Naifa Lamki Busaidy

Background: Germline RET codon 634 pathogenic variants (PVs) are at high-risk for early-onset medullary thyroid carcinoma (MTC), but prior reports suggest that RET p.C634R PV may confer a more aggressive phenotype. Methods: We compared MEN2A phenotype and MTC outcomes with germline RET p.C634R vs other RET p.C634X PVs. We conducted a retrospective single-center cohort study of patients harboring a germline RET p.C634 PV, enrolled in the MTC Collaborative Registry (MTCCoRe) and seen at least once between May 2012 and May 2024. Results: One hundred and thirty-five patients included: p.C634R (n = 60) and other p.C634X variants (n = 75). The p.C634R PV was associated with higher penetrance of pheochromocytoma (PHEO) (67% vs 37%, P < .001) and primary hyperparathyroidism (PHPT) (30% vs 15%, P = .036). Prevalence of MTC (87% vs 80%, P = .362), cutaneous lichen amyloidosis (17% vs 9% P = .296), and median age at initial thyroidectomy (18 vs 20 years, P = .479) did not differ significantly between groups. Medullary thyroid carcinoma characteristics, including stage, multifocality, extrathyroidal extension, vascular invasion, lymph node metastases, and distant metastases, were comparable. There were no significant differences in disease-free survival, overall survival, or distant metastasis-free survival for MTC. Disease status at last follow-up also was similar between p.C634R and other p.C634X PVs: no evidence of disease in 43% vs 62% (P = .059), biochemical evidence of disease in 25% vs 17% (P = .226), and structural evidence of disease in 27% vs 20% (P = .298). Conclusion: In this large single-center cohort, germline RET p.C634R was associated with a higher penetrance of PHEO and PHPT but did not increase MTC aggressiveness or worsen clinical outcomes compared with other RET p.C634 PVs.

PURPOSE: Survivorship care models that extend beyond recurrence surveillance to ones that also address treatment-related symptoms are needed. Using data obtained in routine clinical care, we aimed to examine patient-reported symptom burden among adult thyroid cancer survivors. METHODS: Between September 2019 and September 2022, adults were electronically administered the MDASI-Thy, a patient-reported outcome measure that measures symptom severity and interference, within 7 days before their visit at a dedicated thyroid cancer survivorship clinic. The MDASI-Thy generates (1) core symptom severity, (2) thyroid-specific symptom severity, and (3) symptom interference scores, where lower is better. High alert values (HAVs) were defined for four symptoms: Distress (Upset), Pain, Sad, and Shortness of Breath. Multivariable generalized linear models examined associations of patient, cancer, and treatment factors with scores and any HAV. RESULTS: Among 1,557 thyroid cancer survivors, 864 (55.5%) responded. Respondents were a median of 5 years from diagnosis (IQR, 4-8) and predominantly female (79.1%), and most had papillary thyroid carcinoma (92.5%). Mean (standard deviation) scores were 1.20 (1.34) for core severity, 0.99 (1.26) for thyroid-specific severity, and 1.07 (1.80) for interference. Fatigue (11.5%) and Disturbed Sleep (11.3%) were the most common severe symptoms. HAVs occurred in 72 survivors (8.3%), of whom 54 (75%) had a documented plan addressing the HAV. Higher symptom burden was associated with female sex, Black race, greater comorbidity, active smoking, and total thyroidectomy. CONCLUSION: Routine patient-reported symptom screening in thyroid cancer survivorship identified generally low symptom burden but meaningful variations, with a subset reporting severe symptoms, functional interference, and HAVs requiring action.

Animal body weight information.

GATK important mutations at resistance

Suppl Table S6 from Role of the ETV5/p38 Signaling Axis in Aggressive Thyroid Cancer Cells

Genomic landscape of the cell lines used

Histology of mouse ATC tumors, genotyping of derived cell lines, and MRI images.

FDA approval status of the drugs used in this study and drug structures

Tumor histology in the ATC GEMM model under diverse treatments