Concomitant radiotherapy and hyperthermia for primary carcinoma of the vagina: A cohort study

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Abstract

Objective

To evaluate the supplementary value of adding hyperthermia to radiotherapy in patients with primary vaginal cancer.

Study design

Cohort of 44 patients diagnosed with primary vaginal cancer between 1990 and 2002 was assessed. Survival rates and median survival of patients with primary vaginal cancer undergoing radiotherapy with and without hyperthermia were compared. Hyperthermia was solely added to radiotherapy in case of a tumor size >4 cm in diameter for FIGO stage III disease.

Results

The calculated overall 5-year survival of primary vaginal cancer was 63%. In comparison to histologic high grade tumors, higher survival rates for histologic low grade tumors were calculated. For FIGO stage III of disease, the addition of hyperthermia to radiotherapy for tumors >4 cm in diameter resulted similar survival rates and median survival when compared to those achieved by radiotherapy as monotherapy in tumors of <4 cm in diameter.

Conclusions

The addition of hyperthermia to radiotherapy might result in better survival rates in primary vaginal cancer for tumors >4 cm in diameter. The supplementary effect of hyperthermia to radiotherapy may be a feasible and beneficial approach in the treatment of vaginal cancer.

Introduction

Primary vaginal cancer [1] is an uncommon malignancy, comprising 1–3% of all gynaecological malignancies [2]. This malignancy generally occurs at postmenopausal age with a peak incidence between 70 and 79 years of age. However, solely the diethylstilbestrol (DES) related clear-cell carcinoma is in general diagnosed below 40 years of age. The most common histological entity of this malignancy is squamous cell carcinoma (85%), followed by adenocarcinoma (6%) and miscellanous tumors including clear-cell carcinoma (9%), respectively [3].

Tumor stage, as described by the International Federation of Gynecology and Obstetrics (FIGO) is the major prognostic factor [3], [4]. Other prognostic factors are tumor size, tumor extent within the vagina, histological grading, and lymphatic involvement [3], [5].

Most patients with primary vaginal cancer are primarily treated by radiotherapy [6]. Although surgery may be treatment of first choice in the early stages of disease [7], the application of this modality is limited due to the low performance status of these elderly patients [8]. There is limited data on the application of radiotherapy with concomitant chemotherapy and hyperthermia [6], [8], [9]. Hyperthermia is an effective cell killing agent especially to cells in an hypoxic, nutrient deprived and low pH environment, commonly present in malignant tumors. The addition of hyperthermia to radiotherapy provides supra-additive cytotoxic effects [10], [11].

This cohort study was initiated to assess survival and morbidity in patients with primary carcinoma of the vagina undergoing radiotherapy with or without the addition of hyperthermia or chemotherapy. The supplementary effect of the addition of hyperthermia to radiotherapy was assessed by comparing treatment outcome of patients undergoing radiotherapy with and without hyperthermia for primary vaginal cancer.

Section snippets

Materials and methods

Patients who presented with primary cancer of the vagina and eligible for radiotherapy with or without hyperthermia or chemotherapy between December 1990 and November 2002 were identified from the Erasmus MC/Daniel den Hoed Cancer Center registry files. All patients with histologically confirmed malignancy of the vagina were included in the study. Patients with a history of malignancy (cervical, endometrium, vulva, rectum, or bladder carcinoma) that may explain the presence of vaginal cancer

Results

A total of 44 patients with primary vagina cancer were included in the study. Four patients elected to refrain from any form of therapy and were, as a consequence, not analyzed in terms of survival. Median age of patients at time of initial diagnosis was 67 years (range 32–95). The main symptom in these patients prior to diagnosis was vaginal bleeding (n = 35), pain (n = 5), voiding difficulties (n = 2) or vaginal discharge (n = 2) (Table 1).

Six patients were diagnosed with FIGO stage I, 23 patients

Discussion

This retrospective analysis represents the outcome of a cohort of 44 patients with primary invasive carcinoma of the vagina between 1990 and 2002. Characteristics of the population with respectively a mean age of 67 years, symptoms of vaginal bleeding, size of the tumor at time of diagnosis, and histological characterization were comparable with previous reports (Table 1) [4], [12].

The overall survival of 63% was comparable with other studies [4], [6], [13]. However, no statistically

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