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Purpose This study prospectively evaluated the efficacy and safety of concurrent chemo-proton therapy (CCPT) using adaptive planning for unresectable stage III non-small cell lung cancer (NSCLC). Methods and Materials The primary endpoint was overall survival (OS). Secondary endpoints were local control rate (LCR), progression-free survival (PFS), incidence of grade 3 or higher adverse events, and changes in quality of life (QOL). Patients received cisplatin (60 mg/m2) on day 1 and S-1 (∼40 mg/m2 twice daily) on days 1 to 14, q4w, for up to 4 cycles, plus concurrent proton therapy at a total dose of 70 GyRBE for the primary lesion and 66 GyRBE for lymph node metastasis with 2 GyRBE per day. Proton therapy was performed using respiratory-gated and image guided techniques, and adaptive plans were implemented. Results Forty-seven patients were enrolled between August 2013 and August 2018. Four cycles of cisplatin plus S-1 were completed in 34 patients. The mean number of cycles was 4 (range, 1-4). The median follow-up of all and surviving patients was 37 (range, 4-84) and 52 months (range, 26-84), respectively. The mean number of replanning sessions was 2.5 (range, 1-4). The 2- and 5-year OS, LCR, and PFS were 77% (95% confidence interval 64%-89%) and 59% (43%-76%), 84% (73%-95%) and 61% (44%-78%), and 43% (28%-57%) and 37% (22%-51%), respectively. The median OS was not reached. No grade 3 or higher radiation pneumonitis was observed. There was no significant deterioration in the QOL scores after 24 months except for alopecia. Conclusions CCPT with adaptive planning was well tolerated and yielded remarkable OS for unresectable stage III NSCLC.

A 69-year-old woman without pre-existing disease visited our hospital due to general malaise, diarrhea, and arthralgia 3 days after a uterine cancer test. We diagnosed her with sepsis of unknown focus and started treatment immediately, but she died 20 hours after the first visit due to multi-organ failure and septic shock. Later, group A streptococcus was detected from the blood culture, and streptococcal toxic shock syndrome (STSS) was diagnosed. The strain had the emm28 genotype and a mutation in csrR with increased NADase activity. These virulence factors were considered to be related to STSS development in this patient.

A 68-year-old man visited our hospital due to anorexia, weight loss and a fever. We diagnosed the patient with disseminated Mycobacterium avium complex (MAC) and confirmed the presence of interferon (IFN)-γ neutralizing autoantibodies (IFN-γAb). His lesions improved following antibiotic therapy, but chylous ascites (CA) developed seven months after treatment. CA was able to be controlled by subcutaneous octreotide and diet therapy. IFN-γAb is recognized as having a critical role in the pathogenesis of disseminated MAC disease, but its clinical features are not fully understood. CA may be a complication that develops during the treatment of disseminated MAC infection.

Background Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. Methods Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naive patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. Results Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. Conclusions Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.

We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.

Mycobacterium abscessus subspecies abscessus is major subspecies in the M. abscessus complex and is usually refractory to standard antibiotherapy. Genetic tracing of erm (41) T28 is a mechanism for monitoring macrolide resistance. We treated a patient with a pulmonary infection caused by M. abscessus subsp. abscessus with the erm (41) T28 polymorphism, which was susceptible to clarithromycin, and his clinical treatment course was good. The identification of the M. abscessus complex genotype is important, but clinical confirmation of clarithromycin susceptibility is also needed to plan individual treatment strategies.

Objective: Gastroesophageal reflux disease (GERD) is an important cause of chronic cough. Substance P (SP) has been implicated in the pathophysiology of cough. Proton pump inhibitors (PPIs) and pro...

Purpose/objective(s) Although the PACIFIC trial did not suggest that the administration of durvalumab increased the risk of radiation pneumonitis (RP) compared to placebo, the timing of durvalumab administration following concurrent chemo-radiotherapy was various and the method used to evaluate RP including interstitial pneumonia was unclear. Thus, further studies are needed to better understand the development of immune-related adverse event (irAE), in particular RP. In the present study, we performed a preliminary analysis to investigate RP after concurrent chemo-proton therapy (CCPT) followed by durvalumab. Materials/methods Between October 2018 and March 2020, 17 patients were administered durvalumab (mg/kg, q2w) within 14 days after CCPT (70 GyRBE/35 fractions and cisplatin (60 mg/m2) on day 1 and S-1 (w40 mg/m2 twice daily) on days 1 to 14, q4w, for up to 2 cycles). As a control, 47 patients who underwent CCPT in our previous phase II trial conducted between August 2013 and December 2017 were analyzed. These 47 patients were administered adjuvant chemotherapy (same regimen for up to 2 cycles) after CCPT. In patients suspected to have developed RP as a result of irAE, their treatment plans were compared with CT images obtained at the time of RP onset to examine the association between the dose distribution and RP. Results In our previous study, acute grade 2 RP within 3 months after the end of irradiation was observed in 4 patients (8.5%), and no patients developed grade 3 or higher RP. However, all occurred after completion of adjuvant chemotherapy, that is, within 2-3 months after the end of irradiation. On the other hand, 6 patients developed symptomatic grade 2 RP within 1 month of treatment among 17 patients who were administered durvalumab. Unlike CT findings of RP in the control patients, RP in 6 patients who received durvalumab was identified in the areas that received low-to-medium doses of proton irradiation and/or outside of the irradiation field, whereas the areas that received a high dose of proton irradiation exhibited little to no inflammatory response. In 3 patients who were subsequently administered steroids, CT revealed a rapid decrease in the lung volume and inflammatory response that progressed every week, in addition to traction ectasia and rapid progression of fibrosis. For the remaining 3 patients, the symptoms were mild without fever and improved only by stopping durvalmab without using steroids, and the course of CT images were similar. Conclusion Administration of durvalumab soon after CCPT resulted in the unexpected or unusual course of development of RP, which was likely an irAE. Further studies are needed to better understand the cause of immune-related RP.

Mycobacterium abscessus subspecies abscessus is major subspecies in the M. abscessus complex and is usually refractory to standard antibiotherapy. Genetic tracing of erm (41) T28 is a mechanism for monitoring macrolide resistance. We treated a patient with a pulmonary infection caused by M. abscessus subsp. abscessus with the erm (41) T28 polymorphism, which was susceptible to clarithromycin, and his clinical treatment course was good. The identification of the M. abscessus complex genotype is important, but clinical confirmation of clarithromycin susceptibility is also needed to plan individual treatment strategies.

平成30年度

e20070 Background: Concurrent chemo-radiotherapy is the standard treatment for locally advanced (LA) non-small cell lung cancer (NSCLC). Recent phase II studies have demonstrated that S-1 plus cisplatin (CDDP) with concurrent radiotherapy yields promising results against LA NSCLC. Proton-beam therapy (PBT) is an alternative modality that is expected to reduce toxic effects against normal tissues compared with X-ray radiotherapy. We conducted a phase II trial of S-1 plus CDDP combined with concurrent PBT for patients (pts) with LA NSCLC. Methods: The eligibility criteria included unresectable stage III NSCLC, chemo-naïve status, PS 0 or 1, and age < 75 years. Pts received CDDP (80 mg/m2) on day 1 and S-1 (30-40 mg/m2 twice daily) on days 1 to 14, q4w, up to 4 cycles, plus concurrent PBT at a total dose of 70 GyE in 35 fractions for primary lesion and 66 GyE in 33 fractions for lymph node metastasis. PBT was performed using respiratory-gated and image-guided techniques, and adaptive plans were implemented according to a verification plan at 10, 20, and 30 days. Results: Thirty-two pts were enrolled between August 2013 and December 2016. The patient characteristics were as follows: median age, 66 (31-74); male/female, 24/8; PS 0, 26 pts; stage IIIA/IIIB, 19/13; non-squamous histology, 17 (53%). Twenty pts were out of indication for radical chemo-radiation with X rays. All 4 cycles of S-1 plus CDDP could be completed in 24 pts and the median number of cycles was 3.3 (range: 2 to 4). Grade 3/4 toxicities per pt were: neutropenia 28%, anemia 13%, thrombocytopenia 9.4%, fatigue, anorexia, esophagitis, mucositis and enteritis 3.1%, and radiation pneumonitis 0%. One case of febrile neutropenia was observed. PR + CR was achieved in 24 of 28 evaluable pts. The median PFS was 12.5 months, and 2-year OS was 63%, with a median follow-up period of 19.5 (range: 1.5-40.0) months. Conclusions: Concurrent chemo-PBT using S-1 plus CDDP with image-guided and adaptive techniques is considered to be effective and well tolerated for LA NSCLC. Further evaluations in a large randomized controlled trial are warranted.

We analysed the patient characteristics among adult asthmatics hospitalized to our hospital to clearfy the residual problems in the prevention and treatment of asthma.We identified the adult asthmatics hospitalized to our hospital during the period A: Jan 2004-Dec 2005 and the period B: Jan 2009-Dec2010 and analysed retrospectively around age, smoking history, and the use of ICS (including combination medicine) and so on.The total patient numbers were A: 161 and B: 88, decreasing to almost half. The rates of the patients older than 65 years were equivalent between the 2 groups. Categorized according to age, in the group65 years old, the rates of ICS use were A: 22.9% and B: 35.8% and the current smoking rates were A: 42.7% and B: 49.1% respectively. In the group 65≤ years old, the rates of ICS use were A: 46.2% and B: 48.6%, and the current smoking rates were A: 19.7% and B: 22.9%.In the group65 years old, ICS has become more popular but smoking rate has increased among hospitalized adult asthmatics. It is estimated that smoking leads to reduce the effect of ICS and the strategy of smoking cessation will be needed to reduce acute exacerbations. In the group 65≤ years old, ICS is relatively more popular than youth and smoking rate is limited. Asthma among elder people may be refractory and more efficient strategies must be required.