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 (

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.

Changes in fatigue among cancer patients before, during, and after radiation therapy: A meta-analysis.

BACKGROUND: Fatigue is a common symptom in cancer patients receiving radiotherapy. However, previous studies report inconsistent patterns of fatigue change. AIM: The aim of this study was to estimate changes in fatigue among patients with cancer before, during, and after radiotherapy. METHODS: Five databases (PubMed, SDOL, CINAHL Plus with Full Text, Medline [ProQuest], and ProQuest Dissertations) were searched for studies published from January 2006 to May 2021. Three effect sizes of fatigue change (immediate, short-term, and long-term) were calculated for each primary study using standardized mean difference. A random-effect model was used to combine effect sizes across studies. Subgroup analyses and meta-regression were performed to identify potential categorical and continuous moderators, respectively. RESULTS: Sixty-five studies were included in this meta-analysis. The weighted mean effect size for immediate, short-term, and long-term effects was 0.409 (p < .001; 95% CI [0.280, 0.537]), 0.303 (p < .001; 95% CI [0.189, 0.417]), and 0.201 (p = .05; 95% CI [-0.001, 0.404]), respectively. Studies with prostate cancer patients had a significantly higher short-term (0.588) and long-term weight mean effect size (0.531) than studies with breast (0.128, -0.072) or other cancers (0.287, 0.215). Higher radiotherapy dosage was significantly associated with a higher effect size for both immediate (ß = .0002, p < .05) and short-term (ß = .0002, p < .05) effect. LINKING EVIDENCE TO ACTION: Findings from this meta-analysis indicated that radiotherapy-induced fatigue (RIF) exist for more than 3 months after the completion of treatment. Assessment of radiation-induced fatigue in cancer patients should extend long after treatment completion, especially for patients with prostate cancer and patients receiving a higher radiation dose. Interventions to reduce fatigue tailored for different treatment phases may be developed.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

Risk Management for Radiation-Induced Cardiovascular Disease (RICVD): The 2022 Consensus Statement of the Taiwan Society for Therapeutic Radiology and Oncology (TASTRO) and Taiwan Society of Cardiology (TSOC).

Advances in cancer management have significantly improved survival in patients with cancers. Cardiovascular complications of cancer treatment are becoming significant competing causes of death in these patients. Radiotherapy is an indispensable component of cancer treatment, and irradiation of the heart and vasculature during cancer radiotherapy is now recognized as a new risk factor for cardiovascular diseases. It is important to involve multidisciplinary expertise and provide practical recommendations to promote awareness, recognize risks, and provide adequate interventions without jeopardizing cancer control. In this consensus paper, experts from the Taiwan Society for Therapeutic Radiology and Oncology and Taiwan Society of Cardiology provide a focused update on the clinical practice for risk stratification and management of radiation-induced cardiovascular disease (RICVD). We believe that implementing RICVD care under a collaborative cardio-oncology program will significantly improve cancer treatment outcomes and will facilitate high quality clinical investigations.

Hypothyroidism and risks of cerebrovascular complications among patients with head and neck cancer after radiotherapy.

BACKGROUND: Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. METHODS: Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. RESULTS: 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. CONCLUSIONS: Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.

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 scoping review of medical education research for residents in radiation oncology.

BACKGROUND: Both medical education and radiation oncology have progressed significantly in the past decade, but a generalized overview of educational research for radiation oncology residents has not been produced. This study examines recent research trends in medical education for residents in radiation oncology through a scoping review. METHODS: We conducted a scoping review of medical education research for residents in radiation oncology to survey the research trends. We used publications available on MEDLINE, PubMed, and Scopus to conduct this scoping review. RESULTS: We screened 221 full-text articles, 146 of which met our inclusion criteria. These publications showed increased activity in medical education research for residents, most involving affiliations in the United States. We identified persistent interest in training-, contouring-, and technology-related issues. An increase in research related to career, treatment quality, and multidisciplinary training was also observed. However, no research about teacher training was identified. CONCLUSIONS: This scoping review presents the trends in study interests among stakeholders of medical education research in radiation oncology. With an investigation of existing studies, this research identifies areas of high priority and a lack of studies about teacher training. This study provides potential future directions for medical education research for residents in radiation oncology.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

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.

Body image in head and neck cancer patients treated with radiotherapy: the impact of surgical procedures.

BACKGROUND: In this study, we aimed to investigate the impact of surgical procedures on the body image of head and neck cancer patients treated with radiotherapy and with or without radical surgery. METHODS: A cross-sectional survey of 150 patients with head and neck cancer was conducted. Sixty patients had nasopharyngeal cancer treated with definitive radiotherapy without surgery, and 90 patients had oral cavity cancer treated with radical surgery plus adjuvant radiotherapy. All participants completed a 10-item Body Image Scale (BIS) questionnaire to assess body image dissatisfaction. Among all patients, the socio-demographic and clinical variables were age, gender, partnership, education, employment, and radical surgery. In surgically-treated patients, the clinical variables were facial skin sacrificed, mouth angle sacrificed, glossectomy, maxillectomy, and mandibulectomy. ANOVAs, t-tests, and multiple regressions were used to evaluate the relationships between these variables and BIS results. RESULTS: In all patients, radical surgery was the strongest independent predictor of BIS scores. Surgically-treated patients had significantly worse BIS scores than the patients without surgery. In surgically-treated patients, facial skin sacrificed, mouth angle sacrificed, maxillectomy, and mandibulectomy were significantly associated with body image. According to multivariable analyses, inferior maxillectomy and segmental mandibulectomy were independent prognosticators of a poor BIS score in surgically-treated patients. CONCLUSION: Radical surgery for head and neck cancer patients has a significant impact on their body image, especially for those undergoing facial bone destructive surgery.

Roles of preoperative C-reactive protein are more relevant in buccal cancer than other subsites.

BACKGROUND: C-reactive protein (CRP) is an early marker for inflammation, and a relationship between serum CRP levels and survival in oral cancer has been demonstrated previously. In this study, we investigated the roles of CRP in different oral cancer subsites. METHODS: Three hundred and forty-three oral squamous cell carcinoma patients between June 1999 and March 2015 were retrospectively reviewed. Serum CRP levels were measured preoperatively. RESULTS: The elevation of CRP levels (≥5.0 mg/L) was significantly correlated with pathologic tumor status, pathologic nodal status, nodal extracapsular spread, tumor stage, skin invasion, tumor depth (≥10 mm), and bone invasion. The correlation between elevation of CRP and clinicopathologic factors was more evident in the buccal cancer compared to other tumor subsites. The disease-free survival and overall survival correlation was significant in buccal cancer (p = 0.003 and p < 0.001) but not in tongue cancer (p = 0.119 and p = 0.341) or other oral cancer subsites (p = 0.246 and p = 0.696). CONCLUSIONS: Preoperative serum CRP level was a prognosticator in oral squamous cell carcinoma, and its effect was more prominent in buccal cancer that occurs more frequently in areca-quid (AQ) endemic regions.

What should we expect from robotic surgery for second primary oropharyngeal cancer?

The outcomes of second primary oropharyngeal cancer (SPOPC) may not be determined by oropharyngeal cancer but from the other index cancer as well. The management of (SPOPC) remains inconclusive and limited. Transoral robotic surgery (TORS) to maximize the functional outcomes without reducing oncologic effect is suggested as the primary treatment for selected oropharyngeal cancer. This study aimed to evaluate the feasibility and outcomes of TORS for the management of SPOPC. Patients who underwent TORS from January 2011 to June 2015 at a tertian referral center in Taiwan were recruited. Loco-regional status, overall survival (OS), disease-specific survival (DSS), and postoperative functional status were evaluated. Fifteen patients received TORS for SPOPC with curative intent, including eleven with tongue-base carcinomas, and four with tonsil carcinomas. One case was terminated because of inadequate exposure and the other 14 cases were completed with negative pathologic margins. Two-year OS and DSS were 53 and 77%, respectively. Patients with SPOPC occurring within 6 months had poorer outcomes (p = 0.044). The median time to feeding-tube removal was 5 days, and one patient had long-term gastric-tube dependence. Patients of age <65 years with synchronous SPOPC and esophageal cancer as the other index cancer were significant worse in oncologic outcomes. We concluded that TORS is a feasible alternative treatment in selected patients with SPOPC. Patients with metachronous T1-2 SPOPC without an esophageal primary can achieve excellent survival after TORS, while TORS can maximize functional preservation with limited destruction in patients with low life expectancy.

Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer.

BACKGROUND/PURPOSE: Significant ethnic differences in susceptibility to the effects of chemotherapy exist. Here, we retrospectively analyzed the safety and efficacy of induction chemotherapy (ICT) with dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) in Asian patients with borderline resectable or unresectable head and neck squamous cell carcinoma (HNSCC). METHODS: Based on the incidence of adverse events that occurred during daily practice, TPF90 (90% of the original TPF dosage; docetaxel 67.5 mg/m2 on Day 1, cisplatin 67.5 mg/m2 on Day 1, and 5-fluorouracil 675 mg/m2 on Days 1-5) was used for HNSCC patients who were scheduled to receive ICT TPF. RESULTS: Between March 2011 and May 2014, 52 consecutive patients with borderline resectable or unresectable HNSCC were treated with ICT TPF90 followed by concurrent chemoradiotherapy. Forty-four patients (84.6%) received at least three cycles of ICT TPF90. The most commonly observed Grade 3-4 adverse events included neutropenia (35%), anemia (25%), stomatitis (35%), diarrhea (16%), and infections (13.5%). In an intention-to-treat analysis, the complete and partial response rates after ICT TPF90 were 13.5% and 59.6%, respectively. The complete and partial response rates following radiotherapy and salvage surgery were 42.3% and 25.0%, respectively. The estimated 3-year overall survival and progression-free survival rates were 41% [95% confidence interval (CI): 25-56%] and 23% (95% CI: 10-39%), respectively. The observed median overall survival and progression-free survival were 21.0 months (95% CI: 13.3-28.7 months) and 16.0 months (95% CI: 10.7-21.3 months), respectively. CONCLUSION: TPF90 is a suitable option for Asian patients with borderline resectable or unresectable HNSCC who are scheduled for ICT.

Heterogeneity of (18)F-FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma.

The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC.

RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: Results from a pilot study.

BACKGROUND/AIM: We prospectively investigated the potential usefulness of PET using a new tracer targeting integrin αvß3 (termed RGD-K5) in patients with head and neck cancer (HNC) undergoing definitive concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: Newly diagnosed patients with locally advanced HNC scheduled for definitive CCRT were eligible. RDG-K5 PET and FDG PET scans were performed at three different time points (baseline, 2 weeks, and 3 months post-treatment). RESULTS: Nine patients completed all of the three scans, whereas two patients withdrew after two scans only. Uptake of both RGD-K5 and FDG generally decreased following CCRT. However, the observed decrease did not differ significantly between complete responders and non-responders. At 3 months post-treatment, the uptake of both RGD-K5 and FDG at the main tumors was significantly lower in those who achieved complete responses than in those with residual tumors. CONCLUSION: RGD-K5 PET has the potential to identify patients with incomplete responses to CCRT.

Dynamic contrast-enhanced MRI, diffusion-weighted MRI and 18F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation.

OBJECTIVES: We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation. METHODS: Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and 18F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates. RESULTS: Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K ep)-tumour < 3.79 min-1 (P = 0.001), relative volume of extracellular extravascular space (V e)-node < 0.23 (P = 0.004) and SUVmax-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001). CONCLUSIONS: K ep-tumour, V e-node and SUVmax-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification. KEY POINTS: • K ep -tumour, V e -node and SUV max -tumour are independent predictors of survival rates. • The combination of these three prognosticators may help stratification of survival. • MRI and FDG-PET/CT play complementary roles in prognostication of head and neck cancer.

Outcomes and prognostic factors for surgery followed by modern radiation therapy in parotid gland carcinomas.

OBJECTIVE: To evaluate the outcomes and prognostic factors in patients with parotid gland cancers treated with adjuvant radiotherapy with or without chemotherapy. METHODS: Eighty-five patients with parotid gland cancers were identified between October 2001 and September 2011. The median radiation dose was 66 Gy (range, 9-76 Gy). The outcomes assessment included overall survival, locoregional control, distant metastasis-free survival and disease-free survival. RESULTS: The stage distribution was 20 patients  (23.5%) in stage I, 28 (32.9%) stage II, 14 (16.5%) stage III and 23 (27.1%) stage IV. Fifty-five patients (64.7%) had positive margins and 23 patients (27.1%) had close margins (<0.5 cm). Lymph node extracapsular spreading occurred in nine patients. The adjuvant therapy included radiotherapy alone in 47 patients (55.3%) and concurrent chemoradiotherapy in 38 patients (44.7%). With a median follow-up of 4.5 years (range, 0.4-11 years), the 5-year overall survival, locoregional control, distant metastasis-free survival and disease-free survival were 82.0, 88.4, 82.4 and 77.5%, respectively. Based on multivariate analysis, N1/N2 was a significant negative prognostic factor for distant metastasis-free survival, disease-free survival and overall survival. Perineural invasion was a significant negative prognostic factor for locoregional control, distant metastasis-free survival and disease-free survival. Patients 50 years or older had significantly worse distant metastasis-free survival, disease-free survival and overall survival. CONCLUSIONS: Surgery and radiotherapy treatment could achieve excellent outcomes in a modern cohort. However, N1/N2, perineural invasion and age ≥50 years, but not positive margins, are significant factors associated with a worse prognosis.

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PURPOSE: The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. METHODS: We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. RESULTS: Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. CONCLUSION: ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment.

BACKGROUND: Head and neck cancer (HNC) is a prevalent cancer worldwide; however, clinically useful tumor markers for HNC have not been identified. Here, we aimed to identify secretory proteins from the tumor microenvironment as candidate circulating tumor markers. METHODS: Samples derived from seven pairs of tumor interstitial fluid (TIF) and normal interstitial fluid (NIF) samples from patients with HNC were analyzed. The proteomes were determined by gel-based-mass-spectrometry proteomic methods. The most up-regulated protein, fascin was confirmed in the cancer tissues and cell culture supernatant by immunoblotting and immunohistochemistry assays. Serum fascin was determined in 40 HNC and 40 normal individuals by ELISA. RESULTS: After proteomics analysis, 189 peptides were identified, corresponding to 75 proteins. Of the 21 proteins which were identified more than twice, five up-regulated proteins identified most frequently including fascin. The most elevated fascin was over-expressed in cancer tissues and cell culture supernatant. Serum fascin was significantly up-regulated in the cancer patients (p<0.001) and correlated with pathological lymph node metastasis (p=0.022). To assess the diagnostic efficacy, serum levels of fascin and another potential biomarker SCCA were determined. Fascin showed a high predictable value with an area under the curve (AUC) of 0.808 (95% CI 0.723-0.901) in the receiver operator curve (ROC), compared to 0.501 (95% CI 0.378-0.634) for SCCA. CONCLUSIONS: We have identified 75 potential circulating tumor markers associated with HNC, including fascin. Serum fascin could discriminate cancer patients from healthy individuals; thus, it may serve as a circulating biomarker for HNC.