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Various proteins are highly expressed in cancer (e.g., epidermal growth factor receptor); however, the majority are also expressed in normal cells, although they may differ in expression intensity. Recently, we reported that CD271 (nerve growth factor receptor), a glycosylated protein, increases malignant behavior of cancer, particularly stemlike phenotypes in squamous cell carcinoma (SCC). CD271 is expressed in SCC and in normal epithelial basal cells. Glycosylation alterations generally occur in cancer cells; therefore, we attempted to establish a cancer-specific anti-glycosylated CD271 antibody. We purified recombinant glycosylated CD271 protein, immunized mice with the protein, and screened hybridomas using an ELISA assay with cancer cell lines. We established a clone G4B1 against CD271 which is glycosylated with O-glycan and sialic acid. The G4B1 antibody reacted with the CD271 protein expressed in esophageal cancer, but not in normal esophageal basal cells. This specificity was confirmed in hypopharyngeal and cervical cancers. G4B1 antibody recognized the fetal esophageal epithelium and Barrett's esophagus, which possess stem cell-like characteristics. In conclusion, G4B1 antibody could be useful for precise identification of dysplasia and cancer cells in SCC.

Objective Early enteral nutrition is essential for enhancing recovery after surgery. However, to date, no detailed study has been conducted on the feasibility of early enteral nutrition in patients undergoing head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) and the risk factors for difficulty with early enteral nutrition. Methods We retrospectively analyzed 102 patients who underwent HNS-FTTR at our institution; 61 underwent free jejunal reconstruction (FJ) and 41 did not. We investigated the achievement of early enteral nutrition within 24 and 48 h after surgery and the discontinuation of enteral nutrition after its initiation within 7 days after surgery. Results Enteral nutrition could be started in 81/102 (79.4%) and 99/102 (97.1%) patients within 24 and 48 h, respectively. Cases of difficulty with early enteral nutrition accounted for 21/102 (20.6%) patients. The multivariate analysis revealed that FJ was a significant independent risk factor for difficulty with early enteral nutrition (odds ratio: 4.054, P = 0.042). The risk factors for difficulty with early enteral nutrition in patients who underwent FJ were also investigated, and the multivariate analysis showed that blood loss of ≥158 mL was a significant independent risk factor (odds ratio: 3.505, P = 0.044). Conclusions Early enteral nutrition seemed to be provided with no problems in patients without FJ. FJ was a significant risk factor for difficulty with early enteral nutrition. Increased intraoperative blood loss was a significant risk factor for difficulty with early enteral nutrition in patients undergoing FJ; therefore, patients’ abdominal symptoms and gastric residual volume should be carefully monitored in such cases.

Background We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy. Methods In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs). Results Overall, 256 patients received a median of 6.0 doses (range: 1–52) of nivolumab over a median duration of 72.5 days (range: 1–736). Median OS was 9.5 months [95% confidence interval (CI) 8.2–12.0] and median PFS was 2.1 months (95% CI 1.8–2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9–11.9) and 3.5 months (95% CI 2.3–5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis. Conclusions Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.

Purpose Radiation dermatitis is one of the most common acute toxicities induced by chemoradiation therapy (CRT) for head and neck cancer (HNC). The benefit of topical steroids in the management of radiation dermatitis is still unclear. This phase 3, multi-institutional, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of topical steroids for radiation dermatitis in patients with locally advanced HNC receiving CRT. Methods and Materials Eligible patients were scheduled to receive bilateral neck irradiation (≥66 Gy) with concurrent cisplatin (≥200 mg/m2) as definitive or postoperative CRT. Patients were randomly assigned to receive either topical steroid or placebo when grade 1radiation dermatitis was observed or the total radiation dose reached 30 Gy. Basic skin care including gentle washing and moistening in the head and neck region was performed in both groups. The primary endpoint was the frequency of grade ≥2 radiation dermatitis, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Grading of radiation dermatitis was performed by independent central review using photographs taken weekly. Results A total of 211 patients were enrolled (intention to treat: steroid 101 and placebo 102). The frequency of grade ≥2 radiation dermatitis was not significantly reduced with the steroid (73.3%; 95% confidence interval, 64.6%-81.9%) compared with the placebo (80.4%; 95% confidence interval, 72.7%-88.1%; P = .23), whereas the steroid significantly reduced the frequency of grade ≥3 radiation dermatitis (13.9% vs 25.5%; P = .034). No significant differences in adverse events, including local infection or compliance with CRT, were observed between the groups. Conclusions Topical steroid may reduce the severity of radiation dermatitis in patients with HNC and thus may become an important therapeutic tool in the management of radiation dermatitis.

Radiation has been utilized as a direct cytotoxic tumorcidal modality, however, the effect of radiation on tumor vasculature influences response to anticancer therapies. Although numerous reports have demonstrated vascular changes in irradiated tumors, the findings and implications are extensive and at times contradictory depending on the radiation dose, timing, and models used. In this review, we focus on the radiation-mediated effects on tumor vasculature with respect to doses used, timing postradiation, vasculogenesis, adhesion molecule expression, permeability, and pericyte coverage, including the latest findings.

Background To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer. Methods Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included. Results Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively. Conclusions These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.

Background Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab–chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67). Results At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09–0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25–1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31–1.41]). Pembrolizumab–chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23–2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55–2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55–2.22]). Median PFS was similar for pembrolizumab and pembrolizumab–chemotherapy versus EXTREME in all subgroups. Grades 3–5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab–chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab–chemotherapy died because of treatment-related pneumonitis. Conclusion These results support the use of first-line pembrolizumab and pembrolizumab–chemotherapy for Japanese patients with R/M HNSCC. Clinical trial registry ClinicalTrials.gov, NCT02358031.

TGF-β is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-β blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-β type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer.This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/mBetween Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred.The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials.Eli Lilly via ExIST program, The Providence Foundation.

CD271 is a common receptor for all neurotrophins that is localized to neurons, endothelial cells, and the basal layer of the epithelium in normal tissue. Recently, we and others reported that CD271 plays essential roles in the development of squamous cell carcinoma, especially in tumor-initiating cells. Since little is known about how CD271 regulates cancer cell initiation and proliferation, antibodies that recognize different domains of CD271 are needed to enable investigation. Therefore, this study aimed to develop an antihuman CD271 antibody by immunizing mice with a CD271 antigen produced by a baculovirus. The antibody was named hCD271mAb#13, and it recognized cysteine-rich domain 1 with a higher affinity than the commercially available antibody ME20.4. We determined that hCD271mAb#13 is suitable for flow cytometry, Western blotting, immunocytochemistry, and immunohistochemistry of formalin-fixed paraffin-embedded tissue. Use of hCD271mAb#13 for CD271 labeling could enable detailed analyses of cancer cell regulation and other biological processes.

In the treatment of head and neck cancer, radiation therapy is an effective modality and is often used in routine clinical practice. Although rare, pyogenic spondylitis has been reported as a complication of radiation therapy. Here, we report a case of nasopharyngeal carcinoma resulting in pyogenic spondylitis from a catheter-related bloodstream infection after chemoradiotherapy. The initial symptoms were fever and posterior cervical pain. Streptococcus dysgalactiae subspecies equisimilis was detected in blood cultures. Magnetic resonance imaging showed abnormal enhancement of the C6 and C7 vertebrae and an anterior epidural abscess. The infection was successfully treated with antibacterial therapy.

Instantaneous patterning on soft material surfaces, such as hydrogels, is important in various research fields; however, it is extremely challenging. Existing strategies for soft material surface patterning are time-consuming and have poor chemical versatility. Herein, we show how micropatterns can be rapidly created on tough double-network (DN) hydrogel surfaces via sacrificial bonds and mechanical force-triggered radical polymerisation. Micropatterning is performed by local mechanical forces, which initiate radical polymerisation in a process zone in the presence of unsaturated monomers, resulting in on-demand functional patterns with a variety of geometries and chemistries. Such force-triggered activation occurs within seconds and is applicable to diverse monomers. To demonstrate potential applications, we engineered topographies and chemistries on DN hydrogel surfaces to control cell adhesion and water droplet directional transport.

Cardiac metastases from head and neck cancers are sometimes found at autopsy, but are rarely found before death; therefore, case reports are uncommon. In this report, we describe a case of cardiac metastasis from head and neck cancer. Although asymptomatic at the time of detection, positron emission tomography–computed tomography was effective in ascertaining the diagnosis. However, patients with cardiac metastases usually have a poor prognosis, and unfortunately, the patient died shortly after detection. At autopsy, the patient had a “hyperdense armored heart” owing to a huge pericardial metastases. Here, we report the imaging and autopsy findings of a hyperdense armored heart owing to cardiac metastases from head and neck cancer.

The clinical utility of systemic therapy and genomic profiling in non-squamous-cell head and neck cancer (NSCHNC) has not been fully elucidated. This phase II trial evaluated the efficacy and safety of docetaxel and cisplatin combination in the first-line setting. Eligibility criteria were recurrent and/or metastatic NSCHNC; progressive disease within the last 6 months; no prior systemic therapy; and ECOG performance status of 0–1. Patients received docetaxel (75 mg/m2 on day 1) and cisplatin (75 mg/m2 on day 1), repeated every 21 days for 6 cycles. The primary endpoint was confirmed objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Next-generation sequencing (NGS) was performed using the Ion AmpliSeq Cancer Hotspot Panel v2. Twenty-three patients were enrolled from November 2012 to October 2016, of whom 8 were male. Median age was 57 years. Ninety-six percent of cases were metastatic. Among 22 evaluable patients, confirmed ORR was 45% (95% confidential interval 24–68%). With a median follow-up period of 18.8 months, median PFS and OS were 6.7 and 20.1 months, respectively. Grade 3/4 adverse events included febrile neutropenia (39%) and anemia (22%). No treatment-related deaths were observed. NGS analysis revealed potential treatment targets, including ERBB2, KIT, and ALK. The docetaxel and cisplatin combination regimen can be considered a new treatment option in recurrent and/or metastatic NSCHNC, although primary prophylaxis for febrile neutropenia should be considered. Diverse genomic alterations may lead novel treatment options. This trial was registered with the UMIN Clinical Trials Registry as UMIN000008333 on [September 1st, 2012].

BACKGROUND: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.METHODS: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031.FINDINGS: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45-0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64-0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71-1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63-0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45-0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53-0·80], pINTERPRETATION: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC.FUNDING: Merck Sharp & Dohme.

Background Head and neck (H&N) cancer patients are often malnourished and have diminished immunity. H&N surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with a relatively high incidence of postoperative complications. Methods Associations between possible risk factors and postoperative Clavien–Dindo (C–D) grades ≥ II and ≥ IIIa wound healing- or infection-related complications, postoperative overall complications and prolonged hospital stay were investigated in 188 patients who underwent HNS-FTTR during 2014–2018. The preoperative prognostic nutritional index (PNI) was calculated using the serum albumin level and total lymphocyte count. Results C–D ≥ II and ≥ IIIa complications were seen in 66 (35.1%) and 37 (19.7%) patients, respectively. Multivariate analysis showed that (i) previous irradiation was significantly associated with C–D ≥ II wound healing- or infection-related complications and prolonged hospital stays [odds ratio (OR) 3.096 and 3.328; P = 0.007 and 0.008, respectively]; and (ii) operation time of ≥9 h 20 min was a significant risk factor for C–D ≥ IIIa wound healing- or infection-related complications, and C–D ≥ IIIa overall complications (OR 2.987 and 2.257; P = 0.021 and 0.047, respectively). (3) Only preoperative PNI ≤ 40 was associated with all occurrences of C–D ≥ II and ≥ IIIa wound healing- or infection-related complications, C–D ≥ II and ≥ IIIa overall complications, and prolonged hospital stays (OR 3.078, 2.918, 2.627, 3.132 and 3.116; P = 0.020, 0.046, 0.036, 0.023 and 0.025, respectively). Conclusions PNI, easily calculated, was the lone risk factor significantly predicting all C–D ≥ II and ≥ IIIa postoperative wound healing- or infection-related complications, C–D ≥ II and ≥ IIIa postoperative overall complications and prolonged hospital stay after HNS-FTTR.

3617 Background: Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine upregulated in colorectal cancer. Preclinical data demonstrated improved response to chemoradiation with TGFβ blockade in colorectal adenocarcinoma. Here we report the results of our single arm Phase II study combining the TGFβ type I receptor kinase inhibitor, galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal adenocarcinoma. Methods: Eligible patients had T3+ or N+ rectal adenocarcinoma planned for surgical resection. Enrolled patients completed a 14-day course of galunisertib, followed by chemoradiation with continuous infusion 5-fluorouracil or capecitabine with radiation to 50.4-54Gy in 28-30 fractions. On day 30, patients underwent another 14-day course of galunisertib concurrent with ongoing chemoradiation. Five to nine weeks after completing neoadjuvant therapy, patients underwent response assessment. Those with complete response by physical exam, proctoscopy, and MRI, could opt for non-operative management and proceed to mFOLFOX6. Those with less than a complete response underwent surgical resection. The primary endpoint was complete response rate (CR), which was a composite of pathologic complete responses in those patients who proceeded to surgery, and clinical complete responses maintained at 1 year after completion of therapy for those who chose non-operative management. Using a Simon Two-Stage approach with 90% power and α = 0.05, to detect a 20% improvement in complete response rate compared to historical control (15% vs 35%); we reject the null hypothesis if ≥10/38 patients have a CR. 38 patients were enrolled with 35 patients evaluable. Results: Median age was 51y, 68% of patients were male, 87% of patients were Stage III, 97% of patients were node-positive, and 97% were proficient in mismatch repair. 95% of patients completed study therapy. Toxicity attributed to galunisertib was Grade 1-2. 28 patients went to surgery, with a mean neoadjuvant rectal (NAR) score (NAR = 5pN-3(cT-pT)+12]2/9.61) of 11.29, and pCR in 7 patients. 7 patients underwent non-operative management, with 5 achieving cCR at 1 year. Therefore, complete responses were observed in 12 patients. Peripheral immune monitoring revealed percent change in CD3+CD4-CXCR3+ T cells and activated CD8EM T cells correlated with response to therapy. 2y PFS and OS were 81.5% and 97%. Conclusions: The addition of TGFβ inhibition to neoadjuvant chemoradiation in locally advanced rectal cancer markedly improved response to therapy, was well tolerated, and warrants further investigation. Clinical trial information: NCT02688712.

The variability of bioparticles remains a key barrier to realizing the competent potential of nanoscale detection into a digital diagnosis of an extraneous object that causes an infectious disease. Here, we report label-free virus identification based on machine-learning classification. Single virus particles were detected using nanopores, and resistive-pulse waveforms were analyzed multilaterally using artificial intelligence. In the discrimination, over 99% accuracy for five different virus species was demonstrated. This advance is accessed through the classification of virus-derived ionic current signal patterns reflecting their intrinsic physical properties in a high-dimensional feature space. Moreover, consideration of viral similarity based on the accuracies indicates the contributing factors in the recognitions. The present findings offer the prospect of a novel surveillance system applicable to detection of multiple viruses including new strains.

Background To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice. Methods This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records. Results Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141. Conclusions The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Recently, the incidence of human papillomavirus (HPV)-related head and neck cancers (oropharynx and oral) has increased rapidly. Secondary HPV-related cancers after an initial index cancer at a site associated with an HPV infection have been reported, including invasive cervical, vaginal, vulval, anal, penile, and oropharyngeal cancer. Here, we describe two female oropharyngeal cancer patients who had been treated for secondary cervical cancers with chemoradiotherapy and achieved a good clinical response.

Neck dissection results in a high probability of postoperative shoulder functional impairment, even when the spinal accessory nerve is preserved. Therefore, surgeons must inform patients about the expected functional and qualitative recovery of shoulder function after surgery.The present study included a prospective cohort of 66 patients (85 neck dissection sides) who underwent neck dissection between December 2015 and July 2017 at a single institution. The active shoulder abduction angles of the affected side and the patient-reported shoulder-specific quality-of-life recovery score of the Western Ontario Rotator Cuff (WORC) questionnaire were examined at 1, 3, 6, 9, and 12 months postoperatively. Additionally, the association between these outcomes and risk factors for shoulder impairment were investigated.The average active shoulder abduction angles were significantly improved at 3 and 6 months postoperatively compared with 1 month postoperatively (96.5 ± 4.3° at 1 month versus 110.1 ± 4.7° at 3 months, p = 0.035, and versus 142.0 ± 4.6° at 6 months, p 0.0001). The proportion of patients who were unable to abduct their shoulders by 150° or more was significantly lower at 6 months postoperatively (41.5%) compared with 1 month postoperatively (82.4%, p 0.0001). The WORC score significantly improved from 60.4 ± 2.4% at 1 month postoperatively to 67.9 ± 2.6% at 6 months postoperatively (p = 0.036). Multivariate analysis revealed that postoperative radiotherapy was a significant risk factor for shoulder impairment at 3 and 6 months postoperatively (p = 0.003 and p = 0.027, respectively), and that level V dissection and head and neck irradiation were significant risk factors for a worse shoulder outcome at 6 and 9 months postoperatively (respective p values for level V dissection and head and neck irradiation were p = 0.049 and p = 0.030 at 6 months postoperatively, and p = 0.016 and p = 0.013 at 9 months postoperatively).Satisfactory functional and qualitative recovery of shoulder function was achieved at 6 months after neck dissection. Postoperative radiotherapy was a predictor of poor shoulder function in the early postoperative period; both level V dissection and head and neck irradiation were predictors of poor shoulder function at 6 and 9 months after neck dissection.