头颈部鳞癌患者同步放化疗和(或)分子靶向治疗继发口腔黏膜炎的防治

目的 探讨接受同步放化疗和(或)分子靶向药物治疗的中晚期头颈部鳞癌患者口腔黏膜炎的防治.方法 回顾性分析2007年11月至2010年11月期间接受同步放化疗和(或)分子靶向药物治疗的179例中晚期头颈部鳞癌患者口腔黏膜炎发生情况及治疗效果.男155例,女24例.临床分期:Ⅲ期124例,Ⅳ期55例.口腔黏膜炎发生情况:Ⅰ级49例,Ⅱ级50例,Ⅲ级67例,Ⅳ级13例.接受同步放化疗的同时采取预防口腔黏膜炎的方法,对发生黏膜炎的患者采用常规治疗结合喹诺酮类抗生素的方法进行治疗.结果 99例Ⅰ、Ⅱ级和4例Ⅲ级口腔黏膜炎患者经常规治疗达到有效控制,即口腔黏膜炎性反应范围减少,疼痛明显减轻,可进食.76例Ⅲ、Ⅳ级口腔黏膜炎患者通过常规治疗结合喹诺酮类抗生素,得到有效控制.无一例患者出现放疗中断及抗生素药物相关的毒副作用.结论 对接受同步放化疗和(或)分子靶向药物治疗的中晚期头颈部鳞癌患者发生的口腔黏膜炎,轻度患者采用常规治疗有效,中重度患者采用抗生素治疗有效.

Abstract：

Objective To investigate the prevalence and treatment of oral mucositis caused by concurrent chemoradiotherapy and/or molecular targeted therapy in the patients with advanced squamous cell carcinoma of the head and neck. Methods A retrospective study of the incidence and treatment of oral mucositis was performed in 179 patients (155 male and 24 female; 124 patients at stage Ⅲ and 55 patients at stage Ⅳ) receiving concurrent chemotherapy and (or) molecular targeted therapy between November 2007 and November 2010. Grade Ⅰ , Ⅱ , Ⅲ and Ⅳ oral mucositis occurred respectively in 49, 50, 67 and 13 patients. All the patients received oral mucositis prophylaxis. After the occurrence of oral mucositis, conventional treatment of mucositis combined with quinolone antibiotics were applied. Results Of the patients, 99 patients with grade Ⅰ or Ⅱ and 4 patients with grade Ⅲ oral mucositis were effectively managed by conventional treatment; 76 patients with grade Ⅲ or Ⅳ oral mucositis were also significantly controled by conventional treatment plus antibiotics. After the treatments, all patients with oral mucositis were under control, with the decrease in the grade of oral mucositis, the reduction of oral pain and the improvement in ability to eat None of them had radiation treatment breaks. Conclusions Combined modality therapy can effectively control chemoradiation-induced oral mucositis in patients with head and neck squamous cell carcinoma, grade Ⅰ and Ⅱ oral mucositis were cured by conventional treatment and quinolone antibiotics play a key role in the treatmeats for grade Ⅲ and Ⅳ oral mucositis.     

Neuroblastoma of the head and neck

We reviewed 105 cases of neuroblastoma, which were seen at the Buffalo Children's Hospital between 1936 and 1976. We describe seven patients with primary neuroblastoma of the head and neck. The results of postmortem examination in two of these patients proved without any doubt that the tumor was primarily in the head and neck region. Although metastasis of neuroblastomas to the head and neck from more common primary sites in the abdomen, pelvis, or thorax is common, to our knowledge, well-documented primary head and neck lesions are quite rare. The prognosis of invasive neuroblastoma of the head and neck is poor, with rapid and widespread metastasis being the rule. However, some success has been reported with early and massive therapy that involves surgery, chemotherapy, and radiation therapy.     

Combined therapy for resectable head and neck cancer. A phase 3 intergroup study

This Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeastern Cancer Study Group) phase 3 randomized prospective trial was opened for registration January 1985. It is an evaluation of the role of chemotherapy for previously untreated advanced stage resectable squamous cell carcinoma of the head and neck. As of March 1, 1988, there has been a total of 535 patients registered. There are 266 patients analyzable with 133 in each treatment group. The surgical, chemotherapy, and radiation therapy toxic reactions are in the tolerable range with the worst toxic reactions reported in those patients receiving both surgery and radiation therapy. Compliance continues to be a major challenge to patient accrual. The most common cause for cases not being randomized involves positive margins of surgical resection. Patient refusal or surgical complications are other common reasons.     

Rhabdomyosarcoma of the head and neck in children

Rhabdomyosarcoma is the most common soft-tissue sarcoma in infants and children, with the head and neck being the most frequent site of involvement. Treatment for this neoplasm has undergone many changes, with a much improved prognosis using a combination of surgery, radiation therapy, and chemotherapy. This retrospective analysis presents the management and outcome of 60 children (aged 3 months to 18 years) with rhabdomyosarcoma of the head and neck evaluated at the Children's Hospital of Philadelphia (Pa) between 1970 and 1987. The overall death rate for all head and neck sites decreased from 50% in 1970 to 1979 to 23% in 1980 to 1987, reflecting the improved management protocol.     

Decreased hearing after combined modality therapy for head and neck cancer

PURPOSE: Combined platinum-based chemoradiation therapy is frequently being used as therapy for head and neck cancer at multiple sites. These therapies are individually ototoxic, but little has been reported on their combined toxicity. MATERIALS AND METHODS: A retrospective investigation of 37 patients known to have undergone therapy with both agents, in combination, for head and neck malignancy was performed. Sixty percent of the patients had complaints of hearing loss subjectively. Reliable pretreatment and posttreatment audiograms were obtained on 15 of these patients. Audiograms were analyzed for sensorineural changes at 0.5, 1, 2, 4, and 8 kHz. RESULTS: By paired t test analysis, there were significant changes in the patients with pretreatment and posttreatment audiograms at all frequencies. More than 50% of the patients had a change of 10 dB or greater in their pure-tone average. More than 85% of the patients experienced changes in their hearing at 4 and 8 kHz. CONCLUSIONS: We conclude that patients undergoing combined modality therapy for head and neck cancer experience hearing loss. We recommend that hearing assessment, including pretreatment and posttreatment audiometry, be performed in all patients undergoing combined platinum-based chemotherapy and radiation for the treatment of head and neck cancer.     

Current thoughts on the role of chemotherapy and radiation in advanced head and neck cancer

PURPOSE OF REVIEW: The management of advanced malignancies of the head and neck continues to be a challenging clinical problem. During the last three decades, the traditional treatments of surgery and/or radiation have not yielded significant improvements in survival in this patient population. In addition, surgery for advanced disease can create significant functional and cosmetic defects that adversely impact a patient's quality of life. Newer "organ preservation" approaches using chemotherapy and radiation are currently being studied in an attempt to improve survival while maintaining the functional integrity of the disease site. RECENT FINDINGS: Recent studies have demonstrated that for advanced head and neck squamous cell cancers, concurrent chemoradiation is superior to radiation alone for local tumor control and perhaps overall survival. With the exception of laryngeal cancer, phase III data comparing chemoradiation with surgery is lacking for most head and neck subsites. However, comparisons with historical controls suggest that chemoradiation strategies may offer improved outcomes when compared with more traditional treatment regimens. SUMMARY: This review emphasizes recent phase III trials that support the use of chemoradiation strategies in the treatment of advanced head and neck squamous cell cancers.     

Neue Aspekte zur aktuellen Therapie von Oropharynxkarzinomen

Beside the surgical treatment of head and neck cancer, the concept of organ and function preserving therapy of locally advanced HNSCC (head and neck squamous cell carcinoma) especially of oropharyngeal origin is becoming increasingly important. The comparison of induction chemotherapy plus chemoradiation and primary concomitant chemoradiation has recently been the subject of randomized clinical trials. New combinations of different (chemo)radiation regimens and targeted therapies are also under investigation for HNSCC. Molecular markers predicting treatment efficacy as well as new potential targets are also being evaluated in several clinical trials. The good prognosis of HPV-associated HNSCC has sparked efforts to deintensify treatment to minimize therapy-related toxicities. The impact of specific therapies is growing due to the increasing incidence of young patients with HPV-positive carcinomas.     

Developmental Aspects of the Rat Endolymphatic Sac and Functional Implications

Merkel cell carcinoma (MCC) is an uncommon cutaneous neoplasm which arises in adults with a peak incidence in the sixth and seventh decades. MCC most often arises in the head and neck area and extremities. Among head and neck primary sites, auricular MCC has proven to be rare and only 20 cases have been reported in the literature. Auricular MCC follows the same aggressive course as has been documented for MCC arising elsewhere: the tumor has a propensity for recurring locally and metastasizing to regional lymph nodes and distant sites. Location of MCC in the auricular regions does not appear to confer any survival advantage compared with MCC arising elsewhere. The mainstay of treatment is surgery, with attempts at complete surgical excision being of paramount importance. What role regional node dissection, radiation therapy and chemotherapy may play in the standard treatment of auricular MCC remains to be clearly established.     

The role of surgery in rhabdomyosarcoma of the head and neck in children

The role of surgery in the treatment of rhabdomyosarcoma of the head and neck has diminished during the past 25 years. Treatment of this tumor in the pediatric population has involved radical radiation therapy and chemotherapy with little or no role for surgery. However, the potential effect of irradiation on facial growth and the appearance of secondary irradiation-induced tumors has raised the question as to whether surgery may once again play a role in the treatment of these patients. Advances in skull base and reconstructive surgery and microsurgical techniques have permitted a reconsideration of initial ablative surgery. The head and neck surgical team must be prepared to respond in those patients in whom craniofacial development is at risk or recurrence has occurred after radical chemotherapy and/or radiation therapy.     

Merkel cell carcinoma of the auricle

Merkel cell carcinoma (MCC) is an uncommon cutaneous neoplasm which arises in adults with a peak incidence in the sixth and seventh decades. MCC most often arises in the head and neck area and extremities. Among head and neck primary sites, auricular MCC has proven to be rare and only 20 cases have been reported in the literature. Auricular MCC follows the same aggressive course as has been documented for MCC arising elsewhere: the tumor has a propensity for recurring locally and metastasizing to regional lymph nodes and distant sites. Location of MCC in the auricular regions does not appear to confer any survival advantage compared with MCC arising elsewhere. The mainstay of treatment is surgery, with attempts at complete surgical excision being of paramount importance. What role regional node dissection, radiation therapy and chemotherapy may play in the standard treatment of auricular MCC remains to be clearly established.     

Is glutathione-S-transferase-pi expression a reliable predictor of chemoradiation response in cancer of the head and neck?

PURPOSE: Concurrent radiation and chemotherapy is being evaluated as an alternative treatment to surgery for patients with advanced squamous cell carcinoma of the head and neck, because organ preservation maybe possible without compromising survival. However, the response to concurrent chemoradiation treatment varies from patient to patient, and there is currently no available molecular predictor of response for this particular treatment modality. There is some evidence to indicate that glutathione S-transferase-pi (GST-pi), which is one of the drug detoxifying enzymes, may decrease the effectiveness of platinum-based chemotherapy in the treatment of a variety of tumor types. This study was performed to investigate whether GST-pi expression was correlated with response to concurrent chemotherapy and radiotherapy in patients with advanced squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: Diagnostic biopsy specimens of 36 patients who underwent concurrent chemoradiotherapy for the treatment of advanced squamous cell carcinoma of the head and neck were examined for GST-pi expression by using immunohistochemistry with polyclonal antihuman GST-pi antibodies. GST-pi expression scores were compared among responders and nonresponders. RESULTS: Although the staining rate with antiGST-pi was slightly lower in the responder group in comparison with the nonresponders (82% vs 100%), the difference was not statistically significant. CONCLUSION: GST-pi expression is unlikely to be a valuable predictor of response to concurrent chemotherapy and radiation treatment in patients with advanced squamous cell carcinoma of the head and neck.     

Initial adjuvant therapy in advanced squamous cell carcinoma of the head and neck employing weekly high dose methotrexate with leucovorin rescue.

Our initial experience with weekly high dose methotrexate with leucovorin rescue (MTX-LCV), in advanced recurrent or metastatic squamous cell carcinoma of the head and neck with a 77% tumor response rate and high therapeutic index, prompted a trial of MTX-LCV as initial adjuvant therapy in high risk nonmetastatic patients. Results in 11 patients are presented and confirm the high response rate to MTX-LCV and the low incidence of myelotoxicity and mucositis, when concurrent urinary alkalinization is employed. Initial MTX-LCV administrations has not compromised subsequent optimum aggressive combinations of surgery and radiation therapy. Cytoreduction with MTX-LCV may be safely used initially in combined therapy for high risk squamous cell carcinoma of the head and neck.     

Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: new trends in pathophysiology, prevention and treatment

Mucositis is the intensity-limiting toxicity in the management of locally advanced non-resectable head and neck cancer with radiotherapy and chemotherapy. New radiation modalities (hyperfractionation and/or acceleration) as well as combined modality regimens in this situation induce higher rates of acute toxicity. Hyperfractionation, for example, allows higher control rates, with few late toxicities, but it slightly increases acute mucositis. The addition of chemotherapy introduces systemic toxicity and can exacerbate local tissue reactions when used concurrently with radiotherapy. Mucositis is recognized as the principal limiting factor to further treatment intensification. As local regional control and overall survival are related to dose-intensity in this case, further research into the assessment, analysis, prevention and treatment of mucosal toxicity is not only crucial to improvement in quality of life, but certainly also to improved rates of disease control. Several topical and systemic treatments are directed to the decrease and the acceptance of this acute toxicity, but few have shown a significant preventive effect. The efficacy of low-level laser therapy in the management of such toxicity could hence yield important developments with this method in the field of oncology. Received: 1 May 2001 / Accepted: 15 May 2001     

Modified radical neck dissection and minimal invasive tumor surgery in the middle of split course of concomitant chemoradiotherapy of advanced HNSCC

OBJECTIVE: The effectiveness of modified radical neck dissection with concomitant chemoradiotherapy in patients with N2/3 advanced head and neck cancer was evaluated. STUDY DESIGN AND SETTING: Retrospective study of 35 patients treated at the University Hospital, Medical University, Innsbruck. The treatment consisted of a split course radiation up to 70 Gy with concomitant chemotherapy with Mytomicin C and 5-fluorouracil. Neck dissection and/or tumor resection was performed between the two cycles of radiation and chemotherapy. RESULTS: The 2-year progression-free survival was 64%, locoregional control 92% and overall survival 55. Observed toxicities included mucositis (grade 3, 35%; grade 4, 16%), neutropenia (grade 4, 28%), and thrombocytopenia (grade 4, 26%). No complications related to modified radical neck dissection were observed. CONCLUSION: Intermittent neck dissection was highly effective in controlling the neck disease. Mitomycin C-based chemoradiotherapy for treatment of locally advanced cancer seems to be an option to cisplatin-based regimens.     

Frequency of esophageal stenosis after simultaneous modulated accelerated radiation therapy and chemotherapy for head and neck cancer

BACKGROUND: Chronic esophageal toxicity after radiotherapy alone for cancer of the head and neck (HNCa) is rare: 2.6% for strictures and 0.8% for stenosis after a 60-Gy dose. With combined modality therapy, stricture rates of 22% to 37% have been reported. We report the frequency of esophageal toxicity after simultaneous modulated accelerated radiation therapy (SMART) with chemotherapy for HNCa. METHODS: The records of the otolaryngology/head and neck surgery department of Emory University, Atlanta, GA, were screened for patients undergoing combined modality therapy using SMART for HNCa. Radiation Oncology records were reviewed for target and critical normal structure dosimetry, with detailed analysis of esophageal and supraglottic laryngeal dosimetry. Hospital and clinic records were reviewed for evidence of esophageal toxicity. RESULTS: From January 2003 to August 2005, 99 patients underwent definitive therapy for squamous cell HNCa using SMART and chemotherapy. Follow-up was documented in all cases. Median dose to sites of gross primary or nodal disease was 70.29 Gy, at 2.13 Gy per fraction. Median dose to the ipsilateral neck was 63.03 Gy at 1.91 Gy per fraction. Median dose to the contralateral neck in 97 patients treated was 57.75 Gy at 1.75 Gy per fraction. Thirteen (13%) patients developed esophageal strictures. Five (5%) patients had complete esophageal stenosis. Four (14%) of the 29 patients with either a hypopharyngeal primary or a N2c nodal disease developed complete stenosis. A statistically larger esophageal volume of esophagus reactivity > or = 60 Gy (V(60)) was found in patients who developed stenosis/stricture when compared with a randomly selected population of N2a/b patients who did not develop those toxicities. Esophageal stenosis/stricture was also numerically more common in patients receiving taxane-based chemotherapy, developing in 23%, as opposed to 9% in patients treated with platinum-based chemotherapy. CONCLUSION: The risk of esophageal stenosis may increase with SMART and chemotherapy for HNCa. Potential mechanisms to reduce this include (a) contouring the esophagus as a dose-limiting structure; (b) early flexible examination posttreatment, with early intervention with dilation; (c) improved therapy for mucositis.     

Ionized serum calcium levels following combined treatment for cancer of the head and neck

Thyroid function may be reduced after treatment of cancer of the head and neck, and hypothyroidism is much more common after combination therapy. Whether hypoparathyroidism and subsequent hypocalcemia also occur after such treatment is unknown. Few related studies have been published in which changes in total serum calcium have been studied after cancer treatment with radioactive iodine or external radiation. Twenty-two disease-free head and neck cancer patients were studied, 1 to 3 years after multimodal treatment, to determine if changes in serum ionized calcium levels or thyroid function were present. Our results suggest that parathyroid function, as represented by ionized calcium levels remains normal after multimodality (surgery, radiation and/or chemotherapy) combined treatment.     

Salvage surgery with free flap reconstruction: factors affecting outcome after treatment of recurrent head and neck squamous carcinoma

OBJECTIVE: To determine factors predicting the outcome after salvage surgery with microvascular flap reconstruction for recurrent squamous cell cancer (SCC) of the head and neck. STUDY DESIGN: This is a retrospective analysis of patients treated at an academic medical center. METHODS: One hundred six patients underwent salvage surgery and microvascular flap reconstruction after prior unsuccessful cancer treatment using surgery, radiation, or chemotherapy. All patients had a follow-up interval after salvage surgery of at least 24 months unless cancer rerecurrence occurred within 24 months after salvage surgery. Factors including age, sex, comorbidity level, tobacco use, alcohol use, disease-free interval since prior therapy, prior radiation, prior chemotherapy, prior surgery, recurrent tumor T class, recurrent tumor N class, recurrent cancer stage, and tumor location were examined to determine their association with cancer rerecurrence after salvage surgery. Successful treatment was defined as patients who remained free from cancer rerecurrence for a minimum 2 year period after salvage surgery. RESULTS: Advanced recurrent T class (P = .02) was significantly associated with cancer recurrence. Recurrent cancer stage and patient smoking status approached statistical significance (P = .06). CONCLUSION: Patients with recurrent T1 and T2 class are the best candidates for salvage surgery and microvascular flap reconstruction for treatment of recurrent SCC of the head and neck. Patients with T3 and T4 class recurrent cancers and patients who continue to smoke after initial diagnosis and treatment of head and neck SCC are poor candidates to undergo salvage surgery.     

Antivascular strategies--a new concept for diagnosis and therapy of head and neck cancer. A review

BACKGROUND: The development of a blood supply is a crucial step in the progression and metastasis of head and neck cancer. While conventional therapeutic approaches, e. g. chemotherapy and radiation, are focusing on tumor cells, antivascular therapy is directed against the tumor supplying blood vessels. Antivascular treatment can be divided in anti-angiogenesis and vascular targeting. While antiangiogenic therapy prevents neovascularisation by inhibiting new blood vessel growth, the aim of vascular targeting is the destruction of already existing tumor vasculature. METHODS: This review will summarise current pathophysiological mechanisms underlying tumor angiogenesis and the concepts of antivascular therapy with respect to possible applications in head and neck cancer. RESULTS: With experimental antivascular strategies a retardation of tumor growth or tumor remission may be achieved, demonstrating proof of principle. At present, numerous drugs are preclinically and clinically evaluated. CONCLUSIONS: Antivascular strategies are a promising concept for treatment of patients with head and neck carcinomas. They will most likely exhibit their potential in combination with standard tumor therapies in the future.     

Systemic therapy strategies for head-neck carcinomas: current status

Head and neck cancers, most of which are squamous cell tumours, have an unsatisfactory prognosis despite intensive local treatment. This can be attributed, among other factors, to tumour recurrences inside or outside the treated area, and metastases at more distal locations. These tumours therefore require not only the standard surgical and radiation treatments, but also effective systemic treatment. The main option here is antineoplastic chemotherapy, which is firmly established in the palliative treatment of recurrent or metastatic stages of disease, and is used with curative intent in the form of combined simultaneous or adjuvant chemoradiotherapy in patients with inoperable or advanced tumour stages. Neoadjuvant treatment strategies for tumour reduction before surgery have yet to gain acceptance. Induction chemotherapy protocols before radiotherapy have to date been used in patients at high risk of distant metastases or as an aid for decision-making ("chemoselection") in those with extensive laryngeal cancers, prior to definitive chemoradiotherapy or laryngectomy. Triple-combination induction therapy (taxanes, cisplatin, 5-fluorouraeil) shows high remission rates with significant toxicity and, in combination with (chemo-)radiotherapy, is currently being compared with simultaneous chemoradiotherapy the current gold standard with regards to efficacy and long-term toxicity. A further systemic treatment strategy, called 'targeted therapy', has been developed to help increase specificity and reduce toxicity. An example of targeted therapy, EGFR-specific antibodies, can be used in palliative settings and, in combination with radiotherapy, to treat advanced head and neck cancers. A series of other novel biologicals such as signal cascade inhibitors, genetic agents, or immunotherapies, are currently being evaluated in large-scale clinical studies, and could prove useful in patients with advanced, recurring or metastatic head and neck cancers. When developing a lasting, individualised systemic tumour therapy, the critical evaluation criteria are not only efficacy and acute toxicity but also (Iong-term) quality-of-life and the identification of dedicated predictive biomarkers.     

Recent advances in radiation therapy for head and neck cancer

The treatment of locally advanced or recurrent head and neck cancers has improved from single modality interventions of surgery and radiation therapy alone to include combined modality therapy with surgery, chemotherapy and radiation. Combined therapy has led to improved local control and disease-free survival. New developments in radiation oncology such as altered fractionation, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, stereotactic radiosurgery, fractionated stereotactic radiotherapy, charged-particle radiotherapy, neutron-beam radiotherapy, and brachytherapy have helped to improve this outlook even further. These recent advances allow for a higher dose to be delivered to the tumor while minimizing the dose delivered to the surrounding normal tissue. This article provides an update of the new developments in radiotherapy in the management of head and neck cancers.