CT staging and surveillance of the thorax in patients with newly diagnosed and recurrent squamous cell carcinoma of the head and neck: is it necessary?

The detection of distant metastases or synchronous primary tumours at initial presentation, or at recurrence in patients with head and neck squamous cell carcinoma (HNSCC), frequently alters the selection of therapy in these patients. A number of series report appreciably high rates for these lesions. This study evaluated 108 computed tomography (CT) scans and chest radiographs (CXR) of the thorax, in 80 patients presenting with HNSCC over a 4 year period. There were three clinical settings; (a) at original diagnosis n = 61, (b) clinical evidence of local/regional recurrence n = 19 (c) suspicion of recurrence due to neck symptomatology n = 28. CT thorax detected two out of 61 (3%) distant metastases at the initial diagnosis stage (both were either stage III or IV) and one out of 19 (5%) patients evaluated at the time of loco/regional recurrence. CXR failed to reveal evidence of pulmonary metastases in the two patients at initial diagnosis stage, but correctly identified pulmonary metastases in the loco-regional recurrence patient. There was no thoracic malignancy detected in the surveillance CT scans, and no synchronous second primary tumour detected during the study. CT is known to be more sensitive than conventional CXR in detecting thoracic pathology in HNSCC patients, however, we feel CT is of limited value in stage I or II disease. We no longer carry out routine staging CT scans of the thorax in patients presenting with stage I or II HNSCC, or with neck symptomatology with no clinical evidence of recurrence.Presented at the Royal Academy of Medicine in Ireland, Otolaryngology Head and Neck Surgery Section 2005.     

A prospective study of PET-FDG imaging for the assessment of head and neck squamous cell carcinoma

The main aim of the study was to evaluate the use of positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging for the detection of squamous cell carcinoma of the head and neck. Fifty-four consecutive patients with malignancies involving the head and neck were studied prospectively. Thirty-one patients presented with primary disease and 23 were suspected of recurrent or residual disease. All patients underwent full clinical staging, PET-FDG scans and anatomical imaging, 37 underwent computed tomography (CT), 13 magnetic resonance (MR) and four had both CT and MR. Clinical assessment, CT/MR, PET-FDG and histological examination were all evaluated independently of each other. All 31 primary head and neck malignant tumours were detected by PET-FDG. Based on 16 patients who underwent neck dissections, the sensitivity and specificity of PET-FDG for detecting nodal disease was 67% and 100% respectively, compared with clinical assessment of 58% and 75% and CT/MR of 67% and 25%. In all 12 patients, PET-FDG correctly identified the presence or absence of recurrent or residual disease. PET-FDG staged 13 post-treatment necks with an accuracy of 100%, as compared to CT/MR which was accurate in 7 of 13 and clinical assessment which was accurate in eight. Three sites of abnormal tracer uptake unrelated to malignancy were recorded as incidental findings (mandibular osteomyelitis, 1; post glossectomy site, 2). PET-FDG was more accurate than CT/MR for identifying primary and recurrent tumours as well as metastatic lesions in the neck. If these diagnostic properties of PET-FDG are confirmed in further prospective studies, it could prove a valuable adjunct for the management of head and neck cancer.     

The role of positron emission tomography scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy

OBJECTIVE: The objective of this study was to determine the sensitivity, specificity, and predictive value of 18-fluorodeoxyglucose positron emission tomography (PET) in predicting residual cervical metastatic disease in patients with N-positive necks undergoing curative radiotherapy and chemoradiotherapy for squamous cell carcinoma (SCC) of the upper aerodigestive tract. METHODS: The authors studied a prospective case series of patients (2003-2005) of patients undergoing radiotherapy and chemoradiotherapy for advanced head and neck SSC. Study entry criteria included N-positive neck disease, a complete response to treatment at the primary tumor site, posttreatment PET scan (8-12 weeks after completion of treatment), followed by salvage neck dissection. The posttreatment PET scan neck findings were correlated to the salvage neck dissection pathology report. The sensitivity, specificity, and predictive values of the PET scan to predict residual cervical metastatic disease after curative chemoradiotherapy were calculated. RESULTS: Twenty-one neck dissections (pretreatment N1 = 5, N2a = 2, N2b = 8, N3 = 6) were entered into the protocol. Four (19.0%) of the 21 neck specimens were positive for residual cervical metastatic disease, whereas the remaining 17 (80.9%) specimens demonstrated no residual carcinoma. The overall sensitivity and specificity were 75.0% and 64.7%, respectively. The positive predictive value was 33% and the negative predictive value was 91.7%. CONCLUSIONS: Although the role of posttreatment neck dissection remains controversial, the surgeon must rely on clinical examination and imaging studies. Our practice has been to perform planned staged neck dissections on all N2 and N3 necks, as well as N1 necks with an incomplete response to treatment. Based on this small prospective study, it appears that PET imaging lacks adequate sensitivity and specificity to reliably predict the presence of residual cervical metastatic disease after completion of chemoradiotherapy. With a negative predictive value of 91.7%, however, a negative PET scan appears to be a reliable predictor of the absence of residual tumor.     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。     

正电子发射断层摄影术在头颈部恶性肿瘤诊断中的应用

目的 :探讨18F FDG正电子发射断层摄影术 (PET)在头颈部恶性肿瘤诊断中的价值。方法 :回顾性分析应用18F FDGPET检查的 75例头颈部肿瘤患者 (鼻咽癌 36例 ,食管癌 18例 ,甲状腺癌 13例 ,喉癌 6例 ,下咽癌 2例 )的临床资料 ,其18F FDGPET显像结果与病理结果进行比较 ,部分与CT、MRI比较。结果 :18F FDGPET显像结果与病理结果相符率极高 ,鼻咽癌的灵敏度为 91.30 % ,特异度为 76 .92 % ,准确率为 86 .11% ;食管癌的灵敏度为 10 0 .0 0 % ,特异度为 83.33% ,准确率为 94 .4 4 % ;甲状腺癌、喉癌和下咽癌的灵敏度、特异度及准确率均为 10 0 %。结论 :18F FDGPET在头颈部恶性肿瘤的诊断中具有明显的优势。     

Patterns of bone metastases from head and neck squamous cell carcinoma

ObjectiveTo report clinical features of bone metastases (BM) from head and neck squamous cell carcinoma (HNSCC).MethodsAmong 772 patients with HNSCC diagnosed at our hospital over 9 years, 30 patients (3.9%) had clinical evidence of BM (24 men and 6 women; mean age: 63 years). We assessed the time interval from the primary diagnosis to BM development, symptoms attributable to BM, presence of distant metastases to other organs, number of BM, sites of BM, morphologic changes on computed tomography (CT) images, treatment for BM, and overall survival (OS).ResultsBM at the initial stage were found in 9 patients with HNSCC (30%), and in 21 patients (70%) with HNSCC during the course of the disease. In the later patients, the median time interval from the primary diagnosis was 11.5 months. Nineteen patients (63%) did not have BM-related symptoms, 6 (20%) had pain, 3 (10%) had neurologic symptoms resulting from vertebral or skull metastases, and 2 (7%) had hypercalcemia. Seventeen patients (57%) showed bone-exclusive metastases, and 13 (43%) had distant metastases in other organs. Eleven patients (37%) had monostotic metastases (solitary BM), and 19 patients (63%) had polyostotic metastases (multiple BM). When combined, 9 patients (30%) showed bone-exclusive and monostotic metastases. The most commonly affected site was the thoracolumbar spine, accounting for 34% of total BM, followed by the pelvis (24%), shoulder and thorax (21%), and the extremities (17%). Notably, metastases to bones above the clavicle (craniofacial bones and cervical spine) accounted for only 3% of all bone lesions. CT images showed variable morphologic patterns with osteolytic type in 17 patients (57%), intertrabecular in 7 (23%), osteoblastic in 4 (13%), and mixed in 2 (7%). Systematic chemotherapy for BM was performed in 19 patients and radiotherapy in 18. The median survival time for patients with bone-exclusive and monostotic metastases was significantly longer than that for patients with multi-organ metastases or polyostotic metastases at 18.2 months vs. 5.7 months (p = 0.02). Neither chemotherapy nor radiotherapy extended OS.ConclusionThirty percent of BM cases from HNSCC showed bone-exclusive and monostotic metastases. These patients tended to show a more favorable prognosis than patients with multi-organ metastases or polyostotic metastases.     

新辅助免疫治疗在头颈部鳞状细胞癌中的研究进展

头颈部鳞状细胞癌(HNSCC)是全球第八大常见癌症,超过一半的HNSCC患者可出现局部复发或远处转移。随着医学的发展,免疫治疗药物的陆续问世为复发/转移性HNSCC患者带来了新的希望。目前多项研究已经证实,以程序性死亡受体1(PD-1)检查点抑制剂为代表的新辅助免疫治疗具有较好的疗效,且安全性良好,而以新辅助免疫治疗为基础的联合治疗也成为研究热点,包括新辅助免疫治疗联合化疗、放疗、放化疗、靶向治疗以及新辅助双免疫联合治疗等新型治疗模式。本文将对新辅助免疫治疗在HNSCC中的研究进展作一综述。     

Evaluation of the impact of addition of PET to CT and MR scanning in the staging of patients with head and neck carcinomas

The addition of whole body positron emission tomography (PET) to the investigation of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) was assessed over a 6-month period. Staging investigations included laryngoscopy, oesophagoscopy, CXR, CT and MRI. In addition, all patients had an extended-field (whole body) FDG-PET scan and were restaged. Standardised Uptake Values (SUV) were used to measure FDG uptake. SUV levels above 5 were considered indicative of the presence of tumour, values below 3 indicative of benign aetiology and values equal to and between 3 and 5 were considered equivocal. Forty-eight consecutive patients with biopsy proven HNSCC were included for study. Three patients presenting with neck disease had unknown primary tumours. Of the remaining 45 patients, CT scan correctly identified 40 of the primary tumours (89%). MRI and PET both identified 41 primary tumours (91%). Thirty-two patients underwent neck dissection. Of these patients 12 had pathologically N0 necks and 20 had positive nodal disease. CT scan and MRI each correctly staged pN0 necks in 10 of 12 patients (83%) whereas PET alone had a lower true negative rate of 8 out of 12 patients (67%). PET correctly staged the N+ necks in 14/20 patients (70%) versus 12/20 (60%) for MRI, and 8/20 (40%) for CT alone. All four patients who were judged to have distant metastases by PET had these metastases deemed negative by other investigation. None of the three imaging modalities was able to identify the tumour site in the three patients with unknown primaries. In conclusion, although PET has got a higher sensitivity in detecting nodal disease, it has only slightly improved the classification of N+ necks. The findings of this study cast doubt on the merit of routine addition of PET to the current investigative protocols for HNSCC patients.Presented at the Irish Otolaryngology Society annual meeting, Oct 2003     

Whole-body MRI for staging patients with head and neck squamous cell carcinoma

Conclusions. Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. Objective. To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. Material and methods. This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43–80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CT of the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10±3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. Results. In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases.     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.     

Cancer stem cells in head and neck squamous cell carcinoma

Recent studies have demonstrated that cancer stem cells (CSC) play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). This subpopulation of undifferentiated, self-renewing cells is responsible for resistance to conventional anti-cancer therapy, cancer recurrence, metastasis and ability to form a heterogeneous tumor. CSC are identified on the basis of specific markers, including membrane proteins or cell enzymes, or by using their self-renewal properties. As their resistance to standard HNSCC treatment may eventually lead to the lack of treatment success, there is an urgent need to better understanding CSC biology and identify them as potential target new treatment modality.     

Zwint-1蛋白在头颈部鳞状细胞癌中表达上调及其与临床特征的相关性

目的探讨Zeste white 10（ZW10）相互作用着丝粒蛋白1 (ZW10 interacting kinetochore protein 1,Zwint 1),在头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）肿瘤组织中的蛋白表达情况,以及其与临床病理特征之间的关系。方法采用免疫组织化学检测的方法,对16例HNSCC患者的肿瘤组织样本,以及7例相应的癌旁正常组织样本中Zwint 1蛋白进行检测。同时,分析HNSCC相关组织芯片中Zwint 1蛋白表达与HNSCC临床特征的相关性。结果临床样本与组织芯片的检测结果显示,Zwint 1蛋白在HNSCC肿瘤组织中的蛋白表达高于正常组织,其差异具有统计学意义（t=2.399, P<0.05）。组织芯片的检测结果显示,Zwint 1蛋白表达量与HNSCC患者的肿瘤大小（F=2.889,P<0.05）、淋巴结转移（t=2.110,P<0.05）、分化（F=3.667,P<0.05）以及临床分期（F= 2.864,P<0.05）均具有相关性。但是卡方检验结果显示,Zwint 1蛋白阳性表达与肿瘤大小（χ2=3.236,P>0.05）、淋巴结转移（χ2=1.463,P>0.05）、分化（χ2=1.271,P>0.05）、临床分期（χ2=4.179,P>0.05）,差异无统计学意义。结论Zwint 1蛋白在HNSCC的发生发展过程中发挥有重要作用,可能是HNSCC潜在的靶向治疗目标。     

细胞焦亡在头颈部鳞状细胞癌中的作用及其研究进展

头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症,5年生存率仍低于50%。近年来,细胞焦亡作为一种新发现的细胞程序性死亡方式引起了广泛关注。这一过程由炎性半胱氨酸天冬酶(Caspase)激活,并通过依赖gasdermin蛋白家族来形成质膜孔。研究表明,细胞焦亡在肿瘤进展和治疗抵抗中起着重要作用。活化的炎性小体,作为核苷酸结合寡聚化结构域样受体(NLR)的一个成员,能激活Caspase-1,从而诱导炎症效应和细胞焦亡,进一步影响肿瘤疾病的进展。然而,关于细胞焦亡和HNSCC之间关系的研究仍然有限。本文综述了现有的研究成果,并强调了更多针对细胞焦亡在HNSCC中的作用研究的重要性。     

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.     

免疫疫苗在头颈部鳞状细胞癌中的研究进展

头颈部鳞状细胞癌系头颈部肿瘤中最常见的病理类型,其发病率逐年上升,发现时多属中晚期,预后差,死亡率高。随着研究的深入,头颈鳞癌的治疗机制愈加清晰,治疗方式呈现多元化。免疫疫苗作为一种新兴的免疫治疗方式,因其独特的优势,正逐步成为头颈部鳞状细胞癌治疗的热点之一。其可分为预防性疫苗和治疗性疫苗,两者分别以不同的机制在头颈鳞癌的治疗中发挥疗效。相较其他免疫治疗方法,免疫疫苗可以更精准治疗头颈肿瘤且不良反应更轻微。随着免疫疫苗向个体化定制方向发展,其有望成为抗癌免疫治疗的强大工具。回顾头颈部鳞状细胞癌研究中关于免疫疫苗的进展,同时对其前景进行了展望。