Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen.

BACKGROUND: In recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population. METHODS: This study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS. RESULTS: A total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 - 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44-13.61), 7.5 months (95% CI 7.33-8.17), and 4.01 months (95% CI 3.94-4.08), respectively, with a log-rank test p-value < 0.001. CONCLUSION: This study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study.

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Prophylactic Versus Reactive Megestrol Acetate Use for Critical Body Weight Loss in Patients with Pharyngeal and Laryngeal Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

BACKGROUND: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. METHODS: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. RESULTS: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81]). CONCLUSION: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

Effect of prophylactic tube feeding in head and neck cancer patients with high Mallampati score undergoing definitive concurrent chemoradiotherapy.

PURPOSE: There is no consensus on the selection of appropriate prophylactic tube feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the effect of prophylactic tube feeding in patients with HNSCC who presented with a high Mallampati score and underwent CCRT. METHODS: We prospectively enrolled 185 consecutive patients with stage II to IVa HNSCC and a pre-treatment Mallampati score of 3 or 4 who received CCRT between August 2017 and December 2018 with follow-up data collected retrospectively. Patients were divided to either with or without prophylactic tube feeding group for comparison of treatment tolerance, toxicities, and quality of life(QOL). Propensity score matching (PSM) was used to achieve balanced covariates across the two groups. RESULTS: Of the cohort, 52 (28.1%) and 133 (71.9%) patients were allocated to the prophylactic and non-prophylactic tube feeding groups, respectively. Before and after PSM, patients in the tube feeding group had a significantly lower incidence of incomplete radiotherapy, incompletion of chemotherapy, emergency room visits, and grade 3 or higher infection, and improved symptoms of quality of life after CCRT than those in the non-tube feeding group. CONCLUSION: Prophylactic tube feeding was associated with better treatment tolerance, safety profiles, and quality of life in patients with HNSCC and high Mallampati scores who underwent CCRT. Therefore, Mallampati score might serve as a clinical tool for proactive selection of patients receiving prophylactic tube feeding in HNSCC patients upon receiving CCRT.

Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial.

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Factors impacting posttraumatic growth in head-and-neck cancer patients with oncologic emergencies.

PURPOSE: To identify factors associated with posttraumatic growth (PTG) of head-and-neck cancer squamous cancer (HNC) patients with oncologic emergencies (OE) within the first six months post-treatment. METHODS: We conducted a cross-sectional study of HNC patients in Taiwan from May 2019 to April 2021 using patient-reported outcomes. Patients were assessed for symptom distress, anxiety, fear of recurrence (FCR), and PTG. Multiple regression analysis was conducted to identify factors associated with PTG. The independent-samples t-test was used to compare PTG and its five specific domains in patients with low FCR, high FCR, low anxiety, and high anxiety. RESULTS: Of the 114 patients surveyed, 46.5% reported little-to-no PTG, and 53.5% had moderate-to-high PTG. Greater PTG was associated with greater FCR, longer time since OE, less anxiety, having a cancer recurrence, and greater educational attainment. These factors explained 38.6% of the variance in PTG. CONCLUSION: A notable proportion of HNC patients with OE-reported PTG but almost half-reported little-to-no PTG. PTG occurred most in the domain of appreciation of life. The study results also suggest that training patients in coping skills and inviting them to group growth experiences can help them increase PTG and cope with cancer-related psychological threats related to OE.

Circulating EGFR Mutations in Patients with Lung Adenocarcinoma by Circulating Tumor Cell Isolation Systems: A Concordance Study.

Background: We developed a hybrid platform using a negative combined with a positive selection strategy to capture circulating tumor cells (CTCs) and detect epidermal growth factor receptor (EGFR) mutations in patients with metastatic lung adenocarcinoma. Methods: Blood samples were collected from patients with pathology-proven treatment-naïve stage IV lung adenocarcinoma. Genomic DNA was extracted from CTCs collected for EGFR mutational tests. The second set of CTC-EGFR mutational tests were performed after three months of anti-cancer therapy. Results: A total of 80 samples collected from 28 patients enrolled between July 2016 and August 2018. Seventeen patients had EGFR mutations, including Exon 19 deletion (n = 11), L858R (n = 5), and de-novo T790 and L858R (n = 1). Concordance between tissue and CTCs before treatment was 88.2% in EGFR- mutant patients and 90.9% in non-mutant patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EGFR mutation tests for CTCs were 89.3%, 88.2%, 90.9%, 93.8%, and 83.3%, respectively. Conclusions: CTCs captured by a hybrid platform using a negative and positive selection strategy may serve as a suitable and reliable source of lung cancer tumor DNA for detecting EGFR mutations, including T790M.

Reduced System Complexity of Heart Rate Dynamics in Patients with Hyperthyroidism: A Multiscale Entropy Analysis.

Studying heart rate dynamics would help understand the effects caused by a hyperkinetic heart in patients with hyperthyroidism. By using a multiscale entropy (MSE) analysis of heart rate dynamics derived from one-channel electrocardiogram recording, we aimed to compare the system complexity of heart rate dynamics between hyperthyroid patients and control subjects. A decreased MSE complexity index (CI) computed from MSE analysis reflects reduced system complexity. Compared with the control subjects (n = 37), the hyperthyroid patients (n = 37) revealed a significant decrease (p < 0.001) in MSE CI (hyperthyroid patients 10.21 ± 0.37 versus control subjects 14.08 ± 0.21), sample entropy for each scale factor (from 1 to 9), and high frequency power (HF) as well as a significant increase (p < 0.001) in low frequency power (LF) in normalized units (LF%) and ratio of LF to HF (LF/HF). In conclusion, besides cardiac autonomic dysfunction, the system complexity of heart rate dynamics is reduced in hyperthyroidism. This finding implies that the adaptability of the heart rate regulating system is impaired in hyperthyroid patients. Additionally, it might explain the exercise intolerance experienced by hyperthyroid patients. In addition, hyperthyroid patients and control subjects could be distinguished by the MSE CI computed from MSE analysis of heart rate dynamics.

Impact of early nutrition counseling in head and neck cancer patients with normal nutritional status.

BACKGROUND: Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer (HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT). METHODS: A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks, n = 105, 43.2%), late (> 2 weeks, n = 102, 42.0%), and no nutritional counseling groups (n = 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison. RESULTS: The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (p = 0.035), respectively. The median body weight changes at end of CCRT were - 4.8% (range, - 13.3 to 8.7%), - 5.6% (range, - 21.9 to 5.6%), and - 8.6% (range, - 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively. CONCLUSIONS: Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.

A prospective nutritional assessment using Mini Nutritional Assessment-short form among patients with head and neck cancer receiving concurrent chemoradiotherapy.

BACKGROUND: No gold standard of nutritional assessment is established among patients with head and neck cancer (HNC) receiving concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the clinical significance of pre-treatment nutritional status using the Mini Nutritional Assessment-short form (MNA-SF) among HNC patients receiving CCRT. METHODS: A total of 461 consecutive patients with newly diagnosed HNC treated with definitive CCRT at three medical institutes were prospectively enrolled. Nutritional status was assessed using MNA-SF within 7 days before CCRT initiation. Patients were classified as having normal nutrition, at risk of malnutrition, and malnourished groups according to MNA-SF for comparison. RESULTS: The 1-year overall survival rates were 89.8%, 76.8%, and 67.7% in the normal nutrition, at risk of malnutrition, and malnourished groups, respectively. Patients with normal nutrition had significantly lower rates of uncompleted radiotherapy and chemotherapy (4.5% and 4.1%, respectively) compared with patients at risk for malnutrition (14.1% and 11.5%, respectively) and those malnourished (11.1% and 11.1%, respectively). Patients with normal nutrition had significantly lower treatment-related complication rates regarding emergency room visits, hospital admission, and need for tubal feeding than those with at risk of malnutrition and malnourished. Patients with normal nutrition had significantly fewer severe hematologic toxicities (p = 0.044) and severe non-hematologic toxicities (p = 0.012) of CCRT than those malnourished. CONCLUSION: Pre-CCRT nutritional status identifies HNC patients vulnerable to treatment interruption and treatment complications. We suggest that nutritional assessment with MNA-SF should be incorporated in pre-CCRT evaluation for all HNC patients.

Comparison of 18F-FDG PET/MRI, MRI, and 18F-FDG PET/CT for the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma.

PURPOSE: In this prospective study, we sought to compare the clinical utility of fluorodeoxyglucose PET/MRI, MRI, and PET/CT in the detection of synchronous cancers and distant metastases in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OHSCC). METHODS: We examined 198 consecutive patients with biopsy-proven OHSCC who agreed to receive chemoradiation. All patients underwent pretreatment PET/MRI and PET/CT on the same day. Patients were followed-up for a minimum of 12 months or until death. The McNemar's test and receiver-operating characteristic (ROC) curves were used to compare sensitivity/specificity and the diagnostic capabilities of PET/MRI, MRI, and PET/CT, respectively. RESULTS: We identified 55 patients (27.7%) who had synchronous cancers and/or distant metastases (number of involved sites: 83). The results of site-based analysis revealed that the sensitivity of PET/MRI was 15.7% higher than that of MRI (73.5% versus 57.8%, p < 0.001) and 3.6% higher compared with PET/CT (73.5% versus 69.9%, p = 0.083), whereas the sensitivity of PET/CT was 12.1% higher than that of MRI (69.9% versus 57.8%, p = 0.012). On a patient-basis, ROC curve analysis demonstrated that PET/MRI yielded a greater area under curve than MRI (0.930 versus 0.905, p = 0.023). There were no significant differences in terms of diagnostic capability between MRI and PET/CT (0.905 versus 0.917, p = 0.469) and between PET/MRI and PET/CT (0.930 versus 0.917, p = 0.062). CONCLUSIONS: In our cohort, PET/MRI showed a significantly higher diagnostic capability than MRI and no significant difference compared with PET/CT for the detection of synchronous cancers or distant metastases in patients with OHSCC.

A combined analysis of maximum standardized uptake value on FDG-PET, genetic markers, and clinicopathological risk factors in the prognostic stratification of patients with resected oral cavity squamous cell carcinoma.

OBJECTIVE: Clinical outcomes of patients with resected oral cavity squamous cell carcinoma (OCSCC) chiefly depend on the presence of specific clinicopathological risk factors (RFs). Here, we performed a combined analysis of FDG-PET, genetic markers, and clinicopathological RFs in an effort to improve prognostic stratification. METHODS: We retrospectively reviewed the clinical records of 2036 consecutive patients with first primary OCSCC who underwent surgery between 1996 and 2016. Of them, 345 underwent ultra-deep targeted sequencing (UDTS, between 1996 and 2011) and 168 whole exome sequencing (WES, between 2007 and 2016). Preoperative FDG-PET imaging was performed in 1135 patients from 2001 to 2016. Complete data on FDG-PET, genetic markers, and clinicopathological RFs were available for 327 patients. RESULTS: Using log-ranked tests based on 5-year disease-free survival (DFS), the optimal cutoff points for maximum standardized uptake values (SUV-max) of the primary tumor and neck metastatic nodes were 22.8 and 9.7, respectively. The 5-year DFS rates were as follows: SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7 (n = 77) versus SUVtumor-max < 22.8 and SUVnodal-max < 9.7 (n = 250), 32%/62%, P < 0.001; positive UDTS or WES gene panel (n = 64) versus negative (n = 263), 25%/62%, P < 0.001; pN3b (n = 165) versus pN1-2 (n = 162), 42%/68%, P < 0.001. On multivariate analyses, SUVtumor-max ≥ 22.8 or SUVnodal-max ≥ 9.7, a positive UDTS/WES gene panel, and pN3b disease were identified as independent prognosticators for 5-year outcomes. Based on these variables, we devised a scoring system that identified four distinct prognostic groups. The 5-year rates for patients with a score from 0 to 3 were as follows: loco-regional control, 80%/67%/47%/24% (P < 0.001); distant metastases, 13%/23%/55%/92% (P < 0.001); DFS, 74%/58%/28%/7% (P < 0.001); and disease-specific survival, 80%/64%/35%/7% (P < 0.001) respectively. CONCLUSIONS: The combined assessment of tumor and nodal SUV-max, genetic markers, and pathological node status may refine the prognostic stratification of OCSCC patients.

Tumor Depth of Invasion (Tumor > 4 cm/Depth > 10 mm and Depth > 20 mm) and Through Cortex/Skin Invasion are Both Valid Criteria for Classifying Tumors as pT4a in AJCC 2018 Oral Cavity Cancer Staging System.

BACKGROUND: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease. METHODS: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes. RESULTS: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates. CONCLUSIONS: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer.

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

PURPOSE: Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. METHODS: We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. RESULTS: PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. CONCLUSIONS: For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.

Clinical characteristics and survival outcomes of terminally ill patients undergoing withdrawal of mechanical ventilation.

BACKGROUND: Withdrawal of mechanical ventilation is an important, but rarely explored issue in Asia during end-of-life care. This study aimed to describe the clinical characteristics and survival outcomes of terminally ill patients undergoing withdrawal of mechanical ventilation in Taiwan. METHODS: One-hundred-thirty-five terminally ill patients who had mechanical ventilation withdrawn between 2013 and 2016, from a medical center in Taiwan, were enrolled. Patients' clinical characteristics and survival outcomes after withdrawal of mechanical ventilation were analyzed. RESULTS: The three most common diagnoses were organic brain lesion, advanced cancer, and newborn sequelae. The initiator of the withdrawal process was family, medical personnel, and patient him/herself. The median survival time was 45 min (95% confidence interval, 33-57 min) after the withdrawal of mechanical ventilation, and 102 patients (75.6%) died within one day after extubation. The median time from diagnosis of disease to receiving life-sustaining treatment and artificial ventilation support, receiving life-sustaining treatment and artificial ventilation support to "Withdrawal meeting," "Withdrawal meeting" to ventilator withdrawn, and ventilator withdrawn to death was 12.1 months, 19 days, 1 day, and 0 days, respectively. Patients with a diagnosis of advanced cancer and withdrawal initiation by the patients themselves had a significantly shorter time interval between receiving life-sustaining treatment and artificial ventilation support to "Withdrawal meeting" compared to those with non-cancer diseases and withdrawal initiation by family or medical personnel. CONCLUSION: This study is the first observational study to describe the patients' characteristics and elaborate on the survival outcome of withdrawal of mechanical ventilation in patients who are terminally ill in an Asian population. Understanding the clinical characteristics and survival outcomes of mechanical ventilation withdrawal might help medical personnel provide appropriate end-of-life care and help patients/families decide about the withdrawal process earlier.