Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1.

OBJECTIVE: Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications. DESIGN, PATIENTS AND MESUREMENT: A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ2 tests, were employed for survival analysis and gene mutation comparisons. RESULTS: Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data. CONCLUSIONS: Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

BACKGROUND: Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. METHODS: We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. RESULTS: In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival. CONCLUSION: CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

Risk factors for incomplete resection with pharyngeal endoscopic submucosal dissection and long-term prognosis after resection.

BACKGROUND: Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD. METHODS: This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed. RESULTS: The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection. CONCLUSION: Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.

Elective neck dissection for T3-T4N0 laryngeal carcinoma: evidence from Japan's National Head and Neck Cancer Registry.

BACKGROUND: Although total laryngectomy is the standard treatment for advanced laryngeal cancer, the significance of elective neck dissection (END) for N0 laryngeal cancer remains unclear in Japan, which is an aging society. METHODS: We conducted a retrospective nationwide observational study on patients with T3-T4N0 laryngeal squamous cell carcinoma treated with curative total laryngectomy from 2011 to 2018 in Japan. RESULTS: A total of 1,218 patients were analyzed. The median patient age was 72 years, with 735 cases of T3N0 and 483 cases of T4N0. END was performed on the affected side in 850 patients (70%) and on the contralateral side in 502 patients (41.2%). END on the affected side was omitted in patients aged > 80 years (40.4%) and in patients with an advanced performance status. The occult lymph-node metastasis rate did not differ by age (18.8%-19.6%); it tended to increase chronologically from 2011 (11.1%) and was higher in cT4a (22.5%) and pT4a (24.3%) cases. In this study, coherent clinical information and follow-up data were available for 252 patients. Both univariate and multivariate analyses showed no significant prognostic factors for overall survival or recurrence-free survival for either affected or contralateral END. Older age and subglottic location were poor prognostic factors, but death due to factors other than laryngeal cancer could not be ignored in older patients. CONCLUSION: Omission of END during laryngectomy for T3-T4N0 laryngeal cancer is acceptable for older patients who want their operation to be completed in a short time.

Internal jugular vein reconstruction using a triple-paneled great saphenous vein graft.

BACKGROUND: Donor-recipient diameter discrepancy can be problematic when using an autologous great saphenous vein graft for internal jugular vein reconstruction. A triple-paneled method of saphenous vein grafting is one solution. CASE PRESENTATION: A 54-year-old man with a thyroid papillary carcinoma underwent total thyroidectomy and bilateral neck dissection. An 8-cm segment of the right internal jugular vein was resected. For reconstruction, a 30-cm segment of the great saphenous vein was harvested and divided into three pieces of equal length. After opening each piece longitudinally, they were sutured together in a side-by-side fashion to create a cylinder that was used to reconstruct the internal jugular vein defect. The graft was patent 10 months after the surgery. CONCLUSION: The triple-paneled method is feasible for autologous great saphenous vein graft reconstruction of the internal jugular vein.

Tumor-stroma ratio can predict lymph-node metastasis in cT1/2N0 oral tongue squamous cell carcinoma independent of tumor budding grade.

BACKGROUND: cT1/2 oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. However, predicting neck lymph-node metastasis (NLM) remains challenging. Pathomorphological evaluation of tumor budding grade (TBG) and tumor-stroma ratio (TSR) reportedly can predict lymph-node metastases. Hence, this study aimed to evaluate TBG and TSR in OTSCC and investigate their relationship to occult NLM and cancer relapse. METHODS: Clinicopathological data of patients with cT1/2N0 OTSCC treated at the University of Tokyo Hospital between 2007 and 2017 were collected. TBG and TSR were evaluated using hematoxylin-eosin staining and cytokeratin AE1/AE3 immunostaining. RESULTS: Out of 70 patients, 16 underwent elective neck dissection in addition to primary-tumor resection, whereas 54 did not. During follow-up, NLM was found in 35 patients. NLM correlated with the pathological depth of invasion (pDOI) (p < 0.001), TBG (p = 0.008), and TSR (p < 0.001) in univariate analysis and pDOI (p = 0.01) and TSR (p = 0.02) in multivariate analysis. The 5-year recurrence-free survival rate (RFS) was 78% for patients with a pDOI ≤ 5 mm and stroma-poor tumors and 33% for patients with a pDOI > 5 mm and stroma-rich tumors. CONCLUSION: Patients with a pDOI > 5 mm and stroma-rich tumors have a high risk for cancer relapse. TSR and pDOI may be promising NLM predictors in cT1/2N0 OTSCC.

The prognostic value of TP53 mutations in hypopharyngeal squamous cell carcinoma.

BACKGROUND: TP53 is the most frequently mutated gene in human cancers. Previous studies reported that TP53 mutations correlated with poor prognoses in patients with head and neck squamous cell carcinoma (HNSCC). However, the relationship between TP53 mutations and hypopharyngeal squamous cell carcinoma (HPSCC) is not known. The current study aimed to evaluate TP53 mutation status as a predictive biomarker in patients with HPSCC. METHODS: We retrospectively reviewed the clinical charts of 57 HPSCC patients treated with initial surgery between 2008 and 2014. TP53 mutation status was determined by Sanger sequencing, and patients were classified into wild-type, missense mutation, and truncating mutation groups. Additionally, p53 expression was determined using immunohistochemistry in surgical specimens. RESULTS: TP53 mutations were identified in 39 (68%) patients. The 3-year disease-specific survival (DSS) rate of wild-type, missense mutation, and truncating mutation group were 94%, 61%, and 43%, respectively. The TP53 mutation group displayed significantly worse DSS and overall survival rates than the wild-type group (P = 0.01 and P = 0.007, respectively). Multivariate analyses revealed that the presence of TP53 mutations and ≥4 metastatic lymph nodes were independent adverse prognostic factors for HPSCC. p53 immunopositivity was detected in 22 patients, including 5 (28%) and 17 (71%) patients in the wild-type and missense mutation groups, whereas none of the patients with truncating mutation exhibited p53 immunopositivity (P = 0.0001). CONCLUSION: The TP53 mutation status correlated with poor prognosis in surgically treated HPSCC patients. Specifically, truncating mutations which were not detected by p53 immunohistochemistry were predictive of worst survival.

Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma.

OBJECTIVES: Temporal bone squamous cell carcinoma (TSCC) is a rare malignancy. Due to its low incidence rate, studies involving TSCC treatment are limited. The aim of this study is to define the prognostic factors of surgery for TSCC by evaluating our clinical experience. METHODS: We reviewed the clinical charts of patients presenting at the University of Tokyo Hospital between 2001 and 2014 and identified 33 patients with TSCC who had been treated with surgery as initial curative treatment. RESULTS: Lateral and subtotal temporal bone resections were performed in 17 and 16 patients, respectively. The 5-year disease-specific and overall survival rate were 71 and 62%, respectively. The significant poor prognostic factors were pathological T4 (P = 0.03), dural invasion (P = 0.008), temporomandibular joint invasion (P = 0.04), and a positive surgical margin (P = 0.009). CONCLUSION: We demonstrated that the outcome of curative surgery for TSCC as initial treatment was favorable. However, because of the difficulty to ensure an adequate or clear surgical margin due to anatomical complexity, the surgical indication for T4 TSCC with temporomandibular joint invasion should be reconsidered.

Natural History of Asymptomatic Papillary Thyroid Microcarcinoma: Time-Dependent Changes in Calcification and Vascularity During Active Surveillance.

BACKGROUND: Prospective trials of non-surgical observation have shown progression rates of only 5-10% in patients with asymptomatic papillary microcarcinoma (PMC). This study investigated time-dependent changes in calcification patterns and tumor vascularity on ultrasonography (US) to clarify the natural course of PMC. METHODS: We examined calcification patterns and tumor vascularity for 480 lesions in 384 patients. Calcification patterns were classified as: (A) none; (B) micro; (C) macro; or (D) rim. Tumor vascularity was classified as rich or poor via color Doppler US. RESULTS: After a mean of 6.8 years of observation, 29 lesions (6.0%) had increased in size. Mean age for initial calcification pattern was 52.1 years for A (n = 135), 54.2 years for B (n = 235), 56.3 years for C (n = 96), and 60.1 years for D (n = 14), and the incidence rates of tumor enlargement were 9.6, 5.5, 3.2, and 0%, respectively. The cumulative rate of upgrade in calcification pattern was 51.8% at 10 years. Lesions with initially rich vascularity (n = 70) had significantly higher rate of tumor enlargement than those with poor vascularity (n = 410); however, the majority of tumor (61.4%) with initially rich vascularity had decreased their blood supply during the follow-up. Multivariate analysis showed that strong calcification (C or D) and poor vascularity at last examination correlated significantly with non-progressive disease. CONCLUSIONS: PMCs in older patients showed significantly stronger calcification patterns and poorer vascularity. Both consolidation of calcification and loss of vascularity occurred in a time-dependent manner during observation and were significant indicators for non-progressive disease.

Ultra-high combined positive score and high serum albumin are favorable prognostic biomarkers for immune checkpoint inhibitors in head and neck squamous cell carcinoma.

BACKGROUND: Biomarkers that predict response to immune checkpoint inhibitor (ICI) in recurrent metastatic squamous cell carcinoma of the head and neck (RMHNSCC) are not well known. METHODS: We prospectively measured the combined positive score (CPS) and administered ICI to patients with RMHNSCC. RESULTS: Of 51 patients, 23 patients had a CPS <20 and 12 patients (23.5%) had a CPS ≥90. CPS showed a negative correlation with serum albumin. Survival analysis showed a 2-year survival rate of 24.1%. In multivariate analysis, CPS ≥90 (HR 0.3026, p = 0.02614) and albumin >3.5 (HR 0.3463, p = 0.01354) were the significant factors and plus chemotherapy (HR 0.4648, p = 0.07632) was not significant. Seven patients (14%) with CPS ≥90 and albumin >3.5 showed a 2-year survival rate of 66. 7%. CONCLUSIONS: CPS ≥90 and albumin >3.5 cases are a subgroup of RMHNSCC that respond extremely well to ICI.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:228-235, 2024.

TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas.

BACKGROUNDS: The importance of TERT promoter (pTERT) mutation of oral cavity squamous cell carcinoma (OCSCC) with clinical features and genetic alterations are not well recognized. METHODS: We retrospectively analyzed genetic data from multiple databases, including 260 cases from the C-CAT database, 407 cases from the MSK-MetTropism database, and 40 OCSCC datasets from in-house clinical samples. RESULTS: From C-CAT database, TP53 (66%), CDKN2A (51%), and pTERT (29%) were the most frequent mutations observed. pTERT mutations were more prevalent in OCSCC (63%), younger individuals, and women (46%), with lower rates of alcohol abuse and smoking and co-mutated with TP53, HRAS, and CASP8. MSK-MetTroposim data validated with the enrichment of pTERT mutations in OCSCC, among women and Asian individuals. In-house datasets OCSCC with pTERT mutation (50%) characterized by fewer recurrent neck metastases. CONCLUSION: The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.

p16 status and high-risk human papilloma virus infection in squamous cell carcinoma of the nasal vestibule.

OBJECTIVE: The status of human papilloma virus (HPV) and p16 overexpression for nasal vestibule squamous cell carcinoma (NVSCC) is unclear. The purpose of this retrospective study was to analyze the presence of HPV and the role of p16 overexpression as a surrogate marker in cases of NVSCC. METHODS: Retrospective analysis was performed on patients who were diagnosed and treated for NVSCC at the University of Tokyo Hospital, Japan. p16 immunohistochemistry was considered positive with at least moderate staining intensity and diffuse staining (≥75% of tumor cells), according to the 8th edition of the American Joint Commission on Cancer. HPV-DNA testing was performed using multiplex polymerase chain reaction. RESULTS: Five patients were included in the study. Ages ranged from 55 to 78 years; there were two men and three women; two had T2N0, and three had T4aN0. Surgery was performed in one case, surgery plus radiation therapy (RT) in one case, and chemoradiation therapy (CRT) in three cases. Four of the five tumors showed p16 overexpression. One of five cases had an HPV-16 genotype. The mean follow-up period was 73 months, and all the patients survived. One patient with p16-negative carcinoma had local recurrence and underwent salvage surgery. Of the four patients with p16-positive carcinoma, one with CRT and one with surgery plus RT, each had delayed cervical lymph node metastasis, which was salvaged with neck dissection subsequent RT. CONCLUSIONS: In NVSCC, four of the five cases were p16-positive, and one was high-risk HPV infection.

Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer.

In head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.

Subcutaneous axillary primary epithelioid hemangioendothelioma: report of a rare case.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare and slow-growing malignant vascular neoplasm composed of epithelioid endothelial cells within a distinctive myxohyaline stroma. It most commonly involves somatic soft tissue, lungs, liver and bone. Herein, we describe a case of EHE arising in the axillary region. CASE PRESENTATION: A 61-year-old man was under observation for multiple hepatic hemangiomas. Fluorodeoxyglucose-positron emission tomography/computed tomography showed specific uptake in a right axillary tumor. The patient was referred to our department for further investigation of the axillary tumor. An elastic-soft and poorly mobile tumor was palpable in the right axilla. Contrast-enhanced computed tomography showed a right axillary tumor and enlarged hepatic hemangiomas. In addition, multiple nodules in both lungs, a left renal angiomyolipoma, and left adrenal adenoma were revealed. Ultrasonography showed masses in both lobes of the thyroid gland, and a 30-mm lobulated hypoechoic mass in the axilla with well-defined and rough borders, showing internal heterogeneity. Fine-needle aspiration cytology was performed on the thyroid and axillary tumors: the thyroid tumor was class V, raising suspicion of papillary thyroid cancer (PTC); the left superior internal jugular node was class V, raising suspicion of metastasis of PTC; and the axillary tumor was class III, raising suspicion of a mesenchymal tumor with few epithelioid cells. The multiple lung nodules were diagnosed as metastatic tumors derived from thyroid cancer. We diagnosed these diseases as PTC of T1b(m)N1bM1(lung) Stage IVB and a right axillary tumor of unclear origin. However, it was assumed to be a primary mesenchymal tumor or a lymph node metastasis from lung cancer or occult breast cancer. We performed total thyroidectomy, left cervical lymph node dissection, and right axillary tumor excision. Histopathologic examination revealed the thyroid tumor as a PTC and the axillary tumor as an EHE. The EHE showed nuclear atypia, necrosis and high mitotic figures. Hence, it was considered to be a high-risk EHE. CONCLUSIONS: We experienced a rare primary subcutaneous axillary EHE with metastatic thyroid cancer in the lung. Since our case was classified as a high-risk EHE, a close follow-up would be appropriate.

Total Maxillectomy and Free Flap Reconstruction in Hemodialysis Patients: Report of Two Cases.

Currently, an increasing number of patients are undergoing hemodialysis. However, little is known regarding the outcome or perioperative management of head and neck cancer reconstruction in patients undergoing hemodialysis. Here, we report two cases of patients with maxillary squamous cell carcinoma undergoing hemodialysis. The patients underwent total maxillectomy and free abdominal flap transfer. A short-thread double-needle was used in one patient because arterial calcification and intimal dissection were observed during microvascular anastomosis. Maintenance hemodialysis was performed the day before and after the surgery. Nafamostat mesylate, an ultra-short acting anticoagulant, was used in the postoperative hemodialysis for 2-3 weeks to prevent bleeding. The flaps survived completely, and no major postoperative complications occurred in either case. One patient showed no evidence of disease at 1 year following the surgery, whereas the other patient died of cancer metastasis 6 months following the surgery. Although further standardization of perioperative hemodialysis management is needed, free flap reconstruction could be considered a safe and effective therapeutic strategy for patients with head and neck cancer undergoing hemodialysis.

[Primary syphilis with initial lower-lip sclerosis--a case report].

We report a case of primary syphilis with initial lower-lip sclerosis. 54-year-old man seen for a left lower-lip lesion was found in serological testing to have elevated syphilis-rapid plasma regain (STS-RPR) and treponema pallidum lipid antigen (TPLA), diagnosed as primary syphilis. Following four weeks of 1500 mg/day amoxicillin administration, the lesion had almost disappeared. Serological data had improved to within the negative range six months after antibiotic treatment started. This case underscores the need to recognize syphilis of the lip even in the outpatient setting.

[Mohs' ointment use in controlling advanced head and neck cancer].

Mohs' chemosurgery, originally developed to treat skin cancer, uses zinc chloride in Mohs' ointment to fix tissues, and is applicable in different clinical settings. In advanced head and neck cancer, Mohs' chemosurgery relieves main skin-infiltration symptoms such as bleeding, infection, exudation, and severe pain. Mohs' chemosurgery conducted in two cases of advanced head and neck cancer yielded an acceptable result free of bleeding, pain, exudation, and infection. Steps in palliative care are repeated until the tumor surface is completely fixed. Using Mohs' ointment provides acceptable relief without technical complications. Although not a topical chemotherapeutic agent, it fixes the lesion well.

Active Surveillance for T1bN0M0 Papillary Thyroid Carcinoma.

BACKGROUND: Prospective trials of active surveillance for asymptomatic papillary microcarcinoma (T1aN0M0) since the 1990s have shown progression rates of only 5-10%. Late rescue surgery after progression had no deleterious effects on mortality and morbidity. The 2015 American Thyroid Association guidelines approved active surveillance for very low-risk papillary thyroid carcinoma (PTC) as an alternative method to immediate surgery. However, there is no study that evaluates long-term active surveillance for T1b tumors. METHODS: A prospective trial of active surveillance with 360 very low-risk PTC (T1aN0M0) patients has been conducted since 1995. Of the 392 T1bN0M0 patients, 61 selected active surveillance over surgery and eventually participated in this trial, while the remaining 331 patients underwent surgery. To find an appropriate management strategy for patients with T1bN0M0 PTC, the outcomes of active surveillance for T1bN0M0 to T1aN0M0 PTC were investigated and compared, and the outcomes of surgery for T1bN0M0 PTC were studied. RESULTS: After a mean of 7.4 years of active surveillance, 29 (8%) T1aN0M0 tumors and four (7%) T1bN0M0 tumors had increased in size (p = 0.69). Development of lymph node metastasis was seen in three (0.8%) patients and two (3%) patients, respectively (p = 0.10). No significant difference in progression rate was seen between groups. Among T1bN0M0 tumors, weak calcification and rich vascularity were risk factors for tumor-size increase, and younger age was a predictor for the development of lymph node metastasis. Mean initial tumor size was significantly greater in T1bN0M0 patients who underwent immediate surgery (14.5 ± 2.8 mm) than it was in patients who chose observation (11.7 ± 1.1 mm; p < 0.0001). No postoperative recurrence was seen in patients with tumor <15 mm in diameter. CONCLUSIONS: Active surveillance is an option for selected patients with T1bN0M0 PTC.