Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer.

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies.

BACKGROUND: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. METHODS: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug-drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. RESULTS: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3-|34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9-|81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1-NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). CONCLUSION: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. CLINICAL TRIAL INFORMATION: FIH study, NCT02564900; DDI study, NCT03383692.

Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that consists of an anti-human epidermal growth factor receptor 2 (HER2) antibody bound by a cleavable tetrapeptide-based linker to a cytotoxic topoisomerase I inhibitor. Prior to marketing approval in Japan in September 2020, this expanded-access study was conducted to provide T-DXd to previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas. METHODS: This multicenter, open-label, expanded-access study was conducted between March 25 and September 25, 2020 at 17 Japanese sites. Previously treated patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinomas received T-DXd 6.4 mg/kg via intravenous infusions at 3-week intervals. Serious adverse events (SAEs), all potential cases of interstitial lung disease (ILD)/pneumonitis, all liver-related events potentially meeting Hy's Law criteria, and all cases of overdose were reported on the case report forms. RESULTS: A total of 64 patients were treated with T-DXd. Among the 17 (26.6%) patients with reported SAEs, 10 (15.6%) had SAEs related to T-DXd treatment. Febrile neutropenia was the most common SAE (n = 6). SAEs led to death in six patients; drug-related SAEs (sepsis and febrile neutropenia) led to death in one patient. Drug-related ILD, as determined by the external Adjudication Committee, occurred in three patients (Grade 1, Grade 2, and Grade 3: all n = 1). CONCLUSION: This expanded-access study provided T-DXd to a broader population of Japanese patients prior to marketing approval in Japan, bridging the gap between clinical trials and drug approval. No new safety concerns were identified.

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.

BACKGROUND: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer. METHODS: In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progression-free survival, confirmed response (response persisting ≥4 weeks), and safety. RESULTS: Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P<0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group. CONCLUSIONS: Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.).

Prospective analysis of the expression status of FGFR2 and HER2 in colorectal and gastric cancer populations: DS-Screen Study.

PURPOSE: Fibroblast growth factor receptor 2 (FGFR2) and human epidermal growth factor receptor 2 (HER2) proteins are both molecular targets for cancer therapy. The objective of this study was to evaluate the expression status of FGFR2 and HER2 in patients with gastric cancer (GC) or colorectal cancer (CRC). METHODS: Archived tumor tissue samples from patients with histologically-confirmed GC or CRC suitable for chemotherapy were analyzed for FGFR2 and HER2 expression using immunohistochemistry and fluorescence in situ hybridization (HER2 in CRC only). RESULTS: A total of 176 GC patients and 389 CRC patients were enrolled. Among patients with GC, 25.6% were FGFR2-positive and 26.1% were HER2-positive. Among patients with CRC, 2.9% were FGFR2-positive and 16.2% were HER2-positive. No clear relationship was found between FGFR2 and HER2 status in either GC or CRC. In GC, FGFR2 and HER2 statuses did not differ between different primary cancer locations, whereas there were some differences between histological types. Based on FGFR2- and/or HER2-positive status, 117 patients were identified as potentially suitable for inclusion in clinical trials of therapeutic agents targeting the relevant protein (GC = 45, CRC = 72; FGFR = 56, HER2 = 62), of whom 7 were eventually enrolled into such clinical trials. CONCLUSIONS: This study indicated the prevalence of FGFR2 and HER2 in GC and CRC in the Japanese population. The screening performed in this study could be useful for identifying eligible patients for future clinical trials of agents targeting these proteins. TRIAL REGISTRATION: Clinical trial registration Japic CTI No.: JapicCTI-163380.  https://www. CLINICALTRIALS: jp/cti-user/trial/ShowDirect.jsp?directLink=RNlzx1PPCuT.PrVNPxPRwA .

[A Case of Second Primary Small Cell Lung Carcinoma after Radiotherapy for Breast Cancer].

We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.

A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors.

Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23-82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and 800 mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8 h (AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses. Pexidartinib exposure and plasma levels of adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433).

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study.

BACKGROUND: Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive gastric or gastro-oesophageal junction cancer who received trastuzumab deruxtecan at the recommended doses for expansion. METHODS: This was an open-label, dose-escalation and dose-expansion phase 1 trial done at eight hospitals and clinics in the USA and six in Japan. Eligible patients were at least 18 years old in the USA and at least 20 years old in Japan and had advanced solid tumours (regardless of HER2 expression in dose escalation or HER2 expression or mutation in dose expansion). The recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan were administered intravenously to patients once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. In this Article, all patients with HER2-positive gastric or gastro-oesophageal junction cancer with previous trastuzumab treatment who received trastuzumab deruxtecan were analysed together. The primary endpoints of the study were safety and preliminary activity (proportion of patients who achieved an objective response as assessed by the investigators). The activity evaluable set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion, and for whom both baseline and post-treatment activity data were available. The safety analysis set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. Enrolment for patients with gastric or gastro-oesophageal junction cancer has completed. This trial is registered at ClinicalTrials.gov, number NCT02564900, and ClinicalTrials.jp, number JapicCTI-152978. FINDINGS: Between Aug 28, 2015, and Aug 10, 2018, 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. All patients had at least one treatment-emergent adverse event. The most frequent grade 3 or worse treatment-emergent adverse events included anaemia (13 [30%]) and decreases in neutrophil (nine [20%]), platelet (eight [18%]), and white blood cell (seven [16%]) counts. Serious treatment-emergent adverse events occurred in 11 (25%) patients. There were four pneumonitis cases (three grade 2 and one grade 3). There were no drug-related deaths due to treatment-emergent adverse events. 19 (43·2%; 95% CI 28·3-59·0) of 44 patients had a confirmed objective response. INTERPRETATION: Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in heavily pretreated patients with HER2-positive gastric or gastro-oesophageal junction cancer. These results support further investigation of trastuzumab deruxtecan for HER2-positive gastric or gastro-oesophageal junction cancer post-trastuzumab. FUNDING: Daiichi Sankyo Co, Ltd.

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study.

BACKGROUND: Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and potent topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing, advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion. METHODS: We did an open-label, dose-escalation and dose-expansion phase 1 trial at eight hospitals and clinics in the USA and six in Japan. Eligible patients were at least 18 years old in the USA and at least 20 years of age in Japan and had advanced solid tumours (regardless of HER2 expression in dose escalation or HER2 expression or mutation in dose expansion). The recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan were administered intravenously to patients once every 3 weeks until withdrawal of consent, unacceptable toxicity, or progressive disease. In this Article, all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion were analysed together. The primary endpoints of the study were safety and preliminary activity (proportion of patients who achieved an objective response as assessed by the investigators). The activity evaluable set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion, and for whom both baseline and post-treatment activity data were available. The safety analysis set included all patients who received at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. Enrolment for patients with HER2-positive breast cancer has been completed. This trial is registered at ClinicalTrials.gov, number NCT02564900, and ClinicalTrials.jp, number JapicCTI-152978. FINDINGS: Between Aug 28, 2015, and Aug 10, 2018, 115 of 118 patients with HER2-positive breast cancer were treated with at least one dose of trastuzumab deruxtecan at the recommended doses for expansion. All patients had at least one treatment-emergent adverse event. Frequent grade 3 or worse treatment-emergent adverse events included anaemia (19 [17%] of 115) and decreased neutrophil (16 [14%]), white blood cell (ten [9%]), and platelet (nine [8%]) counts. At least one serious treatment-emergent adverse event occurred for 22 (19%) patients. Investigators reported 20 cases of interstitial lung disease, pneumonitis, or organising pneumonia, including one grade 3 event and two treatment-related deaths due to pneumonitis. One death unrelated to study treatment was due to progressive disease. 66 (59·5%; 95% CI 49·7-68·7) of 111 patients had a confirmed objective response. INTERPRETATION: Trastuzumab deruxtecan had a manageable safety profile and showed preliminary activity in trastuzumab emtansine-pretreated patients with HER2-positive breast cancer. These results suggest that further development in phase 2 and 3 clinical trials for HER2-positive breast cancer is warranted. FUNDING: Daiichi Sankyo Co, Ltd.

Impact of Additional Lipid-Lowering Therapy on New Ischemic Lesions of Diffusion-Weighted Imaging in Carotid Artery Stenting.

BACKGROUND: New ischemic lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS) and sometimes cause neurologic deficit. We investigated the rate and the potential factor of new DWI lesions during the perioperative period of CAS in symptomatic patients at our institution. MATERIALS AND METHODS: Of 187 consecutive patients who underwent CAS (April 2013-August 2016), we investigated 60 symptomatic patients with artery-to-artery embolism from carotid plaque. During hospitalization for ischemic stroke, patients with more than 120 mg/dL of plasma low-density lipoprotein cholesterol (LDL-C) level or more than 100 mg/dL of LDL-C level in case of coronary artery disease were administered additional lipid-lowering therapy (ALL therapy), for example, the same statin as patients took or evolocumab for patients with the maximum tolerated dose of statin. All patients were implanted the same type of carotid stent by the same procedure as we predefined. We implemented data analysis to identify factors on new DWI lesions. RESULTS: New DWI lesions were observed in 17 patients (28%). Baseline plasma triglyceride level was found to be the factor of new DWI lesions. ALL therapy was administered to 26 patients, including 8 patients of evolocumab. The average period from the start of ALL therapy to CAS was 15 days. New DWI lesions occurred in 11.5% of patients with ALL therapy and 41.2% of patients without ALL therapy (P = .019). Multivariate logistic analysis showed that ALL therapy was an independent predictor of absence of new DWI lesions (P = .029). CONCLUSIONS: ALL therapy before CAS may reduce new DWI lesions.

The relationship between low-density lipoprotein cholesterol levels and the incidence of cardiovascular disease in high-risk patients treated with pravastatin: main results of the APPROACH-J study.

This study aimed to evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular disease (CVD) in high-risk patients with hypercholesterolemia without a history of CVD. Patients who were receiving or started treatment with pravastatin, were followed-up for 2 years. Patients were divided into quartiles according to on-treatment LDL-C. The maximum contrast method based on the Cox proportional hazards model was used to evaluate the relationship between achieved LDL-C and the incidence of CVD. Incidence of CVD was also compared according to whether a number of risk factor targets were achieved. A total 6,229 patients were enrolled, with 4,916 having reported LDL-C values. During the 2 years, 69 cases of CVD (6.7/1000 patient years), including 36 coronary artery disease (CAD) (3.5/1000 patient years) and 28 strokes (2.7/1000 patient years), occurred. The comparison of on-treatment LDL-C level quartiles suggested that the incidence of all CVD decreased linearly as the LDL-C levels decreased. Incidence of CAD showed a curvilinear relationship to LDL-C levels, suggesting some attenuation of risk below LDL-C of 119 mg/dL. The incidence of all CVD and CAD tended to be decreased as the number of achieved risk factor targets increased. In conclusion, through our observational study, it was shown that a linear relationship between the incidence of CVD and LDL-C was observed in high-risk hypercholesterolemic patients. The low incidence of CVD in the present study may be associated with multifactorial management of conventional risk factors including high LDL-C levels. However, prospective, randomized studies are needed to confirm these findings.

Innovative use of a stent retriever for temporary revascularization in acute internal carotid artery dissection.

Internal carotid artery dissection is rare but can be a cause of stroke in young people. In a case of revascularization for stroke associated with internal carotid artery dissection, we initially used a stent retriever for thrombectomy. Since an appropriately-sized stent for permanent treatment was not available, we innovatively maintained temporary revascularization with the stent retriever for 90 minutes. Here we demonstrate the adaptability of the stent retriever for emergency care. A 49-year-old man suddenly developed severe right hemiplegia and aphasia. Magnetic resonance imaging showed occlusion of a left internal carotid artery with moderate ischemic changes in the left hemisphere cortex. Angiography showed dissection of the left internal carotid artery at the cervical level and secondary thrombus formation extending into the left middle cerebral artery. We initially attempted thrombectomy with a stent retriever and achieved successful reperfusion in the middle cerebral artery. An appropriately-sized stent was not available in the hospital at that time. During the 90-minute wait, the stent retriever was kept in place and temporary angioplasty was performed in the internal carotid artery dissection to maintain blood flow. Eventually, the stent was delivered and permanent revascularization was achieved. While there is no standard treatment for arterial dissection, endovascular strategies like stenting have been demonstrated to be beneficial. The innovative use of stent retrievers for temporary angioplasty of dissected lesions underscores their efficacy in swift deployment and maintenance of uninterrupted blood flow, particularly during emergency thrombectomy.

Stereotactic radiotherapy of radiation-induced meningioma previously irradiated retrobulbar for Graves' ophthalmopathy: A case report.

A 69-year-old woman was diagnosed with an asymptomatic intracranial tumor nine years ago and has been followed with annual MR imaging studies. Two years ago, the tumor had grown in size, requiring treatment. She experienced ophthalmopathy due to hyperthyroidism 27 years ago and was treated with 20 Gy in 10 fractions using parallel opposed beams to her bilateral posterior eyeballs, supplemented with steroid pulse therapy. The tumor originated in the medial aspect of the right sphenoid border and compressed the temporal lobe, while bone infiltration was observed, partially extending to the soft tissue outside the maxillary sinus. The tumor was removed by craniotomy. The pathological diagnosis was atypical meningioma (WHO grade II). Four months postsurgery, the resection cavity's tumor exhibited growth inclination, necessitating Gamma Knife radiosurgery. Radiation planning was executed at a marginal tumor dose of 30 Gy in 5 fractions. Since the optic nerve had been previously exposed to radiation, a plan was devised to minimize radiation exposure. The dose on the optic nerve was limited to 6.9 Gy in 5 fractions. She did not experience any visual or visual field disruptions postradiation. This is a case of radiation-induced meningioma resulting from radiation therapy for Graves' ophthalmopathy and is the first reported case of a grade II meningioma. The patient's condition calls for adjuvant radiation therapy following surgical removal. Accordingly, a radiation treatment plan that safeguards the optic nerve, which was previously exposed to radiation, was deemed indispensable.

Geriatric Nutritional Risk Index as Prognostic Marker for Elderly Patients With Small Cell Lung Cancer.

Background/Aim: The Geriatric Nutritional Risk Index (GNRI) indicates nutritional status based on serum albumin concentration and ideal body weight. Pretreatment GNRI has been suggested as a prognostic factor for various malignancies. However, little is known about the clinical value of GNRI for small-cell lung cancer (SCLC), especially in elderly patients. Patients and Methods: We retrospectively analyzed 53 elderly (≥71) patients with extensive-disease (ED) SCLC treated with first-line platinum-doublet chemotherapy in relation to the pretreatment GNRI level in a real-world setting. Results: Thirty-six patients with a low GNRI (<92) had statistically poorer progression-free survival (PFS) and overall survival (OS) than 17 patients with a high GNRI (≥92) (median PFS=80 days vs. 133 days, respectively; p=0.002; median OS=123 days vs. 274 days, respectively; p=0.004). In a multivariate analysis, a low GNRI was also an independent poor prognostic factor for PFS [hazard ratio (HR)=0.396; 95% confidence interval (CI)=0.199-0.789; p=0.008] and OS (HR=0.295; 95%CI=0.143-0.608; p<0.001). Conclusion: The GNRI might be a predictive and prognostic marker in elderly patients with ED-SCLC treated with platinum-doublet chemotherapy.

Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer.

BACKGROUND/AIM: Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. RESULTS: A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. CONCLUSION: Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.

A vertebrobasilar junction aneurysm successfully treated with a combination of surgical clipping and flow diverter placement based on the results of computational fluid dynamics analysis: illustrative case.

BACKGROUND: The treatment of vertebrobasilar junction (VBJ) aneurysms is challenging. Although flow diverters (FDs) are a possible treatment option, geometrical conditions hinder intervention. VBJ aneurysms possess dual inflow vessels from the bilateral vertebral arteries (VAs), one of which is ideally occluded prior to FD treatment. However, it remains unclear which VA should be occluded. OBSERVATIONS: A 75-year-old male with a growing VBJ complex aneurysm exhibiting invagination toward the brainstem and causing perifocal edema required intervention. Preoperative computational fluid dynamics (CFD) analysis demonstrated that left VA occlusion would result in more stagnant flow and less impingement of flow than right VA occlusion. According to the simulated strategy, surgical clipping of the left VA just proximal to the aneurysm was performed, followed by FD placement from the basilar artery trunk to the right VA. The patient demonstrated tolerance of the VA occlusion, and follow-up computed tomography angiography at 18 months after FD treatment confirmed the disappearance of the aneurysm. LESSONS: Preoperative flow dynamics simulations using CFD analysis can reveal an optimal treatment strategy involving a hybrid surgery that combines FD placement and direct surgical occlusion for a VBJ complex aneurysm.

Trastuzumab deruxtecan versus treatment of physician's choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study.

BACKGROUND: In the global phase 3 DESTINY-Breast04 study (NCT03734029), the anti-human epidermal growth factor 2 (HER2) antibody-drug conjugate trastuzumab deruxtecan (T-DXd) demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS), with manageable safety compared with treatment of physician's choice (TPC) in patients with HER2-low metastatic breast cancer (mBC) who had received 1-2 prior lines of chemotherapy. METHODS: This subgroup analysis examined the efficacy and safety of T-DXd versus TPC in 213 patients from Asian countries and regions who were enrolled in the DESTINY-Breast04 trial and randomized to T-DXd (n = 147) or TPC (n = 66). RESULTS: Median PFS with T-DXd and TPC was 10.9 and 5.3 months, respectively, in Asian patients with hormone receptor-positive mBC, and 10.9 and 4.6 months, respectively, in the overall Asian population. In both populations, median OS was not reached with T-DXd and was 19.9 months with TPC. The objective response rate was higher with T-DXd versus TPC in all Asian patients. Median treatment duration was 8.4 months with T-DXd and 3.5 months with TPC. The most common grade ≥ 3 drug-related treatment-emergent adverse events in Asian patients treated with T-DXd were neutropenia (16.3%), anemia (12.9%), and leukopenia (11.6%); the incidences of neutropenia and leukopenia were higher with TPC versus T-DXd. Adjudicated drug-related interstitial lung disease or pneumonitis with T-DXd was 14.3%; the majority of events were grade 1-2. CONCLUSIONS: T-DXd demonstrated clinically meaningful survival benefits versus TPC in Asian HER2-low mBC patients, regardless of hormone receptor status, with no new safety signals. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03734029.

Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

Advanced hepatocellular carcinoma with lymph node metastases showing epithelial to mesenchymal transition effectively treated with systemic chemotherapy: Report of a case.

We present a case in which combination chemotherapy was used to successfully treat hepatocellular carcinoma (HCC) with rapid progression of lymph node (LN) metastases after liver resection. In addition, epithelial to mesenchymal transition (EMT) markers were examined immunohistochemically. A 43-year-old man who had been diagnosed with HCC showed an enlarged LN near the hepatic artery proper. After extended left lobectomy with lymphadenectomy in the hepatoduodenal ligament, he experienced rapid progression of metastases to the para-aortic and mediastinal LN. Partial remission was achieved after induction and maintenance of combination chemotherapy using etoposide, carboplatin, epirubicin and 5-fluorouracil. As a consequence of this treatment, the patient survived 10 months. Immunohistochemical studies demonstrated that HCC cells in the metastatic LN showed low expression of E-cadherin and high expression of N-cadherin and vimentin, indicating EMT. Combination chemotherapy may prove effective for patients with HCC accompanied by LN metastases that show features of EMT.

Combined transarterial and transvenous embolization of anterior cranial fossa dural arteriovenous fistula.

Background: Excessive glue injection into the drainage vein in patients with dural arteriovenous fistula (dAVF) can result in venous obstruction. We performed transarterial embolization (TAE) combined with transvenous embolization (TVE) with coils to prevent the glue from migrating into the normal cortical veins. Case Description: A 57-year-old man was pointed out to have a Borden Type III anterior cranial fossa dAVF during a check-up for putaminal hemorrhage. Because a left frontal normal cortical vein drained into the pathological drainage vein, excessive glue injection into the drainage vein may have caused venous obstruction. We performed TVE with coils at the foot of the draining vein to prevent excessive migration of glue into the drainer, followed by TAE with glue. With this technique, complete obliteration of the shunt without venous ischemia was obtained. Conclusion: The combined treatment of TAE and TVE is effective in preventing venous ischemia caused by unintended migration of glue cast into the drainage vein.