tbuckley/cabot-search huggingface dataset:
Genomic and immune profiling of rare non-squamous sinonasal tumors.
Authors: Conor Ernst Steuer, Daniel Lubin, Tolulope Tosin Adeyelu, James Edward Bates, Dong Moon Shin, Mihir R. Patel, Nicole C. Schmitt, William A. Stokes, Dara Mark Bracken-Clarke, Farah R. Abdulla, Charalampos S. Floudas, Matthew James Oberley, Jennifer Maria Johnson, Trisha Michel Wise-Draper, Marshall R. Posner, Nabil F. Saba
Journal: Journal of Clinical Oncology (2024)

e18008 Background: Sinonasal tumors (SNT) are rare tumors and make up less than 3% of all head and neck malignancies. The majority of SNTs have squamous cell histology and less common histologies remain understudied. We present a comprehensive analysis of genomic and immune profiles of rare SNTs that can help identify avenues for prognostic biomarkers and future targeted treatments. Methods: Non-squamous SNT samples (n =124) were profiled through Next Generation Sequencing (NGS) of DNA (592-genes; NextSeq or WES; NovaSeq) and RNA (WTS; NovaSeq) at Caris Life Sciences (Phoenix, AZ). Centralized pathology review was carried out to confirm histological subtypes. PD-L1 expression was tested by IHC (22c3, positive (+) &gt;=1%; SP142, positive (2+)/ &gt;=5%). Deficient mismatch repair/microsatellite instability (dMMR/MSI-H) was accessed by IHC/NGS. Immune cell fraction of the tumor microenvironment (TME) was estimated by quanTIseq, and gene expression profiles (transcript per million, TPM) were analyzed for transcriptional signatures predictive of response to immunotherapy. Mann-Whitney U and ChiSquare/Fisher-Exact tests were applied where appropriate, with p-values adjusted for multiple comparisons. Results: Non-squamous SNT samples included 35.5% (n = 44) adenoid cystic (ACC), 19.4% (n = 24) adenocarcinoma (AD), 10.5% (n = 13) undifferentiated carcinomas (SNUC), and 34.6% (n = 43) Esthesio/Olfactory Neuroblastomas (ENB). Notably, molecular features associated with each histological subtype are reported in the table. Furthermore, analysis of the inferred immune infiltrates showed that ENB had significantly higher fractions of NK cells (ACC: 5.6% vs AD: 4.6% vs SNUC: 4.4% vs ENB:10.5%, p &lt;0.00001), CD8 T cells (0.1% vs 0.88% vs 0.22% vs 1%, p &lt; 0.0001), CD4 T cells (0.4% vs 1.9% vs 0.03% vs 3.6%, p &lt; 0.00001) and dendritic cells (4.5% vs 3.4% vs 2.6% vs 7.3%, p&lt;0.00001) compared to the other sinonasal tumors. M1 macrophage (ACC: 2.6% vs AD: 1.9% vs SNUC: 1.1% vs ENB: 1.1%, p = 0.047) and Treg fractions (ACC: 2.0% vs AD: 1.6% vs SNUC: 1.2% vs ENB: 0.6%, p&lt;0.00001) were significantly higher in ACC. There was also significantly increased expression of immune checkpoint genes in ENB compared to AD ( PD-1: 0.8 vs 0.5 TPM, p = 0.022) and in ENB compared to ACC ( HAVCR2: 3.4 vs 2.9 TPM, p = 0.047). Conclusions: To our knowledge, this is the largest study characterizing the genomic and immune alterations in non-squamous SNTs. Our findings offer potential for future targeted and immune therapeutic applications in these rare diseases. [Table: see text]
High pre-treatment NLR and PLR predict poor prognosis of patients with recurrent/metastatic head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.
Authors: Giuseppe Anile, Chiara Gottardi, Ilaria Micheletto, Piero Nicolai, Badr El Khouzai, Marco Ferrari, Angelica Ghirelli, Greta Pretto, Valentina Guarneri, Maria Grazia Ghi
Journal: Journal of Clinical Oncology (2024)

e18001 Background: The treatment landscape of unresectable recurrent and/or metastatic (R/M) Head and Neck Squamous cell Carcinoma (HNSCC) has profoundly changed with the introduction of Immune checkpoint inhibitors (ICIs). High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with poor outcome in several tumor types. The aim of the present study was to investigate the role of pre-treatment NLR and PLR in predicting overall survival (OS) of patients treated with ICIs. Materials and Methods: We retrospectively reviewed the clinical records of 106 consecutive patients with R/M-HNSCC who received ICIs (single-agent or ICIs-based treatment) between January 2018 and June 2023 at the Istituto Oncologico Veneto of Padua. Patients were grouped into platinum-refractory (patients progressed within 6 months from the last platinum dose) and platinum-sensitive. The cut-off values of pre-treatment NLR and PLR were determined based on percentile distribution (75 th percentile). OS was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to compare survival outcomes. Results: A total of 102 patients were analyzed. Four patients were excluded because of incomplete data. Primary tumor sites were oropharynx (37%), oral cavity (24%), hypopharynx (19%), larynx (15%), nasopharynx (5%) and nasal cavity (1%). 63 patients (62%) with platinum-refractory disease received nivolumab single-agent. All 39 patients (38%) with platinum-sensitive disease were PD-L1 positive (CPS≥1) and received pembrolizumab-based treatment. Median OS was 8.0 months (95% CI 5.8-10.1) in the platinum-refractory cohort and 13.3 months (95% CI 7.3-19.3) in the platinum-sensitive cohort. At the univariate analysis high NLR (≥7) and PLR (≥345) correlated with poor OS in the overall population and in both the platinum-refractory and the platinum-sensitive cohorts (Table1). At the multivariate analysis PLR was an independent predictor of OS. Conclusions: The efficacy results reported in this retrospective series were in line with the literature data. High PLR was an independent predictor of poor outcome regardless of the platinum sensitivity. Prospective studies are needed to better explore the predictive role of easily obtainable blood biomarkers in this poor prognostic population. Univariate analysis for OS [Table: see text]
Imaging and clinical characteristics of incidental abnormal thyroid uptake on PSMA PET/CT.
Authors: Burcak Yilmaz, Kristin Trone, Cameron Chalker, John Sun, James Y Lim, Alexandra Sokolova, Nadine Mallak
Journal: Journal of Clinical Oncology (2024)

e18077 Background: To investigate the incidence, features, and clinical characteristics of unexpected prostate-specific membrane antigen (PSMA) uptake within the thyroid gland of patients with prostate cancer (PCa) who underwent F-18 DCFPyL PSMA PET/CT. Methods: We retrospectively reviewed a cohort of 1148 PCa patients who underwent PSMA PET/CT at our institution between 11/2021 - 09/2023. Scans with abnormal thyroid uptake were identified. Clinical data included patient demographics, PCa history, Gleason score, prostate specific antigen (PSA), ultrasonography (US), fine needle aspirate (FNA) / thyroidectomy, histopathology, and history of neck radiation or prior malignancy. Each scan was further analyzed with lesion-specific iso-contour method (42% cutoff) to obtain PET parameters (most prominent nodule SUVmax, SUVmean, PSMA volume, tumor lesion PSMA, contralateral gland SUVmax, SUVmax-nodule / SUVmax-contralateral gland ratio, most prominent PCa lesion SUVmax), PCa tumor distribution, and tumor volume. CT-related variables (nodule number, dominant nodule size, short/long axis ratio, CT-HU, integral total value) were also collected. Pearson's chi-square testing and Kruskal-Wallis testing was performed for categorical and nonparametric data respectively. Receiver operating characteristic (ROC) curves with area under curve (AUC) value were determined using IBM SPSS (version 29.0). Results: Of the 1148 PSMA PET/CTs, 60 (5.2%) had abnormal thyroid uptake (nodular: 58, diffuse: 2). Diffuse uptake was found to represent thyroiditis in both patients. 43 (56.7%) had an US, 20 (33%) were biopsied (11 benign, 5 indeterminate, 4 malignant), and 5 (8.3%) pursued thyroidectomy (3 malignant, 2 benign). 22 patients (36.7%) had histopathology data and 5 malignancies (2 PCa, 1 CLL, 2 primary thyroid) were identified. Nodule size was larger in those who had an US relative to those who did not. Among those with US data, no significant differences in clinical or histopathological parameters were seen. SUVmax (p: 0.01; AUC: 0.876, 95%CI: 0.731-1.0) and SUVmean (p:0.01; AUC: 0.871, 95%CI: 0.722-1.0) were higher in the malignant group. Nodule SUVmax/contralateral gland SUVmax ratio showed borderline significance (p = 0.05). Conclusions: Incidental PSMA PET uptake in the thyroid gland is seen in approximately 5% of patients. Focal uptake should prompt consideration of US and FNA due to the possibility of prostate cancer metastasis and thyroid cancer. SUVmax/mean is higher in malignant lesions.
Racial and gender disparities in the incidence of thyroid cancer using Nationwide Inpatient Database.
Authors: Kelly Frasier, Saad Javaid, Vivian Li, Julia Vinagolu-Baur, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e18066 Background: This study aimed to conduct a comprehensive evaluation of the ethnic and gender disparities that exist in thyroid cancer. Despite the significant amount of research that has been conducted on the complex and multifaceted differences between races and genders in various forms of cancer, there is still a noticeable gap in the data available in patients with thyroid cancer. Therefore, this study comprehensively assessed these disparities and their potential impact on the risk of developing Thyroid cancer. Methods: Using the National Inpatient Sample 2020, we identified patients with Thyroid cancer as the primary diagnosis (local/regional and advanced metastatic). We analyzed baseline characteristics such as age, gender, insurance, and income status, and several comorbidities to assess the risk associated with Thyroid cancer. Log Binomial regression model was used to calculate the Risk ratios after adjusting for confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 7520 of them (0.1%) had Thyroid cancer. Among these patients, 44.8% were male, and 55.1% were female, p&lt;0.001. Female patients demonstrated a higher risk of developing thyroid cancer as compared to males (RR= 1.41(1.27-1.57); p&lt;0.001). Compared to white females, white males, black males and females exhibited a decreased risk of bladder cancer (RR=0.66(0.58-0.76),p&lt;0.001; RR= 0.24(0.16-0.36),p&lt;0.001 and RR= 0.53(0.40-0.68), p&lt;0.001, respectively). Hispanic females (RR=2.67(2.26-3.16);p&lt;0.001) and females of other races (RR=1.69(1.20-2.37); p=0.002) had increased risk of Thyroid cancer, while no difference in risk was noted in Asian males (RR= 0.38(0.09-1.56); p=0.18), females (RR= 0.94(0.39-2.28); p=0.90) and males of other races (RR=0.81(0.51-1.29); p=0.38). Compared to lower income group patients, patients with high incomes had an increased risk of thyroid cancer ($65,000-$85,999: RR=1.18(1.01-1.38), p=0.03 ; &gt;$86,000: RR=1.30(1.10-1.52), p=0.001). The risk of thyroid cancer decreased with increasing age (36-45:RR=0.59(0.48-0.72),p&lt;0.001; 46-64: RR= 0.25(0.21-0.29),p&lt;0.001; &gt;65: RR =0.24(0.19-0.30), p&lt;0.001). Patients with Diabetes had decreased risk (RR= 0.31(0.27-0.36); p&lt;0.001), while patients with Hypertension had increased risk of thyroid cancer (RR=1.30(1.16-1.47); p&lt;0.001). Conclusions: The disparities in healthcare access and the unique challenges faced by high-risk groups have a profound impact on patients with thyroid cancer. A more comprehensive understanding of these disparities is essential to effectively support this vulnerable patient population and to identify preventive measures that can reduce the incidence of bladder cancer among high-risk demographic segments.
Significance of imaging-detected extranodal extension (iENE) in locally advanced head and neck squamous cell carcinoma (LASCCHN) treated with induction chemotherapy followed by chemoradiotherapy.
Authors: Ryutaro Onaga, Tomohiro Enokida, Takashi Hiyama, Nobukazu Tanaka, Yuta Hoshi, Hideki Tanaka, Takao Fujisawa, Susumu Okano, Hirofumi Kuno, Makoto Tahara
Journal: Journal of Clinical Oncology (2024)

6034 Background: Extranodal extension (ENE) of nodal metastasis is a significant prognostic factor in p16-negative SCCHN and is classified as N3b by the AJCC 8th edition. Therefore, pretreatment determination of ENE has significant clinical implications in SCCHN, and iENE has just recently been proposed. We previously discussed association with pathological ENE and iENE (Jpn J Radiol. 2020;38(6):489-506.). However, the role of iENE in non-surgical sequential therapy remains unclear. Methods: We retrospectively reviewed patients with LASCCHN originating from the oropharynx, hypopharynx, and larynx who received enhanced computed tomography (CT), then treated with induction chemotherapy (IC) with paclitaxel, carboplatin, and cetuximab followed by chemoradiotherapy (CRT) from 2013 to 2022 in our hospital. Two radiologists specializing in head and neck cancer blindly annotated the status of iENE in baseline CT images by the previously reported criteria (Oral Oncol. 2022;125:105716.). Multivariate analysis variables for event-free survival (EFS) and overall survival (OS) included the presence or absence of iENE, a response to IC, clinical T-category, performance status, smoking status, etc. Results: In the 88 patients, 67 (76.1%) had iENE and 21 (23.9%) did not at baseline. In the former and latter group, stage II/III/IV were 10.4%/26.9%/62.7% and 0%/28.6%/71.4%, HPV-positive were 37.3% and 28.6%, respectively. With the median follow-up of 37.4 months (range: 6.7-108.8), the former had significantly shorter EFS (3-y EFS: 41.9% vs. 75.6%, hazard ratio [HR]; 2.9 (1.2-7.4), p-value; 0.02) and OS (3-y OS: 72.8% vs. 100%, HR; Inf (0.01-Inf), p-value=0.003). Multivariate analysis identified the presence of iENE (HR for EFS: 2.80, 95%CI: 0.97-8.05, HR for OS: 2.93, 95%CI: 1.01-8.44) and unresponsiveness to IC (HR for EFS: 2.47, 95%CI: 1.31-4.68, HR for OS: 2.87, 95%CI: 1.13-7.26) as mutually independent unfavorable prognostic factors for both EFS and OS. Furthermore, classification based on the two factors could identify the population with a worse prognosis (Table). Conclusions: In the sequential therapy of IC followed by CRT, the current study revealed for the first time that subjects with an iENE at baseline, together with an unsatisfactory response to IC would require special attention, such as more intensified post-treatment follow-up as well as additional therapeutic interventions to improve their prognosis. [Table: see text]
Survival outcomes of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy.
Authors: Kyunghee Burkitt, Pingfu Fu, Seunghee Margevicius
Journal: Journal of Clinical Oncology (2024)

e18010 Background: There have been reports of higher than expected objective response rate (ORR) to platinum-based combinations following immunotherapy failure in a number of metastatic solid and hematological malignancies. In light of these intriguing results and the fact that the optimal second line regimen for R/M HNSCC after immunotherapy remains unclear, we conducted a prospective cohort study of patients with R/M HNSCC treated with platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy to investigate survival outcomes. Methods: This is a single institutional prospective cohort study which has a total of 12 patients with R/M HNSCC. Within 2 weeks after confirmation of progression from anti-PD-1 monotherapy (pembrolizumab or nivolumab), platinum-based chemotherapy (cisplatin 80mg/m 2 or carboplatin AUC=5) plus paclitaxel 175mg/m 2 every 21 day cycle were initiated and continued for a total of 3-9 cycles. The best overall response (BOR) was assessed by RECIST v1.1. ORR was determined based on binomial distribution theory and Wilson’s method. Progressive-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method. The association between ORR and HPV status, PD-L1 score were determined by the chi-square test. Blood samples were collected prior to the start of chemotherapy and also at the time of restaging scans (every 3 cycles of chemotherapy) for RNA sequencing. Results: Patients were treated from May 2021 to June 2023. There were 10 men and 2 women, median age of 63 years (range, 51-73) and ECOG 0-1. Oropharynx (9, 75%) was the most common primary site (oral cavity: 1, larynx: 1). Eleven (92%) had distant metastatic disease. 45% of patients (5 out of 11) had PD-L1 CPS &lt;50. 58% of patients (7 out of 12) had HPV positive HNSCC. The median follow up of the study was 15.6 (range: 4.9-23.9) months. The ORR was 75% with 95% CI: 0.47- 0.91. The median OS was 17.9 months and median PFS was 6.74 months. The median OS for PDL1 &gt;= 50 is longer than 23.9 months vs 15 months in patients with PD-L1 CPS &lt;50. Compared to HPV negative patients, HPV positive patients had a superior median PFS (8.75 vs 3.9 months, p= 0.069). The ORR by HPV status was higher in HPV positive than HPV negative patients (85.7% vs 60%, p=0.311), and the ORR by PDL1 score was higher in PDL1 ≥ 50 than PDL1 &lt;50 (100% vs 66.7%, p=0.154), but neither ORR by HPV status nor PDL1 was significant. Conclusions: Platinum-based chemotherapy plus paclitaxel after anti-PD-1 monotherapy showed dramatically higher ORR and more favorable median OS compared to the historical data from the pre-anti PD-1 era (ORR: 75% vs 26%, median OS: 17.9 vs 8.1 months), which warrants a larger prospective study for validation. Our ongoing analysis of RNA sequencing may reveal mechanism for immunotherapy induced chemosensitization effect.
Epidemiology of mast cell leukemia: A must!
Authors: Hassan Ali, Rajesh Thirumaran, Krishna Desai
Journal: Journal of Clinical Oncology (2024)

e18537 Background: Mast Cell Leukemia (MCL) is one of the rarest encountered malignancies. It is an aggressive oncologic subtype of systemic mastocytosis (SM) and accounts for &lt;1% of total cases. To make the diagnosis of MCL, in addition to the diagnostic criteria for SM (enlisted in the table), ≥ 20% atypical mast cells should be present in the marrow or ≥ 10% in the peripheral blood. However, an aleukemic form also exists. It can either occur as a de novo mutation or follow mastocytosis. The aim of this epidemiologic study is to aid better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted Systemic Mastocytosis and Mast Cell Leukemia cases diagnosed after 20 years of age, using the ICD Code 9741/3 (SM) and 9742/3 Mast Cell Leukemia (MCL). The analysis was stratified for MCL based on age, sex, race, and treatment modality used. Results: A total of 795 cases of SM were identified, which were diagnosed between 2000 and 2020. Of which, only 35 cases were attributed to MCL over the last two decades. Of these 35 cases, 60% patients were males, and 40% were females. ~82.85% were Caucasians, ~11.42% were African-Americans, ~2.85% belonged to Asians and Pacific Islanders, and ~2.85% belonged to the Hispanic population. No reported cases were found amongst Alaskan Natives. Further analysis based on survival, gender and races was not done, due to small sample size. Conclusions: MCL accounts for only about 4% of total SM cases. Only 35 cases were identified in the past twenty years, making it one of the rarest encountered malignancies. From the reported data, it was slightly inclined to have male predilection, and Caucasians were the most commonly impacted individuals. Given its extremely low incidence, more research and analysis is warranted to understand this lesser known malignancy. [Table: see text]
Differential sensitivities of primary tumor and lymph nodes to induction chemotherapy and definitive radiotherapy in nasopharyngeal carcinoma.
Authors: Juan Wang, Yanshuang Cheng, Ji Sun, Yahua Zhong, Qiuji Wu
Journal: Journal of Clinical Oncology (2024)

e18037 Background: Risk factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy and their impact on clinical outcome in nasopharyngeal carcinoma (NPC) patients are undetermined. Methods: During June 2017 to June 2022, 105 NPC patients treated with comprehensive induction chemotherapy and concurrent chemoradiotherapy in our institute were eligible for analysis. Logistic regression analysis was used to identify factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy (IC). Correlation and regression analysis were used to investigate whether there was a linear relationship between the sensitivity to induction chemotherapy and the efficacy of chemoradiotherapy. COX regression models were used to find prognostic factors, and Kaplan-Meier survival analysis was used to compare prognostic differences among groups with different induction chemotherapy sensitivities. Results: The median patient follow-up time was 26.0 (95%CI: 23.0-34.0) months. Grouped according to the response of the tumor primary site and lymph nodes to induction chemotherapy, we identified potential risk factors associated with different response patterns: primary tumor non-responsive and lymph node non-responsive, performance status (PS) score (OR: 3.824, 95% CI: 1.005-14.558, p = 0.030) ; primary tumor non-responsive but lymph node responsive, hemoglobin level (OR: 1.033, 95% CI: 1-1.067, p = 0.039) ; primary tumor responsive but lymph node non-responsive, N stage (OR: 2.297, 95% CI: 0.103-0.857, p = 0.014), white blood cell count (OR: 1.32, 95% CI: 1.025-1.699, p = 0.030); lymphocyte count (OR: 3.499, 95% CI: 1.196-10.241, p = 0.018) and blood urea nitrogen (OR: 1.416, 95% CI: 1.055-1.901, p = 0.021); primary tumor responsive and lymph node responsive, N stage (OR: 2.02, 95% CI: 1.044-3.907, p = 0.033), red blood cell count (OR: 0.369, 95% CI: 0.157-0.865, p=0.018) and lymphocyte count (OR: 0.359, 95% CI: 0.151-0.856, p = 0.015). Tumor response 6 months after chemoradiotherapy was significantly associated with tumor response after induction chemotherapy (p = 0.037). Similarly, lymph node response 3 months after chemoradiotherapy was significantly associated with lymph node response after induction chemotherapy (p = 0.043) . White blood cell count (HR: 1.327, 95% CI: 1.035-1.701, p = 0.026) and neutrophil count (HR: 1.405, 95% CI: 1.049-1.882, p = 0.022) was risk factors associated with progression free survival. Conclusions: In this study, we identified PS score and hemoglobin as potential factors associated with differential sensitivities of primary tumors and lymph nodes to induction chemotherapy in NPC. However, our study found the efficacy of induction chemotherapy could predict the efficacy of chemoradiotherapy or progression free survival.