Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study.

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients' images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan-Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3-7%) after both surgery and RT, 4% (95% CI = 2-6%) after surgery alone, and 5% (95% CI = 3-7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias.

Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy.

BACKGROUND: Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. PURPOSE: This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. METHODS: One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain Inventory-Short Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. RESULTS: Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians.

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 (

Dose-Escalated Radiation Therapy as Primary Treatment for Residual Bladder Cancer After Transurethral Resection.

Purpose: The aim of this study was to determine whether escalating the local radiation dose can improve the outcome of residual bladder cancer after transurethral resection of bladder tumor without increasing treatment-related toxicity. Methods and Materials: The treatment plans and medical records of patients with bladder cancer treated with curative-intent radiation therapy between 2008 and 2020 were reviewed. Those who had residual tumors in the computed tomography simulation images were included. A cumulative radiation dose higher than 6600 cGy was defined as dose escalation. The effect of dose escalation on 3-year locoregional control, progression-free survival, and overall survival was evaluated. Results: A total of 149 patients with residual tumors were identified. The median follow-up period was 27.5 months. Among them, 51 patients received an escalated radiation dose, and 98 received a standard dose in the residual tumor area. Patients in the dose-escalation group had higher 3-year locoregional control (65.6% vs 27.8%; P < .001) and progression-free survival (42.6% vs 18.2%; P < .001) than the standard-dose group. Overall survival also showed a trend favoring the dose-escalation group (54.9% vs 36.2%; P = .059). In the multivariate analyses, the differences between the dose-escalation and standard-dose groups were significant in terms of locoregional control (hazard ratio, 0.32; CI, 0.18-0.59; P = <.001) and progression-free survival (hazard ratio, 0.51; CI, 0.32-0.82; P = .005). There was no statistical difference in acute and chronic treatment-related toxicities between the 2 groups. Conclusions: The outcome of residual bladder cancer after transurethral resection of bladder tumor could be improved by dose-escalated radiation therapy.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers.

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

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.

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.

Prospective Investigation of 18FDG-PET/MRI with Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Survival in Patients with Oropharyngeal or Hypopharyngeal Carcinoma.

To prospectively investigate the prognostic value of 18F-FDG PET/MRI in patients with oropharyngeal or hypopharyngeal squamous cell carcinomas (OHSCC) treated by chemoradiotherapy. The study cohort consisted of patients with OHSCC who had undergone integrated PET/MRI prior to chemoradiotherapy or radiotherapy. Imaging parameters derived from intravoxel incoherent motion (IVIM), dynamic contrast-enhanced MRI (DCE-MRI), and 18F-FDG PET were analyzed in relation to overall survival (OS) and recurrence-free survival (RFS). In multivariable analysis, T classification (p < 0.001), metabolic tumor volume (p = 0.013), and pseudo-diffusion coefficient (p = 0.008) were identified as independent risk factors for OS. The volume transfer rate constant (p = 0.015), initial area under the curve (p = 0.043), T classification (p = 0.018), and N classification (p = 0.018) were significant predictors for RFS. The Harrell's c-indices of OS and RFS obtained from prognostic models incorporating clinical and PET/MRI predictors were significantly higher than those derived from the traditional TNM staging system (p = 0.001). The combination of clinical risk factors with functional parameters derived from IVIM and DCE-MRI plus metabolic PET parameters derived from 18F-FDG PET in integrated PET/MRI outperformed the information provided by traditional TNM staging in predicting the survival of patients with OHSCC.

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.

Potential Utility of the Mallampati Score for Prediction of Treatment Compliance and Safety Profiles of Patients With Head and Neck Cancer Undergoing Definitive Concurrent Chemoradiotherapy.

BACKGROUND/AIM: Restriction of mouth opening (RMO) is a common manifestation of head and neck cancer (HNC) and a poor prognostic factor following concurrent chemoradiotherapy (CCRT) of patients. This study aimed to explore whether the Mallampati score, a visual assessment of the distance from the tongue base to the roof of the mouth, can be used as a surrogate for RMO in predicting treatment outcomes in patients with HNC undergoing CCRT. PATIENTS AND METHODS: A total of 461 consecutive patients who received definitive CCRT for the treatment of locally advanced HNC between August 2016 and December 2017 at Chang Gung Memorial Hospital in Taiwan (Linkou, Keelung, and Kaohsiung branches) were enrolled in this prospective study. Patients were allocated by the pre-treatment Mallampati score of 1 or 2 (n=24) vs. 3 or 4 (n=207) to compare treatment compliance and treatment-related complications. RESULTS: Patients in the Mallampati score of 3 or 4 group had a higher prevalence of betel quid chewing, oral cavity and oropharynx cancers, advanced tumor stage, poorer performance status, and were more likely to receive platinum monotherapy during CCRT. Patients in the Mallampati score of 3 or 4 group had a 2.08-fold (p=0.002) hazard ratio (HR) for overall survival compared to those in the score of 1 or 2 group in the univariate analysis, the difference remained significant in multivariate analysis (adjusted HR=1.61; 95% CI=1.02-2.61; p=0.047). Patients in the Mallampati score 3 or 4 group had a 2.36-fold (95% CI=1.07-5.19; p=0.033) increased likelihood of incomplete chemotherapy, 2.44-fold (95% CI=1.17-5.06; p=0.017) increased likelihood of incomplete radiotherapy, and 1.84-fold (95% CI=1.18-2.87; p=0.007) risk of unexpected hospitalization compared to those with a Mallampati score of 1 or 2 in multivariate analysis. CONCLUSION: Patients with HNC with higher pre-treatment Mallampati scores had poorer survival outcomes and were at a higher risk of treatment incompletion and treatment-related toxicities when undergoing CCRT. Our results support the utility of Mallampati score as a surrogate for measuring RMO to predict survival outcomes, treatment compliance, and safety profiles in patients with HNC undergoing CCRT.

Head and Neck Cancer Types and Risks of Cervical-Cranial Vascular Complications within 5 Years after Radiation Therapy.

Background and purpose: to investigate the frequency of cervical−cranial vascular complications soon after radiation therapy (RT) and identify differences among patients with various types of head and neck cancer (HNC). Methods: We enrolled 496 patients with HNC who had received their final RT dose in our hospital. These patients underwent carotid duplex ultrasound (CDU) for monitoring significant carotid artery stenosis (CAS). Brain imaging were reviewed to detect vertebral, intracranial artery stenosis, or preexisted CAS before RT. Primary outcome was significant CAS at the internal or common carotid artery within first 5 years after RT. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of significant CAS between the groups using Kaplan−Meier and Cox-regression analyses. Results: Compared to the NPC group, the non-NPC group had a higher frequency of significant CAS (12.7% vs. 2.0%) and were more commonly associated with significant CAS after adjusting the covariates (Adjusted hazard ratio: 0.17, 95% confident interval: 0.05−0.57) during the follow-up period. All the non-NPC subtypes (oral cancer/oropharyngeal, hypopharyngeal, and laryngeal cancers) were associated with higher risks of significant CAS than the NPC group (p < 0.001 respectively). Conclusion: Significant CAS was more frequently noted within 5 years of RT among the patients with non-NPC HNC than among the patients with NPC. Scheduled carotid artery surveillance and vascular risk monitoring should be commenced earlier for patients with non-NPC HNC. By contrast, vascular surveillance could be deferred to 5 years after RT completion in NPC patients.

Utilization of the lymph node-to-primary tumor ratio of PET standardized uptake value and circulating Epstein-Barr virus DNA to predict distant metastasis in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To determine the clinical impact of integrating Epstein-Barr virus (EBV) DNA and lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) in predicting distant metastasis, such as distant metastasis-free survival (DMFS), in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with non-disseminated NPC between 2010 and 2017. The optimal cut-off values of EBV DNA and SUV NTR were determined using receiver operating characteristic analysis. The prognostic values of SUV NTR and EBV DNA on DMFS and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariable analyses were performed using the Wald Chi-squared test and Cox proportional hazards regression, respectively. RESULTS: A total of 488 patients were included in the analysis. The median follow-up period was 61.6 months. The optimal cut-off values of EBV DNA and SUV NTR were 3377.5 copies per mL and 0.64, respectively. The five-year DMFS for patients with high vs low EBV DNA and SUV NTR levels were 64.9% vs 86.6% (p < 0.001) and 78.7% vs 87.4% (p = 0.021), respectively. In subgroup analysis, the high-risk group with high levels of pretreatment EBV DNA and SUV NTR had worse DMFS in either American Joint Committee on Cancer (AJCC) stage I-III or IVA-B (p = 0.001 and <0.001, respectively). Univariate and multivariable analyses showed the statistical significance of EBV DNA, SUV NTR, and their composite in DMFS (p < 0.001 for EBV DNA; p = 0.022 for SUV NTR; p < 0.001 for their composite). CONCLUSION: This study showed that EBV DNA and SUV NTR have independent and additive values as prognosticators for distant metastasis in patients with NPC, suggesting that these two individual factors, except the AJCC staging system, should be included in future studies.

Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion.

Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.

Post-Irradiation Sinus Mucosa Disease in Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Proton Therapy.

In the past decade, patients with nasopharyngeal cancer (NPC) have been deemed candidates for proton radiotherapy, due to the large and comprehensive target volumes and the necessity for the retention of the surrounding healthy tissues. In this study, we aimed to compare the incidence and severity of post-irradiation sinusitis by detecting sinus mucosa diseases (SMDs) via the magnetic resonance imaging (MRI) of patients with NPC after intensity-modulated proton therapy (IMPT) and volume-modulated arc therapy (VMAT). A total of 53 patients in the IMPT group and 54 patients in the VMAT group were enrolled in this study. There were significantly lower endoscopic scores and Lund-Mackay staging scores determined from MRI scans in the IMPT group during different follow-up periods. For the most vulnerable sinuses, the incidence and severity of SMD were the highest during the third post-radiotherapy month in both groups. These decreased steadily, and there was no significant increase in the incidence and severity of SMD during the second post-radiotherapy year in the IMPT group. Our data show that NPC patients with IMPT have a significantly lower incidence and decreased severity of SMD than those with VMAT. A better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed.

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.

Outcomes of re-irradiation for oral cavity squamous cell carcinoma.

BACKGROUND: To predict the outcome of reirradiation (re-RT) for oral cavity squamous cell carcinoma (OSCC). METHODS: Eighty-three patients met the criterion of having previously irradiated OSCC treated via curative intent re-RT for recurrent or new primary OSCC. The exclusion criteria were a suboptimal dose (<45 Gy) for the first RT and palliative intent for the second irradiation. Re-RT was defined as at least 75% volume at second RT after receiving at least 45 Gy at the first RT. RESULTS: The 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 20% and 28%. For LRPFS, four predictors were noted through univariate analyses: performance status (PS) (p = 0.001), a dose of at least 60 Gy (p = 0.001), stage IVB (p = 0.020), and surgery before re-RT (p = 0.041). In multivariate analyses, only PS (p = 0.005) and a dose of at least 60 Gy (p = 0.001) remained significant. For OS, PS (p = 0.001) and a dose of at least 60 Gy (p = 0.042) were still independently associated predictors, but surgery before re-RT became marginally beneficial (p = 0.053). For patients with a poor PS (ECOG = 2-3), the 2-year OS was only 4.5%. Twenty-nine percent of the patients experienced severe late complications (≥Grade 3), and 18% had new episodes of osteoradionecrosis during their follow-up. CONCLUSION: We identified PS and a re-RT dose ≥60 Gy as predictors for LRPFS and OS. Surgery before re-RT might improve OS. However, the treatment results of re-RT for OSCC were suboptimal. Prospective trials using modern RT techniques, in combination with new therapeutic drugs or radioenhancers, are warranted for improving these dismal outcomes.

Efficacy of Postoperative Unilateral Neck Irradiation in Patients with Buccal Mucosa Squamous Carcinoma with Extranodal Extension: A Propensity Score Analysis.

Unilateral radiotherapy (RT) as a postoperative treatment for multiple ipsilateral lymph node (LN) metastases remains controversial. We investigated the efficacy of postoperative unilateral RT for buccal mucosa squamous cell carcinoma (BMSCC) with extranodal extensions (ENEs). We retrospectively reviewed the clinical records of 186 patients with ENE+ BMSCC who received postoperative RT during 1997-2016. Propensity score matching was used to establish comparable cohorts. The endpoints were contralateral nodal control (CLNC), overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), local control (LC), and regional control (RC). After matching, 123 patients were selected for analysis; 45 (36.6%) and 78 (63.4%) patients underwent unilateral and bilateral RT, respectively. The median follow-up was 36.27 months. The survival outcomes in the unilateral and bilateral RT groups were similar: 3-year CLNC (85.6% vs. 89.1%, p = 0.748), OS (53.2% vs. 57.4%, p = 0.229), DFS (46.5% vs. 48.6%, p = 0.515), DMFS (70.7% vs. 72.0%, p = 0.499), LC (78.0% vs. 75.6%, p = 0.692), and RC (79.9% vs. 76.2%, p = 0.465). On multivariable Cox regression analysis, unilateral and bilateral RT showed comparable outcomes; the number of ENEs ≥ 4 was the only significant prognostic factor for all clinical outcomes. Using decision tree analysis, we classified our patients to have a low, intermediate, or high risk of contralateral failure based on three factors: number of ENEs, margin status, and tumor stage. In conclusion, postoperative unilateral RT did not worsen outcomes in patients with ENE+ BMSCC in this cohort. The decision tree model may assist physicians in optimizing and tailoring radiation fields.

Systemic Investigation Identifying Salivary miR-196b as a Promising Biomarker for Early Detection of Head-Neck Cancer and Oral Precancer Lesions.

BACKGROUND: Liquid biopsy is a rapidly growing field, for it may provide a minimally invasive way to acquire pathological data for personalized medicine. This study developed a systemic strategy to discover an effective salivary biomarker for early detection of patients with head-neck squamous carcinoma (HNSC) and oral precancer lesion (OPC). METHODS: A total of 10 miRNAs were examined in parallel with multiple independent cohorts. These included a training set of salivary samples from HNSC patients, the TCGA-HNSC and GSE31277 cohorts to differentiate miRNAs between tumor and normal tissues, and groups of salivary samples from healthy individuals, patients with HNSC and OPC. RESULTS: The combined results from the salivary training set and the TCGA-HNSC cohort showed that four miRNAs (miR-148b, miR-155, miR-196b, and miR-31) consistently increased in HNSC patients. Further integration with the GSE31277 cohort, two miRNAs (miR-31 and miR-196b) maintained at high significances. Further assessment showed that salivary miR-196b was a prominent diagnostic biomarker, as it remarkably discriminated between healthy individuals and patients with HNSC (p < 0.0001, AUC = 0.767, OR = 5.64) or OPC (p < 0.0001, AUC = 0.979, OR = 459). CONCLUSION: Salivary miR-196b could be an excellent biomarker for diagnosing OPC and early detection of HNSC. This molecule may be used for early screening high-risk groups of HNSC.

Intensity Modulated Proton Beam Therapy versus Volumetric Modulated Arc Therapy for Patients with Nasopharyngeal Cancer: A Propensity Score-Matched Study.

(1) Background: We compared the outcomes of patients with nasopharyngeal carcinoma treated with IMPT and VMAT. (2) Methods: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMPT (years: 2016-2018) and VMAT (2014-2018). Survival was estimated using the Kaplan-Meier method. Multivariate Cox proportional hazards regression analysis was used to identify the independent predictors of survival. Binary toxicity endpoint analyses were performed using a Cox model and logistic regression. (3) Results: Eighty patients who received IMPT and VMAT were included. The median follow-up time was 24.1 months in the IMPT group. Progression-free survival (PFS) and overall survival (OS) were not statistically different between the two groups but potentially better in IMPT group. In multivariate analysis, advanced N-stage and body weight loss (BWL; >7%) during radiotherapy were associated with decreased PFS. The IMPT group had significantly less requirement for nasogastric (NG) tube placement and BWL during treatment. The mean oral cavity dose was the only predictive factor in stepwise regression analysis, and IMPT required a significantly lower mean dose. However, IMPT increased the grade 3 radiation dermatitis. (4) Conclusions: IMPT is associated with reduced rates of NG tube insertion and BWL through reducing oral mean dose, potentially producing better oncologic outcomes.

Combing MRI Perfusion and 18F-FDG PET/CT Metabolic Biomarkers Helps Predict Survival in Advanced Nasopharyngeal Carcinoma: A Prospective Multimodal Imaging Study.

We prospectively investigated the prognostic value of imaging parameters for nasopharyngeal carcinoma (NPC) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT). Patients with stage III-IVb NPC underwent F-FDG PET/CT, DCE-MRI, and DWI before treatment. Kaplan-Meier and Cox-regression analyses were used to assess associations of PET and MRI imaging biomarkers with overall survival (OS) and recurrence-free survival (RFS). We used independent prognosticators to establish prognostic models; model performance was examined using Harrell's concordance index (c-index). Sixty-one patients were available for analysis, as 13 patients died and 20 experienced recurrence. Total lesion glycolysis (TLG) (p = 0.002) from PET/CT and the initial area under the curve (iAUC) (p = 0.036) from DCE-MRI were identified as independent prognosticators of OS; Epstein-Barr virus (EBV) DNA (p = 0.027), the extracellular volume fraction (Ve) (p = 0.027) from DCE-MRI, and TLG/iAUC (p = 0.025) were significant predictors of RFS. The c-indices of the prognostic models incorporating TLG + iAUC in predicting OS and incorporating EBV DNA + Ve + TLG/iAUC in predicting RFS were 0.79 and 0.76, respectively. These were significantly higher than the corresponding c-indices of the TNM staging system (p = 0.047 and 0.025, respectively); they were also higher than those of models with only MRI or PET biomarkers. In conclusion, the combination of pretreatment DCE-MRI and 18F-FDG PET/CT imaging biomarkers helps survival prediction in advanced NPC. Integrating MRI perfusion with PET metabolism and plasma EBV information may aid clinicians in planning the optimal personalized management strategy.