Although promising, these results cannot be directly extendend to Western countries whereas Uracil-Tegafur has not been reliably tested so far [32]. Conducting prospective trials restricted (and powered) for stage IB patients would be the only way to unravel this issue. However, the prohibitively large sample
size required undermines the feasibility of such an approach [33]. In addition, other (molecular) prognostic factors are needed to identify #selleck chemicals llc randurls[1|1|,|CHEM1|]# among these borderline patients, those at higher risk. Nonetheless, the worse prognosis observed with increasing T size has been recognized in the VII TNM edition. T2 was divided into T2a (3-5 cm) and T2b (5 -7 cm), with a OS of 58 and 49% at 5 years, respectively (p < .0001) [34]; T2bN0 was upstaged to stage IIA [35]. Correlation with the new staging system failed to validate the 5 cm cut-off in the 9-years update of CALGB 9633, showing a trend towards a significant benefit for adjuvant treatment for patients with tumors > 7 cm [HR = 0.53; p = .051] [31], although interaction should be investigated. Recent studies investigated further pathological prognostic factors for resected VII edition-stage IB (T2aN0), such as the presence of microscopic vascular invasion [36] or intratumoral vascular and/or visceral pleural invasion [37]. Although promising, BB-94 nmr these results require a prospective external validation. Finally, the question of ‘which stage
IB deserves adjuvant treatment’ remains still unanswered. Size may represent a selection criterion, while awaiting for more powerful pathological and biological predictors. Post Operative Radiotherapy (PORT): has the 1998 sentence expired? Few and underpowered randomized clinical trials exploring the role of PORT in patients
after resection of NSCLC have been conducted from the early 90s, with inconclusive results. In order to look for a small survival benefit, the individual patients’ data PORT meta-analysis Cyclic nucleotide phosphodiesterase (initially including 9 randomized clinical trials) was performed [38]. The last update (11 trials, 2343 patients) showed a statistically significant detrimental effect on OS for patients receiving PORT (HR = 1.18; 95% CI 1.07-1.31; p = .0001; 5% 2-years absolute difference). Similar conclusions were reached for local and distant Recurrence-Free Survival (RFS) (HR = 1.12, p = .03 and HR = 1.13, p = .02, respectively). A highly significant interaction according to stage and nodal status was detected, indicating a substantial absence of PORT effect in stage III or N2 patients (HR 0.99 and 0.97), restricting the detrimental difference to lower stage disease [39]. Abandoned techniques, such as Cobalt-60, large irradiation fields (including the entire mediastinum), different total doses (30-60 Gy), unconventional daily fractions (up to 2,6-3 Gy) represent some of the limitations of the trials included in the PORT meta-analysis, thus undermining its validity in a modern setting.