Therapeutic effect of Nivolumab for advanced / recurrent temporal bone squamous cell carcinoma

ObjectiveThe immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC.MethodChart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined.ResultsWe examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2–54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%).ConclusionWe used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC.     

Collision tumor of a hypopharyngeal adenoidcystic carcinoma and a laryngeal squamous cell carcinoma

INTRODUCTION: Malignancies in head and neck cancer are mainly squamous cell carcinomas. Adenoid cystic carcinomas are rare lesions of this site. Laryngeal adenoid cystic carcinoma is estimated to occur in 0.1 - 0.7 % of all laryngeal carcinomas. Adenoid cystic carcinomas are rarely located in the hypopharynx. To our knowledge there is no case report of adenoid cystic carcinoma of the hypopharynx as part of a collision tumor of the larynx. CASE REPORT: A 47-year-old male patient was diagnosed with an adenoid cystic carcinoma of the hypopharynx and a squamous cell carcinoma of the larynx. Because of local extension of both tumors laryngectomy and partial pharyngotomy with bilateral neck dissection was performed followed by radiation therapy. Clinical aspects as well as histomorphological and immunohistochemical criteria of both tumor entities are discussed. DISCUSSION AND CONCLUSIONS: Immunohistochemical characteristics showed two different carcinoma entities in the larynx and hypopharynx. Only by complete histological investigation of a carcinoma those rare cases of a collision tumor can be detected. Both tumor entities need to be considered for therapy strategy and oncological follow-up planning.     

Outcome of chemotherapy following nivolumab treatment for recurrent and/or metastatic head and neck squamous cell carcinoma

ObjectiveAlthough nivolumab treatment is effective in extending the overall survival (OS) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), only a few patients benefit from this treatment. Recent studies have reported that chemotherapy and cetuximab might be effective for R/M HNSCC after nivolumab treatment. In the present study, we aimed to elucidate the effectiveness of chemotherapy after nivolumab treatment in patients with R/M HNSCC.MethodsThis retrospective study included 10 patients with R/M HNSCC who were mainly treated with paclitaxel plus cetuximab (7/10, 70%) or S-1 (3/10, 30%) following nivolumab treatment. Chemotherapy was administered as a second-line or higher palliative treatment. The performance status of all patients ranged from 0 to 2. The progression-free survival (PFS) was analyzed using the Kaplan–Meier method.ResultsThe response rate (RR), clinical benefit rate, and median PFS were 60%, 90%, and 5.4 months, respectively. Regarding adverse effects, Grade 3 neutropenia and hypomagnesemia due to salvage chemotherapy administered after immunotherapy were observed in one patient. The treatment significantly increased the RR compared to that achieved with other palliative chemotherapies reported so far.ConclusionA higher RR and clinical benefit rate were observed for our strategy than for any first-line regimen, suggesting that our strategy might improve the PFS. Palliative chemotherapy with/without cetuximab after nivolumab treatment might be useful in patients with R/M HNSCC. Although the results of this retrospective study are limited, this strategy can be a good treatment option for patients with R/M HNSCC because of its strong clinical benefits and acceptable toxicity.     

Detection of hypopharyngeal squamous cell carcinoma using serum proteomics

Conclusions. The combination of surface-enhanced laser desorption/ionization (SELDI) with bioinformatics tools could help find serum proteome biomarkers and establish a predictive model for early detection of hypopharyngeal squamous cell carcinoma (HSCC). Objectives. Proteomic profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is an emerging technique to identify new biomarkers in biological fluids and to establish clinically useful diagnostic computational models. We used it to find new potential biomarkers and to establish a predictive model for early detection of HSCC. Materials and methods. One hundred serum samples including 48 from HSCC patients and 52 from normal controls which were divided into a training set and a blind testing set were treated on WCX2 and IMAC3 protein chip, and serum protein or peptide patterns were detected by SELDI-TOF-MS. The data of spectra were analyzed by Biomarker Wizard software to screen serum proteome biomarkers of HSCC. A decision tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS). Results. Ranging from 2 to 30 kDa, 45 potential biomarkers could differentiate HSCC patients from normal controls (p?<?0.05). Among them four candidate protein peaks with m/z values of 7796, 4216, 5927, and 5361Da were selected to establish a predictive model by BPS with sensitivity of 94% and specificity of 89%. A sensitivity of 92% and specificity of 82% were validated in the blind testing set.     

Lymphatic metastases to level IIb in hypopharyngeal squamous cell carcinoma

OBJECTIVES: To evaluate the prevalence of level IIb lymph node (LN) metastasis and to identify potential clinical risk factors when level IIb metastatic diseases are present in patients with clinically node-negative (N0) and node-positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This will provide a basis for determining whether this region can be excluded in elective or therapeutic neck dissection in patients with HPSCC. DESIGN: Prospective analysis of a case series. SETTING: University hospital. PATIENTS: Fifty patients with HPSCC who underwent surgical treatment for a primary lesion and simultaneous neck dissection from January 1998 to February 2004. MAIN OUTCOME MEASURES: The incidences and clinical risk factors for level IIb LN metastasis and regional recurrence according to the presence or absence of pathologic LN involvement in level IIb. RESULTS: A total of 93 neck dissections were analyzed in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+ necks had level IIb LN metastases. Level IIb nodal metastases were significantly more prevalent in N+ necks (P=.007) than in N0 necks and in the presence of other positive LNs (P=.01) than in the absence of other positive LNs. Of the 35 patients with pathologic LNs, the regional recurrence rate was significantly higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1 of 23]; P=.04). CONCLUSIONS: Level IIb LN pads may be preserved during elective neck dissection in the treatment of patients with clinically N0 necks with HPSCC. This area should be removed during therapeutic neck dissection in the treatment of clinically N+ necks.     

Detection of hypopharyngeal squamous cell carcinoma using serum proteomics

CONCLUSIONS: The combination of surface-enhanced laser desorption/ionization (SELDI) with bioinformatics tools could help find serum proteome biomarkers and establish a predictive model for early detection of hypopharyngeal squamous cell carcinoma (HSCC). OBJECTIVES: Proteomic profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is an emerging technique to identify new biomarkers in biological fluids and to establish clinically useful diagnostic computational models. We used it to find new potential biomarkers and to establish a predictive model for early detection of HSCC. MATERIALS AND METHODS: One hundred serum samples including 48 from HSCC patients and 52 from normal controls which were divided into a training set and a blind testing set were treated on WCX2 and IMAC3 protein chip, and serum protein or peptide patterns were detected by SELDI-TOF-MS. The data of spectra were analyzed by Biomarker Wizard software to screen serum proteome biomarkers of HSCC. A decision tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS). RESULTS: Ranging from 2 to 30 kDa, 45 potential biomarkers could differentiate HSCC patients from normal controls (p < 0.05). Among them four candidate protein peaks with m/z values of 7796, 4216, 5927, and 5361Da were selected to establish a predictive model by BPS with sensitivity of 94% and specificity of 89%. A sensitivity of 92% and specificity of 82% were validated in the blind testing set.     

Prognostic impact of perineural invasion in hypopharyngeal squamous cell carcinoma

Objectives: The aim of this study was to evaluate the role of PNI in HPSCC.

Methods: The medical records of 105 patients who underwent surgery-based treatment for HPSCC were reviewed. Clinicopathologic parameters including disease-specific survival were correlated with PNI.

Results: PNI was identified in 27 of the 105 (25.7%) cases of HPSCC. Correlation analysis demonstrated that PNI in HPSCC was significantly correlated with pN classification (10.3% in N0/N1 vs 34.8% in N2/N3, p?=?0.006). Patients with PNI had decreased 5-year disease-specific survival with borderline significance (p?=?0.065). In a sub-set of 31 patients who did not receive post-operative radiotherapy, PNI was determined to be a significant prognostic predictor (p?=?0.033). In multivariate analysis, extracapsular invasion was the only independent prognostic factor for disease-specific survival (p?=?0.001).

Conclusion: Perineural invasion (PNI) should be considered an independent predictor for cervical lymph node involvement. PNI status in primary hypopharyngeal squamous cell carcinoma (HPSCC) specimens should be considered in decisions concerning adjuvant radiotherapy.     

Treatments and costs for recurrent and/or metastatic squamous cell carcinoma of the head and neck in the Netherlands

For patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), chemotherapy can prolong life and alleviate symptoms. However, expected gains may be small, not necessarily outweighing considerable toxicity and high costs. Treatment choice is to a large extent dependent on preferences of doctors and patients and data on these choices are scarce. The purpose of this study is to obtain real-world information on palliative systemic treatment and costs of R/M SCCHN in the Netherlands. In six Dutch head and neck treatment centers, data were collected on patient and tumor characteristics, treatment patterns, disease progression, survival, adverse events, and resource use for R/M SCCHN, between 2006 and 2013. 125 (14 %) out of 893 R/M SCCHN patients received palliative, non-trial first-line systemic treatment, mainly platinum + 5FU + cetuximab (32 %), other platinum-based combination therapy (13 %), methotrexate monotherapy (27 %) and capecitabine monotherapy (14 %). Median progression-free survival and overall survival were 3.4 and 6.0 months, respectively. 34 (27 %) patients experienced severe adverse events. Mean total hospital costs ranged from €10,075 (±€9,891) (methotrexate monotherapy) to €39,459 (±€21,149) (platinum + 5FU + cetuximab). Primary cost drivers were hospital stays and anticancer drug treatments. Major health care utilization and costs are involved in systemically treating R/M SCCHN patients with a limited survival.     

晚期下咽癌、喉复发癌术后颈部缺损整复组织的选择

目的:探讨以不同组织移植物Ⅰ期重建晚期下咽癌、喉复发癌术后颈部、下咽食管缺损的适应证及治疗效果。方法:喉复发癌36例, 肿瘤切除后采用胸大肌肌皮 瓣修补组织缺损18例,肩胸皮瓣修补4例,胃代食管修补2例,胸部推移皮瓣重建下颈部与上纵隔组织缺损,并消灭手术死腔12例。晚期下咽癌16例,颈段食管癌8例,以游离空肠整复1例, 健侧喉黏膜瓣修复咽部缺损8例,喉气管代食道8例,胸大肌皮瓣修复咽部缺损2例,胃代食管2例,游离前臂皮瓣修复下咽1例。 结果:术中无一例死亡,术后无修复组织坏死 ,全部组织瓣存活。采用健侧喉黏膜瓣修复者,仅 1例有术前放疗史的患者发生术后咽漏,胸大肌皮瓣 修复者发生咽漏1例,胃代食道术后发生咽漏1例。全部病例愈合后均恢复正常饮食。随访 9～84个月,14例出现吞咽梗阻,可进流质饮食。结论:下咽癌患者术后组织缺损的修复方法各有侧重。肿瘤的部位和手术后组织缺损的大小是选择修复方法的首要因素;其次,应结合患者的年龄和全身状况,考虑减少并发症。     

A retrospective study of dual-energy CT for clinical detecting of metastatic cervical lymph nodes in laryngeal and hypopharyngeal squamous cell carcinoma

Conclusion: After the reconstruction of imaging in dual-energy CT gemstone spectral imaging, the ratio of the two slopes curves, the target lymph node and primary lesion, respectively, might contribute to the clinical diagnosis of cervical lymph nodes in laryngeal and hypopharyngeal squamous carcinoma. Objective: To investigate the value of the dual-energy CT gemstone spectral imaging for clinical detecting of metastatic cervical lymph nodes in laryngeal and hypopharyngeal squamous carcinoma. Methods: Forty-seven cases who were suffering from laryngeal or hypopharyngeal squamous carcinoma and had complete clinical and pathological data were included, and 79 cervical lymph nodes were studied retrospectively (including 31 metastatic nodes and 48 non-metastatic nodes). Contrast-enhanced energy spectral imaging and reconstruction were performed. After the reconstruction, the slope of the curve in the target lymph node and the lesion were calculated. The ratio of the two slopes was studied. The pathological data of cervical lymph node and primary lesion were also collected. Results: The ratios were 1.20 ± 0.09 and 0.82 ± 0.12 in metastatic and non-metastatic lymph nodes, respectively. The difference was statistically significant (p < 0.05). The ratio was positively correlated to the stasis of lymph nodes only, rather than their morphological appearance, the pathological classification, or the individual difference (p < 0.05).     

Spindle cell carcinoma as a locally recurrent malignancy after surgery for early lingual squamous cell carcinoma

Spindle cell carcinoma (SpCC) of the tongue is a relatively rare malignancy. We treated a patient with metachronous early squamous cell carcinoma (SCC) in both margins of the tongue (right side first followed by left side). Eight years after treatment for the first SCC by surgery and radiotherapy, the second SCC occurred in the contralateral margin of the tongue. Surgical resection was performed for the second SCC, with local recurrence 8 months later associated with pathological change from SCC to SpCC. The SpCC was completely resected with wide surgical margins in combination with bilateral neck dissection. However, the patient developed pulmonary metastasis and died of respiratory failure 4 months after the final surgery. Postoperative inflammatory reaction followed by scar formation in the previously irradiated surgical site might have caused the transition from SCC to SpCC during the process of recurrence.     

PD-1/PD-L1 inhibitor monotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck: a meta-analysis

PurposeTo evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy compared to the standard of care in the first-line setting for recurrent or metastatic head and neck squamous cell carcinoma.Materials and methodsThe PubMed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials. The clinical outcomes of overall survival, progression-free survival, objective response rates, and grade 3 or higher adverse events were analyzed using Stata SE 15 software with a significance level set to 0.05.ResultsWe identified four randomized controlled trials (1 nivolumab, 2 pembrolizumab, and 1 durvalumab), including a total of 2474 patients. The results of the meta-analysis showed pooled hazard ratios of overall and progression-free survival for programmed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy of 0.82 (95% CI: 0.73–0.91, p < 0.001) and 0.96 (95%CI: 0.84–1.07, p < 0.001) and pooled odds ratios of objective response rates and grade 3 or higher adverse events of 1.04 (95%CI: 0.46–2.37; p = 0.926) and 0.28 (95%CI: 0.22–0.35, p < 0.001), respectively. Subgroup analysis showed that inhibitors for both programmed cell death-1 (nivolumab and pembrolizumab) and programmed cell death-ligand 1 (durvalumab) were associated with significantly longer overall survival (HR = 0.80, 95% CI: 0.70–0.90, p < 0.001 and HR = 0.88, 95%CI: 0.70–1.06, p < 0.001, respectively).ConclusionsProgrammed cell death-1/programmed cell death-ligand 1 inhibitor monotherapy showed more clinical benefit versus the standard of care in patients with recurrent or metastatic head and neck squamous cell carcinoma, with an acceptable safety profile.     

Spindle cell carcinoma as a locally recurrent malignancy after surgery for early lingual squamous cell carcinoma

Spindle cell carcinoma (SpCC) of the tongue is a relatively rare malignancy. We treated a patient with metachronous early squamous cell carcinoma (SCC) in both margins of the tongue (right side first followed by left side). Eight years after treatment for the first SCC by surgery and radiotherapy, the second SCC occurred in the contralateral margin of the tongue. Surgical resection was performed for the second SCC, with local recurrence 8 months later associated with pathological change from SCC to SpCC. The SpCC was completely resected with wide surgical margins in combination with bilateral neck dissection. However, the patient developed pulmonary metastasis and died of respiratory failure 4 months after the final surgery. Postoperative inflammatory reaction followed by scar formation in the previously irradiated surgical site might have caused the transition from SCC to SpCC during the process of recurrence.     

Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for hypopharyngeal squamous cell carcinoma

Objective: The aim of this work was to analyze the clinical characteristics and pretreatment peripheral blood cell counts of patients with hypopharyngeal squamous cell carcinoma (HPSCC) and determine their relationship with clinical outcomes.

Methods: One hundred ninety-seven patients were eligible for the study. The relationship between survival and pretreatment peripheral absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were analyzed by one-way analysis of variance, t-test, and univariate and multivariate analysis.

Results: The median follow-up time was 30.95 months (range 1–82 months). The 3-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates for all patients were 40.8, 51.0, and 48.1%, respectively. The ANC, AMC, NLR, and LMR were significantly associated with tumor stage and clinical stage (p?p?=?.035, .047, and .045, respectively).

Conclusion: The pretreatment LMR should be considered as an independent prognostic factor for patients with HPSCC.     

eIF4E与FHIT在下咽癌中的表达

目的检测eIF4E与FHIT在下咽癌中的表达,探讨二者与下咽癌的关系及其相互之间的内在关系.方法用免疫组化法检测43例下咽癌组织,30例下咽癌切缘,20例正常黏膜组织中eIF4E与FHIT基因蛋白的表达.结果eIF4E与FHIT在下咽癌中表达的阳性率分别为95.3%,34.9%.eIF4E显著高于对照组,FHIT显著低于对照组.结论过度表达的eIF4E是下咽癌恶性改变及判断其恶性程度的分子标志;FHIT的低表达与下咽癌的生长及恶性程度相关;二者在下咽癌的表达呈负相关,为下咽癌的治疗提供了理论基础和临床指导.