尼妥珠单抗联合多西他赛和顺铂一线治疗复发或转移性头颈部鳞癌疗效观察

目的 观察尼妥珠单抗联合多西他赛和顺铂一线治疗复发或转移性头颈部鳞癌的疗效及安全性.方法 回顾性分析28例尼妥珠单抗联合多西他赛+顺铂(观察组)及30例多西他赛+顺铂(对照组)一线治疗复发或转移性头颈部鳞癌患者的临床资料,比较两种方案的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存时间(PFS)及总生存时间(O...     

Elderly Patients With Squamous Cell Carcinoma of the Head and Neck and the Benefit of Multimodality Therapy

Background.

Limited data are available regarding outcomes in elderly head and neck cancer patients. This retrospective study was designed to characterize head and neck cancer in geriatric patients.

Patients and Methods.

This study included all patients in a large university-based tumor registry who were diagnosed with head and neck cancer from January 1, 1990, to December 31, 2005. Patients aged ≥70 years at the time of diagnosis were defined as older. Overall survival and progression-free survival were censored at 60 months. Survival differences were compared using the log-rank test. Hazard ratios were estimated using a Cox proportional hazards model, adjusting for potential confounders.

Results.

Of 1,598 patients identified, 1,166 patients were aged <70 years (i.e., younger) and 281 patients were aged ≥70 years (older). When controlling for possible confounders, older patients were nearly twice as likely to die within 5 years as their younger counterparts (hazard ratio: 1.92). The median life expectancy for older patients was nearly 5 years for stage I–II disease and <2 years for stage III–IV disease. Older patients with stage III–IV disease who received multimodality therapy had 5-year survival similar to that younger patients with stage III–IV disease who were treated similarly (33.2% vs. 44.0%). Older patients with stage III–IV disease who received single-modality therapy had extremely poor survival compared with all other patients (hazard ratio for progression-free survival: 1.5).

Conclusion.

This study highlights the need for better understanding of the factors affecting head and neck cancer outcomes in elderly patients. Information about life expectancy in elderly head and neck cancer patients may help guide treatment decisions.     

无法切除的复发头颈部鳞癌的姑息放疗

为评价头颈部鳞癌术后复发患者行姑息放疗的疗效及其影响因素，对１９８８年７月至１９９６年２月在我科接受姑息放疗的１０６例患者的资料行回顾性分析。结果：放疗后ＣＲ２２．６％（２４／１０６），ＰＲ３８．７％（４１／１０６），ＮＲ３８．７％（４１／１０６）；总有效率为６１．３％（６５／１０６）；放疗后挽救性手术成功率为４／９；疗后６３．２％（６７／１０６）的患者Ｋａｒｎｏｆｓｋｙ得分上升，症状减轻，生存质量提高；１、２、３年生存率分别为５４．７％（５８／１０６）、２１．７％（２３／１０６）和５．７％（６／１０６）；远处转移率２９．２％（３１／１０６），放疗并发症１０．４％（１１／１０６）。结论：姑息放疗是晚期头颈部鳞癌术后复发患者一种较好的治疗选择；为了提高疗效，放射剂量应尽可能高于５０Ｇｙ，采用超分割连续放疗技术和避免分段。     

Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival

AimsWe conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS).Materials and methodsSCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables.ResultsIn total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21–30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5–0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis.ConclusionA large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.     

调强放疗对头颈部肿瘤患者甲状腺功能的影响

目的 探讨调强放疗对头颈部肿瘤患者甲状腺功能的影响.方法 40例头颈部恶性肿瘤(不包括甲状腺来源的恶性肿瘤),接受调强适形放射治疗,采用放射免疫法检测放疗前及放疗后3、6、12、18及24个月的T3、T4以及TSH水平.结果 40例头颈部非甲状腺癌的恶性肿瘤患者中,放疗后3、6、12、18及24个月T3、T4下降及TSH升高分别有1例(2.5％)、3例(7.5％)、5例(12.5％)、7例(17.5％)和10例(25％),其中2例(5％)伴有轻度的表情淡漠等临床症状,给予补充甲状腺素治疗后好转.结论 调强放射治疗可导致甲状腺功能不同程度的改变,且随着随访时间的延长,甲状腺功能损伤发生率呈增高趋势,应引起临床关注.     

Characteristics and Impact of HPV-Associated p16 Expression on Head and Neck Squamous Cell Carcinoma in Thai Patients

Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy in Asia. Infection by human papilloma virus (HPV) has been recognized as an etiological risk for HNSCC, especially oropharyngeal region. While the association between HPV and HNSCC has been well evaluated in Western countries, only a few investigated the HPV-associated HNSCC in Southeast Asia. This study evaluated the prevalence, the characteristics, and the impact of HPV on the treatment outcomes in Thai HNSCC patients. Methods: Non-nasopharyngeal HNSCC patients treated at Ramathibodi Hospital during 2007-2013 were identified through the cancer registry database. Baseline patient, treatment data and survivals were retrospectively reviewed. The formalin-fixed paraffin-embedded (FFPE) tissue sections were retrieved for p16 analysis. The HPV status was determined by p16 immunohistochemistry. The survival outcomes were analyzed in cases which p16 status was confirmed. Results: Total of 200 FFPE tissues of HNSCC patients was evaluated for p16 expression. Positive p16 status was observed in 24 cases (12%); majority of p16-positive were men (20:4 cases). The oropharynx (37.9%) was the most common site found in p16-positive while oral cavity (3.2%) was the least common site. Interestingly, 66.7% of p16-positive were former/current smokers, and 70.8% of this subgroup was categorized as clinical AJCC stage III-IV. The p16-positive HNSCC was significantly superior in 5-year overall survival [5-yrs OS 63% vs. 40%, p=0.03], 5-year disease-free survival [5-yrs DFS 61% vs. 36%, p=0.03] and in 5-year locoregional relapse-free survival [5-yrs LRFS 93% vs. 68%, p=0.018] when compared with p16-negative. Conclusions: In comparison to the results from the Western countries, the prevalence of HPV-related HNSCC in Thai patients was less, and differences in some characteristics were observed. Nevertheless, improvement in OS, DFS and LRFS were observed in p16-positive patients. Our analyses suggested that p16 status is also a strong prognostic marker for HNSCC patients in Thailand.     

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

The molecular status of the epidermal growth factor receptor (EGFR) has not been as well studied in head and neck squamous cell carcinoma (HNSCC) as in lung cancer. We examined the frequencies of EGFR mutations as well as the expression/phosphorylation status of the EGFR protein in HNSCC patients. Moreover, we tried to elucidate associations between EGFR molecular status and patient characteristics and disease‐free survival. In this prospective cohort study, clinical data and samples were obtained from 82 consecutive patients who had not been treated with EGFR molecular targeting therapy. Full‐length EGFR was sequenced, and expression and phosphorylation of the EGFR protein were measured by Western blotting. Four novel mutations (E709K, V765G, Ins770G, and G1022S) and one mutation well‐known in lung cancer (L858R) were identified in six HNSCC samples (7%), but we could not find any mutations in the extracellular domain of EGFR, such as EGFRvIII, in this study. E709K and Ins770G as well as L858R appear to be functional mutations based on the use of Ba/F3 cells. In terms of patient characteristics, the number of metastatic lymph nodes and node stage were associated with phosphorylation of EGFR. No patients with EGFR mutations relapsed during the study period. Excluding mutated cases, patients whose tumor samples showed phosphorylated EGFR relapsed significantly earlier than those without phosphorylated EGFR. This finding was still significant after adjusting for mutation and overexpression of EGFR protein using the Cox proportional hazard model. In conclusion, phosphorylated EGFR without mutations may be a marker of poor prognosis in patients with HNSCC.     

Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy

Background/Aim: The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods: The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results: The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion: The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.     

Efficacy and Tolerance of Carboplatin plus Cetuximab (Simplified EXTREME Regimen) in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

AimsThe EXTREME regimen is the standard for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). However, many patients have a poor performance status and/or comorbidities, making them unfit for this regimen. We have treated them with carboplatin and cetuximab (simplified EXTREME regimen) since 2007. Our aim was to assess the efficacy and tolerance of this regimen in this frail population.Materials and methodsA retrospective chart review of all patients treated with the simplified EXTREME regimen for recurrent and/or metastatic HNSCC in three academic hospitals between 2007 and 2017 was carried out. The primary end point was overall survival. Secondary end points were progression-free survival (PFS), overall response rate (ORR) and toxicity.ResultsOne hundred and three patients were included. The median age was 63 years, 40% had performance status 2–3. The median follow-up was 30.2 months. The median overall survival and PFS were 7.2 and 3.7 months, respectively. The median overall survival was 10.1 months in patients with performance status 0–1 versus 4.6 months in patients with performance status 2–3 (P = 0.01). ORR was 39%. Acute grade 3–4 haematological and non-haematological toxicity rates were 25.2% and 27.2%, respectively. Patients with grade 1 or more skin toxicity had a higher ORR (hazard ratio = 3.44; P = 0.03), a prolonged overall survival (hazard ratio = 0.37; P < 0.0001) and PFS (hazard ratio = 0.29; P < 0.0001). During treatment, 29% of patients had pain reduction, 13.5% had weight gain and 17.2% had an improvement in performance status.ConclusionsThis is the largest cohort of patients treated with simplified EXTREME for HNSCC. It was well tolerated, with a high ORR. Interestingly, skin toxicity correlated with treatment efficacy.     

头颈鳞癌的术前化疗效果

[目的]研究术前化疗能否提高手术切除率,降低局部复发率。［方法］104例头颈鳞癌病人分成试验组（58例）：术前化疗 手术 术后放疗组;对照组（46例）：手术 术后放疗,但不用术前化疗。手术方式为原发癌切除 颈淋巴结清扫术,用或不用肌皮瓣修复头颈部组织缺损。术后放疗剂量50Gy～60Gy。术前化疗用PFP方案即DDP＋5－Fu＋PYM。［结果］试验组部分缓解67.2%,微效17.2%。试验组和对照组3年局部复发率分别为27.6%、52．2％（P＜0.01）;但3年内远处转移率无差异,分别为34．5%、34．8%,中位生存期分别为23个月和22个月,3年生存率分别为65．5%和56．5%（P＞0.05）。［结论］术前新辅助化疗,可以缩小瘤体,提高手术切除率,减少局部复发。     

Accuracy of Response Assessment Positron Emission Tomography-Computed Tomography Following Definitive Radiotherapy Without Chemotherapy for Head and Neck Squamous Cell Carcinoma

Aim

There are few data to inform on the use of response assessment 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following radical radiotherapy without chemotherapy for head and neck squamous cell carcinoma (HNSCC). This retrospective study evaluated the accuracy of PET-CT in HNSCC following radical radiotherapy.

头颈部鳞癌肿瘤间质液压的检测

目的：为了检测头颈部鳞癌病人的肿瘤间质液压（TIFP）。方法：采用国产ZYH－3型组织液压测量仪，检测了16例头颈部鳞癌原发灶及4例转移灶的TIFP。结果：发现头颈部鳞癌原发灶和转移灶的TFFP都增高，测得的TIFP值与肿瘤体积具有良好的相关关系。结论：TIFP增高是恶性肿瘤的一项重要病理生理学特征。TIFP增高是抗癌药和免疫因子进入肿瘤的病理学障碍，因此，设法降低TIFP具有重要意义。     

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacityfor self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells areconsidered the ‘‘drivers’’ of the tumorigenic process in some tumor types, and have been named cancer stemcells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to theacquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype thatmay contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamouscell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase(ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive frontswhere endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment hasbeen shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel targetof study given their slow growth and innate mechanisms conferring treatment resistance. Further understandingof their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomesin patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells,with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due totreatment failure.     

Tissue Expression,Serum and Salivary Levels of IL-10 inPatients with Head and Neck Squamous Cell Carcinoma

Background: Head and neck SCC is a common cancer related to various factors. IL-10, a pleiotropic cytokineproduced by macrophages, T-helper-2 cells, and B lymphocytes, is thought to play a potential pathogenetic ortherapeutic role in a number of human conditions, such as inflammation, autoimmunity and cancer. The presentstudy was designed to evaluate the relation between tissue expression, serum and salivary levels of IL-10 in headand neck squamous cell carcinomas (HNSCCs) and their correlation with clinicopathologic features. Materialsand Methods: Samples were collected from 30 patients with HNSCCs and 24 healthy volunteers. IHC analysiswas used to examine the tissue expression and ELISA was employed to measure serum and salivary levels.Results: Our study showed tissue expression of IL-10 to be significantily higher in patients (P: 0.001), but therewas no relation between tissue expression , serum and salivary levels of the marker (P>0.05). Also except for apositive correlation between tissue expression of IL-10 and stage (P: 0.044), there was no relation between thismarker and clinicopathologic features. There was no correlation between serum and salivary levels in eitherpatients or controls. Conclusions: It seems there is no correlation between level of IL-10 in serum and salivaand this marker in saliva and serum does not reflect tissue expression.     

Cisplatin as Second Line Chemotherapy in Advanced or Recurrent Squamous Cell Carcinoma of Head and Neck Region

Thirty-two patients with advanced or recurrent carcinoma of the head and neck were treated with cis-dichlorodiaminoplatinum II (CDDP) 75 mg/m² every third week as second line chemotherapy. The response rate was 3 per cent with one complete and no partial responders, 16 patients with no change and 10 with progressive disease. Five were not evaluated concerning response. Median time to progression was 12 weeks (confidence limits 10--17 weeks) and median survival time 21 weeks (confidence limits 10 to 33 weeks, range 4 to 109). No severe hematologic toxicity was seen. Two patients had progressive polyneuropathy, one had a severe decline in Cr-EDTA-clearance and in one decline in auditory function was suspected. It is concluded that CDDP in this schedule has no role as second line chemotherapy in advanced cancer of head and neck.