Simultaneous radio- and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital

Several randomized studies and meta-analyses have shown that simultaneous radio- and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 x 2 Gy) and chemotherapy [cisplatinum 100 mg/m(2) or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side-effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio- and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.     

Preoperative chemotherapy in advanced resectable head and neck cancer: final report of the Southwest Oncology Group

In 1980, the Southwest Oncology Group instituted a multi-institutional, prospective, randomized phase III trial to evaluate whether inductive chemotherapy improved survival in patients with advanced stage resectable squamous cell carcinoma of the head and neck. From a group of 158 eligible patients, 76 were randomized to conventional treatment (surgery and postoperative radiotherapy), and 82 were assigned to experimental treatment (induction chemotherapy, surgery, postoperative radiotherapy). Median follow-up for living patients was approximately 5 years. These analyses include chemotherapy responses and toxicities, surgical complications, radiotherapy toxicities, patient compliance, survival time, and patterns of treatment failure. Overall chemotherapy response was 0.70 (0.19 CR, 0.51 PR). The median survival time for conventional treatment was longer than the time for patients receiving preoperative chemotherapy, although the survival time differences were not statistically significant. This final analysis demonstrates no benefit in survival using preoperative chemotherapy for advanced stage, resectable head and neck squamous cell carcinoma.     

Adjuvant chemotherapy in stage III and IV squamous cell carcinoma of the head and neck

Initial combination drug regimen containing cisplatin in patients with stage III and IV head and neck cancer produced a high percentage of clinical response. This trial was initiated to assess the role of multimodality treatment (chemotherapy plus radiotherapy) versus chemotherapy alone. Ninety-six patients entered into this study; 80 patients were evaluable at time of analysis (Table I). Patients were randomized between chemotherapy and radiotherapy (group I) and chemotherapy alone (group II). The chemotherapy administered consisted of cisplatin, bleomycin and methotrexate and was given in 2 cycles over 35 days. Local radiotherapy followed. In group II 3 cycles of chemotherapy were given without radiotherapy. The overall tumour response after chemotherapy rose up to 75 per cent. After radiotherapy in group II the response rate sank to 59 per cent. In both regimes the remission duration was very short. Patients receiving only two cycles of chemotherapy do not have a statistically shorter survival than patients, who were treated by chemotherapy plus radiotherapy, or by a 3rd cycle of chemotherapy.     

Pretreatment with chemotherapy in patients with advanced head and neck cancer

Average survival for advanced head and neck cancer (AHNC) is 18 months. In an attempt to improve this we treated 29 AHNC patients between 1978-82 with two courses of chemotherapy. Chemotherapy consisted of cyclophosphamide, methotrexate, 5 fluorouracil and bleomycin; or bleomycin, cisplatinum and methotrexate. Chemotherapy was given prior to definitive therapy of radiotherapy or radiotherapy and surgery. All patients were stage 3 or 4. All patients were Eastern Co-operative Oncology Group status performance 0 or 1. Response to chemotherapy did not improve survival. Pretreatment with chemotherapy should be investigational until increased survival has been documented.     

Neoadjuvant chemotherapy in multiple synchronous head and neck and esophagus squamous cell carcinomas.

A consecutive series of 22 patients with multiple synchronous squamous cell carcinomas of the upper aerodigestive tract was retrospectively reviewed. These patients were treated initially with cis-platinum combination chemotherapy before definitive locoregional therapy (surgery and/or radiation therapy). Sixteen of 21 patients had simultaneous head and neck and esophageal primaries, 3 patients had multiple synchronous head and neck primaries, 2 patients had head and neck (HN) and a bronchial epidermoid cancer, and 1 patient had simultaneous esophageal and bronchial carcinomas of epidermoid lineage. Sixteen (77%) of the 21 patients responded to chemotherapy in all the tumor sites evaluated, and a clinically complete response was obtained in 6 (29%). After definitive locoregional treatment, the complete local control rate was 68%, with 34 complete responses for 50 primary tumor sites in 21 patients. Twelve patients were free of disease after locoregional treatment. Six patients are still alive 27 to 57 months after complementary definitive locoregional treatment and a minimum follow-up of 27 months. Median survival for the overall group is 17 months. The response to chemotherapy is remarkable, which may be due to the small tumoral volume present in many of the cases (T1 to T2). Nevertheless, the present report stresses the importance of an aggressive combined therapeutic approach in this difficult clinical situation.     

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.     

A comparison of combined modalities and single modality in the management of advanced head and neck tumors

Advanced head and neck cancer patients can be managed by single modality or combined modalities, Between 1976 and 1979, three treatment groups were retrospectively identified. One group received induction chemotherapy, surgery, and postoperative radiation therapy. The second group received chemotherapy followed by radiotherapy. The third group was treated during the same time period with radiation alone. These groups were matched with respect to age, site of primary tumor, nodal status, absence of metastatic disease, and no prior cancer treatment. The combined modality groups were initially treated with two doses of cis-platinum and a bleomycin infusion. Evaluation of tumor response was done 2 weeks following chemotherapy; 24 patients had surgery and postoperative radiation, 23 had radiotherapy without surgery and 24 patients were treated with radiotherapy alone. Median survival was 22 and 13 months respectively for the 2 combined modality groups and 4.7 months for the radiotherapy group. Disease-free survival was a projected value of 40 and 35 months for the combined modality groups and an actual 3 months for the radiotherapy group. Combined modality treatment with chemotherapy and surgery and/or radiotherapy offers a higher response rate and prolonged survival than radiotherapy alone.     

Concurrent cisplatin and radiotherapy in advanced head and neck cancer

Management of Head and Neck Cancers poses a challenge inspite of several advances because of poor success in terms of response rate, survival and reduced morbidity of the patients. In the present study 30 untreated histologically proven cases of head and neck cancers were subjected to weekly radiotherapy with adjuvant chemotherapy (cisplatin 30 mg/m² intravenously). This study group was compared with a group of 30 patients who were given only radiotherapy. Results have shown that combination of chemotherapy with radiotherapy gives a significantly better results in tumour as well as nodal response with minimal toxicities.     

Murine subrenal capsule assay: prediction of chemoresponsiveness in head and neck cancer

If chemotherapy is to be used with the greatest efficacy in head and neck cancer, a predictive test that will indicate tumor sensitivity or resistance in individual patients may be desirable. This report demonstrates that the in vivo murine subrenal capsule assay was an efficient, sensitive method for retrospectively predicting the clinical response of squamous cell carcinomas of the head and neck to chemotherapy. Twenty-five courses of chemotherapy in 22 patients were compared to responses in the in vivo assay. The assay correctly identified sensitivity to chemotherapy in 86% of clinically responding patients. The specificity of the assay was 78%. A 60% efficiency for predicting clinical response and a 93% efficiency for predicting clinical resistance were demonstrated. Eighty percent of the results were correctly classified. The murine subrenal capsule assay has potential in planning of chemotherapy for selected patients.     

Treatment of hypopharyngeal carcinoma: analysis of nationwide study in the Netherlands over a 10‐year period

Objective: To analyse different treatment strategies and treatment results of hypopharyngeal carcinoma in the Netherlands. Design: Retrospective study. Setting: Eight head and neck centres in the Netherlands. Participants: A total of 893 patients were treated between 1985 and 1994. Patients were mostly treated with radiotherapy alone, combined surgery and radiotherapy and surgery alone. Results: The 5‐year survival for the whole group was 26%. The 5‐year survival for patients treated with curative intention was 32% and treated with palliative intention was 5%. The 5‐year disease‐free survival after radiotherapy alone was 37%, after surgery alone 41% and after combined therapy 47%. The role of chemotherapy could not be investigated because of a small number of patients treated with chemotherapy in this period. Conclusion: Combined therapy with surgery and radiotherapy has a better survival for patients with a hypopharyngeal carcinoma in comparison with radiotherapy alone. The N‐stage is more important for the prognosis than the T‐stage.     

Phase II study with pirarubicin in pretreated progressive head-neck neoplasms]

Sixteen heavily pretreated patients (pts) (4 surgery + chemotherapie + radiotherapy; 4 chemotherapy + radiotherapy: 6 surgery + radiotherapy; 2 chemotherapy) and one previously untreated patient, who refused surgery and or radiotherapy, all with progressive disease, with advanced squamous cell carcinoma of the head and neck were included in a phase II study with pirarubicin 60 mg/m2 i.v. day 1 every 3-4 weeks (CT). All pts received at least one course of CT. 15 pts were evaluable for response, all 17 pts were evaluable for toxicity. Female (male ratio 1/16; mean age 56 (42-68) yrs, mean performance status 70% (50-70). Seventeen pts received a mean of 3 (1-8) courses, 2 pts had received only one course of CT. Response and toxicity were assessed according to WHO classification. Results after 1-8 courses of CT: 1 (7%) complete remission; 1 (7%) partial remission; 9 (60%) no change; 4 (26%) progressive disease. No toxicity of grade IV was observed. Mean duration of remission 16 weeks. Median survival time 7 (1-10) months. 9 pts died and 8 pts are alive; six of them had progressive disease.     

A comparison of radiotherapy or radiochemotherapy with symptomatic treatment alone in patients with advanced head and neck carcinomas

The choice of palliative treatment and the prognostic factors in unresectable head and neck cancer cases continue to be controversial. In the present study we compared the survival rates of untreated stage IV head and neck cancer patients with cases managed prospectively at A.C. Camargo Hospital for Cancer with neoadjuvant chemotherapy, concomitant chemotherapy or radiotherapy alone. Previous results had shown that while the type of treatment did not influence survival rates (P = 0.706), tumor response to treatment (whether complete, partial or none) significantly influenced survival (P = 0.00002). In the present study we compared the survival rates in the groups with untreated patients (who remained untreated until death) with the same demographic and clinical characteristics of patients receiving treatment. We found that there was a significant difference between the survival rates of the untreated group and those of the treated groups that was independent of the type of treatment performed (P < 0.00001) or the tumor response to treatment (P < 0.0001). Received: 19 October 1998 / Accepted: 15 April 1999     

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.     

The status of sequential chemo-/radiotherapy in inoperable head and neck cancers. Personal results and review of the literature

Between March 1986 and October 1987 75 patients with advanced cancer of the head and neck were treated with initial chemotherapy before surgery and/or radiotherapy. Chemotherapy consisted of three courses of cisplatin or carboplatin combined with 5-fluorouracil (5-FU). Three weeks after the last course of chemotherapy 34 patients with unresectable tumours received conventional fractionated radiotherapy (60-64 Gy). Of these 34 patients, 32 were evaluated for response and survival with a minimal follow-up of 3 years (22% stage III, 78% stage IV). As the response to cisplatin/5-FU and carboplatin/5-FU was similar (72% versus 64%), survival rates of both chemotherapeutic regimens are presented together. At the end of sequential chemo-radiotherapy 11 patients (34%) were clinically free of disease with an overall response rate of 69%. The survival after 3 years was 12.5% (4 patients) with a median of 15 months. Disease-free survival was 27% (3/11). These poor results confirm the results of other investigators. They indicate that induction chemotherapy does not improve the results of conventional radiotherapy in unresectable carcinomas of the head and neck, even when using highly effective platinum-containing regimens.     

头颈部横纹肌肉瘤8例报告

目的 :提高临床对头颈部横纹肌肉瘤 (RMS)的诊疗水平。方法 :报告经病理确诊的 8例头颈部 RMS的临床资料。 8例均经手术治疗 ,其中手术加放疗 5例 ,加化疗 1例。结果 :7例获随访 ,3例分别于术后 4个月、16个月、2年死亡 ,4例生存≥ 5年。结论 :对发生在耳鼻咽喉 -头颈部的无痛性或痛性肿块 ,应注意 RMS的可能。根据影像学检查、病理活检及免疫组化标志等确诊 ;采用手术加化疗或放疗 ,可以提高 RMS患者的生存率。     

Outcomes of patients with n3 neck nodes treated with chemoradiation

Objective: To evaluate the outcomes of patients with locally advanced head and neck squamous cell carcinoma with N3 neck nodes treated with definitive chemoradiation. Study Design: Retrospective review. Methods: Thirty‐two patients with nonmetastatic locally advanced head and neck squamous cell carcinoma and N3 neck disease treated with concurrent chemoradiation therapy were evaluated. Overall survival, disease‐ free survival, locoregional control, and distant control were recorded. Results: Median follow‐up for surviving patients was 25 (range, 3–93) months. Seventeen of 32 (53%) patients failed, 13 in distant sites only, 2 in the neck only, 1 in the neck and a distant site, and 1 in the neck and primary site. The absolute rates of locoregional control and distant control were 88% and 56%, respectively. Actuarial overall survival and disease‐free survival at 2 years were 51% and 29%, respectively. Conclusion: Patients with N3 neck disease treated with chemoradiation experience a very high rate of distant failure. Future studies investigating the role of additional systemic therapy in these patients are warranted.     

Induction chemotherapy by superselective intra-arterial high-dose carboplatin infusion for head and neck cancer

To evaluate the feasibility, maximum dose of drug tolerated, technical problems, systemic and local toxicity, response rate, overall and disease-free survival, we studied superselective intra-arterial infusion of high-dose carboplatin as part of a multimodality treatment for head and neck cancer. Forty patients with untreated stage II–IV head and neck squamous cell carcinomas received induction chemotherapy with high-dose carboplatin (three cycles at 2-week intervals using 300–350 mg/m² per cycle), delivered via superselective transfemoral angiography followed by radiotherapy or surgery plus radiotherapy. No technical complications occurred during or after the infusion. Systemic toxicity was minimal, and local toxicity was moderate. At the end of chemotherapy the overall complete and partial response rate was 90% (36/40) at the primary site and 64% (16/25) at the neck nodes. The median follow-up was 24.4 months (range 3–52). To date 21 patients are alive without disease, 2 are alive with disease, 13 have died of disease, and 4 have developed a metachronous lung tumor. There was a good correlation between the response to chemotherapy and disease-free survival. No statistically significant benefit in survival was observed with respect to other series of head and neck tumors treated with different protocols. However, discriminating between responding and nonresponding patients, this procedure can have a prognostic significance in planning integrated treatments for these types of tumors. Received: 14 January 1999 / Accepted: 2 July 1999     

Chemotherapy or chemotherapy and radiotherapy in advanced head and neck tumors. A prospective, randomized study comparing the 2 therapeutic modalities

Initial combination drug regimens containing Cisplatin in patients with stage III and IV head and neck cancer produce a high percentage of clinical response. We initiated the current trial to assess the role of multimodality treatment (CT plus RT) versus CT alone in eliciting tumour response rates, and the duration of tumour free survival. Patients were randomised to CT followed by RT (arm A: 36 patients) or CT alone (arm B: 44 patients). Of 96 patients entered into this study 80 are evaluable at the time of analysis. There were 13 women and 67 men with a median age of 52 years and a median performance status of 90%. All of them presented measurable stage T4N0-3M0-1 or T3N2-3M0-1 carcinomas. The chemotherapy consisted of Cisplatinum, Bleomycin and Methotrexate and was given in 2 cycles over 35 days. Local radiotherapy with 6,000 rad followed. In arm B, 3 cycles of chemotherapy were given without radiotherapy. The overall tumour responses after CT were 75% in arm B, and 70% in arm A. After RT the tumour response fell to 59%. Median tumour remission was 4 months and median survival 11 months. Toxic effects were mild mainly consisting of alopecia, nausea and vomiting. Myelotoxicity was moderate, but significant renal or ototoxic side effects did not occur. 10 cases of Bleomycin related pulmonary fibrosis were found. Our main findings show that patients receiving 2 cycles of CT do not have a statistically shorter survival compared to those who were treated by CT plus RT.     

Neck dissection in the management of regional metastases in patients with undifferentiated nasopharyngeal carcinomas

Residual regional disease after the primary treatment of nasopharyngeal carcinoma is still considered to be a therapeutic problem. The limitations of prophylactic radical radiation, further doses of irradiation as a useful salvage procedure, and the effects on vital structures were the reasons that we employed a therapeutic protocol consisting of radical neck dissection after 40 Gy of radiotherapy and a full tumor dose after surgery. The initial treatment consisted of chemotherapy. Between 1977 and 1991 surgical removal of residual neck metastases was performed in 44 patients with undifferentiated nasopharyngeal carcinomas who had regional metastases at the time of diagnosis. Fourteen patients (group A) had radical neck dissections after initial chemotherapy (using doxorubicin, etoposide, bleomycin and/or 5-fluouracil) and between two courses of locoregional radiotherapy. The remaining 30 patients (group B) were operated on after finishing chemotherapy and locoregional radiotherapy (group B 1) or receiving only full-dose locoregional radiotherapy (group B 2). All patients had histopathologically proven complete remission of primary tumors before neck surgery. The five-year survival rates for group A were 78%, 40% for group B 1 and 27% for group B 2. There were statistically significant differences between groups A and B (P < 0.01), but not between groups B 1 and B 2. In group A one patient died from subsequent distant metastases and two from local tumor recurrences. Twenty patients died in group B, regional relapses occurred in 40% of the patients in group B 1 and 33% in group B 2, while distant metastases developed in 40% of group B 2. These findings again showed that radical neck dissection was an effective approach for controlling neck disease. When performed after initial chemotherapy and between two courses of radiotherapy, surgery significantly improves the prognosis of patients with positive regional lymph nodes at the time of diagnosis. Received: 2 June 1998 / Accepted: 21 October 1998     

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clincial evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck – particularly those patients having neck dissections or total laryngectomies – have routine thyroid function studies performed following the cessation of treatment.