br We evaluated time based events
We evaluated time-based events of relapse in stage III NSCLC patients after definitive CRT to characterize posttreatment intervals at high risk for relapse. We also analyzed whether symptomatic presentation versus identification on surveillance imaging influenced patient outcomes after initial relapse.
Patients and Methods
After institutional review board approval, we performed a retro-spective review of a prospectively collected clinical database of pa-tients with pathologically confirmed unresectable locally advanced NSCLC treated with definitive CRT from 2005 through 2014. Over the span of this study, mediastinal staging was performed using combinations of imaging, endobronchial ultrasound, and mediastinoscopy or mediastinotomy. Patients were excluded if they presented with metastatic disease or had prior oncologic interven-tion for lung cancer.
Patient, tumor, treatment, and outcome data were abstracted from the electronic medical charts. Particularly, patient de-mographics, Eastern Cooperative Oncology Group (ECOG) per-formance status (PS), disease stage according to American Joint Committee on Cancer (AJCC; 7th edition) staging for NSCLC,13 smoking status during treatment, and total pack-years were evaluated.
Regarding treatment, all patients received concurrent platinum-based chemotherapy and RT delivered with 70 Gy in 35 fractions utilizing 3D-conformal RT or intensity-modulated RT planning, which has been the standard at our institution since 2005. Beginning in 2006, elective nodal irradiation was not part of the treatment approach. Additionally, treatment for all patients was planned with 4D-CT imaging, and strict normal tissue constraints were used.
All patients underwent routine posttreatment surveillance with physical examination, comprehensive metabolic panels, and imaging studies. Over the course of this analysis, the method of posttreat-ment surveillance was heterogeneous, although the majority of treating physicians followed our institutional standards and sched-uled a follow-up evaluation every 3 months with CT or 18-fluoro-deoxy-glucose positron emission tomography (18FDG-PET)/CT imaging for the first 2 to 3 years and then annually thereafter. 18FDG-PET/CT was used to confirm suspicious findings on CT imaging. Magnetic resonance imaging (MRI) α-CEHC scans with and without contrast were obtained when patient symptoms warranted
further investigation. All posttreatment CT, 18FDG-PET/CT im-ages, or MRI brain scans were evaluated for first event of disease recurrence and compared to the radiologists’ formal assessment. Of note, routine CT chest imaging at our institution extends to the level of the adrenal glands.
Assessment of Relapse Events
The events of local relapse (LR), regional relapse (RR), and distant relapse (DR) were evaluated from the conclusion of RT to the first evidence of relapse on posttreatment imaging; patients with multisite relapses were categorized by the most advanced site. Relapse events were defined as follows: LR indicated relapse within the RT field (overlapping the planning target volume); RR indicated relapse in hilar/mediastinal lymph nodes (defined in the 7th edition of AJCC staging for NSCLC) outside the RT field; and DR indi-cated any relapse in the contralateral lung parenchyma/pleura or outside the thorax. A major limitation to surveillance imaging after RT is the poor discriminatory ability of defining residual versus recurrent versus posttreatment changes in the lung.14 For this reason, final designation of a relapse event required an additional oncologic intervention in the patients’ care plans in addition to imaging findings. No distinction was made between a second pri-mary tumor and recurrence.
Patients who experienced relapse were further stratified by detection of relapse on the basis of scheduled surveillance imaging or presentation with relapse-related symptoms. Examples of relapse-related symptomology included new-onset hemoptysis, increased shortness of breath or dyspnea, chest pain, nonthoracic pain related to metastatic disease, or neurologic symptoms resulting from brain metastases.
A cumulative incidence table was generated by assigning relapse events into graded posttreatment intervals in the following manner: relapses within to 12 months were grouped into 3-month intervals; relapse events from > 12 to 24 months were grouped into 4-month intervals; and relapses > 24 months were grouped into 6-month intervals. All relapses > 48 months were within their own grouping. The Kaplan-Meier method was used to estimate time to relapse and OS between analyzed cohorts, and results were compared by log-rank test. Univariate analysis with chi-square comparison was used to assess for the significance of clinical vari-ables in defined end points. All tests were 2 sided, and an a (type I) error < 0.05 was considered to be statistically significant. Analyses were performed by SPSS 24.0 (IBM, Chicago, IL).