多西他赛联合奥沙利铂治疗晚期头颈部恶性肿瘤

目的:观察多西他赛联合奥沙利铂治疗晚期头颈部肿瘤的疗效及不良反应.方法:52例晚期头颈部肿瘤患者按住院号随机分为A组26例和B组26例.A组多西他赛75mg/m2,静脉滴注,第1天;奥沙利铂130mg/m2,静脉滴注,第1天;3周为1周期,连用2周期～4周期.B组顺铂25mg/m2,静脉滴注,第1天～3天;5-氟脲嘧啶...     

Promising New Approaches in the Treatment of Advanced Head and Neck Cancer

Squamous cell carcinoma (SCC) of the head and neck (H&N) represents a major international health problem. The overwhelming majority of H&N cancers are strongly associated with tobacco use, and the intense global marketing of tobacco products suggests that it is unlikely there will be a decrease in H&N cancer incidence in the near future. Ongoing advances in surgical techniques continue to diminish treatment-related morbidity for patients with advanced disease. New developments in radiation and chemotherapy suggest that nonoperative treatment strategies will increasingly accomplish effective disease control, particularly with the refinement of concurrent chemoradiotherapy regimens and the use of new molecular agents which modulate H&N tumor growth. In this article, we highlight selected advances in surgery, radiation, and chemoradiation, which hold particular promise for the future of H&N cancer therapy. The evolution of surgical techniques includes the increasing use of selective neck dissection, the use of conservation techniques in the management of selected laryngeal and hypopharyngeal tumors, the use of free tissue transfer for optimal reconstruction and the increased availability of expertise in combined surgical approaches for tumors of the skull base. Altered radiation fractionation has evolved to a mature state of knowledge in recent years based primarily on clinical trials performed in patients with advanced H&N cancer. A major current challenge involves how to best interdigitate optimal radiation fractionation with concurrent chemotherapy regimens in H&N cancer. Among a series of new molecular agents under active investigation in H&N cancer, two specific examples with high promise are discussed, which exploit tumor hypoxia (tirapazamine) and overexpression of the epidermal growth factor receptor (EGFR inhibitors), respectively. These and other stepwise advances are contributing to the gradual reduction in global mortality rates for H&N cancer patients observed over the last decade, as well as to diminishing the adverse impact on patient quality of life that commonly accompanies treatment for this complex tumor site.     

Weekly Cisplatin-Based Concurrent Chemoradiotherapy for Treatment of Locally Advanced Head and Neck Cancer: a Single Institution Study

Background: The organ preservation approach of choice for the treatment of locally advanced head and neckcancers is concurrent chemoradiation with three weekly high doses of cisplatin. Although this is an efficacioustreatment policy, it has high acute systemic and mucosal toxicities, which lead to frequent treatment breaksand increased overall treatment time. Hence, the current study was undertaken to evaluate the efficacy ofconcurrent chemoradiation using 40 mg/m2 weekly cisplatin. Materials and Methods: This is a single institutionalretrospective study including the data of 266 locally advanced head and neck cancer patients who were treatedwith concurrent chemoradiation using 40 mg/m2 weekly cisplatin from January 2012 to January 2014. A p-valueof < 0.05 was taken to be significant statistically for all purposes in the study. Results: The mean age of the studypatients was 48.8 years. Some 36.1% of the patients had oral cavity primary tumors. The mean overall treatmenttime was 57.2 days. With a mean follow up of 15.2 months for all study patients and 17.5 months for survivors,3 year local control, locoregional control and disease free survival were seen in 62.8%, 42.8% and 42.1% of thestudy patients. Primary tumor site, nodal stage of disease, AJCC stage of the disease and number of cycles ofweekly cisplatin demonstrated statistically significant correlations with 3 year local control, locoregional controland disease free survival. Conclusions: Concurrent chemoradiotherapy with moderate dose weekly cisplatin isan efficacious treatment regime for locally advanced head and neck cancers with tolerable toxicity which canbe used in developing countries with limited resources.     

A Review of Modern Radiation Therapy Dose Escalation in Locally Advanced Head and Neck Cancer

The management of head and neck cancer is complex and often involves multimodality treatment. Certain groups of patients, such as those with inoperable or advanced disease, are at higher risk of treatment failure and may therefore benefit from radiation therapy dose escalation. This can be difficult to achieve without increasing toxicity. However, the combination of modern treatment techniques and increased research into the use of functional imaging modalities that assist with target delineation allows researchers to push this boundary further. This review aims to summarise modern dose escalation trials to identify the impact on disease outcomes and explore the growing role of functional imaging modalities. Studies experimenting with dose escalation above standard fractionated regimens as outlined in National Comprehensive Cancer Network guidelines using photon therapy were chosen for review. Seventeen papers were considered suitable for inclusion in the review. Eight studies investigated nasopharyngeal cancer, with the remainder treating a range of subsites. Six studies utilised functional imaging modalities for target delineation. Doses as high as 85.9 Gy in 2.6 Gy fractions (EQD2 90.2 Gy₁₀) were reportedly delivered with the aid of functional imaging modalities. Dose escalation in nasopharyngeal cancer resulted in 3-year locoregional control rates of 86.6–100% and overall survival of 82–95.2%. For other mucosal primary tumour sites, 3-year locoregional control reached 68.2–85.9% and 48.4–54% for overall survival. There were no clear trends in acute or late toxicity across studies, regardless of dose or addition of chemotherapy. However, small cohort sizes and short follow-up times may have resulted in under-reporting. This review highlights the future possibilities of radiation therapy dose escalation in head and neck cancer and the potential for improved target delineation with careful patient selection and the assistance of functional imaging modalities.     

Extra-mandibular Osteoradionecrosis after the Treatment of Head and Neck Cancer

AimsOsteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database.Materials and methodsIn total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%).ResultsMaxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3–42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22–66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months.All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20–68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2–65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream.ConclusionExtra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.     

Radiochemotherapy in Locally Advanced Squamous Cell Carcinomas of the Head and Neck

Squamous cell carcinoma of the head and neck (SCCHN) is a common disease that develops in the upper aerodigestive epithelium. The most important risk factors are tobacco and alcohol consumption. There is also increasing evidence that human papillomavirus plays an important role in the cause of SCCHN. The complex anatomy, the vital functions of the upper aerodigestive tract and the close proximity to vital structures, explain that the goal of treatment is not only to improve survival outcomes, but also to preserve organ function. Radiotherapy and surgery are the standard modalities of treatment, reflecting the locoregional predominance of SCCHN. Chemotherapy plays an important role in the treatment of patients with locoregionally advanced disease, in conjunction with radiotherapy and surgery. Indeed, standard therapy for resectable locoregionally advanced (stage III or IV) SCCHN cancers consists either of surgery and adjuvant chemoradiotherapy or definitive concomitant chemoradiotherapy, depending upon disease site, stage and resectability of the tumour, or institutional experience. Concomitant chemoradiotherapy has been shown in several randomised trials to improve disease-free and overall survival in the postoperative setting for resected disease with poor prognostic factors. Furthermore, multiple randomised studies and meta-analyses have shown that definitive chemoradiotherapy, as well anti-epidermal growth factor receptor treatment in one randomised study, improved disease-free and overall survival when compared with radiotherapy alone. This overview reviews the most relevant published studies on the multidisciplinary management of SCCHN and discusses future strategies to reduce locoregional failures.     

Role of Concomitant Chemoradiation in Locally Advanced Head and Neck Cancers

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation.However, survival of this patient population has not improved during the past 20 years. Many differentmultimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organpreservation. The present study was intended to establish the efficacy of concomitant chemoradiation with asingle agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility ofconcomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacuteside effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conductedwherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx,hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weeklycarboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy)to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease.Neck dissection was recommended for all patients with neck disease showing less than a complete responseafter chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highestincidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumoursconstituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% ofthe patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had gradeII mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions,65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion oftreatment 65% of patients had complete response at the primary and regional sites, and 35% of patients hada partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at theprimary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease.Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head andneck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary siteconservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primarymanagement of head and neck cancers.     

Concomitant Chemoradiotherapy for Advanced Head and Neck Cancer

Head and neck cancer is mostly curable in the early stages byeither surgery or radiotherapy alone, but the control rate foradvanced stages is low, even with combined surgery and postoperativeradiotherapy. From September, 1990, to January, 1992, 35 patientswith locoregionally advanced head and neck cancers were enteredin a prospective study of concomitant chemoradiotherapy. Thirty-threecompleted the treatment. There were 29 males and four femaleswith a median age of 53 years. All except one patient were instage IV. Radiotherapy was delivered using a telecobalt unitand by conventional fractionation (1.8 Gy/fraction, 5 fractions/wk).Chemotherapy with cisplatin (10 mg/m²/day, daily, days 1-5)and 5-FU (500 mg/m²/day continuously infused for five days)was given concurrently during the first and fifth weeks of radiation.Twenty-four among 31 eligible patients achieved complete response(77.4%) and the other seven (22.6%) partial response, resultingin a 100% response rate. The toxicities experienced were increasedcompared with those caused by radiotherapy alone. The most commonside effects were gastrointestinal and hematologic toxicitiesbut the whole treatment was well tolerated. The two-year actuarialsurvival rate is 45%. We found the primary origin and overalltreatment time to affect survival significantly. The survivalrate for tumors arising from the nasopharynx or paranasal sinusis better than for those arising from other regions of the headand neck. The shorter treatment times (within eight weeks) hada better survival rate. Our preliminary experience suggeststhat concomitant chemoradiotherapy is both feasible and effectivefor head and neck cancer. The optimal scheduling and dosageof concomitant chemoradiotherapy should be further researched.     

Impact of Adaptive Radiotherapy on Locally Advanced Head and Neck Cancer - A Dosimetric and Volumetric Study

Objective of the study is to evaluate volumetric and dosimetric alterations taking place during radiotherapy for locally advanced head and neck cancer (LAHNC) and to assess benefit of replanning in them. Materials and Methods: Thirty patients with LAHNC fulfilling the inclusion and exclusion criteria were enrolled in a prospective study. Planning scans were acquired both pre-treatment and after 20 fractions (mid-course) of radiotherapy. Single plan (OPLAN) based on initial CT scan was generated and executed for entire treatment course. Beam configuration of OPLAN was applied to anatomy of interim scan and a hybrid plan (HPLAN30) was generated. Adaptive replanning (RPLAN30) for remaining fractions was done and dose distribution with and without replanning compared for remaining fractions. Results: Substantial shrinkage of target volume (TV) and parotids after 4 weeks of radiotherapy was reported (p<0.05). No significant difference between planned and delivered doses was seen for remaining fractions. Hybrid plans showed increase in delivered dose to spinal cord and parotids for remaining fractions. Interim replanning improved homogeneity of treatment plan and significantly reduced doses to cord (Dmax, D2% and D1%) and ipsilateral parotid (D33%, D50% and D66%) (p<0.05). Conclusions: Use of one or two mid-treatment CT scans and replanning provides greater normal tissue sparing alongwith improved TV coverage     

Assessment of Treatment Response after Chemoradiation of Head and Neck Cancer

Accurate early diagnosis and staging is an essential step in the management of recurrent head and neck cancer. Nevertheless, the diagnosis and staging of recurrent head and neck cancer previously treated by radiation therapy often combined with chemotherapy, remains a challenge. The differentiation between radiation induced reaction and recurrent cancer is a difficult clinical and radiological problem. It is clear that timely diagnosis in case of residual or recurrent tumor is of great importance to increase the possibility of cure. A variety of interventions such as office clinical examinations, blood tests, serum tumor marker measurements, imaging studies and endoscopies are being used to follow-up these patients. No single intervention proved to be absolute or complete in being simultaneously sensitive, specific, inexpensive, safe and efficient at detecting suspected recurrence of head and neck cancer, particularly after chemoradiation. In addition to that, there is no clear evidence of what surveillance regimen or frequency is considered the most adequate or effective in this setting. In this article, we analyze the diagnostic difficulties of tumor recurrence after combined treatment with chemotherapy plus radiation therapy and review the role of clinical, endoscopic and imaging techniques in the follow-up of these patients.     

Efficacy of Neck Dissection in the Management of Isolated Nodal Recurrence after Head and Neck Cancer Treatment

The status of the regional cervical lymphatics is one of the most significant prognostic indicators in head and neck cancers. The traditional treatment for cancers with cervical nodal metastasis has been surgical. With the global trend towards organ-preserving therapy, chemoradiation has gained increasing popularity over primary surgical therapies for cancers in the head and neck region. The subsequent management of the neck for those with residual or recurrent nodal metastasis, however, has become one of the most debated topics in the field of head and neck oncology. This review addressed several important controversies, including the optimal assessment of the nodal response to chemoradiation, the potential role and the oncological results of planned and salvage neck dissection after chemoradiation, as well as the type and extent of neck dissection required in order to achieve the optimal balance between tumour control and surgical morbidities. Further clinical trials and on-going research will help us to define the best therapeutic option in such circumstances.     

Current Trends in the Follow-up of Head and Neck Cancer Patients in the UK

AimsThe follow-up of patients with head and neck cancer is an essential aspect of their management. Follow-up provides support and reassurance for patients and will allow early detection of recurrence and second primary tumours. However, there is little evidence of a survival benefit from follow-up. With prolonged follow-up periods, multidisciplinary teams may be under increasing pressure to see more patients and this could have a negative effect on the time and quality of consultations given to individual patients. The aim of the present study was to analyse the current trends in the follow-up of head and neck cancer patients after treatment with curative intent in the UK.Materials and methodsA postal questionnaire was sent to all members of the British Association of Head and Neck Oncologists.ResultsThree hundred and twenty-seven questionnaires were sent and 214 were returned, making a response rate of 65.4%. One hundred and ninety-eight (61%) of these were deemed appropriate for evaluation and of these 111 (56%) clinicians followed up patients for a minimum of 5 years with 25 (13%) following patients for 10 years and 44 (22%) for life. Within the set of clinicians following patients for 5 years, 24 (12%) followed up patients with salivary gland and thyroid malignancies for a longer period of time. All clinicians concurred that the reasons for follow-up are to support patients, to detect local recurrences or metastases, second primary tumours and to monitor and manage the complications of treatment.ConclusionsMost of the clinicians followed up their patients up to a minimum of 5 years, with a significant minority who followed up the patients treated for cancers of the head and neck for longer periods. More studies are needed to elucidate the rationale and evidence for follow-up and to determine the adequate period of surveillance.     

Radiation Therapy and Concurrent Cisplatin Administration in Locally Advanced Head and Neck Cancer a Hellenic Co-Operative Oncology Group Study

In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a ⁶⁰Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m² on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned.