Masahiro Endo

Purpose To investigate the agreement in apparent diffusion coefficient (ADC) values and the image quality of abdominal computed diffusion-weighted imaging (cDWI) generated by two software programs. Methods This retrospective study included 154 patients (64 males, 90 females; mean age: 70.1 ± 10.7 years) who underwent abdominal diffusion-weighted imaging (DWI) between November 2023 and October 2024. DWI was acquired with a b = 0 and 1000 s/mm² using a 3.0T scanner. cDWIs with b 1500 and 2000 were generated by a scanner console software and a commercially available software program. The ADC and signal-to-noise ratio (SNR) were measured in normal tissues. The contrast-to-noise ratio (CNR) of normal tissues relative to the paraspinal muscle was also measured. Agreement and reliability of ADC value were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICC), respectively. SNR and CNR were compared using paired t-tests. Results ADC bias and limits of agreement ranged from − 0.2 to 0.7% and 0.3–2.1%, respectively. ICCs for ADC values ranged within 0.991 and 1.000 (p < 0.05) for all tissues. Significant SNR differences were observed in b1500 (liver, spleen, kidney) and b2000 (liver, bile). Significant CNR differences were noted in b1500 (liver, pancreas, kidney) and b2000 (excluding spleen). Conclusion There is strong agreement and high reliability in ADC values between the two software programs. Although significant differences in SNR and CNR were observed, their clinical impact appears minimal. These findings indicate that the ADC values and image quality of cDWI are consistent between the two software programs.

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.

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.

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. 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. Our findings suggest that physicians need to be aware of severe infections due to immunodeficiency with thymoma.

Summary: 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.

To measure the effective temporal resolution (eTR) and image quality for three reconstruction modes for non-helical volume scanning in area detector CT. Temporal sensitivity profiles (TSPs) were obtained and the full width of the TSP at half maximum was used as an index of the eTR. Image quality was assessed by image noise and the corrected artifact index. The half reconstruction mode had a higher eTR than the full and automatic patient motion collection (APMC) reconstructions. Compared to full reconstruction, the image noise with APMC and half reconstruction were increased by 16% and 35%. The corrected artifact index was lowest with APMC. The square root of full width at tenth maximum of the TSP showed a high coefficient of determination (R² = 0.934) for image noise. This study revealed the TSPs and eTRs for non-helical volume scanning in area detector CT. A high eTR resulted in higher image noise.

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.

Cancer cachexia in elderly patients may substantially impact physical function and medical dependency. The aim of this study was to estimate the impact of cachexia on activity of daily living (ADL), length of hospital stay, and inpatient medical costs among elderly patients with advanced non-small-cell lung cancer (NSCLC) receiving chemotherapy. Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to receive first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. ADL was assessed using the Barthel index. The disability-free survival time (DFS) was calculated as the time between the date of study entry and the date of onset of a disabling event, which was defined as a 10-point decrease in the Barthel index from that at baseline. The mean cumulative function of the length of hospital stay and inpatient medical costs (¥, Japanese yen) was calculated. The study patients comprised 11 women and 19 men, with a median age of 74 (range, 70–82) years. Cachexia was diagnosed in 19 (63%) patients. Cachectic patients had a shorter DFS (7.5 vs. 17.1 months, p < 0.05). During the first year from study entry, cachectic patients had longer cumulative lengths of hospital stay (80.7 vs. 38.5 days/person, p < 0.05), more frequent unplanned hospital visits or hospitalizations (4.2 vs. 1.7 times/person, p < 0.05), and higher inpatient medical costs (¥3.5 vs. ¥2.1 million/person, p < 0.05) than non-cachectic patients. Elderly NSCLC patients with cachexia showed higher risks for disability, prolonged hospitalizations, and higher inpatient medical costs while receiving chemotherapy than patients without cachexia. Our results might indicate that there is a potential need for an early intervention to minimize progression to or development of cachexia, improve functional prognosis, and reduce healthcare resource burden in this population. Trial registration number: UMIN000009768 . Name of registry: UMIN (University hospital Medical Information Network). Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.

Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non–small cell lung cancer (NSCLC). Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm2/m2), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression. Altogether, 11 women and 19 men with a median age of 74 (range, 70–82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm2/m2, 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005). Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy. Trial registration number: UMIN000009768 Name of registry: UMIN (University hospital Medical Information Network). URL of registry: Date of registration: 14 January 2013. Date of enrolment of the first participant to the trial: 23 January 2013.