Altered fractionation and/or adjuvant chemotherapy in definitive irradiation of squamous cell carcinoma of the head and neck

OBJECTIVE: To review the roles of altered fractionation and adjuvant chemotherapy in the treatment of patients with squamous cell carcinomas of the head and neck. STUDY DESIGN: Review of the pertinent literature. METHODS: The literature pertaining to altered fractionation and/or adjuvant chemotherapy for patients with squamous cell carcinomas of the head and neck was reviewed to define the optimal combination of radiotherapy and adjuvant chemotherapy. RESULTS: The efficacy of altered fractionation compared with conventional fractionation depends on the fractionation schedule employed. Some hyperfractionated and accelerated fractionation schedules have resulted in improved locoregional control but no significant improvement in overall survival. In contrast to induction and maintenance chemotherapy, concomitant chemotherapy appears to result in improved locoregional control and survival. CONCLUSIONS: Altered fractionation and/or concomitant chemotherapy results in improved locoregional control and, in some instances, survival for patients with advanced head and neck cancer. Depending on primary site, the applicability of these aggressive treatment regimens is limited by an enhanced probability of severe complications as tumor volume increases. The optimal combination of these modalities is unclear and will be defined by future prospective trials.     

Sequential methotrexate and Radiotherapy in advanced laryngeal cancer

Surgery and/or Radiotherapy offers poor cure rate in the cases of advanced laryngeal cancer. Due to this fact a number of combined modality programmes have been piloted in which sequential chemotherapy and radiotherapy play an important role in the primary treatment plan. In present paper we have compared the results of sequential chemotherapy followed by external radiotherapy and radiotherapy alone. This study was carried out in 55 cases of advanced laryngeal carcinoma (Stage III and Stage IV). The chemotherapeutic agent used in this study was parenteral methotrexate. There was marked improvement in cure rate of advanced squamous cell carcinoma of larynx who received sequential methotrexate followed by external beam radiotherapy.     

A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma

Summary Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706).     

Role of combined therapy in advanced carcinoma of the larynx and hypopharynx

The present prospective preliminary study is based on treatment of stage III and IV cancers of the larynx and hypopharynx with a planned combined regimen of radiotherapy and radical surgery. There is a reduction in the failure rate in these cases as compared to those treated in this centre with a single modality of therapy like radiotherapy or surgery alone. 69% of the patients thus treated are surviving disease-free for follow ups varying 18–30 months with a median follow up of 24 months following combined treatment.     

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.     

Laryngeal penetration and aspiration during swallowing after the treatment of advanced oropharyngeal cancer

OBJECTIVE: To determine whether laryngeal penetration and aspiration in oropharyngeal cancer survivors differ by treatment group. DESIGN: Cross-sectional study of patients with stage III or IV oropharyngeal squamous cell carcinoma who were at least 12 months removed from combined modality therapy and clinically free of disease. SUBJECTS: Potential subjects were stratified by tumor site and tumor T stage to achieve a similar comparison between chemoradiotherapy (n = 10) and surgery/radiotherapy (n = 11) groups. Validated instruments used to evaluate swallowing included the Penetration-Aspiration Scale and the M. D. Anderson Dysphagia Inventory. RESULTS: Patients with oropharyngeal cancer treated with chemoradiotherapy demonstrated greater airway protection according to Penetration-Aspiration Scale scores than those treated with surgery and radiotherapy on 5-mL (P = .02), 10-mL (P = .04), and 20-mL (P = .04) liquid barium swallows. Also, the oropharyngeal chemoradiotherapy group had better self-perceived swallowing ability than the surgery-radiotherapy group on the basis of the M. D. Anderson Dysphagia Inventory (P = .02). CONCLUSION: The present study suggests that patients with oropharyngeal cancer who successfully complete chemoradiotherapy protocols without surgical salvage retain greater airway protection during swallowing and better swallowing-related quality of life than patients treated with primary surgery and radiotherapy.     

保留喉功能的梨状窝癌的综合治疗

探讨综合治疗对保留喉功能的梨状窝癌的作用。方法：对梨状窝癌进行保留喉功能治疗的３３例进行回顾性分析。（１）３３例术前分别给予１周期或２周期诱导化疗;（２）手术治疗经化疗后的肿瘤切除;（３）术后放射治疗。结果：化疗后有效率４２．４％。３年生存率５４．８％,５年生存率３８．７％。     

39例环后癌的外科治疗及临床疗效分析

目的探讨环后癌的外科治疗方法及临床疗效。方法回顾性分析2010~2018年行外科治疗的39例环后癌患者,其中男38例,女1例;年龄39～70岁。根据2002年UICC分期规定：I期7例,II期7例,III期8例,IV期17例。行保留喉功能者25例,不保留喉功能者14例;在完整切除肿瘤后进行咽喉功能的修复重建。术前诱导化疗+手术+术后辅助放疗者15例,手术+术后辅助放疗者14例,术前诱导化疗+手术者8例,单纯手术者2例。结果术后出现咽瘘5例,下咽狭窄2例,分别予换药和食管镜下扩张后II期愈合。随访时间5～65个月,随访5年及以上者5例 ,健在1例;随访3年以上者18例,健在7例,其余未随访至3年,7例失访。经Log rank检验,是否保留喉功能组间、进行术前诱导化疗联合术后辅助放疗的患者与仅进行术后辅助放疗的患者组间、患者有无淋巴结转移组间、及I II期与III IV期组间生存率差异均无统计学意义（P＞0.05）。结论随着环后癌外科治疗的发展,在安全切除癌灶的基础上可酌情保留中晚期喉功能,结合外科综合治疗可一定程度提升患者生活质量。     

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.     

Effect of radiation techniques in treatment of oropharynx cancer

OBJECTIVES: To compare the toxicity and outcomes of three radiotherapy techniques-three-dimensional conformal (3D-RT), accelerated fractionation with concomitant boost (AFxCB), and intensity modulated radiotherapy (IMRT)-in the combined modality treatment of stage III-IV squamous cell carcinoma (SCC) of the oropharynx. STUDY DESIGN: Retrospective review. METHODS: Between 1998 and 2007, a total of 87 patients were treated; 23 were treated with 3D-RT, 32 with AFxCB, and 32 with IMRT. Systemic therapy consisted of platinum-based chemotherapy in 81 and anti-epidermal growth factor receptor (anti-EGFR)-targeted therapy in 6 cases. Median radiotherapy doses were 70Gy with 3D-RT, 72Gy with AFxCB, and 69.3Gy with IMRT. Locoregional control, survival outcomes, and feeding tube (PEG) dependence were compared using log-rank method. The incidence of acute mucositis and skin reaction, and grade > or = 2 xerostomia at 6, 12, and 18 months after radiotherapy was compared using Fisher's exact test. RESULTS: Median follow-up was 24 months (range 3 to 103 months) for living patients. Two-year overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were 77.3%, 69.5%, and 86.4%, respectively. There was a trend toward improvement in LRC in patients treated with IMRT. Acute grade > or = 3 skin and mucosal toxicity were significantly lower with IMRT compared to AFxCB (P < .001). Grade > or = 2 xerostomia was significantly reduced with IMRT compared to AFxCB and 3D-RT (P < .001). There was no difference in the actuarial rate of PEG dependence (P = .96). CONCLUSIONS: Compared to AFxCB and 3D-RT, IMRT confers an improvement in toxicity and appears to have similar efficacy in patients with SCC of the oropharynx.     

Functional and oncological results of non-surgical vs surgical treatment in squamous cell carcinomas of the oropharynx

INTRODUCTION AND OBJECTIVES: Squamous cell carcinomas of the oropharynx are aggressive tumours usually diagnosed at advanced stage. Their optimal treatment has not been established. The aim of this study was to compare the oncological and functional outcomes in patients with carcinomas of the oropharynx treated by radiotherapy (with chemotherapy in advanced stages) vs surgery (with radiotherapy in advanced stages). METHODS: A retrospective study on 50 patients with squamous cell cancer of the oropharynx treated by radiotherapy (with or without chemotherapy) at our institution between 1998 and 2008 was carried out. The oncological and functional results were compared with patients with same cancer location and stage treated by surgery (with or without radiotherapy). In both groups, the patients were classified as follows: 10% Stage I, 12% Stage II, 16% Stage III, 48% Stage IVa and 14% Stage IVb. RESULTS: The 5-year disease-specific survival was 33% in the radiotherapy group and 52% in the surgical group (P=.17). Five-year disease-specific survival for Stage I and II patients was 82% in the radiotherapy group and 70% in the surgical group. In Stage III and IV disease, 5-year disease-specific survival was higher in the surgical group (47% vs 17%). The functional results were similar; anatomical and functional preservation of the larynx was higher in the radiotherapy group but the successful return to oral food intake was higher in the surgical group. CONCLUSIONS: The prognosis of squamous cell carcinoma of the oropharynx is poor. Oncological results in Stages I and II were similar for radiotherapy and surgical treatments. In advanced stages, the prognosis was better in patients treated by surgery with or without radiotherapy. Functional results were similar in both treatment modalities.     

Therapeutic outcomes of laryngeal cancer at Kyoto University Hospital for 10 years

CONCLUSION: It is important to prevent regional lymph node recurrence and distant metastasis to achieve better survival of laryngeal cancer. OBJECTIVE: Therapeutic outcomes of 130 cases with laryngeal cancer treated at Kyoto University Hospital between 1995 and 2004 were reviewed. PATIENTS AND METHODS: In all, 121 males and 9 females were involved. Their ages ranged from 40 years to 92 years (average 66 years). All tumors were squamous cell carcinoma - arising at the glottis in 111 cases, the supraglottis in 18, and the subglottis in 1 case. Most glottic cancers (77.5%) were classified as stage I or II, while most supraglottic cancers (77.8%) were at stage III or IV. Stage I/II cancers were basically treated by conventional radiotherapy (60-66 Gy) and twice-daily hyperfractionated radiotherapy (70-74 Gy), respectively, attempting to preserve the larynx. Total laryngectomy with neck dissection was performed in the treatment of stage III/IV cases. RESULTS: Five-year disease-specific survival rates were 100%, 96%, 100%, and 68% for stage I, II, III, and IV, respectively. Five-year laryngeal preservation rates were 98%, 100%, 86%, 0%, and 0% for T1a, T1b, T2, T3, and T4 of glottic cancer, respectively. Local recurrence occurred in five cases of stage I/II glottic cancer, which was successfully salvaged. Regional lymph node recurrence occurred in five cases including four patients with glottic cancer and one with supraglottic cancer. Two of them died of disease despite undergoing salvage therapy. Distant metastasis occurred in the lung in four cases including one glottic and three supraglottic cancer patients after initial treatment.     

Combined therapy in advanced head and neck cancers.

The results of single modality treatment using surgery or radiotherapy alone in advanced head and neck cancers are known to be unsatisfactory. The present study analyses 252 cases with stage III and IV resectable cancers of the head and neck region selected to be treated by a combined regime of pre- or post-operative radiation and radical surgery. Only 193 patients completed the treatment protocol. There were 58 cases (33.5 per cent) who failed either at primary or regional sites or both. Nine cases (five per cent) developed distant metastasis. Absolute and determinate four year disease-free survival was 55 per cent and 61 per cent respectively. Early lesions (stage I and II) have been excluded from the study. The study indicates that a reduction in primary and regional failures correlates well with a combined therapy, though prolonged treatment may affect patients' compliance to some extent.     

原发性鼻腔癌128例的治疗分析

目的 探讨鼻腔癌的最佳治疗手段和影响预后的因素。方法 对本院自１９７７年３月～１９９３年８月收治的１２８例鼻腔癌进行回顾性分析。治疗方式：单纯放射治疗８９例,术前放射治疗＋手术２１例,手术＋术后放射治疗１３例,单纯手术５例。结果 １２８例鼻腔癌患者的总５年生存为４２．２％;单纯放射治疗５年生存率为３３．７％;术前放射治疗＋手术的５年生存率５７．１％（Ｐ〈０．０５）;手术＋术后放射治疗的５年生存率为     

Prognostic factors and outcome for nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal cancer (NPC) is a distinct form of cancer of the upper respiratory or digestive tract in which the epidemiologic features, origin, histopathologic types, treatment, and prognosis are different from those associated with other malignant neoplasms of this anatomical area. Recent publications have demonstrated the advantage of aggressive multimodality treatment for advanced NPC. OBJECTIVES: To evaluate the results of standardized treatment of NPC during 11 years and to identify pertinent factors for clinical outcome. METHODS: Between January 1, 1989, and December 31, 2000, 173 patients with newly diagnosed NPC were treated at Instituto Nacional de Cancer. Clinical records and radiographic studies of the patients were retrospectively reviewed. Documented data of the initial presenting symptoms, head and neck examination, radiotherapy protocols, chemotherapy regimens, and surgical technique were analyzed. To determine important prognostic factors, we correlated survival rates with age, clinical stage, tumor extent, histopathological type, and therapeutic approach. The major end point used for assessment was relapse-free survival. Survival curves were estimated by the Kaplan-Meier product-limit method. Multivariate analysis was performed using the Wilcoxon signed rank and Cox proportional hazards regression tests. RESULTS: Most patients (88.5%) had locoregional advanced disease, mostly (53.4%) of the nonkeratinizing subtype. Forty-seven percent of patients had clinical cervical nodal metastases at first consultation. Gross extension of the primary tumor involving the facial bones and skull base was observed in 39.3% and 20.8%, respectively. Just under 75% of patients were treated with radiotherapy (median dose, 6600 cGy), and 25.4% underwent concomitant chemoradiotherapy with adjuvant chemotherapy (cisplatin plus 5-fluorouracil) (median dose, 6800 cGy). The 5-year disease-specific survival for the 173 patients was 32.3%. The disease-specific survival for the radiotherapy group was 22.5%, compared with 61.4% for the chemoradiotherapy plus adjuvant chemotherapy group (P =.004). Factors associated with adverse outcomes were age older than 40 years at treatment (P =.001), advanced TNM stage (P =.002), skull base invasion (P =.004), and facial bone invasion (P<.001). CONCLUSIONS: Compared with radiotherapy alone, concomitant chemoradiotherapy with adjuvant chemotherapy improved the treatment outcome of patients with NPC treated in our institution. Advanced age, local extension, and stage of the disease adversely affected the prognosis in our patients. Compared with reirradiation, salvage brachytherapy and radical neck dissection for local and regional residual or recurrent NPC were associated with increased rates of locoregional control and survival.     

Pearson术式治疗晚期喉癌28例报告

目的：探讨Pearson术式在治疗晚期喉癌中的作用。方法：采用Pearson术式治疗28例晚期喉癌，对其中的26例同期行颈清扫术或分区性颈清扫术。结果：术后随访3～5年，27例(96．4％)能发声，其中发声良好者11例，一般14例，差2例。无一例误咽。3年生存率为78．6％，5年生存率为68．4％。结论：Pearson术式治疗晚期喉癌，既能保留喉的大部分功能，又能根治病变，提高了一部分传统上需做喉全切除术患者的生活质量。     

Results of radiotherapy with, or without, salvage surgery versus combined surgery and radiotherapy in advanced carcinoma of the hypopharynx

There is considerable controversy surrounding the optimum treatment of advanced hypopharyngeal cancers. Curative radiotherapy with surgical salvage in reserve is an accepted protocol as is also a combined treatment of surgery and radiotherapy. The present study is a retrospective analysis of the survival results of 195 cases treated in a single centre. The combined surgery and radiotherapy group comprised a greater number of pyriform fossa and post-cricoid tumours whereas, the curative radiotherapy group had a higher proportion of posterior pharyngeal wall tumours. Actuarial two-year disease-free survival rates were significantly better with combined treatment when results of stage III and IV lesions (164 patients) of all sites are taken together, as compared to those obtained with curative radiotherapy without salvage (p = 0.000) or radiotherapy with surgical salvage for residual/recurrent tumours (p = 0.0021).     

Lokal fortgeschrittene Nasopharynxkarzinome

Background

The excellent results yielded by hyperfractionated and accelerated radiotherapy associated with concurrent chemotherapy in locally advanced oropharyngeal and hypopharyngeal carcinomas led to investigation of this therapeutic regimen in nasopharyngeal carcinomas also.

Methods

Thirty-five patients with stage III and IV nasopharyngeal carcinomas received accelerated hyperfractionated radiotherapy with concurrent chemotherapy (5-FU, mitomycin C + leucovorin). In the first 3 weeks of treatment five 2-Gy doses per week were delivered to the primary tumour and regional lymph nodes. The fractionation was then accelerated, with 1.4 Gy given twice daily until a total dose of 72 Gy had been administered.

Results

The overall objective response rate was 100%. The median follow-up period was 71 months. Salvage surgery of the lymph nodes was performed in 10 patients, revealing vital tumour tissue in 6 of these. The actuarial 5-year local control rate was 64% (95%CI: 47–81%), while overall actuarial survival at 5 years was 70% (95%CI: 53–86%).

Conclusion

Hyperfractionated accelerated radiotherapy with concurrent chemotherapy is effective and feasible in locally advanced nasopharyngeal carcinoma.     

Results of laryngeal cancer surgery in four ENT centers in poland

The results of laryngeal cancer surgery were assessed in a group of 832 patients treated in four major ENT centers in Poland. Five-year survival rates were as follows: stage I, 86%; stage II, 71%; stage III, 54%; and stage IV, 42%. In experienced hands and for properly selected cases, cure rates after partial (conservation) laryngeal surgery were similar to those after total laryngectomy. For early stages (I and II), the survival after partial surgery was better than that found after radiotherapy.     

Accelerated hyperfractionated irradiation with concomitant boost for stage II laryngeal cancer and locally advanced head and neck cancer

OBJECTIVE: This study was conducted to evaluate the efficacy and feasibility of our accelerated hyperfractionation with concomitant boost for stage II laryngeal cancer and stages III-IVb locally advanced head and neck cancer. PATIENTS AND METHODS: From January 2000 to October 2001, eight patients with AJCC 1998 stage II laryngeal cancer and 11 patients with AJCC 1998 stages III-IVb locally advanced head and neck cancer underwent accelerated hyperfractionated radiation therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8 and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For stages III-IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with 1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients, 16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin. Acute toxicity based on RTOG criteria and tumor response at 1 month post-treatment were estimated as initial effects. RESULTS: The overall response rate was 100% in patients with stage II laryngeal cancer and 91% in patients with stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute effects was 47%. Eighteen patients (95%) completed radiation therapy without interruption related to acute side effects, while one had prolongation of the treatment for more than 1 week because of neutropenia. CONCLUSIONS: Our results demonstrated that accelerated hyperfractionation, mostly combined with concomitant chemotherapy, had a good overall response rate with acceptable toxicity in stage II laryngeal cancers and stages III-IVb head and neck tumors.