The"2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer"released by the American Thyroid Association(ATA)in 2025 include several important updates regarding nuclear medicine diagnosis and treatment for post-operative differentiated thyroid cancer(DTC).This article systematically reviewed advances in the nuclear medicine aspects of post-operative DTC assessment,decision-making for radioactive iodine therapy(RAIT),dynamic response evaluation,and follow-up strategies,guided by the 2025 ATA guidelines'DATA clinical management framework—Diagnosis,risk/benefit Assessment,Treatment decisions,and response Assessment.Building on the 2015 ATA guidelines and recent research evidence,the 2025 ATA guidelines emphasize the critical importance of post-operative response assessment(including serological and imaging evaluations)for the real-time refinement of risk stratification.It further subcategorizes recurrence risk from the original three categories(low,intermediate,high)to four categories(low,low-intermediate,intermediate-high and high)to more accurately predict the risk of structural recurrence.Regarding RAIT strategy,the 2025 ATA guidelines clearly state that remnant ablation is no longer routinely recommended for low-risk patients to avoid unnecessary radiation exposure,and highlight the preferred use of recombinant human thyroid stimulating hormone(rhTSH)for RAIT preparation in low-and intermediate-risk patients.The 2025 ATA guidelines further clarify the appropriate clinical application scenarios for nuclear medicine molecular imaging methods such as diagnostic whole-body scan(DxWBS)and 18F-FDG positron emission tomography and computed tomography(PET/CT).At the same time,concerning post-RAIT follow-up strategies,indications for repeated RAIT,as well as the diagnostic criteria and management principles for radioactive iodine-refractory DTC(RAIR-DTC),this article highlighted the key updated points in the 2025 ATA guideline.

In 2025,the American Thyroid Association(ATA)divided the management of thyroid nodules and differentiated thyroid cancer(DTC)into two separate guidelines for the first time.This review highlighted the imaging-related updates and compared them with the 2015 ATA guidelines.The 2025 ATA guidelines introduce the following key updates:① Clarifying recommendations for screening of familial non-medullary thyroid cancer,and proposing that thyroid ultrasound screening is not recommended before treatment for patients who will receive glucagon-like peptide-1 receptor agonist(GLP-1 RA)therapy;② Refined the sonographic malignancy risk stratification system,enabling classification of all nodule types;③ Increasing size thresholds for fine-needle aspiration(FNA)and emphasized individualized decisions based on age,comorbidities and other factors;④ Follow-up intervals for nodules not meeting FNA criteria or with benign cytology have been adjusted,and clear ultrasound surveillance endpoints have been proposed;⑤ A standardized ultrasound protocol is established for active surveillance of cT1aN0M0 papillary thyroid cancer;⑥ Additional suspicious features,including abnormal blood flow in cervical lymph nodes,are introduced with quantitative evidence;⑦ Proposing dynamic risk stratification,adjusting follow-up intervals based on the patient's risk of residual lesion or disease recurrence and their response to treatment,and adding new endpoints for postoperative follow-up for low-risk DTC patients with sustained excellent response;⑧ Stressing the preoperative use of computed tomography(CT)or magnetic resonance imaging(MRI)to evaluate distant metastasis,while no longer recommending them as routine imaging tools during follow-up;⑨ Defining indications for thermal ablation:benign nodules,low-risk microcarcinomas and recurrent or metastatic lesions.Guided by evidence-based medicine,the 2025 ATA guidelines promote the transformation of thyroid ultrasound towards"precision,minimal invasiveness,individualization",providing a new paradigm for the whole-process clinical management of thyroid diseases.

The"2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer"introduce significant updates in genotyping.This article systematically interpreted the role and clinical applications of genotyping in pre-diagnostic differentiation,post-diagnostic familial analysis,surgical approach guidance,postoperative recurrence risk stratification,as well as targeted therapy and immunotherapy with a focus on mutation-based medical decision-making.Key updates on standardized genotyping applications include:① In pathological diagnosis,genotyping was first applied in pathological differentiation.The 2025 ATA guidelines further clarify the distribution patterns of different genetic mutations across pathological subtypes,enabling more precise classification,particularly for tumors of very low malignant potential,to avoid overtreatment.② In familial analysis and genetic counseling,systematic familial evaluation is recommended post-diagnosis.The 2025 ATA guidelines propose strict clinical evidence-based categorization and selective germline genetic testing,with tailored genetic counseling strategies based on genotype.③ In surgical approach and recurrence risk stratification,the 2025 ATA guidelines refine the auxiliary role of genotyping in surgical decision-making and recurrence risk stratification,reiterating that genotyping complements traditional risk stratification systems.④ In targeted therapy,the 2025 ATA guidelines establish genotyping-guided precision therapy,mandating genetic testing for all radioiodine-refractory differentiated thyroid cancer(DTC)patients before targeted therapy to select mutation-specific agents.For patients progressing on target-specific drugs,re-biopsy is recommended to identify actionable targets.If no treatable target exists,multi-kinase inhibitors are advised.⑤ In immunotherapy,pre-treatment genetic testing is recommended,with immunotherapy indicated for radioiodine-refractory DTC patients exhibiting high tumor mutational burden(TMB-H).This article provided a comprehensive review and in-depth analysis of the clinical applications of genotyping in DTC management as outlined in the 2025 ATA guidelines.

In recent years,the incidence of differentiated thyroid cancer(DTC)continues to rise,with increasing attention to perioperative management and postoperative thyroid-stimulating hormone(TSH)suppression therapy strategies.The American Thyroid Association(ATA)released the"2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer"in 2025,which include significant updates on perioperative parathyroid function protection and TSH suppression therapy.In terms of perioperative management,the 2025 ATA guidelines recommend intraoperative application of novel methods to identify and protect the parathyroid glands,and adoption of parathyroid hormone(PTH)-guided calcium and vitamin D supplementation protocols following total thyroidectomy.Regarding TSH suppression therapy,the 2025 ATA guidelines eliminate specific TSH target value recommendations for initial treatment,emphasizing that TSH targets should be dynamically adjusted based on patients'initial recurrence risk and treatment response to achieve individualized management and avoid overtreatment.

Background and purpose:Intracellular deubiquitylating enzymes,such as ubiquitin-specific peptidase 2(USP2),play a pivotal role in regulating protein degradation and cellular homeostasis by modulating protein ubiquitin deconjugation,which have been implicated in the proliferation and survival of multiple myeloma(MM)cells.Targeting the inhibition of USP2 activity in MM cells might modulate their biological behavior.This study aimed to investigate regulatory effects of the leukotriene receptor antagonist montelukast sodium on USP2 in MM cells and its subsequent biological effects.Methods:An in vitro deubiquitination reaction system was established using purified USP2 protein and its substrate,the glutathione S-transferase(GST)tagged ubiquitin A-52 residue ribosomal protein fusion product(UbA52),known as GST-UbA52 protein.This system was used to characterize inhibitory effects of montelukast sodium on USP2 deubiquitinase activity.The MM cell lines MM1.S and H929 were used as in vitro models.Cellular thermal shift assay(CETSA)was subsequently employed to test interaction mode between montelukast sodium and USP2 in MM cells.Western blot assay was applied to detect expression levels of USP2 and its targeting regulators,including cell cycle supervisors cyclin D1(CCND1)and cyclin A1(CCNA1),classical signaling transducer KRAS and glucose regulated protein 78kD(GRP78),as well as apoptotic molecule C/EBP-homologous protein(CHOP)in MM1.S and H929 cells before and after the treatment with different concentrations of montelukast sodium.MM cells with either overexpression(H929-OE,MM1.S-OE)or knockdown(H929-LE,MM1.S-LE)of USP2 were generated using a lentiviral vector.Cell counting kit-8(CCK-8)and flow cytometry were utilized to detect the proliferation and apoptotic rates of H929-OE,MM1.S-OE,H929-LE and MM1.S-LE cells treated with montelukast sodium.Results:Montelukast sodium was found to inhibit USP2 mediated degradation of GST-UbA52 protein in a concentration-dependent manner,with a half inhibitory concentration(IC50)of 3.814 μmol/L.Additionally,montelukast sodium significantly enhanced the thermal stability of USP2 at temperatures of 49.1,53.2 and 56.4℃.It was also shown that montelukast sodium could down-regulate expressions of CCND1,CCNA1 and KRAS,while increase levels of GRP78 and CHOP in MM1.S and H929 cells.Furthermore,after treating with 40 μmol/L montelukast sodium for 24 h,the proliferation inhibition and apoptotic rate of H929-OE cells reached to(37.68±1.10)%and(18.99±0.26)%,while the proliferation inhibition and apoptotic rate of MM1.S-OE cells reached to(24.48±0.49)%and(33.29±0.75)%,which were significantly lower than those in H929 and MM1.S cells[H929:(57.19±1.93)%and(45.65±0.24)%;MM1.S:(50.04±0.53)%and(40.25±0.91)%;P＜0.05,n=3].Conversely,the proliferation inhibition and apoptotic rates of H929-LE and MM1.S-LE cells were significantly higher[H929-LE-1#:(80.70±1.60)%and(89.08±0.49)%;H929-LE-2#:(75.30±3.80)%and(82.41±1.07)%;MM1.S-LE-1#:(70.64±0.84)%and(67.63±0.21)%;MM1.S-LE-2#:(68.47±1.32)%and(85.90±0.18)%;P＜0.05,n=3].Conclusion:Montelukast sodium can target ubiquitin proteasome regulator USP2 and inhibit its deubiquitylating activity,which may modulate USP2 directing protein and trigger endoplasmic reticulum stress to induce cell cycle arrest and apoptosis in MM cells.

Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.

Background and purpose:Despite Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors,there is limited evidence for small cell lung cancer(SCLC).The purpose of this study was to investigate whether the absolute lymphocyte count before and after radiotherapy could predict the clinical outcomes for limited-stage SCLC(LS-SCLC)patients.Methods:This was a single-center,retrospective cohort study.A retrospective analysis of patients evaluated at Fudan University Shanghai Cancer Center from January 2007 to December 2017 was conducted.Inclusion criteria:⑴ pathologically confirmed small-cell lung cancer;⑵ limited-stage disease defined by positron emission tomography and computed tomography(PET/CT)and contrast-enhanced brain magnetic resonance imaging(MRI)[American Joint Committee on Cancer(AJCC)8th edition TNM stage M0];⑶ receipt of definitive chemoradiotherapy;⑷ availability of complete blood counts before,during and within 1 month after radiotherapy;⑸ complete survival,relapse,and last-follow-up information retrievable.Exclusion criteria:⑴ distant metastasis at baseline(AJCC 8th edition TNM stage M1,including any distant nodal,visceral,or bone-marrow involvement);⑵ total radiotherapy dose＜50 Gy[calculated as an equivalent biological dose at 2 Gy/fraction,i.e.,a biological effective dose(BED)＜40 Gy];⑶ incomplete laboratory data at any scheduled time point;⑷ inability to ascertain survival or relapse status or insufficient follow-up records.The study protocol was approved by the ethics committee of Fudan University Shanghai Cancer Center(approval number:2303271-15),and the requirement for informed consent was waived.Clinical data extracted comprised age,sex,Eastern Cooperative Oncology Group performance status(ECOG PS)score,smoking history,TNM stage,chemotherapy regimen and number of cycles,radiotherapy dose and fractionation schedule,use of concurrent chemoradiotherapy and administration of prophylactic cranial irradiation(PCI).Laboratory data comprised serial absolute lymphocyte counts obtained within 1 month before,during and after radiotherapy;lymphopenia was graded according to the Common Terminology Criteria for Adverse Events(CTCAE)version 4.0.Progression-free survival(PFS)and overall survival(OS)were estimated using the Kaplan-Meier method and compared with the log-rank test.Results:A total of 170 patients were included.The median age of the patients was 57 years,with 77.6%being male.The median radiation therapy dose was 60 Gy(range:45-66 Gy).For the entire cohort,the median PFS was 22.0 months,the 5-year PFS rate was 31.3%,and the 10-year PFS rate was 19.8%.The median OS was 38.0 months,the 5-year OS rate was 37.5%,and the 10-year OS rate was 24.2%.Before radiation therapy,14 patients(8.2%)had grade 1-2 lymphocytopenia.During radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 7(4.1%),22(12.9%),111(65.3%),and 24(14.1%),respectively.One month after radiation therapy,the number of patients with grade 1,2,3 and 4 lymphocytopenia was 36(21.2%),36(21.2%),11(6.5%)and 1(0.6%),respectively.There were no significant differences in PFS and OS among patients with different grades of lymphocytopenia before,during,or after radiation therapy.Conclusion:Before immunotherapy,radiotherapy-induced lymphopenia did not appear to affect the prognosis of patients with LS-SCLC.

Gastric cancer presents a high incidence rate and substantial disease burden,posing significant therapeutic challenges.Recent advances have yielded significant benefits for gastric cancer patients through novel anti-tumor agents,including immune checkpoint inhibitor(ICI),human epidermal growth factor receptor 2(HER2)-targeted therapies,and claudin 18.2(CLDN18.2)-directed agents.Both monotherapy and various combination regimens demonstrate considerable promise in gastric cancer treatment.However,a critical safety concern potentially limiting patient benefit is drug-induced interstitial lung disease(ILD)/pneumonitis,particularly associated with ICI and antibody-drug conjugate(ADC).The risk and underlying mechanisms of ILD vary considerably across different anti-tumor drug classes,and its often insidious onset makes early detection difficult.Therefore,a deep understanding of the distinct ILD risks and mechanisms associated with different agents,coupled with rational,individualized drug monitoring and patient management,is paramount.This review systematically analyzes the incidence rates,clinical characteristics,and risk factors associated with ILD/pneumonitis reported in recent clinical trials of anti-tumor therapies for gastric cancer.It aimed to elucidate the risk stratification and mechanistic differences between drug classes,thereby enhancing clinical awareness and ultimately helping to maximize clinical outcomes for gastric cancer patients.

The axillary management of breast cancer patients after neoadjuvant therapy(NAT)is undergoing optimization.Sentinel lymph node biopsy(SLNB)has become an important means for evaluating the status of axillary lymph node(ALN),especially in early-stage breast cancer patients with initially clinically negative ALN(cN0),where it can replace traditional ALN dissection(ALND)to reduce unnecessary surgical risks and complications.However,SLNB has some limitations in terms of false negative rate(FNR)and variability when applied to breast cancer patients with initially clinically positive ALN(cN+)after NAT.By removing≥3 SLN,using dual tracers(such as radioactive isotopes combined with blue dye),and conducting pathological assessment in combination with immunohistochemistry(IHC),the FNR can be significantly reduced to an acceptable range(4.9%-9.1%).Moreover,various optimization schemes have been developed,such as marking ALN with radioactive iodine(MARI),targeted axillary dissection(TAD),and radioactive iodine seed placement in the axilla with SLNB(RISAS),all of which demonstrate low FNR.Not only that,non-invasive imaging techniques such as positron emission tomography and computed tomography(PET/CT),magnetic resonance imaging(MRI),conventional ultrasound and contrast-enhanced ultrasound(CEUS)can all be used to evaluate the axillary response after NAT,with varying diagnostic efficacies.This article summarized recent studies on the optimization of axillary management and SLNB diagnosis and treatment for breast cancer patients with cN+after NAT.

Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.