Other studies have reported on the
Other studies have reported on the prognostic significance of the LCSS ASBI and patient-reported outcomes in general [, , , , , ]. From a meta-analysis of 30 randomized controlled trials of 11 different tumor types from the European Organization for Research and Treatment of Cancer, select health-related QoL parameters of physical functioning, appetite loss, and pain provided significant prognostic value in addition to sociodemographic and clinical variables . Prognostic outcomes specific to the LCSS have been reported in a phase III trial of malignant pleural mesothelioma. Again, patient-reported symptom burden was dichotomized by LSB and HSB as measured by ASBI. In the multivariable analysis adjusted for demographic/clinical variables, the ASBI was prognostic because patients with LSB (ASBI < 25) had longer OS than those with HSB (ASBI ≥ 25) .
In patients with nonsquamous advanced NSCLC, Obasaju et al. used this Midostaurin (PKC412) same approach to demonstrate how baseline ASBI and ECOG PS may better inform clinicians to identify the appropriate patients for using maintenance pemetrexed . Whereas patients with LSB (ASBI < 25) had improved PFS and OS after treatment with maintenance pemetrexed, patients with HSB (ASBI ≥ 25) demonstrated greater difficulty in receiving benefit and only had a small improvement in PFS and no improvement in OS . Obasaju et al. also substantiated through multivariable analyses that ECOG PS and ASBI were independent predictors of this differential response . In our study, patients treated with ramucirumab-docetaxel with baseline HSB had significant OS and PFS benefits, and patients treated with ramucirumab-docetaxel with baseline LSB had a significant PFS benefit. Median OS in patients with LSB was just over 12 months in both treatment arms, which is higher than that observed for the REVEL ITT population, but not significantly different between treatment arms in this analysis. However, these results should be interpreted with caution due to the exploratory nature of these analyses. Determining the prognostic value of clinician-reported performance status was not an objective in this study; however, similar to the populations analyzed by Obasaju et al., REVEL patients with HSB were more likely to have ECOG PS 1 when compared with patients with baseline LSB (Table 2; 77% vs 57%). Thus, it is possible that both baseline ASBI lung cancer symptom data and clinician-reported performance status may be used as complementary tools, in addition to efficacy and safety data, to better inform clinical decision making for patients with advanced NSCLC . The consistency of the literature regarding the prognostic value of symptoms at the common cut-point suggests a level of reliability and robustness from these REVEL post hoc ASBI-defined subgroups. The relative similarity of the PFS and OS HRs with those determined from the aggressive disease subgroups previously reported from the REVEL ITT population suggests a consistency of the effect of ramucirumab plus docetaxel on aggressive disease subgroups [7,8,11].
Funding This work was supported by Eli Lilly and Company.
Role of funding source
Conflict of interest statement
Introduction The 2015 World Health Organization (WHO) classification introduced tumor spread through air spaces (STAS) officially as a new tumor invasion characteristic and presented it as a new exclusion criterion for minimally invasive adenocarcinoma . Tumor STAS is defined as tumor cells within the air spaces in the lung parenchyma beyond the edge of the main tumor and is composed of three morphological patterns: single cells, micropapillary structures, and solid nests or tumor islands . Although it remains controversial whether tumor STAS is caused by an in vivo effect or an artifact of cutting through a tumor with a knife [3,4], tumor STAS has recently been described as a novel pattern of tumor invasion that differs from traditional invasion characteristics, such as the presence of nonlepidic patterns and the infiltration of stroma and blood vessels into structures such as the visceral pleura . Regarding the association between tumor STAS and prognosis, tumor STAS was reported as a significant independent risk factor associated with reduced recurrence-free survival (RFS) and overall survival (OS) in patients with lung adenocarcinoma of any stage following surgical resection [2,, , , ]. Furthermore, an unfavorable prognostic impact of STAS has also been reported in squamous cell carcinoma [, , ] and lung pleomorphic carcinoma .