). During the study period, there was a substantial improvement in 4-year survival among surgically resected patients, from 52.5% (2001 to 2003) to 56.1% (2004 to 2006; P = .001). There has been a rapid uptake of ACT for NSCLC, which was not associated with an increased rate of hospitalization. The adoption of ACT was associated with a substantial improvement in overall survival, suggesting that the benefits seen in clinical trials are generalizable to the general population.

Adoption of adjuvant chemotherapy for non-small cell lung cancer: A population-based outcomes study.

7018 Background: Since 2004 several clinical trials have demonstrated that adjuvant chemotherapy (ACT) improves survival in patients with non-small cell lung cancer (NSCLC). Here we evaluate the uptake of ACT and its impact on outcomes in the general population of Ontario, Canada. Methods: All cases of NSCLC diagnosed in Ontario 2001-2006 who underwent surgical resection (N=6,311) were identified using the population-based Ontario Cancer Registry (OCR). The OCR captures diagnostic and demographic information on ∼98% of all incident cancer cases in Ontario. We linked electronic records of treatment to the registry. We described time trends in the uptake of ACT and compared hospitalizations and survival of all surgical patients diagnosed 2001-2003 with those diagnosed 2004-2006. Results: Demographic, disease, and treatment-related characteristics did not differ between the 2001-2003 and 2004-2006 cohorts. Over the study period the proportion of cases receiving ACT increased from 7% (192/2,953) to 31% (1,034/3,358, p<0.0001). In 2004-2006, ACT was used in 60% of cases with resected stage II/III disease. Among cases for which drug details were available, 82% of patients received cisplatin and 16% received carboplatin-based therapy. The proportion of cases admitted to hospital remained stable between 2001-2003 and 2004-2006: 36 and 37% within 6 months of surgery. However, within 2 years of surgery there was a 34% reduction in cases admitted to hospital with metastatic disease (p<0.0001). During the study period there was a substantial improvement in 4-year survival among all surgical cases from 52.5 to 56.1%, p=0.007. Younger age, less co-morbidity, shorter length of surgical hospital stay, more extensive surgery, stage II/III disease, and region where surgery was performed were independently associated with administration of ACT. Conclusions: There has been rapid uptake of ACT for NSCLC which is not associated with an increased rate of hospitalization. The adoption of ACT is associated with a substantial improvement in overall survival suggesting benefits seen in the relevant clinical trials are generalizable to the general population. Efforts to reduce underutilization of ACT in clinical practice are needed. No significant financial relationships to disclose.