Mechanisms for radiation-induced oral mucositis and the consequences

Radiation therapy remains the primary method of treatment for patients with head and neck cancer. The tissue destruction and functional alterations in the oral cavity lead to the development of oral mucositis. The purpose of this review is to describe the mechanisms, risk factors, prevalence, and magnitude of radiation therapy-related oral mucositis and its morbidities in patients with head and neck cancer. The review concludes with a discussion of the implications for clinical practice. This review provides cancer nurses with the information necessary to identify patients with head and neck cancer who are at high risk for oral mucositis and the significant comorbidities associated with this complication of radiation therapy.     

Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

We treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.     

The effects of mucositis on quality of life in patients with head and neck cancer

A search of the literature from 1993-2005 revealed four articles on quality-of-life issues for patients with head and neck cancer who develop mucositis. This article reviews four views on quality-of-life issues for patients who receive cancer treatments and develop mucositis. Small samples were utilized in each of the reviewed articles; however, because of the studies' qualitative designs, researchers concluded that quality-of-life issues exist among patients with head and neck cancer who are undergoing radiation and chemotherapy. Nurses play a significant role in assisting patients to tolerate their treatments. Further research is necessary to develop effective nursing interventions to improve quality of life for patients who develop mucositis while undergoing chemotherapy and radiation therapy.     

局部或区域晚期头颈鳞癌放化疗联合治疗现状和展望

头颈部鳞状细胞癌的全身治疗包括细胞毒药物治疗（简称化疗）、靶向治疗和支持治疗;而局部治疗主要包括放射治疗和手术。放化疗联合是局部晚期或区域晚期头颈部鳞癌主要治疗模式,包括同步化放疗、诱导化疗、序贯化放疗。本文综述了原发于口腔、口咽、下咽、喉的鳞癌的化放疗联合治疗现状和进展。     

Treatment of small cell carcinoma of the lung with methotrexate, doxorubicin, cyclophosphamide, and lomustine: a community-based study

Forty-four patients with undifferentiated small cell carcinoma of the lung (SCCL) were diagnosed and treated at community hospitals. Patients with limited disease were treated with surgical resection or primary radiation therapy (RT) followed by chemotherapy; those with extensive disease received chemotherapy followed by RT if there was not a complete primary response. The chemotherapy used was a combination of methotrexate, doxorubicin, cyclophosphamide, and lomustine. Median survival for patients with both limited and extensive disease was 12 months, with a six-month survival of 89%. Half of the patients had recurrence in the lung. The toxicity was moderate and tolerable. We conclude that this combination chemotherapy plus radiation therapy carries acceptable toxicity and can be used in a community hospital to achieve response rates and survival of SCCL equivalent to that obtained in large cancer centers.     

Combined cisplatinum and laser thermal therapy for palliation of recurrent head and neck tumors

In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m(2)) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients.     

奈达铂联合化疗治疗恶性肿瘤的临床分析

目的观察奈达铂联合其他化疗药物治疗头颈部肿瘤、非小细胞肺癌、食管癌、妇科癌症的近期疗效和不良反应。方法入组共82例。奈达铂80～100mg/m2,加入500ml生理盐水中静脉滴注2h,每4周重复。结果头颈部肿瘤治疗组15例,CR4例(26·7%)PR7例(46·6%),有效率73·3%。非小细胞肺癌观察组25例,CR3例(12%),PR5例(20%),SD10例(40%),PD7例(28%),有效率RR为32%(8/25)。食管癌22例,CR2例(9%)、PR7例(31·8),RR40·9%。妇科癌症20例,结合放疗,全组病例有效率35%。不良反应主要有骨髓抑制,胃肠道反应少见,肝肾功能损害轻微。结论奈达铂对食管癌、头颈部肿瘤疗效优于顺铂。在非小细胞肺癌、妇科肿瘤疗效与顺铂相近,但是不良反应轻,主要为骨髓抑制,多数患者耐受良好。     

Head and neck cancer: changing epidemiology, diagnosis, and treatment

Head and neck cancers account for less than 5% of all cancers and for less than 3% of all cancer deaths in the United States. The populations at risk for head and neck cancers are those who have a long-standing history of smoking and alcohol use. More recently, the incidence of oropharyngeal cancer in younger populations has been increasing and is associated with exposure to the human papillomavirus. This subset of patients appears to have a better overall prognosis and to respond better to treatment. This review is limited to head and neck cancers of squamous cell histology, which constitute more than 90% of head and neck cancers. Because treatment of head and neck cancers is complex and involves multiple modalities, a multidisciplinary approach is needed. This review focuses on the goal of organ preservation and postoperative treatment of high-risk patients with the concurrent use of chemotherapy and radiation therapy. This review also highlights recent advances in treatment using molecularly targeted therapies, specifically the role of inhibitors of the epidermal growth factor receptor in locally advanced and recurrent/metastatic squamous cell cancer of the head and neck. Studies in the English language were identified by searching the MEDLINE, EMBASE database (1980-2007) using the search terms head and neck, squamous cell, carcinoma, chemotherapy, radiation, human papillomavirus, epidermal growth factor receptor, and targeted therapy.     

Radiation-Induced trismus in head and neck cancer patients

Purpose To determine the incidence of trismus in patients who had previously received curative doses of radiation therapy (RT) for head and neck cancer. In addition, we assessed if trismus was associated with quality of life deficits and radiation toxicity. Methods and materials Between February, 2005 and December, 2006, 40 patients with histologically confirmed head and neck cancer who had received curative doses of RT to the area(s) of the masticatory muscles and/or the ligaments of the temporomandibular joint (TMJ) were enrolled in this study. Differences in trismus incidence were compared between cancer treatment modalities [i.e., RT vs RT/chemotherapy (CT) and conventional RT vs intensity modulated RT]. Quality of life (QOL) was measured by using four questions from the EORTC QLQ-C30 that address pain and difficulty opening the jaw. Scores regarding impaired eating as a result of decreased range of motion of the mouth were derived from the Modified Common Toxicity Criteria (CTCAE Version 3.0). Results Trismus was identified in 45% of subjects who had received curative doses of RT. No differences were noted in the incidence of trismus between RT and RT/CT or between conventional RT and intensity modulated RT (IMRT). Those with trismus demonstrated more QOL deficits than the non-trismus group. Conclusions Curative doses of RT for head and neck cancer result in trismus in a high percentage of patients, independent of other treatment modalities. Trismus has a negative impact on quality of life in this population. Presented at the American Academy of Oral Medicine 2006 Annual Meeting, San Juan, Puerto Rico.     

Quantification of Dose-Volume and Dose-Length Parameters for Cervical Esophageal Stricture in Head and Neck Irradiation with the 3DCRT and IMRT Technique

PurposeTo quantify and compare dose-volume and dose-length parameters of cervical esophagus between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) and to correlate with incidence of cervical strictures in head and neck cancer irradiation with radical intent.Materials and MethodsForty consecutive head and neck cancer patients who received radical radiation therapy, either with 3DCRT (n = 20) or IMRT (n = 20), between December 2011 and August 2012 were retrospectively analyzed and followed up for at least 4 years post-treatment completion.ResultsThe volumes of cervical esophagus receiving ≥54 Gy (V54) and ≥60 Gy (V60) and lengths receiving circumferential dose of ≥50 Gy (L50) and ≥54 Gy (L54) were significantly higher in patients treated with IMRT as compared to 3DCRT (P ≤ .05). At the end of minimum 4 years' post-treatment, nine patients had documented symptomatic strictures; three patients were treated with 3DCRT and six patients with IMRT technique.ConclusionIMRT technique in entire-neck irradiation is associated with increased spillage dose to the cervical esophagus, and thereby increased risk for late sequelae. The cervical esophagus has to be considered as an organ at risk and constraints need to be given in IMRT planning, particularly for lower-neck irradiation.     

Integration of molecular targeted therapy with radiation in head and neck cancer

Approximately 600,000 new cases of head and neck cancer arise worldwide each year. Of these, a large majority are head and neck squamous cell carcinomas (HNSCC). Conventional treatments, including surgical excision followed by radiation and/or chemoradiotherapy have limited efficacy and are associated with substantial toxicity. To date, key targets for molecular targeted therapy in HNSCC are epidermal growth factor receptors and angiogenesis-related factors. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) and it is the only targeted therapy approved by the United States Food and Drug Administration for the treatment of HNSCC. Cetuximab in combination with radiotherapy represents a standard approach for newly diagnosed patients who are unable to tolerate platinum chemotherapy. Despite efficacy in preclinical HNSCC models, cetuximab is only effective in a subset of HNSCC patients, most likely due to the high heterogeneity of this cancer. Additional targets under active investigation include the PI3K/Akt pathway, the Ras-MAPK-ERK pathway and the JAK/STAT pathway, among others. Combining molecular targeted therapies and radiation may allow for deintensification of radiotherapy thereby reducing radiation toxicities and improving treatment outcomes. Here we review the preclinical and clinical data in support of treatment strategies that combined targeted therapy with radiation in HNSCC.     

The relationship between factors that impair wound healing and the severity of acute radiation skin and mucosal toxicities in head and neck cancer

PURPOSE: To determine which wound-healing factors impact on the severity of radiation skin and oral mucosal reactions in head and neck cancer and to test modifications to the Radiation Therapy Oncology Group (RTOG) acute toxicity scoring system. METHODS: A consecutive sample of 53 head and neck cancer patients who were scheduled for curative or palliative radiation therapy. Therapy was planned using traditional computerized techniques. A new RTOG subscale for tongue reactions was developed. Information on potential predictors was collected during the first week of treatment. Reactions were observed and documented each week throughout treatment using the RTOG Acute Reaction Scoring System scores of acute oropharyngeal reactions and various personal factors. RESULTS: Significant relationships were found between severe skin and oral reactions and age, commencing radiation within 2 months of surgery and smoking. Significant relationships for severe oral mucosal reactions were found with weight at the commencement of treatment, inadequate or poor diet, having had mucositis with previous chemotherapy, and the use of a custom-made Perspex tongue immobilizer. CONCLUSIONS: Three conclusions can be derived from this study: (1) structures within the oral cavity should be considered separately for toxicity scoring, (2) the newly developed tongue RTOG subscale adds accuracy and specificity to the RTOG acute toxicity scoring system, and (3) wound healing factors are an important component of understanding risk for side effects in head and neck cancer treatment.     

Hepatic metastasis from neuroblastoma

Neuroblastoma is a common solid tumor of infancy and childhood. From 1967 to 1986 we evaluated and treated 58 children with neuroblastoma; in ten (17%) of these children, symptomatic hepatic metastasis developed. The ten children ranged in age from 2 days to 2 years 3 months. The most common symptoms attributable to hepatic metastasis were abdominal enlargement, abdominal pain, respiratory difficulty due to upward pressure on the diaphragm, and obstruction of the inferior vena cava. At the time of initial diagnosis, two children had stage III disease, three had stage IV disease, and five had stage IV-S disease. Six were initially given chemotherapy; all six of these patients required radiation therapy when hepatic enlargement progressed. In the other four cases, radiation therapy was used alone or in combination with chemotherapy. Irradiation or irradiation plus chemotherapy produced complete resolution of local symptoms in seven cases, and a partial response in one case. The seven children who had a complete response are alive without evidence of recurrent disease; the remaining three children died of their tumor. The roles of chemotherapy, surgery, and radiation therapy in the management of symptomatic hepatic metastasis from neuroblastoma are discussed.     

紫杉醇联合顺铂及卡培他滨治疗晚期胃癌

目的探讨紫杉醇联合顺铂及卡培他滨一线治疗晚期胃癌的疗效和安全性。方法回顾性分析2004年6月-2008年6月收治的使用PCX方案化疗的32例晚期胃癌患者的临床资料。化疗方案：紫杉醇（PTX）150mg／m^2,静脉滴注2h,第1天;顺铂（DDP）25mg／m^2,静脉滴注,第1—3天;卡培他滨1250mg／m^2,口服,第1—14天。21d为1周期,用药至少2个周期后进行疗效评价。结果32例患者均可评价疗效,完全缓解1例,部分缓解12例,稳定13例,进展6例,总有效率40．6％;中位疾病进展时间（TTP）6．1个月（2～14个月）,中位生存时问（MST）11个月（2-31个月）。主要不良反应为胃肠道反应和骨髓抑制,多为Ⅰ或Ⅱ度。Ⅲ／Ⅳ度不良反应主要有恶心、呕吐（21．9％,7／32）、中性粒细胞减少（15．6％,5／32）和乏力（9．4％,3／32）。12．5％（4／32）的患者出现中性粒细胞减少性发热。所有患者均无化疗相关性死亡。结论紫杉醇联合顺铂及卡培他滨一线治疗晚期胃癌有较好的疗效,不良反应可以耐受。     

Prevalence of secondary lymphedema in patients with head and neck cancer

ContextBecause surgery, radiation, and/or chemotherapy disrupt lymphatic structures, damage soft tissue leading to scar tissue formation and fibrosis, and further affect lymphatic function, patients with head and neck cancer may be at high risk for developing secondary lymphedema. Yet, no published data are available regarding the prevalence of secondary lymphedema after head and neck cancer treatment.ObjectivesThe aim of this study was to examine prevalence of secondary lymphedema in patients with head and neck cancer.MethodsThe study included 81 patients with head and neck cancer who were three months or more post-treatment. External lymphedema was staged using Foldi's lymphedema scale. Internal lymphedema was identified through a flexible fiber-optic endoscopic or mirror examination. Patterson's scale was used to grade degrees of internal lymphedema.ResultsOf the 81 patients, 75.3% (61 of 81) had some form of late-effect lymphedema. Of those, 9.8% (6 of 61) only had external, 39.4% (24 of 61) only had internal, and 50.8% (31 of 61) had both types.ConclusionLymphedema is a common late effect in patients with head and neck cancer, and it develops in multiple external and internal anatomical locations. During physical examination and endoscopic procedures, clinicians should assess patients with head and neck cancer for late-effect lymphedema. Referral for treatment should be considered when lymphedema is noted. Research is needed to examine risk factors of lymphedema in patients with head and neck cancer and its effects on patients' symptoms, function, and quality of life.     

Safety and efficacy of S-1 chemotherapy in recurrent/metastatic head and neck cancer

S-1 is an oral 5-fluorouracil (5-FU) anticancer agent and has shown promising effects in the treatment of a wide range of carcinomas, including head and neck cancer. In addition to being used as adjuvant chemotherapy, S-1 is a promising agent for palliative treatment. Its ease of administration makes it an ideal drug to treat patients in the outpatient setting while maintaining adequate quality of life. However, the clinical role of S-1 in patients with recurrent/metastatic head and neck cancer is still uncertain. We retrospectively reviewed 16 patients with recurrent/metastatic head and neck cancer who received S-1 monotherapy. Thirteen patients with squamous cell carcinoma (SCC) and 3 patients with non-SCC who had recurrent/metastatic disease received S-1 monotherapy as outpatients. One patient with nasopharyngeal undifferentiated carcinoma and 1 patient with maxillary adenosquamous carcinoma showed complete response (CR), while all SCC patients showed stable disease (SD) or progressive disease (PD). Median time to progression (TTP) was 12 weeks. Five patients showed grade 3 and 4 adverse reactions, all hematological. Except for one episode of grade 4 leucopenia which required hospitalization and granulocyte colony-stimulating factor (GCSF) treatment, all adverse events resolved with dose reduction or dose omission. S-1 was safely administered in outpatients and showed some efficacy in the treatment of recurrent/metastatic head and neck cancer in patients who had received previous chemotherapy. S-1 could be used as palliative treatment in patients with recurrent/metastatic head and neck cancer.     

PET／CT对头颈部癌放射治疗计划的临床价值

目的前瞻性研究以评估PET／CT对头颈部癌患者CT放射治疗计划和治疗模式的临床价值。方法24例头颈部癌患者（鼻咽癌6例、上颌窦癌5例、舌癌8例、牙龈癌5例）进入本研究。每例患者先在治疗体位下作CT平扫和增强扫描，然后行FDG-PET／CT检查。由同一放疗医师和物理师作CT和PET／CT放射治疗计划。每例患者的二个计划作对比，以评估PE丁／CT对CT放疗计划肿瘤区（GTV）体积、放疗野和治疗模式的影响。结果PET／CT检查后54．2％（13／24）的患者GTV体积变化≥15％。125％（3／24）的患者发生放射野改变：2例患者增加下颈部放射野（原CT扫描颈部阴性，PET／CT显示下颈部淋巴结阳性浓聚）；1例鼻咽癌放疗后复发患者原计划放射鼻咽部和颈部，PET／CT显示鼻咽部阴性和颈部阳性，取消鼻咽部放射野仅放疗颈部。该患者随访1年以上未发现肿瘤病灶。另2例患者PET／CT检查确定有远处转移（1例肺转移，1例骨转移），从而改变治疗方案为始息放疗和化疗。结论PET／CT检查使本组头颈部放疗患者的CT放疗计划和治疗模式产生明显改变，增加PET／CT检查具有很大的临床价值。     

帕尼单抗联合化疗治疗晚期头颈部肿瘤的研究

目的探讨帕尼单抗联合顺铂和氟尿嘧啶作为转移性头颈部恶性肿瘤患者一线治疗的临床疗效和不良反应。方法将79例临床确诊的头颈部恶性肿瘤患者随机的分为试验组和对照组,其中试验组40例,对照组39例。两组患者均接受4个周期的静脉注射顺铂（每周期第1天100mg／m^2）和氟尿嘧啶（每周期第1—4天1000mg／m^2）治疗,每个周期持续3周;试验组在此基础上再给予静脉注射帕尼单抗（每周期第1天9mg／kg）。观察两组患者疗效及不良反应。结果40例试验组患者中总有效为16例（40．0％）,完全缓解2例（5．0％）,部分缓解14例（35．0％）,无变化18例（45．0％）,进展6例（15．0％）;而39例对照组患者中总有效为11例（28．21％）,完全有效2例（5．13％）,部分缓解9例（23．08％）,与试验组的有效率有统计学差异（P〈0．05）。试验组Ⅲ级及Ⅲ级以上不良反应事件的发生要多于对照组,给予相应的治疗可以控制;无化疗相关死亡病例发生。结论帕尼单抗联合顺铂和氟尿嘧啶对晚期头颈部恶性肿瘤患者具有较好的疗效,并且其不良反应大多数患者可以耐受。     

Characteristics and outcomes of patients with unresected early-stage non-small cell lung cancer

BACKGROUND: This study describes the characteristics, management, and outcomes of patients with unresected early-stage non-small cell lung cancer (NSCLC). METHODS: A retrospective review was conducted to identify all patients with unresected stage I or stage II NSCLC diagnosed between 1990 and 1998. RESULTS: Ninety-seven patients were identified who met our criteria. The median age at diagnosis was 68 years; 78% of patients were white, 81% were male, 81% had stage I disease, and 67% had squamous cell carcinoma. Cancer-specific treatment, including chemotherapy, radiation therapy, and combined chemotherapy and radiation therapy, was administered to only 27 patients. The median survival time was 22 months for the treated group and 11 months for the untreated group. CONCLUSION: The majority of patients with unresected early-stage NSCLC do not receive cancer therapy. They should be thoroughly considered for treatment, however, especially in light of recent advances in surgery and radiation therapy, and the development of more active, less toxic chemotherapeutic agents.     

鱼腥草、丹参注射液合剂雾化吸入治疗重度放射性口腔黏膜反应24例效果观察

目的:探讨鱼腥草、丹参注射液合剂雾化吸入治疗头颈部恶性肿瘤患者放疗所致重度口腔黏膜反应的效果。方法:将47例因放疗出现重度口腔黏膜反应的头颈部恶性肿瘤患者随机分为观察组24例和对照组23例,观察组给予鱼腥草注射液、丹参注射液各20 ml+生理盐水30 ml超声雾化吸入,3次/d,每次20 min;对照组给予康复新注射液2 ml+维生素B12注射液0.5 mg+生理盐水50 ml雾化吸入,3次/d,每次20 min。结果:观察组显效率33.33%,有效率100.00%,对照组显效率13.04%,有效率65.22%,两组比较差异有统计学意义(P<0.01)。结论:鱼腥草、丹参注射液合剂雾化吸入治疗头颈部恶性肿瘤患者放疗所致重度口腔黏膜反应临床效果显著。