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Background We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). Methods We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. Results The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656–0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478–0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high‐risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p, This relatively large cohort reports a comparative result: pretreatment high neutrophil‐to‐lymphocyte ratio (NLR) was an independent unfavorable risk factor for both overall survival and distant metastasis in patients with oral cavity squamous cell carcinoma (OSCC) who underwent surgery and postoperative radiotherapy. Lymphocyte‐to‐monocyte ratio (LMR) and platelet‐to‐lymphocyte ratio (PLR) were not significant.

Objectives To investigate the prognostic value of the preoperative systemic immune‐inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC‐SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). Materials and Methods We retrospectively reviewed the clinical records of patients with OC‐SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden’s index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). Results The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p, The SII is defined as platelet × neutrophil/lymphocyte counts. Increased SII values predict poor distant control and overall survival in patients with oral cancer treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a tight follow‐up surveillance schedule or adjuvant systemic treatment may be advisable pending independent confirmation of our data.

Radiotherapy (RT) of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)–expressing CRC cells systemically. However, abscopal tumor remissions are extremely rare, and the postirradiation immune escape mechanisms in CRC remain elusive. Here, we found that irradiated CRC cells used ATR-mediated DNA repair signaling pathway to up-regulate both CD47 and PD-L1, which through engagement of SIRPα and PD-1, respectively, prevented phagocytosis by antigen-presenting cells and thereby limited TAA cross-presentation and innate immune activation. This postirradiation CD47 and PD-L1 up-regulation was observed across various human solid tumor cells. Concordantly, rectal cancer patients with poor responses to neoadjuvant RT exhibited significantly elevated postirradiation CD47 levels. The combination of RT, anti-SIRPα, and anti–PD-1 reversed adaptive immune resistance and drove efficient TAA cross-presentation, resulting in robust TAA-specific CD8 T cell priming, functional activation of T effectors, and increased T cell clonality and clonal diversity. We observed significantly higher complete response rates to RT/anti-SIRPα/anti–PD-1 in both irradiated and abscopal tumors and prolonged survival in three distinct murine CRC models, including a cecal orthotopic model. The efficacy of triple combination therapy was STING dependent as knockout animals lost most benefit of adding anti-SIRPα and anti–PD-1 to RT. Despite activation across the myeloid stroma, the enhanced dendritic cell function accounts for most improvements in CD8 T cell priming. These data suggest ATR-mediated CD47 and PD-L1 up-regulation as a key mechanism restraining radiation-induced immune priming. RT combined with SIRPα and PD-1 blockade promotes robust antitumor immune priming, leading to systemic tumor regressions.

BackgroundWe sought to investigate the prognostic impact of missed RT sessions in patients who had undergone surgery for oral cavity squamous cell carcinoma (OCSCC).MethodsThe study sample consisted of 905 patients with surgically treated OCSCC who fulfilled criteria of RT course ≤8 weeks. The study participants were divided into three groups based on the characteristics of missed RT, as follows: 1) early missed RT, 2) late missed RT, and 3) RT as scheduled.ResultsThe 5-year overall survival (OS) rates in the early missed RT, late missed RT, and RT as scheduled groups were 53.0, 58.1, and 64.5%, respectively (p = 0.046). In multivariate analysis, early missed RT was independently associated with both OS (hazard ratio (HR) = 1.486; 95% confidence interval (CI): 1.122–1.966;p = 0.006) and the occurrence of distant metastasis (HR = 1.644; 95% CI: 1.047–2.583;p = 0.031).ConclusionEarly missed RT was independently associated with a higher occurrence of distant metastasis and less favorable OS in patients who had undergone surgery for OCSCC.

Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.

Simple Summary Chronic rhinosinusitis (CRS) is a common treatment complication in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. In this study, we aimed to investigate the incidence and severity of CRS in NPC patients who underwent intensity-modulated proton therapy (IMPT) by evaluating the sinus mucosa change in imaging studies, and we compared these patients with those who underwent volume-modulated arc therapy (VMAT). This was a retrospective case–control study in which 53 and 54 patients were treated with IMPT and VMAT, respectively. We noted that patients in the IMPT group had a significantly lower incidence and decreased severity of sinus mucosa abnormality than those with VMAT. Better and faster recovery of sinonasal function after radiotherapy in the IMPT group was also observed. IMPT techniques deposit the bulk of their radiation doses in highly confined areas, allowing lower exposure of non-target organs during irradiation, which results in more sinonasal mucosa being retained. Abstract 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.

OBJECTIVE To investigate the clinical utility of short-course induction chemotherapy followed by low-dose radiotherapy without a tumor bed boost in patients with primary central nervous system (CNS) germinomas. METHODS We retrospectively reviewed the clinical records of patients with primary CNS germinomas who received short-course induction chemotherapy (2 cycles of cisplatin 20 mg/m2 plus etoposide 40 or 100 mg/m2 for 5 days) followed by low-dose radiotherapy (dose: 2340 cGy) without a tumor bed boost. Disease-free survival and overall survival served as the main outcome measures. RESULTS Between February 2002 and June 2018, 24 patients (20 males and 4 females; median age: 14.1 y; age range: 7.9 to 21.2 y) with pathology-proven CNS germinomas were included. The median follow-up time was 106 months (range: 17 to 169 mo). Isolated and multifocal lesions were identified in 13 and 11 patients, respectively. Tumor location was as follows: pineal gland (n=17), suprasellar region (n=13), periventricular region (n=7), and basal ganglia (n=2). Five patients had increased levels (>5 mIU/mL) of beta-human chorionic gonadotropin (β-hCG), whereas alpha-fetoprotein concentrations were within the reference range in all participants. A total of 16 patients achieved remission after induction chemotherapy. The complete response rates of patients with increased and normal β-hCG levels were 40.0% and 72.2%, respectively (P=0.208). Low-dose radiotherapy without a tumor bed boost was subsequently delivered to either the whole ventricle (n=16) or the whole brain (n=8), resulting in complete remission in all participants. Compared with patients without increased β-hCG levels, those with β-hCG-secreting germinomas had less favorable 5-year disease-free survival rates (100% vs. 60%, respectively, P=0.000115). CONCLUSIONS Some children with primary CNS germinoma may benefit from short-course induction chemotherapy followed by low-dose radiotherapy to the whole ventricle without a tumor bed boost. The validity of our findings needs to be confirmed in a randomized phase II study for children with β-hCG levels

Additional file 1: Table S1. Guidelines for postoperative treatment of oral cavity cancer in our institution.

Simple Summary The application of unilateral neck irradiation may be able to reduce the toxicities associated with postoperative radiotherapy. However, the feasibility of using unilateral neck irradiation in patients with buccal mucosa squamous cell carcinoma (BMSCC) with extranodal extension (ENE) remains unexplored. The aim of our retrospective study was to evaluate whether unilateral irradiation is safe for ENE+ patients with well-lateralized BMSCC. We demonstrated in propensity-matched cohorts (123 patients) the comparability of clinical outcomes in patients treated with postoperative unilateral versus bilateral radiotherapy. We identified the number of ENEs ≥ 4 as a potent risk factor for contralateral nodal recurrence and established a prognostic model accordingly. This study shall justify the use of unilateral neck irradiation and help physicians optimize radiation fields. Abstract 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.

Objectives The prognostic value of radiologic extranodal extension (rENE) in nasopharyngeal carcinoma remains controversial. In this study, a meta-analysis was performed to assess the prognostic value of ungraded rENE and unambiguous advanced rENE. Methods A literature search through PubMed, Cochrane Library, EMBASE and manual searches was conducted until May 2021. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival and distant metastasis-free survival were extracted and pooled. Results Nine eligible studies were published between 2012 and 2021. The pooled patient number was 7532 (range 61–1887). Seven studies were eligible for the analysis of ungraded rENE, while 3 studies were eligible for unambiguous advanced rENE. The results showed that ungraded rENE was associated with worse overall survival (HR 1.85, 95% CI 1.04–3.27) and significantly associated with worse distant metastasis-free survival (HR 2.07, 95% CI 1.36–3.13). On the other hand, unambiguous advanced rENE was significantly associated with worse overall survival (HR 2.62, 95% CI 2.12–3.25) and worse distant metastasis-free survival (HR 3.14, 95% CI 1.85–5.33). Conclusions In nasopharyngeal carcinoma, both ungraded and unambiguous advanced rENE are significant prognosticators of overall survival and distant metastasis-free survival. More prospective studies are required to determine its role in risk stratification or clinical staging.

BackgroundBackground: Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically; however, incidences of abscopal tumor remission are extremely rare. We sought to unravel the post-irradiation immune escape mechanisms in CRC.MethodsMethodsFlow cytometry, gene knockdown, RNA and T cell receptor sequencing, and multiple murine syngeneic CRC models were used to interrogate mechanisms of CRC immune evasion following radiotherapy. Comparison of immunohistochemistry staining between pretreatment biopsy and post-irradiation surgical specimens was performed in rectal patients who underwent neoadjuvant radiotherapy with 5 Gy for 5 fractions.ResultsResultsWe find that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells (APCs) to phagocytose them thereby preventing TAA cross-presentation. This post-irradiation CD47 and PD-L1 upregulation can be observed in CRC cells treated with either photon or proton radiotherapy and across a wide variety of human solid tumor cells. Concordantly, rectal cancer patients who responded poorly (tumor regression grade 4–5, n = 10) to neoadjuvant radiotherapy exhibited significantly elevated post-irradiation CD47 levels (P = 0.005). In murine CRC models, the combination of radiotherapy, αSIRPα, and αPD-1 (RSP) profoundly enhances TAA uptake, activation of innate immune sensors, and TAA cross-priming across various antigen-presenting myeloid populations in the irradiated tumor microenvironment and facilitates TAA-presenting APC migration to secondary lymphoid organs. Furthermore, we observed robust production of TAA-specific CD8 T cells, functional activation of effector T cells, and increased tumor-infiltrating T cell clonality and clonal diversity in mice treated with RSP. Importantly, radiotherapy coupled with phagocytosis checkpoint blockade significantly improves complete response rates in both irradiated and abscopal tumors and prolongs survival in three distinct murine CRC models, including a cecal orthotopic model. In addition, αSIRPα exerts superior tumoricidal efficacy than αCD47 in combination with RT and αPD-1. We find RSP efficacy to be STING dependent as knockout animals lose most benefit of phagocytosis checkpoint blockade.ConclusionATR-mediated CD47 and PD-L1 upregulation restrains radiation-induced immune priming in CRC. Blockade of the phagocytosis checkpoints SIRPα and PD-1 during radiotherapy promotes vigorous anti-CRC immune priming leading to systemic tumor regression.AcknowledgementsThis study is supported in part by NIH grant P30 CA16672, the MD Anderson Andrew Sabin Family Fellowship, and Chang Gung Memorial Hospital grant CMRPG3K1751. RCH was supported by the CPRIT Research Training Grant (RP170067) and Ralph B. Arlinghaus Ph.D. Scholarship. The authors are grateful to the members of the Advanced Cytometry & Sorting Facility at South Campus, Tissue Bank of Chang Gung Memorial Hospital at Linkou, and MHC Tetramer Core Facility at Baylor College of Medicine for their invaluable help.Ethics ApprovalThis study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan; approval number: 202001191B0C601.

(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, &gt, 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.

We aimed to compare the overall survival (OS) of patients with bone metastases (BM) from solid tumors after standard‐dose radiotherapy ([RT]; 30 Gy administered in 10 fractions; EQD2Gy = 32.5 Gy) and dose‐escalated RT (EQD2Gy > 32.5 Gy). We retrospectively reviewed the clinical charts of 1795 patients (median age, 62.3 years; age range, 18–96 years) with BM from solid tumors who were referred for RT to our institute between 2000 and 2013. These patients were assigned to the standard‐dose (n = 1125; 63%) and dose‐escalated (n = 670; 37%) RT groups. OS, estimated as the duration between the first RT session and death, served as the main outcome measure. The dose‐escalated RT group had a significantly better OS than the standard‐dose RT group (P = 0.000). After allowing potential confounders in multivariate analysis, the RT dose retained its independent association with OS (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.753–0.929, P = 0.001). After propensity score matching of the baseline characteristics of both groups, RT dose retained its independent association with OS (HR, 0.887; 95% CI, 0.737–0.951; P = 0.011) on multivariate analysis. Dose‐escalated RT exerted more favorable effects on OS in patients with non‐lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. Dose‐escalated RT was significantly associated with better OS in patients with BM from solid malignancies, particularly among those with non‐lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis.

e16113 Background: Management of advanced hepatocellular carcinoma (HCC) remains a challenge. IMbrave150, a pivotal trial reported impressive overall survival benefit using combination strategy of atezolizumab and bevacizumab compared to sorafenib. We wonder the efficacy and safety when combining radiotherapy with immune checkpoint inhibitors (ICIs), which radiation might provide better local treatment and possible trigger abscopal effect. The aim of this study is retrospectively reporting the real-world efficacy and tolerability of proton beam or photon radiation plus ICIs in patients with advance stage HCC. Methods: We retrospectively reviewed all BCLC stage C HCC patients who have received combination therapy with ICIs plus proton or photon therapy with well documented basic characteristics and prompt treatment efficacy evaluation between 1st of January 2016 to 31st of October 2019 at a single medical center in Taiwan. 20 patients had ICIs plus proton and 32 patients had ICIs plus photon were included for analysis. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier estimator. Results: Baseline characteristics were generally similar between ICIs plus proton or ICIs plus photon, while most patients in proton group did not receive prior systemic treatment and had less local therapies prior ICIs combine with radiotherapy. Median follow-up time was 10.7 months. The median Progression free survival (PFS) was not reached in ICIs plus proton group and 3.6 months (95% CI 2.7-4.6) in ICIs plus photon group (P = 0.007). The median OS was not reach in ICIs plus proton group and 12.1months (95% CI 6.4-17.7) in ICIs plus photon group (P = 0.007). Comparing ICIs plus proton group versus photon group, objective tumor response is 50% versus 9%, disease control rate is 80% versus 47% in each group. During follow-up, 7 patients (35%) in proton group achieved complete remission (CR). There was difference in radiation filed, 19 patients (95%) in proton group and 15 patients (47%) in photon group targeted on liver tumors, and more patient received > 50Gy treatment dose in proton group compared to photon group (90% versus 20%). Proton group has lower failure rate in both inner- or out-field compared to photon group. Grade 1 to grade 2 skin-dermatological and gastrointestinal toxicity remained the most frequent reported adverse events in both groups. There are only one therapy related grade 3 dermatitis in ICIs plus proton group and one grade 3 hepatitis, one grade 5 pneumonitis in ICIs plus photon group. Conclusions: This study reported real-world efficacy and safety of ICIs in combination with proton or photon therapy. Most adverse events were manageable. The combination of ICIs and proton therapy has impressive CR rate and OS benefit. Further prospective randomized trial is warranted for confirm our finding.

PURPOSE To assess whether primary tumor and nodal F-FDG uptake may predict prognosis in patients with salivary gland carcinoma. METHODS We conducted a 2-center, retrospective study on 117 patients with salivary gland carcinoma who underwent F-FDG PET/CT before treatment and were subsequently treated with curative intent between 2004 and 2014. Pretreatment SUVmax of the primary tumor (SUVmax-T) and that of positive nodes (SUVmax-N) were analyzed in relation to clinical outcomes. RESULTS Patients were followed up for a median of 61 months. The following 5-year rates were observed: locoregional control (LRC), 78%; distant metastasis-free survival (DMFS), 67%; progression-free survival (PFS), 62%; and overall survival (OS), 68%. A cutoff value of 7.0 maximized the prognostic impact of both SUVmax-T and SUVmax-N for PFS. Compared with patients with SUVmax-T and SUVmax-N values below the optimal cutoff, those with SUVmax-T and SUVmax-N of 7 or greater showed less favorable 5-year LRC (P < 0.001 and P < 0.001), DMFS (P < 0.001 and P < 0.001), PFS (P < 0.001 and P < 0.001), and OS (P < 0.001 and P < 0.001) rates. Both SUVmax-T of 7 or greater and SUVmax-N of 7 or greater were identified as independent predictors of LRC (P = 0.010 and 0.022), DMFS (P = 0.001 and P = 0.001), PFS (P < 0.001 and P = 0.007), and OS (P = 0.007 and P = 0.002) in multivariable analysis. We therefore devised a prognostic scoring system based on these 2 variables, which was found to be strongly associated with 5-year LRC (P < 0.001), DMFS (P < 0.001), PFS (P < 0.001), and OS (P < 0.001) rates. CONCLUSIONS SUVmax of the primary tumor and SUVmax-N on pretreatment F-FDG PET/CT images may be a useful guide in predicting treatment outcomes, especially when combined in a prognostic scoring system.

Figure S1. Perineural tumor recurrence at (A) lingual (solid arrow), inferior alveolar (arrow head) and facial (dashed arrow) nerves (#12) and (B) hypoglossal nerve (#11). (PDF 63 kb)

Table S1. Patient characteristics in selected patients with risk factors. (DOCX 334 kb)

Background The patterns of nodal relapse in submandibular gland carcinoma (SMGC) patients treated with postoperative radiotherapy (PORT) remain unclear. This study aims to investigate the nodal failure patterns and the utility of elective nodal irradiation (ENI) in SMGC patients undergoing PORT. Methods We retrospectively enrolled 65 SMGC patients who underwent PORT between 2000 and 2014. The nodal failure sites in relation to irradiation fields and pathological parameters were analyzed. ENI regions were categorized into three bilateral echelons (first, levels I–II; second, level III; and third, levels IV–V). Extended ENI was defined as coverage of at least the immediately adjacent uninvolved echelons bilaterally; otherwise, limited ENI was administered. Results Thirty patients (46%) were stage III–IV, and 18 (28%) were pN+. Neck irradiation included limited (72%) and extended ENI (28%). With a median follow-up of 79 months, 11 patients (17%) developed nodal failures (ipsilateral, N = 6; contralateral, N = 7), 7 (64%) of whom relapsed in the adjacent uninvolved echelons. We identified pN+ (P = 0.030), extranodal extension (ENE, P = 0.002), pT3–4 (P = 0.021), and lymphovascular invasion (LVI, P = 0.004) as significant predictors of contralateral neck recurrence. Extended ENI significantly improved regional control (RC) in patients with pN+ (P = 0.003), ENE (P = 0.022), pT3–4 (P = 0.044), and LVI (P = 0.014), and improved disease-free survival (DFS) in patients with pN+ (P = 0.034). For patients with ≥2 coincident adverse factors, extended ENI significantly increased RC (P

ZrN thin films were successfully deposited by DC magnetron sputtering on die steel substrates. The objective of this study was to investigate heat treatment on the microstructure, morphology, nanohardness properties determined by X-ray diffraction, field-emission scanning electron microscope (FE-SEM), nanoindentation, and pin-on-disk, respectively. The XRD result shows that ZrN has intensity of (111) and (200) peak after 400 °C for 1 h at lower nitrogen flow rates. The surface of coatings revealed smaller grains and smooth surface under heat treatment. ZrN coatings consisted of lower nitrogen flow rate had much lower friction coefficient, better mechanical properties by annealing treatment process.

ZrN films were prepared by magnetron sputtering on die steel substrates. The objective of this study was to investigate the effect of nitrogen flow rate on the microstructure ,morphology, nanohardness properties determined by X-ray diffraction, field-emission scanning electron microscope, nanoindentation, and pin-on-disk, respectively. The XRD shows that ZrN has (111) and (200) preferred orientation under lower nitrogen flow rates. The surface of coatings revealed smaller grains and uniform dense under lower nitrogen flow rates. With increasing the nitrogen flow rates, this result showed ZrN films lead to poor mechanical properties and hardness values. However, films consisted of up high ernitrogen flow rate had much lower friction coefficient.

TiN/NbN multilayers on steel substrates (SKD11) are produced using DC magnetron sputtering process. The multilayer obtained are characterized in composition by means of X-ray diffraction techniques, Microhardness and adhesion to the substrate were studied by atomic force microscopy and scratch tests. The morphological analysis and coating structure are studied using scanning electron microscopy, and atomic force microscopy. The film thickness is measured by a stylus profiler (XP-2 stylus profiler). Wear tests were performed on pin-on-disk configuration and dry sliding conditions, at 5N load by using hardened steel ball. On mechanical properties, higher Young’s modulus and hardness values follow to increase the TiN/NbN layers number. The multilayer films of 64 layers at 500°C 1h annealing indicated that the microhardness and Young’s modulus had the highest values.