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.

Rapidly Growing Chest Wall Lipoma: Case Report and Calculating Volume Doubling Time.

Chest wall lipoma is a rare disease that might be asymptomatic and discovered incidentally. Chest wall lipomas are presumed to grow slowly, but no reports have evaluated the tumor volume doubling time (TVDT). The present study herein reports the case of a 35-year-old female patient with a relatively fast-growing chest wall lipoma. Lipomas have their characteristic shape and grow very slowly, so they are rarely completely resected, even though they are monitored and repeated imaging studies are performed. Homogeneous very low density, clear margins, and no invasion to the surrounding structure are characteristic finding on imaging, but some patients without these characteristics here have been reported here. As there has been no report of TVDT for chest wall lipoma, comparison was not possible, but TDVT for lipoma in this patient ranged from 235-412 days. Compared with reports that patients with non-small cell lung cancer showed TVDT of less than 450 days, TVDT in the patient described here did not appear to be slow. Accumulation of knowledge about this rare disease will help to elucidate it further.

Myasthenia gravis that has developed long after radical resection of lung cancer: A case report.

Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission and is a heterogeneous disorder generally caused by auto-antibody to the nicotinic acetylcholine receptor. The current study presented a rare case of MG that occurred a long time after surgical resection of lung cancer. A 58-year-old man with lung adenocarcinoma underwent upper lobectomy and mediastinal lymph node dissection. Severe myasthenic symptoms began 7 years after the operation, and emergent mechanical ventilation was needed because of myasthenic crises. Levels of serum anti-acetylcholine receptor antibody were high and typical decremental responses to repetitive stimulation on electromyography were observed. Appropriate therapies for a severe acute condition were performed, and MG has been controlled for 6 years since then. There is no recurrence of lung cancer or appearance of thymoma. In conclusion, although very rare, physicians should be aware of MG as a potential comorbidity developing in patients with a history of lung cancer.

Imaging characteristics of nontuberculous mycobacterial pulmonary nodules.

Introduction. Nontuberculous mycobacteriosis (NTM) of the lungs can develop nodules. In order to clarify some of the characteristics of lung NTM nodules, we examined volume doubling time (VDT) and maximum standardized uptake value (SUVmax) in positron emission tomography (PET) of pathologically diagnosed NTM nodules. Methods. From November 2012 to August 2018, clinical and radiological information were retrospectively investigated in eight patients who were surgically resected and diagnosed as NTM. These eight patients were followed up until November 2020 and were confirmed to have no appearance of lung cancer or reappearance of lung NTM nodules. The VDT was calculated using the Schwartz formula. Results. The median maximum diameter of the nodule at the time of the first CT scan was 16.0 (range: 9.9-20.0) mm. The median maximum diameter of the nodule on CT performed before the surgical biopsy was 18.8 (range: 10.4-32.8) mm. The median doubling time calculated from these results was 203 (range: 20-568) days. Caseous granulomas and acid-fast bacilli were histologically confirmed in all eight patients. Culture of excised nodules revealed Mycobacterium intracellulare in five patients and Mycobacterium avium in three patients. Six patients received PET, and median SUVmax was: 7.0 (range: 3.3-21.0). Median VDT was around 200 days. Some patients had irregular-shaped nodules. Conclusions. CT/PET-CT characteristics of lung nodules are not reliable in differentiating lung NTM nodules from malignant ones. To avoid unnecessary resection, it may be better to collect various information on imaging findings in the nodule itself and in opacities other than the nodule.

A population-based study of outcomes in patients with surgically resected non-small cell lung cancer with anaplastic lymphoma kinase-rearranged mutations: A matched-pair study.

The present study aimed to evaluate clinical outcomes in patients with surgically resected non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearranged mutations. A matched-pair analysis in completely resected ALK-rearranged NSLC patients and those with neither ALK nor epidermal growth factor receptor (EGFR) mutations diagnosed at 11 institutes was performed between April 2008 and March 2019. A total of 51 patients with surgically resected ALK-rearranged NSCLC were included. Women constituted 68.6%, and smokers 29.4%. The median age was 65 years. In matched-pair analysis, disease-free survival and overall survival did not differ between patients with ALK-rearranged mutations and those without mutations. Post-recurrence survival in patients with ALK mutations was longer than that of patients with neither ALK nor epidermal growth factor receptor mutations. ALK genetic testing should be performed, even in elderly patients with NSCLC. Favorable prognosis might be expected after appropriate treatment for patients with recurrent ALK-mutated disease.

Metachronous Isolated Contralateral Lung Metastasis from Pulmonary Adenosquamous Carcinoma with EGFR Mutation.

Lung metastasis and metachronous double primary lung cancer are both common and often present diagnostic challenges. We present a case of metachronous isolated contralateral lung metastasis from pulmonary adenosquamous carcinoma with EGFR mutation. A 75-yearold woman presented with left lung nodule on a routine follow-up chest radiograph. She had had surgery for pulmonary adenocarcinoma with EGFR Ex21 L858R mutation 6 years ago. She underwent surgical resection, and histologic findings revealed adenosquamous carcinoma with the same EGFR mutation. Re-assessment of the resected specimen of the primary tumor resected 6 years ago revealed the morphologically similarity to the left lung tumor. Based on morphological and genetic identity, final diagnosis was adenosquamous cell carcinoma and metachronous isolated contralateral lung metastasis. The diagnosis of metachronous isolated metastasis is difficult but important for appropriate management and prediction of prognosis. A careful pathological examination and evaluation of genetic abnormality are needed to make the correct diagnosis.

Treatment of Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in Clinical Practice.

BACKGROUND/AIM: To describe real clinical outcomes in patients with non-small cell lung cancer who have uncommon epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: We performed a retrospective chart review from 15 medical institutes that cover a population of three million people from April 2008 to March 2019. RESULTS: There were 102 patients with uncommon EGFR mutation. Progression-free survival (PFS) tended to be longer in patients receiving afatinib compared with first-generation EGFR tyrosine kinase inhibitors. PFS in patients treated with afatinib or osimertinib was significantly longer than in patients treated with gefitinib or erlotinib (p=0.030). Multivariate analysis also revealed the contribution of afatinib or osimertinib to increased survival. In patients with exon 20 insertions, chemotherapy was efficacious. CONCLUSION: In treating patients with uncommon EGFR mutations, our results indicate longer-term survival might be achieved with second-generation or later TKIs and cytotoxic chemotherapeutic drugs.

Blood flow velocity is reduced in a tumor micro-dissemination in the visceral pleura in anesthetized open-chest rat lung.

BACKGROUND: Recently we developed a method to observe pulmonary micrometastasis by labeling cancer cells with green fluorescent protein (GFP). We applied the method for observation of micro-dissemination on the visceral pleura. MATERIALS AND METHODS: RCN9 rat colon cancer cells labeled with GFP were injected into the pleural cavity of Fischer F344 rats. Six weeks after injection, the chest wall was resected under general anesthesia and the lung surface was observed by real-time confocal laser-scanning microscopy. Blood flow was visualized by intravenous injection of fluorescein isothiocyanate-labeled red blood cells, by which blood flow velocity was measured. RESULTS: Dissemination was created in 4 out of 5 rats. Fifteen sites of micro-dissemination were observed (mean diameter, 35.8+/-13.3 microm). Blood flow velocity was 114.1+/-26.1 microm/s in the tumor tissue and 183.4+/-35.0 microm/s out of the tumor tissue. CONCLUSION: We were able to observe pleural micro-dissemination. Blood flow velocity was significantly lower in the tumor tissue.

[S-1 activity in non-small cell lung cancer in clinical practice].

OBJECTIVE: We evaluated retrospectively single-agent S-1 chemotherapy in non-small cell lung cancer patients in clinical practice. METHODS: Sixteen consecutive patients treated with single-agent S-1 for NSCLC between July 2005 and June 2007 at the Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital. The treatment schedule comprised oral administration of S-1 at 80-120 mg/day. One cycle of S-1 consisted of consecutive administration to 14 (10 cases)or 28(6 cases)days followed by a 14-day rest. RESULTS: Patients profiles were: M/F: 11/5, median age 68 years old(range 51-83), PS 0/1/2/3: 2/6/5/3, adeno/squamous/large: 13/2/1, clinical stage 3A/3B/4: 3/4/9, prior chemotherapy regimens 0/1/2/3/4: 2/3/4/5/2, prior surgery/radiation: 12/5 were performed. Median number of delivered cycles was 5 cycles(range 1-13). Grade 3 hematological toxicities were anemia(6%)and thrombocytopenia(6%). Grade 3 non-hematological toxicities were nausea(6%)and vomiting(6%). Response of 13 patients could be evaluated after 2-4 cycles of S-1. Four partial responses were observed, for a response rate of 31%. The survival time was 67-852 days(average 14.0 months), 1-year survival rate was 74.0%, median time to progression was 4.6 m, and 1- year progression free survival was 25.0%. CONCLUSION: Single-agent S-1 chemotherapy has modest activity and is the one of the important regimens and tolerable for elderly, poor-PS, recurrent patients with NSCLC in clinical practice.

Oligo-recurrence from anaplastic lymphoma kinase-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase rearranged non-small-cell lung cancer is arare disease. Among them, asubset of patients exist who exhibit relatively slowly progressing symptoms and have oligo-metastases. In this article, we present two cases of ALK rearran-ged lung adenocarcinoma in patients who experienced postoperative oligo-recurrence. Both cases were treated with surgical resection and gamma knife irradiation for oligo-recurrence. After local therapy, the first patient remained disease free for over 23 months; the second for over 18 months. It appears that some patients with ALK rearranged NSCLC experience oligo-recurrence in their clinical course. For such patients, appropriate local therapy may be beneficial in improving both the quality of life and the prognosis.

Chronic expanding hematoma in the chest: A case report.

Chronic expanding hematoma (CEH) is a rare disease that is usually present as a large solitary pulmonary nodule. CEHs are slow growing, but processes underlying their development remain unknown. The present study herein reports the case of a 76-year-old male patient with CEH and discusses a number of CEH cases published in the literature. The majority of these previously described patients were Asians. The CEH in the present case was not a successfully resected one, but the patient's clinical course provided information concerning the natural history of the disease. During the clinical course, the patient underwent several chest computed tomography scans. For the present case report, the doubling time and volume change of the mass was calculated, which revealed that the lesion had an inconstant growth rate and that its onset was between 8.2-11.0 years before the patient succumbed to this disease. Accumulation of knowledge about this rare disease will help to elucidate it further.

Pulmonary metastasis from uterine leiomyosarcoma in a patient with limited cutaneous systemic scleroderma.

A 51-year-old woman, who was diagnosed as having limited cutaneous systemic scleroderma, presented with pulmonary nodules incidentally detected in a chest radiograph. The patient had surgical biopsy of the nodules. In microscopic examination of the specimens, proliferation, mitotic activity, and cellular anaplasia of spindle cells were present. Fluorodeoxyglucose-positron emission tomography showed tumors in lungs as well as uterus. The diagnosis of the tumor was pulmonary metastases from uterine leiomyosarcoma. We should be on alert the possibility of developing malignant disease in patient with this autoimmune disease. If it is certain that there is metastasis, we believe that therapy for the primary lesion will be preceded by biopsy and surgery for the metastatic lesions.

Isolated spleen recurrence in a patient with lung adenocarcinoma: A case report.

Spleen metastasis is extremely rare in patients with lung cancer. However, recent improvements in imaging modalities may enable the antemortem diagnosis of spleen metastasis. The present study reports the case of a female patient with lung adenocarcinoma and spleen metastasis. The patient developed isolated spleen metastasis in the postoperative course. This rare metastasis was detected in a follow-up abdominal computed tomography (CT) scan without any symptoms, and was confirmed by fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan. Although very rare, chest physicians and thoracic surgeons should be alert to the possibility of spleen metastasis development when evaluating the follow-up abdominal CT scan. FDG-PET/CT scanning and an interventional approach should be considered to clarify the possibility of spleen metastasis.

Video-assisted thoracoscopic conservative repair of postoperative lobar torsion.

Postoperative lobar torsion is a rare and life-threatening complication. Several previous cases have been treated with completion lobectomy. We report successful surgical repair of middle lobar torsion after upper lobectomy. On postoperative day 4, the middle lobe was rotated approximately 150 degrees counterclockwise. The surface of the middle lobe appeared congestive, but its surface color, elasticity, and compliance improved 1 h after detorsion. We preserved the middle lobar function and prescribed warfarin for pulmonary vein thrombosis. When preserving a twisted lobe, it is important to consider the damage to the twisted lung, risk of thrombosis, and residual pulmonary function.