Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab.

OBJECTIVE: Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab. METHODS: This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score. RESULTS: No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3 months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24 months. CONCLUSIONS: MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.

Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.

Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer of unknown primary.

A biomarker that is useful for the detection of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in-house droplet digital polymerase chain reaction. Seventy-four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66-92) and 100% (95% CI = 88-100), 85% (95% CI = 69-94) and 94% (95% CI = 73-100), and 93% (95% CI = 81-99) and 97% (95% CI = 84-100), respectively, for HPV16-related OPC, while those were 20% (95% CI = 1-72) and 100% (95% CI = 3-100), 0% (95% CI = 0-52) and 100% (95% CI = 3-100), and 100% (95% CI = 54-100) and 100% (95% CI = 16-100), respectively, for HPV16-related CUP. The sensitivity of ctHPV16DNA for HPV16-related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16-related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16-related OPC, while further studies are required for HPV16-related CUP.

Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck.

Positron emission tomography and computed tomography (PET-CT) is widely used to assess the response to radiotherapy. However, the ability of PET-CT to predict treatment failure in human papillomavirus (HPV)-related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16-related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow-up of 21 months, ctHPV16DNA and PET-CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET-CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio [HR], 138.8; 95% confidence interval [CI], 15.5-3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8-36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One-year event-free survival rates of each risk group were 0%, 88% (95% CI, 46-98) and 95% (95% CI, 72-99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET-CT and helps guide decisions managing patients with HPV16-related HNSCC after radiotherapy.

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

Immediate tracheal reconstruction with forearm flap and bone graft.

BACKGROUND: "Window" resection of the trachea is sometimes performed to remove tumors invading the trachea. Here, we present a novel reconstructive procedure to this end. METHODS: Eleven patients (mean age, 64 years; range, 46-80 years) were included. Primary diagnoses included thyroid cancer and adenoid cystic carcinoma of the trachea. All defects were partial and located in the neck (mean width and length, 3/5 circle and 7.5 rings; range, 1/2-2/3 circle and 5-9 rings). Immediate 2-stage reconstruction was performed using a forearm flap and free bone graft. The bone graft was utilized as a supportive skeleton. A tracheostoma was left open for several months following the initial surgery, and then closed. RESULTS: The mean flap size was 6.1 × 9.7 cm (range, 6-7 × 7-16 cm). Mean number of grafted bone strips and length were 1.6 (range, 1-3) and 6.1 cm (range, 4.5-7 cm). All flaps survived. Five patients developed complications in the neck, including surgical site infections (SSIs), recurrent nerve palsy, and lymphorrhea. Four patients developed donor site complications, including clavicular fracture and SSIs. Mean postoperative follow-up lasted 85 months (range, 11-149 months). Normal speech was restored in 9 patients. Stoma closure was abandoned in 2 patients, because 1 patient showed vocal cord fixation with advanced age and the other showed bone graft loss following SSI. CONCLUSIONS: Creating a tracheostoma during the first operation prevents postoperative airway compromise. Our bone graft placement easily achieves tracheal rigidity. This procedure is simple and safe for tracheal window defect repair.

Metabolic tumor volume of primary tumor predicts survival better than T classification in the larynx preservation approach.

We aimed to determine whether pretreatment metabolic tumor volume of the primary tumor (T-MTV) or T classification would be a better predictor of laryngectomy-free survival (LFS) and overall survival (OS) after chemoradiotherapy in patients with locally advanced laryngeal or hypopharyngeal cancer requiring total laryngectomy. We analyzed 85 patients using a Cox proportional hazards model and evaluated its usefulness by Akaike's information criterion. A T-MTV cut-off value was determined by time-dependent receiver operating characteristic curve analysis. Interobserver reliability for measuring T-MTV was estimated by the intraclass correlation coefficient (ICC). After adjustment for covariables, T-MTV, irrespective of whether a continuous or dichotomized variable, and T classification remained independent predictors of LFS and OS. Large T-MTV (>28.7 mL) was associated with inferior LFS (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.97-8.70; P = 0.0003) and inferior OS (HR, 3.18; 95% CI, 1.47-6.69; P = 0.004) compared with small T-MTV (≤28.7 mL). The T-MTV model outperformed the T classification model in predicting LFS and OS (P = 0.007 and 0.01, respectively). Three-year LFS and OS rates for patients with small versus large T-MTV were 68% vs 9% (P < 0.0001) and 77% vs 25% (P < 0.0001), respectively, whereas those for patients with T2-T3 versus T4a were 61% vs 31% (P = 0.003) and 71% vs 48% (P = 0.10), respectively. ICC was 0.99 (95% CI, 0.99-1.00). Given the excellent interobserver reliability, T-MTV is better than T classification to identify patients who would benefit from the larynx preservation approach.

Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan.

BACKGROUND: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers. METHODS: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients. RESULTS: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372). CONCLUSION: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.

Selective neck irradiation for supraglottic cancer: focus on Sublevel IIb omission.

OBJECTIVE: To estimate selective neck irradiation omitting surgical Sublevel IIb. METHODS: Bilateral necks of 47 patients (94 necks) were subjected to definitive radiotherapy for supraglottic cancer. Sixty-nine and 25 necks were clinically node negative (cN-) and clinically node positive (cN+), respectively. We subdivided Sublevel IIb by the international consensus guideline for radiotherapy into Sublevel IIb/a, directly posterior to the internal jugular vein, and Sublevel IIb/b, which was behind Sublevel IIb/a and coincided with surgical Sublevel IIb. Bilateral (Sub)levels IIa, III, IV and IIb/a were routinely irradiated, whereas Sublevel IIb/b was omitted from the elective clinical target volume in 73/94 treated necks (78%). RESULTS: Two patients presented with ipsilateral Sublevel IIb/a metastases. No Sublevel IIb/b metastasis was observed. Five patients experienced cervical lymph node recurrence; Sublevel IIb/a recurrence developed in two patients, whereas no Sublevel IIb/b recurrence occurred even in the cN- necks of cN+ patients or cN0 patients. The 5-year regional control rates were 91.5% for Sublevel IIb/b-omitted patients and 77.8% for Sublevel IIb/b treated patients. CONCLUSIONS: Selective neck irradiation omitting Sublevel IIb/b did not compromise regional control and could be indicated for cN- neck of supraglottic cancer.

Trends in the Detail of the Stage and Survival Rate in Hypopharyngeal Cancer over 20 Years.

Background: Hypopharyngeal cancer frequently presents at an advanced stage and has one of the worst prognosis among the head and neck cancers. Recently, superficial hypopharyngeal cancers with a good prognosis have been detected with a novel endoscopic technique, such as narrow band imaging. Objectives: To evaluate trends in the detail of the stage and survival rate in hypopharyngeal cancer over 20 years. Patients and methods: Between 1993 and 2012, 722 patients with hypopharyngeal cancer treated at the Osaka Medical Center for Cancer and Cardiovascular Disease were studied retrospectively. The 20-year period was subdivided into 5-year periods; Period A (1993-1997, n=101), Period B (1998-2002, n=123), Period C (2003-2007, n=196) and Period D (2008-2012, n=302). The patients at Stage I-II were divided into superficial cancer as Stage I-IIs and invasive cancer as Stage I-IIi. In every period, a transition of the staging and overall survival rate were compared. Results: The 5-year overall survival in Period A, B, C and D were 34%, 39%, 54% and 60%, respectively. The patients at Stage III-IV in Period A, B, C and D comprised 32%, 36%, 47% and 54%, respectively. Both survival rates improved significantly from Period B to C. The ratio of Stage 0 and Stage I-IIs increased significantly from Period C to D. Whereas the 5-year overall survival rates of Stage 0 and Stage I-IIs were similar (80% vs 88%), the 5-year overall survival of Stage I-IIi was significantly poor. Excluding Stage 0 and Stage I-IIs, the 5-year overall survival had little change from Period C to D. Conclusion: The reason for the improvement in hypopharyngeal cancer prognosis was the prognostic improvement of advanced cancer from Period B to C, and an increase in superficial cancer from Period C to D.

Endoscopic submucosal dissection as minimally invasive treatment for superficial pharyngeal cancer: a phase II study (with video).

BACKGROUND AND AIMS: Although endoscopic submucosal dissection (ESD) has been applied for superficial pharyngeal cancer, no prospective trials have been reported. To investigate the efficacy and safety of ESD for superficial pharyngeal cancer, we conducted a prospective phase II trial. METHODS: Fifty-four patients with 73 lesions were enrolled from September 2010 to August 2014, and ESD was performed. The primary endpoint was the complete resection rate. Secondary endpoints were safety, recurrence-free survival, overall survival, and incidence of metachronous pharyngeal cancer. RESULTS: Fifty-four patients had stage 0-III cancer: stage 0, n = 22; stage I, n = 14; stage II, n = 17; and stage III, n = 1. The en bloc resection rate was 100%, and the complete resection rate was 79.5% (58/73 lesions; 95% confidence interval, 68%-88%). No serious adverse events related to ESD were encountered. Four patients required nasogastric intubation and feeding. No patients required percutaneous endoscopic gastrostomy and tracheotomy. Swallowing, speech, and airway functions were preserved in all patients. One of the 54 patients died of an unrelated illness. Median follow-up was 27 months (range 6-55 months). Local cervical lymph node metastasis was observed in 1 patient, and the case was salvaged successfully with lymph node dissection. The 3-year overall and recurrence-free survival rates were 97.7% and 98.1%, respectively. Cumulative development of multiple cancers of the pharynx at 3 years was 18.4%. CONCLUSIONS: ESD appears to be a safe and effective minimally invasive treatment in patients with superficial pharyngeal cancer. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000003623.).

Treatment outcomes of external-beam radiotherapy for squamous cell carcinoma of the base of the tongue.

PURPOSE: To evaluate definitive external-beam radiotherapy (EBRT) for patients with base of the tongue (BOT) cancers. METHODS: We reviewed results for 26 patients with BOT cancers who were treated with EBRT. Clinical stages T1, T2, T3, and T4a were observed for 10, 7, 4, and 5 patients, respectively, and stages N0, N1, N2a, N2b, N2c, and N3 were observed for 4, 2, 5, 6, 8, and 1 patients, respectively. More than half of the patients (n = 19) were stage IVA. Standard total delivered doses were 70 Gy to primary tumors and cervical lymph node (CLN) metastases and 40-46 Gy to elective nodal regions. Eleven patients with advanced loco-regional disease received concurrent or neoadjuvant chemotherapy. Four T3 patients and one T2 patient received 2 or 3 cycles of concurrent intra-arterial cisplatin with EBRT (RADPLAT). RESULTS: Three-year overall survival was 69 % (95 % CI 47-83 %), with a median follow-up period of 33 months. Three-year local control was 100, 86, 100, and 20 % for T1, T2, T3, and T4 patients, respectively. Three-year regional control was 100 % for N0, N1, and N2a, 83 % for N2b, 75 % for N2c, and 0 % for N3 patients. Treatment failed for 7 patients. All 5 patients undergoing RADPLAT achieved complete responses and did not develop local recurrence. CONCLUSIONS: We achieved favorable outcomes for patients with T1-T3 BOT cancers by use of definitive EBRT with or without chemotherapy.

[Videofluoroscopic Examination of Swallowing Using the AsR Score for Postoperative Swallowing Function in Oral Cancer Patients].

To evaluate the postoperative swallowing function in head and neck cancer patients, videofluoroscopic examination of swallowing (VF) proved useful as a qualitative evaluation, but was complex as a quantitative evaluation. We made use of the AsR score which consisted of a 10-point scale as a quantitative evaluation of VF. To identify the usefulness of the AsR score, 146 patients who had undergone extensive resection and reconstruction with free flaps or pedicle grafts were reviewed. The AsR score of VF for the first time after surgery was defined as "first score", and at the last time in the hospital was defined as "last score". The correlations between the first score and continuity of direct therapy, and between the last score and way of nutrition at the time of discharge were examined. Using the ROC (receiver operator characteristic) analysis and the AUC (area under the curve) the cut-off values of the AsR score were estimated. One hundred and thirty one patients could continue direct therapy after the first time of VF. The first score detected continuity of direct therapy with high accuracy (AUC = 0.946), furthermore using a cut-off of 5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were about 96.2%, 86.6%, 98.4%, and 72.2%, respectively. At the time of discharge, 138 patients had no limitation of oral intake and 8 patients had a limitation e.g. PEG (n = 7) and a total laryngectomy for preventing aspiration (n = 1). The last score detected oral intake ability with no limitation with high accuracy (AUC = 0.925). Using a cut-off of 6, the sensitivity, specificity, PPV and NPV were about 82.6%, 87.5%, 99.1% and 22.6%, respectively. The AsR score is useful as a quantitative evaluation of postoperative swallowing function in oral cancer patients.

[Outcome of tongue cancer treated with surgery and postoperative radiotherapy].

A retrospective analysis of 263 patients with previously untreated squamous cell carcinoma of the tongue between 2000 and 2010 was performed. Those patients, who received preoperative chemotherapy, had a history of head and neck cancer or had previously received radiotherapy for the other disease, were excluded. All patients underwent a surgical procedure as a part of the initial treatment. Patients with close or microscopically involved margins of resection, INF (Infiltrative growth pattern) gamma or at least two involved nodes were classified as high risk patients. Postoperative radiotherapy (PORT) was undertaken for the high risk patients. After a median follow-up of 72 months, the 5-year overall survival and 5-year cause-specific survival were as follows: 79.1%, 85.0% in all stages, 82.7%, 91.2% in Stage I (n = 76), 86.7%, 89.0% in Stage II (n = 98), 71.5%, 78.6% in Stage III (n = 57), and 61.5%, 69.1% in Stage IV (n = 32). Patients without high risk features had significantly higher overall survival rate than those in the case of high risk patients, despite receiving no PORT. For high risk patients, PORT significantly improved the locoreginal control rate, but the overall survival rate did not improve.

Changes in serum lactate dehydrogenase as a prognostic factor in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Lactate dehydrogenase (LDH) is involved in the Warburg effect. Elevated serum LDH is a prognostic marker for metastatic solid cancer. AIM: To investigate the prognostic impact of serum LDH in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: This retrospective study included 129 patients treated with ICIs between 2017 and 2023. The effects of pretreatment LDH, LDH at 3 months, and change in LDH during the first 3 months (ΔLDH) on overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and Cox regression model. RESULTS: The 1-year PFS and OS rates for high and low groups were 6.0% and 30.1% for pretreatment LDH (p = 0.044), 25.7% and 38.3% for on-treatment LDH (p = 0.079), and 14.3% and 38.7% for ΔLDH (p = 0.008), as well as 42.1% and 60.9% for pretreatment LDH (p = 0.109), 56.0% and 80.5% (p < 0.001) for on-treatment LDH, and 31.0% and 81.0% for ΔLDH (p < 0.001), respectively. ΔLDH was an independent prognostic factor for both PFS and OS. CONCLUSIONS AND SIGNIFICANCE: ΔLDH can be used to predict ICI treatment outcomes and as a marker in deciding to continue ICI therapy.

Temporal recovery and prognostic factors for dysphagia following cardiovascular surgery: Retrospective analysis and development of predictive score.

OBJECTIVE: Dysphagia is a common complication associated with cardiovascular surgery (CVS). This study sought to better understand recovery timelines, identify risk factors, and create a prognostic model for oral intake restoration. METHODS: This retrospective study included 134 patients who had CVS between April 2022 and March 2024. We assessed swallowing ability through fiberoptic endoscopic evaluation of swallowing (FEES). We randomly divided the patients' data into a training dataset and a test dataset in a ratio of 70/30 and Kaplan-Meier analyses and Cox regression were used to assess predictors of total oral intake. We also created a scoring system using the estimated regression coefficients. RESULTS: Most patients with CVS achieved total oral intake in 7-11 days after extubation. Over 168 h of intubation, the presence of penetration or aspiration, a poor FEES score (score > 6), and perioperative complications were significant risk factors for delayed total oral intake. The predicting score was calculated by adding the scores for each individual factor, including FEES score, penetration/aspiration, and preoperative complications. Scores ranged 0-8, categorizing patients into 0-2, 3-5, and 6-8 groups, clearly demonstrating that the higher the predicting score, the longer the time to total oral intake in both the training and the test dataset. CONCLUSIONS: All risk factors for unsuccessful or delayed total oral intake were intubation for more than a week, poor swallowing ability, and the presence of perioperative complications. The scoring system accurately predicts the restoration of oral intake following CVS.

Association of circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma.

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC.

Small-cell carcinoma in the head and neck region: A propensity score-matched analysis of the effect of surgery.

BACKGROUND: Head and neck small-cell carcinoma (HNSmCC) is a rare and aggressive cancer with a high tendency for distant metastasis. It is treated with multimodal treatment involving chemotherapy. Occasionally, surgery is performed for the management of locoregional HNSmCC. However, the benefits of surgery in this context have not yet been elucidated. Therefore, in this study, we aimed to investigate whether surgery could improve the survival of patients with HNSmCC. PATIENTS AND METHODS: We obtained data from patients with locoregional HNSmCC treated with chemoradiation therapy (CRT) from the Surveillance, Epidemiology, and End Results database. Patients who did and did not undergo surgery were matched using propensity scores. The overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios (HRs) were calculated using the Cox proportional hazard model. RESULTS: The 5-year OS rates of the patients who did and did not undergo surgery were 57.2% and 50.6%, respectively (P = 0.689); the corresponding 5-year DSS rates were 61.0% and 57.5% (P = 0.769). The adjusted HRs for surgery were 0.85 (95% confidence interval [CI]: 0.54-1.33) for OS and 0.87 (95% CI: 0.51-1.49) for DSS. CONCLUSION: The addition of surgery to CRT did not improve the survival of patients with locoregional HNSmCC.

Survival of Metastatic Human Papillomavirus (HPV)-Related Head and Neck Cancer Receiving Platinum-Based Triplet Induction Chemotherapy and Relevance of Circulating Tumor HPV DNA.

Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods  Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, P = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, P = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients (P = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.

Circulating Plasma Exosomal PD-L1 Predicts Prognosis of Head and Neck Squamous Cell Carcinoma After Radiation Therapy.

Purpose: Radiation therapy is widely used to treat head and neck squamous cell carcinoma (HNSCC). This study evaluated the association between circulating plasma programmed death-ligand 1 (PD-L1) and the outcomes of patients with HNSCC after radiation therapy. Methods and Materials: In this retrospective observational study, plasma samples of 76 patients with HNSCC who underwent radiation therapy from June 2019 to August 2021 were analyzed. These plasma samples were obtained before radiation therapy. The median follow-up was 32.5 months. Total and exosomal PD-L1 was measured by enzyme-linked immunosorbent assay and retrospectively analyzed for association with overall survival (OS), progression-free survival (PFS), and local control (LC). Prognostic factors among patients' characteristics and circulating PD-L1 in plasma were evaluated by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses. Results: The median concentration of total PD-L1 in plasma was 115.1 pg/mL (95% CI, 114.7-137.9 pg/mL), and the median concentration of exosomal PD-L1 was 2.8 pg/mL (95% CI, 6.0-13.0 pg/mL). Univariate and multivariate analyses showed exosomal PD-L1 as a prognostic factor for PFS and LC. Patients with high exosomal PD-L1 in plasma had poor PFS and LC compared with those with low exosomal PD-L1, indicating that 1-year PFS was 79.2% versus 33.3% (P < .001) and 1-year LC was 87.3% versus 50.0% (P < .001) in patients with high and low exosomal PD-L1, respectively. However, exosomal PD-L1 in plasma had no significant effect on OS. Total PD-L1 in plasma did not correlate with PFS, LC, and OS. Conclusions: The pretreatment circulating exosomal PD-L1 in plasma of patients with HNSCC was a prognostic factor after radiation therapy.