bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: A single-arm, phase II trial.
Authors: Wu Wenjie , Yao Jie , Zhang Tong , Zhang Jie 
Published: June 2023

e18072 Background: Previous studies confirmed locally advanced oral or oropharyngeal squamous cell carcinoma (LA OSCC or OPSCC) patients (pts) with a pathological response had higher probability of survival in neoadjuvant settings. Several ongoing trials of neoadjuvant immunotherapy in head and neck cancer showed promising results. However, the optimal regimen remains unclear. This trial aimed to evaluate the efficacy and safety of neoadjuvant therapy with anti-programmed cell death 1 (PD-1) mAb tislelizumab and chemotherapy, followed by surgery and adjuvant radiotherapy/chemoradiotherapy in LA OSCC or OPSCC. Methods: In this phase II, single-arm study, eligible pts aged 18-80 diagnosed with stage III-IV (AJCC v8) resectable or potentially resectable LA OSCC or OPSCC received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (60-75 mg/m2) Q3W for 2 cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. The primary endpoint was major pathologic response (MPR). Secondary endpoints included pathological complete response (pCR), objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Thirty-one pts were enrolled from Mar 2022 to Nov 2022, and completed neoadjuvant therapy, with an ORR of 61.3% (19/31) and CR rate of 6.5% (2/31). Of the 31 pts, 29 pts (18 OSCC, 13 OPSCC) successfully underwent surgery with a median age of 57 (34-72) yrs, smoking history 75.9%, alcohol history 72.4% and 82.8% of male. The clinical stage III, IVA and IVB accounted for 24.1%, 48.3% and 27.6%, respectively. The MPR rate was 65.5% (19/29), of which the pCR rate was 41.4% (12/29). R0 resection rate reached 100%. For the per-protocol population, 58.6% pts (17/29) complaint of symptoms included pain, trismus, dysphagic, and speech disorders, all of them reached remission after 2 cycles of neoadjuvant therapy. No delay of surgery occurred. Grade 3-4 adverse events (AEs) occurred in 3 pts including 3.4% G3 leukopenia, 6.9% G3 anemia and 3.4% G4 thrombocytopenia and mostly chemotherapy related. Grade 1-2 AEs included 13.8% anemia, 3.4% thrombocytopenia, 17.2% leukopenia, 13.8% increased aminotransferase, 3.4% increased creatinine, 3.4% hyperglycemia, 27.6% anorexia, 3.4% vomiting, 3.4% diarrhea, 10.3% constipation, 6.9% rash, 100% alopecia and 17.2% fatigue. Conclusions: Neoadjuvant tislelizumab combined with chemotherapy yielded promising MPR and pCR rates with an acceptable safety proﬁle in LA OSCC or OPSCC. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200056354 .
Re-irradiation for recurrent head and neck cancer: Freedom from cancer recurrence rate.
Authors: Mohamad Issa , Abu Hejleh Taher , Abdelqader Sania , Wahbeh Lina , Taqash Ayat , Al-Mousa Abdelatif , Mayta Ebrahim , Al-Ibraheem Akram , Abuhijla Fawzi , Abu Hijlih Ramiz , Hussein Tariq , Al-Gargaz Wisam , Ghatasheh Hamza , Hosni Ali 
Published: June 2023

e18077 Background: Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. Methods: A retrospective analysis was performed on patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3≥ late toxicities. Results: A total of 49 cases [nasopharygeal (n = 12); laryngeal (n = 12); oral cavity (n = 11); salivary gland (n = 9); and skin (n = 5)] were identified, adjuvant or definitive rRT were delivered to 22 and 27 patients, respectively. Various rRT fractionation schedules were used and 35/49 (71%) of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year OS, DFS, LF, RF, and DM and FCRR were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs 0) and age > 52 years were predictive of worse OS. While, poor PS (1-2 vs 0) and total dose of rRT < 60Gy were predictive of worse DFS. Late RTOG toxicity of grade 3≥ was reported in 9(18.3%) patients. Conclusions: FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important new endpoint to be included in the rRT studies. rRT for rHNC at our cohort was successful; with a manageable level of late sever toxicity.
Real world outcomes of next generation sequencing (NGS) of progressive RAI resistant metastatic thyroid cancer and treatment of these patients with redifferentiation protocol.
Authors: Wheeley Jennifer , Chintapally Nikita , Kulkarni Kanchan , Nair Reshmi , Kundra Priya , Rosen Jennifer , Sharma Meeta , Wexler Jason , Burman Kenneth D , Shobab Leila , Veytsman Irina 
Published: June 2023

e18088 Background: Patients with papillary and follicular thyroid cancer (PTC and FTC) who are refractory to radioactive iodine treatment (RAIR) have poor prognosis. Frequently these patients are found to have BRAF V600E and NRAS Q61R mutations, which can be targeted using BRAF and MEK inhibitors to promote redifferentiation of thyroid cancer (TC) cells to take up RAI. The aim of this study is to define clinical, pathological, and molecular characteristics associated with response to redifferentiation therapy. Methods: NGS was performed to identify targetable mutations. The protocol consisted of 6 weeks of either dual therapy Trametinib and Dabrafenib (BRAF V600E) or Trametinib alone (NRAS Q61R) followed by dosimetry and therapeutic RAI administration. Interim imaging and biochemical analysis were performed at 3 months and 6 months. Statistical analysis was performed using the Kaplan-Meier survival analysis to estimate the mean time to progression from the protocol finish date. Patients who did not progress were censored at the last date of their clinic visit or at 192 days. Exploratory analysis was conducted to look at the change in trends in thyroglobulin (TG) values. Results: 16 patients met eligibility criteria. Previous RAI dosage ranged from 83mCi to 700mCi of Iodine 131 (I-131). 5 patients were African American, and 1 was Hispanic. Upon molecular analysis, 11 patients were found to have BRAF V600E mutation, 4 patients had NRAS Q61R mutation, and 1 was not identified. All but one patient had RAI uptake and received a dosage of 140 – 357 mCi of I-131 after dosimetry scan calculation. Upon interim analysis, 3 patients progressed at 3 months and an additional 3 patients progressed at 192 days. At 192 days, the mean time to progression from protocol finish date was 170 days (SD=9.7). Interim TG level analysis and images analysis are reflected in the table. There were other mutations identified: 11 patients were PDL1 negative, 5 PDL1 positive with range of 1-50%, 8 with TERT mutation, 4 with TP53, 2 with CHEK 2, other mutations were DNMT3A, FGFR3, BLM, EGFR, GNAS, ARID1, PDGFRA, NFE2L2, ARID2, Exon 17, POT1 Exon 14, and NTRK, were only present in one patient each. Conclusions: All but one patient with RAIR TC with BRAF V600E or NRASQ61R mutation who have undergone redifferentiation protocol have increased uptake of RAI after 6 weeks of targeted therapy with excellent response on interim analysis. Our study is ongoing to further define clinical, pathological, and molecular characteristics that help select patients with advanced TC who benefit most from redifferentiation treatment. Clinical trial information: 00005381 . [Table: see text]
Risk factors predictive of cervical lymph node metastasis in papillary thyroid microcarcinoma.
Authors: Jie Liu , Meng Wang , Wei Li , Jingchao Yu , Jinle Lu , Yating Chen 
Published: June 2023

e18091 Background: Papillary thyroid microcarcinoma(PTMC) is defined as a papillary thyroid carcinoma(PTC) measuring less than or equal to 10mm in its greatest diameter.It has the highest incidence among all thyroid carcinomas. However, the clinical characteristics and risk factors predictive of cervical lymph node metastasis in PTMC have not yet been fully elucidated.Our study aimed to investigate the clinicopathological characteristics for PTMC and to identify the risk factors predictive of cervical lymph node metastasis in PTMC.This study was the Medical Science Research Project of Hebei Province (NO.20210957). Methods: We retrospectively reviewed the medical records of 714 pathologically proven conventional PTMC patients who underwent lobectomy or total or near-total thyroidectomy and central neck dissection(CND),with or without lateral neck dissection(LND) in our hospital between January 2019 and December 2020.The data were analyzed in relation to age at diagnosis, gender, tumor size,capsular invasion,multifocal tumor,tumor location,and lymph node metastasis(LNM) that includes central lymph node metastasis(CLNM) and lateral lymph node metastasis(LLNM).Logistic regression model was used to investigate the risk factors for LNM in PTMC.All analyses were performed with STATA 16. Results: There were 714 patients with PTMC, consisting of 491(68.8%) women and 223 (31.2%) men.Among them,331(46.4%) were≥55 years old,and 383(53.6%) were < 55 years old. 256 patients(35.9%) with tumor diameter≤5mm,and 458 patients(64.1%) with tumor diameter > 5mm.Among all patients, 211(30.0%) had multifocal,capsular invasion,566(79.0%) had multiple lobes,and 20(2.8%) had hashimoto's thyroiditis.CLNM occurred in 438(61.3%),while LLNM was found in 219(30.6%).The univariate analysis showed that male gender,age＜55 years,tumor size＞5mmtumor location in the lower third of the thyroid,multifocal,capsular invasion and bilateralism were significantly associated with CLNM.Multivariate analysis showed that the capsular invasion,tumor size＞5mm,multifocal,tumor location in the lower third of the thyroid were independently correlated with CLNM.In addition,univariate analysis showed that tumor size＞5mm,tumor location in the superior pole of thyroid,multifocal,capsular invasion, bilateralism and CLNM were associated with LLNM.However,multivariate analysis showed that tumor location in the superior pole of thyroid,capsular invasion,tumor size＞5mm,and CLNM were independently correlated with LLNM. Conclusions: Capsular invasion,tumor size＞5mm,multifocal,and tumor location in the lower third of the thyroid predict increased CLNM in PTMC patients.The possibility of LLNM should be carefully evaluated for these patients with tumors located in the upper pole of the thyroid gland,capsular invasion,tumor size＞5mm,and CLNM. Clinical trial information: 20210957 .
Association between hyperthyroidism and thyroid cancer in the Congolese hospital setting.
Authors: Bukasa-Kakamba John , Bangolo Ayrton , Onyeka Sonia , Sagireddy Sowmya , Bangura Mary , Rathod Joshua , Gomez Eugenio L. , Naria Mansi , Erikson Conrad , Tabucanon Erwin J. , Bortely Blanka , Dongre Juilee V. , Radhakrishnan Reshma , Tirumala Aditya K.G. , Jarri Amer , Nagesh Vignesh , Chacko Angel Ann , Dey Shraboni , Proverbs-Singh Tracy Ann , Weissman Simcha 
Published: June 2023

e18092 Background: Thyroid cancer accounts for 1% of cancers worldwide. Hyperthyroidism was long considered a protective factor against thyroid cancer. This association was rare in the literature and raised a lot of controversy in the scientific world. There are currently no studies carried out in the Congolese hospital setting to establish the association between hyperthyroidism and thyroid cancer. We hypothesize that there is an association between thyroid cancer and hyperthyroidism in the Congolese hospital setting. Methods: This is a descriptive and retrospective study, which involved 106 cases of thyroid cancer who underwent partial or total thyroidectomy and pathological examination in four laboratories in the city of Kinshasa between 2005 and 2019. These laboratories receive samples from all the medical centers in Kinshasa. Statistical analyses of the data were performed using Statistical Package for the social sciences (SPSS) for Windows version 22 software. Data were expressed as mean +/- standard deviation for metric parameters, and as absolute or relative frequencies in percentages for categorical parameters. For all tests used the p-value < 0.05 was considered as the threshold of statistical significance. This research protocol was approved by the National Health Ethics Committee of the DRC No. 197/CNES/BN/PMMF/2020. Results: Out of 106 cases of thyroid cancer, the association of hyperthyroidism and thyroid cancer was found in 5 cases (4.7%) (3.6% for women vs. 9% for men). The mean age of patients with this association was 51 ± 11 years. Papillary carcinoma (two cases), follicular carcinoma (two cases) and lymphoma (one case) were the types of cancer encountered. Etiologically, toxic multinodular goiter (four cases; 80%) and toxic adenoma (one case; 2%) were found. Conclusions: There is an association between hyperthyroidism and thyroid cancer in the Congolese hospital setting. There is a predominance of the female gender. There was an equal number of papillary and follicular carcinomas. With this study, we hope to encourage clinicians to thoroughly evaluate any suspicious nodule associated with hyperthyroidism. [Table: see text]
Factors associated with positive margins in major salivary gland cancer: An NCDB analysis.
Authors: Keirns Darby , Hsia Beau , Verplancke Kiana , Silberstein Peter T. , Wu Xinxin 
Published: June 2023

e18093 Background: Major salivary gland cancer includes malignancies of the parotid, sublingual, and submandibular glands which represent a diverse spectrum of disease. Surgical resection is often the primary treatment. Positive tumor margins after resection have been associated with disease recurrence and worsened prognosis. This study investigates various factors and their influence on margin status. Methods: 41,705 patients with surgically treated major salivary gland cancer between 2004 and 2020 were identified in the National Cancer Database (NCDB). Factors including facility type, facility volume, surgical approach, primary site, Charlson-Deyo score, age, sex, race, Hispanic origin, income, and high school attainment were compared in patients based on margin status. Both macroscopic and microscopic positive margins were considered. Multivariate binary logistic regression analysis was performed in SPSS version 28 with a significance level of p < 0.05. Results: Patients treated at an Academic/Research facility were 19% less likely to have positive margins than patients treated at a Community Cancer Program. Patients treated at facilities with case volume within the top 10% were 37% less likely to have positive margins. No significant difference was found in the margin status between different surgical approaches including open, endoscopic, and robotic. Patients with non-parotid major salivary gland cancer were 15% more likely to have positive margins than parotid cancers. Patients were more likely to have positive margins with an increasing Charlson-Deyo score and an increasing age. Female and Black patients were both 9% less likely to have positive margins than their counterparts. Other racial categories, ethnicity, income, and high school attainment did not significantly impact margin status. Conclusions: Factors associated with a lower likelihood of positive margins include treatment at an Academic/Research facility, higher volume center, parotid malignancies, lower Charlson-Deyo score, younger age, female sex, and Black race. The surgical approach and other demographic factors did not demonstrate any relationship with margin status. Identifying these associations can lead to a better understanding of prognostic factors and disparities in order to improve future care. [Table: see text]
Retrospective analysis of the multikinase inhibitor (MKI) pazopanib in differentiated thyroid carcinoma (DTC) in the beyond-first-line setting.
Authors: Inampudi Jyothik Varun , Mahadevia Himil , Stone Alexandra , Toby Alana , Koshiya Hiren , Patel Jaydeepbhai , Pandav Vivek , Li Shenduo , Rao Sarika , Chindris Ana-Maria , Manochakian Rami , Lou Yanyan , Zhao Yujie 
Published: June 2023

e18097 Background: Sorafenib and lenvatinib are FDA-approved MKIs for locally recurrent or metastatic, progressive, DTC refractory to radioactive iodine treatment. Cabozantinib showed a survival benefit in radioiodine-refractory DTC previously treated with sorafenib and/or lenvatinib and was granted FDA approval. Our study aims to investigate the benefit of other MKIs in DTC beyond the first-line setting. Methods: DTC patients (pts) treated with multiple lines of MKIs from August 2018 to July 2022 at Mayo Clinic across all sites were identified. Electronic medical records were reviewed. 6-month, 12-month, and 18-month progression-free survival (PFS) were calculated for all lines of therapy using RECIST 1.1 criteria. Results: Among the 9 pts identified, 4 were male. The median age was 65 years (43-75). Most pts (60%) had papillary thyroid cancer. All pts received lenvatinib as first line treatment. The 6, 12 and 18-month PFS were 89%, 89%, and 55% respectively. 6 pts discontinued lenvatinib due to progression of disease (PD). 3 pts discontinued it due to adverse effects (AEs), which included hemoptysis (1 pt), severe rash (1 pt) and multiple psychiatric manifestations (1 pt). 8 pts received pazopanib, and 1 patient received cabozantinib with ipilimumab (1 dose) and nivolumab (6 months - discontinued due to myocarditis) as second-line therapy. Among them, 1 patient received pembrolizumab plus everolimus for 2 months before receiving pazopanib. The 6, 12 and 18-month PFS were 55%, 22%, and 11% respectively. All pts ceased treatment due to eventual PD, and there were no toxicity-related discontinuations. 5 pts subsequently received third-line MKIs, including cabozantinib (3 pts), pazopanib (1 pt), and lenvatinib (1 pt). The pt who received lenvatinib had discontinued it as first line therapy due to toxicity. The 2 pts treated with third-line cabozantinib and the pt rechallenged with lenvatinib showed no PD at 12-months and no toxicity related discontinuation. Conclusions: Pazopanib was associated with durable PFS and good tolerability when offered after PD or intolerance on lenvatinib in this retrospective analysis, warranting a randomized prospective study. [Table: see text]
Thyroid carcinoma showing thymus-like element: A national analysis of demographic features.
Authors: Bitar Gabriel Anthony , Hsia Beau , Wu Xinxin , Silberstein Peter T. , Keirns Darby 
Published: June 2023

e18099 Background: CASTLE, or Thyroid Carcinoma Showing Thymus-Like Elements, is an indolent and uncommon cancer that is believed to originate from either ectopic thymus tissue or remnants from the branchial pouches and affects the thyroid gland. It makes up a small portion, less than 0.1 - 0.15%, of all thyroid carcinomas and tends to affect slightly more females than males. Due to the lack of literature on this malignancy, understanding the trend in its diagnoses can provide valuable information about its epidemiology. The demographic factors of patients diagnosed with CASTLE were analyzed using data from the National Cancer Database (NCDB). Methods: A study was conducted using the NCDB from 2004 – 2020 to examine patients diagnosed with CASTLE (N = 23). Demographic factors such as age, sex, race, Hispanic ethnicity, education level, insurance coverage, type of medical facility, distance from the facility, and Charleson-Deyo score were analyzed using descriptive statistics. Trends in the incidence of the disease were analyzed through regression analysis. Results: The National Cancer Database was analyzed and revealed that 23 patients were diagnosed with CASTLE between the years 2004 to 2020, with a stable incidence rate per year (R2 = 0.1). The average age of diagnosis was 61.0 years (SD = 14.3, range = 31 – 87). The average Charlson-Deyo comorbidity score was 0.5, with 0 being the most common score (69.6%). The majority of patients (87.0%) were non-Hispanic and White. Most patients were found to be in the top two income quartiles (60.8%) earning more than $57,857 per year. A larger portion of patients had private insurance coverage (60.9%) compared to those who were uninsured or covered by Medicare/Medicaid. A greater number of patients lived in metropolitan counties with a population over 1 million (47.8%) than in other metropolitan counties (43.5%). Patients were more likely to receive treatment in a non-academic program (63.6%) such as community cancer programs, comprehensive community cancer programs, or integrated network cancer programs. On average, patients lived 11.4 miles (SD = 11.1, range = 0.7 – 46.7) from the treatment facility. Conclusions: This is the first analysis of CASTLE in the National Cancer Database, filling a significant gap in knowledge on the subject, particularly regarding the socioeconomic characteristics of CASTLE patients. The average CASTLE patient is a 60-year-old White, non-Hispanic male. These patients are more likely to be upper-middle-class citizens, have private insurance, live in densely populated metropolitan areas, and receive treatment at comprehensive community cancer programs. Further investigation is necessary to explore the statistical correlation between demographic and socioeconomic variables and the diagnosis, treatment, and outcomes of CASTLE patients.
Pembrolizumab immunotherapy in advanced and recurrent/metastatic salivary gland carcinoma (R/M SGC): A systematic review and meta-analysis.
Authors: Filogonio Victor , Maia Yara Rafaela , Maia Lucas Henrique 
Published: June 2023

e18101 Background: Treatment options for advanced R/M SGC are a limited and with variable response rates due to their safety/toxicity profile and the heterogenous l histology. Recent clinical trials tested pembrolizumab (PMB), a PD-1 inhibitor, in diverse settings. Methods: We performed a systematic review and single arm meta-analysis of clinical trials of PMB monotherapy or combined therapy in advanced and R/M SGC. PubMed, Scopus, and Cochrane database were searched for clinical trials published up to January 31, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. The primary endpoints of interest were complete/partial response (CR,PR) and disease control (DC= SD or better response) per RECIST v1.1, at any period of the trial. Results: Out of 199 database results, 4 clinical trials and 180 patients were included, all were using some form of PMB therapy. Overall, PMB was associated with a CR,PR ratio of 5.6% (95% CI 0.01-0.10, I²=25%, p=0.262) and DC ratio of 58.4% (95% CI 0.50-0.66, I²=13%, p=0.326), somewhat similar to recent evidence of PD-1/CTLA-4 combined therapy (nivolumab + ipilimumab [CR,PR=6-16%) in ongoing phase II clinical trials or PD-1 monotherapy (nivolumab [CR,PR=6%; SD=50%] in a completed clinical trial. Other systemic therapies, in which the current guidelines are based, include TKI (lenvatinib + sorafenib PR=3-15%; SD=50-94%) for adenoid cystic carcinoma (ACC); NTRK (larotrectinib CR,PR=90%, entrectinib CR,PR=86%), HER2 (transtuzumab associations CR,PR=60-90%), and AR (leuprorelin + bicalutamide CR,PR=42%, enzalutamide PR=4-15%; SD=52%) in non-ACC; and cytotoxic chemotherapy associations CR,PR=16-34% in heterogeneous histology tumors. Conclusions: There are marked limitations to the applicability of these findings in clinical practice, therefore a cautionary approach to this data is recommended, given their overall low statistical power, heterogenous histology, and tolerability to adverse effects. New trials with better standardized outcomes and comparative arms for different therapy associations and populations will help clarify the effects PD-1 inhibitors in the treatment of advanced and R/M SGC. [Table: see text]