Vendor-Specific Correction Software for Apparent Diffusion Coefficient Bias Due to Gradient Nonlinearity in Breast Diffusion-Weighted Imaging Using Ice-Water Phantom.

OBJECTIVE: This study aimed to evaluate a vendor-specific correction software for apparent diffusion coefficient (ADC) bias due to gradient nonlinearity in breast diffusion-weighted magnetic resonance imaging using an ice-water phantom. METHODS: The phantom consists of 5 plastic tubes with a length of 100 mm and a diameter of 15 mm, filled with distilled water and immersed in an ice-water bath. Diffusion-weighted images were acquired by echo-planar imaging sequence on a 3.0-T scanner. ADC maps with and without correction were calculated using 4 b-values (0, 100, 600, and 800 s/mm2). The mean ADCs were measured using a rectangular profile with 5 × 40 pixels in the anterior-posterior (AP) and a square region of interest with 5 × 5 pixels in the right-left (RL) and superior-inferior (SI) directions on the ADC map. ADC was compared with and without correction using a paired t test. Additionally, ADC of the ice-water phantom was measured at the magnet isocenter. RESULTS: ADC increased in the AP and RL directions and decreased in the SI direction with increasing distance from the isocenter before correction. After the correction, ADC at the off-center positions in the AP, RL, and SI directions was reduced to within 5% of the expected value. There were significant differences in the ADC at the off-center positions without and with correction (P < 0.001); however, ADC at the magnet isocenter did not vary after correction (1.08 ± 0.02 × 10-3 mm2/s). CONCLUSIONS: The vendor-specific software corrected the ADC bias due to gradient nonlinearity at the off-center positions in the AP, RL, and SI directions. Therefore, the software will contribute to the accurate ADC assessment in breast DWI.

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.

Ultrahigh-Resolution Computed Tomography Improves Preoperative Computed Tomography Angiography for Deep Inferior Epigastric Artery Perforator Flap Reconstruction.

OBJECTIVE: The aim of the study was to compare computed tomography (CT) angiography (CTA) imaging of deep inferior epigastric artery perforator (DIEP) using the ultrahigh-resolution CT (UHRCT) and conventional multidetector CT (MDCT). METHODS: This retrospective study enrolled 20 patients who underwent CTA of DIEP flap with UHRCT and MDCT. Computed tomography values were measured at 4 large vessels (thoracic aorta, abdominal aorta, common iliac artery, and external iliac artery) and 5 peripheral vessels (proximal and distal internal thoracic artery, proximal and distal deep inferior epigastric artery, and DIEP). RESULTS: There were no significant differences in mean CT values of the major vessel between UHRCT and MDCT. Ultrahigh-resolution CT shows higher CT values of the peripheral vessels than MDCT (P < 0.05 for all). The median CT values of the DIEP in UHRCT were approximately 3 times higher than those in MDCT (P < 0.001). CONCLUSIONS: Ultrahigh-resolution CT provides higher-quality CTA of DIEP compared with MDCT.

Proposing synchronous oligometastatic non-small-cell lung cancer based on progression after first-line systemic therapy.

Despite the importance of accurate disease definitions for effective management and treatment decisions, there is currently no consensus on what constitutes oligometastatic non-small-cell lung cancer (NSCLC). Predominant patterns of initial progressive disease (PD) after first-line systemic therapy have been shown to be a substantial basis for local ablative therapy (LAT) for all disease sites in patients with oligometastatic NSCLC, suggesting that these patterns could be helpful in defining synchronous oligometastatic NSCLC. Therefore, this retrospective study aimed to propose a threshold number of metastases for synchronous oligometastatic NSCLC, based on the pattern of initial PD after first-line systemic therapy. The cut-off threshold number of metastases compatible with synchronous oligometastatic NSCLC was determined using receiver operating characteristic (ROC) curve analyses of PD at the initially involved sites alone. ROC analysis of 175 patients revealed that the presence of 1-3 metastases before first-line treatment (sensitivity, 85.9%; specificity, 97.3%; area under the curve, 0.91) was compatible with oligometastatic NSCLC, therefore we divided patients into oligometastatic NSCLC and non-oligometastatic NSCLC groups. Multivariate logistic regression analyses revealed oligometastatic NSCLC to be the only independent predictor of PD at initially involved sites alone (odds ratio 165.7; P < .001). The median survival times in patients with oligometastatic or non-oligometastatic NSCLC were 23.0 and 10.9 mo (hazard ratio, 0.51; P = .002), respectively. Based on these findings, we propose synchronous oligometastatic NSCLC as 1-3 metastases in accordance with patterns of initial progression. The result of our study might be contributory to provide a common definition of synchronous oligometastatic NSCLC.

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.

Clinical Implication of Node-negative Resectable Pancreatic Cancer.

BACKGROUND: Lymph node metastasis is one of the strongest prognostic factors of pancreatic cancer. However, the clinical implication of pathologically node-negative pancreatic cancer (pN0-PC) has not been fully investigated. METHODS: Patients who underwent surgical resection for radiologically resectable pancreatic cancer between 2002 and 2018 were included in this study. A clinicopathological examination focusing on pN0-PC was performed. RESULTS: Of all 533 patients, 155 (29.1%) were diagnosed with pN0-PC and 378 (70.9%) were diagnosed with node-positive pancreatic cancer (pN1/2-PC). The 5-year survival rates of patients with pN0-PC and pN1/2-PC were 57.1% and 25.0%, respectively (p < 0.001). A multivariate analysis revealed six prognostic factors in pN0-PC: age ≥ 70 years, nonadministration of adjuvant chemotherapy, anterior serosal invasion, nerve plexus invasion, and microscopic lymphatic and venous invasions. The 5-year survival rates of patients who had pN0-PC with 0-1 risk factor, with 2-3 risk factors, and with 4-6 risk factors were 87.6%, 47.9%, and 16.4%, respectively. Survival of patients who had pN0-PC with 4-6 risk factors was comparable to that of pN1/2 patients. The diagnostic capability of metastasis-negative lymph node was unsatisfactory, with a predictive value of < 43%. CONCLUSIONS: Although the prognosis of patients with pN0-PC was better than that of patients with pN1/2-PC, it is not satisfactory. Survival of patients who had pN0-PC with 0-1 risk factors was extremely favorable; however, survival of patients who had pN0-PC with 4-6 risk factors was similar to those with pN1/2-PC.

Retrospective analysis of osimertinib re-challenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small cell lung carcinoma.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has exhibited efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a fatal adverse event of osimertinib treatment, and it requires treatment discontinuation. There are few reports regarding the safety and efficacy of osimertinib re-challenge in patients who experienced osimertinib-induced ILD. This retrospective study assessed this treatment option. We retrospectively collected data for patients treated with osimertinib who developed ILD at Shizuoka Cancer Center from April 2016 to March 2020. ILD was diagnosed by two doctors based on imaging tests and blood tests to exclude other causes. Among 215 patients treated with osimertinib, 28 developed ILD. The median age of patients with ILD was 69.5 years (range, 39.0-80.0). In addition, 29% of patients were men, and 46% had a history of smoking. Eleven patients were re-administered EGFR TKIs, including eight patients treated with osimertinib and three patients treated with alternative EGFR TKIs. Among patients re-challenged with osimertinib, none who previously experienced grade 1 ILD exhibited ILD relapse, even with the same osimertinib dose and without the concurrent administration of systemic steroids. Meanwhile, one of the four patients who previously exhibited grade 2 ILD experienced despite a dose reduction for osimertinib and systemic steroid administration. For patients with EGFR-mutant NSCLC who experience grade 1 ILD during osimertinib therapy, osimertinib re-challenge may be suitable when no other treatments are available.

Comparison of clinical features between immune-related sclerosing cholangitis and hepatitis.

Background Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis. Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness. Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥ grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P < 0.001). A ≥ grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥ grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥ grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively. Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020).

Association between oligo-residual disease and patterns of failure during EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer: a retrospective study.

BACKGROUND: Local ablative therapy (LAT) may be beneficial for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with oligo-residual disease after treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI). However, this has not been fully established. This study aimed to evaluate the predominant progressive disease (PD) pattern limited to residual sites of disease after treatment with EGFR-TKI. METHODS: Patients with advanced EGFR-mutated NSCLC treated with EGFR-TKIs as first-line therapy were retrospectively analysed during a 7-year period. Oligo-residual disease was defined as the presence of 1 - 4 lesions (including the primary site) at 3 months from the start of EGFR-TKI treatment. The predictive factors of PD patterns after EGFR-TKI treatment were evaluated. RESULTS: A total of 207 patients were included. Three months after the start of EGFR-TKI treatment, 66 patients (32%) had oligo-residual disease. A total of 191 patients had PD, 60 with oligo-residual disease and 131 with non-oligo-residual disease. Regarding the pattern, 44 patients (73%) with oligo-residual disease and 37 patients (28%) with non-oligo-residual disease had PD limited to the residual sites. Multivariate logistic regression analysis at 3 months from the start of EGFR-TKI treatment revealed that oligo-residual disease (P < 0.001), the lack of residual central nervous system metastases (P = 0.032), and initial treatment with osimertinib (P = 0.028) were independent predictors of PD limited to residual disease sites. CONCLUSIONS: This study provided a rationale for LAT to all sites of residual disease in patients with oligo-residual disease during EGFR-TKI treatment.

Comparison of five-phase computed tomography images of type 1 autoimmune pancreatitis and pancreatic cancer: Emphasis on cases with atypical images.

BACKGROUND/OBJECTIVES: International consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images. METHODS: Five-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items. RESULTS: ICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase. CONCLUSIONS: Ordinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. "Delayed enhancement" is characteristic to ordinary AIPs, however, "pancreatic-phase enhancement" is more diagnostic for atypical AIPs.

Negative impact of malignant effusion on osimertinib treatment for non-small cell lung cancer harboring EGFR mutation.

3rd-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, have reasonable efficacy in non-small-cell lung cancers (NSCLC) with EGFR mutations. However, the efficacy of osimertinib in NSCLC patients with fluids, such as pleural, pericardial and abdominal effusions, is unclear. We evaluated the efficacy of osimertinib in this specific setting. NSCLC patients harboring EGFR T790 M mutations who experienced progressive disease after first EGFR-TKI treatment and started osimertinib treatment between April 2016 and August 2018 were retrospectively screened. In particular, we assessed the efficacy of osimertinib for NSCLC with EGFR T790 M mutations in patients who were diagnosed with EGFR T790 M mutation by malignant effusion. Among 90 patients with EGFR T790 M mutation who started osimertinib treatment after EGFR-TKI failure, 21 were diagnosed from malignant effusions excluding cerebrospinal fluid (F group) and 69 using other methods including tissue biopsies (NF group). Patient characteristics were well-balanced between the two groups. Overall response was 50%, and significantly worse in the F group (29%) than the NF group (57%; P = 0.025). Median progression-free survival with osimertinib treatment in the F group (7.1 months, 95% confidence interval [CI]: 2.3-14.0) was significantly shorter than that in the NF group (11.9 months, 95% CI: 9.5-16.0; P = 0.046)). Median drainage-free time was 10.9 months (95% CI: 1.4 months- not reached). The present study showed that the efficacy of osimertinib for NSCLC in which EGFR T790 M mutation is detected by malignant effusion may be less than in EGFR T790 M-mutated NSCLC detected by other methods.

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer.

Introduction Durvalumab has been shown to confer a survival benefit after definitive chemoradiotherapy in the patients with locally advanced non-small cell lung cancer, but no studies have attempted to identify risk factors for pneumonitis after durvalumab therapy. The purpose of this study was to investigate associations between clinical and radiation dose-volume factors, and the severity of pneumonitis. Methods We retrospectively assessed the cases of 30 patients who had been started on durvalumab therapy between July 2018 and February 2019. In this study we evaluated the percentage of lung volume receiving radiation dose in excess of 20 Gy (V20) as radiation dose-volume factor. We compared V20 and some baseline factors between a grade 0 or 1 (Gr 0/1) pneumonitis group and a grade 2 or more (≥Gr 2) pneumonitis group, and we performed a logistic regression analysis to establish the associations between variables and ≥ Gr 2 pneumonitis. Results Pneumonitis had developed in 22 patients (73.3%): Gr 1/2/3-5 in 8 (26.7%)/14 (46.7%) /0 (0%), respectively. The difference in V20 between the Gr 0/1 group and Gr 2 group (median: 20.5% vs. 23.5%, p = 0.505) was not statistically significant, and thus V20 was not a risk factor for Gr 2 pneumonitis (odds ratio: 1.047, p = 0.303). None of the clinical factors, including sex, age, smoking history, presence of baseline pneumonitis, type of radiation therapy, location of lesion and facility, were risk factors. Conclusions Our study suggest that the severity of pneumonitis after durvalumab is unrelated to V20 or any of the clinical factors assessed in this study.

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.

Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

BACKGROUND AND OBJECTIVE: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. METHODS: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. RESULTS: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. CONCLUSION: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.

Leptomeningeal recurrence after long-term alectinib therapy for non-small cell lung cancer harboring an EML4-ALK fusion protein.

The recent approval of anaplastic lymphoma kinase (ALK) inhibitors for the treatment of ALK-rearranged non-small cell lung cancer (NSCLC) has dramatically transformed cancer therapy. However, leptomeningeal metastases (LM) are frequent and often devastating complications of ALK-rearranged NSCLC, and treatment against LM remains challenging. Herein we report a case of a 19-year-old male diagnosed with ALK-rearranged NSCLC with LM. He experienced heavy treatment before introduction of alectinib therapy, which continued for approximately 5.5 years with marked efficacy. However, he experienced recurrence of a bulbar metastasis after discontinuation of alectinib. Reintroduction of standard-dose alectinib therapy resolved the lesion again. Our findings suggest that ALK-tyrosine kinase inhibitor therapy should be continued in patients showing a long-term complete response, unless intolerable toxicities are present, and that rechallenge treatment with alectinib may represent a therapeutic option for central nervous system metastases.

Acquired immunodeficiency associated with thymoma: a case report.

BACKGROUND: Acquired immunodeficiency associated with thymoma is a rare disorder. Here we reported a case of acquired immunodeficiency with thymoma, with an unusual pattern of low CD4+ count with normal gammaglobulin levels. CASE PRESENTATION: A 70-year-old man presented to the emergency room of our hospital with a high-grade fever, headache, and nausea. He had a five-year history of unresectable thymoma treatment, including several cytotoxic regimens. He had received thoracic palliative radiotherapy 2 months prior to the emergent visit. During the previous month, he had experienced multiple febrile episodes, dry cough, fatigue, weight loss, and watery diarrhea. Upon admission, he had a high-grade fever, nausea, and immobility. Physical examination revealed indistinct consciousness, neck stiffness, and oropharyngeal candidiasis. Both cerebrospinal fluid and blood cultures yielded multiple short chains of Gram-positive rods later identified as Listeria monocytogenes, so he was diagnosed with Listeria meningitis. Intravenous administration of antibiotics was initiated, and the patient fully recovered and was discharged. Additional examination found normal immunoglobulin levels. Peripheral-blood cell counts revealed low CD4+ cell count (108 CD4+ cells/µl). His CD4+ cell count remained low after discharge. CONCLUSIONS: Our findings suggest that physicians need to be aware of severe infections due to immunodeficiency with thymoma.

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.

Overranging and overbeaming measurement in area detector computed tomography: A method for simultaneous measurement in volume helical acquisition.

PURPOSE: We propose a novel method to assess overbeaming and overranging, as well as the effect of reducing longitudinal exposure range, by using a dynamic z-collimator in area detector computed tomography. METHODS AND MATERIALS: A 500-mm diameter cylindrical imaging plate was exposed by helical scanning in a dark room. The beam collimation of the helical acquisitions was set at 32 and 80 mm. Overbeaming and overranging with the dynamic z-collimator were measured. RESULTS: The actual beam widths were approximately 39 and 88 mm at 32 and 80 mm collimation, respectively, and were relatively reduced owing to increased beam collimation. Overranging was 27.0 and 48.2 mm with a pitch of 0.83 and 1.49 at 32 mm collimation and 72.5 and 83.1 mm with a pitch of 0.87 and 0.99 at 80 mm collimation. The dynamic z-collimator relatively reduced the overranging by 17.3% and 17.1% for the 32 and 80 mm collimation, respectively. CONCLUSION: We devised a method to simultaneously measure overbeaming and overranging with only one helical acquisition. Although the dynamic z-collimator reduced the overranging by approximately 17%, wider collimation widths and higher pitch settings would increase the exposure dose outside the scan range.