Ayako Tanaka

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

In this phase Ib study, four combination therapies of nivolumab 10 mg/kg and standard chemotherapy (cisplatin/gemcitabine, cisplatin/pemetrexed, carboplatin/paclitaxel/bevacizumab, or docetaxel) showed acceptable toxicity profiles in patients with advanced non-small-cell lung cancer. Furthermore, these combination therapies presented encouraging antitumor activities.

Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non–small cell lung cancer

Programmed death‐ligand 1 (PD‐L1) expression status is inadequate for indicating nivolumab in patients with non–small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation‐related parameters) on progression‐free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27–87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil‐to‐lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44–5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

External Validation of Preoperative Nomograms Predicting Biochemical Recurrence after Radical Prostatectomy

OBJECTIVE Preoperative nomograms can accurately predict the rate of biochemical recurrence after radical prostatectomy. Although these nomograms were shown to be valid in several external validation cohorts of Caucasian patients, they have not been validated in non-Caucasian patients from Asian countries. We therefore validated these preoperative nomograms in a Japanese cohort, using different cutoff values of prostate-specific antigen concentrations for biochemical recurrence. METHODS We analyzed 637 patients who underwent radical prostatectomy for clinically localized prostate cancer at the Tokyo Medical University Hospital between February 2000 and January 2011. We evaluated two prostate-specific antigen cutoff values for biochemical recurrence, 0.2 and 0.4 ng/ml. Using c-index and calibration plots, we validated the previously developed Kattan and Stephenson nomograms. RESULTS Overall, the mean 5-year non-biochemical recurrence rate was 72 ± 4%. Using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Kattan nomogram were 0.714 and 0.733. Similarly, using a prostate-specific antigen cutoff values of 0.2 and 0.4 ng/ml, the c-indices for the Stephenson nomograms were 0.717 and 0.671. The calibration plots showed that the predictive value of the Stephenson nomogram at a prostate-specific antigen cutoff of 0.2 ng/ml was close to the actual outcomes compared with other combinations of nomograms and prostate-specific antigen cutoff levels. CONCLUSIONS Because the c-indices of both nomograms were generally high, these nomograms can be applied to our cohort. The addition of biopsy information did not markedly improve the c-index but resulted in good calibration, indicating that the Stephenson nomogram may be a better fit for our patient cohort.

Successful retreatment with osimertinib after osimertinib-induced acute pulmonary embolism in a patient with lung adenocarcinoma: A case report

Pulmonary embolism (PE) can be life-threatening, and it is challenging to diagnose because of its nonspecific signs and symptoms. PE is also an important potential risk of osimertinib treatment, however, clinical courses regarding retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We described a 77-year-old woman with postoperative recurrent lung adenocarcinoma who developed osimertinib-induced acute PE. She received apixaban and was later successfully retreated with osimertinib. This case suggests that retreatment with osimertinib after osimertinib-induced acute PE may be a treatment option when alternative therapeutic options are limited.

Effective Management of Persistent Pneumothorax Using a Thopaz® Digital Drainage System Combined with an Endobronchial Watanabe Spigot.

A 72-year-old man with salivary gland cancer and multiple pulmonary metastases suffering from intractable pneumothorax was transferred to our institution; he was inoperable because of a low pulmonary function. A chest tube had been placed more than a month prior to this admission. A digital drainage system was used for 24-h monitoring of air leaks (Thopaz®). Using the Thopaz® system, we performed endoscopic bronchial occlusion using an endobronchial Watanabe spigot (EWS) to reduce air leaks. Finally, the air leaks ceased, and the chest tube was removed five days after EWS placement. We herein report a case of persistent pneumothorax that was successfully treated by endoscopic bronchial EWS placement with the aid of a Thopaz® system.

Torsion of a seminoma in an intrascrotal testis: a case report and review of the literature

An intrascrotal testicular torsion with malignant testicular tumour is extremely rare. We report a case of a 26-year-old male who was diagnosed with testicular torsion by magnetic resonance imaging and with testicular seminoma after orchiectomy. Through this case, we found that if the possibility of testicular torsion remains during the diagnosis of acute scrotum cases, additional examination adding to colour Doppler sonography should be performed. Furthermore, we should be aware of the possibility of testicular tumours during the diagnosis and treatment of acute scrotums. If the affected testis is preserved in the treatment of testicular torsion, a postoperative examination by ultrasound and/or tumour markers for the remaining testis is essential to confirm the absence of testicular tumour.

Emphysematous cystitis following a transrectal needle guided biopsy of the prostate

BackgroundEmphysematous cystitis (EC) is a comparatively rare urinary tract infection characterized by air within the bladder wall and lumen and is usually associated with immunosuppression or poorly controlled diabetes mellitus.Case presentationWe report a case of EC in a 70-year-old man who recently underwent transrectal ultrasound needle-guided prostate biopsy, after which he underwent pylorogastrectomy. He did not have any history of diabetes mellitus or any immunosuppressive disease. The patient developed severe sepsis, requiring intravenous antibiotics and urinary catheterization. Despite therapy, the patient developed disseminated intravascular coagulopathy and acute respiratory distress syndrome. Therefore, he was admitted to the intensive care unit, antibiotic coverage was broadened, and danaparoid sodium and sivelestat sodium hydrate was administered. After 20 days, the patient’s condition improved, and on the 28th day, the patient was discharged to home in a good condition without any sequelae.ConclusionPrompt diagnosis and treatment are warranted to prevent potential morbidity of and mortality in cases of EC.

Afatinib successfully treated leptomeningeal metastasis during erlotinib treatment in a patient with EGFR-mutant (Exon18:G719S) lung adenocarcinoma as a second-line chemotherapy

Exon18 mutations are detected in 3.6% of epidermal growth factor receptor mutations. Exon 18 mutations as driver mutations have higher sensitivities in vitro to second‐generation (G)‐tyrosine kinase inhibitors (TKIs) than to first G‐ and third G‐TKIs at clinically relevant doses. In clinical trial, first G‐TKIs have moderate but insufficient efficacy, and afatinib was more active in uncommon epidermal growth factor receptor mutations. Here, we present a case of a woman who was initially prescribed erlotinib for lung adenocarcinoma with an exon18 mutation. She developed a leptomeningeal metastasis during treatment and was switched to afatinib. Subsequently, her symptoms improved and she is currently treated with maintenance afatinib therapy. This report suggests improved efficacy of afatinib compared to erlotinib for refractory leptomeningeal metastasis in exon18 mutation.

Osimertinib Treatment was Unsuccessful for Lung Adenocarcinoma with G719S, S768I, and T790M Mutations

Epidermal growth factor receptor (EGFR) T790M mutations are the most frequent mechanism of resistance to first- and second-generation tyrosine kinase inhibitors, and osimertinib is an effective treatment for patients with both EGFR-activating mutations and T790M resistance mutations. We describe the case of a 68-year-old woman with lung adenocarcinoma with G719S, S768I, and T790M mutations in which osimertinib treatment was unsuccessful. The patient died of disease progression one month after discontinuing osimertinib treatment. This case suggests that osimertinib may be ineffective for treating patients with uncommon mutations such as G719S when the patient has also acquired a T790M resistance mutation.

Successful osimertinib rechallenge after osimertinib-induced pneumonitis in a patient with lung adenocarcinoma

Pneumonitis is a serious adverse event of EGFR-TKI treatment. Although several cases of EGFR-TKI rechallenge after EGFR-TKI-induced pneumonitis have been reported, little is known about post-pneumonitis osimertinib rechallenge. We describe a 69-year-old never-smoking Japanese woman with postoperative recurrent lung adenocarcinoma retreated with osimertinib after osimertinib-induced pneumonitis. Although osimertinib rechallenge must be carefully chosen based on risk/benefit analysis, osimertinib rechallenge after osimertinib-induced pneumonitis may be an option, with limited alternative therapeutic options.