Impact of 18F-FDG PET on TNM Staging and Prognosis in Thymic Epithelial Tumors.

BACKGROUND: Preoperative fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) of thymic epithelial tumors (TETs) is well known for identifying malignant-grade TETs; however, its predictive power for determining locally advanced tumors, lymph node (LN) metastasis, and prognosis remains unknown. PATIENTS AND METHODS: We retrospectively evaluated patients with resectable TETs who were preoperatively assessed using 18F-FDG PET from January 2012 to January 2023. The receiver operating characteristic curve was used to evaluate the cutoff value of the maximum standardized uptake value (SUVmax) to predict advanced-stage disease. Recurrence/progression-free survival (RFS/PFS) was analyzed using the Kaplan-Meier method. The staging was classified according to the tumor-node-metastasis system. RESULTS: Our study included 177 patients; 145 (81.9%) had pathological early-stage TET (stage I or II), and 32 (19.1%) had advanced stage (stage III or IV). The area under the curve value for predicting the advanced stage was 0.903, and the cutoff value was 5.6 (sensitivity 81.3%, specificity 84.8%). SUVmax > 5.6 was associated with worse prognosis for RFS/PFS. LN metastasis was preoperatively detected by FDG uptake in 30.8% of patients with pathological LN positivity, whereas LN metastasis was not pathologically detected in patients with SUVmax < 5.9. In patients with advanced-stage TETs, LN recurrence was more frequent in patients who were preoperatively detected by 18F-FDG PET than those who were not (75.0% versus 7.1%). CONCLUSIONS: 18F-FDG PET is a potentially valuable tool for predicting advanced stage and poor prognosis of recurrence in patients with TETs. SUVmax can help thoracic surgeons to guide them in selecting appropriate therapeutic strategies for TETs.

Nivolumab-induced radiation recall pneumonitis in non-small-cell lung cancer patients with thoracic radiation therapy.

The role of previous thoracic radiation therapy as a risk factor of immune-related pneumonitis is unclear. Furthermore, some patients develop radiation recall pneumonitis, which is characterized by a radiation pneumonitis-like imaging pattern with consolidation progressing within a previous radiation field. In this multicenter retrospective study, we analyzed the relationship of previous thoracic radiation therapy with immune-related pneumonitis and the characteristics of radiation recall pneumonitis. The medical records of patients with non-small-cell lung cancer who had received nivolumab between December 2015 and March 2017 at five institutions were retrospectively reviewed. Incidence, imaging patterns, clinical course, and risk factors of immune-related pneumonitis and radiation recall pneumonitis were evaluated. A total of 669 patients were evaluated, and the incidences of all-grade and grade 3 or higher immune-related pneumonitis were 8.8% and 2.6%, respectively. The incidences of immune-related pneumonitis were 13.2% (34/257) and 6.1% (25/412) in patients with and those without previous thoracic radiation therapy, respectively. A history of previous thoracic radiation therapy was associated with immune-related pneumonitis (odds ratio, 2.11; 95% confidence interval, 1.21-3.69 in multivariate analysis). Among the patients with previous thoracic radiation therapy, 6.2% (16/257) showed radiation recall pattern. This study found an increased risk of nivolumab-induced immune-related pneumonitis associated with a history of thoracic radiation therapy. Radiation recall pattern was one of the major patterns of immune-related pneumonitis among the patients with previous thoracic radiation therapy. Incidence, risk factors, and clinical outcome of radiation recall pneumonitis were elucidated.

Clinical and imaging features of interstitial lung disease in cancer patients treated with trastuzumab deruxtecan.

BACKGROUND: Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. METHODS: Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. RESULTS: The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25-143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. CONCLUSIONS: This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome.

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF. METHODS: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS). RESULTS: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment. CONCLUSIONS: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

Tumor size in patients with severe pulmonary emphysema might be underestimated on preoperative CT.

OBJECTIVES: To evaluate the effect of emphysema on tumor diameter measured on preoperative computed tomography (CT) images versus pathological specimens. MATERIALS AND METHODS: We investigated patients who underwent primary lung cancer surgery: 55 patients (57 tumors) with severe emphysema and 57 patients (57 tumors) without emphysema. The tumor diameters measured in the postoperative pathological specimens were compared with those measured on the axial CT images and on multiplanar reconstruction (MPR) CT images by two independent radiologists; a subgroup analysis according to tumor size was also performed. A paired or unpaired t test was performed, depending on the tested subjects. RESULTS: In the emphysema group, the mean axial CT diameter was significantly smaller than the mean pathological diameter (p = 0.025/0.001 for reader 1/2), whereas in the non-emphysema group, the mean axial CT diameter was not significantly different from the pathological one for both readers. The difference between CT axial diameter and pathological diameter (= CT diameter - pathological diameter) was significantly smaller (i.e., had a stronger tendency toward underestimation on radiological measurements) in the emphysema group compared with the non-emphysema group (p = 0.014/0.008 for reader 1/2), and the difference was significantly smaller in tumors sized > 30 mm than tumors sized ≤ 20 mm in both groups. CONCLUSIONS: Tumor size is significantly smaller on preoperative CT in patients with severe emphysema compared to patients without emphysema, especially in the case of large tumors. MPR measurement using the widest of three dimensions should be used to select T-stage for patients with severe emphysema. KEY POINTS: • The presence of emphysema affects the accuracy of tumor size measurements on CT. • Compared to patients without emphysema, the tumor size in severe emphysema patients tends to be measured smaller in preoperative CT than the pathological specimen. • This trend is more evident when large tumors are measured on axial CT images alone.

Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay.

INTRODUCTION: This study explored the predictors of a histological aggressive component in ground glass opacity-containing lung adenocarcinoma. METHODS: Of the 2388 patients who underwent resection for lung cancer at our institute between 2017 and 2020, we collected data on the 501 patients with ground glass opacity-containing adenocarcinoma with a total diameter of ≤2 cm. Using a historical cohort, we identified histological aggressive components that were related to a poor prognosis in early-stage adenocarcinoma. A multivariable analysis was conducted to identify predictors for the presence of a histological aggressive component. RESULTS: Lymphovascular invasion and predominant micropapillary or solid patterns were identified as histological aggressive components by a prognostic analysis using a historical cohort. Of the 501 patients included, 36 (7.2%) had at least one histological aggressive component. A multivariate analysis showed that a consolidation/tumour ratio > 0.5 (P < 0.01), maximum standardized uptake value on positron emission tomography ≥1.5 (P = 0.01) and smoking index >20 pack-years (P = 0.01) were predictors of the presence of a histological aggressive component. A total of 98% of cases without any of the above factors did not have a histological aggressive component. CONCLUSIONS: Approximately 7% of ground glass opacity-containing small adenocarcinomas contained histological aggressive component. A consolidation/tumour ratio > 0.5, maximum standardized uptake value ≥ 1.5 and smoking index >20 pack-years were predictors for such cases. These predictors may be useful for screening patients with a potentially high risk of a poor prognosis and for prioritizing resection without delay.

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.

Treatment and relapse of interstitial lung disease in nivolumab-treated patients with non-small cell lung cancer.

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD.

Diagnostic performance for pulmonary adenocarcinoma on CT: comparison of radiologists with and without three-dimensional convolutional neural network.

OBJECTIVES: To compare diagnostic performance for pulmonary invasive adenocarcinoma among radiologists with and without three-dimensional convolutional neural network (3D-CNN). METHODS: Enrolled were 285 patients with adenocarcinoma in situ (AIS, n = 75), minimally invasive adenocarcinoma (MIA, n = 58), and invasive adenocarcinoma (IVA, n = 152). A 3D-CNN model was constructed with seven convolution-pooling and two max-pooling layers and fully connected layers, in which batch normalization, residual connection, and global average pooling were used. Only the flipping process was performed for augmentation. The output layer comprised two nodes for two conditions (AIS/MIA and IVA) according to prognosis. Diagnostic performance of the 3D-CNN model in 285 patients was calculated using nested 10-fold cross-validation. In 90 of 285 patients, results from each radiologist (R1, R2, and R3; with 9, 14, and 26 years of experience, respectively) with and without the 3D-CNN model were statistically compared. RESULTS: Without the 3D-CNN model, accuracy, sensitivity, and specificity of the radiologists were as follows: R1, 70.0%, 52.1%, and 90.5%; R2, 72.2%, 75%, and 69%; and R3, 74.4%, 89.6%, and 57.1%, respectively. With the 3D-CNN model, accuracy, sensitivity, and specificity of the radiologists were as follows: R1, 72.2%, 77.1%, and 66.7%; R2, 74.4%, 85.4%, and 61.9%; and R3, 74.4%, 93.8%, and 52.4%, respectively. Diagnostic performance of each radiologist with and without the 3D-CNN model had no significant difference (p > 0.88), but the accuracy of R1 and R2 was significantly higher with than without the 3D-CNN model (p < 0.01). CONCLUSIONS: The 3D-CNN model can support a less-experienced radiologist to improve diagnostic accuracy for pulmonary invasive adenocarcinoma without deteriorating any diagnostic performances. KEY POINTS: • The 3D-CNN model is a non-invasive method for predicting pulmonary invasive adenocarcinoma in CT images with high sensitivity. • Diagnostic accuracy by a less-experienced radiologist was better with the 3D-CNN model than without the model.

Adenocarcinoma in situ and minimally invasive adenocarcinoma in lungs of smokers: image feature differences from those in lungs of non-smokers.

PURPOSE: We aimed to examine the characteristics of imaging findings of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) in the lungs of smokers compared with those of non-smokers. MATERIALS AND METHODS: We included seven cases of AIS and 20 cases of MIA in lungs of smokers (pack-years ≥ 20) and the same number of cases of AIS and MIA in lungs of non-smokers (pack-years = 0). We compared the diameter of the entire lesion and solid component measured on computed tomography (CT) images, pathological size and invasive component diameter measured from pathological specimens, and CT values of the entire lesion and ground-glass opacity (GGO) portions between the smoker and non-smoker groups. RESULTS: The diameters of AIS and MIA on CT images and pathological specimens of the smoker group were significantly larger than those of the non-smoker group (p = 0.036 and 0.008, respectively), whereas there was no significant difference in the diameter of the solid component on CT images or invasive component of pathological specimens between the two groups. Additionally, mean CT values of the entire lesion and GGO component of the lesions in the smoker group were significantly lower than those in the non-smoker group (p = 0.036 and 0.040, respectively). CONCLUSION: AIS and MIA in smoker's lung tended to have larger lesion diameter and lower internal CT values compared with lesions in non-smoker's lung. This study calls an attention on smoking status in CT-based diagnosis for early stage adenocarcinoma.

Association of immune-related pneumonitis with the presence of preexisting interstitial lung disease in patients with non-small lung cancer receiving anti-programmed cell death 1 antibody.

The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3-2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2-14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.

Ciliated Muconodular Papillary Tumor of the Lung: Thin-Section CT Findings of 16 Cases.

OBJECTIVE. The purpose of this article was to assess thin-section CT features of ciliated muconodular papillary tumors (CMPTs) of the lung and correlations between radiologic and pathologic findings. MATERIALS AND METHODS. Thin-section CT findings of 16 patients (10 men and six women; mean age, 70.7 years) with surgically resected CMPTs were retrospectively analyzed. Size, location, and internal characteristics of the tumors were evaluated. The amount of mucin in the tumors was assessed histopathologically and compared with CT findings. Tumor growth speed was calculated on the basis of size changes on thin-section CT. RESULTS. In all 16 patients, tumors were detected as a solitary pulmonary nodule. Thirteen tumors (81.3%) were located in the lower lobes, and 10 (62.5%) were adjacent to the pleura. Mean maximal diameter of the tumors was 9.1 mm (range, 6-14 mm). One tumor (6.3%) presented as a pure ground-glass nodule (GGN), seven (43.8%) as dense GGNs, and eight (50.0%) as solid nodules. Pathologically, the pure GGN and five of seven dense GGNs had a large amount of mucin, whereas seven of eight solid nodules had an intermediate or small amount of mucin. The mean annual tumor growth rate (in diameter) was 0.49 mm/y. CONCLUSION. CMPTs appear as solitary, small, and peripheral pulmonary nodules with very slow growth rates. CMPTs appearing as pure GGNs and dense GGNs tend to contain more mucin than CMPTs appearing as solid nodules.

Radiologic Assessment for Endoscopic US-guided Biliary Drainage.

Endoscopic US-guided biliary drainage (BD) is performed for various types of biliary obstruction and is mainly indicated for unsuccessful conventional transpapillary endoscopic retrograde cholangiodrainage. In endoscopic US BD, an extra-anatomic drainage route between the gastrointestinal (GI) tract and the biliary system is created with a covered metallic stent or plastic stent. Procedural types of endoscopic US BD include hepaticogastrostomy, hepaticojejunostomy (after gastrectomy), choledochoduodenostomy, hepaticoduodenostomy, and endoscopic US-guided gallbladder drainage. The technical and clinical success rates of endoscopic US BD are reported to be 94%-97% and 88%-100%, respectively. CT is crucial both in preprocedural assessment and postprocedural monitoring. CT is used to determine the indications for endoscopic US BD, which include the type of biliary obstruction, collateral vessels in the puncture route, ascites, the volume of the liver segment, the distribution of an intrahepatic tumor, and GI tract patency. After endoscopic US BD, common subclinical findings are a small amount of intraperitoneal gas, localized edematous change in the GI tract, a notch in the placed stent, and localized biliary dilatation caused by stent placement. Stent malfunction after endoscopic US BD is caused by impaction of debris and/or food, stent migration into the GI tract, or tumor overgrowth and/or hyperplasia. Complications that can occur include internal stent migration, intraperitoneal biloma, arterial bleeding or pseudoaneurysm, perforation of the GI tract, and portobiliary fistula. The incidence of clinical endoscopic US BD-related complications is 11%-23%. ©RSNA, 2020.

Epithelioid hemangioendothelioma of the lung: CT findings and clinical course of 35 cases.

OBJECTIVES: To evaluate computed tomography findings and assess the clinical course of patients with pulmonary epithelioid hemangioendothelioma. METHODS: Patients diagnosed with pulmonary epithelioid hemangioendothelioma at our institution between 2000 and 2019 were retrospectively analyzed. Patients with pleural involvement were excluded. Computed tomography findings of the lung at diagnosis were classified into three patterns: multiple small nodules pattern (˂15 mm), multiple nodules with large lesions pattern (≥15 mm) and single lesion pattern. Additionally, the clinical course of patients was evaluated. RESULTS: Thirty-five patients (15 men and 20 women; median age, 44 years) with pulmonary epithelioid hemangioendothelioma were identified. The multiple small nodules pattern, multiple nodules with large lesions pattern and single lesion pattern were observed in 25 (71.4%), 8 (22.9%) and 2 (5.7%) patients, respectively. In 22 (62.9%) patients, extra-pulmonary epithelioid hemangioendothelioma lesions were found. Most patients were followed without initial treatment, while two patients with single lesion pattern underwent surgical resection. The median follow-up period was 63 months. Five-year overall survival rate of all patients was 96.3%. Latest clinical information revealed that 20 (20/25, 80%) patients with multiple small nodules pattern were alive without symptoms. In patients with multiple nodules with large lesion pattern, four (4/8, 50%) patients were alive without symptoms, three (3/8, 37.5%) patients were alive with symptoms and one (1/8, 12.5%) died. No recurrence was observed in patients with single lesion pattern. CONCLUSIONS: Multiple small nodules pattern was the most common findings of pulmonary epithelioid hemangioendothelioma. Patients with pulmonary epithelioid hemangioendothelioma have good prognosis.

Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan.

OBJECTIVE: Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan. METHODS: Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018. RESULTS: The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9-78.9) and 53.2% (95% CI, 51.3-55.1) and overall survival rates were 88.3% (95% CI, 87.2-89.4) and 75.4% (95% CI, 73.8-77.0), respectively. CONCLUSIONS: These data support the currently established benefit-risk assessment of osimertinib in this patient population.

Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive non-small-cell lung cancer in Japan.

We conducted a large-scale surveillance study as a post-marketing commitment to investigate the safety and effectiveness of alectinib in patients with ALK-positive non-small-cell lung cancer (NSCLC) in Japan. Patients receiving 300 mg twice-daily alectinib (September 2014 to June 2015) were monitored until termination of alectinib or completion of 18 months of treatment at 519 Japanese study sites. The primary endpoint was the incidence of adverse drug reactions (ADR), which are important identified risks for alectinib in Japanese patients. Overall survival (OS), a key secondary endpoint, was assessed according to information on outcome. Overall, 1251 patients were enrolled. The median patient age was 62.0 years; 12.9% of patients were aged ≥75 years. At baseline, 63.0% of patients had received crizotinib and 40.6% had brain metastases. Altogether, 1512 ADR occurred in 654 patients (53.6%), with 164 grade ≥3 ADR in 123 patients (10.1%). Commonly occurring ADR were hepatic disorders (all grades, 19.8%; grade ≥3, 2.0%), decreased neutrophil and/or white blood cell count (all grades, 7.6%; grade ≥3, 1.1%), and interstitial lung disease (all grades, 3.8%; grade ≥3, .7%). Median OS was not estimable. The 18-month cumulative OS rate was longer in patients with ECOG performance status ≤1 (vs 2 or ≥3; 83.7% vs 44.5% or 27.2%), without prior crizotinib (vs with; 81.1% vs 73.4%), receiving first-line alectinib (vs second and third or later line; 83.0% vs 79.2% or 71.9%), without brain metastases (vs with; 79.5% vs 71.5%). These data confirm the favorable safety and effectiveness of alectinib in patients with ALK-positive NSCLC in Japan.

Radiologic features of pneumonitis associated with nivolumab in non-small-cell lung cancer and malignant melanoma.

Aim: To assess the clinical features/imaging characteristics of pneumonitis reported during nationwide nivolumab postmarketing surveillance in Japan. Patients & methods: Clinical and radiological data were collected from pneumonitis cases reported during/after nivolumab treatment for melanoma or non-small-cell lung cancer. The expert central review committee evaluated each case. Results: Among 144 cases analyzed, 91 (63.2%) had radiological patterns considered typical for drug-induced pneumonitis and 53 (36.8%) patients had previously unobserved patterns with one or more atypical features, including 23 cases (16.0%) with ground glass opacity confined to the area around the tumor (peritumoral infiltration). A higher proportion of patients with (vs without) peritumoral infiltration had an antitumor response to nivolumab. Conclusion: Images of nivolumab-induced pneumonitis showed previously unobserved radiological patterns.