Mixed beam radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study

Three hundred and twenty-two patients with inoperable squamous cell carcinomas of the head and neck were entered on a randomized study comparing “mixed beam”f radiation therapy with photon radiation therapy. Patients with histologically proven tumors of T-stage T2, T3, or T4 and any N-stage originating in the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were eligible. One hundred forty-five patients were randomized to photon treatment and 177 were randomized to mixed beam treatment. No significant differences could be demonstrated between the experimental and control groups for primary tumor control or overall survival, although there was an advantage for mixed beam treatment over photon treatment for patients with metastatic cervical adenopathy (69 vs. 55% complete response rate in the nods, p = .024). It is concluded that mixed beam radiation therapy does not offer a significant advantage over photon radiation therapy for patients with advanced squamous cell carcinomas of the head and neck.     

Response of epidermoid and non-epidermoid cancers of the head and neck to fast neutron irradiation: the Fermilab experience

One hundred and six patients with locally advanced cancers of the head and neck were treated with neutrons at the Fermilab Neutron Therapy Facility. Of these, 44 patients were previously untreated, 33 were recurrent following attempted surgery and 29 patients had previously received a full course of radiation therapy with conventional radiation. Results were analyzed to study the influence of stage, previous management, site of origin and tumor histology on local control of the disease. The most significant factor determining the outcome in this series of patients is the histological type. For epidermoid carcinoma, long term local control was achieved in 17/35 patients (49%) in the previously unirradiated group. With non-epidermoid tumors (adenocarcinoma, cylindroma, muco-epidermoid carcinoma), the local control rate was 28/39 (72%). Disease-free survival analysis also shows a survival advantage in non-epidermoid lesions treated with neutrons. It is concluded that neutron beam therapy may probably be the treatment of choice for non-resectable or recurrent non-epidermoid cancers of the head and neck and requires a clinical trial to establish this observation.     

Fast neutron radiation therapy for unresectable squamous cell carcinomas of the head and neck: the results of a randomized RTOG study

Forty patients with advanced, unresectable squamous cell carcinomas of the head and neck were entered on a prospective, randomized study comparing fast neutron radiation therapy with conventional photon radiation therapy. Twenty-six patients were randomized to neutrons, and 14 patients were randomized to photons. The randomization was purposefully unbalanced in favor of the experimental treatment. The complete response rate for the neutron-treated group of patients was 52%. The complete response rate for the photon-treated group of patients was 17%. The difference is statistically significant at the p = .04 level. The two-year survival rates for the neutron-treated group and the photon-treated group were 25 and 0%, respectively. The major complication rates were not statistically significantly different for the two groups (18% for neutrons, and 33% for photons).     

头颈部恶性肿瘤的靶向治疗进展

手术和放疗技术的进步对局部晚期或晚期头颈部肿瘤患者并未带来长期生存率的明显提高,靶向治疗日渐成为包括头颈部肿瘤在内的重要治疗选择。表皮生长因子受体在头颈部肿瘤中有较高水平表达,其表达情况与疾病的预后密切相关,并成为靶向治疗的重要靶点。针对该受体的抑制剂在头颈部肿瘤中应用取得了令人满意的疗效,目前临床资料显示该类药物单药及与其它治疗手段的联合在头颈部肿瘤中应用均取得较好疗效,但是靶向药物的作用机制及其敏感性的预测分子尚不明确。针对复发转移的头颈部肿瘤的二线治疗的Ⅲ期临床正在进行,与其他治疗手段的联合治疗的方法正在探索和验证,新的预测分子也在涌现。本文将对以上内容进行综述。     

Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck

Purpose

Boron neutron capture therapy (BNCT) is among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma.

Methods

Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4.

Results

All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater.

Conclusions

Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated.     

头颈部鳞状细胞癌靶向治疗进展

每年全世界大约有65万例新的头颈癌病例出现,其中绝大多数是头颈部鳞状细胞癌.晚期头颈部鳞状细胞癌的治疗需要综合治疗,尽管放化疗及手术治疗手段在不断发展,但是预后仍不理想且具有一定的毒副反应.靶向治疗是目前治疗研究头颈部鳞癌的热点,其在针对头颈部鳞癌的治疗特别是对局部晚期或复发/转移性头颈部鳞癌治疗中展现出了希望.本文综...     

Fast neutron therapy for locally advanced head and neck tumors

Between October 1972 and April 1979, 187 patients with locally advanced head and neck tumors were treated with 50 MeV_d→Be neutrons or with conventional treatment in the M. D. Anderson Hospital-Texas A & M University variable energy cyclotron (MDAH-TAMVEC) program. Of these, 114 patients were treated in pilot studies and 73 in a randomized clinical trial. In the pilot studies, 49 patients were treated with neutrons alone, 25 with mixed-beam irradiation (two neutron and three photon fractions per week), and 40 with conventional treatment (surgery, photons, or combined surgery and photons). There was no appreciable difference among patients in these studies with regard to local tenor control or servival. However, the patients in the conventional-treatment pilot study had less advanced disease than those in either of the other studies. The complication rates in the neutrons-only and conventional-treatment studies were significantly greater than the complication rate observed in the mixed-beam pilot study. In the randomized clinical trial, 41 patients were treated with mixed-beam irradiation and 32 with photon irradiation. The preliminary results of this trial show a slight superiority with mixed-beam irradiation. In the mixed-beam group, 61% had local tumor control, 7% developed major complications, and 4996 were alive at the time of analysis; whereas in the photon group, 47% had local tumor control, 3% developed major complications, and 25% were alive at the time of analysis.     

Fast neutron therapy for squamous cell carcinoma in the head and neck region: results of a randomized trial

A randomized trial of fast neuron therapy compared with 4MV photons for patients with head and neck cancer is reported. One hundred and sixty-eight patients were recruited between 1977 and 1984. The minimum follow-up is 2 years. Three patients were withdrawn before treatment began. Eighty-five were allocated to neutron therapy and 80 to receive photon therapy. All patients had squamous cell cancers in one of four primary sites: oral cavity, oropharynx, larynx, and hypopharynx. Local tumor control was similar in both groups: 44.7% after neutrons and 45.0% after photons. Salvage surgery was performed on 18 patients in each treatment group for residual or recurrent cancer. Acute radiation reactions of the mucous membranes were significantly more severe after photons. The number of patients with serious late reactions was greater after neutron therapy but the difference was not statistically significant. There were six deaths related to late morbidity after neutron therapy but none after photon therapy. Survival was better after photon therapy but the difference compared with the neutron group failed to reach statistical significance. When intercurrent deaths are excluded, the difference is less marked. Photon therapy was clearly better in terms of disease-free survival giving a 2-year local disease-free rate of 41.3% (s.e. 5.5%) compared with 29.4% (s.e. 4.9%) after neutrons.     

Re-irradiation for head and neck squamous cell carcinoma

Introduction

Local recurrences after curative treatment have a potential for cure with salvage surgery or with re-irradiation.

The emerging era of personalized therapy in squamous cell carcinoma of the head and neck

Over the past three decades there has been a move toward organ preservation protocols in the management of locally advanced mucosal head and neck squamous cell carcinomas (LAHNSCC) with combinations of radiotherapy (RT), chemotherapy and, more recently, biological agents. Current standard chemoradiation strategies have reached the upper limits of toxicity. In addition, the traditional one size fits all approach of grouping patients according to traditional clinicopathological features fails to take into account the vast underlying biological heterogeneity of tumors and their host. A number of recent advances such as highly conformal RT, molecular profiling and targeted agents, and improvements in treatment response assessment have set the scene for a fundamental paradigm shift toward greater tailoring of therapy with the aim of improving outcomes and reducing the burden of survivorship. This review focuses on the recognition of the prognostic value of tumor human papillomavirus (HPV) status, the incorporation of biologically targeted therapies and the evolving role of molecular imaging in predicting tumor response and prognosis in the curative management of LAHNSCC.     

Radiobiological intercomparisons of fast neutron beams used for therapy in Japan and the United States.

A variety of portable biological systems have been used to intercompare the neutron beams used for radiotherapy in Japan and in the United States. The two neutron centers in Japan have been compared with the four in the United States; all of the machines differ in energy and consequently the biological effectiveness varies from one to another. The biological systems used included survival in three lines of mammalian cells cultured in vitro, the response of mouse skin, the survival of crypt cells in the mouse jejunum, and the loss of weight or DNA in the mouse testes. Based on the biological data, estimates have been made of the relative potency of the various neutron beams that will be invaluable when the time comes to evaluate clinical results.     

TNP方案在头颈部鳞状细胞癌中的疗效探讨

目的 比较头颈部鳞状细胞癌(SCCHN)治疗中TNP(紫杉醇+奈达铂+替加氟)与PF(氟尿嘧啶+顺铂)组的近期疗效以及不良反应。方法 分析2009年-2014年在襄阳市中心医院接受治疗的SCCHN患者的临床资料。根据治疗方案将患者划分为PF组和TNP组。比较两组患者的一般资料、临床特征、治疗疗效以及治疗不良反应。结果 本研究纳入患者54例,其中TNP组和PF组各27例,两组患者的临床资料并无统计学差异(P＞0.05);两组患者的肿瘤部位、临床分期及分化程度均无统计学差异(P＞0.05);TNP组患者的治疗疗效优于PF组,差异具有统计学意义(χ²=7.864,P=0.048);TNP组患者的胃肠道反应发生率显著低于PF组(χ²=4.854,P=0.028),其余不良反应均无统计学差异(P均＞0.05)。结论 在SCCHN治疗中,TNP方案疗效优于PF方案,且治疗过程中的胃肠道不良反应发生率更低。     

Phase II double-blind randomized study of lonidamine and radiotherapy in epidermoid carcinoma of the lung

Patients with non metastatic squamous cell lung cancer were treated with radiotherapy (RT) plus lonidamine (LND) or placebo (PLAC), according to a randomized double-blind study design.

Treatment with lonidamine 150 mg t.i.d (27 patients) or placebo (23 patients) started 3 days before RT,lasted up to 7 months. Partial responses were observed in 14 and 6 patients respectively in the LND+RT and PLAC+RT groups. Statistical analysis of the survival curves showed no significant difference between the LND+RT (median 311 days) and PLAC+RT (median 193 days) groups.

Stage III patients survived significantly longer (p<0.05) when treated with LND+RT (median 318 days) than with PLAC+RT (median 163 days). No synergistic toxic effects between radiation and LND were noted.

To confirm these data a new and larger multicentric study is now in progress.     

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin-5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel-PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42-82 and 71-100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.     

Unilateral big hockey stick incision for neck dissection in head and neck carcinoma

Objective: To investigate for the feasibility and advantages performed by the unilateral big hockey stick incision (BHSI) in head and neck carcinoma. Methods:Neck dissection by using the unilateral big hockey stick incision (BHSI) was performed on 93 patients with head and neck carcinoma. Results: The big hockey stick incision has a cosmetic scar and not scar contraction and is barely visible and easily covered in hair and clothing; sufficient exposure of the operation field; a small area of marginal necrosis was occasionally seen at the apex of the skin flap due to having preoperative radiotherapy. Conclusion: The unilateral big hockey stick incision has adequate surgical access, good healing of skin flaps, and a good cosmetic result.     

Targeted therapy for squamous cell carcinoma of the head and neck

Targeted agents have emerged as novel drugs in the oncology field based on our understanding of the biology of individual malignancies, and have had a promising impact in several tumors. Squamous cell carcinoma of the head and neck (SCCHN) is a common disease with little progress made in survival over the past few decades. SCCHN is characterized by overexpression of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), both of which appear to have a prognostic value. Hence these receptors and their downstream pathways make attractive therapeutic targets. This review discusses targeted therapies currently being evaluated for their role in squamous cell carcinoma of the head and neck.     

头颈部鳞癌TNM分期的进展与展望

头颈部鳞癌的第8版TNM分期在前版基础上做出了许多重要改进,进一步提高了该分期在评估患者预后、指导治疗方案方面的价值.但很多研究表明,该分期的某些方面仍存在改进的空间.该文将对第8版与第7版TNM分期的主要差异、仍旧存在的不足之处,头颈部鳞癌分期的最新研究进展以及未来的发展方向作简要综述.     

Iressa治疗复发或转移性头颈鳞状细胞癌的临床研究

目的：探讨Iressa治疗复发或转移性头颈鳞状细胞癌的疗效和安全性。方法：对接受过二线化疗方案（至少一个化疗方案包括铂类）失败的复发或转移性头颈鳞状细胞癌患者,给予Iressa每日250mg口服,持续到患者出现不可接受的不良反应或疾病进展。结果：15例患者入组,Iressa 250mg日/口服治疗能够很好耐受,只出现1级和2级不良反应,但全组无1例患者获得部分反应或全消,中位疾病进展时间为4个月,中位总生存时间为16个月。结论：Iressa能够很好耐受,但是该组患者有效率很低,它在头颈鳞状细胞癌的使用除临床研究外不推荐使用。     

Bleomycin, cyclophosphamide and radiotherapy in regionally advanced epidermoid carcinoma of the head and neck

We have treated 24 patients with squamous carcinoma of the head and neck and advanced regional (N2-3) disease. The regimen consisted of 3 cycles, each of 28 days. Cyclophosphamide (1 gm/m2 I.V.) was given on day 1, bleomycin (15 u I.M.) on days 2, 4, 9 and 11, and ionizing radiation (60Co, 180 rad/fraction) days 1-5, and 8-12. No therapy was given on days 13-28. After three cycles of therapy, 13 patients had a complete response; following further therapy (surgery, interstitial or external beam radiation), 16 patients were free of disease. However, remissions were not durable and 11/16 patients recurred loco-regionally with a median time to recurrence of 5 months; most (7/11 also developed distant metastases. These patients have biologically aggressive disease and may have a worse prognosis than patients who are Stage IV based on a T4 primary lesion only.