Search

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.

Introduction As most patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) develop progressive disease after treatment with osimertinib, it is important to develop more effective treatment options. Afatinib has been shown to be more effective in in vitro studies than osimertinib when used in cancer cell lines containing some specific EGFR mutations. Therefore, afatinib may be an effective solution, especially when used in combination with an anti-VEGF agent such as bevacizumab. Methods A phase II multicenter, open-label, single-arm trial has been initiated to evaluate the efficacy and safety of afatinib and bevacizumab combination as salvage therapy for EGFR-mutated lung cancer in patients previously treated with osimertinib. The primary endpoint will be the objective response rate (ORR) and secondary endpoints are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Discussion A previous study indicated that afatinib inhibits lung cancer cells with specific EGFR mutations more effectively than other EGFR-TKIs such as osimertinib. Therefore, we expect that combination therapy using afatinib and bevacizumab will be effective in patients previously treated with osimertinib (registration no. jRCTs031190077).

Objective: Although Mycobacterium avium complex (MAC) lung disease has been shown to be associated with lung cancer and hematologic malignancies, there have been few studies of its relationships with other types of cancer. The aim of this study was to assess the effect that coexisting advanced extrapulmonary solid tumors have on the progression of MAC lung disease. Methods: This was a retrospective study of patients diagnosed with MAC lung disease, on the basis of the American Thoracic Society (ATS) criteria, between October of 2005 and March of 2019. The patients were divided into three groups: those with advanced-stage cancer (A-SC group); those with early-stage cancer (E-SC group); and those without cancer (control group). Progression of MAC lung disease was defined as exacerbation seen on imaging. Patient characteristics and the time to progression were compared among the three groups. Results: A total of 286 patients met the ATS diagnostic criteria for MAC lung disease, and 128 of those were excluded. Of the remaining 158 patients, 20 (7.0%) were in the A-SC group, 36 (12.6%) were in the E-SC group, and 102 (35.7%) were in the control group. The median time to progression in the A-SC, E-SC, and control groups was 432, 3,595, and 2,829 days, respectively (p < 0.01). A proportional hazards model showed that the significant predictors of MAC lung disease progression were advanced-stage cancer (hazard ratio [HR] = 6.096; 95% CI: 2.688-13.826; p < 0.01), cavitary lesions (HR = 2.750; 95% CI: 1.306-5.791; p < 0.01), and a high Nodule-Infiltration-Cavity-Ectasis score (HR = 1.046; 95% CI: 1.004-1.091; p = 0.033). Conclusions: A coexisting advanced extrapulmonary solid tumor could hasten the progression of MAC lung disease. RESUMO Objetivo: Embora tenha sido demonstrado que a doença pulmonar por Mycobacterium avium complex (MAC, complexo M. avium) está associada a câncer de pulmão e neoplasias hematológicas, há poucos estudos sobre sua relação com outros tipos de câncer. O objetivo deste estudo foi avaliar o efeito da coexistência de tumores sólidos extrapulmonares avançados na progressão da doença pulmonar por MAC. Métodos: Estudo retrospectivo de pacientes diagnosticados com doença pulmonar por MAC, segundo os critérios da American Thoracic Society (ATS), entre outubro de 2005 e março de 2019. Os pacientes foram divididos em três grupos: grupo câncer em estágio avançado (grupo CEA), grupo câncer em estágio inicial (grupo CEI) e grupo sem câncer (grupo controle). Progressão da doença pulmonar por MAC foi definida como exacerbação observada em exame de imagem. As características dos pacientes e o tempo para progressão foram comparados entre os três grupos. Resultados: Um total de 286 pacientes preencheu os critérios diagnósticos da ATS para doença pulmonar por MAC, sendo 128 deles excluídos. Dos 158 pacientes restantes, 20 (7,0%) eram do grupo CEA, 36 (12,6%), do grupo CEI e 102 (35,7%), do grupo controle. A mediana de tempo para progressão nos grupos CEA, CEI e controle foi de 432, 3.595 e 2.829 dias, respectivamente (p < 0,01). Um modelo de riscos proporcionais demonstrou que os preditores significativos de progressão da doença pulmonar por MAC foram câncer em estágio avançado (razão de risco [RR] = 6,096; 95%IC: 2,688-13,826; p < 0,01), lesões cavitárias (RR = 2,750; 95%IC: 1,306-5,791; p < 0,01) e pontuação alta no sistema Nódulo-Infiltração-Cavidade-Ectasia (RR = 1,046; 95%IC: 1,004-1,091; p = 0,033). Conclusões: A coexistência de tumor sólido extrapulmonar avançado poderia acelerar a progressão da doença pulmonar por MAC.

Backgrouds: Durvalumab has become a standard treatment for patients with unresectable stage III NSCLC after concurrent chemoradiotherapy (CRT). Although frequencies of grade 3 or 4 pneumonitis or radiation pneumonitis between groups in PACIFIC trial were not significant, there is still a concern for severe pneumonitis at clinical practice. Purpose: To identify predictive factors for severe pneumonitis or radiation pneumonitis causing discontinuation of durvalumab. Methods: From July 2018 to February 2020, stage III NSCLC patients treated with durvalumab after CRT at Yokohama City University Medical Center were enrolled in retrospective observational study. Factors mentioned below were analyzed to identify predictors of durvalumab discontinuation. Age, sex, performance status, planning target volume(PTV), mean lung dose, volumes of normal lung receiving > 20Gy(V20) and > 5Gy(V5), histological type, initiation time after the completion of CRT, atelectasis at the CRT initiation, smoking status, low attenuation volume ratio (LAV) for entire lungs. Results: Total 11 patients were enrolled. Two of eleven patients were discontinued durvalumab due to severe pneumonitis or radiation pneumonitis. All discontinued subjects had a lobular atelectasis. Discontinued group also showed higher PTV (Durvalmub continued vs discontinued; 433.2 vs 1036, SD=602.4±208.1, p = 0.0178), V20 over (1-LAV) (0.299 vs 0.458, 0.159±0.07, p = 0.085) and V5 over (1-LAV) (433.2 vs 1036, 0.265± 0.08, p = 0.0223). Conclusion: Lobular atelectasis, higher PTV and V20 and V5 over (1-LAV) could be predictive factors for durvalumab discontinuation after CRT for NSCLC.

For comparison with known phosphodiesterases, the mode of action of phosphodiesterase-phosphomonoesterase from Fusarium moniliforme toward some key substrates was examined. The enzyme catalyzed the hydrolysis of either thymidine 3′-(4-nitrophenylphosphate) or thymidine 5′-(4-nitrophenylphosphate). The former substrate was hydrolyzed processively into thymidine, inorganic phosphate and 4-nitrophenol, whereas the latter was split into 4-nitrophenol and thymidine 5′-phosphate. The kinetic constants determined on the basis of 4-nitrophenol liberation were: Km=4.6 mmol dm−3 and kcat=115 s−1 for thymidine 3′-(4-nitrophenylphosphate); Km=0.46 mmol dm−3 and kcat=19.7 s−1 for thymidine 5′-(4-nitrophenylphosphate) at pH 5.3 and 37 °C. 4-Nitrophenyl phenylphosphonate was a good substrate for the enzyme showing kinetic constants Km=1.4 mmol dm−3 and kcat=360 s−1 at pH 5.3 and 37 °C. However, its chiral thio analogue, O-(4-nitrophenyl) phenylphosphonothioate, was hydrolyzed by the enzyme only very slowly in a stereo-n...