A Population-Based Study of Outcomes in Surgically Resected T3N0 Non-Small Cell Lung Cancer in The Netherlands, Defined Using TNM-7 and TNM-8; Justification of Changes and an Argument to Incorporate Histology in the Staging Algorithm.

OBJECTIVE: The objective was to study outcomes in patients in a population registry who were surgically staged as having pT3N0 NSCLC according to the seventh and eighth editions of the TNM staging classification. METHODS: Details of patients who underwent surgery for NSCLC staged as pT3N0M0 from 2010 to 2013 on the basis of the seventh edition of the TNM classification were retrieved from the Netherlands Comprehensive Cancer Organization. These data were next matched with corresponding pathology data from a nationwide registry. Patients were categorized into four major pT3 subgroups as follows: those with a tumor diameter more than 7 cm, those with separate tumor nodules in the same lobe (two or more nodules), those with parietal pleural invasion, and a mixed group (consisting mainly of those with a tumor diameter larger than 7 cm combined with parietal pleural invasion). RESULTS: A total of 683 patients were eligible for analysis. The 3- and 5-year overall survival (OS) rates for the subtype tumor diameter larger than 7 cm were 59.9% and 47.2%, respectively, and were comparable to the rates for the subtype with pleural invasion (50.4% and 45.3%), respectively. The mixed group had worse 3- and 5-year OS rates (37.5% and 28.7%, respectively), which were comparable to the outcomes for TNM eighth edition-staged IIIB and pT4 cases in the International Association for the Study of Lung Cancer database. For the subtype two or more nodules, the 3- and 5-year OS rates were 70.6% and 62.8%, respectively, with patients with adenocarcinoma showing a significantly better OS than did patients with squamous cell carcinoma: a 5-year OS rate of 65.1% versus 47.2%, respectively (p < 0.001), suggesting that the prognosis for the adenocarcinoma subgroup may be comparable to that for the pT2 category, whereas squamous cell carcinoma nodules can remain pT3. CONCLUSION: This population analysis of overall survival rate by pT3N0 subcategory for NSCLC suggests that histologic type is a relevant descriptor in the category two or more nodules. The findings do not support migration of the group with a tumor diameter larger than 7 cm to the category pT4in the eighth edition of the TNM classification, and they suggest that a combination of two pT3 descriptors (the mixed group) merits migration to pT4.

Measuring the population impact of introducing stereotactic ablative radiotherapy for stage I non-small cell lung cancer in Canada.

BACKGROUND: The Cancer Risk Management Model (CRMM) was used to estimate the health and economic impact of introducing stereotactic ablative radiotherapy (SABR) for stage I non-small cell lung cancer (NSCLC) in Canada. METHODS: The CRMM uses Monte Carlo microsimulation representative of all Canadians. Lung cancer outputs were previously validated internally (Statistics Canada) and externally (Canadian Cancer Registry). We updated costs using the Ontario schedule of fees and benefits or the consumer price index to calculate 2013 Canadian dollars, discounted at a 3% rate. The reference model assumed that for stage I NSCLC, 75% of patients undergo surgery (lobectomy, sublobar resection, or pneumonectomy), 12.5% undergo radiotherapy (RT), and 12.5% undergo best supportive care (BSC). SABR was introduced in 2008 as an alternative to sublobar resection, RT, and BSC at rates reflective of the literature. Incremental cost effectiveness ratios (ICERs) were calculated; a willingness-to-pay threshold of $100,000 (all amounts are in Canadian dollars) per quality-adjusted life-year (QALY) was used from the health care payer perspective. RESULTS: The total cost for 25,085 new cases of lung cancer in 2013 was calculated to be $608,002,599. Mean upfront costs for the 4,318 stage I cases were $7,646.98 for RT, $8,815.55 for SABR, $12,161.17 for sublobar resection, $16,266.12 for lobectomy, $22,940.59 for pneumonectomy, and $14,582.87 for BSC. SABR dominated (higher QALY, lower cost) RT, sublobar resection, and BSC. RT had lower initial costs than SABR that were offset by subsequent costs associated with recurrence. Lobectomy was cost effective when compared with SABR, with an ICER of $55,909.06. CONCLUSION: The use of SABR for NSCLC in Canada is projected to result in significant cost savings and survival gains.

Design of clinical trials of radiation combined with antiangiogenic therapy.

Clinical trials showing longer survival when chemotherapy is combined with antiangiogenic agents (AAs) have led to growing interest in designing combined modality protocols that exploit abnormalities in tumor vasculature. Approved agents include bevacizumab, a recombinant monoclonal antibody that binds to vascular endothelial growth factor, and two small molecule multitargeted tyrosine kinase inhibitors of angiogenesis (SU11248 and BAY-43-9006) that have been approved for therapy of renal cancer. Targeting tumor vasculature has a strong biological rationale in radiation therapy, and preclinical studies consistently show an increase in radiosensitization with combined treatment. Preclinical studies indicate that excessive damage to tumor vasculature can result in radioresistance in some situations, and early clinical data suggest that treatment sequencing may be important when combining AAs with radiation. Radiation itself appears to antagonize any hypoxia that can be induced by long-term administration of AAs. The optimal biological doses of AAs with radiotherapy are unknown, and surrogate markers of efficacy remain to be validated. Early clinical trials should therefore include studies designed to identify mechanisms of interaction and increases in tumor hypoxia. This review highlights preclinical and early clinical data that are relevant for clinical trial design. Optimal radiation planning and delivery is required to minimize the volume of irradiated normal organs and to establish safe dose-volume parameters for phase II-III clinical trials.