Biomedical subjects

Shunji Takahashi

Publications and source records attributed to Shunji Takahashi.

3 recordsLinked to original sources

PubMed2026

Continuous administration of lenvatinib after first documented disease progression in patients with radioiodine-refractory thyroid cancer.

PURPOSE: To determine the efficacy and safety of lenvatinib beyond first documented disease progression (LBP) and prognostic factors after progression in patients with radioiodine-refractory thyroid cancer. METHODS: This retrospective study included adults with radioiodine-refractory thyroid cancer who received lenvatinib between January 2012 and November 2023 and continued treatment after initial RECIST 1.1 progression. Patients who subsequently received other multikinase inhibitors or selective targeted therapies were excluded. Time to second treatment failure (second TTF) was defined as time from initial progression to permanent lenvatinib discontinuation for any reason; second progression-free survival (second PFS) as time from initial progression to subsequent radiographic progression or death; and post-progression survival (PPS) as time from initial progression to death. Outcomes were estimated by Kaplan–Meier methods, and prognostic factors were explored by Cox regression. Safety was assessed. RESULTS: Twenty-four patients met the eligibility criteria for LBP. The objective response rate after progression was 0%, whereas the disease control rate was 50.0%. Median second PFS and second TTF were 6.0 months and 8.0 months, respectively. Median PPS was 14.8 months. At 12 months after initial progression, 37.5% of patients remained on lenvatinib and 56.5% were alive. Baseline progressive disease at initial progression (tumor burden returning to or exceeding the pretreatment baseline) was associated with shorter second TTF, with similar trends for second PFS and PPS. The most common adverse events were hypertension, proteinuria, peripheral edema, and renal dysfunction. CONCLUSION: Continuation of lenvatinib beyond disease progression achieved modest additional disease control with acceptable safety in selected patients. In settings where access to subsequent-line systemic therapies is limited or no actionable targets are identified, LBP may serve as a pragmatic bridging approach for carefully selected patients.

Humans↗

PubMed2026

Immunological Features of Neuroendocrine Neoplasms and Adrenal Tumors.

Neuroendocrine neoplasms, which occur throughout the human body, as well as adrenocortical carcinoma and pheochromocytoma, which originate in the adrenal gland, are primarily classified as rare malignancies. Immunotherapy, including immune checkpoint inhibitors (ICIs), is generally not incorporated into the standard care protocols for these tumors. The clinical efficacy of ICIs in these tumors has been modest. This may be due to the biological heterogeneity of these tumors. The tumor immune microenvironment profiles are heterogeneous among the molecular subtypes of pheochromocytoma/paraganglioma, suggesting a potential benefit observed in selected subgroups. Poorly differentiated neuroendocrine carcinoma (NEC) exhibits spontaneous activation of adaptive immunity, unlike well-differentiated neuroendocrine tumors. A delta-like ligand 3-directed T-cell-engaging bispecific antibody, tarlatamab, has recently demonstrated prolonged survival in small cell lung cancer, and investigations into its use in extrapulmonary NEC are underway. This review examines the immunological features of representative neuroendocrine and adrenal tumors (neuroendocrine tumor, neuroendocrine carcinoma, adrenocortical carcinoma, and pheochromocytoma/paraganglioma). In the future, elucidating the relationship between specific molecular subtypes and immunophenotypes may facilitate the development of personalized therapies and guide clinical investigations in promising patient subpopulations.

Humans↗

PubMed2025

The first case of GOLGA5-RET fusion-positive malignant spindle cell sarcoma of the head and neck responsive to selpercatinib.

Soft-tissue sarcoma (STS) is a rare malignancy that accounts for less than 1% of all cancers, and recent advances in molecular biology have led to its classification based on genomic information. Some RET-rearranged neoplasms have been reported to present pathological features similar to Neurotrophic Tyrosine Kinase Receptor-rearranged spindle cell neoplasms. Here, we report the first case of head and neck spindle cell sarcoma with a GOLGA5-RET fusion that demonstrated a sustained clinical response to selpercatinib, identified through targeted next-generation sequencing (NGS). The patient was a 43 year-old man with a tumor in the arytenoid region that was resected and diagnosed as a malignant spindle cell tumor. Despite initial treatment with surgical resection alone, local recurrence was confirmed, requiring salvage therapy with total laryngectomy and bilateral cervical dissection. Surgical specimen revealed a spindle tumor with a patternless pattern and collagenous stroma. Immunohistochemistry (IHC) with positivity for CD34, bcl-2 (focally), S100, and weak nuclear staining for STAT6, with absence of expression of CK AE1/3, desmin, c-kit, smooth muscle actin, myogenin, synaptophysin, and SOX10. Trk A/B/C were also negative on IHC. Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Targeted NGS identified GOLGA5-RET rearrangement, FGF14 amplification (equivocal), CDKN2B loss, and CDKN2A loss. GOLGA5-RET rearrangements were validated through fluorescence in situ hybridization. The patient subsequently was enrolled in a phase 1/2 trial for the selective RET inhibitor selpercatinib, resulting in a sustained partial response over 5 years. Although solitary fibrous tumor (SFT) was initially considered as a differential diagnosis based on immunohistochemical findings, the lack of strong and diffuse STAT6 expression made this diagnosis unlikely. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.

Next-generation sequencing↗