Radiotherapy for sinonasal undifferentiated carcinoma

Purpose

To evaluate the long-term effectiveness of radiotherapy (RT) in the treatment of sinonasal undifferentiated carcinoma (SNUC).

Materials and methods

The medical records of 23 patients treated with definitive or postoperative RT between 1992 and 2010 at the University of Florida were retrospectively reviewed. Fifteen patients (65%) received primary surgery and postoperative RT. Radiation doses ranged from 59.0 to 74.8 Gy (median, 70.2 Gy). The median follow-up time for all patients was 3.0 years (range, 0.9–19.9), and for living patients was 7.7 years (range, 2.5–19.9).

Results

The actuarial 5-year survival outcomes were as follows: progression-free survival, 42%; cause-specific survival, 43%; and overall survival, 32%. Actuarial 5-year disease control rates were as follows: local control (infield or marginal), 74%; local-regional control (excluding leptomeningeal spread), 58%, regional control 78%, freedom from leptomeningeal recurrence, 72%, and distant metastasis-free survival, 73%. Five of the 8 (62.5%) patients treated with definitive RT died with disease, and 6 of the 15 patients (40%) treated with primary surgery and postoperative RT died with disease. Three patients (13%) experienced severe complications including unilateral eye removal, osteoradionecrosis of the maxilla requiring hyperbaric oxygen and surgery, and brain necrosis. One patient died due to an infected bone graft and brain abscess.

Conclusions

A multimodal approach is best when treating SNUC patients. The prognosis for patients treated with definitive RT ± chemotherapy is less promising than for those who receive surgery and postoperative RT ± chemotherapy. Severe complications occur in about 17% of patients due to the high dose of RT alone or combined with surgery required for acceptable disease control.     

An alternative therapeutic procedure for sinonasal undifferentiated carcinoma

We describe two cases of sinonasal undifferentiated carcinoma, a rare and highly aggressive neoplasm of the paranasal sinuses. Case 1 had first been diagnosed as esthesioneuroblastoma, and intra-arterial and systemic chemotherapy and radiotherapy were performed. The tumor became smaller but did not disappear, and the patient died 2 months later. Case 2 received systemic chemotherapy and chemoradiotherapy, with daily venous administration of cisplatin during radiotherapy. The tumor became much smaller but also remained, and the patient died a month later. Although the therapy failed, chemoradiotherapy has some possibility of controlling the disease. Received: 15 February 2001 / Accepted: 10 April 2001     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。     

Minimally invasive endoscopic resection of sinonasal undifferentiated carcinoma

Purpose

The purpose of the study was to review a single-institution experience with endoscopic resection of sinonasal undifferentiated carcinoma (SNUC).

Materials and Methods

Thirteen patients underwent treatment of SNUC between January 2002 and July 2009. Retrospective data were collected including demographics, tumor characteristics, surgical strategy, adjuvant therapies, local and regional recurrence, distant metastasis, overall survival, and disease-free survival.

Results

The mean age was 51.8 years. The most common tumor stage at presentation was T4 (92%). Seven patients (53%) were treated with minimally invasive endoscopic resection (MIER) with negative intraoperative margins. Endoscopic anterior skull base resection was performed in 5 patients, and endoscopic-assisted bifrontal craniotomy was performed in 1 patient to clear the superior tumor margin. Six patients received pre- or postoperative chemoradiation. One patient underwent palliative chemoradiation, and one patient underwent open craniofacial resection. In the MIER group, simultaneous local and regional recurrence was observed in 1 patient (14%) after 30 months. Distant metastases were observed in 2 other patients (28%) without local or regional recurrence. All 3 patients with recurrences died of their disease. The remaining 4 patients were clinically, endoscopically, and radiographically free of disease, resulting in overall and disease-free survival rates of 57% with mean follow-up of 32.3 months.

Conclusions

These preliminary data suggest a potential role for MIER in the comprehensive management algorithm of SNUC in appropriately selected patients. Patient outcomes including local and regional recurrence, distant metastases, and overall and disease-free survival were comparable to a treatment strategy using traditional craniofacial resection.

Level of evidence

2b.     

Postoperative radiation therapy for squamous cell carcinoma of the head and neck

PURPOSE: To discuss the role of postoperative radiation therapy (RT) for patients with squamous cell carcinoma of the head and neck. RESULTS: Patients with adverse pathologic features have a high likelihood of local-regional recurrence and a decreased probability of survival after surgery alone. Postoperative RT reduces the risk of local-regional failure and probably improves survival. Patients who are at high risk for recurrence after surgery benefit from more aggressive dose-fractionation schedules that may include altered fractionation to decrease the overall time from surgery to the completion of RT. Adjuvant chemotherapy also appears to improve the probability of cure in high risk patients. CONCLUSION: Patients who have a high likelihood of local-regional recurrence after surgery have improved disease control and survival after postoperative RT.     

Work-up and treatment planning for head and neck cancer. A multi-modality approach

The work-up of any patient with cancer in the head and neck area reveals that each is unique. Treatment planning must respect this. A "team" that embodies the attributes of such a group is necessary to uncover the multitude of facts, to formulate a plan of management, and to carry out treatment successfully.     

Radiolabeled antibody therapy for squamous cell carcinoma of the head and neck.

Immunohistochemical staining for ferritin was performed on 11 human head and neck squamous cell carcinomas transplanted in nude mouse xenografts. Seven tumors were found to be positive. Using ferritin as a tumor antigen target, escalating doses of yttrium-90-labeled antiferritin antibodies were injected intravascularly into nude mice that were transplanted with a ferritin-positive human squamous cell carcinoma. Forty-five days after injection, the mean treated tumor size was 25.6% of control in the 100-microCi group, and 20.6% of control in the 200-microCi group. Ninety days after injection the mean tumor size was 27.5% that of control in the 100-microCi group and 31.7% in the 200-microCi group. Higher doses of radiation (300 and 400 microCi per mouse) caused death of most of the animals due to radiation toxicity. Presensitization of the animal, before antibody injection, with a bolus intraperitoneal injection of 7.5 mg of cisplatin per kilogram of body weight, resulted in further reduction in tumor size when compared with antibody alone or cisplatin alone. This study demonstrates that radioimmunotherapy with selected doses of yttrium-90-labeled antiferritin antibodies is effective against human head and neck squamous cell carcinoma xenografts in nude mice.     

Esthesioneuroblastoma and sinonasal undifferentiated carcinoma: impact of histological grading and clinical staging on survival and prognosis

OBJECTIVES: Hyams proposed a histological grading system for esthesioneuroblastoma in which grade I tumors have an excellent prognosis and grade IV tumors are uniformly fatal. The Hyams grading system predated advanced craniofacial techniques, extensive use of immunohistochemistry, and the recognition of sinonasal undifferentiated carcinoma (SNUC) as a distinct entity. Therefore we aimed to determine whether Hyams classification is useful in predicting outcome for esthesioneuroblastoma and SNUC. STUDY DESIGN: A retrospective review of cases from 1970 to 1999. METHODS: Twenty-six patients (12 with esthesioneuroblastoma and 14 with SNUC) were reviewed. The Kadish clinical stage was determined, and histopathological slides were reviewed and graded using the Hyams system. RESULTS: Kadish staging was available for 26 patients (2 patients with stage A tumors; 7 with stage B; and 17 with stage C). Of the 8 evaluable patients with Kadish stage A or B tumors, 6 remained disease free for more than 2 years compared with only 5 of the 17 Kadish stage C tumors. Slides were available for Hyams grading in 21 patients (2 patients with grade I tumors; 4 with grade II; 4 with grade III; and 11 with grade IV). Of the 6 patients with Hyams grade I or II tumors, 4 remained disease free for more than 2 years compared with only 4 of the 15 patients with Hyams grade III or IV tumors. Of note, three patients with Kadish stage C tumors (two with esthesioneuroblastoma, one with SNUC) and two patients with Hyams grade IV tumors (one with esthesioneuroblastoma and one with SNUC) survived for more than 5 years. CONCLUSIONS: Both the Hyams grading system and the Kadish staging system can be used as independent predictors of outcome. Although limited by small numbers, the results of this study demonstrate that patients with either advanced clinical stage or pathological grade of esthesioneuroblastoma or SNUC have poor prognosis, but that long-term survival is possible in these patients if aggressive treatment is used.     

Squamous cell carcinoma of the sinonasal cavity arising as a second primary in individuals with head and neck cancer

OBJECTIVES/HYPOTHESIS: Second primary tumors occur frequently in patients with head and neck carcinoma. This may be caused by generalized exposure to carcinogens resulting in "field cancerization" or to the individuals' generalized susceptibility to cancer. The paranasal sinuses are not commonly included in the sites considered at risk for this process. We therefore sought to assess the overall risk of contracting a primary cancer in this region after having a tumor elsewhere in the upper aerodigestive tract. STUDY DESIGN: Retrospective. METHODS: Two thousand four hundred seventy-five patients with squamous cell carcinoma of the upper aerodigestive tract were analyzed using a tumor registry at a tertiary care institution. RESULTS: Five (0.2%) patients were identified as having a second primary in the sinonasal tract. The average interval between the index and second primary tumors was 28.4 (range 8-60) months. All five patients presented with symptoms typical of sinus inflammatory disease and had advanced sinus lesions at the time of diagnosis. These findings are typical of those with sinonasal carcinoma in that they present with nonspecific signs and symptoms and were diagnosed with locally advanced disease despite being in a surveillance program for their index cancer. CONCLUSIONS: Although uncommon, the data reported here support inclusion of the sinonasal tract in these surveillance programs. This could result in earlier detection and greater opportunity for curative intervention.     

Role for postoperative radiation therapy in adenoid cystic carcinoma of the head and neck

OBJECTIVE: Clarify the role for postoperative radiation for adenoid cystic carcinoma (ACC) of the head and neck as it relates to tumor site, T-stage, and surgical margin status. STUDY DESIGN: Retrospective cohort study at an academic tertiary care hospital. METHODS: A review of 129 patients with biopsy-proven ACC was performed. Previous treatment failures and nonoperative candidates were excluded, with 75 patients considered eligible for further study. Patients were grouped according to treatment modality and Kaplan-Meier estimates of overall survival, locoregional control, and distant control were compared using log-rank tests. Patients were also stratified according to tumor site, T-stage, and surgical margin status, and pair-wise comparisons of treatment outcome within each group were performed using Wald tests from Cox proportional hazards models. RESULTS: Twenty-five patients were treated with surgery alone, and 50 were treated with surgery and postoperative radiation. There was no significant difference in outcome between treatment groups when correlated with tumor site (P =.89). However, postoperative radiation was associated with improved overall survival for advanced T-stage (T4) tumors (P =.019) and greater locoregional control for patients with microscopically positive margins (P =.018). There was no demonstrated benefit of postoperative radiation for patients with microscopically negative margins (P =.93). CONCLUSIONS: The findings of this study suggest that advanced T-stage and positive microscopic margins are important factors in determining the necessity for postoperative radiation therapy for ACC of the head and neck and that radiation therapy may not be necessary for patients with early T-stage tumors and negative surgical margins.     

Radiotherapy alone for clinical T4 skin carcinoma of the head and neck with surgery reserved for salvage

PURPOSE: To evaluate the outcomes of definitive radiotherapy in the treatment of clinical stage T4 cutaneous carcinomas of the head and neck. PATIENTS AND METHODS: Between October 1964 and September 1997, 85 patients with 88 biopsy-proven clinical AJCC stage T4 carcinomas of the skin of the head and neck received radiotherapy with curative intent. A total of 43 lesions were previously untreated, and 45 were recurrent after other treatment modalities. Histologic types of carcinoma included squamous cell (37 lesions), basal cell (41 lesions), and metatypical basal (basosquamous) cell (10 lesions). Minimum follow-up was 2 years. The product-limit method was used to determine the rates of disease control, severe late complications, and survival. Multivariate analyses included histology, previous treatment, involvement of bone or nerve, number of structures invaded, node stage, external beam dose, and overall treatment time. RESULTS: At 5 years, the rates of local control after radiotherapy and ultimate local control after salvage surgery were 53% and 90%, respectively. Local control rates were better for patients having previously untreated lesions (P =.05). Regional and ultimate regional control rates were 93% and 100%, respectively, and were better for previously untreated lesions (P <.01), basal cell histology or its metatypical variant (P =.04), and absence of bone invasion (P =.08). At 5 years, the risk of severe late complications was 17%, the risk of distant metastasis was 5%, and the overall absolute and cause-specific survival probabilities were 56% and 76%, respectively. CONCLUSION: Radiotherapy alone results in a relatively high probability of cure for selected patients with T4 skin cancers.     

Basosquamous carcinoma of the head and neck

Clinical experience with two cases of basosquamous are described. Wide surgical excision is the preferred method of treatment. In some cases, however, radiation therapy or chemotherapy may be useful treatment adjuncts. Unfortunately, prognosis is poor.     

Chronic pain therapy for patients with head and neck tumors

Patients with tumors of the head and neck region commonly suffer from chronic pain, which is often treated insufficiently. Pain management according to the WHO analgesic ladder can effectively reduce pain in most patients. For head and neck cancer, specific aspects of tumor localization and psychosocial factors must be taken into consideration.     

Photodynamic therapy in the treatment of squamous cell carcinoma of the head and neck

Photodynamic therapy is an experimental modality for tumor treatment based on the combined action of the tumor-localizing agent, ie, hematoporphyrin derivative, and red light. From 1985 through 1989, 26 patients were treated using hematoporphyrin-derived drugs and 630-nm light delivered by a tunable dye laser. All patients had biopsy-proved squamous cell carcinoma of the head and neck, and they had either failed the traditional treatment modalities or refused conventional therapies. Histological complete responses were achieved in 20 (77%) of 26 patients and partial responses in 5 (19%) of 26 patients for periods up to 48 months. Only minimal toxic reaction was noted in the group. As a guide to treatment planning for a patient group with large tumors, we used an optical dosimetry model based on tissue optics. The rate of complete responses to this treatment was 8 (73%) of 11. Our data indicate that photodynamic therapy is capable of inducing significant clinical and histological responses in the majority of those treated, and in some patients a prolonged response is produced. In certain select head and neck malignancies, photodynamic therapy has an important role as a treatment modality.     

白细胞介素-2基因联合放疗对小鼠头颈鳞癌治疗作用的研究

目的：观察白细胞介素-2（IL-2）基因联合放疗对小鼠头颈鳞癌的抗肿瘤作用。方法：将25只小鼠平分为5组。利用SCCⅦ细胞株在C3H/HeJ小鼠口底建立头颈鳞癌荷瘤动物模型,IL-2组和联合组在荷瘤部位直接注射IL-2基因;EP组和对照组分别注射无目的基因的空载体和PBS,次日联合组与放疗组给予2Gy直线加速器的局部肿瘤放疗。4d后重复IL-2基因治疗,观察肿瘤治疗前后大小变化;检测肿瘤组织中CD4^ ,CD8^ 的表达,IL-2的分泌水平及自然杀伤细胞（NK）和细胞毒T淋巴细胞（CTL）的活性。结果：联合组肿瘤生长明显受抑制,疗效显著优于IL-2组,放疗组,EP组和对照组,IL-2组中,小鼠IL-2分泌水平明显升高,脾细胞NK活性和CTL杀伤活性增强,肿瘤组织内可见大片坏死,并含有大量的CD4^ ,CD2^ 淋巴细胞浸润,结论：IL-2基因治疗可提高肿瘤局部和全身的抗肿瘤免疫应答。能加强放疗的抗肿瘤效果。