British Journal of Radiology 75 (2002),238-242 © 2002 The British Institute of Radiology
Severe complications after hypofractionated high dose rate intracavitary brachytherapy following external beam irradiation for oesophageal carcinoma
Y Hama, MD
1
M Uematsu, MD
1
A Shioda, RTT
1
A Suda, RTT
1
S Aida, MD
2 and
S Kusano, MD
1
Departments of 1 Radiology and 2 Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-0042, Japan
Correspondence: Minoru Uematsu, MD
 |
Abstract
|
|---|
The purpose of this study was to evaluate severe complications that developed after high dose rate (HDR) intracavitary brachytherapy for oesophageal carcinoma. Six consecutive patients with oesophageal carcinoma were treated by external beam irradiation (60 Gy in 30 fractions over 6 weeks) followed by hypofractionated intracavitary HDR brachytherapy (10 Gy in 2 fractions). Two of the six patients were alive and well for more than 2–3 years following therapy, but three of the six patients developed treatment-related oesophageal fistulae and died. HDR intracavitary brachytherapy following external beam irradiation is an effective method for radical treatment of oesophageal carcinoma. However, hypofractionated HDR brachytherapy should be used with care.
|
Introduction
|
|---|
Despite major advances in treatment technique, the prognosis of oesophageal cancer remains poor owing to the high incidence of local recurrence and distant metastases. Many authors have reported that intracavitary brachytherapy of oesophageal carcinoma is a highly effective and safe therapeutic modality, not only as a palliative therapy but also as a radical treatment [1–6]. It has been widely recommended that 10–20 Gy in 2–4 fractions is the optimal dose for intracavitary brachytherapy after external beam irradiation to 55 Gy in 22 fractions in 5.5 weeks or 60 Gy in 30 fractions in 6 weeks [1–7], if treated without chemotherapy. However, a few reports, emphasize severe complications such as treatment-related fistulae [3, 5, 8–11]. This paper reviews our experience with six consecutive patients.
|
Patients and methods
|
|---|
From January 1996 to April 1997, six consecutive patients with newly diagnosed squamous cell carcinoma of the oesophagus were treated with hypofractionated high dose rate (HDR) intracavitary brachytherapy following standard external beam irradiation. Patient sex and age, and tumour site, primary length and clinical stage, as well as irradiation doses are listed in Table 1
. All patients were male, with ages ranging from 49–78 years (mean 66 years).
Pre-treatment staging evaluation included chest radiography, barium swallow, and chest and abdominal CT. Each patient underwent an oesophagoscopy and had biopsy-proven squamous cell carcinoma of the oesophagus. Bronchoscopy and endoscopic ultrasound were performed when indicated.
All six patients received conventional external beam irradiation to 60 Gy with 6 or 10 MV X-rays. The initial treatment volume included the entire oesophagus, the entire mediastinum, the coeliac nodes and the bilateral supraclavicular nodes. Parallel opposed anterior and posterior shaped fields were used for the initial 40–45 Gy in 22–25 fractions in 24–37 days, and three or four field arrangements were used for the additional 15–20 Gy in 5–8 fractions in 12–22 days. The field included the primary tumour with 2–3 cm proximal and distal margins and was irradiated to a total of 60 Gy. All patients were treated daily, 5 times per week.
Intracavitary brachytherapy was performed with a HDR remote afterloader 3–14 days after completion of external beam irradiation. Cobalt-60 seeds were used, in all patients. HDR brachytherapy was delivered with a balloon expandable applicator, inserted transorally (RALS-T (Toshiba); Create Medic, Tokyo, Japan). To avoid faulty balloon technique, a double balloon applicator was used, which is commonly used in Japan. The outer diameter of the brachytherapy applicator was 15 mm, and its length was 10 cm. The dose was prescribed 5 mm below the surface of the mucosa. The brachytherapy dose was 10 Gy in 2 weekly fractions of 5 Gy each, or 13 Gy at a point 10 mm from the axis of the irradiation source. The median tissue volume receiving 100% of the brachytherapy prescription dose (10 Gy in 2 fractions) was 30.1 ml (range 25.3–33.7 ml). Verification that inflation of the balloon remained identical at each session was done using an X-ray simulator, and radiographs of the application were performed before each fraction. Figure 1 shows an example of the irradiation field and dose distribution. The oesophageal tumour length was determined from the CT scans, barium swallow and endoscopy findings, taking the longest of the three available measurements. Chemotherapy was given in only one case (patient 4), 3 weeks before the external beam irradiation, with cisplatin 50 mg m-2 bolus infusion on days 1–3 followed by 5-fluorouracil 1000 mg m-2 by 24 h infusion for 5 consecutive days. Tumour involvement of the tracheobronchial tree was noted in one patient (patient 5).
View larger version (129K):
[in this window]
[in a new window]
|
Figure 1. (a) Posteroanterior and (b) lateral views of dose distributions (patient 4). Numbers indicate the total dose in per cent stemming from the application. The dose reference point is 5 mm below the oesophageal mucosa.
|
|
Patients were followed up every 1–3 months after therapy. Follow-up evaluation was performed by physical examination, barium swallow, chest CT and endoscopy. Endoscopy was performed 1–3 months following completion of therapy, but post-treatment biopsies were performed only if suspicious areas were identified.
Patients with no evidence of tumour on barium swallow, CT and endoscopy were considered "complete responders" to treatment. Those with histologically confirmed tumour were judged as "treatment failures". There was no definition of partial response in this study.
|
Results
|
|---|
All patients showed significant improvement in symptoms during the external beam irradiation. Intracavitary brachytherapy was well tolerated and did not result in any severe acute toxicity. Within 3 months after therapy, barium swallows showed complete response in all the patients (Figure 2). The final status of each patient is shown in Table 2.
View larger version (158K):
[in this window]
[in a new window]
|
Figure 2. Radiographic response of oesophageal cancer to external beam and intracavitary irradiation (patient 4). (a) Before therapy. (b)After therapy, the tumour has disappeared almost completely.
|
|
One patient (patient 1) died of pneumonia, but with the primary site controlled. Patient 3 was in complete remission for 6 months, but due to severe ulceration at the irradiated site he underwent oesophagectomy. Pathologic examination of the surgical specimen showed transmural fibrosis and necrotic changes in tumour tissues, although a few viable tumour cells still remained. The diagnosis of local recurrence was made on the basis of pathological findings in this excised specimen.
Oesophageal fistula was recognized in patients 4, 5 and 6, leading to death in all of them. The fistula was oesophagotracheal in patients 4 and 5, oesophageal–mediastinal in patients 4 and 6, and between the oesophagus and thoracic cavity in patient 5.
Patient 4 developed an oesophagotracheal fistula 7 months after therapy, and this was also complicated by mediastinitis and a pulmonary abscess (Figure 3). Endoscopic and histopathological findings did not show relapse in the irradiated field, however, a pulmonary metastasis was noted on CT. He was treated with antibiotic therapy but his condition deteriorated and he died 16 months following initial treatment. An autopsy was not performed.
View larger version (85K):
[in this window]
[in a new window]
|
Figure 3. CT of patient 4 shows a thin walled abscess cavity with air–fluid levels representing the connection to the bronchial system.
|
|
In patient 5, the oesophagotracheal fistula was identified 4 months after therapy (Figure 4). The fistula was treated by a metallic covered stent, but the patient died of empyema 3 weeks later. At autopsy, the distal end of the stent was found to have perforated through the oesophageal mucosa into the right thoracic cavity. A small oesophagotracheal fistula was also noted proximal to the site of initial disease. There was no recurrence found at autopsy.
View larger version (119K):
[in this window]
[in a new window]
|
Figure 4. Oesophagograph demonstrating the connection between the mid oesophagus and a right lower lobe bronchus (patient 5).
|
|
The fistula in patient 6 was identified 4 months after therapy, without evidence of recurrence on CT and endoscopic examination. This patient subsequently developed mediastinitis caused by oesophagomediastinal fistula. He received antibiotic therapy and the mediastinitis improved. 2 months after antibiotic therapy he suddenly developed a massive haematemesis and died. He did not undergo endoscopic examination, but an aortooesophageal fistula was suspected.
Of the six patients, three developed fistula and died from fistula-related diseases. The mean survival of the entire group was 15.8 months (range 5–34 months). Owing to the high complication and mortality rates, we have not continued this therapy since May 1997, although two of the six patients were alive and well for more than 2–3 years following therapy.
|
Discussion
|
|---|
Oesophageal intracavitary brachytherapy has been advocated as a radiotherapeutic technique enabling irradiation of locoregional disease to a high dose with relative sparing of the surrounding normal tissues, potentially increasing tumour control whilst minimizing late complications [2, 3, 13, 14]. A comparison of survival in patients treated with or without a brachytherapy boost following external beam irradiation suggested that although 5-year survival was not definitely improved, local control at 2 years was significantly better in the brachytherapy group [4, 7, 15–17]. Cause of death following brachytherapy was mostly attributed to local failure in some series [5, 14–16].
In our own experience, 50% (3/6) of patients developed oesophageal fistulae, despite undergoing the recommended treatment regimen [2, 3, 8, 13, 14]. In view of suboptimal primary tumour control, giving an adequate radiation dose is important. However, employing hypofractionated oesophageal brachytherapy as used in this study (10 Gy in 2 fractions) following conventional 60 Gy external beam irradiation may expose patients to the risk of overdosage [2, 3, 8, 13, 14]. Owing to the high incidence of late complications (60%; 6/10) following a brachytherapy fractionation dose of 4–5 Gy, Akagi et al [18] decreased the dose to 2–2.5 Gy. Their brachytherapy fraction dose of 4–5 Gy was the same as that used in our series, and the complication rate (60%) was also close to ours (50%). They suggested that following 60 Gy external beam irradiation, a higher number of brachytherapy fractions with a lower fraction size reduces the incidence of late complications whilst maintaining the local control probability [18]. The high incidence of fistulae in our study may be related to the high fraction size (5 Gy at 5 mm depth from the mucosa, or 6.5 Gy at 10 mm from the source) and low fraction number (two) delivered by the intracavitary brachytherapy, but also to the higher number of cases with infiltrative lesions. Radiobiologically, a lower dose at each session and a greater number of fractions may reduce late complications. Only six patients were treated with this protocol, which may be too small a number to draw any conclusions. However, the high incidence of oesophageal fistulae in our experience is alarming [10]. Pending the results of further prospective studies, a brachytherapy boost as given in this study should be used with caution.
|
Acknowledgments
|
|---|
We thank Dr T Matsubara, Department of Surgery, Cancer Institute Hospital, Tokyo, Japan, for supplying the histological sections.
Received for publication June 4, 2001.
Revision received August 10, 2001.
Accepted for publication August 20, 2001.
|
References
|
|---|
-
Dokiya T, Yorozu A. Current status of radiotherapy for esophageal carcinoma. Jpn J Cancer Chemother 1995;22:863–8.
-
Flores AD, Nelems B, Evans K, Hay JH, Stoller J, Jackson SM. Impact of new radiotherapy modalities on the surgical management of cancer of the esophagus and cardia. Int J Radiat Oncol Biol Phys 1989;17:937–44.[Medline]
-
Hareyama M, Nishio M, Kagami Y, Narimatsu N, Saito A, Sakurai T. Intracavitary brachytherapy combined with external-beam irradiation of squamous cell carcinoma of the thoracic esophagus. Int J Radiat Oncol Biol Phys 1992;24:235–40.[Medline]
-
Hishikawa Y, Kamikonya N, Tanaka S, Miura T. Radiotherapy of esophageal carcinoma: role of high-dose-rate intracavitary irradiation. Radiother Oncol 1987;9:13–20.[Medline]
-
Micaily B, Miyamoto CT, Freire JE, Brady LW. Intracavitary brachytherapy for carcinoma of the esophagus. Semin Surg Oncol 1997;13:185–9.[Medline]
-
Nishio M, Horikawa Y, Morita K, Sakurai T, Kagami Y, Narimatsu N. The usefulness of intracavitary brachytherapy in esophageal cancer. Gan No Rinsho 1988;34:261–8. [In Japanese.] [Medline]
-
Okawa T. Clinical optimization study of radiotherapy for esophageal cancer. J Jpn Soc Ther Radiol Oncol 1999;11:53–8.
-
Gaspar LE, Qian C, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy and concurrent chemotherapy in localized cancer of the esophagus (RTOG 92-07): preliminary toxicity report. Int J Radiat Oncol Biol Phys 1997;37:593–9.[Medline]
-
Okawa T, Tanaka M, Kita-Okawa M, et al. Superficial esophageal cancer: multicenter analysis of results of definitive radiation therapy in Japan. Radiology 1995;196:271–4.[Abstract/Free Full Text]
-
Gaspar LE, Winter K, Kocha WI, Coia LR, Herskovic A, Graham M. A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207). Cancer 2000;88:988–95.[Medline]
-
Gasper LE, Nag S, Herskovic A, Mantravadi R, Speiser B, and the Clinical Research Committee of the American Brachytherapy Society. American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal carcinoma. Int J Radiat Oncol Biol Phys 1997;38:127–32.[Medline]
-
Behars OH, Henson DE, Hutter RVP, Kennedy BJ. Manual for staging of cancer (4th edn). Philadelphia, PA: Lippincott, 1992:57.
-
Bottrill DO, Plane JH, Newaishy GA. A proposed afterloading technique for irradiation of the oesophagus. Br J Radiol 1979;52:573–4.[Abstract/Free Full Text]
-
Harvey JC, Fleischman EH, Belloti JE, Kagan AR. Intracavitary radiation in the treatment of advanced esophageal carcinoma: a comparison of high dose rate versus low dose rate brachytherapy. J Surg Oncol 1993;52:101–4.[Medline]
-
Hishikawa Y, Kurisu K, Taniguchi M, Kamikonya N, Miura T. High-dose-rate intraluminal brachytherapy for esophageal cancer: 10 years experience in Hyogo College of Medicine. Radiother Oncol 1991;21:107–14.[Medline]
-
Hishikawa Y, Kurisu K, Taniguchi M, Kamikonya N, Miura T. High-dose-rate intraluminal brachytherapy (HDRIBT) for esophageal cancer. Int J Radiat Oncol Biol Phys 1991;21:1133–5.[Medline]
-
Marks RD, Scruggs HJ, Wallace KM. Preoperative radiation therapy for carcinoma of the esophagus. Cancer 1976;38:84–9.[Medline]
-
Akagi Y, Hirokawa Y, Kagemoto M, et al. Optimum fractionation for high-dose-rate endoesophageal brachytherapy following external irradiation of early stage esophageal cancer. Int J Radiation Oncology Biol Phys 1999;43:525–30.[Medline]
Top
Abstract
Introduction
