Survival patterns in patients with carcinoma base of tongue treated with external beam irradiation and salvage surgery

Objective

The current study was designed to assess the treatment results and survival in the patients with carcinoma of base of tongue that were treated with primary radiotherapy, radiotherapy with chemotherapy and salvage surgery when indicated.

Design

A prospective study was carried out in 78 cases of carcinoma of the base of tongue between 1995 and 1999.

Methods

The majority of cases belonged to stage IV 60/78 (76.92%) as per AJCC staging. Radiotherapy in the dose of 60 Gy was given primarily to the patients with stage III tongue base cancer. Patients with early stage IV cancer were given split course radiotherapy followed by assessment for surgery. For the patients with advanced stage IV disease with poor general condition, palliative radiotherapy of 24 Gy with or without palliative chemotherapy was given. 15 patients were subjected to salvage surgery in the form of radical neck dissection alone (8 cases), extended total laryngectomy with neck dissection (3 cases), extended total laryngectomy (2 cases) and extended supraglottic laryngectomy with RND in 2 cases.

Results

Two and 5 years Kaplan — Meier actuarial survival rates were 45% and 10% respectively with local control rates equivalent to survival rates. All surviving patients maintained good function and quality-of-life with few tolerable side effects.

Conclusions

External beam radiotherapy with salvage surgery results in satisfactory local and regional control in stage III and IV carcinoma base of tongue.     

Laryngeal cancer treatment outcomes in our department

Laryngeal cancer is one of the most common types of head and neck cancer. Numerous studies have reported treatment outcomes, and therapeutic approaches and results are generally well established. However, the widespread use of concurrent chemoradiation therapy(CCRT)has led to differences among hospitals in laryngeal preservation rates in patients with T2 and T3 tumors. CCRT is the mainstay of treatment for laryngeal cancer in our department, given our goals of achieving organ and functional preservation, as well as radical cure. Our regimen for CCRT is comprised of chemotherapy with S-1 plus nedaplatin, concurrently with radiation therapy(SN therapy). We report outcomes obtained from 60 patients with laryngeal cancer who received first-line treatment in our department from April 2005 through March 2010. Cumulative survival rates according to disease stage were as follows: Stage I, 100%; Stage II, 96. 2%; Stage III, 83. 3%; and Stage IV, 48. 8%. The complete response rate after SN therapy was 84. 3%. After excluding patients with T4 tumors, the laryngeal preservation rate was 85. 7%.     

Chemo-radiotherapy for head and neck cancer

Many randomized trials have investigated the effect on survival of induction chemotherapy; none however, has demonstrated improved survival. A study of the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated the feasibility of induction CDDP/5-FU plus surgical salvage as an alternative to initial laryngectomy, but it did not include a radiation-alone treatment arm. Thus, a three-arm trial (R 91-11) was needed to compare the regimen of induction chemotherapy plus surgical salvage treatment with radiation alone and with concurrent chemo-radiation, to determine whether the addition of chemotherapy led to better results than conventional radiation alone. R 91-11 data revealed that concurrent chemo-radiation significantly increased the time to laryngectomy and chemotherapy suppressed distant metastasis, but there was no difference in overall survival. Single-agent docetaxel is known to induce a response in 22-45% of patients with recurrent squamous cell cancer of the head and neck. When used in combination with CDDP, response rates of between 40 and 54% have been reported. Increased expression the epidermal growth factor receptor (EGFR) is reported in head and neck cancer. Anti-EGFR monoclonal antibody is associated with decreased cell proliferation, inhibition of metastasis and angiogenesis, and it has a synergistic effect with chemotherapy or radiotherapy. It is hoped that further advances will lead to greater realization of the therapeutic potential of these compounds as anticancer agents.     

Role of Chemotherapy in head and neck cancer

For head and neck cancer, a recent meta-analysis of published randomized trial results showed that concurrent chemoradiotherapy, adjuvant chemotherapy and neoadjuvant chemotherapy may increase absolute survival by 12.1%, 6.5%, and 3.7%, respectively. Initial response rates to first line chemotherapy are high, but this responsiveness does not appear to translate into a survival benefit. Thus, chemotherapy can be indicated as the standard therapy for a very limited range of advanced head and neck cancers. With the aim of prolonging survival, N stage advanced nasopharyngeal cancer is a good candidate for neoadjuvant chemotherapy. Among a large number of randomized trials of neoadjuvant chemotherapy, organ function preservation studies showed the possibility of laryngeal preservation for locally resectable T2 and T3 laryngeal and hypopharyngeal cancer. Concurrent chemoradiotherapy may be indicated for advanced T stage head and neck cancers, especially those with locally unresectable lesions. For N stage advanced pharyngeal cancer patients, adjuvant chemotherapy with applied after the standard therapy has a role in the treatment. With palliative treatment in advanced and/or recurrent disease, there is less benefit from chemotherapy and indications for chemotherapy should be selected for individual patients.     

Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma

BackgroundRandomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy.Patients and methodsThis study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX).ResultsMedian follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with ≥1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03).ConclusionsPromising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.     

Organ preservation in multimodality therapy of head and neck cancer

Several conclusions can be drawn from the studies that have been done to evaluate induction chemotherapy and organ preservation. These principles can serve as the foundation for the design of future trials for organ preservation. 1. The addition of chemotherapy to surgery/radiation for advanced head and neck cancer has not improved overall patient survival. 2. Surgery and radiation therapy can safely and effectively be given after chemotherapy to patients who have had induction chemotherapy. 3. Neoadjuvant chemotherapy followed by definitive radiation therapy can achieve laryngeal preservation in a high percentage of patients, without compromise of survival. 4. In order to change the standard of care, organ preservation trials must be conducted in a randomized, prospective fashion. 5. Organ preservation trials must be conducted for specific sites and stages of head and neck cancer. 6. All patients with nonlaryngeal head and neck cancer who are treated with induction chemotherapy for organ preservation should be treated within a protocol setting.     

Sequential chemotherapy and radiotherapy for organ preservation in advanced resectable nonlaryngeal head and neck cancer.

Although there is no definite survival advantage to the use of sequential induction chemotherapy (CT) followed by radiotherapy (RT) in advanced resectable laryngeal cancer, this approach does succeed in preserving the larynx in many of these patients. The authors performed this study to analyze their results using a similar approach for patients with advanced resectable cancer located outside the larynx who would have required a total laryngectomy for oncologic or functional reasons. A retrospective study was performed at a single institution that included all patients with advanced resectable nonlaryngeal head and neck cancer treated with induction CT between January 1990 and August 1995. A total of 19 patients were included, with primary cancers located in the oropharynx in 14 patients, the hypopharynx in four, and the oral cavity and oropharynx in one. Eight patients had clinical stage III disease, and 11 patients had stage IV disease. Our treatment protocol consisted of two cycles of induction CT with cisplatin and 5-fluorouracil, followed by a third cycle of CT and subsequent RT in patients who achieved at least a clinical partial response (PR) after two courses of induction CT. Eighteen of 19 patients were evaluable for response. Overall, 13 patients (72%) had a major response (PR or CR) to induction CT at the primary site, and eight patients (57%) had a major response to chemotherapy in the neck. With a mean follow-up of 53 months (range, 24-71 months), the disease-specific survival was 57% for those patients with cancer of the oropharynx and oral cavity. In the subset of patients with hypopharynx cancer, 3 of 4 patients died of cancer despite achieving major response to induction CT. Organ preservation using sequential CT and RT for advanced resectable nonlaryngeal head and neck cancer is feasible, and the results in our experience with cancer of the oropharynx were similar to those reported for primary laryngeal cancer. Our limited experience using this protocol for cancer of the hypopharynx has been disappointing.     

Long-term regional control after radiation therapy and neck dissection for base of tongue carcinoma

: Minimal literature exists with 10-year data on neck control in advanced head and neck cancer. The purpose of this study is to determine long-term regional control for base of tongue carcinoma patients treated with primary radiation therapy plus neck dissection.

: Between 1981–1996, primary radiation therapy was used to treat 68 patients with squamous cell carcinoma of the base of tongue. Neck dissection was added for those who presented with palpable lymph node metastases. The T-stage distribution was T1, 17; T2, 32; T3, 17; and T4, 2. The N-stage distribution was N0, 10; N1, 24; N2a, 6; N2b, 11, N2c, 8; N3, 7; and Nx, 2. Ages ranged from 35 to 77 (median 55 years) among the 59 males and nine females. Therapy generally consisted of initial external beam irradiation to the primary site (54 Gy) and neck (50 Gy). Clinically positive necks were boosted to 60 Gy with external beam irradiation. Three weeks later, the base of tongue was boosted with an Ir-192 interstitial implant (20–30 Gy). A neck dissection was done at the same anesthesia for those who presented with clinically positive necks, even if a complete clinical neck response was achieved with external beam irradiation. Neoadjuvant cisplatin-based chemotherapy was administered to nine patients who would have required a total laryngectomy if their primary tumors had been surgically managed. The median follow-up was 36 months with a ranged from 1 to 151 months. Eleven patients were followed for over 8 years. No patients were lost to follow-up.

: Actuarial 5- and 10-year neck control was 96% overall, 86% after radiation alone, and 100 after radiation plus neck dissection. Pathologically negative neck specimens were observed in 70% of necks dissected after external beam irradiation. The remaining 30% of dissected necks were pathologically positive. These specimens contained multiple positive nodes in 83% despite a 56% overall complete clinical neck response rate to irradiation. Regional failure occurred in only two patients, neither of whom underwent adjuvant neck dissection. Symptomatic neck fibrosis (RTOG grade 3) was not observed. Actuarial 5- and 10-year local control was 88% and 88%, disease-free survival was 80% and 67%, and overall survival was 86% and 52%.

: For base of tongue cancer, most patients can obtain long-term regional control with no severe complications after definitive radiation therapy, plus neck dissection for those who present with lymphadenopathy. Complete clinical regression of palpable neck metastases after irradiation poorly correlates with pathologic outcome. Our current policy is to include neck dissection at the time of implantation for patients who present with palpable neck metastases. We realize that this therapeutic approach may overtreat some patients, but we are reluctant to change our policy in light of these excellent outcomes.     

Chemotherapy of advanced head and neck cancer with methotrexate, bleomycin, and cis-diamminedichloroplatinum II in an effective outpatient schedule.

Thirty-one patients with advanced cancer of the head and neck, twenty-six of whom had failed prior irradiation, were treated with an out-patient chemotherapy regimen combining methotrexate, bleomycin, and cis-diamminedichloroplatinum (II). The overall response rate among evaluable patients was 61%, with 22.5% complete remission. If 6 additional patients not completing 3 weeks of treatment are included, the response rate was 51.4%. The median duration of partial remission was 3 months, but none of the complete remitters has relapsed with a follow-up of two to twenty months (median six). Response rate was not dependent on performance status, prior irradiation, or primary site. Toxicity was mild. The remission rate and duration suggest that this regimen may be superior to single agents, and as effective as more complicated and toxic regimens using higher doses of the same drugs.     

联合应用紫杉特尔对头颈肿瘤诱导化疗的临床病例总结

背景与目的：联合应用紫杉特尔对头颈肿瘤诱导化疗的报道不多,国外报道晚期头颈肿瘤应用TPF[紫杉特尔(taxotere) 顺铂(cisplatin,DDP) 5-氟尿嘧啶(5-fluorouracil,5-FU)]方案的总有效率可达93％。本研究旨在初步探讨TPF方案对头颈肿瘤诱导化疗的作用。方法：回顾1999年1月～2002年6月在我院应用TPF方案诱导化疗的头颈肿瘤25例。化疗具体实施如下：taxotere 75mg／m^2静脉滴注,第1天;DDP 20mg／m^2,静脉滴注,第1～3天;5-Fu300mg／m^2,静脉滴注,第1～3天;每3周重复。治疗期间密切随访,观察不良反应,化疗结束后进行疗效评定。结果：TPF方案诱导化疗后原发灶呈完全缓解(CR)者6例(24．0％),部分缓解(PR)者12例(48．0％),微小反应或无反应者7例,总的有效率为72．0％。口腔癌的化疗有效率为63．6％(7／11),其它部位癌(包括舌根癌、喉癌、喉咽癌和鼻咽癌)的化疗有效率为71．4％(10／14),两者之间无显著性差异(P=0．504)。本组病例中有9例首次用其它方法治疗失败后出现原发灶复发或转移,应用TPF方案诱导化疗后临床CR者1例,PR者3例,总的化疗反应率为44．4％(4／9)。化疗后36．0％(9／25)的病例出现白细胞下降,按照WHO分度标准I度16．0％(4／25),Ⅱ度16．0％(4／25),Ⅲ度4．0％(1／25);64％(16／25)患者化疗后出现胃肠道反应,按照WHO标准均为Ⅱ度以下;所有病例化疗后均未出现肾功能损害;其它化疗不良反应包括脱发,均低于Ⅱ度。结论：局部晚期的头颈肿瘤应用TPF方案进行诱导化疗可以获得较好的疗效,而且对部分首次用其它方法治疗的复发病例有效,其不良反应相对较少。     

放疗在头颈部晚期肿瘤器官功能保全治疗中的作用

器官功能保全治疗在头颈部肿瘤病人的治疗中有非常重要的地位.目前头颈部晚期肿瘤的非手术治疗方法主要有放射治疗和化疗联合放射治疗.超分割治疗和加速超分割治疗与常规放射治疗比较,能够提高局部控制率和器官功能保全率.诱导化疗加放疗能够使约60%的喉癌患者保留喉功能,与常规放射治疗比较,不能提高生存率.同步放化疗显著提高器官功能保全率,是目前器官功能保全性非手术治疗的主要治疗方案,同步放化疗与非常规分割方式结合能否经一步提高器官功能保全率仍需要进一步研究.一些新的方法如新药及不同给药方式,调强放射治疗,分子靶向治疗,乏氧增敏剂等在头颈肿瘤治疗中的作用的试验正在进行中.     

Surgical treatment in head and neck cancer

Three topics currently important in head and neck surgery are voice-conserving surgical treatment of laryngeal cancer, the role of modified radical neck dissection in the treatment of cervical metastases, and reconstruction and rehabilitation of the head and neck cancer patient. The laser has become an accepted modality for the treatment of early vocal cord cancer and has local control rates comparable to other treatment methods. Partial laryngectomy can conserve voice and yield excellent local control rates. The modified radical neck dissection has been shown to yield rates of local recurrence no greater than radical neck dissection for N0 and N1 neck disease associated with laryngeal cancer. Vocal rehabilitation following total laryngectomy has been revolutionized by the tracheoesophageal puncture procedure. Most patients can be expected to acquire voice using tracheoesophageal puncture following total laryngectomy. Free flaps have improved the functional results of many major head and neck surgical procedures and offer the possibility of better results in the future. However, more conventional reconstructive techniques, including local flaps, continue to have a role in head and neck surgery.     

Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.     

会厌癌声门上喉部分切除术(附40例报告)

目的会厌癌局限于会厌或侵及杓会厌襞者，可采用声门上喉部分切除术治疗。手术中切除甲状软骨上１／３、会厌、会厌前间隙、室带的前部，如切除一侧杓状软骨，也可基本上恢复喉的全部功能。方法采用声门上喉切除术治疗４０例会厌癌患者，并进行了病例整理与随访。根据ＵＩＣＣ１９８７年标准，Ｔ１１７例，Ｔ２１７例，Ｔ４６例。结果１２例行单侧颈淋巴结清除术，１例行双侧颈淋巴结清除术，术后淋巴结转移７例，占５８％。围手术期无死亡，有８例患者早期进食有轻微呛咳，所有患者均拔除套管。术后行放、化疗２９例，占７３％，３年生存率为７４％。结论选择Ｔ分级适当的患者行声门上喉切除术可获得满意的喉功能及预后     

会厌癌声门上喉部分切除术

目的 会厌癌局限于会厌或侵及榴会厌襞者,可采用声门上喉部分切除术治疗。手术中切除甲状软骨上１／３、会厌,会厌前间隙,室带的前部,如切除一侧榴状软骨,也可基本上恢复喉的全部功能。     

Survival analysis of 5595 head and neck cancers--results of conventional treatment in a high-risk population.

This is a study of 5595 head and neck cancer patients treated during 1987-89 at TMH, Mumbai. The study included 1970 oral cancers (ICD 140-145), 1495 oropharyngeal cancers (ICD 1410, 1453, 146), 1255 hypopharyngeal cancers (ICD 148), 125 nasopharyngeal cancers (ICD 147) and 750 laryngeal cancers (ICD 161). The clinical extent of disease at presentation was based on TNM group staging (UICC 1978). For the majority of sites, patients attended the hospital during stage III and stage IV of the disease; the only exception was for cancers of the lower lip, anterior tongue and vocal cord when between 46.2% and 56.5% of patients with localized cancer (stage I and II) were seen. Generally, surgery either alone or with radiation has been administered for oral cancer patients whereas radiation either alone or in combination with chemotherapy was administered for other head and neck sites. The overall 5-year survival rate was in the range of 20-43% for oral cancer, 8-25% for pharyngeal cancers and 25-62% for laryngeal cancer. The 5-year relative survival rates were more or less in agreement with the results published by the Eurocare study for head and neck cancers. The importance of primary prevention in head and neck cancer is stressed.     

喉近全切除术治疗晚期唯癌,下咽癌疗效分析

目的：探讨晚期喉癌、下咽癌保留喉功能的方法，降低全喉切除率。方法：对喉癌Ｔ３、Ｔ４病变和下咽癌Ｔ３病变行喉近全切除术１５例。其中喉癌１３例，梨状窝癌２例。年龄４１￣７６岁，平均５６．３岁。临床分期：Ⅲ期９例，Ⅳ期６例。结果：除１例不能发音外，其余１４例（９３．３％）获得了较好的发音和无呛咳吞咽功能。２年生存率７５．０％（９／１２）。结论：该方法在保存发声功能，降低全喉切除率方面有积极作用。     

Quality of life in treated head and neck cancer patients

Sixty-Seven patients with head and neck cancer have been studied with respect to their quality of life after their treatment. The Grogono Woodgate index was used to evaluate their quality of life, the quality of life of patients treated for laryngeal cancer was excellent, even if they underwent total laryngectomy. On the contrary, however, patients who had hypopharyngeal cancer and had undergone a pharyngolaryngoesophagectomy had the lowest indices. As for patients with an oral cancer, their indices were high if the cancer was being controlled by radiotherapy.     

Neoadjuvant accelerated chemotherapy followed by hyperfractionated radiation therapy in patients with operable, locally advanced head and neck carcinoma

A prospective phase II trial was carried out to evaluate an accelerated chemotherapy (CT) regimen followed by hyperfractionated radiation therapy (RT) in previously untreated Stage III-IV, operable (total laryngectomy), head and neck cancer patients. The current study evaluates overall survival, loco-regional control, organ preservation rates and toxicity. Between April 1997 and December 2002, 68 patients with advanced head and neck cancer were treated with 3 cycles of induction CT (cisplatin and 5-fluorouracil; days 1, 14, and 28) followed by hyperfractionated RT (7440 cGy/62 fractions). Sixty patients received the planned RT-CT treatment. Two months after the end of RT, 96% of patients had a clinical complete remission of the primary and 66% of the neck disease. At a median follow-up of 32 months, the 3-year overall and disease-free survival rates were 66% and 76%, respectively. Seven patients recurred on the primary site, 1 on the neck and 2 patients only had distant metastases. The organ preservation rate was 73%. Acute grade 3-4 mucositis occurred in 75% of patients and an 18% rate of CT-related cardiotoxicity was reported. The accelerated CT-RT regimen achieves a high rate of larynx preservation albeit with considerable toxicity. The current prospective clinical trial was approved by the Ethics Committee of the Centro di Riferimento Oncologico (C.R.O.) on May 27, 1996, # CRO-02-96. Written informed consent was required from all patients entering the study.     

Chemotherapy for head and neck cancer

Chemotherapy for head and neck cancer was initially used as a palliative treatment in advanced and/or recurrent disease. The overall response rate was about 30% but patient survival was sometimes short. It was also observed that complete responders had a significantly longer survival period than non-responders. Cisplatin-containing regimens including cisplatin plus 5-fluorouracil appear to be the most efficacious for this disease. In a large number of randomized trials, organ function preservation studies have shown the possibility of laryngeal preservation for T2 and T3 laryngeal and hypopharyngeal cancer. A survival benefit has been shown clearly in advanced nasopharyngeal cancer. Another survival prolongation has been demonstrated in cases of locally unresectable cancer in the oral cavity, pharynx, nose and paranasal sinus. Thus, we conclude that neoadjuvant chemotherapy can be effective in cases of locally unresectable cancer in the oral cavity, pharynx, and nose and paranasal sinus. In advanced N stage nasopharyngeal cancer, neoadjuvant chemotherapy plus adjuvant chemotherapy may be indicated. Advanced T stage nasopharyngeal cancer is a good candidate for concurrent chemoradiotherapy. For the aim of laryngeal preservation, neoadjuvant and/or concurrent chemoradiotherapy can be indicated for T2 and T3 laryngeal and hypopharyngeal cancer.