Treatment with single agent immune checkpoint inhibitors (ICIs) has tremendously changed second line therapy in NSCLC. However, there are still no reliable biomarkers predicting response and survival in this group of patients. PD-L1 revealed to be a correlating, but no perfect marker. Therefore, we sought to investigate in this prospective study, whether inflammation status and cytokine profile could serve as additional biomarkers guiding treatment decision for single agent ICIs in NSCLC. 29 stage IV NSCLC patients receiving single agent PD-1 checkpoint-inhibitor in second line were prospectively enrolled. Inflammatory scores and cytokine profiles (IL-6, IL-8, IL-10, IFN-γ and TNFα) have been obtained before treatment and at the time of the first staging. Cytokine profiles were correlated with response and survival. Patients with signs of pre-therapeutic inflammation (elevated, NLR, SII, IL-6, IL-8) showed significantly lower response to ICI treatment and reduced PFS. Contrary, elevated levels of IFN-γ revealed to characterize a subgroup of patients, who significantly benefits from ICI treatment. Furthermore, low systemic inflammation and high levels of IFN-γ characterized patients with long term-response to ICI treatment. Pre-therapeutic assessment of inflammation and cytokine profiles has the ability to predict response and survival in NSCLC patients treated with single agent ICIs.

Aims: Non-small cell lung cancer (NSCLC) patients with EGFR mutations do not respond well to checkpoint inhibitors. However, little is known about the activity of immunotherapy in NSCLC with other driver mutations. The increasing use of next-generation sequencing (NGS) leads to molecular findings that face the clinician with problems while choosing the best treatment. This study aims at analyzing response of NSCLC with driver mutations to immunotherapy. Patients and Methods: We retrospectively included 84 NSCLC patients diagnosed and treated at 2 German tertiary-care lung cancer centers using NGS and treatment with immunotherapy. Response to immunotherapy was analyzed in correlation to molecular findings. Results: 51 patients harbored at least 1 driver mutation. PIK3CA, EGFR, and STK11 mutations did not respond to immunotherapy. KRAS, TP53, and MET exon 14 skipping mutations responded well. One patient with NF-1 mutation showed durable response. Conclusions: Molecular testing may be of use in guiding treatment decision making in NSCLC.

Background: Generally, tyrosine kinase inhibitor (TKI) therapy is recommended in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) harbouring a classic epidermal growth factor receptor (EGFR) mutation. However, the response of patients with rare or complex EGFR mutations to TKI treatment is not predictable, nor is the prognosis for such patients. Objectives: In cases of rare or complex EGFR mutations, the right approach to therapy remains challenging. That is why we sought to analyse the characteristics as well as the prognosis and the response to TKI treatment of patients with rare or complex EGFR mutations. Patients and Methods: 343 NSCLC patients tested for EGFR mutation at a German lung cancer centre were analysed for age, gender, and smoking status as well as for the mutation status. For 12 patients with rare and complex mutations, response to TKI treatment was described. Results: 282 of all patients had a wild-type EGFR, whereas 61 harboured an EGFR mutation. 32 of these were classic mutations, followed by 16 rare and 7 complex mutations. EGFR mutations were significantly more frequent in women. Patients with rare or complex mutations were significantly more often smokers compared to those with classic EGFR mutations. Furthermore, rare and complex mutations were less responsive to TKI therapy. Conclusion: Patients with rare or complex EGFR mutations differ from those with classic mutations in terms of smoking status and response to TKIs. As these mutations may not respond well to TKI therapy, first-line TKIs should not be automatically chosen based on the sole presence of an EGFR mutation.

Background: Large language models (LLMs) such as ChatGPT (OpenAI) are increasingly discussed as potential tools for patient education in health care. In radiation oncology, where patients are often confronted with complex medical terminology and complex treatment plans, LLMs may support patient understanding and promote more active participation in care. However, the readability, accuracy, completeness, and overall acceptance of LLM-generated medical content remain underexplored. Objective: This study aims to evaluate the potential of ChatGPT-4 as a supplementary tool for patient education in the context of lung cancer radiotherapy by assessing the readability, content quality, and perceived usefulness of artificial intelligence–generated responses from both clinician and patient perspectives. Methods: A total of 8 frequently asked questions about radiotherapy for lung cancer were developed based on clinical experience from a team of clinicians specialized in lung cancer treatment at a university hospital. The questions were submitted individually to ChatGPT-4o (version as of July 2024) using the prompt: “I am a lung cancer patient looking for answers to the following questions.” Responses were evaluated using three approaches: (1) a readability analysis applying the Modified Flesch Reading Ease (FRE) formula for German and the 4th Vienna Formula (WSTF); (2) a multicenter expert evaluation by 6 multidisciplinary clinicians (radiation oncologists, medical oncologists, and thoracic surgeons) specialized in lung cancer treatment using a 5-point Likert scale to assess relevance, correctness, and completeness; and (3) a patient evaluation during the first follow-up appointment after radiotherapy, assessing comprehensibility, accuracy, relevance, trustworthiness, and willingness to use ChatGPT for future medical questions. Results: Readability analysis classified most responses as “very difficult to read” (university level) or “difficult to read” (upper secondary school), likely due to the use of medical language and long sentence structures. Clinician assessments yielded high scores for relevance (mean 4.5, SD 0.52) and correctness (mean 4.3, SD 0.65), but completeness received slightly lower ratings (mean 3.9, SD 0.59). A total of 30 patients rated the responses positively for clarity (mean 4.4, SD 0.61) and relevance (mean 4.3, SD 0.64), but lower for trustworthiness (mean 3.8, SD 0.68) and usability (mean 3.7, SD 0.73). No harmful misinformation was identified in the responses. Conclusions: ChatGPT-4 shows promise as a supplementary tool for patient education in radiation oncology. While patients and clinicians appreciated the clarity and relevance of the information, limitations in completeness, trust, and readability highlight the need for clinician oversight and further optimization of LLM-generated content. Future developments should focus on improving accessibility, integrating real-time readability adaptation, and establishing standardized evaluation frameworks to ensure safe and effective clinical use.

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.