Optimal management of the elderly patient with head and neck cancer: Issues regarding surgery, irradiation and chemotherapy

Head and neck cancer(HNC) represents the sixth most common malignancy and accounts for approximately 6% of new cancer cases annually worldwide. As life expectancy constantly increases, the onset of HNC in patients older than 65 years of age at diagnosis is not rare and up to one fourth of cases occurs in patients older that 70 years at age. Because elderly cancer patients are severely under-represented in clinical trials, there is a clear need to address the particular aspects of this specific patient group, especially in the context of novel multidisciplinary therapeutic approaches. The frailty of elderly patients with HNC is attributed to the high incidence of smoking and alcohol abuse in this malignancy and the presence of substantial cardiovascular, respiratory or metabolic comorbidities. In the current work, I provide an overview of current and emerging treatment approaches, in elderly patients with HNC. In particular, I discuss modern surgical approaches that improve radical excision rates while preserving functionality, the incorporation of modern radiotherapeutic techniques and the introduction of novel chemotherapeutic combinations and molecular targeted agents in an effort to reduce toxicity without compromising efficacy. Finally, there is an urgent need to increase accrual and active participation of elderly patients with HNC in clinical trials, including biomarker evaluation in biopsy specimens towards an individualized therapeutic approach.

THE EFFECT OF INTERNAL AND EXTERNAL CAROTID ARTERIAL INFUSION CHEMOTHERAPY ON 41 ADVANCED HEAD AND NECK CANCER PATIENTS

advanced head and neck cancer patients who couldn't be cured by surgery were treated by internal and external carotid arterial infusion via thyroid superior artery,temporal superficial artery or carotid artery with Fluorocuracil (SFu),Pingyangmycini(PYM),Carmustine (BCNU),Nidran Ampooles (ACNU) and Methotrexate (MTX).The results suggested that, the combining application of different drugs acting at different phases in cell replication cycle might play a coordinated role,before chemotherapy the application of hyperosmotic mannitol and corticoid might open the blood brain barrier temporarily and increase the drug uptake by brain tissue.As compared with ultra-selective internal carotic arterial chemotherapy,the treatment intubating into internal carotid artery via thyroid superior artery and leaving the tube in the artery is much easier, safer and cheaper and has fewer complications,so it is readily accepted by patients.

Characteristics of Patients with Upstaging by Sentinel Lymph Node Biopsy of the N0 Neck in Head and Neck Cancer

Introduction: To investigate the possible role of sentinel lymph node biopsy (SLNB) to upstage the N0 neck in patients with oral and oropharyngeal squamous cell carcinoma. Methods: Patients with T1-T2 oral and oropharyngeal squamous cell carcinoma accessible to injection and staged N0 into the neck by palaption and CTscan were enrolled in the study. All patients underwent regular follow-up to identify possible recurrence. Results: A sentine lymph node biopsy was performed by 21 consecutive patients. 4 of the 21 patients were upstaged by SNLB. There was a mean follow-up of 31 months. Two patients developed subsequent disease after having been staging by SLNB, respectively negative in one case and positive in the other case. Tumor site, the staging of the primary tumor, presence of ulceration, tumor thickness were the same in the upstaged initially N0 patients. Conclusions: Sentinel lymph node biopsy can be used to upstage the N0 neck patients in perhaps well defined patients.

Chemotherapy advances in locally advanced head and neck cancer

The management of locally advanced unresectable head and neck squamous cell cancer(HNSCC) continues to improve. One of the major advances in the treatment of HNSCC was the addition of chemotherapy to radiation in the treatment of non-surgical patients. The majority of the data regarding chemotherapy in HNSCC involve cisplatin chemotherapy with concurrent radiation. However, several new approaches have included targeted therapy against epidermal growth factor receptor and several recent studies have explored the role of induction chemotherapy in the treatment of HNSCC. The purpose of this article is to provide an overview of the role of chemotherapy in the treatment of locally advanced HNSCC.

Prognostic value of post-treatment ^(18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.

Treatment Outcomes in Head and Neck Cancer Patients 80 Years Old and over

Background: With the recent aging of society, the need for medical treatment of elderly patients with head and neck cancer seems to have been increasing. Method: The present study analyzed all 103 patients with head and neck cancer ≥80 years, and we compared results with those of the previous generation (Group P;range: 75 - 79 years) comprising 104 patients treated in the same period. Results: We provided treatment just as wanted and could not choose it often. The reasons were oncological factors such as unresectable tumor or distant metastasis, refusal of treatment, and physical factors such as poor PS or number of comorbidities. Conclusion: Treatment choices should be based on the wishes and motivations of the patient and the medical assessment of physical function. When a patient ≥80 years old is treated, the high incidence of complications and severity of the disease should be considered.

Clinical and scientific impact of human papillomavirus on head and neck cancer

Head and neck cancer(HNC) arises from the skull base to the clavicles and is the fifth most common cancer in the world by incidence. Historically, in the developed world HNC was associated with tobacco use and alcohol consumption, and the combination of the two produced a synergistic increase in risk. However, beginning in 1983, investigators have found a significant and growing proportion of HNC patients with human papillomavirus-positive(HPV) tumors who neither drank nor used tobacco. Since that time, there has been increased interest in the molecular biology of HPV-positive HNC. Multiple studies now show that HPV has shifted the epidemiological landscape and prognosis of head and neck squamous cell carcinoma(HNSCC). These studies provide strong evidence for improved survival outcomes in patients with HPV-positive HNSCC compared to those with HPV-negative HNSCC. In many reports, HPV status is the strongest predictor of locoregional control, disease specific survival and overall survival. In response to these findings, there has been significant interest in the best management of HPV-positive disease. Discussions within major cooperative groups consider new trials designed to maintain the current strong survival outcomes while reducing the long-term treatment-re-lated toxicities. This review will highlight the epidemiological, clinical and molecular discoveries surrounding HPV-related HNSCC over the recent decades and we conclude by suggesting how these findings may guide future treatment approaches.

Relationship between head and neck cancer therapy and some genetic endpoints

Head and neck cancer(HNC) is the sixth most common human malignancy worldwide. The main forms of treat ment for HNC are surgery, radiotherapy(RT) and che motherapy(CT). However, the choice of therapy de pends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is stil the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in theoral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects.

Targeting head and neck tumoral stem cells： From biologicalaspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

Identifying pain-related concerns in routine follow-up clinics following oral and oropharyngeal cancer

AIM:To describe clinical characteristics of head and neck cancer(HNC)patients with pain and those wishing to discuss pain concerns during consultation.METHODS:Cross-sectional,questionnaire study using University of Washington Quality of Life,version 4(UWQOL)and the Patients Concerns Inventory(PCI)in disease-free,post-treatment HNC cohort.Significant pain on UW-QOL and indicating"Pain in head and neck"and"Pain elsewhere"on PCI.RESULTS:One hundred and seventy-seven patientscompleted UW-QOL and PCI.The prevalence of selfreported pain issues was 38%(67/177)comprising25%(44/177)with significant problems despite medications and 13%(23/177)with lesser or no problems but wishing to discuss pain.Patients aged under 65years and patients having treatment involving radiotherapy were more likely to have pain issues.Just over half,55%(24/44)of patients with significant pain did not express a need to discuss this.Those with significant pain or others wanting to discuss pain in clinic had greater problems in physical and social-emotional functioning,reported suboptimal QOL,and also had more additional PCI items to discuss in clinic compared to those without significant pain and not wishing to discuss pain.CONCLUSION:Significant HNC-related pain is prevalent in the disease-free,posttreatment cohort.Onward referral to a specialist pain team may be beneficial.The UW-QOL and PCI package is a valuable tool that may routinely screen for significant pain in outpatient clinics.

Mechanisms involved in cancer stem cell resistance in head and neck squamous cell carcinoma

Despite scientific advances in the Oncology field,cancer remains a leading cause of death worldwide.Molecular and cellular heterogeneity of head and neck squamous cell carcinoma(HNSCC)is a significant contributor to the unpredictability of the clinical response and failure in cancer treatment.Cancer stem cells(CSCs)are recognized as a subpopulation of tumor cells that can drive and maintain tumorigenesis and metastasis,leading to poor prognosis in different types of cancer.CSCs exhibit a high level of plasticity,quickly adapting to the tumor microenvironment changes,and are intrinsically resistant to current chemo and radiotherapies.The mechanisms of CSC-mediated therapy resistance are not fully understood.However,they include different strategies used by CSCs to overcome challenges imposed by treatment,such as activation of DNA repair system,anti-apoptotic mechanisms,acquisition of quiescent state and Epithelial-mesenchymal transition,increased drug efflux capacity,hypoxic environment,protection by the CSC niche,overexpression of stemness related genes,and immune surveillance.Complete elimination of CSCs seems to be the main target for achieving tumor control and improving overall survival for cancer patients.This review will focus on the multi-factorial mechanisms by which CSCs are resistant to radiotherapy and chemotherapy in HNSCC,supporting the use of possible strategies to overcome therapy failure.

基于医院-社区-家庭的营养管理方案对头颈部肿瘤放化疗患者营养及并发症的影响研究

目的探讨基于医院-社区-家庭的营养管理方案对头颈部肿瘤放化疗患者营养状况的影响。方法选择2022年2月至2023年3月于江苏省人民医院接受放化疗的150例头颈部肿瘤患者作为研究对象,采用随机数字法将患者分为干预组与对照组,每组患者75例。对照组给予常规营养管理,干预组给予基于医院-社区-家庭的营养管理方案,干预3个月后使用患者主观整体评估(PG-SGA)、营养风险筛查2002(NRS 2002)评估两组患者营养水平,比较两组患者入院及放化疗治疗结束后体质指数(BMI)、总蛋白、白蛋白、并发症发生率及严重程度。结果干预组患者放化疗治疗结束后总蛋白[(67.62±6.09)g/L比(61.75±5.28)g/L]、白蛋白[(37.78±4.12)g/L比(33.17±3.98)g/L]、前白蛋白[(214.23±45.19)g/L比(191.08±42.58)g/L]、淋巴细胞计数[(1.13±0.39)×10^(9)/L比(0.74±0.43)×10^(9)/L]均高于对照组(P<0.05);并发症发生率(30.67%比54.67%)及严重程度(25.33%比56.67%;5.33%比8.00%)均低于对照组(P<0.05);根据NRS 2002结果,干预组低营养风险患者比例高于对照组(86.67%比77.33%,P<0.05),高营养风险患者比例低于对照组(13.33%比22.67%,P<0.05);PG-SGA评分[(6.98±5.17)分比(7.42±4.63)分]及BMI[(20.93±2.74)kg/m^(2)比(19.62±2.81)kg/m^(2)]均优于对照组(P<0.05);干预后干预组患者每日肠内营养摄取能量高于对照组[(691.83±264.29)kcal比(348.12±153.28)kcal,P<0.05]。结论基于医院-社区-家庭的营养管理方案对头颈部肿瘤放化疗患者有着良好干预效果,可显著改善患者营养状况及并发症严重程度。

提高头颈癌手术患者营养支持达标率

目的提高头颈癌手术患者营养支持达标率。方法开展问题解决型品管圈活动,运用质量管理工具对头颈癌手术患者营养支持现状进行持续改进,措施包括多学科联动构建头颈癌患者营养管理方案、落实早期吞咽摄食训练、构建智慧化全程管理模式、开展多元化培训等。结果头颈癌手术患者营养支持达标率从活动前的54.36%提高至活动后的84.88%,为头颈癌手术患者提供了安全、有效的营养管理方案。结论通过开展品管圈活动,提高了头颈癌手术患者营养支持达标率,有效改善了患者的治疗效果,提升了医疗质量与护理品质。

癌症信息超载对头颈部恶性肿瘤放化疗患者恐惧疾病进展的影响:决策冲突的中介作用

目的探讨决策冲突在头颈部恶性肿瘤放化疗患者癌症信息超载(Cancer information overload,CIO)与恐惧疾病进展间的中介作用。方法2022年8月至2023年1月,采用便利抽样法选取承德医学院附属医院肿瘤科收治的241例头颈部恶性肿瘤行放化疗患者作为研究对象,采用一般资料调查表、癌症信息超载量表(cancer information overload scale,CIOS)、决策冲突量表(decisional conflict scale,DCS)、恐惧疾病进展量表(fear of progression questionnaire-short form,FoP-Q-SF)进行调查。结果头颈部恶性肿瘤放化疗患者的CIOS、DCS及FoP-Q-SF的总得分分别为(19.48±8.43)、(30.82±7.66)、(34.92±13.73)分;Pearson相关性分析结果显示,头颈部恶性肿瘤放化疗患者的CIOS与DCS、FoP-Q-SF呈两两正相关(均P<0.01);Bootstrap分析显示,DCS占头颈部恶性肿瘤放化疗患者CIOS和FoP-Q-SF中介效应值的32.19%。结论DCS在头颈部恶性肿瘤放化疗患者CIOS与FoP-Q-SF间起到部分中介作用,提示医务人员可以通过制定系统完善的健康宣教策略提高患者癌症信息素养,以缓解患者CIOS和DCS,从而改善患者FoP-Q-SF心境状态。

口腔菌群变化影响放射治疗和化学治疗相关性口腔黏膜炎病程的研究进展

头颈部放射治疗和化学治疗(简称放化疗)会引起口腔菌群多样性及群落结构的改变,包括与健康相关共生菌的丰度降低,一些革兰阴性菌增加,以及以白色念珠菌增加为主的真菌群落改变,这些改变可导致口腔黏膜炎(OM)的罹患风险及严重程度增加,尤其与严重OM关系密切。放化疗直接或通过活性氧间接导致DNA损伤,同时促进微生物菌群失调,破坏免疫系统,促进炎症发生;细胞损伤形成溃疡,导致细菌易位和定植,激活核因子-κB、Toll样受体等信号通路,诱导更多促炎细胞因子产生,促进OM发展。目前针对调节口腔菌群改善OM的治疗也是研究热点,可采用益生菌或益生菌混合物防治OM,预防性使用抗真菌剂也可降低口腔念珠菌的数量。本文就近年来头颈部放化疗对口腔菌群变化的影响及其与OM相关性的研究进行综述,以期为放化疗相关OM的防治提供新思路。

复方苦参注射液辅助化疗对局部晚期、晚期头颈部肿瘤患者临床疗效及免疫功能的影响

目的:探讨复方苦参注射液辅助化疗对局部晚期、晚期头颈部肿瘤患者临床疗效及免疫功能的影响。方法:回顾性选取2020年6月~2022年10月某院收治的94例局部晚期、晚期头颈部肿瘤患者,按照治疗方案分为对照组和观察组,每组47例。对照组给予紫杉醇联合奈达铂(TP化疗方案)化疗,观察组在对照组治疗基础上加用复方苦参注射液。观察两组免疫功能指标、生活质量临床疗效及不良反应发生情况。结果:治疗后,观察组的T淋巴细胞亚群指标CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均升高(P<0.05),CD8^(+)水平下降(P<0.05),对照组CD3^(+)略有升高,但与治疗前比较无统计学差异(P>0.05);观察组卡诺夫斯凯计分(KPS)提高者多于对照组(P<0.05),KPS下降者少于对照组(P<0.05)。观察组客观缓解率、疾病控制率均高于对照组(P<0.05)。治疗期间,观察组局部疼痛、骨髓抑制等不良反应发生率低于对照组、恶心呕吐的发生率高于对照组,但无统计学差异(P>0.05)。结论:复方苦参注射液辅助化疗治疗局部晚期、晚期头颈部肿瘤患者的临床疗效较佳,可有效改善患者的免疫功能,提高生活质量,且安全性良好。

放射治疗和化学治疗诱发性口腔黏膜炎的防治

口腔黏膜炎(OM)是接受放射治疗和化学治疗的头颈部肿瘤患者常见的不良反应和剂量限制因素之一,OM的黏膜破损会给患者带来难以忍受的疼痛,影响机体的营养摄入,还可使感染通过黏膜破损扩散到全身,进而影响肿瘤治疗计划。目前虽然防治方式多样,但临床上还未有疗效确切的防治方法被大家公认,本文将对近年来针对防治OM的研究进展进行综述。

参芪扶正注射液对头颈部肿瘤放化疗患者生活质量的影响

目的观察参芪扶正注射液联合同步放化疗对头颈部肿瘤患者生活质量的影响。方法将70例头颈部肿瘤患者根据治疗方式不同分为对照组与治疗组。对照组35例采用三维适形放疗同步联合PF方案化疗及对症支持治疗,治疗组35例同时加用参芪扶正注射液250 mL/d静滴。治疗结束时评估2组患者体质量、KPS评分及放化疗不良反应发生率。结果治疗结束时,治疗组与对照组体质量增加稳定率及KPS有效率分别为91%和69%,86%和63%,2组比较有显著性差异(P<0.05)。治疗组Ⅱ级以上血液学毒性、消化道反应、放射性皮肤损伤及口腔溃疡发生率均低于对照组(P均<0.05)。治疗组治疗后CD3、CD4、CD4/CD8水平较治疗前及对照组升高(P均<0.05)。结论参芪扶正注射液联合放化疗治疗头颈部肿瘤,可改善患者生活质量,减轻放化疗毒副反应,提高免疫力,值得临床推广。

数字减影血管造影术在头颈部恶性肿瘤区域性动脉灌注化疗中的应用

目的:探讨数字减影血管造影术在头颈部恶性肿瘤区域性动脉灌注化疗中的应用。方法:选择10例头颈部恶性肿瘤患者,在数字减影血管造影监控下,经颞浅动脉逆行插管,然后行区域性动脉灌注化疗。结果:所有化疗泵插管都获成功。术中显影剂准确灌注入靶动脉;化疗前行亚甲蓝灌注,病变区域显色良好。化疗后8例患者的目标肿瘤病灶长径总和缩小率≥30%。结论:应用数字减影血管造影术进行区域性动脉灌注化疗定位准确、疗效显著。

化疗药物对头颈癌敏感性的研究

目的 在化疗前进行肿瘤药敏试验 ,以提高疗效。方法 用 MTT法对 3 2例头颈癌患者术后的肿瘤标本进行体外细胞培养 ,用 8种抗癌药进行敏感性试验 ,选用 2～ 3种敏感药物应用于同一患者进行化疗。结果 3 2例患者治疗有效 ,未出现明显的毒副作用 ,均存活 3年以上。结论 在化疗前进行药敏试验 ,选择高效药物用于同一患者 ,对于提高恶性肿瘤的疗效及增加生存率 ,减少毒副作用的产生具有较重要的意义和实际应用价值。