Continuous immunotherapy beyond progression in clinical practice for small cell lung cancer.

In non-small-cell lung cancer, continuous immune-checkpoint inhibitors (ICIs) beyond progression are often used in clinical practice. On the other hand, there is almost no data on whether the concept of continuous ICIs beyond progression can be adopted in small-cell lung cancer (SCLC). We describe the effectiveness of continuous ICIs beyond progression in SCLC. Medical courses of SCLC patients treated with chemo-immunotherapy were retrospectively reviewed at our hospital. The study included 36 patients with a median age of 73 years (range 46-83 years) who introduced chemo-immunotherapy between September 2019 and December 2022. Atezolizumab and durvalumab in combination with platinum plus etoposide were administered in 24 and 12 patients, respectively. The overall response rate was 67% and the disease control rate was 86%. The median progression-free survival and time to treatment failure (TTF) were 5.1 and 10.3 months, respectively. The median cycle of ICIs was 5 (range 1-42). The median overall survival was 13.6 months. ICIs were administered beyond progression in 14 (39%) patients: five were treated again with chemo-immunotherapy and local ablative radiotherapy, four with local ablative radiotherapy and continuous ICIs, three with chemo-immunotherapy, and two with continuous ICIs alone. TTF exceeded 12 months in 12 (86%) of the 14 cases, six of which were still on ICIs. Adverse events ≥grade 3 were observed in 21 (58%) patients. A notable TTF suggested a benefit of continuous ICIs beyond progression. The concept could be suitably adopted and provide a favorable prognosis in selected cases of SCLC that were previously regarded as an aggressive malignancy.

Heterogeneity or transformation? A whack-a-mole case of EGFR-mutant lung adenocarcinoma and small cell carcinoma: A case report.

Histological transformation from adenocarcinoma to small cell lung cancer (SCLC) occurs ~10% after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. Transformed SCLC generally responds well to chemotherapy regimens for SCLC such as platinum plus etoposide. After the response, histological nature and clinical course could be complicated by possible heterogeneity or transformation. Therefore, monitoring rebiospy is desirable to seize its histological nature at that moment. We report a case of EGFR-mutated adenocarcinoma, where histological transformations from adenocarcinoma and SCLC alternated. In this case, first rebiopsy after gefitinib revealed adenocarcinoma, but second rebiopsy after osimertinib identified SCLC transformation. After failure of platinum plus etoposide, adenocarcinoma-induced leptomeningeal metastases were controlled by osimertinib reintroduction. Optimal therapies could be provided according to the result of monitoring rebiopsy.

Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

Lazarus Response to Tepotinib for Leptomeningeal Metastases in a Patient With MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma: Case Report.

The spread of next-generation sequencing enables clinicians to identify rare oncogene alterations, including MET exon 14 skipping mutation, in clinical practice for NSCLC. Several tyrosine kinase inhibitors for MET exon 14 skipping mutation such as capmatinib and tepotinib have elucidated their effectiveness. Only a few reports have suggested their efficacy against central nervous system lesions, especially leptomeningeal metastases. We here report a case of a patient with NSCLC with MET exon 14 skipping mutation and poor performance status salvaged by marked leptomeningeal metastases response to tepotinib. We further provide measures of plasma/cerebrospinal fluid concentrations of tepotinib and its cerebrospinal fluid penetration rate.

[How to Preserve QOL of Patients with Small Cell Lung Cancer-Cutting‒Edge Treatment of Brain and Bone Metastases].

Small cell lung cancer(SCLC)frequently develops both brain metastases and bone metastases. Considering the negative effects on quality of life(QOL), it is essential to manage properly these metastases. In patients with limited‒disease(LD) SCLC who have a good response to chemoradiotherapy, prophylactic cranial irradiation(PCI)is given to decrease brain metastases. As for brain metastases in patients with extensive‒disease(ED)SCLC, whole brain radiation therapy(WBRT)is a standard of care, because patients with brain metastases tend to develop multiple brain metastases. However, both PCI and WBRT are associated with adverse events such as neurocognitive decline, which leads to QOL deterioration in some patients. Therefore, in patients not receiving PCI, regular magnetic resonance imaging surveillance and treatment with stereotactic radiosurgery(SRS)or WBRT upon detection could be a reasonable alternative in some patients. As for brain metastases in ED‒SCLC, front‒line SRS might be preferred rather than WBRT in some cases. Bone metastases could cause pain, bone fracture, epidural spinal cord compression and hypercalcemia, which could require radiation therapy or surgery. Since these morbid conditions called skeletal‒related events substantially reduce QOL, providing appropriate treatments as early as possible is important. Therapeutic options include analgesia, radiation therapy, surgery, and bone modifying agents. Choosing best treatments among them according to patients' condition is required. Optimal treatment of brain and bone metastases requires proper local control, which is important in preserving QOL. As treatment method differs in individual patients, multidisciplinary approach is essential.

Higher osimertinib introduction rate achieved by multiple repeated rebiopsy after acquired resistance to first/second generation EGFR-TKIs.

BACKGROUND: Indication for treatment with osimertinib after first/second generation (1/2G) epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance depends on T790M mutation detected by rebiopsy. The aim of our study was to analyze the data on clinical practice at our hospital where histological rebiopsy is actively carried out multiple times. METHODS: We retrospectively reviewed our electronic medical records of EGFR-mutant non-small cell lung cancer (NSCLC) patients to examine clinical rebiopsy situation, T790M detection rate, osimertinib introduction rate and associated outcomes. RESULTS: Among 95 patients with EGFR-mutant NSCLC, 72 patients received 1/2G EGFR-TKIs. Of 60 with progressive disease on 1/2G EGFR-TKIs, 50 (83%) underwent rebiopsy. T790M was detected in 40 (80%) of 50, resulting in a 79% osimertinib introduction rate, as one patient refused osimertinib. T790M was detected by first rebiopsy in 18 (36%) of 50 patients, and by second or subsequent rebiopsy in 22 (44%). Median time to treatment failure of T790M-positive patients at first rebiopsy was 22.6 (95% confidence interval [CI]: 10.2-32.8) months, and those at multiple repeated rebiopsy was 20.9 (95% CI: 8.6-not reached) months (p = 0.64). Median overall survival (OS) in osimertinib introduced group was 92.5 (95% CI: 62.9-not reached), while in nonosimertinib median OS was 39.0 months (95% CI: 22.2-not reached) (p = 0.04). CONCLUSIONS: T790M detection rate was increased by multiple repeated rebiopsy, achieving a higher osimertinib introduction rate. This higher introduction rate could contribute to better prognosis of EGFR-mutant NSCLC patients.

Endobronchial metastases 20 years after prostate cancer excision.

A 78-year-old Japanese man who had undergone total prostatectomy for prostate cancer (pT3cN1M0, Gleason score 3 + 3) 20 years previously was referred to the Respiratory Medicine Department of our institution because of a 1-week history of chest pain and cough. Computed tomography showed multiple small nodules and mediastinal lymph node enlargement. Bronchoscopy revealed multiple soft polypoid masses and obstruction of the lingular segment. Prostate-specific antigen (PSA) concentrations had increased markedly from 0.48 ng/mL in 2014 to 741 ng/mL in 2018. The diagnosis of prostatic cancer metastases was confirmed by revealing the presence of PSA via immunohistological staining of a bronchoscopically obtained biopsy of one of the masses. The patient had not been attending scheduled follow-up visits for the past 4 years. Treatment with degarelix (a gonadotropin-releasing hormone) was started, and the PSA concentration decreased dramatically (29 ng/mL). Metastases from prostate cancer are rarely first diagnosed two decades after radical prostatectomy. This patient illustrates the importance of obtaining a complete medical history.

Left ventricular outflow tract obstruction caused by massive mitral annular calcification in a patient with hypertensive heart disease.

Mitral annular calcification (MAC) is frequently observed, but it rarely causes left ventricular outflow tract (LVOT) obstruction (LVOTO). An 83-year-old woman with hypertension, diabetes, and dyslipidemia was admitted to our hospital because of exertional dyspnea. She was diagnosed with hypertensive heart disease. Her symptoms were exacerbated by exertion, and she had no symptoms at rest. Transthoracic echocardiography showed massive posterior MAC, a sigmoid septum, and LVOTO, with a peak gradient of 15.4 mmHg at rest. Systolic anterior motion of the anterior mitral leaflet was not found. Moreover, the LVOT gradient in the stress condition was evaluated, and an increased LVOT gradient (47.3 mmHg) and chest discomfort was noted after 20 µg/kg/min of dobutamine was administered and the Valsalva maneuver was used. Hence, the patient was diagnosed with latent LVOTO. Interestingly, the distance between the septal wall, which was protruding into the left ventricular cavity, and the mitral valve coaptation, which was pushed up by the posterior MAC, had become closer, causing dynamic LVOTO. Since it is difficult to treat LVOTO with medication, ultimately, septal myectomy and mitral valve replacement were performed, which improved her symptoms. Evaluating the LVOT pressure gradient in stress condition is important in patients with MAC. .

Evaluation of platelet reactivity using P2Y12 reaction units in acute coronary syndrome with essential thrombocythemia: A case report.

Essential thrombocythemia (ET) has been reported to cause acute coronary disease. However, the efficacy of anti-platelet therapy for ET is unclear since there are individual differences in the platelet function of ET patients. Here we report a case of a 62-year-old man with ET who was admitted to our hospital because of acute coronary syndrome. He underwent coronary angioplasty. Dual anti-platelet therapy with aspirin (81 mg/day) and clopidogrel (75 mg/day) was subsequently initiated. We evaluated platelet reactivity in P2Y12 reaction units, and subsequently determined anti-platelet drugs and corresponding doses. .