Safety and efficacy of afatinib for the treatment of non-small-cell lung cancer following osimertinib-induced interstitial lung disease: A retrospective study.

Background Osimertinib is one of the first-line treatments for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. However, the occurrence rate of osimertinib-induced interstitial lung disease (ILD) is particularly high in Japanese patients and little information on subsequent cancer treatment options after recovery from osimertinib-induced ILD is currently available. Thus, this study aims to determine the safety and efficacy of afatinib for the treatment of NSCLC following osimertinib-induced ILD. Methods We retrospectively investigated the clinical courses of all NSCLC patients with EGFR mutations at our facility between August 2018 and September 2019, who received osimertinib as first-line treatment and were subsequently treated with afatinib after developing osimertinib-induced ILD. Results Forty-two patients received osimertinib treatment at our facility during the study period, and four patients received afatinib after developing osimertinib-induced ILD. All events of ILD improved either spontaneously or with steroid therapy before the initiation of afatinib. For the four patients who were retrospectively reviewed, the overall response rate to afatinib therapy was 75%, and the disease control rate was 100%. During the study period, no ILD recurrence was observed in any of the four patients. Conclusions According to our study findings, afatinib treatment after osimertinib-induced ILD is considered safe and effective and it can be used as one of the treatment options for NSCLC following osimertinib-induced ILD.

Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer.

Background Bevacizumab (Bev) is generally well-tolerated, and Bev-associated intestinal perforation (BAP) is a rare albeit serious side effect in cases of non-small cell lung cancer (NSCLC). Therefore, the present study aimed to identify clinical predictors of BAP to help predict and manage the development of life-threatening intestinal complications among patients receiving Bev. Methods This retrospective study evaluated demographic, clinical, and treatment factors for patients with NSCLC who were treated with Bev between February 2010 and August 2015 at our center. Results We identified 314 regimens (208 patients; median age: 65 years; 115 women) for analysis, which included 119 first-line regimens, 74 s-line regimens, and 121 third-line or later regimens. BAP occurred in 7 cases (2.23% among all regimens and 3.37% among all patients), which generally occurred during first- or second-line treatment and was caused by ulcerative colitis (1 case), colon diverticulitis (1 case), and idiopathic perforations (5 cases). Univariate analyses revealed that BAP was significantly associated with deteriorating PS during the first cycle of chemotherapy (odd ratio [OR]: 11.07, 95% confidence interval [CI]: 2.37-51.63, p = 0.0022), grade ≥ 3 diarrhea (OR: 11.37, 95% CI: 2.37-54.50, p = 0.0024), febrile neutropenia (OR: 9.16, 95% CI: 1.98-42.49, p = 0.0047), and stomatitis (OR: 4.60, 95% CI: 1.01-21.04, p = 0.0492). Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane.

Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations.

Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536).

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study.

BACKGROUND: In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies. METHODS: We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines. RESULTS: Patient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0-1/2/3-4: 24/4/2; Stage IIB-IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P < 0.005). Non-hematological adverse events of Grade ≥ 3 were observed in 5 (16.7%) of 30 patients. One CRC patient experienced Grade 3 hemoptysis and another 2 experienced Grade 3 anaphylaxis. One patient with cholangiocellular carcinoma and gastric cancer experienced Grade 3 pseudomembranous colitis as a result of a Clostridium difficile infection. One patient (3.3%) died of pemetrexed-induced pneumonitis. The success of the anti-MTB chemotherapy was 70.0%. There were no MTB-related treatment failures. The median overall survival (months, 95.0% confidence interval) was 10.5 (8.7-36.7), 8.7 (4.7-10.0), 36.7 (minimum 2.2), and 14.4 (minimum 9.6) for all patients combined, LC, CRC, and Other malignancies, respectively. LC patients experienced delayed MTB diagnosis and shorter overall survival. CONCLUSIONS: Concurrent chemotherapy is effective and safe for treating cancer patients with active MTB.

Radial endobronchial ultrasound with a guide sheath for diagnosis of peripheral cavitary lung lesions: a retrospective study.

BACKGROUND: Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic outcomes of peripheral lung lesions. However, to our knowledge, reports on the use of EBUS-GS for diagnosis of cavitary lesions are unavailable. Therefore, this study aimed to assess the effectiveness and safety of EBUS-GS for diagnosis of peripheral cavitary lung lesions (PCLLs). METHODS: This study was a single-institution retrospective review of PCLLs examined by using EBUS-GS between July 2013 and October 2015. The diagnostic results of different EBUS-GS samples, including cytologic, histopathologic, and microbiologic samples, were analysed separately. RESULTS: Of 696 radial EBUS procedures performed during the study period, 50 were performed for examination of PCLLs. The overall diagnostic yield for EBUS-GS was 80 % (40/50). Regarding 27 malignant lesions, the diagnostic yields for cytologic and histopathologic samples were 63.0 % (17/27) and 74.1 % (20/27), respectively. Regarding 23 benign lesions, the diagnostic yields for histopathologic and microbiologic samples were 69.6 % (16/23) and 47.8 % (11/23), respectively. Uni- and multivariate analyses indicated that the EBUS probe being within the lesion was the only factor significantly associated with increased diagnostic yield (odds ratio, 7.04; P = 0.03). Although pulmonary infection occurred after the procedure in 1 patient (2.0 %), no other complications, including pneumothorax or significant haemorrhage, were reported. CONCLUSION: EBUS-GS was found to be an effective and safe procedure for diagnosis of PCLLs.

[Evaluation of the Safety of a Generic Formulation of Cisplatin in Patients with Thoracic Malignancies].

Cisplatin (CDDP) is a key drug in the systemic treatment of various solid tumors. Brand-name CDDP may differ across generic formulations considering various clinical parameters. Therefore, in this study, we aimed to assess the safety of a generic CDDP formulation. To compare brand-name CDDP with a generic formulation, the incidence of adverse events, especially renal toxicity, was investigated in 500 patients with thoracic malignancies who received chemotherapy with more than 60 mg/m2 of either brand-name or generic CDDP. We compared the maximum serum creatinine (Cr) level after chemotherapy in the 2 groups. The correlation coefficients between the pretreatment Cr and the maximum Cr after CDDP administration did not differ between brand-name CDDP and generic CDDP (0.610 and 0.644, respectively; p=0.528). Furthermore, the correlation coefficients did not differ in subgroup analysis according to sex or adjuvant therapy. The severity of adverse events was similar in the 2 groups. In conclusion, generic CDDP can safely be used as an alternative to brand-name CDDP in the clinical setting.

[Retrospective Analysis of the Afatinib Clinical Pathway during the 28-Day Introductory Period-The Japanese Style of Collaborative Drug Therapy Management(J-CDTM)].

Afatinib is a newly approved second-generation epidermal growth factor receptor-tyrosine kinase inhibito r(EGFR-TKI). Afatinib has been shown to prolongthe overall survival of patients with non-small cell lungcancer (NSCLC) with EGFR mutations compared with the standard chemotherapy. However, Grade 3 or 4 toxicities, includingdiarrhea, rash, paronychia, and stomatitis, have been observed more frequently in patients treated with afatinib than in those treated with first-generation EGFR-TKIs. Accordingly, our institution developed an afatinib clinical pathway (the afatinib pathway), which was designed by certified nurses, medical physicians, and certified pharmacists, with the goal of reducing the severity of diarrhea and rash that occur most frequently duringthe 28-day introductory period of afatinib treatment. Between May and October 2014, afatinib was administered accordingto the afatinib pathway to 14 patients with NSCLC and EGFR mutations. Of these patients, only one (7.1%) experienced Grade 3 diarrhea. No other patient experienced Grade 3 or 4 toxicity. The afatinib pathway was effective in reducingthe severities of the diarrhea and rash duringthe 28-day introductory period of the afatinib treatment. Our implementation of the afatinib pathway could be considered the Japanese style of collaborative drugtherapy management (J-CDTM).

Comparison of the clinical courses and chemotherapy outcomes in metastatic colorectal cancer patients with and without active Mycobacterium tuberculosis or Mycobacterium kansasii infection: a retrospective study.

BACKGROUND: Although active Mycobacterium tuberculosis (MTB) or Mycobacterium Kansasii (MK) infection could be present in patients with metastatic colorectal cancer (m-CRC), no study is available on the clinical courses and chemotherapy outcomes of these patients. The present study therefore aimed to retrospectively examine whether m-CRC patients with and without active MTB or MK infection could receive cancer chemotherapy similarly. METHODS: This study enrolled 30 m-CRC patients who received first-line chemotherapy between January 31, 2006 and January 31, 2013 at our institution, The clinical courses and tumor response of those with and without active MTB or MK infection were examined and compared. RESULTS: Of 30 m-CRC patients, 6 had active MTB infection, 1 with active MK and the other 23 had neither MTB nor MK. No significant demographic differences were observed between patients with MTB or MK and those without. Chemotherapy response rates of all patients, those with MTB or MK, and those without were 40.0%, 28.6% and 43.5%, respectively. Among patients with MTB or MK, 1 treated with bevacizumab experienced grade-3 hemoptysis while others did not report any severe toxicity. Median survival time of all studied patients, those with MTB or MK, and those without was 26.3, 36.7 and 22.6 months, respectively. No significant difference in overall survival was observed between patients with MTB or MK and those without. Multivariate analysis revealed that performance status and liver metastasis were significant prognostic factors of overall survival (P = 0.004 and 0.030, respectively), whereas other factors, including MTB or MK infection, were not. In our study, all 7 patients with MTB or MK did not experience infection relapse during or after cancer chemotherapy. CONCLUSIONS: Our results indicate that m-CRC patients with MTB or MK should be able to safely and effectively continue cancer chemotherapy to subsequently achieve comparable survival duration to those without the infection if they receive proper MTB or MK treatment.

Stratification of malignant pleural mesothelioma prognosis using recursive partitioning analysis.

PURPOSE: Prognostic factors and complicated prognostic models have been proposed for malignant pleural mesothelioma (MPM). This study was designed to stratify MPM prognosis by using a simple model. METHODS: Patients diagnosed with MPM in the past 10 years (n = 122) were examined retrospectively. Data on the presence of chest pain, performance status (PS), asbestos exposure, smoking status, white blood cell count (WBC), haemoglobin (Hb) concentration, platelet count (PLT), lactate dehydronate (LD), histology, stage, and date of death or censored status were collected. After the factors were examined in the univariate analysis, recursive partitioning analysis was performed. RESULTS: Statistically significant factors related to survival were the type of histology, stage, PS, WBC, PLT, Hb concentration, and LD. Histology, stage, PS, and Hb concentration were used in multivariate analysis. Stage and Hb concentration showed good statistical significance, whereas PS was borderline significant. The survival analyses were stratified into five groups by PS, stage, Hb concentration, and chest pain using recursive partitioning analysis. Group A comprised patients showing the most favourable prognoses (PS 0-2 and Hb concentration >12.1 g dL(-1) or PS 0-2 and Hb concentration ≤12.1 g dL(-1) without pain), and group B comprised the remaining patients. The median overall survival in groups A and B was 563 days (95 % confidence interval [CI] 502-779) and 157 days (95 % CI 115-224), respectively (hazard ratio of 5.44 [3.46-8.53, P < 0.0001]). CONCLUSIONS: The MPM patients with PS 0-2 and Hb concentration >12.1 or ≤12.1 g dL(-1) without chest pain had favourable prognoses.

[Denosumab for bone metastasis of thoracic tumors-preparation of a practice manual and evaluation of its effectiveness].

The anti-receptor activator of nuclear factor-kB ligand (RANKL) antibody denosumab is thought to be useful in the improvement of the quality of life of patients with bone metastasis from thoracic tumors, given the ease of its subcutaneous administration. However, attention has to paid to the onset of hypocalcemia when determining the optimal dosage, especially since data and methods on its prevention are limited. Our project team monitored serum calcium levels in patients receiving denosumab treatment, evaluated methods to supplement calcium and vitamin D in cases of hypocalcemia, and developed an evidence-based common manual. Subsequently, denosumab administration and hypocalcemia were evaluated as per the manual. Grade 3 hypocalcemia was observed in 2 cases before the preparation, with no new cases seen since adopting the new protocol in the manual. We conclude that the development of severe hypocalcemia associated with denosumab treatment can be avoided by prompt management of this condition in the early stages and by adopting measures listed in the practice manual.

Impact of pneumonia on hyperactive delirium in end-stage lung cancer patients.

PURPOSE: Patients with incurable lung cancer often receive palliative care. Hyperactive delirium is a burden not only for the patient's family but also for caregivers. There are no reports describing the risk factors for delirium among lung cancer patients. The present study investigated the frequency of incidence and risk factors for hyperactive delirium among end-stage lung cancer patients. METHODS: Patients who died of lung cancer in our institute from January 2010 to December 2010 were retrospectively investigated. Information was obtained from medical records, and patients who developed hyperactive delirium (delirium group, group D) were compared with patients who did not (control group, group C) based on clinical and laboratory data. RESULTS: A total of 146 patients (median age, 70 years; 80 % male) died of lung cancer. Thirty-one (21.2 %) patients developed hyperactive delirium. Sex (P = 0.0093) and pneumonia (P = 0.023) were statistically significant variables in univariate analysis. Pneumonia occurred in 27.4 % of all patients. The incidence of pneumonia was 45.2 % in group D and 22 % in group C. Only pneumonia (odds ratio, 2.89; 95 % confidence interval, 1.22-6.85; P = 0.016) was identified as a significant factor for predicting hyperactive delirium in multivariate analysis. CONCLUSIONS: Pneumonia was identified as a significant risk factor for the development of hyperactive delirium among end-stage lung cancer patients.

Diagnostic yield of combined bronchoscopy and endobronchial ultrasonography, under LungPoint guidance for small peripheral pulmonary lesions.

BACKGROUND AND OBJECTIVE: The yield of biopsy performed during bronchoscopy is reduced if the lesion is smaller than 30 mm. We evaluated the performance of a new diagnostic technique combining endobronchial ultrasonography with a guide sheath (EBUS-GS) and a virtual bronchoscopic navigation system, LungPoint (Broncus Technologies, Inc., Mountain View, CA, USA), for the diagnosis of small (≤30 mm) peripheral pulmonary lesions (PPL). METHODS: Between May 2011 and December 2011, we recruited 68 consecutive patients presenting with a PPL 30 mm or less in diameter determined by chest computed tomography. We used the LungPoint system before bronchoscopy to identify the bronchus into which the bronchoscope should be advanced. We used a thin bronchoscope. EBUS-GS was performed using an endoscope ultrasonography system equipped with a 20-MHz mechanical radial-type probe. We used a guide sheath with an external diameter of 1.95 mm, thin forceps and brushing. RESULTS: The diagnostic yield of the 68 PPL was 77.9%; it was 83.7% and 68.0% for the malignant and benign lesions, respectively. Notably, three cases were diagnosed by transbronchial needle-aspiration cytology alone. Univariate and multivariate analyses showed that the EBUS probe localization was the most significant contributor to successful diagnosis (diagnostic yield: within vs adjacent to the lesion = 92.1% vs 60.0%, respectively; P = 0.004 and P = 0.003, respectively). CONCLUSIONS: The combination of EBUS-GS and LungPoint was useful for diagnosing small PPL.

The relationship between tyrosine kinase inhibitor therapy and overall survival in patients with non-small cell lung cancer carrying EGFR mutations.

For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.

Extracellular Water-to-total Body Water Ratio as an Objective Biomarker for Frailty in Lung Cancer Patients.

BACKGROUND/AIM: Our previous study revealed the association between extracellular water-to-total body water ratio (ECW/TBW) and the therapeutic durability of chemotherapy and/or immune checkpoint inhibitors in advanced lung cancer. We retrospectively examined the usefulness of ECW/TBW in detecting frailty compared to other bioelectrical impedance (BIA) parameters in a larger number of patients. PATIENTS AND METHODS: Lung cancer patients underwent BIA before anti-cancer therapy at our hospital between June 1, 2018 and July 31, 2020. RESULTS: Of 99 patients, 26 were assigned to ECW/TBW≥0.4 (higher group: HG) and 57 to ECW/TBW<0.4 (lower group: LG). ECW/TBW increased significantly with performance deterioration and ageing. HG patients had significantly shorter time-to-treatment failure (TTF) than LG patients. In patients with performance status 0-1, those in the HG had shorter TTF than those in the LG. ECW/TBW was the only independent predictor of TTF according to multivariate analysis. CONCLUSION: ECW/TBW is an objective biomarker for detecting frailty among lung cancer patients.

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis.

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.

[Renal salt-wasting syndrome progressing to severe hyponatremia after chemotherapy--a case report].

A 66-year-old woman with small-cell lung cancer was administered chemo-radiotherapy consisting of cisplatin (CDDP) and etoposide (ETP). From day 3, she developed vomiting and hyponatremia that persisted despite fluid infusion and cortico-steroid administration. On day 7, the hyponatremia worsened (serum sodium level, 109 mEq/L), leading to disturbed consciousness and convulsions. The serum sodium level gradually increased after intravenous administration of hypertonic saline; on day 22, the serum sodium level was almost normal without any neurological implication. We diagnosed this clinical condition as renal salt-wasting syndrome (RSWS) on the basis of dehydration and high urinary sodium excretion at the onset. In the second course of chemotherapy, CDDP was replaced with carboplatin (CBDCA); consequently, hyponatremia was not observed. Hyponatremia that develops after the administration of CDDP may be due to not only the syndrome of inappropriate secretion of anti diuretic hormone (SIADH) but also RSWS. When RSWS is suspected, hypertonic saline should be administered.

The Association Between Extracellular Water-to-Total Body Water Ratio and Therapeutic Durability for Advanced Lung Cancer.

BACKGROUND/AIM: Extracellular water-to-total body water ratio (ECW/TBW) measured by bioelectrical impedance analysis (BIA) reportedly predicts clinical outcomes of various diseases. The aim of this retrospective study was to examine the association between ECW/TBW and therapeutic durability of chemotherapy and/or immune checkpoint inhibitors in advanced lung cancer. PATIENTS AND METHODS: Patients with advanced lung cancer underwent BIA before chemotherapy and/or treatment with immune checkpoint inhibitors at our hospital between June 2018 and November 2019. RESULTS: Of 75 patients, 18 with ECW/TBW ≥0.4 were assigned to the overhydrated group (OH-G) and 57 patients ECW/TBW <0.4 were assigned to the non-overhydrated group (NOH-G). The median time-to-treatment failure was significantly shorter in the OH-G than in the NOH-G (p=0.003). Multivariate analysis revealed that ECW/TBW ≥0.4 predicted treatment failure [hazard ratio (HR)=2.508, 95% confidence interval (CI)=1.19-5.27; p=0.01]. CONCLUSION: The ECW/TBW may be an objective parameter for predicting therapeutic durability in advanced lung cancer.

Development of Severe Heart Failure in a Patient with Squamous Non-small-cell Lung Cancer During Nivolumab Treatment.

Cardiac side effects associated with immune checkpoint inhibitors (ICIs) are an uncommon but serious complication with a relatively high mortality. We experienced a case of cardiomyopathy induced by nivolumab. Echocardiography showed diffuse hypo-kinesis of the left ventricular cardiac wall and a significant decrease in the ejection fraction, like dilated cardiomyopathy. The myocardial biopsy showed non-inflammatory change; cardiac function gradually improved after treatment of acute heart failure without a corticosteroid. Although non-inflammatory left ventricular dysfunction induced by ICIs is rare, it is a reported cardiovascular toxicity. Physicians should consider this complication when treating patients with ICIs for malignant diseases.

Significance of Quantitative Interferon-gamma Levels in Non-small-cell Lung Cancer Patients' Response to Immune Checkpoint Inhibitors.

BACKGROUND/AIM: We aimed to study the association between the quantitative interferon-gamma (IFN-γ) levels and clinical outcomes in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Sample collection for IFN-γ release assay (IGRA) was performed within 14 days before treatment (T1), on day 22±7 (T3), and on day 43±7 (T4). The stored specimens over 10 IU/ml in IGRA were re-examined using the dilution method (with saline as the dilution medium). The patients were classified into Lower and Higher groups by 7.06 IU/ml as a cut-off of IFN-γ levels at T1. RESULTS: Median progression-free survival in the Higher group was significantly longer than that in the Lower group. IFN-γ levels in the non-progression disease group were significantly higher than those in the progression disease group. IFN-γ levels at T1 in patients with immune-related adverse events were significantly lower compared to those at T3. CONCLUSION: IFN-γ could be a biomarker for NSCLC patients receiving ICIs.

Significance of Pre-treatment Interferon-gamma Release in Patients With Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitors.

BACKGROUND/AIM: We retrospectively investigated the significance of pre-treatment interferon-gamma release (IGR) as a biomarker for predicting the efficacy of immune checkpoint inhibitor treatment (ICI-tx). PATIENTS AND METHODS: This study included non-small-cell lung cancer patients who received ICI-tx between January 1, 2016 and April 30, 2019. IGR was measured using the positive control of an enzyme-linked immunosorbent assay. We defined the pre-treatment cut-off level of IGR as 10 IU/ml. RESULTS: Fifty-four patients were divided into two groups; those with an IGR ≤10 IU/ml (lower group: LG) (n=15) and those with >10 IU/ml (higher group: HG) (n=39). The time to treatment failure (TTF) in the HG was significantly longer than that in the LG. In multivariate analyses, C-reactive protein and IGR levels were significant risk factors for TTF. CONCLUSION: Pre-treatment IGR level of >10 IU/ml is recommended to identify those patients who will respond favourably to ICI-tx.