Adenoid Cystic Carcinoma Research Articles

Primary tracheal cancer: Demographics, histology, and treatment outcomes in the United States from 2000-2018.

e18060 Background: Primary tracheal cancers (PTC) account for 0.2% of all respiratory malignancies and have an estimated incidence of 2.6 new cases per one million people in the US. Given the rarity of these cancers and paucity of data in the literature, we sought to determine the demographic and treatment patterns of PTC in the US. Methods: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database sponsored by the National Cancer Institute (NCI) was conducted for patients with a diagnosis of PTC between 2000 and 2018. Univariate, multivariate, and survival analyses were performed using 95% confidence intervals [CI] and a p-value < 0.05 indicating significance. Results: 689 patients with PTC were identified, with 53% of these cases being squamous cell carcinoma (SCC) and 17% being adenoid cystic carcinoma (ACC). Comparison of five-year overall survival (OS) stratified by treatment modality, disease stage, and histology can be found in the table. Multi-factor analysis demonstrated significance with only disease histology (p=0.005). Asian patients with SCC had decreased five-year OS compared to White or Black patients (n=12; hazard ratio (HR)=0.19 and 0.20, and p=0.003 and 0.006, respectively). Patient age < 65 years was associated with increased survival (hazard ratio (HR)=0.48; p<0.001); no difference in survival based on sex or marital status was seen (sex: HR=1.03; p=0.733, marital status: HR=1.07; p=0.568). Conclusions: Patients with tracheal ACC had greater five-year OS compared to patients with tracheal SCC. Those with local or regional SCC that received surgery or RT saw survival benefit; patients with regional SCC had survival benefit with chemotherapy. Patients with ACC had no survival benefit from any treatment modality regardless of stage. Patients aged < 65 years had increased survival and Asian patients with SCC had decreased survival. Further investigation into the potential differences in survival among various chemotherapeutic regimens and socioeconomic factors is warranted.[Table: see text]

Study update of the oral CDK9 inhibitor KB-0742 in relapsed or refractory transcriptionally addicted advanced solid tumors.

3102 Background: KB-0742 is a potent, and selective, oral inhibitor of CDK9 being evaluated in a phase I/II study in patients with transcriptionally addicted advanced solid tumors (NCT04718675). Interim data from the first 4 dose levels were presented previously noting manageable safety (MTD not reached), a 24-hour plasma half-life, linear PK, CDK9 target engagement in peripheral blood mononuclear cells (PBMCs), and anti-tumor activity in patients with transcription factor fusion (TFF) driven sarcomas. Here we present updated KB-0742 safety, pharmacokinetics (PK), pharmacodynamic data (PD) and anti-tumor activity for patients from the ongoing dose escalation through 5 dose levels and 60 mg expansion. Methods: Study objectives include evaluation of safety, tolerability, PK, PD, and identification of KB-0742 MTD and RP2D. KB-0742 is administered orally once daily for 3 consecutive days followed by 4 days off, weekly in 28-day cycles, until unacceptable toxicity or disease progression. Eligible patients were enrolled in 5 escalation cohorts (10, 20, 40, 60 and 80 mg) or 60 mg dose expansion. Eligibility criteria include age >18 years, relapsed or refractory solid tumors, and ECOG PS < 2. PD is assessed in (PBMCs) and tumor tissue from pre- and on-treatment biopsy samples. Results: As of January 4, 2024, 112 patients were enrolled, 42 in dose escalation and 70 in expansion. Patients received a median of 3 lines of prior therapy. The most common tumor types enrolled were soft tissue sarcoma (STS) (n=36; 18 TFF positive) and adenoid cystic carcinoma (ACC) (n=18). Treatment-emergent adverse events occurring in >15% of patients include nausea, vomiting, anemia, fatigue, diarrhea, and constipation; none assessed as grade 4 or 5. The most common reason for treatment discontinuation was disease progression (54.5%). Across 5 dose levels, PK remains linear with a terminal half-life of 24 hours. At 60 mg, evidence of target engagement was observed in post-treatment paired tumor tissue biopsies. Within STS, TFF positive patients displayed a trend towards improved outcomes vs. those without a TFF with a disease control rate (DCR) of 42.8% vs. 29.4%, and one partial response was observed in a patient with TFF positive myxoid liposarcoma at 60mg. The best observed response was durable stable disease (SD) yielding a DCR of 53.8% in ACC (n=18), and 83% in NSCLC (n=6). Two patients (MYCL1+ ovarian, NSCLC) with prolonged SD (>140 days) continue treatment on 60mg. Conclusions: KB-0742 treatment at 60 and 80 mg was well tolerated, with manageable toxicity. Achievement of long-term SD and some preliminary anti-tumor efficacy in highly pretreated patients motivates continued enrollment of patients with transcriptionally addicted tumors. Dose escalation and expansion in transcriptionally addicted ( MYC amplification/overexpression) or TFF driven tumors continues. Clinical trial information: NCT04718675 .

Dosimetry of lutetium-177-PSMA-I&T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&T injection at cycle 1. Tumors >1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

The Number of Positive Lymph Nodes Instead of Extranodal Extension and Nodal Diameter is an Independent Predictor of Survival and Treatment Outcome of High-Grade Parotid Gland Carcinoma

BackgroundThere is emerging evidence that current 8th edition of the American Joint Committee staging system is not sensitive enough to predict parotid gland carcinoma (PGC) survival outcomes. PurposeThe present study aimed to analyze pathological nodal factors related to survival and treatment outcomes in a cohort of patients surgically treated with PGC. Study Design, Setting, SampleWe performed a retrospective cohort study of consecutive patients surgically treated with PGC at the authors’ institution from January 1993 to December 2018. Inclusion criteria were as follows: confirmed high-grade parotid gland malignancy on histopathology, first surgical treatment to the parotid cancer with neck dissection with curative intent at the study clinic and sufficient data for review. Exclusion criteria were previous treatment in another institution, low-grade carcinomas, cases where neck dissection was not performed, incurable local disease and distant metastases at the time of first diagnosis and patients lost to follow-up. Predictor variablePredictor variable comprised pathological nodal factors grouped as the number of cervical node metastases, extranodal extension (ENE, largest diameter of nodal metastasis and involvement of parotid lymph nodes. Main outcome variablesOutcomes evaluated were overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). OS was calculated from the day of biopsy or definitive surgery to the last known hospital follow-up date, or the date of death found in the hospital records or social security data. DSS was calculated from the day of biopsy or definitive surgery until the last known follow-up or death from PGC reported in the patient record. Patients who died from causes other than the disease being studied are not counted in this measurement. Treatment outcome was evaluated through occurrence of locoregional relapse of the disease or development of distant metastases. RFS was defined as the time from the date of biopsy or definitive surgery to the date of LRFS or DMFS reported in the patient record. Covariates.Covariates were composed of a set of heterogeneous variables grouped into the following categories: demographic, pathologic and clinical. Analyses.Unadjusted and adjusted hazard ratios for each variable were calculated with univariate and multivariable Cox regression. Statistical significance was defined at p value of <.05. ResultsThe cohort of 112 patients included 62 males (55%) and 50 (45%) females. The mean age of the patients was 60.52±15.22 years. The median follow-up time was 59 months (3-221 months). Adenoid cystic carcinoma was the most common tumor type with the incidence of 45%. Cumulative OS for the 5-and 10-year follow-up period was 75% and 61% respectively. Locoregional recurrences occurred with 27 (24%), distant metastases occurred with 25 (22%) and both were diagnosed with 5 patients (6%). The number of metastatic nodes was the most important nodal prognostic factor related to OS (p=0.02; HR = 2.67; CI = 0.03-6.35), DSS (p=0.011; HR = 2.55; CI = .61-6.83) and DMFS (p=0.005; HR = 2.85; CI = 0.12-4.76). Presence of pathological parotid nodes was associated with poorer RFS (p=0.015; HR = 3.45; CI = 0.25-6.02). Conclusion and relevanceNumber of metastatic lymph nodes, instead of extranodal extension and largest nodal diameter, was the contributing factor associated with survival and treatment outcomes of surgically treated patients with high-grade PGC. Since the main function of staging system is to predict outcomes, the significance of ENE and nodal dimension in salivary gland cancer staging system requires further clarification. Important finding in present study was that the presence of positive parotid lymph nodes was associated to locoregional treatment failure.

Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing head and neck tumors: Outcomes from DESTINY-PanTumor02 (DP-02).

6037 Background: In DP-02, T-DXd demonstrated an objective response rate (ORR) by investigator (INV) of 37.1% (95% CI 31.3, 43.2) and clinically meaningful survival outcomes in 267 pretreated pts with HER2-expressing tumors. In this post-hoc analysis, we report outcomes and characterize those with an objective response (OR) in a subset of pts with head and neck cancers (previously included in the ‘other tumor’ cohort), most of which were salivary gland tumors. Methods: This open-label, Phase 2 study (NCT04482309) evaluated T-DXd (5.4 mg/kg Q3W) in pts with HER2-expressing (immunohistochemistry [IHC] 3+/2+ by local or central testing) locally advanced/metastatic disease after ≥1 systemic treatment or without treatment options. The primary endpoint was confirmed ORR by INV. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), and safety. Exploratory endpoints included efficacy outcomes by HER2 expression. Results: At data cutoff (June 2023), 24 pts with head and neck tumors (n=19 salivary gland, n=3 squamous cell carcinoma [SCC], n=1 adenoid cystic carcinoma, n=1 lacrimal gland) had received treatment (median [m] follow up: 20.8 months [range: 4.7–31.6]). Of these pts, 15 (62.5%) had received ≥2 prior treatment regimens. 10/24 pts (41.7%; 95% CI 22.1, 63.4; n=8 salivary gland, n=1 SCC, n=1 lacrimal gland) had a confirmed OR by INV; 9 responders had received prior radiation therapy, and 4 had known PD-L1 immune cell status ≥1%. The Table shows efficacy outcomes in all pts and by HER2 expression (central testing). Grade (G) ≥3 drug-related adverse events occurred in 10/24 (41.7%) pts. Adjudicated drug-related interstitial lung disease / pneumonitis occurred in 3/24 (12.5%) pts (n=1 G1; n=1 G2; n=1 G5). Conclusions: T-DXd showed clinically meaningful benefit in pretreated pts with head and neck tumors. Responses were observed across HER2 expression levels. Safety was consistent with the known profile. These data support T-DXd as a potential treatment for pretreated pts with HER2-expressing head and neck tumors. Clinical trial information: NCT04482309 . [Table: see text]

Long term outcomes in patients with recurrent/metastatic (R/M) salivary gland cancer (SGC) treated with immune checkpoint inhibitors (ICI).

e18063 Background: There is no standard of care systemic therapy in R/M SGC. Regimens containing ICIs are of interest, but overall response rates (ORRs) are low, and median duration of response (mDOR) and long term overall survival (OS) data are limited. We pooled mature data from two clinical trials evaluating the use of ICIs in SGC to evaluate long term outcomes. Methods: We combined the results of two phase I/II, open label, single arm trials utilizing ICIs in R/M SGC. NCT02538510 administered pembrolizumab 200 mg IV q3 weeks and vorinostat 400 mg PO 5 days on/2 days off. NCT03749460 administered nivolumab 3mg/kg IV q2 weeks x 12 doses, followed by 480 mg IV q4 weeks x 8 doses and ipilimumab 1 mg/kg IV q6 weeks x 4 doses with hypofractionated radiotherapy at 1-5 metastatic sites to a total dose of 24Gy/3 fractions over 1 week initiated 2 weeks after immunotherapy. All patients were ≥18 years with R/M disease, evidence of progression within 3 months of study entry, measurable disease per RECIST 1.1, EGOG PS 0-1, and adequate organ function at enrollment. PDL1 expression was not required for participation and prior ICI was not allowed. ORRs were evaluated by RECIST 1.1. OS and progression free survival (PFS) were estimated via the Kaplan-Meier method. Results: 45 patients were enrolled in the two studies from 11/2015-5/2022. The combined median age was 57 (IQR 46, 66). 26 (57.8%) were male; 33 (73.3%) were white and 10 (22.2%) were Asian. 27 (60.0%) had an ECOG PS of 0. Most common histology types were adenoid cystic carcinoma (21, 46.7%), acinic cell carcinoma (5, 11.1%), and salivary duct carcinoma (5, 11.1%). The ORR was 17.8% with all responders having a PR (n=8, histology types: 3 acinic cell, 2 adenoid cystic, 1 adenocarcinoma, 1 salivary duct, 1 lymphoepithelioma-like carcinoma). 20 (44.4%) had SD, with 16 (80.0%) of these responses lasting greater than 6 months. 16 (35.6%) had PD. One patient was not evaluable for RECIST due to rapid disease progression and death. At analysis, median follow up was 29.2 months (IQR 27.1-50.0) among survivors, mDOR was 26.7 months (range 7.1-69.5+), with three patients with ongoing response. Median OS and PFS were 25.4 (95% CI 14, 43.2) and 6.2 months (95% CI 3.9, 15.5) respectively. 23 (51.1%) patients received systemic therapy after trial ICI. Patients received: 4 additional ICI (3 PD-1 monotherapy, 1 ipi/nivo), 5 androgen deprivation therapy, 5 chemotherapy, 9 other treatments (dabrafenib/trametinib, everolimus, fam-trastuzumab deruxtecan, osimertinib, lenvatinib, investigational agents). Conclusions: Although SGC is heterogenous, responses to ICI were observed in multiple subtypes and were durable, similar to observations in other solid tumors. A significant proportion received subsequent lines of therapy post ICI, and exploration of ORR and PFS to next lines of therapy is of interest. Clinical trial information: NCT02538510 and NCT03749460 .

Axitinib plus avelumab for recurrent/metastatic adenoid cystic carcinoma (R/M ACC): Biomarker analysis of the phase II trial.

6104 Background: In the phase II axitinib (VEGFR inhibitor) plus avelumab (PD-L1 inhibitor) trial in R/M ACC, response rate was 18% with a median progression-free survival (PFS) of 7.3 months, with subsequent inclusion of the combination in NCCN guidelines as a possible treatment for ACC (category 2B). We sought to identify potential biomarkers predictive of axitinib plus avelumab benefit in R/M ACC. Methods: The phase II trial included 28 R/M ACC patients (pts). Pre-treatment tumors were analyzed by whole exome sequencing (n=24), using Twist Human Core Exome V2 kit, and transcriptome profiling (n=26), using HTG Transcriptome Panel (19,616 probes). For 17 pts, imaging mass cytometry (IMC) was performed with 35 metal-tagged markers and analyzed with Visiopharm software. Microbiome composition was assessed in tumor (n=20), oral rinse (n=20) and fecal (n=19) samples via 16s rRNA gene sequencing. All results were assessed for association with PFS on therapy with a Cox proportional hazards model, maintaining ACC subtype (ACC-I vs. ACC-II) as a covariate. Results: Only 1 (6%) of 17 assessed tumors were PD-L1 positive. By WES, tumor mutational burden (TMB) was overall low (median 1.4 mut/Mb, range 0.7 – 18.7), but higher TMB was associated with worse PFS. Four mutational signatures significantly correlated with worse PFS, including SBS86, associated with previous chemotherapy exposure. Immune deconvolution of RNA-seq data revealed that a higher neutrophil-to-lymphocyte ratio and more T follicular helper cells associated with worse PFS, while presence of cytotoxic cells, T effector memory cells, and mast cells associated with longer PFS. Notably, a 167-gene predictive signature was developed and validated in the phase II ipilimumab plus nivolumab salivary gland cancer trial. This 167-gene signature was not prognostic in ACC pts who did not receive immunotherapy. IMC single-cell immune mapping revealed that pts with longer PFS had increased presence of CD8 T cells, CD73+ macrophages in tumor, a higher stromal CD8 T cell:Regulatory T cell ratio, increased stromal SIGLEC15 positive cells, and a higher tumor-to-stroma ratio of fibroblasts. Conversely, Ki67-positive T cells, cancer stem cells, and M2 macrophages were associated with worse PFS. Through microbiome analysis, 13 bacterial genera in tumor samples, 25 in stool, and 8 in oral rinse were significantly associated with therapy outcomes. Of note, in stool microbiome, presence of Akkermansia spp. and Bifidobacterium spp. were significantly correlated with improved PFS, with the latter association also seen in oral rinse. Conclusions: Correlative analysis of the phase II axitinib plus avelumab trial revealed potential biomarkers predictive of combination clinical benefit in ACC, including a gene-expression signature. These findings may guide patient stratification for combinatorial therapy.

Tracheal cancer epidemiology and survival trends: A SEER database analysis.

e20078 Background: Tracheal cancer is one of the rarest malignancies of the respiratory system and, hence one of the least studied ones. It has a poor prognosis and understanding its epidemiology can help with effective diagnosis and management. Here we present the Surveillance, Epidemiology, and End Results (SEER) analysis of tracheal cancer. Methods: Information was obtained from the SEER database November 2022 with 17 registries for years 2000-2022. Case selection was done for the Primary labeled site Trachea C 33.9. Only patients with age &gt;20 years and with one primary cancer were included. A total of 537 Patients were analyzed for incidence and survival based on Histology, Age, Gender, Race, Household Income, Area of residence, and treatment received. Results: The most common histology was squamous cell carcinoma (34%),followed by adenoid cystic carcinoma (23%) and Small cell carcinoma (4%). Other histologies (39%) included but were not limited to Large cell carcinoma, adenoid carcinoma, mucoepidermoid carcinoma, etc. The age group studied was 15 years and above. The most common age group affected was 65-69 years (12.3%), closely followed by 60-64 years (12.1%). The mean age of population was 62.5 +/- 14.7 years. Out of the total,56% were males and 44% were females (P value (P) &lt; 0.002). 68.7% of cases were observed in Non-Hispanic Whites, (P &lt;0.0001) followed by Blacks (11.4%), Hispanics (9.3%), Asian/Pacific Islanders (9.9%). 83% of the population was residing in metropolitan versus 17% in non-metropolitan regions (P&lt;0.0001). 38% cases were observed in Annual household Income of &gt;75,000 US dollars (USD) versus 62% in &lt;75,000 USD (P &lt;0.0006). Overall 5-year survival of tracheal cancer was noted to be 27%. Surgery was done in 40% of the cases. Poor 5-year survival was observed in those who did not have surgery compared to those who did(Hazard ratio (HR)=1.45, Confidence Interval (CI) 1.23-1.71, P &lt;0.0001). Radiation was done in 28.1% of cases. Patients who received no radiation therapy had poor outcome compared to those who did. (HR=1.214, CI 1.066-1.383, P &lt;0.0001). White race had worse outcomes compared to other races (HR 1.14, CI 1.003-1.289, P&lt;0.023). The risk of death at 5 years in Males was slightly higher than in females but not statistically significant (HR 1.067, CI 0.96-1.18). Difference was also not significant in those with Household income &lt;75,000 USD compared to those with more than &gt;75,000 USD (HR 0.92 CI 0.83-1.01), Metropolitan versus non-metropolitan areas of residence (P=0.14). Conclusions: Statistically significant improvement in survival has been noted in patients who received the treatments including surgery or radiation in tracheal cancer versus patients who didn’t. Our study suggests that less than half of the patients received surgery and less than one-third of the patients received radiation therapy. Efforts should be made to emphasize the continued utilization of these therapy options for better outcomes.

Comparison of 5-year survival rate and analysis of prognostic factors influencing the prognosis of adenoid cystic carcinoma and squamous cell carcinoma of the maxillary sinus: based on the SEER database

Objective:To analyze the difference in 5-year survival between maxillary sinus adenoidal cystic carcinoma（maxillary sinus adenoid cystic carcinoma, MSACC） and squamous cell carcinoma（maxillary sinus squamous cell carcinoma, MSSCC） using the National Cancer Institute's Surveillance, Epidemiology, and End. Results:database（SEER） and to explore the factors associated with the prognosis of the two tumors. Methods:The data of 161 patients with MSACC and 929 patients with MSSCC were collected from SEER database, and the 5-year overall survival rate（OS） and tumor specific survival rate（CSS） were compared between the two groups before and after propensity score matching. The forest map of multivariate Cox proportional hazard regression model was established to analyze the prognostic factors affecting the survival rate of patients with MSACC and MSSCC. Results:There were statistical differences in 5-year OS and CSS between MSACC and MSSCC before and after propensity score matching（P<0.001）. Multivariate regression analysis showed that age, side of the disease, lymph node metastasis, operation and radiotherapy were the influencing factors of OS in MSACC, while age and operation were the influencing factors of CSS. Age, race, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of OS of MSSCC. Age, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of CSS. Conclusion:The 5-year survival rate of MSACC is higher than that of MSSCC. Surgery plays a positive role in the prognosis of the two kinds of tumors. The analysis results can provide some reference for their survival expectations and treatment choices.

Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.

1106 Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score&lt;100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P&lt;0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P&lt;0.05), no lymph node metastasis ( P&lt;0.05), and high-grade tumor infiltrating lymphocytes ( P&lt;0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score&lt;100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P&lt;0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]

Clinical analysis of resection and dura skull base reconstruction of cranionasal communication tumor in 31 cases

Objective:To explore the methods of resection, dura and skull base repair and reconstruction of cranionasal communication tumor. Methods:Data of 31 patients with cranionasal communication tumor who underwent dura and skull base reconstruction after tumor resection from 2018 to 2022 were collected. Follow-up lasted for 3 to 41 months. Results:A total of 31 patients were enrolled, including 20 males and 11 females. The ages ranged from 19 to 74 years, with a median age of 57 years old. There were 17 benign lesions（one case of hemangioma, one case of Rathke cyst, one case of squamous papilloma, one case of craniopharyngioma, two cases of meningocele, two cases of varus papilloma, two cases of meningioma of grade Ⅰ, three cases of schwannoma, four cases of pituitary tumor） and 14 malignant lesions（one case of osteosarcoma, one case of poorly differentiated carcinoma, two cases of varus papilloma malignancy, two cases of olfactory neuroblastoma, two cases of adenocarcinoma, two cases of adenoid cystic carcinoma, four cases of squamous cell carcinoma） . Sixteen cases underwent nasal endoscopy combined with craniofacial incision and 15 cases underwent nasal endoscopy surgery alone. Complete resection of the mass and dura and skull base reconstruction were performed in all 31 patients, and free graft repair was performed in 8 cases（fascia lata in 5 cases and nasal mucosa in 3 cases）. Twenty-three cases were repaired with pedicled flaps（septal mucosal flap alone in 11 cases, septal mucosal flap combined with free graft in 6 cases, and cap aponeurosis combined with free graft in 6 cases）. Eight out of 31 patients underwent skull base bone repair. Postoperative cerebral hemorrhage occurred in 1 case, cerebrospinal fluid leakage in 1 case, intracranial infection in 2 cases. All patients were successfully treated without severe sequelae. Cerebrospinal fluid leakage and intracranial infection occurred in one patient after radiotherapy, who recovered after conservative treatment. All 17 patients with benign lesions survived. Thirteen out of 14 patients with malignant lesions received radiotherapy after surgery, nine survived without recurrence, five cases recurred, of which 2 survived with tumor, one underwent reoperation and 2 died. Conclusion:Cranionasal communication tumors are high-risk diseases of anterior and middle skull base, and various surgical repair methods could be selected after complete resection of the tumor. Successful reconstruction and multidisciplinary cooperation are crucial for treatment outcome.

Treatment patterns of adenoid cystic carcinoma of the breast: A systematic review.

e13147 Background: Adenoid cystic carcinoma of breast (ACC-B) is a rare subtype of breast cancer (BC) accounting for 0.1% of all BCs. It shares histologic features with ACCs arising in the salivary glands and other locations. Given the hormone receptor (HR) negative phenotype [negative expression of the estrogen receptor (ER), progesterone receptor (PR)], some clinicians treat ACC-B as a basal subtype of BC, which is predominantly treated with chemotherapy. However, ACC-B has a more indolent and favorable clinical behavior. There are no established treatment guidelines for ACC-B. We conducted a systematic review of the literature on the treatment patterns for ACC-B. Methods: We followed the PRISMA criteria using the database in Cochrane, Embase, PubMed, Scopus, and Web of Science. The Covidence software was used for screening and data extraction. Eligible studies discussed the management of stage I-III ACC-B from 1960 to 2022. Individual patient (pt) demographics, tumor characteristics, treatment and outcomes were collected, when available. Results: The database search found 2864 studies, of which 187 articles met the inclusion criteria in the study protocol. Given the rarity of this subtype of BC, most studies were case reports (n=104). A total of 4370 pts with a median age of 57 years were eligible for analysis. Information on ER, PR and HER2 status was not available for all cases. For the cases in which this was reported, most were ER and/or PR negative (76% ER negative and 83% PR negative). Surgery was the primary treatment reported for 3984 pts. A total of 21.5% underwent mastectomy, 40.7% lumpectomy and 37.7% were treated with other modalities of surgery. In the group of patients for which information was available regarding the receipt of systemic therapy (n=3147), 82% did not receive neoadjuvant or adjuvant chemotherapy. Metastatic disease was reported to have developed in 2.2% of the total patients (n=98). Median time to recurrence was 31 months (0-460) with a median overall survival of 134 months (1-462). The most common site of metastases were the lungs (60%). Among the patients who developed metastatic disease and for whom initial treatment information was available; radiation was given to 32 pts, 26 received adjuvant chemotherapy and 15 received both radiation and chemotherapy. No patients that developed metastatic disease received neoadjuvant chemotherapy. Conclusions: Our results suggests that ACC-B has a clinical behavior different from basal subtype of BC. In our review, only 2.2% of pts relapsed with metastatic disease, even though most of the pts did not receive prior systemic therapy. We need to better understand the genomic landscape of ACC-B, to identify pts who may be at risk for recurrence and develop specific guidelines to treat this rare type of BC.

Effect of RGT-61159 on inhibition of oncogene c-MYB synthesis and tumor growth inhibition in a broad range of ACC PDX models, at well tolerated doses in rodents and non-human primates.

6107 Background: RGT-61159 is a first in-class oral inhibitor of the oncogenic transcription factor c-MYB via selective alteration of its RNA splicing machinery. RGT-61159 selectively induces the inclusion of the cryptic “poison” exon into the c-MYB RNA transcripts, resulting in the robust elimination of c-MYB canonical mRNA transcript and consequently of its protein in cells. Overactivation of the c-MYB oncogene, primarily due to chromosome rearrangements, is a hallmark of adenoid cystic carcinoma. (ACC). ACC is a rare and aggressive type of cancer for which effective treatment does not exist. By inhibiting oncogenic MYB protein production, RGT-61159 has the potential to efficiently and selectively inhibit proliferation or induce cell death of cancer cells overexpressing MYB protein. Methods: RGT-61159 cell killing activity was measured against a broad panel of cancer cell lines in a CellTiter-Glo assay. MYB RNA and MYB protein levels were assessed after drug treatment by RT-qPCR and JESS assay respectively. Anti-tumor activity of RGT-61159 as single agent or in combination was evaluated in a panel of ACC PDX mouse models harboring different molecular alterations in c-MYB, including ACCX6, ACCX11, ACCx5M1 and ST105B2. Results: Here, we showed that RGT-61159 has potent cancer cell killing activity (EC50 – 100nM -200nM) against a large panel of cancer cell lines overexpressing c-MYB, while sparing normal cells. Robust c-MYB RNA and c-MYB protein depletion (&gt;80%) was observed in treated cells confirming RGT-61159 on-target cell killing effect. In addition, RGT-61159 single agent showed a remarkable anti-tumor activity (up to 90% TGI) at tolerated doses in the four ACC PDX models evaluated: ACCX6, ACCx11, ACCx5M1 and STB105B2. Importantly, we confirmed that RGT-61159 anti-tumor activity correlated with c-MYB target modulation. RGT-61159 efficacious doses reduced c-MYB transcript and c-MYB protein levels (by &gt;80%) in all ACC PDx models evaluated. In addition, RNAseq analysis of ACC tumor after treatment showed that RGT-61159 drug treatment reversed the published ACC overexpression gene signature. Notably, the optimal RGT-61159 regimen was well tolerated, as assessed by changes in animal body weight and clinical signs in rodents and non-human primate. Finally, we showed that the combination of RGT-M001, an analog of RGT-61159, with the NOTCH Inhibitor AL-101 resulted in significant tumor regression at well tolerated doses. Conclusions: Altogether, these data demonstrated that RGT-61159 efficiently and safely targets the undruggable oncogenic transcription factor c-MYB. Down-regulation of c-MYB by the RGT-61159 RNA-targeting small molecule is a very promising therapeutic strategy to treat ACC and other cancers driven by c-MYB dysregulation.

PRIMARY MALIGNANT MELANOMA OF THE PAROTID GLAND, A RARE ENTITY: A CASE REPORT

The prevalence of primary malignant tumors of the salivary gland is 1 per 100,000 people. Most salivary gland tumors originate in the parotid gland (80%), of which 25% are malignant. Adenoid cystic carcinoma, mucoepidermoid carcinoma and acinar duct carcinoma are among the most common types of salivary gland cancer [1]. Around 25% of parotid tumors are metastatic, originating mainly in the head and neck region. The main metastatic tumors of the parotid gland are squamous cell carcinoma and malignant melanoma [2]. Parotid melanoma is generally secondary to a primary location on the skin of the head and neck. When its primary site cannot be found, we speak of primary melanoma of the parotid gland, an even rarer entity. Here, we report the case of a primary malignant melanoma of parotid gland in a 66-year-old male subject.

Differential Expression of Mucin in Salivary Gland Tumours.

Background and Objectives: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods: Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results: A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma (p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands (p = 0.000). Conclusions: Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours.

Adenoid Cystic Carcinoma of the hard palate -rehabilitation with a modified surgical obturator: A case report

Adenoid Cystic Carcinoma of the hard palate -rehabilitation with a modified surgical obturator: A case report

Vascular Endothelial Growth Factor Receptor Inhibitors for Recurrent or Metastatic Adenoid Cystic Carcinoma

There is no systemic therapy for recurrent or metastatic adenoid cystic carcinoma (ACC) approved by the US Food and Drug Administration. To examine the efficacy, safety, and tolerability of vascular endothelial growth factor receptor (VEGFR) inhibitors in recurrent or metastatic ACC. PubMed, Embase, and Cochrane Library were systematically searched for studies of VEGFR inhibitors in recurrent or metastatic ACC from database inception to August 31, 2023. Inclusion criteria were prospective clinical trials of recurrent or metastatic ACC treated with VEGFR inhibitors, reporting at least 1 outcome of interest specifically for ACC. Of 1963 identified studies, 17 (0.9%) met inclusion criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline was followed to extract data. Data were pooled using a random-effects generalized linear mixed model with 95% CIs. The primary efficacy outcome was best overall response to VEGFR inhibitors, including objective response, stable disease, or progressive disease (PD). Safety and tolerability outcomes included incidence of grade 3 or higher adverse events, rates of exit from trial due to PD or drug-related toxic effects, and dose reduction rate (DRR). A total of 17 studies comprising 560 patients with recurrent or metastatic ACC treated with 10 VEGFR inhibitors were included. The objective response rate was 6% (95% CI, 3%-12%; I2 = 71%) and stable disease was the most frequent best overall response (82%; 95% CI, 74%-87%; I2 = 67%). The 6-month disease control (defined as objective response and stable disease) rate was 54% (95% CI, 45%-62%; I2 = 52%). The rate of grade 3 or higher adverse events was 53% (95% CI, 42%-64%; I2 = 81%) and of DRR was 59% (95% CI, 40%-76%). Most patients (57%; 95% CI, 44%-70%; I2 = 83%) continued therapy until PD; 21% (95% CI, 15%-28%; I2 = 62%) of patients suspended therapy for toxic effects. In subgroup analysis by specific VEGFR inhibitor, the objective response rate was 14% (95% CI, 7%-25%; I2 = 0%), stable disease rate was 76% (95% CI, 63%-85%; I2 = 0%), proportion treated until PD was 61% (95% CI, 14%-94%; I2 = 94%), and DRR was 78% (95% CI, 66%-87%; I2 = 39%) with lenvatinib. Corresponding axitinib results were objective response rate of 8% (95% CI, 4%-15%; I2 = 0%) and stable disease rate of 85% (95% CI, 72%-92%; I2 = 69%), with 73% (95% CI, 63%-82%; I2 = 0%) of patients treated until PD, and the DRR was 22% (95% CI, 12%-38%; I2 = 77%). Rivoceranib had the highest objective response rate (24%; 95% CI, 7%-57%) but high heterogeneity among studies (I2 = 95%) and the lowest rate of patients who continued therapy until PD (35%; 95% CI, 20%-55%; I2 = 90%). This systematic review and meta-analysis found that VEGFR inhibitors were associated with high rates of disease stabilization in recurrent or metastatic ACC. Of 10 included VEGFR inhibitors, lenvatinib and axitinib were associated with the best combined and consistent efficacy, safety, and tolerability profiles, substantiating their inclusion in treatment guidelines.

Is epithelial-mesenchymal transition related to the biological behavior of salivary gland neoplasms?

ObjectiveTo evaluate and compare the expression of E-cadherin, Snail1 and Twist1 in pleomorphic adenomas (PAs), adenoid cystic carcinomas (AdCCa) and carcinoma ex-pleomorphic adenomas (CaexPA) of salivary glands, as well as investigate possible associations with clinicopathological parameters. Study designE-cadherin, Snail1 and Twist1 antibody immunostaining were analyzed semiquantitatively in 20 PAs, 20 AdCCas and 10 CaexPAs. Cases were classified as low and high expression for analysis of the association with clinicopathological parameters. ResultsCompared to PAs, AdCCas and CaexPAs exhibited higher nuclear expression of Snail1 (p = 0.021 and p = 0.028, respectively) and Twist1 (p = 0.009 and p = 0.001). Membranous and cytoplasmic expression of E-cadherin were positively correlated in PAs, AdCCas and CaexPAs (r = 0.645, p = 0.002; r = 0.824, p < 0.001; r = 0.677, p = 0.031). In PAs, positive correlation was found between nuclear expression of Snail1 and membrane expression of E-cadherin (r = 0.634; p = 0.003), as well as between nuclear expression of Snail1 and Twist1 (r = 0.580; p = 0.007). Negative correlations were detected between membrane expression of E-cadherin and cytoplasmic expression of Snail1 in AdCCas (r = − 0.489; p = 0.029). ConclusionsE-cadherin, Twist1, and Snail1 may participate in modulating events related to cell differentiation and adhesion in PAs and to biological behavior in AdCCas and CaexPAs, which indicates the involvement of EMT in these processes. Furthermore, the expression of these proteins in these carcinomas may reflect the plasticity feature of EMT.

Prosthetic Rehabilitation of a Maxillectomy Patient with Restricted Mouth Opening Using an Altered Cast Technique: A Case Report

Deformity in the maxillofacial region caused by surgical resection of a tumor have an adverse effect on the patient's ability to swallow, masticate, phonate, and psychological state. These patients may have restricted mouth opening capacity due to several surgical procedures and scar contracture resulting from radiation therapy. Therefore due to restricted access to the oral cavity prosthetic rehabilitation of these patients becomes a challenging task. A precise impression of the resection defect is necessary for accurate obturation. This is not practical for patients who have restricted mouth opening, hence this crucial first step in the making of a good prosthesis is frequently accomplished by altering the conventional impression method. This clinical report details the prosthetic rehabilitation of a patient who was diagnosed with Adenoid cystic carcinoma of the left maxillary sinus. Patient underwent maxillectomy for tumor removal, which was worsened by trismus as a result of the procedure and radiation therapy. For orofacial rehabilitation and defect obturation, the patient was restored with a removable dental prosthesis with a hollow bulb obturator. An altered cast technique was used in the final impression making. This rehabilitation approach was successful in restoring lost function and appearance of the patient. Keywords: Maxillectomy, Hollow Obturator, Altered cast technique

Case series on the management and outcomes of Bartholin gland carcinoma

ObjectiveTo evaluate the management and outcomes of Bartholin gland cancer at a single tertiary institution. Study DesignA single institution retrospective review of 9 cases of BGC between 2004 and 2022 was conducted. Demographics, pathological characteristics, treatment, follow up and oncologic outcomes were extracted from clinical records. Data are summarised using descriptive statistics and survival probabilities are presented with Kaplan Meier graphs. ResultsTen cases of BGC were identified at our institution over a period of 18 years. Nine out of ten clinical records were available for analysis. Eight patients presented with vulval swelling and four were treated initially for Bartholin cyst or abscess. One patient had a histological diagnosis of adenoid cystic carcinoma while the remaining were squamous cell carcinomas. With the exception of stage I disease chemoradiation was the primary mode of treatment. Adverse events included skin desquamation (4/9), venous thrombo-embolism (2/9), gastro-intestinal (1/9) and neurotoxicity (1/9). Median follow up was 60 months with a 5-year recurrence free and overall survival at 76 % and 64 % respectively. ConclusionBGC may present after a long duration of symptoms and at advanced stages. Primary chemoradiation appears to be a feasible treatment option in advanced disease with the benefit of decreased morbidity.