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Histopathological study of carcinoma showing thymus-like differentiation (CASTLE)

Okubo Y, Sakai M, Yamazaki H, Sugawara Y, Samejima J, Yoshioka E, et al.

Malays J Pathol, 2020 08;42(2):259-265.
PMID: 32860379

INTRODUCTION: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival.
CASE REPORT: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE.
DISCUSSION: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.
Cytototoxic constituents from the bark of Chisocheton cumingianus (Meliaceae)

Katja DG, Farabi K, Nurlelasari, Harneti D, Mayanti T, Supratman U, et al.

J Asian Nat Prod Res, 2016 Jun 22.
PMID: 27329305 DOI: 10.1080/10286020.2016.1196671

A new lanostane-type triterpenoid, 3β-hydroxy-25-ethyl-lanost-9(11),24(24')-diene (1), along with 3β-hydroxy-lanost-7-ene (2) and β-sitosterol-3-O-acetate (3) was isolated from the stem bark of C. cumingianus. The chemical structure of the new compound was elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against P-388 murine leukemia cells. Compounds 1-3 showed cytotoxicity against P-388 murine leukemia cells with IC50 values of 28.8 ± 0.10, 4.29 ± 0.03, and 100.18 ± 0.16 μg/ml, respectively.
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer

Lee SH, Menis J, Kim TM, Kim HR, Zhou C, Kurniawati SA, et al.

ESMO Open, 2024 Nov 29;9(12):103996.
PMID: 39615406 DOI: 10.1016/j.esmoop.2024.103996

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC), published in January 2023, was modified according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with oncogene-addicted mNSCLC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with oncogene-addicted mNSCLC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Korean Society for Medical Oncology (KSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with oncogene-addicted mNSCLC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, while respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies between the different regions of Asia.
Fulltext Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA

Felip E, Cho BC, Gutiérrez V, Alip A, Besse B, Lu S, et al.

Ann Oncol, 2024 Sep;35(9):805-816.
PMID: 38942080 DOI: 10.1016/j.annonc.2024.05.541

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups.
PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR).
RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004].
CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.