Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.     

18F-FDGPET-CT显像在头颈部肿瘤的临床诊断中的效果研究

目的评价18F-FDGPET-CT对头颈部肿瘤患者的临床诊断价值。方法患者均行18F-FDGPET-CT显像,对图像进行分析。结果 PET/CT的总检出率高于PET和CT,PET/CT的定位准确率高于PET。结论 18F-FDGPET-CT能够有效地鉴别头颈部肿瘤治疗后瘢痕与肿瘤复发、淋巴结及远处脏器转移,可提高对其诊断的敏感性和准确性。     

Phase I study of oral S-1 and concurrent radiotherapy in patients with head and neck cancer

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m² b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64–70 Gy in 32–35 fractions over 6–7 weeks. A total of 12 patients (3 patients at 40 mg/m², 6 patients at 60 mg/m², and 3 patients at 80 mg/m²) were enrolled in this trial. At the dose of 80 mg/m², two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m². Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m².     

Performance and quality of life outcome in patients completing concomitant chemoradiotherapy protocols for head and neck cancer

This study evaluated post-treatment performance and quality of life (QOL) outcome in head and neck cancer (HNC) patients treated with organ preservat ion, intens ive chemoradiotherapy (FHX). Participants were 47 Stage II-IV HNC patients with no evidence of disease at least one year post-completion of organ preservation, concomitant FHX treatment. Patients were assessed via a semi-structured in-person interview, standardized measures of QOL (FACT-H, CES-D), performance (PSS-HN) and patients' perception of residual side effects. Disease, treatment and toxicity data were retrieved from medical charts and protocol records. The most salient performance impairment was inability to eat a normal solid food diet, with 50% of patients able to eat soft foods or take liquids only. This specific functional deficit was not related to global QOL, nor to specific quality of life dimensions. Dry mouth, the most frequent and severe residual effect, was not associated with outcome diet, depression or QOL. Residual pain, seen in only 15% of patients, appeared to influence both functional and QOL parameters as well as being a marker for other troublesome symptoms. Twenty-three per cent of patients were depressed; depression was associated with past problems related to alcohol abuse. Decreased QOL and increased depressive symptomatology were related to total number and severity of residual effects. The data highlight the importance of systematic study of QOL dimensions and caution against making assumptions about patients' experience of particular disease and treatment sequelae.     

头颈部肿瘤同步放化疗中应用PICC行肠外营养的临床研究

目的研究头颈部肿瘤同步放化疗患者经外周静脉行中心静脉置管(PICC)途径行肠外营养支持的可行性和安全性。方法选择头颈部肿瘤同步放化疗患者36例,超声引导下行PICC后进行肠外营养,统计PICC穿刺的成功率、完成同步放化疗的患者数,并观察PICC的不良反应。结果超声引导下置管成功率高,PICC不良反应发生率低。32例经PICC营养支持下完成同步放化疗,2例治疗中因PICC不良反应改用经胃管营养(1例出现静脉血栓、1例插管部位疼痛),2例因放化疗不良反应未完成治疗。结论头颈部肿瘤同步放化疗中,经PICC途径行肠外营养有效、安全,可有效协助抗癌治疗的进行。     

Nasogastric tube feeding and percutaneous endoscopic gastrostomy tube feeding in patients with head and neck cancer

Background: For patients with a diagnosis of head and neck cancer, oral nutrition may not provide adequate nutrition during radical radiotherapy or chemoradiation treatment, resulting in enteral feeding initiation. Enteral feeding may be delivered via a nasogastric tube or by a gastrostomy tube. The present study aimed to determine how different treatment modalities impact on requirement for enteral feeding and which method of enteral feeding provided the most benefit to the patient, as demonstrated by weight loss and the number of unscheduled radiotherapy treatment interruptions. Methods: Patients who were treated with radical radiotherapy or chemoradiation between January 2004 and June 2007 were reviewed retrospectively (n = 196, male = 149, female = 47). Data were collected on demographics, diagnosis, T and N classification, nutritional status, unscheduled radiotherapy treatment interruptions, and type and duration of enteral feeding. Subjects were divided into three subgroups depending on the treatment received. Comparisons were then made between methods of enteral feeding. Results: Combined modality treatment (Induction Chemotherapy and Chemoradiation) results in a higher proportion of patients requiring enteral feeding (66–71% compared to 12% for radiotherapy). Patients fed via a prophylactic percutaneous endoscopic gastrostomy lost the least amount of weight during treatment (?4.6% to +1.4%), although the method of enteral feeding did not statistically influence weight difference at the end of treatment. The enteral feeding method did not influence unscheduled radiotherapy treatment interruptions. Conclusions: Combined modality treatment results in a greater requirement for enteral feeding, with these patient groups having the greatest weight loss. The findings obtained in the present study indicate that the method of enteral feeding did not statistically influence weight loss at the end of treatment or unscheduled radiotherapy treatment interruptions.     

Prospective study of resting energy expenditure changes in head and neck cancer patients treated with chemoradiotherapy measured by indirect calorimetry

OBJECTIVE: The prevalence of malnutrition is high in patients with head and neck cancer due to tumor location and coadjuvant treatment. We studied changes in resting energy expenditure (REE) during treatment with chemoradiotherapy and compared the measured REE by indirect calorimetry (IC) with the value estimated by the Harris-Benedict (HB) formula. METHODS: Eighteen patients with head and neck cancer (15 men and 3 women, mean age 57 +/- 10.7 y, age range 30-71 y) entered the study. All patients were treated with radiotherapy (70.8 +/- 1 Gy, range 70-72) and received 37.4 +/- 3.5 fractions (range 32-42) and concurrent chemotherapy with cisplatinum (absolute doses of 400 to 1000 mg). Nutrition assessment included anthropometry (body mass index, triceps skinfold thickness, subscapular skinfold thickness, midarm circumference, and midarm muscle circumference) and tetrapolar bioimpedance (Holtain BC). The IC (kcal/24 h; Deltatrac II MBM-200) was performed after an overnight fast. Measurements were done before treatment, at weeks 2, 4, and 6 of treatment, at the end of treatment, and 2 wk after treatment. RESULTS: Body mass index decreased during treatment from 24.7 +/- 4.4 kg/m(2) (range 16.9-31.4) to 22.3 +/- 4.2 kg/m(2) (range 15.1-29.6). REE (kcal/24 h) changed significantly during treatment (IC P < 0.05, HB formula P < 0.001). REE measured by IC appeared as a U-shaped curve, but REE estimated by the HB formula decreased during treatment. The HB underestimated REE measurements compared with IC. These differences were statistically significant before treatment, at the end of treatment, and 2 wk after treatment (P < 0.05) and showed a limited clinical agreement with the Bland-Altman method. CONCLUSIONS: REE measured by IC significantly changed during chemoradiotherapy. It was higher before treatment, at the end of treatment, and 2 wk after treatment. The HB formula underestimated REE in these patients. IC is a suitable method for measuring REE in this cohort of patients.     

Postoperative enteral immunonutrition in head and neck cancer patients

AIMS: to determine if postoperative feeding of head and neck cancer patients, using an enteral diet supplemented with arginine, improves immunological and nutritional status, and clinical outcome, i.e., reduces postoperative infectious/wound complications and length of stay, when compared with an isocaloric, isonitrogenous control diet. METHODS: at operation 44 patients were randomized into two groups to receive: a) an enriched diet (n=23);b) an isocaloric, isonitrogenous control diet (n=21). Thirteen patients with a history of significant weight loss (> or = 10% over the last 6 months) were considered malnourished. Preoperatively and on postoperative days 1, 4 and 8 the following parameters were evaluated: albumin, prealbumin, transferrin, total number of lymphocytes, lymphocyte subsets (CD3, CD4, CD8 and CD4/CD8 ratio) and immunoglobulins. Postoperative complications and length of stay were recorded. RESULTS: 'visceral' serum proteins and immunological parameters decreased on postoperative day 1 in both groups. However, only the enriched group demonstrated a significant increase (P<0.05) in the total number of lymphocytes, CD4, CD4/CD8 on postoperative day 4, and total number of lymphocytes, CD3, CD4, CD4/CD8 on postoperative day 8. In the malnourished subgroup the administration of the enriched formula significantly reduced both postoperative infectious/wound complications and length of stay compared with the control group (P<0.05). CONCLUSIONS: enteral immunonutrition of head and neck cancer patients improves postoperative immunological response. Significant clinical advantages were observed in malnourished patients.     

头颈恶性肿瘤放射性口腔黏膜炎危险因素meta分析

目的 系统评价头颈恶性肿瘤放疗后放射性口腔黏膜炎的危险因素,为在临床工作中预防头颈恶性肿瘤患者放射性口腔黏膜炎的发生提供循证证据。 方法 通过计算机检索数据库PubMed、Embase、MEDLINE、Ovid、Web of Science、Cochrane Library、中国知网、维普、万方中公开发表的与头颈恶性肿瘤患者放疗过程中引起放射性口腔黏膜炎的危险因素有关的文献,检索各数据库从建库起至2020年6月的相关文献,由两位研究人员独立完成文献筛选、资料提取、质量评价,运用Rev Man 5.3软件和Stata 12.0软件进行分析。 结果 共计纳入14篇文献(英文5篇,中文9篇),结果显示,联合化疗(OR=2.24,95％CI:1.66～3.02)、吸烟(OR=2.12,95％CI:1.45～3.10)、饮酒(OR=1.58,95％CI:1.09～2.29)、糖尿病(OR=1.99,95％CI:1.46～2.70)、口腔pH≤7(OR=3.11,95％CI:2.13～4.55)、口腔卫生差(OR=4.38,95％CI:2.19～8.73)、未使用抗生素(OR=5.92,95％CI:2.91～12.04)、未使用黏膜保护剂(OR=5.39,95％CI:2.89～10.04)是头颈恶性肿瘤放射性口腔黏膜炎的危险因素,差异均有统计学意义(P＜0.05)。 结论 联合化疗、吸烟、饮酒、糖尿病、口腔pH≤7、口腔卫生差、未使用抗生素、未使用黏膜保护剂是头颈恶性肿瘤放射性口腔黏膜炎的危险因素,医务人员在临床工作中可采取相应预防措施降低放射性口腔黏膜炎的发生率及严重程度。     

Audit of nutritional guidelines for head and neck cancer patients undergoing radiotherapy

BACKGROUND: Head and neck cancer patients being treated with radiotherapy are at an increased risk of malnutrition due to the severe side-effects, e.g. mucositis, odynophagia and xerostomia, impacting on the ability to eat and drink. Effective dietetic management involves identifying those patients malnourished or at risk of becoming so and incorporating nutritional intervention into their treatment plan. The use of gastrostomy tubes in this patient group has been shown to be acceptable. By placing them prophylactically, the aim is to prevent a disruption to treatment and avoid an unnecessary admission for feeding. This audit was carried out to determine whether the implementation of locally produced nutritional guidelines improved the dietetic management of this patient group. METHOD: A prospective audit tool was used to collect data on 32 head and neck cancer patients undergoing radiotherapy. Data was collected weekly during the course of treatment and compared with data from previous audits. Weight change was the nutritional outcome measured. RESULTS: More patients underwent combined treatment (radiotherapy postoperatively or with concurrent weekly chemotherapy) when compared with previous audits. However, implementation of the guidelines appeared to contribute to an improvement in dietetic management, as fewer patients lost weight over the course of radiotherapy and there were no admissions for feeding. The presence of a dietitian at the multidisciplinary head and neck clinic improved access and communication and this is also likely to have contributed to the improved management. CONCLUSIONS: Implementation of the guidelines led to an improvement in the nutritional management of this patient group. Implementation may be more likely if a dietitian is present at the combined head and neck clinic.     

Temporal assessment of quality of life of head and neck cancer patients receiving radical radiotherapy

The study was undertaken to evaluate physical, psychological and functional aspects in quality of life (QoL) assessment prospectively in biopsy-proven head and neck cancer patients receiving radical radiotherapy. Fifty male patients were assessed using Karnofsky's Performance Status (KPS), Beck's Depression Inventory (BDI) and the Functional Living Index – Cancer (FLIC). Patient questionnaires were completed before radiotherapy, during 3–4 weeks of radiotherapy and 3 months after radiotherapy. Before the start of radiotherapy, KPS was 91±10.26, FLIC was 129.98±33.41 and BDI was 7.10±4.57. This indicated good performance and functional status with lower depression. In weeks 3–4 of radiotherapy, KPS (71.00±20.12) and FLIC (81.34±45.23) decreased, while BDI(16.56 ±9.01) increased, indicating impairment in QoL. Three months after radiotherapy, KPS (78.37±23.0), FLIC (119.51± 43.62) and BDI(9.02±7.81) improved but were not restored to pre-treatment levels. When patients were scheduled for radical radiotherapy, maximum deterioration in QoL was seen in weeks 3–4. This is the time when maximum supportive care and psychologic counselling is required.     

Initial experience of radiotherapy plus cetuximab for Japanese head and neck cancer patients

In Japan, cetuximab with concurrent bioradiotherapy (BRT) for squamous cell carcinoma of head and neck (SCCHN) was approved in December 2012. We herein report our initial experience of BRT, with special emphasis on acute toxicities of this combination therapy. Thirty-one non-metastatic SCCHN patients who underwent BRT using cetuximab between July 2013 and June 2014 were retrospectively evaluated. All patients received cetuximab with a loading dose of 400 mg/m² one week before the start of radiotherapy, followed by 250 mg/m² per week during radiotherapy. The median cycle of cetuximab was seven cycles and the median dose of radiotherapy was 70 Gy. Twenty-five patients (80.6%) accomplished planned radiotherapy and six cycles or more cetuximab administration. Six patients (19.4%) discontinued cetuximab. Grade 3 dermatitis, mucositis and infusion reaction occurred in 19.4%, 48.3% and 3.2%, respectively. One patient experienced Grade 3 gastrointestinal bleeding caused by diverticular hemorrhage during BRT. Grade 3 drug-induced pneumonitis occurred in two patients. The response rate was 74%, including 55% with a complete response. BRT using cetuximab for Japanese patients with SCCHN was feasible as an alternative for cisplatin-based concurrent chemoradiation, although longer follow-up is necessary to evaluate late toxicities.     

头颈部肿瘤放疗中真菌感染的诊治

目的探讨头颈部肿瘤放疗中真菌感染的诊治疗效。方法回顾性分析14例头颈部肿瘤真菌感染病例的诊治过程及治疗方法。结果 8例患者均在接受治疗2~3 d后症状即有减轻、体温下降,7~10 d后症状基本消失,体温恢复正常,维持治疗1~3周后停药,随访2~6个月无复发;1例伴糖尿病、高血压者,在接受治疗的同时控制血糖、血压;2例在治疗前肝功能检查:谷丙转氨酶、谷草转氨酶均偏高,治疗后第2周后复查转氨酶有逐渐增高趋势,考虑患者临床上已基本痊愈,即予停药。结论真菌感染的治疗以抗真菌为主,可选用抗菌谱广、不良反应小的氟康唑、伊曲康唑等治疗。     

基于QLICP-HN(V2.0)量表的头颈癌患者生命质量影响因素及干预对策研究

[目的]分析头颈癌患者生命质量影响因素,为制定提高头颈癌患者生命质量的干预措施提供科学依据。[方法]收集云南省肿瘤医院133例头颈癌住院患者,采用t检验、方差分析等单因素分析以及多重线性回归法分析头颈癌患者生命质量的影响因素。[结果]单因素研究显示,不同性别、文化程度头颈癌患者生命质量差异有统计学意义(P≤0.05);不同年龄头颈癌生命质量在特异模块领域差异有统计学意义(P=0.025);家庭经济在共性模块得分上差异有统计学意义,家庭经济较好者生命质量较高。多重线性回归结果显示,性别均纳入了分别以共性模块、特异模块、总量表得分为因变量的3个回归模型;以共性模块、总量表得分为因变量的回归模型还将文化程度、医疗形式纳入了模型;以生命质量特异模块得分、总量表得分为因变量的回归模型中还纳入了手术情况。[结论]影响头颈癌患者生命质量的主要因素有性别、年龄、是否手术、家庭经济、文化程度、医疗形式、职业、婚姻、吸烟酗酒、抑郁症状,在后续进行头颈癌干预对策探讨时应着重考虑这几方面。     

Early-onset dropped head syndrome after radiotherapy for head and neck cancer: dose constraints for neck extensor muscles

Dropped head syndrome (DHS) is a famous but unusual late complication of multimodality treatment for head and neck carcinoma. We reported this early-onset complication and analyzed the dose to the neck extensor muscles. We examined the records of three patients with DHS after radiotherapy. The doses to the neck extensor muscles were compared between three patients with DHS and nine patients without DHS. The mean dose to the neck extensor muscles of the three patients with DHS were 58.5 Gy, 42.3 Gy and 60.9 Gy, while the dose was <50 Gy in all nine patients in the control group. The onset of this syndrome was 5 months, 6 months and 15 months. The early-onset DHS may have something to do with dose to the neck extensor muscles. The proposed dose to the neck extensor muscles might be <46 Gy (or at least <50 Gy).     

Perioperative enteral nutrition and quality of life of severely malnourished head and neck cancer patients: a randomized clinical trial

BACKGROUND AND AIMS: This study evaluated the use of perioperative nutritional support on Quality of Life (QOL) in malnourished head and neck cancer patients undergoing surgery. METHODS: 49 Malnourished (weight loss >10%) head and neck cancer patients who were included in a nutrition intervention trial were randomized to receive either no preoperative and standard postoperative tube-feeding (group I), standard preoperative and postoperative tube-feeding (group II) or arginine-supplemented preoperative and postoperative tube-feeding (group III). Of these patients, 31 completed a full QOL assessment on the first day of preoperative nutritional support, one day before surgery, and 6 months after surgery. Both a disease-specific (EORTC QLQ-C30) and a generic questionnaire (COOP-WONCA) were used. One way analysis of variance (ANOVA) and the Kruskal-Wallis test were applied for testing differences in scores between groups. RESULTS: Between baseline and the day before surgery, both preoperatively fed groups revealed a positive change for the dimensions physical and emotional functioning and dyspnea (with significance in group II, P=0.050,0.031,0.045 respectively). Group III showed a negative change in appetite (P=0.049). Between baseline and 6 months after surgery, there were no differences between group I and both pre-fed groups. There were no differences in favour of group III compared to group II. CONCLUSION: Enteral nutrition improves QOL of severely malnourished head and neck cancer patients in the period preceding surgery. No benefit of preoperative enteral feeding on QOL could be demonstrated 6 months after surgery.