Advanced Oral Cavity Squamous Cell Carcinoma Research Articles

Socioeconomic Status, Length of Stay, and Postoperative Complications in Oral Cavity Squamous Cell Carcinoma.

Background: Despite universal healthcare in Canada, low socioeconomic status (SES) has been associated with worse survival in oral cavity squamous cell carcinoma (OCSCC) patients. However, the relationship between SES and outcomes during the acute postoperative period is poorly defined. Hamilton, Ontario, presents a unique population with widely varying SES within the same geography. The objective of this study was to examine the relationship between SES, length of hospital stay (LOHS), and postoperative complications in OCSCC. Methods: Newly diagnosed OCSCC patients receiving primary surgical treatment from 2010 to 2014 were identified within a prospectively collected database. Inclusion criteria included age >18 years old, pathological diagnosis of oral cavity cancer, and primary surgical treatment with curative intent. Patients were excluded if they were undergoing palliative treatment or had previous head and neck surgery/radiotherapy. Postal codes were used to identify neighborhood-level socioeconomic variables via 2011 Canada Census data. Income quartiles were defined from groups of neighboring municipalities based on Canada Census definitions. Demographic, social, pathological, staging, and treatment data were collected through chart review. Results: One hundred and seventy-four patients were included in the final analysis. OCSCC patients with lower SES were more likely to be younger (P = .041), male (P = .040), have significant tobacco and alcohol use (P = .001), higher Charlson Comorbidity Index (CCI; P = .014), lower levels of education (P = .001), and have lower employment levels (P = .001). Lower SES patients had higher clinical tumor (P = .006) and clinical nodal (P = .004) staging and were more likely to receive adjuvant therapy (P = .001) and G-tubes (P = .001). Multivariable regression analysis showed that low SES was a statistically significant predictor of postoperative complications [β 2.50 (95% confidence interval (CI) 0.200, 3.17); P = .014] and LOHS [β 2.03 (95% CI 1.06, 2.99); P = .0001]. Tobacco and alcohol use, clinical tumor, and nodal stage, CCI, and planned adjuvant therapy were also statistically significant predictors of postoperative complications and LOHS (P < .05). Conclusion: Patients with lower SES have more advanced OCSCC disease with increased comorbidities that owes itself to more acute postoperative complications and LOHS within this study population. Patients with low SES should be identified as patients that require more support during their cancer treatment.

Prospective Evaluation of Locoregional Control in Oral Cavity Squamous Cell Carcinoma with Infratemporal Fossa Involvement Treated with Surgery and Adjuvant Concurrent Chemoradiotherapy

Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancer in India. Definitive surgery with or without post-op radiotherapy (PORT) with or without chemotherapy (CT) provides better outcomes in locally advanced OCSCC as compared to definitive chemoradiotherapy. T4b OCSCC with infra temporal fossa (ITF) involvement has varied outcome depending on the extent of ITF involvement, with low and mid ITF having relatively favorable prognosis. We aimed to prospectively evaluate outcomes in patients of OCSCC with low or mid ITF involvement treated with curative surgery followed by adjuvant concurrent chemoradiotherapy (CCRT). A total of 20 patients of T4b OCSCC (as per AJCC 8th edition) with low or mid ITF involvement were included in this single arm prospective interventional study from January 2021 to October 2022. Patients with involvement of skull base, carotid artery, prevertebral fascia and/or pterygomaxillary fissure were excluded. All patients were treated with definitive surgery with ITF clearance followed by adjuvant CCRT as indicated. Loco-regional control (LRC), Disease free survival (DFS), Overall survival (OS) were assessed using Kaplan-Meier survival analysis. Acute toxicities were assessed according to the CTCAE v5.0. Patient characteristics are summarized in table 1. Median follow-up was 11.5 months (4-21months). All patients received adjuvant CCRT with weekly cisplatin 40mg/m2 to a median number of 6 cycles (5-7 cycles). Median RT dose was 64Gy (60-64Gy). All patients tolerated treatment well. Grade 3 oral mucositis, odynophagia were seen in 8 (40%) patients each and skin toxicity, oral pain in 6 (30%) and 5 (25%) patients respectively. No grade 4 toxicities were observed LRC at three month was 73.68% with 4 local and 1 locoregional failure only. LRC at one year was 36.8% with 8 local, 1 locoregional, 2 locodistant and 1 distant failure only. Median DFS was 10.4 months. Median OS was not reached; four patients died. LRC at three months was better for patients with low ITF disease as compared to mid ITF disease (85.7% vs. 40% (p = 0.04) and at one year was 42.8% vs. 40% (p = 0.50). Selected patient of locally advanced OCSCC with low ITF involvement may benefit from trimodality therapy of surgery with ITF clearance followed by adjuvant CCRT. Acute toxicity profile was acceptable in our study.

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.

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.

Survival-Weighted Health Profiles in Patients Treated for Advanced Oral Cavity Squamous Cell Carcinoma

ObjectivesFor patients with oral cavity squamous cell carcinoma (OSCC), particularly for those with advanced disease, quality of life (QoL) is a key outcome measure. Therefore, we estimated survival-weighted psychometric scores (SWPS), life expectancy (LE), and quality-adjusted LE (QALE) in patients with advanced OSCC.Methods and MaterialsFor estimation of survival function, we enrolled 2313 patients with advanced OSCC diagnosed between January 1, 2007, and December 31, 2013. The patients were followed until death or December 31, 2014. To acquire the QoL data, data from 194 patients were collected by employing the Taiwan Chinese versions of the Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Head and Neck 35 developed by the European Organisation for Research and Treatment of Cancer and the EQ-5D-3L between October 1, 2013, and December 31, 2017. The LE of the patients with OSCC were estimated through linear extrapolation of a logit-transformed curve. SWPS and QALE were determined by integrating the LE and corresponding QoL outcomes.ResultsFor the patients with advanced OSCC, the estimated LE and QALE were 8.7 years and 7.7 quality-adjusted life years (QALYs), respectively. The loss of LE and QALE was 19.0 years and 20.0 QALYs, respectively. The estimated lifetime impairments of swallowing, speech, cognitive functioning, physical functioning, social functioning, and emotional functioning were 8.3, 6.5, 6.5, 6.1, 5.7, and 5.4 years, respectively. The estimated lifetime problems regarding mouth opening, teeth, social eating, and social contact were 6.6, 6.1, 7.5, and 6.1 years, respectively. The duration of feeding tube dependency was estimated to be 1.6 years.ConclusionsPatients with advanced OSCC had an estimated LE of 8.7 years and QALE of 7.7 QALYs. SWPS provided useful information regarding how advanced OSCC affects the subjective assessment of QoL. Our study results may serve as a reference for the allocation of cancer treatment resources.

Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma.

Simple SummaryA comprehensive analysis based on mutational signatures and oncogenic signaling pathways to identify a specific subgroup of patients that had a significantly negative impact on both disease-free and overall survival in oral cavity squamous cell carcinoma (OCSCC) from whole exome-sequencing data. This analysis has revealed a variety of biologically relevant candidate target genes. Thirty percent of 165 tumors had multiple targetable alterations in multiple pathways. This suggests the complex interplay and crosstalk of oncogenic signaling pathways play an important role on the outcome of patients with OCSCC, and the candidate genes and pathways identified may include prognostic genetic biomarkers or therapeutic targets for OCSCC.Mutational profiling of patients’ tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (p = 0.0005) and overall survival (p = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (p = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy

PurposeTo assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. Material and methodsData from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. ResultsOverall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. ConclusionTNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Role of induction chemotherapy for oral cavity squamous cell carcinoma.

Patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC) have a poor survival outcome. Treatment involves extensive surgery, adjuvant radiation, or chemoradiation and results in high morbidity. In this study, the authors' objective was to evaluate their experience with induction chemotherapy (IC) in the treatment of locoregionally advanced OCSCC. A retrospective review of the medical records of all patients with locoregionally advanced (stage III and IV) OCSCC who received IC followed by definitive local therapy was conducted. Outcomes included response to IC and survival. In total, 120 patients were included in the study. The overall stage was stage IV in 79.2% of patients. After 2 cycles of IC, 76 patients (63.3%) achieved at least a partial response, including 13 who had a complete response. Stable disease was observed in 30 patients (25%), and 14 patients (11.7%) had progressive disease. Among responders, 16 patients received definitive chemoradiation or radiation therapy, and 60 underwent surgical resection, of whom 15 had less extensive surgery than was originally planned. Overall, organ preservation was achieved in 40.8% of patients who had a favorable response to IC. The 5-year overall and disease-specific survival rates were 51.4% and 66.9%, respectively. Patients who had at least a partial response had better 5-year overall survival (60.1%) and disease-specific survival (78.5%) compared with nonresponders (33.8% and 46.4%, respectively). The results demonstrate a response rate to IC in patients with advanced OCSCC similar to what has been observed in patients with cancer in other head and neck subsites. Patients who achieved at least a partial response to IC had a more favorable outcome, with ensuing organ preservation. Further studies are warranted.

Postoperative Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Advanced Oral Cavity Cancer in the Era of Modern Radiation Techniques.

Background/PurposeSurgery followed by postoperative radiotherapy (RT) has been considered the standard treatment for oral cavity squamous cell carcinoma (OCSCC) of advanced stages or with adverse prognostic factors. In this study, we compared the outcomes in patients with OCSCC who received postoperative concurrent chemoradiotherapy (CCRT) or postoperative RT alone using modern RT techniques.MethodsA total of 275 patients with OCSCC treated between 2002 and 2018 were retrospectively analyzed. Adverse prognostic factor was defined as extranodal extension (ENE), microscopically involved surgical margin, involvement of ≥2 lymph nodes, perineural disease, and/or lymphovascular invasion (LVI). In total, 148 patients (54%) received CCRT and 127 patients (46%) received RT alone. More patients in the CCRT group had N3 disease and stage IVB disease (46.6% vs. 10.2%, p<0.001), ENE (56.1% vs. 15.7%, p<0.001), LVI (28.4% vs. 13.4%, p=0.033).ResultsWith a median follow-up of 40 (range, 5–203) months, there were no significant differences in the 5-year overall survival (OS) and PFS between treatment groups. In the subgroup analysis according to high risk, the concurrent use of chemotherapy showed significantly improved OS in patients with ENE (HR 0.39, p=0.003).ConclusionOur retrospective study showed that postoperative CCRT group had comparable survival outcomes to those in the RT alone group for advanced OCSCC in the era of modern RT techniques and indicated that concurrent chemotherapy should be administered to patients with ENE. Prospective randomized studies for confirmation are needed.

Predictors of early progression after curative resection followed by platinum-based adjuvant chemoradiotherapy in oral cavity squamous cell carcinoma

ABSTRACT Objectives Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown. Methods In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical–pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for DFIs. Survival was estimated using the Kaplan–Meier method and log-rank tests, and a scoring system for predicting early progression was established. Results One-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0–1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or <2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively. Conclusions The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.

Predictive score for recurrence after complete resection in locally advanced oral cavity squamous cell carcinoma.

e17536 Background: Early progression, usually defined disease-free interval (DFI) less than six months after completing adjuvant platinum-based chemoradiotherapy (CRT), has very poor outcome for oral cavity squamous cell carcinoma (OCSCC). But there are no biomarkers to predict such early progression. Methods: Locally advanced OCSCC patients, after complete surgical resection and followed-up platinum-based adjuvant CRT, were retrospectively enrolled from Chung Shan Medical University Hospital (CSMUH, training cohort) and Taipei Veterans General Hospital (TPE-VGH, validating cohort) in Taiwan. Clinicopathologic variables of patients with DFI &lt; or ≥ 6 months were compared by using the χ2 test. The Cox proportional hazards model was applied to identify independent factors for DFI. Survival was estimated using the Kaplan-Meier method and log-rank test. Results: A total of 350 high-risk OCSCC patients were enrolled, including 146 patients in training cohort and 204 in validating cohort. In multivariate Cox regression, pN &gt; 0, extracapular spread, and depth of invasion ( ≥ 1cm) were independent factors for DFI in training cohort. If each factor scored one point, the scoring system could effectively predict early progression that sensitivity/specificity/area under curve (AUC) of training and validating cohort were 57.7%/91.2%/0.771 and 58.1%/83.9%/0.730, respectively (the cutoff level ≤ 2 or &gt; 2). DFI between lower- (score 0–2) and high- (score 3) risk groups were also significantly different in both training (median DFI, 59.6 vs. 4.5 months, P &lt; 0.001) and validating cohorts (NA vs. 9.3 months, P &lt; 0.001). Conclusions: The established score system was effective to predict early progression after adjuvant CRT for locally advanced OCSCC.

Clinical impact of PET/CT imaging after adjuvant therapy in patients with oral cavity squamous cell carcinoma.

This single-center retrospective study of prospectively collected data was aimed at comparing the clinical outcomes of positron emission tomography/computed tomography (PET/CT) for patients with oral cavity squamous cell carcinoma (OSCC) with symptomatic recurrences identified by PET/CT imaging following adjuvant therapy (Group A) versus those of cases with asymptomatic recurrences diagnosed through periodic post-adjuvant therapy PET/CT surveillance (Group B). We also sought to establish the priority of salvage therapy in the two study groups. We identified 111 patients with advanced resected OSCC who developed recurrences following adjuvant therapy (51 in Group A and 60 in Group B). Histopathology served as the gold standard for recurrent lesions. The impact of post-adjuvant therapy PET/CT surveillance was examined with Kaplan-Meier curves and Cox proportional hazards regression models. The 2-year DSS and OS rates were marginally or significantly higher in Group B than in Group A (P=0.073 and P=0.025, respectively). Time-dependent ROC curve analysis demonstrated that the optimal cutoff values for time to positive PET/CT findings in relation to OS were 12months for Group A and 9months for Group B, respectively. Independent risk factors identified in multivariate analyses were used to devise two prognostic scoring systems for 2-year DSS and OS in each study group (all P<0.001). Scheduled periodic PET/CT surveillance is a valuable tool for early detection of recurrent lesion(s) in asymptomatic OSCC patients who bear risk factors for disease recurrence. The presence of clinical symptoms and a short time to positive PET/CT findings were adverse prognostic factors for clinical outcome in patients with advanced OSCC. The priority of salvage therapy is discussed in each patient subgroup according to the devised prognostic scoring systems.

Differences in Survival With Surgery and Postoperative Radiotherapy Compared With Definitive Chemoradiotherapy for Oral Cavity Cancer

Because locally advanced oral cavity squamous cell carcinoma (OCSCC) is often treated with surgery followed by postoperative radiotherapy (S+PORT), the effectiveness of organ preservation with concurrent chemoradiotherapy (CRT) remains unclear. To compare the differences in survival between patients with locally advanced OCSCC treated with S+PORT or CRT. Using the National Cancer Database, this study compared 6900 patients with stage III to IVA OCSCC treated with S+PORT and CRT from 2004 through 2012 at academic and community-based cancer clinics. Comparisons were made using Kaplan-Meier methods and Cox proportional hazards regression models using the entire cohort and a propensity score-matched cohort of 2286 patients. Overall survival (OS). Of the 6900 study patients, 4809 received S+PORT (3080 male [64.0%] and 1792 [36.0%] female) and 2091 received CRT (1453 male [69.5%] and 638 [30.5%] female). Median follow-up for the entire group was 23.0 months overall but was shorter for patients receiving CRT (17.3-month) vs S+PORT (25.6 months). Patients receiving CRT were more likely to be older than 60 years, treated before 2007, live within 10 miles of the treating facility, treated at nonacademic centers, have more comorbidities, have T3 to T4a tumors, and have N2a to N2c nodal disease. Propensity score matching identified cohorts of patients with similar clinical variables. S+PORT was associated with improved survival among all patients (3-year OS: 53.9% for S+PORT vs 37.8% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) and in the propensity score-matched cohort (3-year OS: 51.8% for S+PORT vs 39.3% for CRT; difference = 11.9%; 95% CI, 7.8%-16.0%). S+PORT was associated with improved survival among patients with T3 to T4a tumors (3-year OS: 49.7% for S+PORT vs 36.0% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) but was not associated with improved survival among patients with T1 to T2 tumors (3-year OS: 59.1% for S+PORT vs 53.5% for CRT; difference = 5.6%; 95% CI, -3.1% to 14.3%). Compared with CRT, S+PORT was associated with improved survival for locally advanced OCSCCs, especially in T3 to T4a disease. These data support the use of surgery as the initial treatment modality for operable OCSCCs.

Survival outcomes of patients with advanced oral cavity squamous cell carcinoma treated with multimodal therapy: a multi-institutional analysis.

BackgroundThe oral cavity is the most common site for head and neck squamous cell carcinoma. Treatment of advanced stage oral cavity squamous cell carcinoma (OCSCC) has classically involved surgical resection with postoperative adjuvant radiotherapy (S-RT).Despite this aggressive dual modality therapy, the disease outcomes have remained poor. The treatment options expanded in 2004 when two international trials showed the addition of postoperative chemotherapy to radiation improved outcomes. These trials were, however not oral cavity site specific.ObjectiveTo assess survival outcomes of advanced OCSCC treated by differing modalities. The primary goal was to determine if the addition of postoperative chemotherapy (S-CRT) improves survival compared to other treatment regimens.MethodsDemographic, pathologic, treatment, and survival data was obtained from patients diagnosed with OCSCC from 1998–2010 in Alberta, Canada. 222 patients were included in the final analysis from 895 OCSCC patients. Actuarial overall, disease-specific, disease-free, and metastasis-free survivals were estimated with Kaplan-Meier and Cox regression analyses. Patients were grouped by treatment.ResultsPatients receiving S-CRT had improved overall, disease-specific, disease-free, and metastasis-free survival compared to S-RT, CRT or RT(p < 0.05). Two and five year estimated overall survival was significantly higher in the S-CRT group at 77 and 58% (p < 0.05), versus S-RT with 55 and 40% rates(p < 0.05). Results were similar for disease-specific, disease-free, and metastasis free survival with S-CRT being favoured. Patients with extracapsular spread (ECS) treated with S-CRT versus S-RT had 55% survival advantage at 5 years (p < 0.05).ConclusionThis study shows that adding adjuvant chemotherapy to S-RT improves survival outcomes in advanced OCSCC, especially in patients with ECS.

Human Papillomavirus-16 Infection in Advanced Oral Cavity Cancer Patients Is Related to an Increased Risk of Distant Metastases and Poor Survival

BackgroundHuman papillomavirus (HPV) is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC) remains ambiguous.ObjectiveThis study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy.Patients and MethodWe prospectively followed 173 patients with advanced OSCC (96% were stage III/IV) who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival.ResultsThe prevalence of HPV-positive OSCC was 22%; HPV-16 (9%) and HPV-18 (7%) were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4–8.0; P = 0.005), disease-free survival (P = 0.037), disease-specific survival (P = 0.006), and overall survival (P = 0.010), whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥11-mm group and patients without risk factors (P<0.001).ConclusionsHPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.

Induction chemotherapy for organ preservation versus surgery for advanced oral cavity squamous cell carcinoma (OCSCC).

e16014 Background: The objective of the study is to evaluate the outcomes of an induction selection (IS) concurrent chemotherapy protocol versus primary surgical extirpation in advanced OCSCC. Methods: Retrospective quasi-experimental comparison of patients treated by IS versus surgery. The cohorts were matched based on pretreatment characteristics and compared in an intent-to-treat model.19 patients were accrued with resectable stage III/IV OCSCC without bone involvement between 2000-2002 into a phase II IS trial using 1 cycle of IS to select patients for definitive chemoradiation (CRT). Tumor response was evaluated 3-weeks post-infusion. Patients with &gt;50% response underwent concurrent CRT (70Gy; 35 fractions with concurrent cisplatin 100mg/m2 or carboplatin (AUC 6) every 3-weeks for 3 cycles). Those with &lt;50% underwent surgical treatment and radiation therapy. A comparison cohort of patients with primary surgical extirpation was selected from an OCSCC database from 1998-2009. The surgical cohort of 53 patients was identified based on comparable pretreatment variables to the IS cohort. There was no difference in age, gender, pre-treatment AJCC stage, T-class, N-class, smoking status, alcohol status, or subsite between the two cohorts. Results: Kaplan-Meier estimates demonstrated overall survival (OS) at 5-years was 32% in the IS group and 64% in the surgical cohort. Disease-specific survival (DSS) at 5-years was 46% in the IS group and 76% in the surgical cohort. Local-regional control (LRC) at 5-years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better OS, DSS and LRC (p=0.03, p=0.001 and p=0.0002 respectively) in the surgical cohort compared to the IS cohort. Conclusions: Primary surgical treatment showed significantly better OS, DSS and LRC compared to IS in this quasi-experimental designed comparison. These findings support surgery as the principal treatment for OCSCC.