Elsevier

Radiotherapy and Oncology

Volume 53, Issue 2, 1 November 1999, Pages 113-117
Radiotherapy and Oncology

Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome

https://doi.org/10.1016/S0167-8140(99)00102-4Get rights and content

Abstract

Background and purpose: To evaluate the long term clinical significance of tumor oxygenation in a population of head and neck cancer patients receiving radiotherapy and to assess changes in tumor oxygenation during the course of treatment.

Methods and materials: Patients with head and neck cancer receiving primary RT underwent pretreatment polarographic tumor oxygen measurement of the primary site or a metastatic neck lymph node. Treatment consisted of once daily (2 Gy/fraction to a total dose of 66–70 Gy) or twice daily irradiation (1.25 Gy/fraction to 70–75 Gy) to the primary site. Twenty-seven patients underwent a second series of measurements early in the course of irradiation.

Results: Sixty-three patients underwent pretreatment tumor oxygen assessment (primary site, n=24; nodes, n=39). The median pO2 for primary lesions was 4.8 mmHg, and it was 4.3 mmHg for cervical nodes. There was a weak association between anemia and more poorly oxygened tumors, but many non-anemic patients still had poorly oxygenated tumors. Repeat assessments of tumor oxygenation after 10–15 Gy were unchanged compared to pretreatment baselines. Poorly oxygenated nodes pretreatment were more likely to contain viable residual disease at post-radiation neck dissection. Median follow-up time for surviving patients was 20 months (range 3–50 months). Hypoxia (tumor median pO2 <10 mmHg) adversely affected 2 year local-regional control (30 vs. 73%, P=0.01), disease-free survival (26 vs. 73%, P=0.005), and survival (35 vs. 83%, P=0.02).

Conclusion: Tumor oxygenation affects the prognosis of head and neck cancer independently of other known prognostic variables. This parameter may be a useful tool for the selection of patients for investigational treatment strategies.

Introduction

Tumor hypoxia predicts an adverse treatment outcome in the radiotherapeutic management of cancer of the head and neck, uterine cervix, and in soft tissue sarcomas [2], [4], [7], [10], [11], [15]. For cervical carcinoma, the significance is independent of other known variables such as tumor stage [10]. Whether such independent significance exists in head and neck cancer as well is not known.

Reoxygenation has been demonstrated to occur early in the course of preoperative irradiation and hyperthermia for soft tissue sarcomas. Improved tumor oxygenation has been correlated with increased likelihood of favorable pathologic response [3]. Treatment induced changes in the oxygenation of head and neck cancer along with any associated clinical significance are less well understood [13]. In a preliminary report, we described worse local control, disease free survival, and overall survival in head and neck cancer patients with tumor median pO2 values <10 mmHg [4]. At that time, most patients had only undergone pretreatment oxygen assessment. Since then the total number of patients enrolled in this study has more than doubled. Our policy has also been revised to incorporate a second set of measurements early in the course of treatment. This report updates our previous experience, evaluates treatment induced changes in tumor oxygenation, and examines the significance of tumor oxygenation in a multivariate setting.

Section snippets

Methods and materials

Patients with newly diagnosed, non-metastatic head and neck squamous carcinoma who were to receive primary radiotherapy were eligible. Patients with stage I/II disease were treated with conventional fractionation to doses of 66–70 Gy. Accelerated hyperfractionation with or without concurrent CDDP/5-FU chemotherapy was employed for more advanced presentations [5]. Post radiation adjuvant neck dissection was planned for N2–N3 neck disease.

Polarographic electrode1

Results

Sixty-three patients underwent pretreatment tumor oxygen assessment from November 1992 to July 1998. Tumor location and treatment parameters are outlined in Table 1. The majority of primary tumors originated in the oropharynx. Approximately half of all primary tumors were stage T3 or T4 while approximately 3/4 of the patients had N2 or N3 cervical lymphadenopathy (Table 2). The median target dose was 69 Gy. Oxygen measurements were obtained from the primary tumor in 24 (38%) patients and from

Discussion

The present study has reconfirmed our initial observation that tumor hypoxia exerts an adverse effect on the radiotherapeutic management of head and neck cancer. LRC, DFS, and S were better by a factor of two in the group of patients with well-oxygenated tumors. The correlations of oxygenation with the outcome endpoints were independent of other clinically important factors such as stage and treatment.

Repeat assessments of tumor oxygenation after 10–15 Gy were unchanged compared to pretreatment

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