Body ImagingImaging features of gastrointestinal toxicity in non-small cell lung cancer patients treated with erlotinib: A single institute 13-year experience
Introduction
The inhibition of epidermal growth factor receptors (EGFR)-bearing somatic mutations in the tyrosine kinase domain is an important molecular target in the treatment of a number of malignancies. As such, first generation tyrosine kinase inhibitors like erlotinib have been adopted as the standard of care in the treatment of EGFR mutation-positive advanced non-small cell lung carcinoma (NSCLC) and pancreatic adenocarcinoma [[1], [2], [3], [4]].
EGFR-inhibiting therapies are associated with adverse effects including rash, diarrhea, anorexia, fatigue, dyspnea, infection, vomiting, and pruritus [1]. Given the normal expression of EGFR throughout the gastrointestinal and integumentary systems, the most frequent toxicities related to erlotinib therapy include dermatitis and secretory diarrhea [5]. Typically occurring in the first four weeks of treatment, diarrhea is a bothersome side effect resulting in either dose reduction or treatment cessation in up to 10% of patients [[6], [7], [8]]. In erlotinib clinical trials, rates of grade I–II diarrhea and grade III–V diarrhea have ranged from 18 to 55% and 2 to 6%, respectively [1].
Although gastrointestinal toxicities (GTs) in erlotinib therapy are well-recognized, cross-sectional imaging is not a tool commonly used for GT evaluation. However, awareness of expected imaging findings on routine or staging imaging may allow for the early recognition and management of GTs, thereby minimizing dose reductions and therapy interruptions. Despite new third-generation EGFR-inhibitors with similar gastrointestinal effects gaining traction, there continues to be an absence of study on GT imaging in the literature [6,9]. This study aims to characterize the imaging features of erlotinib-related GT as well as to evaluate the corresponding clinical manifestations and management in patients with NSCLC.
Section snippets
Patient population and clinical findings
This single-center retrospective study received institutional review board approval, and the requirement for informed consent was waived. Two hundred consecutive patients diagnosed with NSCLC treated with erlotinib from 2005 to 2018 were identified. Within this group, 157 patients met our inclusion criteria of: 1) patients treated with erlotinib for NSCLC that developed clinical signs and symptoms of gastrointestinal toxicity based on the National Cancer Institute Common Terminology Criteria
Results
A total of 81 out of the 157 reviewed patients had clinical evidence of GT. A total of 24 patients had radiologic evidence of GT regardless of clinical status following the exclusion of 3 patients for incomplete documentation and 1 patient for a history of active Crohn's disease with positive colonoscopy. Of those 24 patients, 15 patients had no further testing, and 9 patients had negative testing in the form of stool culture, Clostridium difficile toxin, and/or stool ova and parasite testing.
Discussion
To date, there are almost a dozen EGFR-inhibitors approved for multiple cancers including NSCLC, head and neck squamous cell, colorectal, and pancreatic cancers [16,17]. These therapies have a high risk for GT resulting in unnecessary treatment delay or cessation [18]. In GT diagnosis, cross-sectional imaging performed for staging or other purposes could embody a useful adjunct besides more invasive measures like colonoscopy or biopsy. A similar role of imaging has previously been substantiated
Conclusion
The increasing adoption of erlotinib and other third-generation EGFR inhibitors has made the identification of specific imaging patterns important for the timely management of treatment-related GTs. Erlotinib-associated GT was identified in 15% patients with NSCLC in our study, indicating a correlation between radiological and clinical findings. Fluid-filled colon and segmental involvement were the most common imaging manifestations.
Declaration of competing interest
None.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
References (30)
- et al.
Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial
Lancet Oncol
(2019) - et al.
Erlotinib in advanced non-small cell lung cancer: efficacy and safety findings of the global phase IV Tarceva Lung Cancer Survival Treatment study
J Thorac Oncol
(2010) - et al.
Third generation EGFR TKIs in EGFR-mutated NSCLC: where are we now and where are we going
Crit Rev Oncol Hematol
(2017) - et al.
MDCT of acute colitis in adults: an update in current imaging features
Diag Interv Imaging
(2015) - et al.
Third generation EGFR TKIs: current data and future directions
Mol Cancer
(2018) - et al.
Diarrhea with epidermal growth factor tyrosine kinase inhibitors in cancer patients: a meta-analysis of randomized controlled trials
Crit Rev Oncol Hematol
(2019) - et al.
Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial
Lancet Oncol
(2019) - et al.
Phase I trial of oxaliplatin, infusional 5-fluorouracil, and leucovorin (FOLFOX4) with erlotinib and bevacizumab in colorectal cancer
Clin Colorectal Cancer
(2010) - et al.
Gastrointestinal perforations in patients treated with erlotinib: a report of two cases with fatal outcome and literature review
Lung Cancer
(2016) - et al.
Multimodal imaging of fibrosing mesenteric tuberculosis
Radiol Case Rep
(2019)