Squamous Cell Research Articles

B-356 Siemens CYFRA 21-1: an assay for measurement of cytokeratin fragment 21-1

Abstract Background Cytokeratins are structural proteins forming the subunits of epithelial intermediary filaments. The soluble fragment of cytokeratin 19, cytokeratin fragment 21-1 (CYFRA 21-1), can be found in the blood of lung cancer patients, primarily those with non-small cell lung cancer (NSCLC). CYFRA 21-1 is the preferred biomarker in the management of NSCLC, particularly squamous cell and large cell carcinoma subtypes. An assay for CYFRA 21-1 on Siemens ADVIA Centaur® XPT and Siemens Atellica® IM (Siemens CYFRA) is being developed and analytical performance is being presented. Methods The Siemens CYFRA 21-1 assay (in development) is a one-step chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of CYFRA 21-1 in human serum and plasma. The specimen is incubated with paramagnetic microparticles coated with the monoclonal antibody (mAb) BM19.21 and acridinium-labeled mAb KS19.1 conjugate on the Siemens ADVIA Centaur XPT System and Siemens Atellica IM System. After incubation and washing, Acid and Base reagents are added. The resulting relative light units (RLUs) are directly proportional to the amount of CYFRA 21-1 in the sample allowing for the quantitative determination of CYFRA 21-1 in the specimen. Results The following performance were determined using 3 unique lots of reagents and calibrators with the calibration range for the assay being 0.00 to 100.00 ng/mL. For the ADVIA Centaur XPT and Atellica IM systems were shown to be equivalent within 4%. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation at 20% CV (LoQ) were determined and met the goal of ≤ 1.00 ng/mL. Linearity according to CLSI EP06 Ed2 was demonstrated for a range of 0.66 through 100.00 ng/mL. A Precision study of 2 controls and 5 panels spanning the range of the assay demonstrated a total %CV ≤ 8% at all levels. In the sample tube type study, a matrix comparison of 61 matched serum and plasma samples were evaluated. Passing-Bablock slopes of < 5% and r > 0.99 were observed when evaluating samples within the measurement range for plasma (LiHep, LiHep separator, K2EDTA and K3EDTA) tubes and serum separator tubes (SST) compared to the Red Top serum samples. Six endogenous substances were evaluated for interference in the CYFRA 21-1 assay. The average percent difference between test and control samples for all endogenous interferents was < 10%. Percent difference in the presence of 20 potentially interfering drugs was ≤ 4.0%. Conclusions The Siemens CYFRA 21-1 assay currently in development is a sensitive and precise assay for the quantitative determination of CYFRA 21-1 in human serum and plasma.

A Rapidly Growing Nodule on the Eyebrow of a Pediatric Patient

A 11-year-old Caucasian girl presented to our Dermatology Unit with a 2-month history of an erythematous nodule, localized to the medial portion of her left eyebrow, rapidly growing in the two weeks before presentation. The histopathological examination revealed a dermal multi-nodular epithelial neoplasm composed of clear cells, squamous cells, and glandular cells, characterized by cytologic atypia, high mitotic activity, and an infiltrative deep growth pattern. The immunohistochemical profile of the lesion was as follows: CKAE1/AE3+, EMA+, CK8/18+, CK7+, CK19+, AR negative, p63 focally +, Ki67 25%, rare cells GCDFP15+, p53+.

Scanning electron microscopy and light microscopy of tongue, fingers, toes, nuptial pad, and humeral gland in Sylvirana nigrovittata (Anura: Ranidae)

The micromorphology and histology of anuran skin, particularly in Thai species, remain relatively understudied. Anurans use their tongues for prey capture and their hands and feet for adhesion and mating, suggesting a close relationship between micro-surface features and histological structure. Information on Sylvirana nigrovittata is particularly limited. This study provides a detailed examination of the micro-surface and histological characteristics of the tongue, fingers, toes, nuptial pad, and humeral gland in S. nigrovittata. Specimens collected from Phu Luang Wildlife Sanctuary in Loei province, northeastern Thailand, were studied using scanning electron microscopy (SEM) for micro-surface features and H&E staining for histological details. SEM micrographs revealed that the tongue was cordate-shaped, with about 75% of its surface covered by filiform papillae and 25% by fungiform papillae housing taste buds. Filiform papillae were trapezoidal, averaging 23.88±5.68 µm in width and 38.83±6.57 µm in length, while fungiform papillae were disc-like, averaging 52.95±14.64 µm in width and 66.70±15.88 µm in length. Digital pads on fingers and toes presented prismatic cells, with fingertip cells averaging 7.09±0.97 µm in width and 11.81±1.24 µm in length, and toe cells averaging 8.40±1.37 µm in width and 11.28±1.63 µm in length. Subdigital surfaces were smoother, containing squamous cells with dimensions of 10.65±3.21 µm in width and 21.29±4.35 µm in length. Subarticular tubercles were composed of prismatic cells with hexagonal or pentagonal surfaces, averaging 10.02±2.85 µm in width and 13.08±1.94 µm in length. Nuptial pad displayed cylindrical structures with dome-like tips, averaging 24.01±3.96 µm in width and 21.16±4.37 µm in length, and feature mucous openings. They consisted of a thick keratinized stratified squamous epithelium and a dense dermis with specialized mucous glands. Humeral gland exhibited rough surfaces with squamous cells and microridges, showing both small and large mucous openings, with average cell dimensions of 16.23±1.70 µm in width and 19.11±2.05 µm in length. Histological analysis confirmed that these structures were predominantly composed of keratinized stratified squamous epithelium, with variations in dermal collagen density and mucous gland distribution. This study enhances our understanding of the skin and gland morphology in S. nigrovittata, highlighting on its anatomical and functional adaptations.

Abstract C120: Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities

Abstract Black persons have the highest mortality rates of both cervical cancer (CC) and pancreatic ductal adenocarcinoma (PDAC) in the United States. Differences in access to quality healthcare and socioeconomic status contribute to these cancer health disparities as well as ancestry and biology. In other cancer types, differences in the inflammatory tumor landscape across races and ancestral populations have been reported. However, the inflammatory tumor microenvironment (TME) as it relates to CC and PDAC health disparities is not well defined. Black patients are often underrepresented in PDAC studies. Meanwhile, CC health disparities studies primarily investigate socioeconomic status, screening, and vaccination rates. Therefore, we aim to characterize the inflammatory TME in these two cancer types with the long-term goal of informing prevention, prognostic, and therapeutic strategies. Clinicopathological characteristics were compared between Black (n = 144) and White (n = 198) patients with CC who received care at Johns Hopkins Medicine between 1995 and 2019. Surgically resected formalin-fixed paraffin embedded (FFPE) CC tissue samples were obtained from Non-Hispanic Black (n = 10), Non-Hispanic White (n = 10), Hispanic Black (n = 5), and Hispanic White (n = 5) women matched on grade, age, and subtype. Tissue microarrays (TMAs) were constructed using archival surgically resected FFPE PDAC tissues from Black (n = 45) and White (n = 45) patients, matched on sex, age, stage, and time of surgery. Multiplexing immunohistochemistry (mIHC) was used to assess markers for i) T cells (CD3, CD8, CD4, FoxP3), M2 macrophages (CD163), mast cells (Tryptase), and fibroblasts (FAP) in PDAC tissues and ii) B cells (CD79A), T cells (CD3, CD8, CD4, FoxP3), plasma cells (CD138/syndecan-1), programmed death-ligand 1 protein (PD-L1), macrophages (CD68, CD163), natural killer cells (NKP46/CD56/CD16), neutrophils (CD66ce), and mast cells (Tryptase) in CC tissues. HALO Image Analysis Platform (version 3.6.4134.137; Indica Labs) was used to quantify marker expression. GraphPad Prism Software (version 10.0.03), was used for graphing and statistical analysis. Squamous cell CC was the most frequent histological subtype in both Black (68%) and White (44%) women. Progression through treatment was more common among Black women (24%) compared to White women (7%). CD163+ M2 macrophages were significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0435), and in tumors from Black women compared to White women (p = 0.0067). FAP+ fibroblasts were also significantly increased in PDAC tumors compared to benign tissues among Black patients (p = 0.0001) and in tumors from Black women compared to White women (p = 0.0013). CD8+ cytotoxic T cells and FoxP3+ regulatory T cells were comparable between races. We observed differences in macrophage and fibroblast distribution between races supporting the effort for future studies that examine the significance of characterizing the TME to address cancer health disparities. Citation Format: Jelani Jarrett, Jae W Lee, Ali Dbouk, Vahinipriya Manoharan, Kennedy Rains, Terri Mason, Kimberly Levinson, Laura D Wood, Michael G Goggins, Janielle P Maynard. Characterization of the inflammatory tumor microenvironment and its association with cancer health disparities [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C120.

Cytomorphologic comparison of upper urinary tract urothelial carcinomas and renal cell carcinomas on urine cytology.

Compared to urothelial carcinomas (UCs), the cytomorphology of renal cell carcinomas (RCCs) is underdescribed. This study aims to investigate whether UCs and RCCS of the upper urinary tract can be differentiated cytologically, and to identify distinguishing cytomorphological features. Consecutive urine cytology specimens with atypical/C3, suspicious/C4 or malignant/C5 diagnoses matched with a nephrectomy or ureterectomy specimen with UC or RCC over a 15-year period were reviewed for cellularity, architecture, background composition and cytomorphologic features. Totally 132 specimens were retrieved, comprising 24 RCCs and 108 UCs. Clear cell RCC (CCRCC) (n = 18) was the most common RCC. Urine cytology specimens from UC showed a trend of higher cellularity (p = 0.071) against RCC and was significant in subgroup analysis with CCRCC (p < .001). Epithelial structures in sheets, tubules, and papillae were exclusive in specimens of UC (p < .05). For background features, squamous cells were more common for RCC (p = .006) including CCRCC (p = .003), whereas polymorphs (p = .011) and necrotic material (p = .010) were associated with UC. Average nuclear size was larger and nuclear size variation (p < .001) and nuclear-cytoplasmic ratio (p = .001) were greater in UC (p = .001) than RCC. Comparing RCC to high-grade UCs only, nuclear-cytoplasmic ratio maintained statistical significance (p = .006) while average nuclear size showed a trend (p = .063). A clean background free of tumor necrosis and polymorphs, and the lack of complex tumor fragments favors RCC. UCs also display larger nuclear size, higher nuclear size variation and nuclear-cytoplasmic ratio. These cytomorphological features with corroboration of clinical/radiological findings, can aid in raising a diagnosis of RCC.

Fine-needle Aspiration Biopsy of Pilomatrixoma (Cytological Features of Six Cases Histologically Approved).

Pilomatrixoma is a rare, benign, slow-growing tumor of the hair matrix. Excisional biopsy is often the preferred method of diagnosis for cutaneous masses including pilomatrixoma. However, fine-needle aspiration is also performed on these lesions. There are very few reports on the cytologic features of pilomatrixoma in fine-needle aspiration. In this study, we aimed to evaluate the clinical and cytological features of six cases of pilomatrixoma, which were confirmed histopathologically. The study includes six cases of pilomatrixoma, which were diagnosed by two cytopathologists in 2019 and 2022. A detailed cytological analysis was done by a semiquantitative method. Cellularity, basaloid cells, squamous cells, giant cells, shadow cells, naked nuclei, calcium deposits, inflammation, and debris were semiquantified from 0 to 3+. The ages of patients ranged from 8 to 63 years old. The male-to-female ratio was 2:1. All cases occurred in the head and neck area. The cytological diagnosis was pilomatrixoma in five cases and epidermoid/dermoid cyst in one case. The surgical excision was performed in all patients. The diagnosis of pilomatrixoma was confirmed histologically in all cases. Fine-needle aspiration biopsy (FNAB) of pilomatrixoma can be a diagnostic challenge. There are very few reports on the cytologic features of pilomatrixoma in FNAB smears. The presence of ghost cells and basaloid cells should suggest the possibility of pilomatrixoma. The presence of giant cells, fibrillary matrix, calcium deposits, squamous cells, naked nuclei, inflammation, and debris are cytological findings supporting the diagnosis.

Phase I summary of the HB0025 efficacy and safety to the heavily pretreated non-small cell lung cancer (NSCLC) population.

e14600 Background: HB0025 is a recombinant humanized bispecific molecule built on IgG1 that targets the human programmed death ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF, VEGF-A, VEGF165). Here we present the NSCLC results in Phase 1 study. Methods: This ongoing, open-label, multicenter, dose escalation and dose expansion, phase 1 trial to evaluate the safety and efficacy of HB0025 for pts with advanced solid tumors. HB0025 is administered intravenously every 14 days (Q2W). Response was evaluated by RECIST v.1.1 every 8 weeks. Results: As of Dec 25, 2023, 12 (7M/5F) NSCLC pts have received HB0025 at doses of 3mg/kg (n=1), 6mg/kg (n=2), 10mg/kg (n=2), 12mg/kg (n=1), 20mg/kg (n=5), 30mg/kg (n=1). Overall, the median age was 61.5 years, the median number of prior treatment lines was 4. The histologic types include squamous cell (Sq)-NSCLC (2 pts) without EGFR/ALK mutation and non- squamous cell (Nonsq)-NSCLC (10 pts), among of Nonsq-NSCLC 9 pts carrying EGFR/ALK mutation. The 3 pts with EGFR/ALK wild-type gene fail to prior anti-PD-1 treatment, 9 pts with EGFR/ALK gene mutation fail to prior TKI therapy. Among the 12 pts having imaging tumor assessment, the ORR was 25% and DCR was 66.7%, which included 3 partial responses (PR) ,5 stable disease (SD), and 4 progressive disease (PD) according to RECIST v1.1.For the 2 Sq-NSCLC pts, one pt achieved PR with 3mg/kg HB0025 treatment, the other pt achieved SD. For the10 Nonsq-NSCLC pts, there were 2 PR (20mg/kg and 30mg/kg treatment, respectively), 4 SD and 4 PD. Till the report date, the PR status and HB0025 treatment are ongoing to 3 PR pts, which includes 1 Sq-NSCLC pt, and 2 Nonsq-NSCLC pts which one pt doesn’t carry EGFR/ALK mutation. The Sq-NSCLC pt whose maximum tumor regression is 60% achieves PR after 4 cycles of treatment, and the duration of response (DOR) is more than 22 months. The one Nonsq-NSCLC pt whose maximum tumor regression is 74% achieves PR after 2 cycles of treatment, and the DOR is more than 11 months. The other Nonsq-NSCLC pt whose tumor regression is 32% achieves PR after 4 cycles of treatment, and the DOR is more than 2 months. Among the 5 SD pts, 1 Sq-NSCLC pt’s progression-free survival (PFS) is more than 14 months and continusous, 2 Nonsq-NSCLC pts’ PFS is more than 6 months and ongoing. For the 12 pts, 11 pts (91.7%) experienced a treatment related adverse events (TRAEs). The most common TRAEs included proteinuria (50%, 6/12), lymphocyte count decrease (50%, 6/12), blood bilirubin increased (33.3%, 4/12), and blood pressure increased (33.3%, 4/12). TRAEs ≥ grade 3 occurred in 2 (16.7%) pts. No TRAE leading to discontinuation and death. Conclusions: HB0025 monotherapy showed an acceptable safety profile and promising anti-tumor activity for prior heavily treated NSCLC, no matter in TKI-resistant population with EGFR/ALK mutation or population failed to anti-PD-1 treatment. Now Phase II studies of combination chemotherapy are ongoing. Clinical trial information: NCT04678908 .

Comparison of chemotherapy to chemo-immunotherapy as first-line treatment in patients with advanced large cell neuroendocrine carcinomas (LCNECs) of mixed histology: A multi-institutional international retrospective study.

8602 Background: LCNECs are a rare subtype of lung cancer, with limited clinical trial data and an unclear consensus on first-line treatment. Even less is known about the optimal treatment approach for pts with mixed LCNECs, a pathologic subtype where tumors contain both LCNEC histology as well as features of adenocarcinoma, squamous cell, or small cell lung cancer. Methods: We conducted an international multi-institutional retrospective analysis (n=13 institutions) of pts with advanced or metastatic mixed LCNECs who received 1st-line systemic therapy with either chemotherapy alone (chemo) or chemo-immunotherapy (chemoIO) between 2010-2023. Clinical outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (trAEs). Survival comparisons were made via the log-rank test. Results: Seventy-three pts with mixed LCNECs received either chemo (n=42, 57.5%) or chemoIO (n=31, 42.5%). The most common chemo regimens were carboplatin/etoposide (n=27) and cisplatin/etoposide (n=8), while the most common chemoIO was carboplatin/etoposide/atezolizumab (n=19). Median age at 1st-line therapy initiation was 65 (IQR: 60-72). 64% of pts were male (n=47). The majority were former smokers (n=41, 56.2%), with 22 current smokers (30.1%), and 10 non-smokers (13.7%). Mixed histologies included LCNEC/NSCLC (n=45, 56.2%), LCNEC/SCLC (n=17), LCNEC/carcinoid (n=1), and unspecified mixed LCNEC (n=10). Median PFS for chemo was 5 months (95% CI 2.7-9.2) vs. 6 months (95% CI 4.4-8.3) for chemoIO ( p=0.86). Median OS for chemo was 14.2 months (95% CI 10.4-22.5) vs. 17.2 months (95% CI 9.4-27.2) for chemoIO ( p=0.66). The ORR did not differ between chemo (n=18, 45%) and chemoIO (n=15, 48.4%) ( p=0.81). In the chemo group, 60% (n=25) experienced trAEs of any grade, with 23.8% (n=10) experiencing grade 3+ events and four requiring hospitalizations. For chemoIO pts, 61% (n=19) experienced trAEs, with 25.8% (n=8) experiencing grade 3+ events and six requiring hospitalizations. Neutropenia was the most common grade 3+ trAE for both chemo (n=5) and chemoIO (n=4). Overall, there were no significant differences between chemo or chemoIO groups for ORR ( p=0.81), all-grade trAEs ( p=0.88), grade 3+ trAEs ( p=0.84), PFS ( p=0.86), or median OS ( p=0.66). There were no significant differences in median PFS ( p=0.46) or OS ( p=0.99) for pts with mixed LCNEC/NSCLC vs. LCNEC/SCLC. Conclusions: For mixed LCNECs, there was no significant difference in PFS or OS between first-line treatment with chemo vs. chemoIO, suggesting limited benefit from immunotherapy for these pts. Additionally, survival outcomes did not differ between mixed LCNEC/NSCLC and LCNEC/SCLC, suggesting a biology primarily driven by their neuroendocrine component.

Disparity in oncology therapy access and differences in clinical pathological features and outcomes in indigenous population lung cancer (LC): A retrospective study from Martinique.

1599 Background: The epidemiology of cancers in terms of incidence and mortality are different in the French overseas compared to mainland France (FRANCIM 2019 data). Indigenous population are under-represented in clinical trials. Little is known about clinic-pathological features and outcomes from Caribbean islands. We report clinico-pathological features and survival in populations of patients with lung cancer (LC) and delays in access to therapy in Martinique. Methods: We conducted an academic retrospective study on patients with lung cancer (LC), treated at the University Hospital in Martinique between 2020-2022. The hospital in Martinique centralized all cancer patients in the territory for treatment. Demographic, risk factors, disease features, and treatment outcomes were collected from medical records. The molecular profile was determined using next-generation sequencing with the Archer FUSION Plex Lung v2 panel, evaluating at least EGFR, ALK, KRAS, ERBB2, MET, ROS1, BRAF, RET, NUTM1, PIK3CA, FGFR1, FGFR2, FGFR3, NRG1, NTRK1, NTRK2, NTRK3. We assessed time from symptoms to diagnosis and treatment, and overall survival (OS). Results: Overall, 268 patients (pts) were included. Pts were male in 51% cases (N=136), had a smoking history in 57% (N=139/243), with a median pack-years of 40 [IQR 22-50]. Median age was 67 years-old [IQR 58-78]. Histology was adenocarcinoma in 78% (N = 208), squamous cell in 13% (N=34), neuroendocrine tumors in 8% (N=21), and others in 2% (N=5). No small cell carcinoma diagnosed. Tumors had high PD-L1 expression (≥50%) in 18% (N=41/227) of cases. An oncogenic addiction was reported in 58% (N =105/181) of non-small cell and non-squamous lung carcinoma: EGFR36% (N=65), ALK3.3% (N=6), BRAF1.1% (N=2), KRAS13.3% (N=24). Pts had an ECOG performance status of 0-1 at diagnosis in 66% (N =162/244). LC was metastatic from diagnosis in 65% cases (N=175), with 18% having brain metastases (N=48). Median time between symptom occurrence and diagnosis was 66 days [IQR 21-171] and time between biopsy and treatment start was 56 days [IQR 31-77]. In pts with stage IV disease, 33% (N=59/175) never received a systemic treatment. In patients with at least 6 months of follow-up in the absence of death, median OS was 12.4 months (95% CI 8.6 – 17.1) overall and 8.6 months (95% CI 5.3 – 13.3) in patients with initial metastases. Conclusions: The lower overall survival rate than expected in this cancer context address the question of disparity population. One-third of LC metastatic patients did not receive systemic therapy. The local inadequacy of care pathways, leading to disparities in access to imaging, may explain the delays and poorer prognosis. A new initiative from a collaborative group with health authorities, caregivers, politicians and patient’s advocacy is actively working to improve cancer patient’s outcomes.

Molecular profiling across histologies in lung cancer: Time to change WHO nomenclature?

8532 Background: Biomarker testing is essential for optimal therapeutic management of Non-Small lung Cancer (NSCLC). However, a not negligible percentage of patients (pts) is not tested in clinical practice for all the relevant actionable biomarkers. Biomarker testing is recommended in lung adenocarcinoma (LUAD), while in tumors with other histologies it is reserved when clinical features indicate a higher probability of an oncogenic driver. Histopathology report and biomarker testing are usually performed sequentially, which is time consuming and delays patient care. Herein we determined the distribution of actionable biomarkers across NSCLC histotypes and other clinic-demographic characteristics. Methods: This is an observational retrospective analysis on histologically confirmed NSCLC cases tested between 2014-2022 using FoundationOne/FoundationOneCDx assay. Histopathologies of all cases were centrally reviewed and confirmed by Board Certified Anatomic Pathologists. Results: 82,328 NSCLC pts were included. Actionable genomic alterations (GA) were found in 35.1% of the cases (Table). LUAD and adenosquamous (ASC) were more commonly associated with actionable GA (45.8% and 40.9%, respectively) as compared with sarcomatoid (29.1%), not otherwise specified (NOS) (27.6%), large cell (LCC) (21.1%), and squamous cell (LUSC) (6.5%) histologies. Sarcomatoid histology had the highest METex14 skipping mutations (muts) frequency (9.9% vs. 2.4% in LUAD). Tumor mutational burden (TMB) ≥10 Mut/Mb was associated with histology (50.9% in LCC, 40.8% in NOS, 39.1% in LUSC, and 36.3% in sarcomatoid vs. 31.2% in LUAD and 29.2% in ASC). Pts with actionable GA usually had a low TMB (80.9%). A significant correlation (p&lt;0.005) between age and actionable GA was reported for BRAF/ ERBB2 muts, ALK/RET/ROS1 rearrangements (RE), and MET amplification. EGFR actionable muts and KRASG12C were more commonly observed in females, whereas no significant correlation between sex and other GA was observed. Finally, genetic ancestry analyses revealed a strong correlation between EGFR actionable muts and South/East Asian and American ancestries, but not for other GA. Conclusions: This is the largest NSCLC dataset analyzed for biomarker distribution across histologies, age, sex and genetic ancestry. This dataset confirms sufficient enough biomarker prevalence across LUAD and ASC carcinoma to be included in WHO nomenclature for lung tumors, and provides reassurance that cases with NOS, LCC and sarcomatoid histologies must be considered for biomarker workup. [Table: see text]

The journey of patients with lung cancer: The gap between symptom onset and treatment.

e23119 Background: Prompt access to health care services is a priority in public health policies. The aim of this study was to map the journey of patients (pts) diagnosed with lung cancer (LC) and determine the time interval (TI) from symptom onset (SO) to treatment initiation and assess the impact on survival. Methods: A retrospective cohort study was conducted at the University Hospital of Larissa. Pts’ demographic and disease-related data were captured from medical records. The TI from SO to first doctor visit (StD), SO to first oncologist visit (StO), diagnosis to treatment initiation (DtT) and SO to treatment initiation (StT) were estimated. Overall survival (OS) was defined as the TI between treatment initiation and the date of death or the date of last follow-up. OS were estimated using the Kaplan–Meier analysis and the comparisons were computed with the log-rank test. Results: Overall, 251 sequential pts with metastatic LC were included in the study. Pts’ mean age was 71 years (range 35-88). The majority were men (82%) and 24%, 32%, 28% and 16% were diagnosed with small cell lung cancer (SCLC), squamous cell (SCC), adenocarcinoma (ADC) and large cell (LCC) LC, respectively. The median StD and StO was 32 (0-212) days and 102 (11-608) days, respectively. No difference was detected across genders, age ( &gt; or &lt; 70), family history of cancer or not, and area of residence (rural, urban). The median StT and DtT was 123 (30-851) days and 26 (1-105) days, respectively, with this time intervals being shorter among pts with SCLC compared to pts with non-small cell LC (NSCLC) ( p: 0.006 and p&lt; 0.001, respectively). Pts with sort StT intervals had significantly improved OS, compared to pts with longer StT intervals (SCLC p:0.044, NSCLC p:0.004). Conclusions: To the best of our knowledge, this is the first study aiming to determine specific TI from SO to treatment initiation for pts with LC in Greece and assess the potential impact on OS. Our data revealed a substantially prolonged StT (~4months) that is associated with worse survival rates. This indicates a need to improve public awareness of LC symptoms, enable pts’ access to specialized health care services and facilitate earlier diagnosis and treatment.

Double lung transplantation in patients with recent history of malignancy.

e20614 Background: Recent history of malignancy has been considered as a contraindication for double lung transplantation (DLT) due to concerns for risk of cancer recurrence and worse outcomes. However, the relationship between the recent malignancy history and lung transplantation mortality remains unclear. Methods: Among patients treated with DLT between 09/2021 and 02/2024 in single institution, patients with a recent history of other cancers were included in this study. All patients had enrolled in cohort C of the DLT registry aimed for lung-limited malignancies (DREAM) study (NCT05671887). Exclusion criteria include extrapulmonary metastatic disease and medical ineligibility for DLT. All patients were followed up with computed tomography every 12 weeks. Results: Four patients were included; three (75%) patients with a histology of NSCLC (squamous cell, stage Ib-IIIb), and one (25%) with prostate adenocarcinoma (stage IIc). The median no-evidence-of-disease (NED) time was 19.5 months (0-41). Patients were aged 57-68, three (75%) were male. The indication for DLT was chronic obstructive pulmonary disease (1/4, 25%), interstitial lung disease (2/4, 50%), and idiopathic pulmonary fibrosis (1/4, 25%). All patients had high oxygen requirements before DLT. The median duration of the waitlist for DLT was sixteen days (3-61). There was no in-hospital mortality and the median hospital stay was 20.5 days (16-32). During a median follow-up of 2.5 months (range 0-9), rejection and post-transplant malignancy did not occur in any of the cases (Table 1). Conclusions: Four patients with history of cancers underwent DLT without significant complications. The median post-transplant follow-up was 2.5 months (0-9). Ongoing DREAM study cohort C will continue to investigate the role of DLT in patients with a recent history of malignancy. Clinical trial information: NCT05671887 . [Table: see text]

Genotyping the human papillomavirus and associated risk factors in mono- and co-infection with human immunodeficiency virus among women attending KIU-TH

The study set out to identify the circulating “high-risk HPV (Hr-HPV) genotype” and examine the risk factors linked to HPV/HIV co-infection and HPV single infection among women receiving medical attention at the Kampala International University Teaching Hospital (KIU-TH). A total of 114 women attending the KIU-TH Clinton Health Accesses Initiative (CHAI) and gynecology units were enrolled. Questionnaires were administered and information regarding the “risk factors associated with Hr-HPV infection” was collected. Subjects were examined for cervical cytological features with use of “visual inspection with acetic acid” (VIA) and Pap smears, and HPV genotype were assessed using the Xpert gene. The analysis of data was done using SPSS v29. The study hypotheses were tested at the common level of P ≤ 0.05. In this study, 37(32%) patients were positive for VIA, 28(24%) were Pap smear-positive, and 3(3%) and 2(2%) were atypical “squamous cells” of undetermined significant (ASCUS) positive for VIA and Pap smears, respectively. Furthermore, a study revealed that 20% of Hr-HPV was from co-infections and 10% from mono-infections. The circulating Hr-HPV genotype were HPV (17.2%), HPV16(9%), and HPV 18/45(7%). Results showed significant relationships (P &lt; 0.05) between condom use, marital status and having many partners as “risk factors” and Hr-HPV infection. In contrast, age, education, vaccination, and educational level were not. This study revealed several factors linked to HPV infection and calls for the integration of cervical cancer screening using the combination of both VIA and Pap smear or gene Xpert, as well as creating awareness and implementation of vaccination programs within Bushenyi District and the country at large.

Trends in lung cancer survival in the Nordic countries 1990–2016: The NORDCAN survival studies

ObjectivesThe aim of this study was to evaluate if the previously reported improvements in lung cancer survival were consistent across age at diagnosis and by lung cancer subtypes. Materials and methodsData on lung cancers diagnosed between 1990 and 2016 in Denmark, Finland, Iceland, Norway and Sweden were obtained from the NORDCAN database. Flexible parametric models were used to estimate age-standardized and age-specific relative survival by sex, as well as reference-adjusted crude probabilities of death and life-years lost. Age-standardised survival was also estimated by the three major subtypes; adenocarcincoma, squamous cell and small-cell carcinoma. ResultsBoth 1- and 5-year relative survival improved continuously in all countries. The pattern of improvement was similar across age groups and by subtype. The largest improvements in survival were seen in Denmark, while improvements were comparatively smaller in Finland. In the most recent period, age-standardised estimates of 5-year relative survival ranged from 13% to 26% and the 5-year crude probability of death due to lung cancer ranged from 73% to 85%. Across all Nordic countries, survival decreased with age, and was lower in men and for small-cell carcinoma. ConclusionLung cancer survival has improved substantially since 1990, in both women and men and across age. The improvements were seen in all major subtypes. However, lung cancer survival remains poor, with three out of four patients dying from their lung cancer within five years of diagnosis.

Incidental pigmented basal cell carcinoma discovered on positron emission tomography (PET)

AbstractBasal cell carcinoma (BCC), which frequently occurs in sun‐exposed areas of the head and neck region, is the most common cutaneous malignancy but the least studied with radiologic imaging techniques. This article outlines the case of a 65‐year‐old male with a pigmented BCC of the right shoulder discovered on positron emission tomography‐computed tomography (PET/CT). The lesion was initially suspected as a melanoma. However, the histopathological features showed a tumor of basaloid cells. PET/CT is an excellent technique for the detection of hypermetabolic tumors, such as melanoma, squamous cell and Merkel cell carcinomas, in lymph nodes and distant organs. The usefulness of PET is limited for slowly growing tumors, such as BCC. However, PET/CT can be useful for the detection of distant metastasis in locally advanced BCC as well as in the follow‐up of locally advanced BCC on Hedgehog inhibitors.

Abstract PO2-17-10: Metaplastic breast cancer: description of 16 cases treated at a reference center and review of the literature

Abstract Background: Metaplastic breast carcinomas (MBC) are very rare and represent less than 1% of all invasive breast carcinomas. It is a heterogeneous neoplasm characterized by a mixture of adenocarcinoma with other histological elements such as squamous cells, spindle cells or other mesenchymal differentiation. Most MBC are hormone receptor and Her2 negative and tend to have a worse prognosis when compared to triple negative carcinomas. Clinically, they manifest as a rapidly growing palpable mass, without necessarily involving lymph nodes. According to the nomenclature of the WHO Classification of Tumors of the Breast (2012), tumors were classified into 4 variants: spindle cell, squamous cell, mesenchymal and mixed. Since publications on MBC are scarce in the literature, we studied the cases that were attended at Hospital Pérola Byington in the period 2010-2021. Methods: A retrospective study was carried out by reviewing the medical records of patients treated at the Reference Center for Women's Health - Pérola Byington Hospital, São Paulo, Brazil. Patients with breast cancer, with anatomopathological result confirming the diagnosis of metaplastic carcinoma were reviewed. Clinical data and histopathological characteristics were evaluated, as well as the type of treatment performed and the evolution. Results: A total of 16 female patients diagnosed with MBC were included. The median age was 56 years (ranging from 34 to 88). The mean initial size observed was 7 cm (ranging from 2 to 20 cm) and 94% of patients presented with a palpable mass. The initial clinical staging were I (12%), II (32%), III (50%) and IV (6%). The most common histological subtype was spindle cell (50%), of which 2 were squamous (12%), 3 mesenchymal (20%), 1 mixed spindle/squamous (6%) and 2 were not classified. Regarding immunohistochemistry, 14 patients (88%) had hormone negative and Her2 negative (triple negative). Of the 16 cases, 8 underwent mastectomy and 6 partial mastectomiy and 2 patients did not undergo surgical treatment because they died despite treatment with neoadjuvant chemotherapy. All operated patients underwent sentinel lymph node biopsy or axillary dissection and 85% of them did not have axillary lymph node involvement. Radiotherapy was indicated in 13 patients. Chemotherapy was performed in 10 patients, 6 of which were neoadjuvant (since the tumors were not resectable) and 4 received adjuvant chemotherapy. Of the 6 patients that underwent neoadjuvant chemotherapy, 2 had disease progression, 3 partial response and 1 complete pathological response. During follow-up, 4 (25%) evolved with locoregional recurrence and 5 (31%) with metastatic disease. Of these women, 44% (7) are still alive. We also found that 6 of the 16 cases (37%) did not receive a diagnosis of MBC in the initial biopsy, requiring revision, a new biopsy or study of the surgical specimen for confirmation. Conclusion: As verified in the literature, MBC is a very rare histological type and corresponded to 0.2% of all cases of breast cancer in the period described above. Most patients have an advanced tumor at the time of diagnosis and little axillary involvement. The most common histological classification is the spindle cell variant and almost all tumors are triple negative. The CMM has an aggressive behavior and little response to chemotherapy treatments. Therefore, radical surgical treatments are preferred. Due to the rarity of this entity there is little data published in the international literature. Citation Format: Andre Mattar, Marcelo Antonini, Marina Diogenes, Andressa Amorim, Francisco Pimentel Cavalcante, Luiz Henrique Gebrim. Metaplastic breast cancer: description of 16 cases treated at a reference center and review of the literature [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-10.

Treatment Complications of Head and Neck Cancers and Rehabilitation Measures: A Narrative Review.

Head and neck cancers (HNCs) are malignant tumors mainly from squamous cells in the head and neck tissues. Treatment involves a multidisciplinary approach with surgery, radiotherapy, and chemotherapy. However, the long-term prognosis for patients with advanced-stage tumors is guarded, with a median survival time of approximately 24 months. HNC patients have very high rates of depression and anxiety and the highest suicide rate among all cancers due to the intense and challenging nature of the treatment, underscoring the importance of our collective efforts. Rehabilitation success depends on various factors, including tumor, patient, and treatment-related factors. Patients may require post-treatment oral rehabilitation measures, including implants, obturators, and flexible dentures. These measures are crucial, but they often need to be more utilized. Patients may face challenges in maintaining oral hygiene and managing mucositis. Additionally, it is essential to address other intricacies such as trismus, xerostomia, gustatory dysfunctions, neuropathy, speech impairments, and psychological disturbances. Unfortunately, there is little literature on post-treatment rehabilitative measures. Despite its crucial role in improving patients' quality of life, rehabilitation often receives inadequate attention compared to treatment. Our narrative review, which covers various factors that affect rehabilitation, including oral rehabilitation measures and post-treatment complications, is anticipated to deliver practical insights to professionals and inspire positive changes in their regular practice.

Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance.

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin.

Three cases of gingival cancer associated with peri‐implantitis and their management

AbstractBackgroundDental implant treatment is effective for missing teeth, but it can cause peri‐implantitis. Chronic inflammation may be involved in the development of malignancy. We report three cases of gingival cancer that may have been associated with peri‐implantitis.Case PresentationAll three patients were referred to our department for detailed examination of a mass or ulcerative lesion around implants placed in their family dental clinics. One case of cancer was associated with oral lichen planus and peri‐implantitis. Two cases of cancer were associated with peri‐implantitis. Surgery for gingival cancer was successfully performed. All three pathological diagnoses were well‐differentiated squamous cell carcinoma.ConclusionChronic inflammation is a risk factor for malignant tumors, suggesting the importance of its maintenance.

Validation of the 2018 FIGO staging system for stage IIIC cervical cancer by determining the metabolic and radiomic heterogeneity of primary tumors based on 18F-FDG PET/CT.

This study aimed to validate the 2018 FIGO staging system of cervical cancer (CC) by determining the metabolic and radiomic heterogeneity of primary tumors between stage IIIC1 and IIIC2. 168 patients with squamous cell CC underwent pre-treatment fluorine-18 fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) and were randomly allocated to training and testing cohorts with a 7:3 ratio. Radiomics features were extracted from the primary tumors based on CT and PET data. Ten metabolic parameters of the primary tumors were also assessed. After feature selection, three logistic regression radiomics models, involving (1) 2 CT features, (2) 3 PET features, and (3) 2 CT features + 3 PET features, respectively, and one random forest model were established. Finally, area under the curve (AUC) values and calibration curves were used to evaluate the 4 models. The IIIC1 and IIIC2 groups did not differ significantly in age, weight, height, or the 10 major metabolic parameters (P > 0.05). The AUCs of the 4 models were 0.577, 0.639, 0.763, and 0.506, respectively, in the training cohort, and 0.789, 0.699, 0.761, and 0.538, respectively, in the testing cohort. The model fit of the logistic regression model based on CT + PET data was good in both the training and testing cohorts. Our study offers additional diagnostic options for PALN metastasis, which could impact treatment decisions. Our results indirectly support the conclusions of previous studies recommending that primary tumors should be considered during IIIC staging.