Dietary patterns linked to lower odds of malnutrition are associated with all-cause and cancer mortality in adults with cancer.

OBJECTIVES: Dietary patterns, characterised by protein, polyunsaturated fatty acids, and vitamin D, reduce the odds of malnutrition in cancer survivors. However, it is unclear whether these dietary patterns also improve prognosis. This study prospectively examined associations between dietary patterns linked to lower odds of malnutrition and the risk of all-cause and cancer mortality in adult cancer survivors from the UK Biobank cohort. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: Cancer survivors from the UK Biobank (mean ± SD, 7.1 ± 6.3 years since diagnosis) were included (n = 2415; 59.7 ± 7.1 years; 60.7% female). MEASUREMENTS: Dietary intake was estimated using the Oxford WebQ 24-h dietary assessment. Dietary patterns ('high oily fish and nuts', and 'low oily fish') were derived using reduced rank regression (response variables: protein (g/kg/day), polyunsaturated fatty acids (g/day) and vitamin D (µg/day)). Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cancer mortality. Nonlinear relationships were examined using restricted cubic splines. Models were adjusted for demographic and health characteristics. Sub-group analyses investigated relationships in sub-samples of adults with i) high nutritional risk (lung, gastrointestinal, haematological, or head and neck tumours) and ii) recent cancer diagnosis (cancer diagnosis within two years prior to assessment). RESULTS: Deaths due to all-causes (n = 305) and cancer (n = 249) were identified during a median 10.4 (IQR: 10.2-10.8) years follow-up. There were no statistically significant linear associations between the dietary patterns and all-cause or cancer mortality. However, a U-shaped association between the 'high oily fish and nuts' pattern, characterised by higher intake of oily fish and nuts and seeds, and all-cause mortality (p-non-linearity = 0.004) was identified, as well as with all-cause (p-non-linearity = 0.006) and cancer mortality (p-non-linearity = 0.035) in adults with a high nutritional risk cancer diagnosis (lung, gastrointestinal, haematological, or head and neck tumours), indicating that both above and below mean intake was associated with increased risk. The 'low oily fish' pattern, characterised by lower oily fish but higher potato intake, also had a non-linear association with all-cause mortality (p-non-linearity = 0.046) where lower but not higher than mean intake increased mortality risk. No dietary patterns were significantly associated with mortality in adults with a recent cancer diagnosis. CONCLUSION: 'High oily fish and nuts' or 'low oily fish' dietary patterns that were protective against malnutrition were associated with risk of all-cause and cancer mortality in adults with cancer. Future research should assess the efficacy of these dietary patterns in the acute treatment period when malnutrition is most prevalent.

Current status of head and neck sarcomas in Japan in 2016-2019: an analysis using the national cancer registry.

BACKGROUND: Head and neck sarcomas are especially rare in Asia, leading to limited clinical evidence. This study aimed to investigate the incidence, clinical features, treatment status, and outcome of these sarcomas using data from the National Cancer Registry in Japan. METHODS: All head and neck sarcomas diagnosed between 2016 and 2019 and recorded in the National Cancer Registry were analyzed. Data on sex, age, primary site, histological type, stage, treatment modality, and prognostic information were collected. Age-adjusted incidence and 3-year survival rates of patients with head and neck sarcomas were calculated. RESULTS: Overall, 635 head and neck sarcoma patients were identified. Head and neck sarcoma occurred more frequently in men and patients in their 70 s. The age-adjusted annual incidence rate was 0.125 per 100,000 patients in the 2015 Japanese model or 0.089 per 100,000 patients in the world population model. The nasal cavity and paranasal sinuses were the most frequent primary sites, with rhabdomyosarcoma as the most common histologic type. Treatment typically involved chemotherapy and/or radiation therapy for rhabdomyosarcoma and Ewing's sarcoma, whereas surgical approaches for other types. Three-year survival rate of head and neck sarcoma patients was 64.8%. CONCLUSIONS: Head and neck sarcomas occurred rarely, but most frequently in the nasal cavity and paranasal sinuses in Japan. Poor outcomes were observed for sarcoma patients than for non-sarcoma head and neck cancer patients.

Criterios PERCIST, Hopkins y parámetros metabólicos de la PET/TC como factores pronósticos en el cáncer escamoso de cabeza y cuello / PERCIST and Hopkins criteria and PET/CT metabolic parameters as prognostic factors in squamous head and neck cancer

Objetivo Valorar la utilidad clínica de los criterios PERCIST, Hopkins y de los cambios en los parámetros cuantitativos de la PET/TC con [18F]FDG como factores pronósticos para la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con cáncer escamoso de cabeza y cuello tratados mediante quimiorradioterapia. Material y métodos Se valoraron retrospectivamente 40 pacientes (34 hombres) diagnosticados de cáncer escamoso de cabeza y cuello durante un intervalo de 8 años. Se utilizaron los criterios PERCIST y Hopkins para determinar la respuesta al tratamiento. Así mismo, se cuantificaron las variaciones de los parámetros metabólicos SUV máximo (ΔSUVmax), volumen metabólico tumoral (ΔMTV) y glicólisis tumoral total (ΔTLG) entre los estudios PET/TC pre- y postratamiento. El modelo de regresión de Cox, las curvas ROC y el método de Kaplan-Meier se aplicaron para el análisis de factores pronósticos y curvas de supervivencia. Resultado El seguimiento medio fue de 39,4 meses produciéndose 24 recidivas-progresiones y 22 muertes. Tanto los criterios PERCIST y Hopkins como los tres parámetros metabólicos fueron factores predictivos en análisis univariante y solo el ΔSUVmax en el multivariante. El análisis de supervivencia mostró curvas de SLP y SCE significativamente diferentes para los cinco parámetros considerados. Conclusión La aplicación de los criterios PERCIST y Hopkins, así como los ΔSUVmax, ΔMTV y ΔTLG de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia en pacientes de nuestro entorno tratados por cáncer de cabeza y cuello. Los resultados podrían ayudar a personalizar el tratamiento (AU)

Aim To assess the clinical utility of PERCIST and Hopkins criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with head and neck squamous cell carcinoma treated by chemoradiotherapy. Material and methods Forty patients (34 men) diagnosed with head and neck squamous cell carcinoma were retrospectively assessed over an interval of 8 years. PERCIST and Hopkins criteria were used to assess response to treatment. Variations in the metabolic parameters maximum SUV (ΔSUVmax), metabolic tumor volume (ΔMTV) and total lesion glycolysis (ΔTLG) between pre- and post-treatment PET/CT studies were also determined. Cox regression model, ROC curves and Kaplan-Meier method were used for the analysis of prognostic factors and survival curves. Results The average follow-up was 39.4 months, with 24 progressions and 22 deaths. Both PERCIST and Hopkins criteria and the three metabolic parameters were predictive factors in the univariate analysis and only ΔSUVmax in the multivariate analysis. Survival analysis showed statistically significant differences in PFS and CSS curves for the five parameters considered. Conclusion Application of PERCIST and Hopkins criteria as well as ΔSUVmax, ΔMTV and ΔTLG from PET/CT studies proved to be prognostic factors for survival in patients in our setting treated for head and neck cancer. The results could help to personalize treatment (AU)

Non-inferior efficacy of non-surgical treatment to surgical treatment in patients with nonmetastatic head and neck rhabdomyosarcoma: a SEER-based study

Purpose Head and neck rhabdomyosarcoma (HNRMS) is a rare but aggressive malignant neoplasm. Given the young patient age and critical anatomy of the head and neck, performing surgery on the primary tumor still remains debatable. This study aimed to evaluate the impact of the non-surgery-based treatment versus surgery-based treatment on patients with nonmetastatic HNRMS. Methods Patients diagnosed with nonmetastatic HNRMS between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in our study. Inverse probability treatment weighting (IPTW) method was employed to balance confounding factors between surgery and non-surgery groups. Kaplan–Meier methods and COX regression analyses were used to analyze survival outcomes of overall survival (OS) and cancer-specific survival (CSS). Prognostic nomogram was established to predict survival. Results A total of 260 eligible patients were extracted from the SEER database. Kaplan–Meier survival curves revealed that there was no significant difference in OS and CSS between the surgery and non-surgery groups both before and after IPTW (p > 0.05). Cox regression analyses and IPTW-adjusted Cox regression analyses for both OS and CSS showed similar survival between the two groups. Prognostic factors were explored and a nomogram for patients in the surgery group was constructed. Risk stratification based on the nomogram indicated that patients in surgery-high-risk group did not benefit from primary surgery. While those in surgery-low-risk group had an equal survival outcome to those in non-surgery group. Conclusions Our study revealed that compared to patients receiving surgery, those not receiving surgery had similar survival outcomes for nonmetastatic HNRMS. Our established nomogram may serve as a practical tool for individual prognostic evaluations (AU)

Nodular type predominance of head and neck cutaneous malignant melanoma in Asian populations leads to poor outcome and low survival.

Cutaneous malignant melanomas of the head and neck (HNM) are proposed to have notable histological and clinical differences from those at other sites (other melanoma); however, HNMs among Asians have remained poorly understood. This study aimed to investigate the clinicopathological features and prognostic factors of HNM in Asians. Asian melanoma patients who underwent surgical treatment from January 2003 to December 2020 were retrospectively reviewed. The clinicopathological features and risk factors for local recurrence, lymph node metastasis, and distant metastasis were analyzed. Among 230 patients, 28 (12.2%) were diagnosed with HNM, and 202 (87.8%) with other melanoma. The histologic subtype significantly differed as the nodular type was predominant in HNM whereas the acral lentiginous type was predominant in other melanoma ( P  < 0.001). HNM was significantly associated with higher local recurrence ( P  = 0.045), lymph node metastasis ( P  = 0.048), distant metastasis ( P  = 0.023), and lower 5-year disease-free survival ( P  = 0.022) than other melanoma. Ulceration was the risk factor for lymph node metastasis based on multivariable analysis ( P  = 0.013). A high proportion of HNM present as the nodular subtype in Asians, leading to poor outcomes and low survival. Therefore, more cautious surveillance, evaluation, and aggressive treatment are required.

The influence of antibiotic administration on the outcomes of head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiation.

PURPOSE: Effects of antibiotic administration on patients' microbiome may negatively influence cancer outcomes, and adverse prognoses after antibiotic application have been demonstrated for cancer patients receiving immune checkpoint inhibitors. While the microbiome may play an important role also in head-and-neck squamous cell carcinoma (HNSCC), the prognostic value of antibiotic treatment here is largely unknown. We therefore analyzed whether antibiotic prescription is associated with impaired oncological outcomes of HNSCC patients undergoing definitive (chemo)radiation. METHODS: A cohort of 220 HNSCC patients undergoing definitive (chemo)radiation between 2010 and 2019 was analyzed. The influence of antibiotic administration on locoregional control, progression-free survival (PFS) and overall survival (OS) was determined using Kaplan-Meier and Cox analyses. RESULTS: A total of 154 patients were treated with antibiotics within 30 days before (chemo)radiation (pretherapeutic) or during (chemo)radiation (peritherapeutic). While antibiotic prescription was not associated with age, ECOG, tumor localization or radiotherapy characteristics, patients treated with antibiotics had significantly higher tumor stages. Peritherapeutic antibiotic administration diminished PFS (HR = 1.397, p < 0.05, log-rank test) and OS (HR = 1.407, p < 0.05), whereas pretherapeutic administration did not. Antibiotic application was an independent prognosticator for OS (HR = 1.703, p < 0.05) and PFS (HR = 1.550, p < 0.05) in the multivariate Cox analysis within the subgroup of patients aged < 75 years. CONCLUSION: Peritherapeutic antibiotic usage was associated with impaired oncological outcomes in HNSCC patients undergoing (chemo)radiation. Further studies including microbiome analyses are required to elucidate underlying mechanisms.

Neck management of pathological N1 oral squamous cell carcinoma: a retrospective study.

This study was performed to compare the effects of neck dissection procedures on the prognosis of patients with pathological N1 (pN1) oral squamous cell carcinoma (OSCC), analyse factors affecting the prognosis, and provide a neck management strategy for clinical N1 (cN1) oral cancer. The study patients were divided into two groups according to the neck dissection: a selective neck dissection (SND) group (n = 85) and a radical or modified radical neck dissection (RND/MRND) group (n = 22). There was no statistically significant difference in recurrence rates at local, regional, and distant sites between the SND and RND/MRND groups. The 5-year overall survival was 68.3% for SND and 65.2% for RND/MRND patients (P = 0.590), while the 5-year disease-specific survival was 70.4% for SND and 75.7% for RND/MRND patients (P = 0.715). Histological grade and postoperative radiotherapy were independent predictors of the outcome for SND patients. For histological grade II/III cases, 5-year overall survival (P = 0.004) and disease-specific survival (P = 0.002) outcomes differed significantly between patients treated with and without postoperative radiotherapy, with worse survival for patients not treated with radiotherapy. Therefore, SND appears appropriate for cN1 OSCC patients, and postoperative radiotherapy is recommended for those with histological grade II or III tumours.

Racial survival disparities in head and neck cancer clinical trials.

BACKGROUND: Survival disparities between Black and White head and neck cancer patients are well documented, with access to care and socioeconomic status as major contributors. We set out to assess the role of self-reported race in head and neck cancer by evaluating treatment outcomes of patients enrolled in clinical trials, where access to care and socioeconomic status confounders are minimized. METHODS: Clinical trial data from the Radiation Therapy Oncology Group studies were obtained. Studies were included if they were therapeutic trials that employed survival as an endpoint. Studies that did not report survival as an endpoint were excluded; 7 Radiation Therapy Oncology Group Studies were included for study. For each Black patient enrolled in a clinical trial, a study arm-matched White patient was used as a control. RESULTS: A total of 468 Black participants were identified and matched with 468 White study arm-specific controls. White participants had better outcomes than Black participants in 60% of matched pairs (P < .001). Black participants were consistently more likely to have worse outcomes. When outcomes were measured by progression-free survival or disease-free survival, the failure rate was statistically significantly higher in Black participants (hazard ratio [HR] = 1.50, P < .001). Failure was largely due to locoregional failure, and Black participants were at higher risk (subdistribution HR =1.51, P = .002). The development of distant metastasis within the paired cohorts was not statistically significantly different. CONCLUSION: In this study of clinical trial participants using self-reported race, Black participants consistently had worse outcomes in comparison to study arm-specific White controls. Further study is needed to confirm these findings and to explore causes underlying this disparity.

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications.

Oral squamous cell carcinoma (OSCC) is particularly prevalent in Taiwan. The goal of this study was to determine the clinicopathological role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) proteins as an indicator of clinical outcomes in OSCC patients. In this study, immunohistochemical (IHC) analysis was used to examine IGF2BP2 protein expression in 244 OSCC patients. We investigated the relationships among IGF2BP2 expression, clinicopathological variables, and patient survival. Our results showed that IGF2BP2 cytoplasmic protein expression was significantly correlated with lymph node metastasis, cancer stage, and patient survival. Kaplan-Meier survival curves revealed that elevated cytoplasmic IGF2BP2 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate cox proportional hazard models revealed that cytoplasmic IGF2BP2 expression, T status, and lymph node metastasis were independent prognostic factors for survival. In conclusion, IGF2BP2 protein was found to be a helpful predictive marker for OSCC patients, as well as a possible therapeutic target for OSCC treatment.

Matched-pair analysis of survival in patients with poorly differentiated versus well and moderately differentiated hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HPSCC) is among the most common malignances of the head and neck and is associated with a poor prognosis. Although both differentiation and tumor-node-metastasis stage affect tumor aggressiveness, the effect of differentiation on the prognosis of HPSCC at different stages is unclear. The aim of this study was to compare survival outcomes between patients with poorly differentiated versus well-differentiated and moderately differentiated HPSCC. Patients with well/moderately differentiated and poorly differentiated HPSCC were matched based on age, sex, smoking status, alcohol use, comorbidity score, tumor stage, and therapeutic strategies. The Kaplan-Meier curve and Cox proportional hazards model were used to analyze survival. A total of 204 patients with newly diagnosed HPSCC were included after matching 102 well/moderately differentiated cases and 102 poorly differentiated cases from Peking Union Medical College Hospital. Patients with well/moderately differentiated HPSCC had significantly better disease-specific survival (P = .003) and overall survival (P = .006) than patients with poorly differentiated HPSCC. Additionally, multivariable analysis indicated that increased differentiation was associated with a significantly reduced risk of overall death (adjusted hazard ratio, 0.51; 95% confidence interval, 0.34-0.78, P = .002), and death due to disease (adjusted hazard ratio, 0.44; 95% confidence interval, 0.28-0.69, P < .001). Survival outcomes differed significantly between the well/moderately differentiated and poorly differentiated HPSCC patients. Treatment strategies based on the level of pathological differentiation might be necessary to improve survival outcomes in patients with HPSCC.

Different inflammatory blood markers correlate with specific outcomes in incident HPV-negative head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma.

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

The Spectrum of Malignant Neoplasms among Liver Transplant Recipients: Sociodemographic Factors, Mortality, and Hospital Burden.

Objective: To determine the nationwide prevalence of malignant neoplasms (excluding hepatocellular carcinoma-HCC) in hospitalized liver transplant recipients and to study the hospital utilization, and mortality to the incidence of malignancies. To the best of our knowledge, few epidemiological studies addressed outcomes in post-liver transplant patients, such as the annual number of hospitalizations, mortality, patient characteristics regarding malignancies. Methods: NIS database was queried between 2016 and 2018 to retrieve records of patients admitted with a principal or secondary diagnosis of liver transplant following the International Classification of Diseases, tenth Revision (ICD-10). The population was divided into case and control groups according to the presence and absence of malignant neoplasm (MN) except for HCC. We also compared the incidence of MN in LTX patients and non-LTX matched cohort. Results: A total of 7.28% admissions were associated with malignant neoplasms (except HCC) in LTX patients. Lymphomas, respiratory, gastrointestinal (excluding HCC), leukemia, and head/neck were commonest cancers with estimated admission rates of 0.97%, 0.90%, 0.80%, 0.53%, and 0.49%, respectively. Lung cancer was the most frequent malignant neoplasm among White and Black racial/ethnic groups (15.78% and 14.8%), whereas lymphoma was pervasive among Hispanics (20.3%). Lung cancer had the highest in-hospital mortality (10.55%), followed by the cancer of the nervous system (9.09%). The LTX and non-LTX cohort comparison showed that LTX patients are at increased risk of head and neck cancers, skin cancers, lymphomas, tumors, and Myelodysplastic syndrome. According to a multivariate analysis, a statistically significant association existed between malignant neoplasms in LTX patients and the following factors: increasing age (P < .001), higher mortality (P < .001), females with 29% lesser odds than males (P < .001), Black race and Hispanic ethnicity with 20% and 26% lesser odds as compared to White (P < .05). Clinical factors included smoking, Alcoholic cirrhosis, Hepatitis B, and Hepatitis C, were statistically significant risk factors of post-liver transplantation malignancies. Conclusions: Malignancies were frequent among elderly patients and predominantly in males. Lymphoproliferative diseases were the most prevalent malignancy types, followed by respiratory/lung cancer- which showed the highest mortality risk of all cancers. LTX patients are at increased risk of head and neck cancers, skin cancers, lymphoma, tumors, and Myelodysplastic syndrome compared to non-LTX patients.

Carbon-ion Radiotherapy for Inoperable Head and Neck Bone and Soft-tissue Sarcoma: Prospective Observational Study.

BACKGROUND/AIM: Bone and soft-tissue sarcomas of the head and neck have very poor prognoses. This prospective study aimed to investigate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for bone and soft-tissue sarcoma of the head and neck. PATIENTS AND METHODS: The present study was a prospective clinical study that included 10 consecutive patients diagnosed with bone and soft-tissue sarcoma of the head and neck who were treated with C-ion RT between 2012 and 2018 at our institution. C-Ion RT consisted of 70.4 Gy (relative biological effectiveness) in 16 fractions. RESULTS: The 3-year local control, overall survival, and progression-free survival rates for patients overall were 72.9%, 77.8%, and 36%, respectively. CONCLUSION: The present study demonstrated the efficacy of C-ion RT for bone and soft-tissue sarcoma of the head and neck; adverse events were within the expected range.

PD-L1 Expression and Survival Rates Using TPS and CPS for Nivolumab-treated Head-and-Neck Cancer.

BACKGROUND/AIM: This study investigated the expression and survival rates of programmed cell death ligand 1 using the tumor proportion score (TPS)and combined positive score (CPS) for recurrent/metastatic head and neck cancer administered nivolumab. PATIENTS AND METHODS: Forty-seven patients with recurrent/metastatic head and neck cancer with a history of platinum-based chemotherapy who received nivolumab between June 1st, 2017, and January 31st, 2019 were included in this study. RESULTS: TPS and CPS were strongly correlated (r=0.546). When the TPS was high (≥40%), overall and progression-free survival were significantly better. The median overall survival was 8.5 months, median progression-free survival was not reached, and the 1-year progression-free survival rate was 71.4%. However, there was no significant difference in overall and progression-free survival between the groups with high CPS (≥20). CONCLUSION: This is the first report to show a strong correlation between TPS and CPS. High TPS (40% or higher) may be used as a predictor of prognosis and efficacy. Further studies are warranted to determine the use of the CPS as a biomarker.

Comparison of Dosage of Nivolumab in Efficacy and Safety for Recurrent Metastatic Squamous Cell Carcinoma.

BACKGROUND/AIM: There are no real-world comparative data of nivolumab doses of 3 mg/kg and 240 mg/body for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We investigated the efficacy and safety of nivolumab in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) at different doses using real-world data. PATIENTS AND METHODS: R/M SCCHN patients who received nivolumab were divided into the 3 mg/kg and 240 mg/body groups and retrospectively examined for efficacy and safety. RESULTS: A total of 199 patients (3 mg/kg and 240 mg/body, 88 and 111 patients, respectively) were included. The 3 mg/kg vs. 240 mg/body groups had similar overall response rates (15% vs. 25, p=0.15), disease control rates (46% vs. 57%, p=0.15), overall survival (9.5 months vs. 10.9 months), and progression-free survival (3.7 months vs. 3.8 months, p=0.95). The incidence of immune-related adverse events was also similar in both groups. CONCLUSION: In R/M SCCHN patients, nivolumab showed similar efficacy and safety at doses of 3 mg/kg and 240 mg/body.

Secondary primary malignancy in patients with head and neck squamous cell carcinoma: 27-year experience from the perspective of diagnostic tools.

BACKGROUND: The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools. METHODS: This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992-2003; Group B: 2004-2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups. RESULTS: Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A. CONCLUSION: Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.

Association of ALDH1 with Response to Radiotherapy and Its Impact on Survival in Patients with Advanced Stage of Head and Neck Squamous Cell Carcinoma (HNSCC).

BACKGROUND: The presence of cancer stem-like cells within tumor microenvironment distinctly governs response to chemo-radiotherapy. The ALDH1 (Aldehyde dehydrogenase 1) has emerged as a cancer stem cell (CSC) marker in various tumors. The aim of the study was to examine the expression of ALDH1 in HNSCC patients undergoing radiotherapy to evaluate its correlation with clinicopathological parameter, treatment response and survival. METHODS: Expression of ALDH1 was evaluated by immunohistochemistry in 90 histopathologically confirmed HNSCC patients and 90 matched controls. The association between ALDH1 expression, clinicopathological parameters and treatment response was determined. RESULTS: The immunohistochemistry results showed that ALDH1 was consistently expressed in all the HNSCC specimens although at different intensities. On the other hand, control specimens did not show similar expression of ALDH1. ALDH1 expression demonstrated statistically significant association with tumor size (p<0.001), lymph node status (p<0.001), stage (p<0.001), grade (p<0.001) and treatment response (p<0.001). Multivariate ordinal logistic regression analysis indicated alcohol and ALDH1 as an independent predictor of responsiveness to radiotherapy in HNSCC patients. Multivariate Cox regression analysis indicated that lymph node status (p=0.020), grade (p=0.006) and recurrence (p=0.002) were potential independent predictors of overall survival. CONCLUSION: From previous studies, ALDH1 has been contemplated not only as a promising prognostic and diagnostic marker but also as a likely drug target. Our study gives new understanding regarding the association between ALDH1, cancer prognosis and radioresistance. Our findings suggest that ALDH1, lymph node status, grade and alcohol could be the viable targets for HNSCC and it also provides new prospects for radiotherapy sensitivity in HNSCC.

Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma.

Background: Inhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC). Methods: The expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model. Results: PD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all P < 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all P < 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; P < 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023). Conclusions: The expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.

Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.