Oral Cavity Squamous Cell Carcinoma Research Articles

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [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 PO4-18-05.

Gingiva squamous-cell carcinoma in a non-smoking patient with occupational exposure to solvent siphoning using mouth: case report and literature review

BackgroundWhile overall head and neck cancer incidence decreases due to reduced tobacco and alcohol consumption, the incidence of HPV negative oral cavity squamous cell carcinoma (SCC) is raising in several industrialized countries, especially in non-smoking and non-drinking patients.Case presentationWe document a case of gingiva SCC in a 56 years old never-smoker patient reporting low alcohol consumption and unusual occupational solvent exposure. The HPV-negative lesion was surgically removed in 2018, and the patient remains in complete remission 4 years after recurrent surgery in 2019. In 2021, the patient was referred to the occupational cancer consultation. The patient worked as screen printer for 18 years. He reported mouth siphoning every 2–3 days to transfer organic solvents (mainly aromatic hydrocarbons and ketones) from containers into smaller recipients, with regular passage of solvents into his mouth.ConclusionAccording to the literature, the frequency of solvent siphoning using mouth is likely to be underestimated. While our review did not find studies reporting longterm consequences to the oral cavity of mouth siphoning, current evidence supports a positive association of upper aero digestive tract SCC with occupational exposures to organic solvents and printing processes. In absence of major extraprofessional factors, the HPV-negative gingiva SCC of this patient might be attributable to the regular occupational oral solvent exposure. While the available evidence remains limited to formally establish a causal relationship, clinicians should investigate this hazardous work practice in patients with OSCC and history of solvent exposures.

Reliability of Ultrasonographic Assessment of Depth of Invasion and Tumor Thickness in Intraoral Mucosa Lesions: A Preliminary Experience

Introduction: Despite the progress made in multidisciplinary care, there has been little improvement in the oncologic outcomes of oral cavity squamous cell carcinomas (OSCCs). In the latest edition of the TNM staging, “depth of invasion” (DOI) has recently been introduced as one of the criteria for determining the T stage, alongside other factors. DOI is widely recognized as an independent risk factor for nodal metastases and is a crucial consideration in the preoperative staging of OSCCs, along with measurements of tumor thickness (TT). While various diagnostic methods exist for assessing DOI, intraoral ultrasonography (IOUS) has gained popularity for its efficacy in evaluating OSCCs. Methods: This study sought to evaluate the diagnostic accuracy and reliability of ultrahigh-frequency ultrasound (UHFUS) in assessing oral cavity lesions compared to histopathological analysis. Results: The results revealed strong reliability in ultrasonographic measurements (ICC TT: 0.94; ICC DOI: 0.97) and distinct ultrasonographic features specific to different oral pathologies. This highlights the potential of UHFUS as a non-invasive imaging tool for precise diagnostic evaluations. Conclusions: Despite limitations such as a small sample size and focus on specific lesions, these promising results suggest that UHFUS could significantly enhance oral lesion diagnostics. Further research involving larger cohorts is necessary to validate and build upon these initial findings.

Differential expression of DNA fragmentation factor 45 in leukoplakia and oral squamous cell carcinoma and its correlation with TNF-α levels

BackgroundDNA fragmentation factor (DFF) - 45, a heterodimeric protein, involved in apoptotic processes is found to play important role in various human cancers. Its role in the development and progression of oral cavity squamous cell carcinoma (OSCC) is still unclear. Tumour necrosis factor-α (TNF-α) has been found to be higher in OSCC, yet, the mechanism of circumventing the antitumor effect of this cytokine is not understood. Thus, the aim of this study was to evaluate the expression of DFF-45 in samples of OSCC, leukoplakia, and healthy oral mucosa (control) and correlate it with salivary and serum TNF-α. Materials and methodsSurgically excised specimens from patients with primary OSCC (n = 20) leukoplakia (n = 30) and normal oral mucosa (n = 25) were immuno stained for DFF-45. The relationship of DFF-45expression with clinical parameters and histological grading was also evaluated. TNF-α levels were measured in serum and saliva collected from study subjects using cytokine ELISA technique. ResultsThe expression of DFF-45 in OSCC was either absent or mild, while a significantly up-regulated expression of this protein was observed in leukoplakia lesions. TNF-α levels in both saliva and serum were significantly higher in OSCC group compared to control and leukoplakia. We observed a negative correlation between TNF-α levels and DFF-45 expression in OSCC, similar observation was found with histological staging of OSCC. ConclusionThe absence of DFF-45 in oral cancer lesion suggests that this protein may suppress tumour progression. Down regulation of DFF-45 by tumor cells may be a mechanism to evade the anti-cancer effect of TNF-α and further investigations may unravel its role into malignant transition.

Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer.

Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC). From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable. A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58). No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC.

Radiomic biomarkers of locoregional recurrence: prognostic insights from oral cavity squamous cell carcinoma preoperative CT scans

IntroductionThis study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients.MethodsComputed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient’s pre-treatment CT. Clinical characteristics were also obtained, including race, sex, age, tobacco and alcohol use, tumor staging, and treatment modality. A feature selection algorithm was used to eliminate the most redundant features, followed by a selection of the best subset of the Logistic regression model (LRM). The best LRM model was determined based on the best prediction accuracy in terms of the area under Receiver operating characteristic curve. Finally, significant radiomic features in the final LRM model were identified as imaging biomarkers.Results and discussionTwo radiomics biomarkers, Large Dependence Emphasis (LDE) of the Gray Level Dependence Matrix (GLDM) and Long Run Emphasis (LRE) of the Gray Level Run Length Matrix (GLRLM) of the 3D Laplacian of Gaussian (LoG σ=3), have demonstrated the capability to preoperatively distinguish patients with and without LR, exhibiting exceptional testing specificity (1.00) and sensitivity (0.82). The group with LRE > 2.99 showed a 3-year recurrence-free survival rate of 0.81, in contrast to 0.49 for the group with LRE ≤ 2.99. Similarly, the group with LDE > 120 showed a rate of 0.82, compared to 0.49 for the group with LDE ≤ 120. These biomarkers broaden our understanding of using radiomics to predict OSCC progression, enabling personalized treatment plans to enhance patient survival.

Loss of Independence in Older Adults With Operable Oral Cavity Cancer: A Retrospective Cohort Study.

To ascertain the effect of curative-intent surgery on loss of independence (LOI) in patients with oral cavity squamous cell carcinoma (OCSCC). Retrospective observational study of patients diagnosed from 2014 to 2021. Single tertiary care academic center. Patients having undergone curative-intent surgical treatment for OCSCC from 2014 to 2021 in the cancer registry. LOI as the primary outcome was measured based on a combination of decrease in activities of daily living (ADLs) and/or decline in mobility during treatment. Descriptive statistics were used to compare baseline demographics and multivariable logistic regression was used to assess the association between LOI and perioperative variables of interest. Of the 180 patients included in this study, 139 (79%) were fully independent in ADLs/instrumental ADLs prior to surgery. The average age of the cohort was 74 with 49% males. Thirty-seven(21%) experienced a decline in mobility or increased care needs following surgery, and 18 (10%) experienced an independent decline in functional status. Increasing age, osseous flap reconstruction, high Charlson Comorbidity Index, and major postoperative adverse events were associated with LOI. Fifty-five percentof patients with LOI had recovered to baseline within 7 months from surgery. LOI was associated with poor treatment tolerance (odds ratio: 4.77, 95% confidence interval: 1.87-12.2) while adjusting for multiple confounders. LOI is common in older adults undergoing curative-intent surgery for OCSCC and associated with poor treatment tolerance.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Abstract LB211: Genetic complexity in OSCC metastasis: From transcription factors to novel therapeutic targets

Abstract Background: The survival of patients with oral cavity squamous cell carcinoma (OSCC) is largely influenced by the extent of locoregional recurrence. Recurrence after standard therapy occurs in about 30% of patients with late-stage OSCC, highlighting the challenge in managing this aggressive form of cancer. The transition of cells from an epithelial to mesenchymal phenotype is a critical event in OSCC invasion and metastasis and is governed by a complex interplay of genes and signaling pathways, with transcription factors such as ZEB1/2 and SNAI1/2 being pivotal players in this process. However, these transcription factors have proven challenging to target therapeutically, and it is likely that additional genes play crucial roles in OSCC pathology. Furthermore, the biology of locoregionally aggressive OSCC cancer cells is poorly understood, and this gap in knowledge is critical to predicting patient outcomes and improving treatment. This lack of understanding underscores the need for further research into identifying the specific molecular mechanisms and genetic factors that drive the locoregional aggressiveness of OSCC. Objective: To evaluate the impact of individual genes on OSCC cell migration, perform a comprehensive analysis of gene-specific effects on cell migration, and develop a valuable platform for the discovery of potential therapeutic targets. Methods: Our lab has created an in vitro model system of “mesenchymal-like” OSCC which exhibits increased migration and chemotherapeutic resistance. Using this model, we generated several cell lines expressing either Cas9 or an activating dCas9. We next transfected genome wide sgRNA libraries. Using a transwell assay platform we are working to identify several key genes necessary for successful cell migration and genes that amplify OSCC cell migratory potential. Results: Our results indicate that OSCC invasion and regional metastasis is a multifaceted process influenced by a network of genes beyond the well-known transcription factors. By subdividing gene expression changes based on E-cadherin protein expression, we are working to therapeutically isolate genes that may be critical during the fleeting transition from an epithelial to mesenchymal phenotype necessary for aggressive OSCC biology. Conclusions: We have identified several genes whose knockout or activation resulted in a significant impact on cell migration, shedding light on potential candidates for therapeutic intervention. The findings from this study will open new avenues for the development of targeted therapies to improve the prognosis of OSCC patients by focusing on previously unexplored genes involved in the invasion and metastatic cascade. Citation Format: Guillermo Flores, Slyn Uaroon, Marisa Buchakjian. Genetic complexity in OSCC metastasis: From transcription factors to novel therapeutic targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB211.

Abstract LB379: HLA-DQB1*05:02: An independent genetic marker for oral cavity squamous cell carcinoma susceptibility

Abstract Environmental exposure to carcinogens causes mucosal damage in the upper aerodigestive tract, which can lead to cancers. The genetic basis of head and neck cancer is controversial. To identify susceptibility genes in head and neck cancers, we enrolled patients with early-onset disease in Taiwan. This case-control study included 54 young male patients with oral squamous cell carcinoma (OSCC) who were treated between March 1996 and December 2016, as well as 2,400 healthy controls. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OSCC. Sequencing-based typing (TBG Biotechnology Corp., Taipei, Taiwan) was used to determine the HLA-DQB1 genotype in another cohort of 147 OSCC patients. We analyzed the allele frequencies of 664,994 autosomal SNPs in the 54 OSCC cases. In a genome-wide association analysis, four SNPs within loci on chromosomes 6, 7, 9, and 12 were significantly different between OSCC patients and controls (corrected P < 1.0 × 10−6). HLA-DQB1 was closest to rs28451423 on chromosome 6. HLA-DQB1*05:02 in OSCC (18.5%) was significantly different from normal population (7.0%) (P = 0.009). The influence of disease onset was independently significant after adjusting cigarette smoking, alcohol drinking and areca-quid chewing (P = 0.015, OR: 3.922, 95% confidence interval: 1.311 - 11.734). Furthermore, HLA-DQB1*05:02 was associated with early-onset OSCC (P = 0.004). HLA-DQB1*05:02 is associated with OSCC independent of environmental exposures. HLA-DQB1*05:02 is also related with early onset of OSCC. It provides evidence of a genetic basis for OSCC. Citation Format: Shiang-Fu Huang, Huei-Tzu Chien, Chi-Kuan Young, Yun-Shien Lee, Chun-Ta Liao, Kai-Lun Cho, Ching-Han Chen. HLA-DQB1*05:02: An independent genetic marker for oral cavity squamous cell carcinoma susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB379.

Abstract LB102: Triaging oral premalignant lesions: Plasma ultrashort cell-free DNA-based liquid biopsy approach

Abstract Background: Rapid advancements in cell-free DNA (cfDNA) based liquid biopsy (LB), has opened avenues of critical clinical importance. Recent discovery of a novel class of cell-free DNA 40-70 bps in length, ultrashort cfDNA (uscfDNA) is demonstrating immense potential as a cancer early detection biomarker. Globally, oral cavity squamous cell carcinomas (OCSCC) make up a significant proportion of head and neck squamous cell cancers. OCSCC commonly arises after the occurrence of oral premalignant lesions (OPLs), making it an ideal target for plasma-based LB screening initiatives. Methods: Current work focuses on preferential extraction of low molecular weight nucleic acids and single-stranded library preparation and sequencing, Broad Range cell-free DNA- Sequencing (BRcfDNA-Seq), to obtain uscf- & 167 bps mononucleosomal cfDNA (mncfDNA), for disease detection. Sequencing data was bioinformatically processed: paired-end reads merged (BBmerge), aligned with BWA-mem, deduplicated using SRSLY UMI, and blacklisted portions removed. This was followed by analysis for non-mutational features like fragmentomics, occurrence of G-Quad structures, 4-mer Motif sequences at the end of cfDNA sequences, functional genomic element peak formation by uscfDNA. These features have been recently described non-mutation metrics which have demonstrated evidence of clinical relevance. With non-mutational multi-modal analysis of uscfDNA, obtained using BRcfDNA-Seq, we were able to categorize oral premalignant disorders into two cohorts: one which progressed into OCSCC (PG-OPL) (n=19) & one which did not (nPG-OPL) (n=19). Results: Bioinformatic processing for fragmentomics, of the relative proportion of 40-53bps fragments to 54-70bps fragments in the uscfDNA population demonstrated a significant difference across 1700 chromosomal bins between PG & nPG-OPL (multiple t test, FDR 10%, p value = 0.044, AUROC = 0.7258). The occurrence of G-quadruplex structures in uscfDNA was also significantly different between the two groups (student t test, p= 0.02, AUROC= 0.6953). Examination of the end-motifs profiles of uscfDNA between PG-OPL & nPG-OPL samples showed the randomness of the motifs as revealed by the Shannon entropy score is significant between the two groups (p = 0.046, AUROC = 0.6482). We further evaluated individual motifs that could discriminate between the two groups and identified CCCC, CCCT, TGGG, etc. are highly discriminatory. uscfDNA contained a substantially higher proportion of functional genomic element sequences in the PG-OPL group than the nPG-OPL group like exon (p = 0.00067, AUROC = 0.7147) & 5’ UTR (p= 0.000006, AUROC= 0.7673) are different between the groups. Conclusion: Results demonstrated clinical relevance of BRcfDNA-Seq for plasma-derived cfDNA in assessment of malignancy progression of OPLs. These non-mutational multi-modal features of cfDNA maybe indicative of local and systemic factors associated with disease affecting cfDNA. Citation Format: Neeti Swarup, Jordan C. Cheng, Irene Choi, Mohammad Arshad Aziz, Kelly Y. Liu, Fang Wei, Feng Li, Yong Kim, Catherine Poh, David T. Wong. Triaging oral premalignant lesions: Plasma ultrashort cell-free DNA-based liquid biopsy approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB102.

Prospective Cohort Study Identifies Medical Predictors of Treatment-Related Oral Toxicities in Oral and Oropharyngeal Cancer Patients.

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

Oncologic outcome with versus without target volume compartmentalization in postoperative radiotherapy for oral cavity squamous cell carcinoma.

The volume treated with postoperative radiation therapy (PORT) in patients with oral cavity squamous cell carcinoma (OCSCC) is a mediator of toxicity affecting quality of life. Current guidelines only allow for very limited reduction of PORT volumes. This study investigated the safety and efficacy of de-intensified PORT for patients with OCSCC by refined compartmentalization of the treatment volume. This retrospective cohort study identified 103 OCSCC patients treated surgically from 2014 to 2019 with a loco-regional risk profile qualifying for PORT according to guidelines. PORT was administered only to the at-risk compartment and according to a refined compartmentalization concept (CC). Oncological outcome of this CC cohort was compared to a historical cohort (HC) of 98 patients treated before the CC was implemented. Median follow-up time was 4.5 and 4.8 years in the CC and HC cohorts, respectively. In the CC cohort, a total of 72 of 103 patients (70%) had a pathological risk profile that allowed for further compartmentalization and, hence, received a reduced treatment volume or omission of PORT altogether. Loco-regional control at 3 and 5 years was 77% and 73% in the CC cohort versus 78% and 73% in the HC (p = 0.93), progression-free survival was 72% and 64% versus75% and 68% (p = 0.58), respectively. Similarly, no statistically significant difference was seen in other outcome measures. De-intensified PORT limiting the treatment volume to the at-risk compartment or avoiding PORT altogether for low-risk patients with OCSCC does not seem to compromise disease control in this retrospective comparison. Based on these hypothesis-generating findings, a prospective study is being planned.

Depth of invasion as an independent prognostic factor in early-stage oral cavity squamous cell carcinoma

PurposeTo determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. Materials and methods344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. ResultsOf 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01–58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01–1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11–1.83, p = 0.006). ConclusionsDepth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

Nanoparticle mediated photodynamic therapy as a method to ablate oral cavity squamous cell carcinoma in preclinical models.

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumour cells by activating the cytotoxicity of photosensitiser dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitiser-containing building blocks (~94,000 photosensitisers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumour ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma: biologically relevant subcutaneous Cal-33 (cell-line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumours selectively uptake PS (10 mg/kg, IV) with 6~40-fold greater concentration versus muscle 24 hours post-injection. Single PS-PDT treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumours yielded significant apoptosis in 65.7% of tumour cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumour models. Complete tumour response was achieved in 65% of Cal-33 and 91% of MOC22 tumour mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumours, respectively. In buccal VX-2 rabbit tumours, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment, whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumours. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes.

Outcomes in Patients with Oral Cavity Squamous Cell Carcinomas with Respect to Initiation of Chemotherapy and Adjuvant IMRT Timing

Outcomes in Patients with Oral Cavity Squamous Cell Carcinomas with Respect to Initiation of Chemotherapy and Adjuvant IMRT Timing

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

BackgroundWhile several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. MethodsBetween 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. ResultsThe group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). ConclusionsOCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.

Prognostic risk factors of buccal squamous cell carcinoma: A case-control study.

To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland

IntroductionThe epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). MethodsA retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. ResultsA total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). ConclusionPrimary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.