Effectiveness of Adjuvant Radiotherapy in Patients With Oropharyngeal and Floor of Mouth Squamous Cell Carcinoma and Concomitant Histological Verification of Singular Ipsilateral Cervical Lymph Node Metastasis (pN1-state)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 209
- 试验地点
- 58
- 主要终点
- Primary study object: overall survival
研究概览
简要总结
Radiotherapy with or without adjuvant chemotherapy represents an important column of modern therapy in advanced squamous cell originated tumours of the head and neck. However to date no studies are available which study the effectiveness of radiotherapy in patients with resected small tumours (T1, T2) and concomitant ipsilateral metastasis of a single lymph node (pN1) for general treatment recommendation. The present study is designed as non-blinded, prospective, multicenter randomized controlled trial (RCT) for comparison of overall-survival as primary clinical target in patients receiving radiation therapy vs. patients without adjuvant radiation following curative intended surgery. Aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (radiation/non-radiation. Secondary clinical endpoints are as follows: Incidence and time to tumor relapse (locoregional relapse, lymph node involvement and metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module) and time from operation to orofacial rehabilitation.
详细描述
Background
Prevailing curative intended therapeutic strategies combine radical resection of the tumor mass with a safety margin followed by radiation of the original tumor site and adjacent locoregional lymphatic drainage areas. To date selection of the individual therapeutic pattern is essentially guided by pre- and post-therapeutic TNM staging parameters. Exceptionally for advanced tumors postoperative radiotherapy and optional combination with (radiosensitizing) chemotherapeutic agents is favorable and recommended. Interdisciplinary guidelines stated the following detailed recommendations for application of adjuvant radiation therapy:
- non in sano resection if reoperation is impossible (R1-, R2-status)
- primary tumor status > pT2 and pN2, pN3
- extranodular spread of the disease
- lymphangiosis carcinomatosa
- facultative: pN1 According to these recommendations postoperative radiotherapy of advanced tumors is feasible while for small tumors indication for adjuvant therapy depends on further parameters like the pN findings. Here verification of more than one singular lymph node metastasis (pN2) leads to additional radiotherapy. In tumors with a diameter less than 4 cm (T1, T2) and concomitant verification of a single lymph node metastasis no explicit therapeutic recommendation is offered to date displaying radiation an optional complement for these cases. Meta-Analysis revealed only a few studies taking this special group of patients into account stating adjuvant radiotherapy an additional risk factor for overall survival, however small patient numbers, inhomogeneous group distribution and ambiguous risk factors exhibited a significant bias.
The methodological key problems which had to be addressed in the protocol were the following:
- extremely different treatment arms with strong preferences for one or the other therapy arm
- low number of eligible patients per center
- Inclusion criterion (pN1) including a pathological diagnosis and surgical treatment with possible differences
- Radiation treatment as one arm with special need for quality control Thus the idea of presenting this paper is, to discuss how these specific issues were taken care of.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histological diagnosis of a primary squamous cell carcinoma of the oral cavity or the oropharynx
- •maximum tumor diameter less than 4 cm in the pathohistological specimen irrespective of histological grading (pT1 or pT2)
- •concomitant histological verification of a singular ipsilateral lymph node metastasis less than 3cm in diameter (pN1) without penetration of the lymph node´s capsule and without presence of invasion of lymphatic vessels (lymphangiosis carcinomatosa)
- •radical resection of the tumor within adequate resection margins (R0)
- •written informed consent from the patient
- •adequate performance status ECOG Index ≤ 2
排除标准
- •an age less than 18 years old
- •pregnant women
- •reported drug addiction
- •intake of remedies with potential influence on compliance or impaired judgment
- •patients with mental disorders or conceivable physical, familial or job related embarrassments which may preclude the patient to realize the study schedule
- •inadequate performance status ECOG Index > 2
结局指标
主要结局
Primary study object: overall survival
时间窗: 9 years
The objective of the clinical study will be to investigate two different patient groups (irradiated/unirradiated) with pT1/2 primary and verification of a singular ipsilateral lymph node metastasis in parallel design in order to evaluate the possible benefit of radiation therapy. The following null hypothesis forms the basis of the present study: Radiation therapy will have no influence on the overall survival in patients with pT1/2, pN1 primary tumor. First patients will be observed for 9 years, last patient in will be followed-up for 5 years.
次要结局
- Time to occurrence of local relapse(2, 3 and 6 months; 1 year to 9 years)
- Time to occurence of distant metastasis(2,3,6 months and 1 year to 9 years annually)
- Time to lymphatic metastasis(2, 3 and 6 months, 1 year to 9 years)
- Quality of Life(after 6 months, 1 year and annually till end of study)
研究者
Bilal Al-Nawas
Prof. Dr. Dr. Bilal Al-Nawas
Johannes Gutenberg University Mainz