Although radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and theoretical advantages of avoiding functional lung during radiotherapy, to our knowledge this premise has never been tested via a prospective randomized clinical trial.

The management of advanced non-small-cell lung cancer (a-nsclc) is currently undergoing one of its rare paradigm shifts. Just as the nihilism of the 1970s gave way to the empiricism of the 1980s and 1990s, so the current decade has seen the first truly rational therapies based on informed design. In addition, molecular markers and traditional parameters can now be combined to provide a framework of knowledge that will guide the application of not just the new therapies, but also the older ones that remain effective. This framework—as important a component of the rational paradigm as the new drugs themselves are—is necessary to decide who should and, crucially, who should not receive the various components of this rapidly expanding armamentarium. Here, I have provided a historical overview of the drug treatment of a-nsclc, a mini-review of important new data, and an integrative approach that tries to ensure that patients receive the optimal treatment choice at the appropriate time. The speed at which new knowledge now arrives, coupled with the persistent high level of unmet medical need, suggests that the traditional pace of evidence-based review needs to be accelerated. Indeed, the increased scope for personalized management constitutes something of a challenge to “business as usual” evidence-based medicine. As a result, substantial investment on the part of payers, which may or may not be possible, will be required. In the meantime, some patients may wish and may be financially able to take advantage of modern developments before they have been fully digested by the public-payer system. Responsive clinicians face difficult tradeoffs as they try to balance the pros and cons of early adoption versus excessive conservatism. The present article is my personal view of how to navigate these waters, and although it is written especially for patients who like to be the captain of their own ship, there is good reason to believe that all patients will eventually be managed by similar, if not identical, means. Nonetheless, the recommendations herein should not be construed as appropriately reviewed provincial or national guidelines. Finally, if appropriate, a clinical trial should always be offered.

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan–Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively.

The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is evolving, as is an understanding of predictive biomarkers for tumour response in non-small-cell lung cancer (NSCLC). In this report, we describe a case of rapidly progressing, borderline-resectable, clinical stage IIIA (micro) papillary adenocarcinoma in a 78-year-old woman who experienced a profound response to neoadjuvant erlotinib without short-term toxicity. On EGFR mutation testing, this patient had an uncommon activating point mutation at L861Q in exon 21. Her response permitted successful surgical resection with negative margins and avoidance of chemoradiation, which she was deemed too frail to tolerate. Our case addresses unique management issues such as preoperative testing for EGFR mutation, utility of histology in predicting EGFR mutations, and use of EGFR-TKIs pre- and postoperatively for potentially resectable NSCLC.