Advanced Oral Cancer Research Articles

Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Oral Cancers: A Retrospective Analytical Study

Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Oral Cancers: A Retrospective Analytical Study

Thoracoabdominal Flap Closure for Large Post Pectoralis Major Myocutaneous Flap Donor Site in Advanced Oral Cancer: An Innovative Approach in Resource Constraint Setting

Thoracoabdominal Flap Closure for Large Post Pectoralis Major Myocutaneous Flap Donor Site in Advanced Oral Cancer: An Innovative Approach in Resource Constraint Setting

RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial

PURPOSE Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities. METHODS PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method. RESULTS Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen. CONCLUSION This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.

Efficacy of tracheostomy for respiratory management in patients with advanced oral cancer

BackgroundMany studies have been reported on tracheostomy to prevent upper airway obstruction after surgery. Among these, the scoring system proposed by Cameron et al. quantifies various factors that influence postoperative respiratory failure. This system provides a basis for surgeons to decide whether to perform an elective tracheostomy. In this study, the authors applied the Cameron scoring system retrospectively to patients undergoing severe oral cancer surgery to reevaluate the indications for elective tracheostomy and to investigate its clinical efficacy in airway management. In this study, a sample of 20 patients who underwent oral cancer surgery was selected and divided into two groups: 10 underwent tracheostomy and 10 did not. The Cameron scoring scores for each patient were extracted, to verify whether elective tracheostomy was performed in accordance with the threshold scores. Differences in scores and significant clinical impact factors between the two groups were analyzed and compared.ResultThe 10 patients who underwent tracheostomy had an average Cameron score of 6.4, all scoring above the recommended threshold of 5 for tracheostomy. For the 10 patients who did not undergo tracheostomy, the average score was 2.5, with 8 out of these 10 patients scoring below 5. Significant clinical impact factors observed included the location and size of the tumor, the performance of mandibulectomy and neck dissection, and the type of reconstruction surgery.ConclusionIn planning surgery for oral cancer patients, it is essential to consider the use of elective tracheostomy based on preoperative assessment of the risk of postoperative airway obstruction using tools like the Cameron scoring system, and patients’ condition. Research confirms that elective tracheostomy effectively enhances airway management in patients with severe oral cancer.

Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer

BackgroundAddition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.MethodsIn this study, 16 evaluable patients with stage III/IV oral cancer were treated...

Intra-arterial chemoradiotherapy for oral cancer: Superiority of intensity-modulated radiation therapy over three-dimensional conformal radiation therapy

PurposeTo determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer. MethodsWe retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m2/week) and nedaplatin (5 mg/m2/day) were administered through a shallow temporal artery using a catheter. ResultsIn total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001). ConclusionIMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia.

Long-term outcomes in virtual surgical planning for mandibular reconstruction: A cost-effectiveness analysis.

This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer, for which the cost effectiveness remains poorly understood. The proposed clinical benefits of VSP must be weighed against the additional upfront costs. A Markov decision analysis model was created for VSP and FHR based on literature review and institutional data over a 35-year time horizon. Model parameters were derived and averaged from systematic review and institutional experience. VSP cost and surgical time saving was incorporated. We accounted for long-term risks including cancer recurrence and hardware failure/exposure. We calculated cost in US dollars and effectiveness in quality-adjusted-life-years (QALYs). A health care perspective was adopted, discounting costs and effectiveness at 3%/year. Deterministic and probabilistic sensitivity analyses tested model robustness. In the base case scenario, total VSP strategy cost was $49,498 with 8.37 QALYs gained while FHR cost was $42,478 with 8.27 QALY gained. An incremental cost-effectiveness ratio (ICER), or the difference in cost/difference in effectiveness, for VSP was calculated at $68,382/QALY gained. VSP strategy favorability was sensitive to variations of patient age at diagnosis and institutional VSP cost with one-way sensitivity analysis. VSP was less economically favorable for patients >75.5 years of age or for institutional VSP costs >$10,745. In a probabilistic sensitivity analysis, 55% of iterations demonstrated an ICER value below a $100,000/QALY threshold. VSP is economically favorable compared to FHR in patients requiring mandibular reconstruction for advanced oral cancer, but these results are sensitive to the patient's age at diagnosis and the institutional VSP cost. Our results do not suggest if one "should or should not" use VSP, rather, emphasizes the need for patient selection regarding which patients would most benefit from VSP when evaluating quality of life and long-term complications. Further studies are necessary to demonstrate improved long-term risk for hardware failure/exposure in VSP compared to FHR.

Can Prophylactic Tracheostomy be Avoided in Advanced Oral Cancer Surgery for Airway Management? An Experience and Guidelines from a Tertiary Care Facility.

To evaluate the surgical and postoperative management strategies that contribute to minimizing the need for prophylactic tracheostomy for airway management in advanced oral cancer surgery. A retrospective review of the patients who underwent surgery for advanced oral cancer, in our institution from February 2015 to January 2024. In the present review, 66 patients (males, n = 54; females, n = 12; mean age 50.3years) who were operated for advanced oral cancer (T3, T4 oral squamous cell carcinoma and osteosarcoma of the mandible requiring mandibular resection) in our institution were included. 60 patients (90.9%) had reconstruction after segmental resection of the mandible without the need for prophylactic tracheostomy. Out of these, eighteen patients (27.27%) required segmental resection of the mandible crossing midline. Six patients (9.1%) underwent prophylactic tracheostomy, of which two patients had unilateral tumor and four patients had tumor crossing midline. Comparison of hospital stays between patients who underwent prophylactic tracheostomy and those who did not yielded mean durations of 13.3days and 7.6days, respectively. Except a subset of patients with old age, obesity, bulky neck, and those with respiratory compromise, following the present guidelines, prophylactic tracheostomy can be avoided in patients undergoing surgery for advanced oral cancer.

Precision Medicine and Clinical Trials in Advanced and Metastatic Oral Cancer.

Oral cancer is a significant global health concern, with high morbidity and mortality rates, particularly in regions with prevalent tobacco usage such as Asia. Majority of oral cancers are detected at an advanced stage resulting in poor survival outcomes. Moreover, the treatment modalities of oral cancers have remained constant with surgery and concurrent chemoradiotherapy being mainstays of the treatment. This review provides a significant progress made in understanding the molecular landscape of oral cancers and the evolution of therapeutic strategies toward precision medicine. A comprehensive literature review was conducted to gather recent studies on the molecular landscape of oral cancers, genomic insights, and clinical trials. Firstly, genomic insights into oral cancers, including key driver mutations and copy number alterations, are discussed in the context of personalized medicine approaches. Subsequently, advancements in therapeutic strategies, particularly focusing on clinical trials investigating immunotherapy and targeted agents, are highlighted. Despite promising results, challenges persist in identifying reliable biomarkers for treatment response and resistance. Continued research efforts are warranted to validate biomarkers and optimize therapeutic interventions, with the goal of enhancing patient outcomes and reducing the global burden of oral cancer.

Evaluating the Efficacy of Adjuvant Radiotherapy in the Management of Advanced Oral Cancer Cases.

Because of its high rates of morbidity and death, especially in its late stages, oral cancer poses a serious threat to world health. Even with improvements in surgical and chemotherapeutic techniques, advanced oral cancer is still difficult to treat and frequently has unfavorable results. Information on demographics, tumor features, treatment options, and results were gathered from medical records. Patients were categorized according to whether they underwent surgery alone or adjuvant radiation treatment after initial surgical resection. For the survival analysis, Kaplan-Meier curves and Cox proportional hazards models were employed. There were 150 patients in all, 75 in each group, who took part in the trial. Comparing adjuvant radiation to surgery alone resulted in considerably better overall survival (P < 0.001) and disease-free survival (P < 0.001). However, problems connected to the adjuvant radiation group affected a portion of the patient population. In conclusion, patients with advanced oral cancer can improve their overall and disease-free survival with adjuvant radiation, a successful therapeutic option. To maximize results, nevertheless, cautious patient selection and effective management of treatment-related problems are crucial. To improve treatment algorithms and investigate cutting-edge therapeutic techniques for this difficult condition, further research is necessary.

Associations of ctDNA clearance and pathological response after neoadjuvant treatment in patients with locally advanced oral cancer.

6043 Background: Neoadjuvant treatment (NAT) has improved clinical outcomes in some patients with locally advanced oral squamous cell carcinoma (LAOSCC). Effective biomarkers assessing the treatment response is still lacking. Previous studies have posed the potential of circulating tumor DNA (ctDNA) in monitoring treatment response, but the underlying mechanisms behind non-shedding in tumors remain unclear. Methods: 29 LAOSCC patients received NAT followed by surgery were enrolled. Seven (24.1%), 9 (31%), and 13 (44.8%) patients received NAT of apatinib+camrelizumab, TPF chemoagents, and toripalimab+paclitaxel+cisplatin, respectively. Tumor tissues before NAT underwent whole exome sequencing and whole transcriptome resequencing. Blood samples at pre-NAT (T0), mid-NAT (T1), before surgery (T2) and after surgery (T3) were analyzed using a tumor-informed, personalized NGS assay. Multi-omics analysis, including ctDNA status, was performed with patients' clinical features and outcomes. Results: Among the 29 patients received NAT, the MPR rate was 55.2% (16/29), and the pCR rate was 27.6% (8/29). At baseline(T0), ctDNA was detectable in 25/29 (86.2%) patients, which decreased over time (T1: 77.8%; T2: 51.7%; T3: 6.9%). Persistent ctDNA at T2 indicates a higher rate of residual disease after NAT (100% non-pCR) compared to ctDNA-negative patients (42.8% non-pCR; p = 0.0047). All patients achieving pCR at T2 were ctDNA-negative (n=8, 100%) including 2 non-shedders. The PPV and NPV for predicting pCR by ctDNA clearance at T2 were 57.1% (8/14) and 100% (15/15), respectively. ARSF, CFAP47, or HAUS8 mutations at baseline were associated with significantly higher pCR rates (p&lt;0.05). Four non-shedders with undetectable ctDNA at T0 were significantly enriched in patients with negative lymph nodes, lower clinical T stage, and high CPS score. The non-shedders had significantly lower tumor mutational burden (TMB), higher stromal score and cancer-associated fibroblast (CAF) (p&lt;0.05). Spatial transcriptome analysis further supports that MHC-II pathway-related genes were significantly up-regulated in the non-shedders. The enhancing communication intensity between CAFs, endothelial cells and T cells might provide an anti-cancer immune microenvironment for non-shedders. Conclusions: Our results indicate that the clearance of ctDNA clearance at T2 was associated with an improved pCR rate. Furthermore, our findings shed light on the factors that prevent ctDNA release from oral squamous cell carcinoma.[Table: see text]

Dynamics of saliva cytokine levels during intraoperative photodynamic therapy in patients with locally advanced oral cancer

Dynamics of saliva cytokine levels during intraoperative photodynamic therapy in patients with locally advanced oral cancer

Quality-of-Life Outcomes in Oral Cancer Patients Reconstructed With Double Free Flaps: A Preoperative and Postoperative Assessment.

This study aimed to evaluate quality of life (QOL) in patients with locally advanced oral cancer who underwent surgical resection followed by simultaneous double free flap reconstruction. Institutional database was reviewed from 2015 to 2021 and prospectively collected University of Washington Quality of Life data that were extracted for patients who met the inclusion criteria. Mean, composite, and best percentage scores were computed. Wilcoxon signed rank test was used to analyze differences between groups. Thirteen patients completed the assessment, all of them being male with a mean follow-up of 2.2 ± 1.2 years. Most common double free flap combination was fibula osteoseptocutaneous flap and anterolateral thigh flap (n = 11). Improvement in pain ( P = 0.01) domain score with decline in speech ( P = 0.01) and taste ( P = 0.02) was noted along with an overall decline in QOL ( P = 0.001) after cancer diagnosis. A decrease in physical function was seen postoperatively. Chewing and saliva were the most cited postoperative patient-reported domain affecting QOL. In double free flap reconstructed patients, in the postoperative phase, pain scores improved, whereas speech and taste scores declined. The overall health-related QOL declined compared with before cancer diagnosis.

2228: Lymphovascular invasion as prognostic factor in locally advanced oral tongue cancer

2228: Lymphovascular invasion as prognostic factor in locally advanced oral tongue cancer

PATIENT EDUCATION: Counseling of oral cancer patients

The purpose of this manuscript is to summarize key aspects of care for patients with advanced oral cancer, metastatic to the head and neck region. Patients with advanced oral cancer are treated with multimodal treatment. Surgical intervention leads to limitation in speech and swallowing abilities while adverse effects of chemotherapy and radiation treatment can include nausea, vomiting, diarrhea, mucositis, cystitis, dehydration, nephrotoxicity, skin dermatitis, myelosuppression, and nutritional deficiencies leading to weight loss. These toxicities could be overcome through self-care measures practiced by the patient. Oncology nurses could impart knowledge about self-care measures via patient and family counseling. Keywords: advanced oral cancer, head and neck cancer, counseling, self-care measures

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.

Evaluation of response to neoadjuvant chemotherapy in technically unresectable moderately advanced oral cavity cancers.

Moderately advanced and technically unresectable oral cavity cancers have a poor prognosis. Neoadjuvant chemotherapy might be beneficial in such patients by reducing tumour bulk and allowing definitive surgery. To evaluate the response of neoadjuvant chemotherapy in moderately advanced technically unresectable oral cavity cancers. Prospective observational study - secondary data analysis of patients with moderately advanced oral cavity cancer, which were treated with neoadjuvant chemotherapy (NACT) during the period November 2014-April 2016. Data was analysed for information on patient characteristics, chemotherapy received, toxicity, clinical response rates, local treatment offered and pathological response rates. The statistical analysis was performed with SPSS version 20. 30 patients, with a median age of 52 years were analyzed. Buccal mucosa was the most common sub site (50%). Three drug regimen was utilized in all patients. Resectability was achieved in 14 patients (46.67%). Febrile neutropenia was seen in 3 patients (10%). The overall response rate was 31%. NACT was effective in converting moderately advanced technically unresectable oral cavity cancers to operable disease in approximately 47% of patients. Post NACT, there is significant association between clinical and pathological findings of response rates. There is no increase in surgical complication rates following NACT.

The role of postoperative radiotherapy or chemoradiation in pT1-2N1M0 oral squamous cell carcinoma

BackgroundPostoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial. MethodsThis retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT. ResultsAmong the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease. ConclusionCCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease.

Neoadjuvant chemotherapy for advanced oral cavity cancer.

Neoadjuvant chemotherapy for advanced oral cavity cancer.

Comparison between upfront surgery vs salvage surgery following definitive chemoradiation in the treatment of potentially curable locally advanced oral cavity cancer: a retrospective study

Background: We conducted a study to compare the outcomes of upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. This study aims to compare the short-term outcomes (postoperative morbidity, recurrence) &amp; long-term outcomes (overall survival, disease-free survival) between upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. Methods: A total of sixty patients with locally advanced oral cavity squamous cell carcinoma (T4a, N1-N2b) were retrospectively analyzed between January 2021 and August 2023. Thirty patients underwent upfront surgery followed by adjuvant radiation (group 1) while another thirty patients underwent salvage surgery following definitive chemoradiation (group 2) (radiation dose- 66-70 Gy) Results: Morbidity was found to be significantly higher in the salvage surgery group (group 2) when compared to the upfront surgery group (group 1) with a p value of 0.003. There was no statistical significance between the two groups in terms of disease-free survival and overall survival. Conclusions: This retrospective study shows that there are no significant differences in overall survival and disease-free survival amongst patients of locally advanced oral cavity squamous cell carcinoma treated with upfront surgery and salvage surgery following definitive chemoradiation. Morbidity is significantly higher in the salvage surgery group.