西妥昔单抗联合术后同步放化疗治疗晚期复发性头颈癌的初步观察

目的 评价西妥昔单抗联合术后同步放化疗治疗晚期复发性喉癌及下咽癌患者的近期疗效和不良反应。方法 晚期复发性头颈癌患者6例,其中喉复发癌2例,下咽复发癌1例,下咽癌伴肺转移1例,气管造瘘口复发癌2例。分别予以手术治疗后3周,西妥昔单抗与同步放化疗,用法：西妥昔单抗第1周初始剂量为400mg/m2,以后每周维持剂量为250mg/m2,共3周。所有患者均采用直线加速器放疗,常规分割调强放疗,总剂量60Gy,6周完成。在放疗的同时给予化疗,方案是：DDP 80mg/m2/d1,5 Fu 800mg/m2,120h持续化疗泵静滴。化疗1次/3周,共3次。结果 所有患者均顺利完成治疗计划。西妥昔单抗主要不良反应为皮疹、口腔炎、疲乏等。中位随访10个月,病例均存活且肿瘤无进展,未发生远处转移。结论 西妥昔单抗联合术后同步放化疗治疗晚期复发性头颈癌安全有效,治疗计划顺利进行,尚需进行进一步临床试验研究。     

Clinical outcomes of platinum-based chemotherapy plus cetuximab for recurrent or metastatic squamous cell carcinoma of the head and neck: comparison between platinum-sensitive and platinum-resistant patients

Background: Combination therapy consisting of a platinum agent, 5-fluorouracil and cetuximab (EXTREME regimen) is recommended for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, it is advisable to use platinum-free regimens as first-line therapy in patients resistant to platinum agents. There has been no report comparing EXTREME regimen outcomes between platinum-resistant and platinum-sensitive patients.

Objectives: We conducted this study to examine the outcomes of the EXTREME regimen as first-line therapy in patients with R/M-SCCHN and a history of platinum agent use and assess whether the EXTREME regimen outcomes differ between platinum-resistant and platinum-sensitive patients.

Materials and methods: The study included 32 patients with R/M-SCCHN who received the EXTREME regimen as first-line therapy. Patients with recurrence or metastasis within 6 months after cisplatin administration were considered platinum-resistant and those with no recurrence or metastasis within 6 months were considered platinum-sensitive.

Results: 17 patients were platinum-resistant and 15 patients were platinum-sensitive. The median survival durations were 10.6 and 19.9 months in the platinum-resistant and platinum-sensitive patients, respectively, and the prognosis was significantly better in the platinum-sensitive patients (p?=?.02).

Conclusions: Our findings suggest that the EXTREME regimen is useful as first-line therapy for R/M-SCCHN in platinum-sensitive patients.     

Surgical treatment for pulmonary metastases of squamous cell carcinoma of the head and neck

Purpose: As locoregional control of head and neck cancer has improved, distant metastases have become increasingly common problems.Patients and Methods: To determine the role of surgical treatment, we reviewed 32 patients with squamous cell carcinoma (SCC) of the head and neck who underwent thoracotomy for pulmonary metastases.Results: The overall 5-year survival rate was 32%. The 5-year survival rate of the patients with SCC of the oral cavity was significantly poorer than that of the patients with other primary site (15.4% v 45.2%; P = .01). In the patients with single nodule, extent of the tumor was a significant prognostic factor (P = .007). Mediastinal lymph node involvement (P = .004) and pleural invasion (P = .04) also correlated with survival.Conclusion: TNM classification of the primary tumor did not have an impact on survival in this study. Further studies of a large series should be performed to determine the indications and modalities of the surgical treatment for pulmonary metastases of the SCC of head and neck.     

Outcome of chemotherapy following nivolumab treatment for recurrent and/or metastatic head and neck squamous cell carcinoma

ObjectiveAlthough nivolumab treatment is effective in extending the overall survival (OS) in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), only a few patients benefit from this treatment. Recent studies have reported that chemotherapy and cetuximab might be effective for R/M HNSCC after nivolumab treatment. In the present study, we aimed to elucidate the effectiveness of chemotherapy after nivolumab treatment in patients with R/M HNSCC.MethodsThis retrospective study included 10 patients with R/M HNSCC who were mainly treated with paclitaxel plus cetuximab (7/10, 70%) or S-1 (3/10, 30%) following nivolumab treatment. Chemotherapy was administered as a second-line or higher palliative treatment. The performance status of all patients ranged from 0 to 2. The progression-free survival (PFS) was analyzed using the Kaplan–Meier method.ResultsThe response rate (RR), clinical benefit rate, and median PFS were 60%, 90%, and 5.4 months, respectively. Regarding adverse effects, Grade 3 neutropenia and hypomagnesemia due to salvage chemotherapy administered after immunotherapy were observed in one patient. The treatment significantly increased the RR compared to that achieved with other palliative chemotherapies reported so far.ConclusionA higher RR and clinical benefit rate were observed for our strategy than for any first-line regimen, suggesting that our strategy might improve the PFS. Palliative chemotherapy with/without cetuximab after nivolumab treatment might be useful in patients with R/M HNSCC. Although the results of this retrospective study are limited, this strategy can be a good treatment option for patients with R/M HNSCC because of its strong clinical benefits and acceptable toxicity.     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.     

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.     

Merkel cell carcinoma of the head and neck associated with Bowen's disease

Summary The Merkel cell carcinoma occurs primarily in the skin of the head and neck, and develops in the dermis with a trabecular growth pattern. Immunohistochemistry reveals positive staining for neuron-specific enolase, neurofilaments, cytokeratin and chromogranin A. Electron microscopically, the tumor cells contain dense-core granules, spinous cytoplasmic processes, desmosomes, zonulae adherentes and paranuclear filament aggregates besides frequent mitoses, focal necroses and lymphocyte and plasma cell infiltrates. The Merkel cell carcinoma is often co-existent with other malignancies such as squamous cell carcinoma or, as in the present study, with Bowen's disease. The definite diagnosis of the Merkel cell carcinoma can be effected only by electron microscopic examination of the tumor.Presented in part at the 62nd Annual Meeting of the German Society for Otorhinolaryngology, Head and Neck Surgery, May 14, 1991, Aachen, FRGDedicated to Prof. K. Burian on the occasion of his 70th birthday     

Papillary squamous cell carcinoma of the head and neck: a clinicopathologic series

Purpose

Papillary squamous cell carcinoma (PSCC) is a rare malignancy that has been associated with human papillomavirus. We present all cases of this disease at a single academic teaching hospital over the last 30 years.

Materials and Methods

A retrospective chart review was performed for all patients with a diagnosis of PSCC. Of 65 patients identified, 52 were included after meeting established diagnostic criteria. Chart reviews were performed for patient demographics, overall survival, and disease-free survival.

Results

Mean age at diagnosis was 65 years, with a male to female ratio of 2.3:1. The majority of lesions (n = 34, 65.4%) arose in areas commonly affected by benign squamous papillomas, with the laryngopharynx the most commonly affected (n = 19, 36.5%), followed by the oral cavity (n = 18, 34.6%), sinonasal tract (n = 8, 15.4%), and oropharynx (n = 7, 13.5%). Two- and 5-year disease-free survival rate was 68% and 46%, respectively. Overall survival rate was 90% and 72% at 2 and 5 years, respectively.

Conclusions

Papillary squamous cell carcinoma of the head and neck is a distinct variant of conventional squamous cell carcinoma with a good prognosis despite high locoregional recurrence rates. Histology and subsite localization corroborate existing evidence that human papillomavirus may be involved.     

Lymph node ratio as a prognostic factor for survival in patients with head and neck squamous cell carcinoma

Objective

The purpose of this study is to validate the concept of lymph node ratio (LNR) in head and neck squamous cell carcinoma (HNSCC).

A murine model for the immunotherapy of head and neck squamous cell carcinoma

A murine model for the immunotherapy of head and neck cancer was established. The AT-84 tumor, a spontaneously arising oral squamous cell tumor of C3H mice, was evaluated for susceptibility to lymphokine-activated killer (LAK) cells. In vitro chromium-release assays demonstrated that AT-84 is sensitive to LAK-cell-mediated killing. Furthermore, in vivo experiments employing a lung metastasis model demonstrated a 50% reduction in the number of metastases in LAK-cell-treated mice as compared with untreated controls (P₂=.001). These experiments showed that AT-84 is an appropriate model for the immunotherapy of head and neck cancer. This model should be invaluable for further study of the mechanisms involved in immune-mediated therapy of head and neck cancer.     

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.     

An in vivo model for squamous cell carcinoma of the head and neck

In recent years, the successful grafting of human tumors into immune deprived animals has spurred the hopes of developing a reliable in vivo model for evaluation of human cancer. The nude mouse has created new perspectives in many different areas of cancer research, and has proved to be the most useful recipient of any animal system for tumor heterotransplantation. This study determined which of several squamous cell carcinoma (SCC) cell lines would reproducibly grow as heterotransplants in nude mice, and allowed an opportunity to determine whether characteristics of the tumor changed as a result of propagation in tissue culture. Sixteen (76%) of the 21 SCC lines heterotransplanted in nude mice remained as viable tumor nodules. Nine (43%) of these lines reproducibly produced progressively enlarging tumor masses. Five (24%) SCC lines failed to grow as heterotransplants. The average lag phase between implantation and the beginning of growth for all SCC lines tested was approximately 7 weeks and emphasizes the need for prolonged observation of nude mice following SCC heterotransplantation. The rate and pattern of growth of SCC in nude mice appears to be related specifically to the tumorigenic factors of a given cell line. The concurrent presence of other SCC or non-SCC tumors in a given mouse do not appear to influence the growth of a specific cell line. In addition, specific host factors that might vary from one mouse to another did not alter the growth patterns of SCC. Histological examination of the SCC lines successfully heterotransplanted in nude mice showed similar histological appearances to the original tumor in the human host.     

Selective neck dissection for the treatment of neck metastasis from squamous cell carcinoma of the head and neck

OBJECTIVE: Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. STUDY DESIGN: A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. METHODS: A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20-85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1-64 mo). Twenty-six patients had clinically negative (cNo) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. RESULTS: Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patientswere surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). CONCLUSIONS: With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.     

Prostaglandins in squamous cell carcinoma of the head and neck: a preliminary study

It has already been demonstrated in human and animal systems that PGE2 is a suppressor signal for many immune functions. These include T-lymphocyte blastogenesis, natural killer cell activity, and cytolytic T-lymphocyte activity. These functions are important for destruction of tumor cells. Conceivably, suppression of these functions by excessive PGE2 restricts tumor cell kill, and reversal of suppression by an inhibitor of prostaglandin synthesis such as indomethacin could increase tumor cell kill. The purpose of this study was to determine the kind of prostaglandins (PGs) produced by tissues with squamous cell carcinoma of head and neck and to measure the concentrations of PGE2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 in the tumor tissue and in the corresponding control tissue. Tumor and normal control tissues at the margin of the resection were obtained from surgical specimens. The production of PGs was determined by incubation of tissue homogenates with 14C-arachidonic acid, by thin layer chromatography, autoradiography, and scintillation counting. Concentrations of PGs were measured by radioimmunoassay. Tumor tissues produced PGD2, E2, TxB2, F2 alpha, and 6-keto-F1 alpha, and 15-, 12-, and 5-monohydroxyeicosatetraenoic acid (HETE). Concentrations of PGE2 were four times higher in the tumor tissues compared to those in control tissues. There was no difference between the levels of TxB2 and 6-keto-PGF1 alpha in the tumor tissues and those in control tissues. The results of this study will serve as basic information necessary for the potential use of inhibitors of PG-synthesis in the treatment of head and neck carcinoma.