Advanced Oral Cavity Squamous Cell Research Articles

Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma

BackgroundLocally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand...

935P Prognostic significance of diagnostic staging in treatment naïve, resectable locally advanced primary oral cavity squamous cell carcinoma for neoadjuvant leukocyte interleukin injection immunotherapy

935P Prognostic significance of diagnostic staging in treatment naïve, resectable locally advanced primary oral cavity squamous cell carcinoma for neoadjuvant leukocyte interleukin injection immunotherapy

199 Comparing survival and recurrence patterns in locally advanced oral cavity squamous cell carcinoma

199 Comparing survival and recurrence patterns in locally advanced oral cavity squamous cell carcinoma

“Clinical Outcomes of Surgically Treated Locally Advanced Oral Cavity Squamous Cell Carcinoma with Infra-Temporal Fossa Involvement: A Tertiary Cancer Centre Experience”

“Clinical Outcomes of Surgically Treated Locally Advanced Oral Cavity Squamous Cell Carcinoma with Infra-Temporal Fossa Involvement: A Tertiary Cancer Centre Experience”

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Exploring lived experiences in oral cavity cancer: An Asia-Pacific perspective on psychosocial challenges and opportunities for enhanced patient-centric care.

12097 Background: Locally advanced oral cavity squamous cell carcinoma (LA OC SCC) is profoundly emotionally taxing, characterized by a dual burden of undergoing treatment and adapting to post-treatment changes. The research explores lived experiences including psychosocial aspects, to identify approaches to establish a resilient supportive system for patients to improve coping and reduce anxiety and distress. Methods: A total of115in-depth interviews were conducted across Australia, Hong Kong, South Korea, Taiwan and Vietnam. Informants were LA OC SCC patients who underwent surgery and adjuvant chemoradiotherapy, their caregivers, multidisciplinary team (surgeons and clinical, radiation and medical oncologists) and supportive care HCPs (nursing, case managers/care coordinators, psychologists, speech therapists, dietitians, and dentists). Interview guide design and thematic analysis were guided by the Psycho-Onco Emotional Anxiety (POEM) framework and the Capability, Opportunity, Motivation, Behaviour (COM-B) model. Results: The POEM framework illuminated patients’ lived cancer experiences, emotions and psychological thoughts and processes influenced by beliefs of the world, others and self which impact coping responses that maintain or drive anxiety. Key themes emerged: physical and functional impairments result in negative psychosocial impact; constraints hinder person-centered care communications with HCPs and interpersonal dynamics with significant others; and personal and interpersonal experiences result in negative coping, exacerbated by inadequate health services and social support. Multimodal therapeutic interventions for LA OC SCC lead to physical and functional impairments implicating psychosocial and psychosexual quality of life. LA OC SCC stigma, societal norms and highly socially constrained patients grapple with distress from inadequate psychosocial support. Furthermore, HCPs may have preconceptions of LA OC SCC patients hindering patient-centered approaches to care and management. In certain regions, insufficient hospital support systems exacerbate the toll of strained interpersonal relationships and caregiver burden on physical, psychological and emotional well-being. Consequently, treatment adherence, self-care and survivorship experiences of patients and caregivers are affected. Conclusions: Utilizing the POEM framework, the study delved into nuanced patient and caregiver-narrated experiences in 5 Asia-Pacific countries/territories with distinctive supportive care systems. Findings underscore the imperative of improving patient-centric care through enhanced psychosocial support for patients and caregivers, identifying specific areas where health services can be better equipped to support holistic patient health delivery, especially psychosocial health.

The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma.

In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC. In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT. Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors. Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

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.

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.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice

BackgroundNeo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. MethodsThis was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. ResultsA total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). ConclusionNACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

144P Correlation of EZH2 expression and response to chemoradiotherapy in patients with locally advanced inoperable oral cavity and oropharyngeal squamous cell cancers

Outcomes of Patients with Oral Cavity Squamous Cell Carcinomas Treated with Adjuvant IMRT with Perineural Invasion

Patients with advanced oral cavity squamous cell carcinoma (OCSCC) have high rates of recurrence and dismal outcomes. Treatment consists of definitive surgery followed by risk-adapted adjuvant radiation therapy based on pathologic review. Perineural invasion (PNI) is thought to be an intermediate risk factor, leading to clinical uncertainty as to adjuvant therapy in the setting of PNI. We performed a single institution retrospective review of patients with OCSCC treated with adjuvant radiation with or without PNI and examined relapse-free survival (RFS) and overall survival (OS). We performed a single-institutional retrospective review of patients with OCSCC treated with adjuvant IMRT +/- chemotherapy after surgical resection from July 2002- August 2021 using our institution's Head and Neck SPORE database. Time to recurrence or death was calculated from end of RT. OCSCC within 5 years of RT was considered a recurrence, beyond this timeframe any OCSCC was considered a new primary. Univariate analysis of predictors for RFS and OS were performed using the Kaplan-Meier method with log-rank test. Factors significant on univariable analysis were entered into parsimonious cox multivariable analysis using forward selection methodology. A p-value <0.05 was considered significant in both analyses. In total, 494 patients with OCSCC were identified that received surgery and adjuvant IMRT. In this cohort, 48.8% of patients had pT4 tumors, 62.2% of patients had nodal involvement, and 40.3% of patients had extranodal extension. PNI was present in 63.6% of patients (n = 314). With regards to tumor subsite, 40.9% originated from the oral tongue, 21.5% originated from the gums, 18% originated from the floor of mouth, and 19.6% from the other sites. Median age was 59 years, and median adjuvant RT dose was 63 Gy (Interquartile range [IQR]) 60-66 Gy). The majority of patient received platinum-based chemotherapy (51.8%), and 44.1% of patients did not receive adjuvant chemotherapy. The 3-year RFS and OS with a median follow-up of 32 months (IQR 12-69 months) is presented in Table 1. On univariable analysis for OS, T stage (p = 0.003), N stage (p<0.001), PNI (p = 0.005), extranodal extension (ENE) (p<0.001), margin status (p = 0.038), and chemotherapy (p<0.001) were significant. On multivariable analysis, T stage (p<0.001), N stage (p = 0.010), PNI (p = 0.017), and ENE (p = 0.007) remained significant. Similar results were seen in the RFS analysis. In this large single institution study, PNI was a significant and independent negative predictive factor for RFS and OS in patients with OCSCC that had received definitive surgery followed by adjuvant IMRT. To our knowledge this is the largest study of its kind, and these findings can help guide clinical decision making for these patients.

10-year outcomes of technically unresectable oral cancers with neoadjuvant chemotherapy: Real-world data and implications for clinical practice.

6085 Background: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in progression free survival (PFS) and overall survival (OS) over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. Methods: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who received NACT. Adults with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 deemed technically unresectable in a multi-disciplinary clinic were included. All patients received 2-3 cycles of 3-weekly NACT. Patients with good general condition (GC) who became resectable underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on GC. The OS was calculated from date of diagnosis to date of death. Kaplan-Meier method was used for estimation of 10-year OS and impact of different regimens on OS was calculated using the log-rank method. Results: A total of 3266 patients were analysed, of which 2857 (87.5%) were males. The median age was 46 years (IQR: 39 - 54). The most common subsites were buccal mucosa (54.7%), tongue (30.4%) and alveolus (7.9%). Patients presented with either stage IVA (51.3%) or IVB (48.7%). The major indications for NACT were edema up to zygoma (42.2%), involvement of hyoid (22.6%), and high infra-temporal fossa (11.5%). The most common NACT was Docetaxel-Cisplatin (50.2%) followed by Docetaxel-Cisplatin-5-Fluorouracil (29.0%) and Paclitaxel-Carboplatin (13.3%). Planned number of NACT cycles could not be completed by 361 (11.1%) patients. Of 3266 patients, 929 (28.4%) underwent surgery followed by adjuvant CTRT (26.7%) or adjuvant RT (1.3%); 13.1% underwent definitive CTRT, 35.8% received palliative chemotherapy, while 11.7% defaulted for definitive treatment. Pathological complete response was seen in 76 (8.2%) patients, while 871 (93.8%) achieved negative margins and 338 (36.4%) had extra-nodal extension. The median OS was 9 months (95% CI: 8.6 – 9.4). NACT with more than 2-drugs had an OS of 13.2 months (95% CI: 12 – 14.4) vs 7.5 months (95% CI: 7.1 – 7.97) for 2-drug regimens. The 10-years OS was also higher for more than 2-drugs regimen - 21% (95% CI - 17.4% – 24.9%) vs 5.14% (95% CI: 3.28% - 7.6%) (p = 0.000). 10-years OS of patients who underwent surgery vs those who did not was 22.28% vs 3.98% (p = 0.000). Conclusions: NACT with more than 2-drug regimens had survival benefit over 2-drug regimens in technically unresectable OCSCC.

Predictors of survival in advanced oral cancers after salvage surgery with free tissue flap reconstruction

ObjectiveTo identify prognostic factors for patients with advanced persistent, recurrent, or 2nd primary oral cavity squamous cell carcinoma (OCSCC) potentially unsuitable for salvage surgery with free tissue flap (FTF) reconstruction.Materials and methodsA population-based cohort of 83 consecutive patients with advanced OCSCC who underwent salvage surgery with FTF reconstruction at a tertiary referral centre between 1990 and 2017. Retrospective uni- and multivariable analyses were performed to identify factors affecting all-cause mortality (ACM), i.e., overall survival (OS), as well as disease-specific mortality (DSM), i.e., disease-specific survival (DSS) after salvage surgery.ResultsMedian disease-free interval until recurrence was 15 months with recurrent stage I/II in 31% and III/IV in 69%. Median age at salvage surgery was 67 years (range 31–87) and the median follow-up (alive patients) 126 months. At 2, 5, and 10 years after salvage surgery, respectively, DSS rates were 61%, 44%, and 37% and OS rates 52%, 30%, and 22%. Median DSS was 26 and OS 43 months. Multivariable analysis identified recurrent clinical regional (cN-plus) disease [HR 3.57; p < .001] and elevated gamma-glutamyl transferase (GGT) [HR 3.30; p = .003] as independent pre-salvage predictors for poor OS after salvage, whereas initial cN-plus [HR 2.07; p = .039] and recurrent cN-plus disease [HR 5.14; p < .001] predicted poor DSS. Among post-salvage factors, extranodal extension according to histopathology [HR ACM 6.11; HR DSM 9.99; p < .001] as well as positive [HR ACM 4.98; DSM 7.51; p < 0.001] and narrow surgical margins [HR ACM 2.12; DSM HR 2.80; p < 0.01] emerged as independent factors for poor survival.ConclusionWhile salvage surgery with FTF reconstruction is the primary curative option for patients with advanced recurrent OCSCC, the present findings may help guide discussions with patients who have advanced recurrent regional disease and high GGT preoperatively, especially if there is a small chance of reaching surgical radicality.

The effect of insurance status on treatment modality in advanced oral cavity cancer

BackgroundInsurance status has been shown to impact survival outcomes. We sought to determine whether insurance affects the choice of treatment modality among patients with advanced (T4) oral cavity squamous cell carcinoma.MethodsThis is a retrospective, population-based cohort study using the Survival, Epidemiology, and End Results Program database. The population included all adult (age ≥ 18) patients with advanced (T4a or T4b) oral cavity squamous cell carcinoma diagnosed from 2007 to 2016. The main outcome was the odds of receiving definitive treatment, defined as primary surgical resection. Insurance status was categorized into uninsured, any Medicaid, and insured groups. Univariable, multivariable, and subgroup analyses were performed.ResultsThe study population consisted of 2628 patients, of whom 1915 (72.9%) were insured, 561 (21.3%) had Medicaid, and 152 (5.8%) were uninsured. The multivariable model showed that patients who were 80 years or older, unmarried, received treatment in the pre-Affordable Care Act (ACA) period, and who were on Medicaid or uninsured were significantly less likely to receive definitive treatment. Insured patients were significantly more likely to receive definitive treatment compared to those on Medicaid or uninsured (OR = 0.59, 95% CI 0.46–0.77, p < 0.0001 [Medicaid vs. Insured]; and OR = 0.48, 95% CI 0.31–0.73 p = 0.001 [Uninsured vs. Insured]), however these differences did not persist when considering only those patients treated following the 2014 expansion of the ACA.ConclusionsInsurance status is significantly associated with treatment modality among adults with advanced stage (T4a) oral cavity squamous cell carcinoma. These findings support the premise of expanding insurance coverage in the US.Graphical

Impact of induction chemotherapy on Resectability in Locally advanced oral cavity Carcinomas

Purpose: We aim to assess resectability in patients with locally advanced oral cavity squamous cell carcinomas with induction chemotherapy (ICT). Methods: All stage III-IVB oral squamous cell carcinoma patients with borderline resectable (suspected R1) or unresectable disease (stage IVB, except internal carotid artery encasement or pterygoid plate or skull base involvement) recruited between January 2020 and August 2021 at a tertiary care hospital received 2-3 cycles of ICT (standard TPF regimen) followed by a surgical assessment. The primary aim was to evaluate the proportion of patients that became resectable by ICT. Results: Out of 40 patients, 21 were unresectable (stage IVB disease), and 19 were borderline resectable (stage IVA disease) with doubtful resection margins as per the multi-disciplinary discussion. After chemotherapy, 21 patients became resectable (13 out of 19; and 8 out of 21). Thus, resectability was achieved in 52.5% of patients (32.5% for stage IVA and 20% for stage IVB). The median overall survival (OS) in patients who underwent surgery was 20.5 months (95% CI: 16.95-28.25 months) versus 8.0 months (95% CI: 5.74-13.46 months) in patients who remained unresectable after induction chemotherapy (p=0.0001). Conclusions: In our study, induction chemotherapy leads to improved surgical resection rates with acceptable toxicities in a significant proportion of unresectable locally advanced oral cancers, with improved overall survival significantly.

Contralateral Neck Irradiation Can Be Omitted for Selected Lateralized Oral Cancer in Locally Advanced Stage.

(1) Background: To investigate the contralateral neck failure (cRF) rates and outcomes among patients with well-lateralized locally advanced oral cavity squamous cell carcinoma (OSCC) with/without ipsilateral or bilateral neck adjuvant irradiation. (2) Methods: Patients with lateralized OSCC diagnosed between 2007 and 2017 were retrospectively enrolled. Patients who had undergone curative surgery with pathologically proven pT3/4 or pN0-2b without distant metastasis were included, while those with cross-midline, neck-level 1a involvement and positive extra-nodal extension (ENE) were excluded. The primary endpoint was the cumulative incidence of 5-year cRF as the first site of failure. The secondary endpoints included cancer-specific survival (CSS), local-regional recurrence-free survival (LRRFS), distant-metastasis-free survival (DMFS), and contralateral-regional recurrence-free survival (cRRFS). (3) Results: In total, 149 patients were analyzed with a median follow-up time of 5.2 years (range, 2.91–7.83). Pathological stages T3 and T4 were 22.7% and 56.8%, respectively. Pathologically negative and positive lymph nodes were 61.4% and 38.6%, respectively. The cumulative 5-year cRF rate was 3.6% (95% CI, 1.3–7.7%). No significant differences in the 5-year CSS, LRRFS, DMFS, and cRRFS were observed among those undergoing unilateral or bilateral neck irradiation. Five patients (3.4%) had contralateral neck recurrence, all simultaneously with local recurrence. No isolated contralateral neck recurrence was identified. (4) Conclusions: The cRF rate was acceptably low in patients with well-lateralized advanced OSCC with the initially uninvolved contralateral neck. Omitting contralateral neck irradiation with active surveillance could be considered without compromising the cure rate in locally advanced OSCC patients.

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients

Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, is currently approved by the US Food and Drug Administration for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The potential neoadjuvant role of programmed cell death 1 inhibitors in primary surgical management of HNSCC and effects on surgical outcomes are poorly understood. To evaluate the incidence of postoperative adverse events in treatment-naive patients with advanced oral cavity cancer receiving neoadjuvant pembrolizumab when compared with matched controls, as part of a window-of-opportunity multi-institutional clinical trial assessing neoadjuvant pembrolizumab for locally advanced HNSCC. This retrospective cohort study at a single tertiary academic institution included treatment-naive patients with local regionally advanced oral cavity squamous cell carcinoma (OCSCC) who were undergoing surgical resection. Patients with local regionally advanced resectable OCSCC who received neoadjuvant pembrolizumab were retrospectively reviewed for postoperative adverse events. Controls were matched by age, race, smoking status, and overall cancer stage based on historical data at the same institution. Matched-cohort analysis was performed using a McNemar test to assess differences between the groups. Incidence of adverse events following surgical resection of advanced OCSCC within 30 days of surgery and on continued follow-up. A total of 64 patients (32 as part of the prospective clinical trial and 32 as controls; mean [SD] age, 59.6 [10.3] years; 28 [44%] women) were included in the analysis. Postoperative adverse events in the 32 patients receiving pembrolizumab included lymphedema (n = 20 [63%]), trismus (n = 7 [22%]), return to operating room (n = 7 [22%]), wound infection (n = 7 [22%]), fistula (n = 6 [19%]), wound dehiscence (n = 4 [13%]), flap failure (n = 3 [9%]), and hematoma (n = 2 [6%]). The matched control group demonstrated similar complication rates without considerable differences, except for trismus (n = 16 [50%]), which was greater by a difference of 28.1% (95% CI, 5.6%-50.6%) in the control group. This cohort study examined surgical complications among patients with local regionally advanced OCSCC treated with neoadjuvant pembrolizumab and found that serious adverse events were similar to those in patients who underwent standard-of-care treatment. This suggests that there is no increased perioperative morbidity in the use of preoperative treatment with immunotherapy. Further prospective studies are needed to validate these findings for oral cavity cancer and other subsites of the head and neck.

Neoadjuvant immunoradiotherapy in patients with locally advanced oral cavity squamous cell carcinoma: a retrospective study.

Although anti-programmed death receptor-1 (PD-1) agents have been evaluated in the neoadjuvant setting for the treatment of locally advanced head and neck cancer, including oral cavity squamous cell carcinoma (OCSCC), the overall response rate is modest. The aim of the present study was to evaluate the efficacy and safety of neoadjuvant nivolumab in combination with stereotactic body radiotherapy (SBRT) for the treatment of locally advanced OCSCC. OCSCC patients who underwent surgical resection within 6months of treatment with nivolumab plus SBRT from December 2018 to February 2021 were analyzed retrospectively. All 30 eligible patients enrolled in this study well tolerated the neoadjuvant treatment with no serious adverse events (AEs). Of them, 27 patients (90.0%) achieved R0 resection, and 5 patients (16.7%) experienced procedure-associated complications. The complete response (CR), partial response (PR) and stable disease (SD) were 10.0%, 46.7% and 43.3% respectively. The major pathological response (MPR), complete pathological response (pCR) and clinical to pathological downstaging rate were 60.0%, 33.3% and 83.3% respectively. During the median follow-up period of 13.5months, 26 patients (86.7%) who underwent surgical resection remained alive. The disease-free survival (DFS) and overall survival (OS) at 24months were 70.4% and 76.4% respectively. Neoadjuvant nivolumab plus SBRT is safe and efficacious, and could be used as a potential neoadjuvant option for the treatment of patients with locally advanced OCSCC.

Prognostic Implications of Skin Invasion in Locally Advanced Oral Cavity Squamous Cell Carcinoma.

To evaluate the effect of histopathologic skin invasion on 2- and 5-year disease-free survival (DFS) and overall survival (OS) in patients treated with primary surgery for locally advanced oral cavity squamous cell carcinoma (OCSCC). A retrospective case-control study was performed comparing previously untreated patients with pT4a OCSCC with and without skin invasion. Academic medical center. Propensity score-matched cohorts were derived by age, sex, surgical margins, pathologic N classification, adjuvant treatment, and primary tumor site. The Kaplan-Meier method was used to evaluate 2- and 5-year OS and DFS, which were compared between cohorts via the log rank (Mantel-Cox) test statistic. Overall 25 patients were identified to have pathologic skin invasion, and 50 were selected for the matched control group. OS was significantly lower for patients with skin invasion as compared with controls at 2 years (30.8% vs 53.3%, P = .018) and 5 years (16.6% vs 42.2%, P = .01). DFS was significantly lower for patients with skin invasion vs controls at 2 years (23.7% vs 47.7, P = .037) and 5 years (15.8% vs 41.4%, P = .024). Histopathologic skin invasion in OCSCC is associated with dismal prognosis in patients who underwent primary surgical treatment. OS outcomes for patients with skin invasion are comparable to survival of patients with recurrent/metastatic disease and T4N2 disease.