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Patients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors.This multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti-spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2.A total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65-74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%-28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%-11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p0.001).Patients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.

Acetaminophen (APAP)-induced liver injury (AILI) is the most common cause of acute liver failure. Although the mechanisms that trigger AILI are well known, it is less understood how to halt AILI progression and facilitate liver recovery. Therefore, it is necessary to understand the pathophysiology of APAP hepatotoxicity in patients and to examine predictive/preventive markers. In a clinical study, we had a case in which aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased in a patient with a low ratio of APAP glucuronide concentration (AP-G)/APAP plasma concentration. Then a reverse translational study was conducted for clarifying this clinical question. The relationship between plasma AP-G/APAP concentration ratio and the levels of AST and ALT was examined by in vivo and in vitro experiments. In in vivo experiments, 10-week-old rats showed lower UGT activity, lower AP-G/APAP concentration ratios, and higher AST and ALT levels than 5-week-old rats. This suggests an inverse correlation between the AP-G/APAP concentration ratio and the AST, ALT levels in APAP-treated rats. Furthermore, as a result of the in vitro experiment, it was confirmed that the cell viability decreased when the AP-G/APAP concentration ratio in the culture medium decreased. Since the decrease in the plasma AP-G/APAP concentration ratio appears earlier than the increase of AST and ALT levels, the ratio might be a presymptomatic marker of AILI. When APAP is used for a long time, it is recommended to perform therapeutic drug monitoring of the AP-G/APAP concentration ratio, which is a predictive/preventive marker of AILI.

We aimed to assess the efficacy and safety of synbiotics, including live microorganisms and non-digestible food ingredients, in patients undergoing high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT). This prospective, randomized, double-blind study, included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomized to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo including dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). The secondary endpoint was safety. A total of 12 patients were included and randomized. The median duration of TPN was 15 days (range, 12–33 days) in the synbiotic group and 17.5 days (range, 0–32 days) in the placebo group, with no clear difference between the two groups. The median duration of grade 3 or higher diarrhea was shorter in the synbiotic group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). Oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Synbiotics may reduce gastrointestinal toxicity leading to nutritional problems and improve the quality of life of patients undergoing auto-HSCT, without severe adverse events. (The Japan Registry of Clinical Trials, No. jRCTs051180026.)

Chemoimmunotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC) in two phase III trials. They set the age-stratified subgroup analyses at 65 years; however, over half of the patients with lung cancer were newly diagnosed at ≥75 years in Japan. Therefore, treatment efficacy and safety in elderly patients ≥ 75 years with ES-SCLC should be evaluated through real-world Japanese evidence. Consecutive Japanese patients with untreated ES-SCLC or limited-stage SCLC unfit for chemoradiotherapy between 5 August 2019 and 28 February 2022 were evaluated. Patients treated with chemoimmunotherapy were divided into the non-elderly (

Background There are many commercially available automated assays for assessing coronavirus disease 2019 (COVID-19) immune responses; however, owing to insufficient data, their validities remain unknown. Here, we examined antibody responses during acute-phase COVID-19 using four assays that detect anti-spike protein IgM (S-IgM), anti-nucleocapsid protein IgG (N-IgG), anti-spike protein total Ig (S-total Ig), and anti-spike protein IgG (S-IgG). Methods We measured antibody levels in 1154 serum samples collected from 286 hospitalized patients with confirmed COVID-19 by a gene amplification method between February and December 2020 in Japan. Sera from 860 healthcare workers were used as negative controls. Results The antibody positivity rates increased on week 2, peaked, and then started to plateau by the beginning of week 3 after symptom onset. On week 1, there were some significant differences in seropositivity rates between assays (p = 0.032): 14.9% (11.0%–19.4%) for S-IgM and 8.9% (6.0%–12.7%) for N-IgG. The seropositivity for the S-total Ig (10.6% [7.3%–14.6%]) assay was considerably better than that for the S-IgG (6.9% [4.3%–10.4%]) assay, although the difference was not statistically significant (p = 0.150). The levels of S-IgM antibodies and the three others peaked on weeks 3 and 5, respectively. All four assays showed high specificities (>99%). Conclusions All four assays had good specificities and were suitable for seropositivity detection after week 3 of symptom onset. Assays of IgM alone or total Ig (containing IgM) were better than those of IgG alone as an adjunct serological test for early-stage COVID-19 diagnosis, albeit the use of a serological assay alone is insufficient.

We herein report a 76-year-old man who developed irritability and forgetfulness 5 months after the introduction of atezolizumab for the treatment of small cell lung cancer (SCLC). Brain magnetic resonance imaging showed lesions of the striatum, and an investigation of the serum revealed a high titer of anti-CRMP5 antibody. After stopping atezolizumab and starting steroid pulse therapy, these clinical features improved. Given these findings, it is considered that CRMP5-assciated striatal encephalitis was induced by atezolizumab in this case with SCLC.

Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), and it has been suggested that lymphocyte recovery affects survival after HSCT. However, few studies have examined lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease. We retrospectively evaluated early lymphocyte recovery after HSCT among Japanese adults who received MMF prophylaxis. Patients were divided into two groups according to their median absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the “low ALC group” (≤ 0.22 × 109 cells/L) and the “high ALC group” (> 0.22 × 109 cells/L). With a median follow-up of 317 days, the high ALC group showed significantly better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02). The high ALC group also tended to have better non-relapse mortality than the low ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P = 0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC on day 28 after HSCT was effective in predicting overall survival and non-relapse mortality.

PURPOSE The complexity of lung cancer treatment is rapidly increasing, necessitating the use of multidisciplinary approaches for improving outcomes. Although it is common for institutions to have their own tumor boards, tumor boards connecting several general hospitals, and therefore allowing for more diverse opinions, are not prevalent. MATERIALS AND METHODS A tumor board connecting eight hospitals was formed to discuss patients for whom formulating a treatment strategy was difficult. Physicians and hospital staff accessed a high-security communication line via LiveOn ( Japan Media Systems Corporation, Tokyo, Japan), which is completely isolated from the Internet and password protected, that enables each hospital to share the electronic medical records and images of relevant patients at other hospitals on desktop computers in real time. The lung cancer tumor board began in April 2017 and has since been held every Tuesday evening for 1 hour. Preparatory records containing the age, sex, histology, TNM classification, background, and discussion points for each patient are created before each tumor board meeting. After the tumor board discussion, all conclusions and related articles used in the board are added to the minutes, which are finalized as Microsoft Word files, consolidated, and archived. These files can be retrieved later using key words. RESULTS From April 2017 to June 2018, 202 patients were discussed. Although TNM classification was not changed for any patient, diverse opinions led to a change in the proposed strategy for 49 of 202 patients. CONCLUSION The multidisciplinary tumor board was useful in obtaining various opinions from the perspectives of different experts. This should be evaluated in a prospective study.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for treating EGFR-mutated lung cancer, and osimertinib is effective in cases that acquired T790M mutations after treatment with the first- and second-generation EGFR-TKIs. However, no study has evaluated its safety and efficacy in older patients. This phase II trial (jRCTs071180002) evaluated osimertinib in T790M mutation-positive Japanese patients who were &ge, 75 years old and had experienced relapse or progression after previous EGFR-TKI treatment. Our previous report that enrolled 36 patients showed the overall response rate (58.3%) and disease control rate (97.2%), while this report describes the results for the progression-free survival (PFS), overall survival (OS), and safety analyses. The median PFS was 11.9 months (95% confidence interval (CI): 7.9&ndash, 17.5), and the median OS was 22.0 months (95% CI: 16.0 months&ndash, not reached). The most frequent adverse events were anemia/hypoalbuminemia (27 patients, 75.0%), thrombocytopenia (21 patients, 58.3%), and paronychia/anorexia/diarrhea/neutropenia (15 patients, 41.7%). Pneumonitis was observed in four patients (11.1%), including two patients (5.6%) with Grade 3&ndash, 4 pneumonitis. These results suggest that osimertinib was relatively safe and effective for non-small cell lung cancer that acquired T790M mutations after previous EGFR-TKI treatment, even among patients who were &ge, 75 years old.

A 49-year-old female was initially diagnosed with acute myeloid leukemia (AML) M4 with a CD45＋CD13＋CD33＋CD34-HLA-DR＋ immunophenotype. She underwent allogeneic bone marrow transplantation, but the disease recurred. The bone marrow was infiltrated with 87.0% blasts negative for myeloperoxidase (MPO) staining. Immunophenotyping by flow cytometry identified the presence of a CD45-negative blast population. These blasts exhibited a CD13＋CD33＋CD19-CD10-CD34-HLA-DR- immunophenotype. The lack of CD45 expression is often observed in B-cell acute lymphoblastic leukemia, whereas CD45-negative AML is extremely rare; only one older male with AML-M0 has been reported. In the present case, the CD45-negative blasts had an MPO-CD13＋CD33＋ phenotype, which is similar to AML-M0.

Background Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. Methods and results We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. Conclusions Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Lessons Learned Non-small-cell lung cancer (NSCLC) represents 85% of lung cancer in elderly patients. In the present study performed in the 36 elderly subjects with epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, osimertinib 80 mg demonstrated statistically significant improvement in the objective response rate, which was comparable to those in the nonelderly population. Osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation; further research in larger scale is warranted. Background Previous findings suggest the possibility of relatively safe use of osimertinib for patients with T790M-positive non-small-cell lung cancer (NSCLC), with few serious adverse events for the elderly in comparison with conventional endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and with an antitumor effect. Methods This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients aged ≥75 years with ineffective prior EGFR TKI treatment or with recurrence in T790M EGFR TKI resistance mutation-positive NSCLC. Results A total of 36 patients were included in the analyses. Among the 36 subjects, 63.9% were female, with mean age of 79.9 years. The objective response rate (ORR) was 58.3% (95% confidence interval [CI], 42.2%–72.9%), demonstrating statistically significant efficacy of osimertinib (p = .0017). The median duration of response (DOR) was 27.9 weeks (95% CI, 21.1–82.0). Complete response (CR) and partial response (PR) were 2.8% and 55.6%, respectively. Disease control rate (DCR) was 97.2%. A waterfall plot revealed that 33 (91.6%) subjects exhibited tumor shrinkage during treatment, including 12 of 14 subjects who had stable disease (SD). All adverse events were not reason for discontinuation of the study drug. Conclusion Osimertinib may be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation.

A 50-year-old man presented with a 12 kg weight loss in 8 months. Upper gastrointestinal endoscopy findings showed strong erosion and diffuse bleeding in the duodenum. Histopathological findings showed PAS staining-positive macrophages consistent with Whipple's disease. He was treated with trimethoprim-sulfamethoxazole. His condition initially improved. However, during his 6-year course of treatment he developed a central nervous system relapse. Tropheryma whipplei DNA was detected by a polymerase chain reaction in his cerebrospinal fluid. This relapse was successfully treated with ceftriaxone sodium (CTRX). We considered that as initial therapy for Whipple's disease, it would be important to administer CTRX for at least a few months, due to its high translatability to CSF.

A 57-year-old man was admitted with headache, vomiting, and bloody sputum. We diagnosed large cell lung cancer T4N2M1 (pituitary metastasis), Stage IV. When hospitalized, low values of cortisol and hyponatremia were found. A hormone stimulation test was performed, because we suspected hypopituitarism. The reaction of adrenocorticotropic hormone (ACTH) to the corticotropin-releasing hormone (CRH) loading test was good, but the reaction of serum cortisol was minimal. After corticosteroid administration, his serum sodium normalized. Limited ACTH reserve according to insufficient pituitary function was suggested as a cause of the hyponatremia. He received gamma-knife therapy, however his pituitary gland tumor did not decrease in size. Clinical symptoms such as visual field disturbance, oculomotor paresis, and visual impairment progressed, and he died about 5 months later. We report a case of hyponatremia in a patient with pituitary metastasis of lung cancer, as it is comparatively rare.

To summarize the effect of Iressa for refractory patients with advanced non small cell lung cancer (NSCLC) failed to prior chemotherapy.Thirty-one patients, with unresectable stage IIIB or IV NSCLC who had disease progression or relapse after prior chemotherapy using platinum-based regimen for at least 2 cycles, were admitted to the Osaka Prefectural Hobikino Hospital. Iressa 250 mg was administered once a day until disease progression was noted. Weekly chest x-ray and monthly CT scan were performed for response assessment each month.Among the 31 patients, one complete response (CR) and 7 partial responses (PR) were observed. CR rate was 3.2% (95% confidence interval: 0-17%), PR rate 22.6% (95% confidence interval: 10%-41%), disease control rate including both tumor responses and stable disease was 80.6% (95% confidence interval: 52%-92%). The rate of symptoms relieves was 51.6% (95% confidence interval: 33%-70%), the most effective symptoms being cough and pain. The median time to improved symptoms was 14 days. The most common adverse events were grade I or II skin rash and diarrhea which were readily manageable and reversible. No patients were withdrawn due to the adverse eventsMonotherapy using Iressa is effective and tolerable for the patients with advanced NSCLC who failed prior chemotherapy.

We report a case of pneumatosis cystoides intestinalis (PCI) in a patient with lung cancer. A 60-year-old woman was admitted with multiple lung tumors and multiple brain tumors. She was given steroid hormones to reduce her brain edema. Total resection of a brain tumor yielded a pathological diagnosis of metastatic squamous cell carcinoma. During treatment, X-ray and CT images revealed intestinal pneumatosis and free air in the abdominal cavity, but a physical examination revealed no abnormal findings. She was given a diagnosis of PCI, and received conservative treatment. Her intestinal gas cysts and intra-abdominal free air disappeared spontaneously. PCI is an uncommon but important condition in which gas is found in a linear or cystic form in the submucosa or subserosa of the bowel wall. It is important to consider PCI as a possible complication in lung cancer patients who are given steroid hormones and systemic chemotherapy in the long-term.

Background: Mucosal melanoma (MUM) is a very rare malignancy and accounts only for approximately 1% of all melanomas in the United States and 3.8% in Japan. In general, the prognosis of MUM is poorer than that of cutaneous melanoma. Recently, targeted therapies for immune-checkpoints and BRAF have shown promising effects in the treatment of recurrent or metastatic melanoma. However, the optimal treatment for MUM remains to be defined. In Japan, dacarbazine (DTIC) is the only available chemotherapeutic drug for melanoma. Thus, we conducted this retrospective study of DTIC monotherapy for recurrent or metastatic MUM (RM-MUM). Methods: We retrospectively reviewed 7 patients with RM-MUM treated with DTIC monotherapy (A, 200 mg/m2/day for 5 days q4wks or B, 1,000 mg/m2/day for 1 day q3wks) between December 2007 and October 2013. Results: Three male and four female patients with a median age of 62 years (range, 44-70 years) were treated with DTIC. Primary tumors were located in the nasal cavity (n = 3), maxillary sinus (n = 1), choroid (n = 1), esophagus (n = 1) and rectum (n = 1). Prior treatments were radiation therapy (n = 4), surgery (n = 3) and adjuvant chemotherapy with a DTIC-based regimen (n = 1). Five patients received the A regimen and two patients received the B regimen. The median number of treatment cycles was 4 (range, 2-15 cycles). Two patients achieved PR and two patients achieved disease stabilization over 12 months, resulting in a response rate of 29% and a disease control rate of 57%. The median time to progression was 2.7 months (range, 1.5-42.1 months) and the median overall survival was 27.5 months (range, 2.6-62.3 months). Toxicities were mild and no serious adverse event was observed. Conclusions: The use of DTIC was feasible irrespective of its dose fractions. DTIC appeared to have modest activity, and some patients achieved durable responses.