Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.

Erkan Topkan,Yurday Ozdemir,Huseyin Mertsoylu,Ozan C Guler,Berrin Pehlivan,Alper Findikcioglu,Berna A Yildirim,Ozgur Ozyilkan,Ali A Besen,Ugur Selek

doi:10.1155/2018/4518935

Abstract

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/TS), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed ≤12 months of C-CRT. All FPHs were diagnosed in patients with TC (N=60): group-specific FPH incidence: 21.6%. TC (P<0.001) was the unique independent factor associated with higher FPH risk in multivariate analysis. Further analysis limited to TC patients exhibited the RCV>0.14 (37.5% versus 11.1% for RCV≤0.14; P<0.001), major RCS group [31.0% versus 19.0% for minor versus 0% for minimum RCS; P=0.008), and baseline hemoptysis (26.3% versus 13.6% for no hemoptysis; P=0.009) as the independent risk factors for higher FPH incidence. FPH was an infrequent (2.6%) complication of C-CRT in stage 3B/C SqCLC patients, but its incidence increased to 37.5% in patients presenting with TC and RCV>0.14. Diagnosis of >90% FPHs ≤12 months of C-CRT stresses the importance of close and careful follow-up of high-risk patients after C-CRT for multidisciplinary discussion of possible invasive preventive measures.

Highlights

Survival advantage exhibited by phase III randomized controlled trials set the concurrent chemoradiotherapy (C-CRT) as the standard treatment decision for inoperable stage III non-small-cell lung cancer (NSCLC) patients [1, 2]
An institutional database search was performed to identify all patients who underwent C-CRT between January 2007 and December 2014 for stages 3B/C squamous-cell lung cancers (SqCLC) according to American Joint Committee on Cancer (8th ed.) and met the following criteria: age of 18-80 years; available diagnostic chest computerized tomography (CT); 18F-fluorodeoxyglucose positron emission CT (PET-CT); Eastern Cooperative Oncology Group (ECOG) performance of 0-1; available pre-C-CRT brain magnetic resonance images, treatment charts, and hospital computerized datasets of RT and chemotherapy; at least 1 concurrent chemotherapy cycle administered; and no prior RT/chemotherapy histories
Present database search identified a total of 505 stage IIIB/C SqCLC patients who met the protocol inclusion criteria

Summary

Introduction

Survival advantage exhibited by phase III randomized controlled trials set the concurrent chemoradiotherapy (C-CRT) as the standard treatment decision for inoperable stage III non-small-cell lung cancer (NSCLC) patients [1, 2]. The established superiority of C-CRT over RT alone and sequential- or split-course CRT modalities undoubtedly came at the cost of notably increased normal tissue complication rates, the RT-induced esophagitis and pneumonitis [3, 4]. Another serious but underestimated complication of RT or C-CRT in NSCLC is fatal pulmonary hemorrhage (FPH) with an incidence rate of 1.5-3.5% for all patients [5, 6]. Decreasing the statistical power, the SqCLC cohort that has the highest risk for TC and FPH incidences constituted only 34.7% of the entire study population

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