Long-term response in a patient with adenocarcinoma harboring both common and uncommon EGFR mutations.

Recently, we read a paper "Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation" published in Investigational New Drugs. Their patient had a very rare compound EGFR mutation. To share our experience, we present a case of 58-year-old man with a long-term response to afatinib in a patient with previously unreported compound EGFR mutation. In patients with rare compound EGFR mutations, afatinib might be one of the treatment option.

Eosinophilic pneumonia with nodular shadows in a patient with rheumatoid arthritis.

We report a rare case of eosinophilic pneumonia with nodules, which required a differential diagnosis of lung cancer. She had been treated for rheumatoid arthritis and bronchial asthma for eight years. Although there were no exacerbations of symptoms of rheumatism, newly development of nodules and ground-glass opacities in both upper lobes of the lung were found in the chest CT scan. A bronchoalveolar lavage obtained from the right middle lobe showed 58.8% eosinophils. The transbronchial biopsy from the lesion of the nodular shadow could not be performed because the patient developed an asthma attack during the examination of bronchoscopy. Chest CT scan performed one month after the start of prednisolone treatment showed that not only GGOs but also nodules showed shrinkage or almost disappeared. In some patients with eosinophilic pneumonia, there may be nodules that need to be differentiated from lung cancer. In such cases, the presence of GGOs around the nodule might be an important finding in imaging examination. To confirm the diagnosis, performing a tissue biopsy should be actively considered. Patients with eosinophilic pneumonia might also have bronchial asthma, and attention should be paid to the onset of asthma attacks during bronchoscopy.

Cluster analysis of deterioration sites after first-line epidermal growth factor receptor-tyrosine kinase inhibitor in epidermal growth factor receptor mutated non-small cell lung cancer.

Introduction: For epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC), no studies have treated the site of recurrence after first-line tyrosine kinase inhibitor (TKI) treatment as a "metastasis pattern". This study aims to assess whether these patients have a specific "metastasis pattern" at the site of recurrence after the treatment. Material and methods: Data were collected from all consecutive EGFR mutated NSCLC patients between 2009 and 2021. Metastatic patterns were analyzed using cluster analysis in patients with EGFR mutated NSCLC. Results: During the study period, 83 EGFR mutated NSCLC patients were treated with EGFR-TKI. Patients who had no metastases at the time of diagnosis were divided into two groups according to the presence or absence of recurrence of metastases after TKI administration. Patients with metastases at diagnosis were divided into 4 groups by cluster analysis. A statistically significant difference in metastasis frequency was confirmed among these 6 groups (χ2 test, p = 0.0001). Furthermore, when the frequency of metastasis recurrence after TKI administration in these 6 groups was examined, a statistically significant difference was confirmed (χ2 test, p = 0.0001). Conclusions: Even in EGFR mutation-positive patients, the knowledge of the recurrent patterns might be useful for clinical practice in the foreseeable future, as it enables more efficient detection of metastatic disease through imaging, and more effective treatment at predicted metastatic sites.

Distant organ metastasis patterns in lung cancer patients with pancreatic metastasis - a cluster analysis.

Introduction: Pancreatic metastasis of lung cancer is rare, but the narrowing or obstruction of the biliary tract from pancreatic metastases limits the choice of antitumour agents. Lung cancer patients with pancreatic metastasis often have metastasis of other organs. For these patients, however, no studies have been conducted to evaluate distant metastasis sites as metastasis patterns. This study aims to assess whether these patients have specific metastasis patterns at the time of diagnosis of lung cancer. Material and methods: Data were collected from consecutive lung cancer patients with pancreatic metastasis between April 2012 and March 2022. Metastatic patterns were analysed using cluster analysis in patients with lung cancer. Results: During the study period, 33 (2.0%) of 1659 patients were diagnosed as having pancreatic metastasis. Of the 33 patients, 28 (84.8%) were male. Eighteen, 14, and one patient had small cell lung cancer (SCLC), lung adenocarcinoma, and large cell neuroendocrine carcinoma, respectively. They were divided into 3 groups by cluster analysis. A statistically significant difference in metastasis frequency was confirmed among these 3 groups (χ2 test, p = 0.001). Conclusions: In lung cancer patients with pancreatic metastasis, knowledge of the metastatic patterns might be useful for clinical practice in the foreseeable future because it enables more efficient detection of metastatic disease through imaging, and more effective treatment at predicted metastatic sites.

A Long-Term Control of Intramedullary Thoracic Spinal Cord Metastasis from Small Cell Lung Cancer.

Radiotherapy with systemic corticosteroid therapy has been used to treat intramedullary spinal cord metastasis (ISCM), but recovery of function and long-term survival of these patients has been rarely observed. We report herein a small cell lung cancer (SCLC) patient with recurrent thoracic ISCM, who was successfully treated with radiotherapy and systemic corticosteroid therapy. A 70-year-old man, who was diagnosed as having SCLC seven months previously, developed thoracic ISCM. Soon after the detection of the lesion, the patient received radiotherapy with systemic corticosteroid therapy. Sensory disturbance in both extremities and neurogenic bladder and bowel dysfunction was recovered. The patient could walk after irradiation again. The patient received additional chemotherapy and survived 20 months after the diagnosis of ISCM recurrence. Prompt diagnosis and appropriate treatment for ISCM and effective chemotherapy for recurrent SCLC might be the favorable factors for such patients. Further studies will be required to define a favorable subset of patients most likely to benefit from a conventional approach.

Long­term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli: A case report.

Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Investigation of age and smoking in NSCLC patients with uncommon EGFR mutations.

Introduction: In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. Materials and Methods: We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Result: Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Conclusions: Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.

Patient Age and EGFR-positive Non-small Cell Lung Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: The median age of subjects in many clinical trials of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor conducted to date has been approximately 60 years. However, it is not uncommon to encounter EGFR gene-positive patients in their 70s or 80s. Based on information obtained from these clinical trials, EGFR gene-positive non-small cell lung cancer (NSCLC) patients are considered to be younger than EGFR-negative patients. In this study, we analyzed clinical data to identify whether this assumption is true. PATIENTS AND METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed in a multicenter clinical practice from 2009 to 2023. Patients included all cases of non-advanced and advanced NSCLC. RESULTS: Information on 2,540 patients, including 605 EGFR gene-positive patients, was collected. The median age of EGFR-positive and EGFR-negative patients was 72 years and 71 years, respectively, and there was no significant difference in the age of patients between these two groups (p=0.7887). The most common age in these two groups was 70 years. Among the EGFR gene subtypes, the frequency of exon 19 deletion decreased with age, whereas that of EGFR L858R increased. CONCLUSION: Patients in their 70s and 80s with non-small cell lung cancer were relatively frequently EGFR gene-positive. To avoid missing out on treatment opportunities, EGFR gene testing should also be performed on patients in this age group.

Relationship Between TTF-1 Expression and PFS of Pemetrexed-containing Chemotherapy in Non-squamous-NSCLC Patients With and Without Driver Genes.

BACKGROUND/AIM: We performed a retrospective study too clarify whether the presence or absence of driver genes affects the relationship between thyroid transcription factor-1 (TTF-1) expression and response to pemetrexed (PEM) in non-squamous non-small cell lung cancer (non-sq-NSCLC) patients. PATIENTS AND METHODS: We reviewed the medical charts of patients treated with PEM-containing chemotherapy during the period from February 2016 to February 2022 at Mito Medical Center-University of Tsukuba, Ryugasaki Saiseikai General Hospital, and University of Tsukuba Hospital. RESULTS: During the period of the study, 185 driver gene-negative patients negative, and 65 driver gene-positive patients were evaluated. Among the 165 driver gene-negative patients, progression free survival (PFS) of TTF-1-expressing patients treated with PEM-containing chemotherapy was significantly longer compared to that of TTF-1-negative patients. In the analysis of 65 driver gene-positive patients, the PFS of TTF-1-positive patients treated with PEM-containing chemotherapy did not differ significantly from that of TTF-1-negative patients. There was no significant difference in PFS between driver gene-negative and driver gene-positive patients treated with PEM-containing chemotherapy. Comparison between four groups defined according to the presence of driver gene and TTF-1 expression indicated shorter PFS only in 'driver gene-negative and TTF-1-negative' patients. CONCLUSION: In driver gene-positive non-sq NSCLC patients, expression of TTF does not affect the survival outcome of PEM-containing-chemotherapy. In other words, in these patients, second-line or later-line PEM-containing chemotherapy after development of resistance for specific-tyrosine kinase inhibitor could be expected to have the same level of efficacy as first-line PEM containing chemotherapy in driver gene-negative, TTF-1-positive non-sq NSCLC patients.

Discontinuation of Immune Checkpoint Inhibitor due to irAEs in NSCLC Patients With EGFR Mutation.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have revolutionized advanced non-small cell lung cancer (NSCLC) treatment. Even patients with epidermal growth factor receptor (EGFR)-mutated NSCLC may choose an ICI after failure of EGFR-tyrosine kinase inhibitor treatment. ICI-mediated immune-related adverse events (irAEs) may prompt NSCLC patients to discontinue their treatment. This study evaluated the effect of ICI treatment discontinuation on the prognosis of patients with EGFR-mutated NSCLC. PATIENTS AND METHODS: We performed a retrospective study that reviewed the clinical courses of patients with EGFR-mutated NSCLC treated with ICI therapy from February 2016 to February 2022. 'Discontinuation' was defined as failure to receive at least two treatment courses of ICI due to grade 2 irAEs (grade 1 in the lung) or higher in patients responding to ICI. RESULTS: During the study period, 13 of 31 patients discontinued ICI therapy due to irAEs. Survival from the initiation of ICI therapy was significantly longer in patients who discontinued ICI therapy compared with those who did not discontinue. In uni- and multivariate analyses, 'discontinuation' was a favourable factor. There was no significant difference in survival from ICI initiation between patients with grade 3 or higher irAEs and those with grade 2 or lower irAEs. CONCLUSION: In this patient cohort, discontinuation of ICI therapy due to irAEs did not adversely affect prognosis in patients with EGFR-mutant NSCLC. Our results suggest that when treating patients with EGFR-mutant NSCLC with ICIs, chest physicians should consider discontinuing ICI with close monitoring.

NSCLC Patients Achieving Long-term Progression-free Survival With Docetaxel Plus Ramucirumab: A Retrospective Study.

BACKGROUND/AIM: The antineoplastic drug docetaxel (DOC) and the antivascular endothelial growth factor inhibitor ramucirumab (RAM) are widely used in combination for second or later-line regimens for advanced non-small cell lung cancer (NSCLC). While the median progression-free survival (PFS) of DOC+RAM has been reported to be less than six months in both clinical trials and clinical practice, there appear to be some patients with long-term PFS. This study aimed to clarify the existence and characteristics of these patients. PATIENTS AND METHODS: We conducted a retrospective review of patients with advanced NSCLC treated with DOC+RAM between April 2009 and June 2022 at our three hospitals. There was no established definition of long-term PFS, thus in this study, a PFS of 12 months or longer was defined as long-term PFS. RESULTS: During the study period, 91 patients received DOC+RAM treatment. Of these, 14 (15.4%) achieved long-term PFS. There were no significant differences in patient characteristics between patients with PFS ≥12 months and those with PFS <12 months, except for 'clinical stage IIIA-C' at DOC+RAM initiation and 'post-surgical recurrence'. In uni- and multivariate analyses, favorable factors for PFS were 'Stage III at the start of DOC+RAM' in driver gene-negative patients, and 'under 70 years old' in driver gene-positive patients. CONCLUSION: Many patients in this study achieved long-term PFS with DOC+RAM treatment. In the future, it is expected that long-term PFS will be defined, and the background of patients who achieve such PFS will become clearer.