Elsevier

Clinical Imaging

Volume 68, December 2020, Pages 210-217
Clinical Imaging

Body Imaging
Imaging features of gastrointestinal toxicity in non-small cell lung cancer patients treated with erlotinib: A single institute 13-year experience

https://doi.org/10.1016/j.clinimag.2020.08.017Get rights and content

Highlights

  • Erlotinib-related colitis can be radiologically identified in NSCLC patients.

  • The most common imaging finding was fluid-filled bowel.

  • Segmental involvement of the colon was the most common pattern.

Abstract

Objectives

To investigate the imaging features of erlotinib-associated gastrointestinal toxicity (GT) in patients with non-small cell lung cancer (NSCLC).

Materials and methods

The electronic medical records of 157 patients with NSCLC who received erlotinib between 2005 and 2018 were retrospectively reviewed to identify patients with GT. Clinical and radiologic evidence of erlotinib-associated GT was evaluated. Imaging findings were cross-referenced with clinical presentation, management, and outcomes.

Results

24 (15%) patients (16 women; median age, 68 years) with radiologic evidence of GT were identified. The median time to detection of GT on imaging was 4.5 months (range: 0–58 months). 3/24 (12.5%) patients had no clinical symptoms, but GT was radiologically identified. Erlotinib-associated GT manifested in the large bowel in either a diffuse (42%) or segmental (58%) pattern. The most common imaging finding was fluid-filled bowel (23/24, 96%).

Conclusion

Erlotinib-associated GT was identified in 15% patients with NSCLC. Fluid-filled colon and segmental involvement were the most common imaging manifestations.

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)

  • J.W. Wachsmann et al.

    Immune-mediated disease in ipilimumab immunotherapy of melanoma with FDG PET-CT

    Acad Radiol

    (2017)
  • M.H. Cohen et al.

    FDA drug approval summary: erlotinib (Tarceva) tablets

    Oncologist

    (2005)
  • Tarceva (erlotinib) label

    (2010)
  • Z. Markóczy et al.

    Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial

    BMC Cancer

    (2018)
  • Y. Kim et al.

    Potentiation of calcium-activated chloride secretion and barrier dysfunction may underlie EGF receptor tyrosine kinase inhibitor-induced diarrhea

    Physiol Rep

    (2020)
  • Cited by (0)

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