ReviewPost-chemotherapy and targeted therapy imaging of the chest in lung cancer
Introduction
Non-small-cell lung cancer (NSCLC) is frequently diagnosed when it is not amenable to local therapies. Thus, systemic agents are the mainstay of therapy for many patients. In recent years, the approach to treating advanced NSCLC has evolved from the empirical administration of cytotoxic chemotherapy, typically platinum doublets, to a more personalised strategy based on detailed molecular characterisation and PD-L1 protein expression of the tumour in combination with other clinical information such as histological subtype and clinical stage.1 Screening for a wide variety of genomic tumour aberrations has become increasingly common in the assessment of patients with NSCLC. When no such targets are identified, chemotherapy and/or immunotherapy may be administered; however, when specific genetic mutations, known as oncogenic driver mutations, are identified, targeted therapies directed at the products of these mutations can be administered2; however, effective molecularly targeted therapies have disproportionately impacted adenocarcinomas compared to squamous cell carcinomas, and never or light smokers compared to heavy smokers, and only a fraction of genomic tumour aberrations are currently targetable.3 Additionally, despite initial impressive anti-tumour activity, the use of targeted therapies in oncogene-addicted NSCLC subgroups is invariably associated with the development of acquired resistance through multiple mechanisms. To improve response rates, duration of response, overcome resistance, and to target additional resistance mutations, newer generations of therapies and combination strategies are heavily investigated.
The objective response of tumours treated with cytotoxic chemotherapeutic agents and those managed with targeted medical therapies can differ based on standardised criteria, such as Response Criteria in Solid Tumours (RECIST), and variations in these imaging patterns should be recognised and taken into account on follow-up imaging. Numerous therapy-related side effects have been described with both chemotherapy and targeted agents and are important for radiologists to recognise and communicate to the treating health care provider. In this article, we review the current state of medical oncology, imaging characteristics of mutations, pitfalls in response assessments and the imaging of complications.
Section snippets
Chemotherapy
Until 2016, chemotherapy combinations of cisplatin or carboplatin with paclitaxel, or docetaxel, or pemetrexed (non-squamous only), or gemcitabine, or nab-paclitaxel were standard of care first-line therapy options. When compared to supportive care, chemotherapy had been associated with a modest improvement in median overall survival (1.5 months) and significant gains in symptom control.4, 5, 6, 7, 8 A deeper understanding of tumour-immune interactions and development of immune checkpoint
Imaging of oncogenic driver mutations
Several studies have compared the imaging features of NSCLC with different oncogenic driver mutations; however, it is important to note that these manifestations are non-specific, and the diagnosis of lung cancer and molecular characterisation of the disease must be performed from analysis of tissue obtained through biopsy or surgical resection. In one study, NSCLCs without EGFR mutations tended to be larger, more likely to contain calcification, and more irregular in shape and contour than
Drug resistance and implications
Most patients with NSCLC and EGFR-activating mutations demonstrate a significant initial response to treatment with TKIs; however, resistance is typically acquired after 9–18 months of therapy.40 This drug resistance is usually observed in EGFR-positive patients with the threonine 790 to methionine (T790M) secondary mutation in exon 20 of EGFR, which is detected in approximately 50% of patients treated with first-generation EGFR-TKIs. Acquired resistance may also be due to other mechanisms,
Response assessment
The response of tumours to cytotoxic therapies such as chemotherapeutic agents has traditionally been assessed by response criteria such as the World Health Organization (WHO) criteria and RECIST. Although the WHO criteria were the first standardised response criteria used widely, several inherent limitations led to its replacement by RECIST 1.0, which was developed by an international group of investigators to improve upon the previous criteria. Revised RECIST criteria, termed RECIST 1.1, were
Chemotherapy
As modern approaches to treating patients with advanced NSCLC may involve chemotherapy, targeted therapy, and/or immunotherapy, when complications arise, attributing toxicity to a specific drug may be difficult; however, side effects in various organ systems that may be due to specific chemotherapeutic agents have been described. For example, in the lungs, gemcitabine and paclitaxel can result in interstitial opacities and gemcitabine may also cause non-cardiogenic pulmonary oedema.61
Conclusion
The treatment of advanced NSCLC continues to evolve and become more personalised. The modern-day approach involves the consideration of molecular data in combination with histological subtype and clinical stage. In the setting of specific oncogenic driver mutations, evidence demonstrates that those patients derive the most benefit from treatment regimens tailored to that biomarker. In those patients without a driver mutation, therapy may involve chemotherapy and/or immunotherapy. As these
Conflict of interest
The authors declare no conflict of interest.
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