Diagnosis, treatment and results of malignant skull base tumours

BACKGROUND: Malignant tumours of the cranial base are rare and present usually in advanced tumour stage due to the lack of early clinical symptoms. PATIENTS AND METHODS: Sixty patients with malignant tumours infiltrating the skull base were treated at the Department of Otorhinolaryngology Head and Neck Surgery, University of Würzburg between 1987 and 1999. Most of the tumours (n = 51) originated from the nose or paranasal sinuses, the epipharynx, the outer ear canal or the middle ear. Seven tumours were malignant brain tumours infiltrating the bony structures of the skull base or originated from the cranial base itself. Two patients suffered from metastases of an adenocarcinoma of the prostata. The histological diagnosis was confirmed in 53 patients preoperatively and in seven patients during tumour resection. Squamous cell carcinoma (n = 24), adenocarcinoma (n = 10) and sarcoma (n = 7) were the most common histologies found. RESULTS: A radical en bloc resection of the tumour was only possible in 26 out of 60 cases. A surgical tumour reduction with postoperative radiation therapy was performed in seven patients as a palliative approach. Eight patients underwent a combined radio- and chemotherapy according to the histological diagnosis. Primary radiotherapy was the treatment of choice in eleven patients, where the tumours were located in the central area of the cranial base. Palliative radiotherapy or solely medical pain control were applied to eight patients who presented either with distant metastases or an advanced tumour growth. The mean postoperative survival following radical surgery was 48 months and after primary radiotherapy 27 months. DISCUSSION: A statistical analysis of the results is not applicable due to the great variety of the disease concerning the histological diagnosis, the tumour size and the location as well as the small number of patients.     

Possibility of the achieving of the therapeutic gain in radiotherapy of head and neck cancer

In nowadays development in radiotherapy head and neck cancers has been achieved step by step in 3 main fields: technological, radiobiological and general strategy of oncological treatment. One of the most important technical changes are: the introducing of three dimensional treatment planning (3 DCRT) system and application of new radiological imaging methods (CT, MRI) in treatment planning with a computer technology calculation of dose distribution. From the radiobiological point of view a very important fact has been to distinguishing two kinds of tissue (acute and late reacting tissue) which response depends on change in fraction dose. It has given the theoretical basis to clinical trials of new methods of fractionation (hyper-, accelerated hyperfractionation). The dynamic development of surgery and chemotherapy have established a new place for radiation therapy in the complex treatment of tumours (adjuvant, elective, concomitant treatment). It has been established that in advanced tumours, the first modality of treatment is surgery in conjunction with postoperative radiotherapy. Routine application of chemotherapy in head and neck cancer is still controversial with exception of radiochemotherapy of nasopharyngeal cancer, particularly in cases of lymph nodes metastases.     

Adenoidzystisches Karzinom des Oropharynx

Purpose

Adenoid cystic carcinomas are rare tumours. Regional lymphatic spread is rather uncommon. Distant metastases occur in approximately half of all patients. High local failure rates of up to 50% after surgery have been reported. Even after adjuvant radiation, the results remain poor for locally advanced tumours after incomplete resection. We report on a safe and effective salvage option in the treatment of adenoid cystic carcinoma.

Material and Methods

A 44 year old woman with the diagnosis of adenoid cystic carcinoma of the oropharynx and simultaneous pulmonary metastases received a mixed beam photon radiotherapy and a neutron boost. Three years later, the patient developed a dysphagia grade 2, dysarthria and pain. A local recurrence in the base of tongue and floor of mouth was histologically confirmed.

Results

Because of the local symptoms, we offered the patient Ir-192-HDR brachytherapy with palliative intent. Under general anaesthesia, eight needles were implanted into the palpable tumour. On the basis of a pretreatment MRI, a single dose of 5 Gy encompassing the palpable tumour was given to a total dose of 15 Gy. The patient remains free from local symptoms at 8 month after brachytherapy.

Conclusion

HDR-Ir brachytherapy is an effective method for the treatment of local recurrences of an adenoid cystic carcinoma, even after preradiotherapy. Excellent palliative effects can be achieved without increased toxicity after previous radiotherapy.     

Therapie der Rezidiv- und Fernmetastasen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs

In many cases squamous cell carcinoma of the head and neck is already in an advanced stage when initially diagnosed. Despite definitive treatment, loco-regional recurrences and metastases are common and patients ultimately require systemic treatment. Epidermal growth factor receptor (EGFR) inhibitors have proven to significantly prolong survival and have therefore become the first line treatment in recurrent and metastatic squamous cell carcinoma of the head and neck in addition to platinum and 5-FU treatment. Good results have also been reported for EGFR inhibitors in cases where platinum-based treatment has failed. Further strategies, such as salvage surgery, platinum-based chemotherapy, targeted therapy, chemoradiation and reirradiation are currently under investigation to reduce toxicity and improve survival and health-related quality of life.     

Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundh?hlenkarzinome

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.     

Treatment of neck nodes after induction chemotherapy in patients with primary advanced tumours

Responsiveness of neck nodes to induction chemotherapy often differs from that of the primary tumour. We have conducted a retrospective study to evaluate the results of treating the neck in a cohort of 350 patients with locally advanced (T3–4) head and neck carcinomas treated with radiation therapy at the primary location of the tumour after induction chemotherapy. One hundred and thirty-nine patients (40%) did not have neck nodes on diagnosis (N0). The treatment of the neck included surgery in 65 patients. Neck dissections were carried out before radiotherapy in 37 patients and after radiotherapy in 28 patients. The frequency of neck treatment failure was 24%. There was a tendency to better neck control when treatment included neck dissection, independently of the neck stage or response to chemotherapy. This tendency was statistically significant in patients with an advanced regional tumour (N2–3) who did not achieve a complete regional response after chemotherapy. In a multivariate analysis the variables that were related to the regional failure were the relapse of the tumour at the primary site, the neck stage (N), the type of treatment used in the neck, and the grade of regional response after induction chemotherapy. Our results lead us to suggest that after induction chemotherapy neck surgery is advisable in all cases with advanced regional disease (N2–3), independently of the grade of response achieved after induction chemotherapy, and is also advisable in N1 patients in whom induction chemotherapy does not achieve a complete response. Received: 27 December 1999 / Accepted: 6 June 2000     

Ploidy in head and neck cancer: a review and meta-analysis

A review is presented of all the series reporting ploidy in squamous cell carcinoma of the head and neck. A total of 1984 patients have been reported in 26 different series: 37% of tumours were diploid, 54% aneuploid and 11 % polyploid. Thus 64% of tumours were non-diploid. The mean age of patients with diploid and aneuploid tumours was very similar (60.9 and 60.3 years respectively) but patients with polyploid tumours had a mean age of 54 years. Although men were 5% more likely than women to have a non-diploid tumour the difference was not significant. Data relating ploidy to performance status are not available. The incidence of non-diploid tumours did not vary between sites, nor with stage grouping, but non-diploid tumours increased in frequency with diminishing degree of differentiation and with the presence of lymph node metastases. There was no difference in ploidy pattern between the primary tumour and node metastases. In the entire series the survival was better for diploid tumours than for non-diploid tumours. Subgroup analysis showed this effect to be due to mouth cancers, whereas ploidy did not affect the outcome in laryngeal cancer. Also, recurrence was more likely in non-diploid tumours. Patients with end-stage cancer treated by chemotherapy had a better survival if their tumour was non-diploid. Ploidy did not influence response to radiotherapy. When a tumour recurred after radiotherapy it was more likely to be diploid than a previously treated tumour. Non-diploid tumours had a greater S-phase fraction and a greater growth fraction than diploid tumours.     

The chemotherapy of head and neck cancer

Chemotherapy in head and neck cancer can be given in metastatic disease at presentation, in locally far advanced disease not amendable for curative treatment with surgery and/or radiotherapy, in the neo-adjuvant setting, in recurrent disease after previous surgery and radiotherapy and either concurrent or alternating with radiotherapy. Most data are gathered in the recurrent and locally far advanced disease setting. Combination therapy (with agents such as cisplatinum, 5-FU and methotrexate) have shown some improvements in response rate, however no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck has been observed. In the neo-adjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New compounds and approaches are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease are the taxanes. With monotherapy docetaxel, response rates of 23%-42% are seen, and, when used in combination with cisplatinum and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neo-adjuvant therapy with cisplatinum and 5-FU is now underway.     

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.     

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     

Concurrent chemotherapy and "concomitant boost" radiotherapy for unresectable head and neck cancer

PURPOSE: For patients with advanced head and neck cancer, various combined chemoradiotherapy regimens have been used to improve local control. This study was carried out to assess the outcome of concomitant chemotherapy with a "concomitant boost" radiotherapy in the treatment of advanced unresectable head and neck cancer patients. MATERIALS AND METHODS: Forty-eight patients were treated with combined chemoradiotherapy between the years of 1990 and 1995. Cisplatinum (100 mg/m2) was given intravenously during week 1 and week 5. A "concomitant boost" external beam radiotherapy approach was used with twice-daily treatment delivered during the last 2 weeks. A total of 70 Gy was delivered over 6 weeks. Median follow-up was 23.5 months (2-79 months). RESULTS: Thirty-one (65%) and 17 (35%) patients achieved complete and partial response, respectively. Median survival in complete responders has not been reached. Overall survival at 2 years, 3 years, and 5 years were 58.7%, 52.8%, and 42.4%, respectively. Median overall survival was 38.8 months. Acute confluent mucositis (Radiation Therapy Oncology [RTOG] grade 3) developed in 50% of patients, but there was no severe long-term treatment-related toxicity. CONCLUSION: This combined chemoradiotherapy approach is safe and efficacious for advanced unresectable head and neck cancer. Treatment-related toxicity was acceptable with 50% of patients developing acute confluent mucositis. There was no severe long-term treatment-related toxicity.     

Assessment of oropharyngeal cancer

The records of 87 patients with squamous cell carcinoma of the oropharynx, treated between 1971 and 1998 at Kitasato University Hospital, were reviewed with the aim of investigating further directions for oropharyngeal cancer treatment. The patients were divided into four major treatment groups: a radiotherapy group; an operation group; a simultaneous chemoradiotherapy group; and a combination treatment group. The 5-year cumulative survival rates for Stages I-IV were 75%, 78%, 68% and 41%, respectively. None of the T4 cases survived for > 5 years. The survival rates of patients with anterior and posterior wall cancers were higher than those with lateral and superior wall cancers. All patients in the operation group survived for 5 years. The survival rates for the combination treatment, radiotherapy and chemoradiotherapy groups were 80%, 57% and 52%, respectively. The 5-year cumulative local control rates for T2-T4 tumors were 61%, 58% and 0%, respectively. The combination therapy (80%) and chemoradiotherapy (66%) groups had significantly higher local control rates than the radiation group (33%). The 5-year cumulative regional control rate according to N classification was approximately 80%, except for N2 lymph nodes, for which only 60% of patients were free of regional recurrences. Approximately 15% of patients with oropharyngeal cancer had either distant metastases or double cancer. We conclude from this review that simultaneous chemoradiotherapy is a good initial therapy for Stages Tl-T3 oropharyngeal cancer. However, for T4 tumors, further combinations of both chemoradiotherapy and surgery and the development of new anticancer drugs for use in chemoradiotherapy, immunotherapy or gene therapy may be needed.     

Assessment of Oropharyngeal Cancer

The records of 87 patients with squamous cell carcinoma of the oropharynx, treated between 1971 and 1998 at Kitasato University Hospital, were reviewed with the aim of investigating further directions for oropharyngeal cancer treatment. The patients were divided into four major treatment groups: a radiotherapy group; an operation group; a simultaneous chemoradiotherapy group; and a combination treatment group. The 5-year cumulative survival rates for Stages I-IV were 75%, 78%, 68% and 41%, respectively. None of the T4 cases survived for >5 years. The survival rates of patients with anterior and posterior wall cancers were higher than those with lateral and superior wall cancers. All patients in the operation group survived for 5 years. The survival rates for the combination treatment, radiotherapy and chemoradiotherapy groups were 80%, 57% and 52%, respectively. The 5-year cumulative local control rates for T2-T4 tumors were 61%, 58% and 0%, respectively. The combination therapy (80%) and chemoradiotherapy (66%) groups had significantly higher local control rates than the radiation group (33%). The 5-year cumulative regional control rate according to N classification was 80%, except for N2 lymph nodes, for which only 60% of patients were free of regional recurrences. Approximately 15% of patients with oropharyngeal cancer had either distant metastases or double cancer. We conclude from this review that simultaneous chemoradiotherapy is a good initial therapy for Stages T1-T3 oropharyngeal cancer. However, for T4 tumors, further combinations of both chemoradiotherapy and surgery and the development of new anticancer drugs for use in chemoradiotherapy, immunotherapy or gene therapy may be needed.     

Radiotherapy of carcinoma of the oropharynx. Results of 10 years' experience at the University Hospital Center, Tours

In our centre, the vast majority of patients with oropharyngeal tumours are treated by irradiation. Over a period of 10 years, between 1976 and 1986 we treated 305 patients with squamous carcinomas of the oropharynx. The mean age was 58.2 years. There were 24 women and 281 men. 59% of the patients had advanced tumours, classified as T3 or T4, 54% of the patients showed the presence of adenopathy at the first examination. All patients received radiation therapy. 69 patients had surgical treatment of the tumour or glands. 21 patients had implant therapy (most often combined with transcutaneous irradiation). 165 patients had induction chemotherapy. Local tumour control was obtained in 124 patients (41%), i.e. 82, 56, 31 and 4% for T1, T2, T3 and T4 respectively. The 5 years survival rate of the overall population was 28%. The principle causes of failure were local progression for T3 and T4 tumours and metastases and second cancers in patients with T1 or T2 tumours. The prognostic factors were gland involvement and general health. The site of the tumour, sex and histological type were not prognostic factors. Induction chemotherapy did not improve the results of treatment.     

Tumor cell death as reflected by the SCC-antigen level?

The serum levels of squamous cell carcinoma (SCC) associated antigen are related to the course of the therapy in 91 cases of advanced head and neck cancers. Without statistical significance the findings may lead to the following statements: 1. Serum levels below 2 ng/ml before treatment are not related to tumour growth. 2. Serum levels above 2 ng/ml before treatment are likely to be regarded as tumour-associated. 3. High and low level curves of not operated patients show a quantitatively different reaction to the course of a combined simultaneous radiochemotherapy. 4. Initially increasing serum levels under combined therapy may be interpreted as related to cell death or result of a production or proliferation stimulus. 5. High serum levels and low serum levels in tumour patients might be regarded as an expression of different biological activities in the tumour. 6. The comparison of the survival rates of high level tumours to low level tumours raises the question as to whether this different biological activity might be related to clinical malignancy.     

Comparative Evaluation of Chemoimmunoradiotherapy and Chemoradiotherapy in the Management of Advanced Head and Neck Cancer

50 patients of advanced squamous cell carcinoma of the head and neck were randomised cither to receive chemotherapy followed by radiation therapy or chemoimmunotherapy followed by radiotherapy. In the chemoimmunotherapy arm, the patients received recombinant interferon alpha 2b 3 M.U. subcutaneously, thrice a week on alterante days for 5 weeks from Day 1, Cisplatinum 70 mg/ m² on Day 1 and 21, and 5 — flurouracil 1000mg/m² on Day 1, 2, 3 and Day 21, 22, 23, followed by from Dav 36, radiotherapy'by Co bait 60 to a tumour dose of 65 Gy in 30 # over 6 weeks. In the control arm, patiens received Cisplatitnum 70 mg/ m² on Day 1 and Day 21, 5 flurouracil 1000 mg/ m² on Dav 1, 2, 3 and Day 21, 22, 23 followed by radiotherapy by Cobalt 60 to a tumour dose of 65 Gy in 30 # over 6 weeks from Day 36. Only Grade II and III toxicity was observed in the two arms which were manageable Patients treated with chemoimmunotherapy followed by radiotherapy showed 60% complete response, 20% partial response and 12% no change/ progressive disease; while the patients on the control arm treated with chemotherapy and radiotherapy showed 12% complete response 44% Partial response and 32% no change“ progressive disease. This trial concludes that chemoimmunotherapy followed by radiotherapy is an excellent alternative therapeutic strategy for the management of advanced head and neck cancers with manageable toxicity.     

局部晚期鼻咽癌新辅助化疗联合同步放化疗

鼻咽癌是我国南部地区最常见恶性肿瘤之一,大部分患者被发现时已处于局部晚期.鼻咽癌对放、化疗比较敏感,过去认为同步放化疗方案是鼻咽癌的标准治疗方式;研究显示新辅助化疗联合同步放化疗对局部晚期鼻咽癌患者的治疗效果更佳.然而调强放疗与传统放疗技术相比,在保证原有治疗效果基础上可进一步降低患者的毒副反应.本文比较在传统放疗与调强放疗技术两种情况下,同步放化疗与同步放化疗联合新辅助化疗的两种方案对局部晚期鼻咽癌患者治疗效果做一综述.     

Radioiodine and radiotherapy in the management of thyroid cancers.

Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients.     

Squamous cell carcinoma of the oral cavity. A review of 176 cases with application of malignancy grading and DNA measurements

This retrospective study comprised 176 patients with squamous cell carcinoma of the oral cavity treated at The Link?ping University Hospital over a 19-year period. Clinical parameters, microscopic malignancy grading (according to Jakobsson et al. and Glanz and Eichhorn), DNA cytofluorometry, analysis of therapeutic modalities and statistics regarding survival and prognosis are reported. The mean age was 70 years with a male: female ratio of 1.3:1 One hundred and four patients had T1 or T2 tumours and 109 an N0 neck. Cervical lymph node metastases were more frequent in patients with larger tumours (T3 + T4) than in those with smaller (T1 + T2) (P less than 0.01), in tumours with a high malignancy grading compared to those with a low (P less than 0.05) and in DNA non-diploid tumours compared to diploid ones (P less than 0.001). The aneuploid tumours responded better to preoperative radiotherapy than did diploid (P less than 0.01) or polyploid (P less than 0.05) tumours. Eighty-nine per cent of the recurrences occurred within 1 year of initial therapy. Secondary treatment was successful in 15 of 37 (41%) patients in whom the tumour recurred either at the primary site or in regional lymph nodes, but only in 1 of 8 (12%) with recurrences in both locations. Surgery alone or combined with radiotherapy resulted in equivalent survival rates for tumours in stages I and II. In advanced stages combined radiotherapy and surgery gave better survival figures than either modality alone (P less than 0.01; Kaplan-Meier). The presence of lymph node metastases (P less than 0.001), tumour size (P less than 0.01) and tumour ploidy (P less than 0.005) were the only clinical and histological parameters that significantly influenced survival (Cox regression analysis). Twenty-four patients developed a secondary primary malignancy; 21 of these were located in the aerodigestive tract.     

Radiotherapy followed by neck dissection for small head and neck cancers with advanced cervical metastases

Patients with small or occult primary carcinomas of the head and neck with advanced cervical metastases present a difficult problem for the otolaryngologist. A retrospective review was performed of patients who presented to UCLA Medical Center between January 1986 and June 1996 with small or occult primary tumors of the head and neck with advanced cervical metastases. The treatment algorithm consisted of initial radiotherapy to the primary site and the neck, followed in 6 to 8 weeks with endoscopy and biopsy of the primary tumor site. As long as the repeat biopsy of the primary tumor site was negative by frozen section, an immediate neck dissection was performed, even if no residual neck disease was present. Almost 40% of patients with no clinical evidence of neck disease following radiotherapy had evidence of metastatic cancer on histopathologic examination. While some would consider a watchful waiting policy when there is no clinically detectable neck disease following radiotherapy, we believe it is preferable to perform immediate surgery in such patients, in light of the high incidence of microscopic metastatic disease.