A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Mean corpuscular volume as a prognostic factor for 30-day mortality in major trauma patients: a retrospective cohort study.

We investigated the clinical implications of the mean corpuscular volume (MCV) in patients with major trauma. This single-center retrospective review included 2021 trauma patients admitted to the intensive care unit between January 2016 and June 2020. We included 1218 patients aged [Formula: see text] 18 years with an injury severity score [Formula: see text] 16 in the final analysis. The clinical and laboratory variables were compared between macrocytosis (defined as MCV [Formula: see text] 100 fL) and non-macrocytosis groups. Cox regression analysis was performed to calculate the hazard ratios (HRs) of variables for 30-day mortality, with adjustment for other potential confounding factors. The initial mean value of MCV was 102.7 fL in the macrocytosis group (n = 199) and 93.7 fL in the non-macrocytosis group (n = 1019). The macrocytosis group showed a significantly higher proportion of initial hypotension, transfusion within 4 and 24 h, and 30-day mortality than the non-macrocytosis group. Age ([Formula: see text] 65 years), hypotension (systolic blood pressure [Formula: see text] 90 mmHg), transfusion (within 4 h), anemia (Hb < 12 g/day in women, < 13 g/day in men), and macrocytosis were significantly associated with 30-day mortality (adjusted HR = 1.4; 95% confidence interval 1.01-1.94; p = 0.046) in major trauma patients. Thus, initial macrocytosis independently predicted 30-day mortality in patients with major trauma at a Level I trauma center.

Transoral robotic vertical partial laryngectomy (hemilaryngectomy) extended to the hypopharynx.

Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.

Transoral robotic surgery in oropharyngeal squamous cell carcinoma: A comparative study between da Vinci Single-Port and da Vinci Xi systems.

BACKGROUND: The recently developed da Vinci single-port (SP) system offers potential advantages in maneuverability within narrower surgical spaces. This study aims to compare intra- and post-operative outcomes, technical advantages, and limitations of transoral resections using the da Vinci SP and da Vinci Xi systems for oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A single-center retrospective cohort study included patients with OPSCC who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT). Data on pre-operative variables, intraoperative data, postoperative complications, and functional outcomes were collected. RESULTS: A total of 209 patients (males: 175; mean age: 59.0 ± 9.3) were included (SP: n = 136; Xi: n = 73). A significantly lower docking time was measured for the SP group (5.7 ± 2.5 min vs. 10.0 ± 4.4 min; p <.001). Similarly, the console time was reduced for the SP group though not reaching statistical significance (76.3 ± 30.7 min vs. 88.1 ± 36.9 min; p =.06). A greater proportion of patients showed wide negative resection margins in the SP group (71 % vs. 56 %; p =.10), although not statistically significant. No significant differences were observed in complication rates or postoperative functional outcomes. DISCUSSION: This study demonstrates the safety and efficacy of the da Vinci SP system in oropharyngeal surgery, with potential advantages in terms of reduced docking and console times. The findings suggest that the SP system offers improved maneuverability and instrument placement compared to the da Vinci Xi system.

Successful endovascular treatment of an obstruction following the surgical repair of a traumatic portal vein injury: a case report.

Traumatic portal vein injury is rare, but the associated mortality rate ranges from 50% to 70%. The management of this injury is difficult and remains controversial. In this case report, we describe the successful endovascular treatment of an obstruction that developed following the surgical repair of a traumatic portal vein injury. A man in his mid-40s who had been injured in a car accident presented to our trauma center with abdominal pain, abdominal distension, and open wounds over both knees. Emergency laparotomy revealed a longitudinal rupture from the upper border of the pancreas to the mid-portion of the portal vein; his hemorrhage was successfully controlled surgically. However, postoperative abdominal computed tomography imaging revealed portal vein obstruction. One week after admission to the intensive care unit, an endovascular stent was successfully inserted into the patient's portal vein via a percutaneous transhepatic approach. The associated injuries, including the distal common bile duct obstruction, were successfully managed by choledochojejunostomy. The patient's postoperative recovery was uneventful. Thus, endovascular stent placement is an effective and safe means of treating an obstruction following the surgical repair of a traumatic portal vein injury.

Neo-adjuvant chemotherapy and transoral robotic surgery in locoregionally advanced oropharyngeal cancer.

PURPOSE: To analyze the oncological outcomes and patterns of recurrence of patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) who underwent neo-adjuvant chemotherapy (NCT) with subsequent transoral robotic surgery (TORS). METHODS: A single-center retrospective cohort study was performed, including 198 patients (mean age: 58.6, SD: 9.2). The primary outcome was disease-free survival (DFS). RESULTS: The median follow-up time was 26.5 months (IQR: 16.0-52.0). Estimated DFS rates (95 % CI) at 1 and 3 years were 86.6 % (81.9-91.7), and 81.4 % (75.7-87.6), respectively. Estimated DSS rates (95 % CI) at 1 and 3 years were 96.7 % (94.1-99.3), and 92.6 % (88.4-97.0), respectively. Estimated OS rates (95 % CI) at 1 and 3 years were 96.2 % (93.4-99.0), and 88.7 % (83.4-94.2), respectively. A total of 31 (15.6 %) patients showed a disease relapse after a median time of 8 months (IQR: 4.0-12.0), but only 12 (6 %) patients died of the disease during the study period. CONCLUSIONS: This study demonstrates that NCT and TORS can obtain excellent tumor control and survival in locoregionally advanced OPSCC. NCT might reduce the need for adjuvant treatments, and randomized clinical trials should be conducted to better define this aspect.

Neoadjuvant chemotherapy and transoral robotic surgery for the posterior pharyngeal wall carcinoma.

BACKGROUND: The squamous cell carcinoma (SCC) of the posterior pharyngeal wall (PPW) is associated with poor oncological outcomes based on current literature data. We reported the preliminary outcomes of a potential new treatment protocol based on neoadjuvant chemotherapy (NCT) and transoral robotic surgery (TORS). METHODS: A retrospective single-center case series was performed including a total of 20 patients diagnosed with a SCC of the PPW between October 2010 and September 2021. All patients successfully completed TORS with neck dissection after NCT. Adjuvant treatment was performed in the presence of adverse pathologic features. Loco-regional control (LRC), overall survival (OS), and disease-specific survival (DSS) were defined as the time from surgery to tumor recurrence or death, as appropriate. Survival estimates were calculated by Kaplan-Meier analysis. Surgical data and post-operative functional outcomes were also reported. RESULTS: Estimated 3-year LRC, OS, and DSS rates (95% Confidence interval) were 59.7% (39.7-89.6), 58.6% (38.7-88.8), and 69.4% (49.9-96.6). The median hospital stay was 21 days (IQR 17.0-23.5). Oral diet and decannulation were achieved after a median of 14 days (IQR 12.0-15.0). Feeding tube and tracheostomy dependence after 6 months was observed in 3 (15%) and 2 (10%) patients, respectively. CONCLUSIONS: The use of NCT followed by TORS for PPW SCC treatment appears to have good oncological and functional outcomes for both early and locally advanced cancers. Further randomized trials and site-specific guidelines are needed.

Development of machine learning models to predict lymph node metastases in major salivary gland cancers.

INTRODUCTION: Indications for elective treatment of the neck in patients with major salivary gland cancers are still debated. Our purpose was to develop a machine learning (ML) model able to generate a predictive algorithm to identify lymph node metastases (LNM) in patients with major salivary gland cancer (SGC). METHODS: A Retrospective study was performed with data obtained from the Surveillance, Epidemiology, and End Results (SEER) program. Patients diagnosed with a major SGC between 1988 and 2019 were included. Two 2-class supervised ML decision models (random forest, RF; extreme gradient boosting, XGB) were used to predict the presence of LNM, implementing thirteen demographics and clinical variables collected from the SEER database. A permutation feature importance (PFI) score was computed using the testing dataset to identify the most important variables used in model prediction. RESULTS: A total of 10 350 patients (males: 52%; mean age: 59.9 ± 17.2 years) were included in the study. The RF and the XGB prediction models showed an overall accuracy of 0.68. Both models showed a high specificity (RF: 0.90; XGB: 0.83) and low sensitivity (RF: 0.27; XGB: 0.38) in identifying LNM. According, a high negative predictive value (RF: 0.70; XGB: 0.72) and a low positive predictive value (RF: 0.58; XGB: 0.56) were measured. T classification and tumor size were the most important features in the construction of the prediction algorithms. CONCLUSIONS: Classification performance of the ML algorithms showed high specificity and negative predictive value that allow to preoperatively identify patients with a lower risk of LNM. LAY SUMMARY: Based on data from the Surveillance, Epidemiology, and End Results (SEER) program, our study showed that machine learning algorithms owns a high specificity and negative predictive value, allowing to preoperatively identify patients with a lower risk of lymph node metastasis.

Compartmental Transoral Robotic Lateral Oropharyngectomy with the da Vinci Single-Port System: Surgical Technique.

BACKGROUND: Transoral robotic surgery (TORS) has renovated the surgical management of oropharyngeal squamous cell carcinoma (OPSCC), allowing a minimally invasive surgical approach with optimal oncological outcomes. The recent introduction of the da Vinci Single Port (SP) system resulted in a considerable improvement of TORS technique. METHODS: In this video, we illustrate the transoral robotic lateral oropharyngectomy performed with the da Vinci SP system in a 50-year-old male patient suffering from a p16+ oropharyngeal squamous cell carcinoma cT4N1M0. RESULTS: The transoral robotic lateral oropharyngectomy is illustrated step by step. The structures encountered during the resection are described, and the surgical margins are defined based on anatomical landmarks. The most critical regions encountered during resection are pointed out, and the tip and tricks of this surgery are reported. CONCLUSIONS: A step-by-step transoral lateral oropharyngectomy is described to increase its reproducibility. The da Vinci SP system owns various benefits for performing transoral lateral oropharyngectomy due to the increased maneuverability in the narrower oral cavity working spaces.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.

Neoadjuvant chemotherapy combined with transoral robotic surgery for stage III and IV laryngeal and hypopharyngeal carcinomas.

OBJECTIVES: To analyze the oncological and functional outcomes of patients with stage III-IV laryngo-hypopharyngeal cancer who underwent neoadjuvant chemotherapy (NAC) with subsequent transoral robotic surgery (TORS). MATERIALS AND METHODS: A single-center retrospective cohort study included a total of 100 patients (median age of 67.0) affected by stage III-IV supraglottic or hypopharyngeal cancer. All patients underwent NAC followed by TORS and risk-adjusted adjuvant therapy. The primary outcome was recurrence-free survival (RFS). RESULTS: The median follow-up time was 24.0 months. Estimated 2-year (95% CI) OS, DSS, and RFS were 75% (66% - 85%), 84% (76% - 92%), and 65% (56% - 76%), respectively. Among the 11 patients who relapsed on the primary site, 3 underwent salvage total laryngectomy, 3 underwent salvage CRT, and the others receive palliation or supportive care. At 6 months from surgery, 17 patients were still tracheostomized or had a stoma retainer, while 15 were gastrostomy dependent. At the Cox multivariable analysis, the clinical stage at presentation, the number of NAC cycles, and the presence of LVI were found to be independently correlated with the RFS. CONCLUSION: This study demonstrates that NAC followed by TORS can obtain good tumor control, survival, and organ preservation rates in stage III-IV laryngo-hypopharyngeal cancer.

Prognostic role of surgical margins in patients undergoing transoral robotic surgery after neo-adjuvant chemotherapy.

PURPOSE: To define if positive and close surgical margins are associated to worse prognosis in patients who underwent transoral robotic surgery (TORS) after neoadjuvant chemotherapy (NCT). METHODS: A retrospective cohort study was carried out at a tertiary referral center. The primary outcome was local-regional control (LRC), and the results were summarized with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 308 patients (median age: 62.0, IQR: 55.0-68.2) were included. Univariable analysis showed a significant reduced LRC for patients with positive margins (HR = 1.82, 95% CI: 1.02-3.24). However, they were not associated with worse LRC after adjusting for adverse tumor variables (HR = 0.81, 95% CI: 0.40-1.65). ROC analysis was performed on 123 patients with negative margins (AUC: 0.54) measuring an optimal threshold of 1.25 mm (sensitivity = 60.0%; specificity = 50.5%). Univariable analysis showed non-significant differences between close and wide negative margins (HR = 1.44, 95% CI: 0.59-3.54). CONCLUSIONS: A positive surgical margin is not an independent predictor of tumor control and survival. A threshold of 1.25 mm was identified as the most appropriate to define close margins, but no difference was measured after distinguishing negative margins in close and wide margins.

Single-Port Versus Multiport da Vinci System for Transoral Robotic Surgery of Hypopharyngeal and Laryngeal Carcinoma.

OBJECTIVE: Da Vinci single port (SP) has been recently approved for transoral robotic surgery (TORS). Its characteristics make it particularly feasible for laryngeal and hypopharyngeal surgery. We report our experience comparing intra- and postoperative outcomes, technical advantages, and shortcomings of transoral laryngeal and hypopharyngeal resections performed with the da Vinci SP and the da Vinci Si/Xi systems. STUDY DESIGN: Retrospective database review. SETTING: Single academic tertiary care hospital. METHODS: Subjects included adult patients with laryngeal and hypopharyngeal carcinoma who underwent TORS between 2008 and 2022. The SP and multiport (MP) systems were compared in terms of intraoperative times, short-term postoperative outcomes, and TORS-related complications after a propensity score matching. RESULTS: A total of 185 patients were enrolled (56 SP vs 129 MP patients), and a cohort of 112 patients was analyzed after matching. The docking time was reduced in the SP group (8.84 ± 4.67 vs 6.45 ± 3.11 minutes; p = .003), as well as console time (53.91 ± 29.38 vs 42.70 ± 13.72 minutes; p = .035). Positive margins were more frequent in the MP group (52% vs 43%; p = .34). The mean decannulation time was 1.86 days longer in the SP group (p = .046). No significant differences emerged from the analysis of the duration of hospitalization, enteral feeding, and TORS-related complications. CONCLUSION: SP safety profile is comparable to that of previous models, while it showed advantages in terms of reduced docking times. Console times were also shortened due to improved maneuverability and field visualization.

Investigation of somatic mutation profiles and tumor evolution of primary oropharyngeal cancer and sequential lymph node metastases using multiregional whole-exome sequencing.

Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. We performed high-depth whole-exome sequencing (200×) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples, and 18 normal tissue samples. Among 40 metastatic LNs, 22 showed extranodal extension (ENE). Mutation profiles of HPV-positive OPSCC and HPV-negative OPSCC were similar to those reported previously. Somatic mutations in CDKN2A and TP53 were frequently detected in HPV-negative OPSCC. Somatic mutations in HPV-positive OPSCC samples showed APOBEC-related signatures. Somatic mutations from metastatic LNs showed a different pattern than the primary tumor. Somatic mutations acquired in the WNT pathway during metastasis showed a significant relationship with ENE. Clonal evolution analysis of primary and metastatic LNs showed that, in some cases, each metastatic LN originated from a different primary tumor sub-clone.

Development of machine learning models for the prediction of positive surgical margins in transoral robotic surgery (TORS).

PURPOSE: To develop machine learning (ML) models for predicting positive margins in patients undergoing transoral robotic surgery (TORS). METHODS: Data from 453 patients with laryngeal, hypopharyngeal, and oropharyngeal squamous cell carcinoma were retrospectively collected at a tertiary referral center to train (n = 316) and validate (n = 137) six two-class supervised ML models employing 14 variables available pre-operatively. RESULTS: The accuracy of the six ML models ranged between 0.67 and 0.75, while the measured AUC between 0.68 and 0.75. The ML algorithms showed high specificity (range: 0.75-0.89) and low sensitivity (range: 0.26-0.64) in detecting patients with positive margins after TORS. NPV was higher (range: 0.73-0.83) compared to PPV (range: 0.45-0.63). T classification and tumor site were the most important predictors of positive surgical margins. CONCLUSIONS: ML algorithms can identify patients with low risk of positive margins and therefore amenable to TORS.

Complications of pectoralis major myo-cutaneous flap, anterolateral thigh flap and radial forearm free flap after total laryngectomy with partial pharyngectomy: A systematic review and network meta-analysis.

BACKGROUND: No consensus exists regarding the most effective reconstruction after total laryngectomy with partial pharyngectomy (TLwPP). This study aims to compare different reconstructive techniques (pectoralis major myo-cutaneous flap, PMMCF; anterolateral thigh flap, ALTF; radial forearm free flap, RFFF) after TLwPP in terms of pharyngocutaneous fistula (PCF), stenosis and feeding tube dependence (FTD) incidence. METHODS: The Scopus, PubMed/MEDLINE, Cochrane Library, and Google Scholar databases were searched. A single-arm meta-analysis was performed for PCF incidence, stenosis incidence, and FTD incidence on the entire cohort. An arm-based network analysis was conducted to compare three different surgical interventions (PMMCF, ALTF, RFFF). RESULTS: A total of 13 studies and 232 patients were included in the network meta-analysis. The lowest PCF absolute risk was measured for the RFFF (11.7%, 95% CI: 2.8%-33.4%), compared to the ALTF (13.4%, 95% CI: 4.5%-32.1%) and the PMMC (49.0%, 95% CI: 19.2%-79.3%). The RFFF showed a stenosis absolute risk of 0.0% (95% CI: 0.0%-1.1%), while a higher stenosis incidence was measured for the ALTF (5.7%, 95% CI: 0.8%-25.2%) and the PMMCF (11.6%, 95% CI: 0.8%-55.1%). The RFFF showed the lowest absolute risk of FTD incidence (6.8%, 95% CI: 0.5%-28.1%) compared to the other reconstructive techniques (PMMCF: 12.4%, 95% CI: 2.4%-42.1%; ALTF: 17.5%, 95% CI: 6.4%-38.9%). CONCLUSIONS: The RFFF seems the best choice for reconstruction of partial pharyngeal defects after TLwPP due to the lower incidence of PCF, stenosis and FTD compared to the ALTF and the PMMCF.

Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer.

BACKGROUND: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies. METHODS: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF). RESULTS: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF. CONCLUSIONS: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered.

Role of postoperative radiotherapy in resected adenoid cystic carcinoma of the head and neck.

PURPOSE: Although postoperative radiotherapy (PORT) is demonstrably effective in local control of head and neck adenoid cystic carcinoma (HNACC), its application is controversial and the subset of patients who would benefit most from PORT is unknown. Herein, we analyzed the data of HNACC patients to clarify the role of PORT. METHODS: We retrospectively reviewed 187 patients with nonmetastatic HNACC who underwent surgical resection between 2005 and 2019. The study endpoints were locoregional failure-free survival (LRFFS), progression-free survival (PFS), and overall survival (OS). Subgroup analysis and recursive partitioning analysis (RPA) were performed to identify patients most likely to benefit from PORT. RESULTS: With a median follow-up of 84.7 months, the 5-year LRFFS, PFS, and OS were 70.0%, 52.6%, and 86.4%, respectively. Survival was significantly shorter in patients who experienced local failure than in those who did not (5-year OS: 88.1% vs. 80.5%, P = 0.001). The local failure rate was significantly lower in patients who underwent PORT (16.9% vs. 31.0%, P = 0.021), despite the high frequency of adverse factors. Especially, significant decreases in local failure and similar OS rates could be obtained after PORT among patients with positive margins, T2-4 stage disease, and minor salivary gland tumors. The RPA model for PFS categorized patients into four groups according to three prognostic factors (T-stage, location, and sex). The RPA model for LRFFS and OS suggested three groups based on two factors (T-stage, margin for LRFFS; T-stage, grade 3 for OS). CONCLUSION: PORT could prevent dismal survival, while significantly reducing local failures in high-risk HNACC patients.

Long-term outcomes of early stage oral tongue cancer: Main cause of treatment failure and second primary malignancy.

Objective: We attempted to investigate the long-term outcomes, prognostic factors, treatment failures, second primary malignancies, and salvage therapies in early (pT1-2N0) oral tongue squamous cell carcinoma (OTSCC). Methods: We retrospectively analyzed the medical records of 295 early stage OTSCC patients. Results: Two hundred ninety-five patients were enrolled. The average follow-up period was 64.5 months (range, 1-190 months). Five-year recurrence-free survival rate was 84.8% and disease-specific survival rate was 91.2%. On multivariate analysis, only the depth of invasion (DOI) exhibited significant correlations with the disease recurrence. Patient's age and DOI demonstrated a significant association with survival. A total of 53 recurrence and 35 death events occurred, with the main cause of treatment failure being regional or local recurrence. In recurrent cases, the success rate of salvage treatment was 42% at 5 years. During the follow-up period, second primary malignancy occurred in 13 patients, and 8 (61.5%) of those patients were successfully treated. Conclusions: In pT1-2N0 OTSCC, regional or local recurrence is the main recurrence pattern, whereas age and DOI >5 mm are significant prognostic factors related to recurrence and survival. Since several patients experienced second primary malignancies in the head and neck, careful and thorough surveillance may be required to detect second primary lesions. Level of Evidence: 4.