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Journal of Cancer Research and Therapeutics, Vol. 4, No. 3, July-September, 2008, pp. 121-125 Original Article Comparative evaluation between re-irradiation and demand endoscopic dilatation vs endoscopic dilatation alone in patients with recurrent/reactivated residual in-field esophageal malignancies Teli Mohmad Ashraf, Mushood GNabi, Zargar SAli, Andrabi Wajahat H Department of Radiotherapy, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar-190 011, Kashmir Code Number: cr08036 Abstract Background: Esophageal cancer has emerged as a major health challenge in many regions of the world, including the valley of Kashmir, which is situated adjacent to the esophageal cancer belt on its Southern side. Radiotherapy is one of the main modalities of treatment. However, residual/recurrent disease is common and salvage options for these patients are limited. Scarce literature is available regarding the use of re-irradiation in this setting though re-irradiation has been successfully used in recurrent tumors at various other anatomical sites.
Keywords: Carcinoma esophagus, dysphagia, endoscopic dilatation, feeding gastrostomy, radiotherapy, re-irradiation Introduction Cancer of the esophagus was first recorded in China some 2000 years back, where it was called ′Ye-Ge.′ Today, esophageal cancer has emerged as a major health challenge in many regions of the world, including in the valley of Kashmir, which has the esophageal cancer belt on its southern side. In Kashmir, hospital-based data has revealed a point incidence of 34.4/100,000 in males and 22.7/100,000 in females, with an age-standardized incidence of 43.6/100,000 and 27.9/100,000 per annum in males and females, respectively. [1] At present, treatment of esophageal cancer is primarily palliative because most of the patients present late [2] and are not suitable candidates for a curative surgical resection. Consequently, other alternate treatments have been used. In this context, definitive radiotherapy has found wide application in the treatment of carcinoma esophagus. In patients with advanced locoregional disease the recurrence rate is high even with high doses of radiation. [3],[4] The effects of local tumor recurrence or reactivation of tumor re-growth are often distressing, and management of these patients presents a great challenge to oncologists. The treatment options available for such patients are limited because of the cost, complications, and comorbidities. [5] In the Kashmir valley, per-oral endoscopic dilatations constitute a major palliative method for these patients. The other options include feeding gastrostomy, laser treatment, and esophageal prosthetic stents. These methods have their own limitations with regard to availability, acceptability, and cost-effectiveness.[6],[7] Re-irradiation for the recurrent/reactivated residual tumors requires the utmost caution because of the side effects and sequelae of re-irradiation. [8] Lately, however, re-irradiation has been successfully used in many recurrent tumors of various sites with encouraging results, [9],[10],[11],[12],[13],[14],[15],[16] which prompted us to undertake this study in this group of patients to assess its feasibility and its impact on quality of life vis-à-vis endoscopic dilatation alone. Materials and Methods The present study was conducted in the Department of Radiation Oncology, SKIMS, Srinagar, in collaboration with the Department of Gastroenterology and the Department of Medical Physics and Bioengineering. Ninety-one patients were enrolled for the present study during a period from May, 2000 to May, 2002. Twenty-two patients were excluded due to various reasons (seven developed tracheoesophageal fistulas (TEF), 12 patients had not completed 6 months since their last radiotherapy regimen, two had no evidence of malignancy on histopathology, and one patient had developed liver secondaries). Salvage surgical option was refused by all our patients. The inclusion criteria were: 1) patients with in-field residual/recurrent tumor; 2) tumor in middle and lower third of the esophagus; 3) presence of tumor confirmed radiologically, endoscopically, and histopathologically; 4) history of having been treated with radical doses of external-beam radiotherapy for the primary tumor, with a time interval of at least 6 months between the initial radical radiotherapy and the re-irradiation treatment protocol; and 5) Karnofsky performance scores of> 50% or WHO performance score ≥4 and dysphagia grade of I-IV. The exclusion criteria were: 1) patients with tracheoesophageal/bronchoesophageal fistula (TEF), 2) radiation-induced stricture/fibrosis, 3) distant metastases to vital organs like brain and lung with life expectancy of less than 2-3 months, 4) patients with comorbid conditions, and 5) Karnofsky performance scores of < 50% or WHO performance score ≤ 4. The patients in the re-irradiation arm were treated on a telecobalt unit (Theratron-780); the target volume included the gross tumor plus a 2-3 cm margin on either side. Two posterior oblique portals were used, avoiding the angles used in the previous portal arrangement. The usual field size was 10 x 6 cm or 12x 6 cm. Isodose distribution in and around the tumor and surrounding critical structures (i.e., lungs, spinal cord, and pericardium/heart) was plotted using PLATO treatment planning system (Nucletron). Re-irradiation doses depended upon the interval after the previous radiotherapy course [Table - 1]. Patients in this group were scheduled to undergo dilatation, if indicated, during the treatment/follow-up period to relieve them of dysphagia and for maintenance of proper nutrition. Patients were evaluated for response with radiological investigations and endoscopy 4 weeks after completion of re-irradiation. Thereafter, patients were followed up at 4-6 week intervals. The treatment protocol for the per-oral demand dilatation alone group (control group) was performed using a flexible fiberoptic endoscope (Olympus CLV-420 with 9 mm cope) with the aim of maintaining the dysphagia level below grade II. Patients were kept fasting for 6-8 h prior to the procedure, which was performed in the left lateral decubitus position using oropharyngeal topical anesthesia and/or intravenous sedation with 1-3 mg midazolam or pentazocine. Savary-Gillard dilators (5, 7, 9, 11, 12.8, 14, and 15 mm) were used for dilatation. The total number of sittings and the time interval between each sitting was recorded. Dilatation was continued, using dilators of increasingly greater sizes, until some blood stain was noticed on the dilator. At each dilatation procedure, patients were admitted for observation for 12-24 h for complications like bleeding, aspiration, etc. In patients who complained of persistent chest pain, an x-ray of the chest and a Conray swallow was performed immediately. The next dilation procedure was scheduled and attempted only when the dysphagia level had reached grade III-IV Results Sixty-nine patients were available for final evaluation and analysis. Of these 34 patients had been randomly assigned to the re-irradiation group and 35 underwent endoscopic per-oral demand dilatation alone. Patients in both the groups were comparable at randomization with respect to their age, sex and other demographic variables, and various other clinical parameters [Table - 2]. The workup included a complete history, with the stress being on the degree of dysphagia and performance status; the dysphagia was graded into five grades with grade 0 representing no difficulty in swallowing and grade IV representing absolute dysphagia. A detailed systemic examination was carried out; this was followed by a battery of investigations, including complete blood counts (CBC), serum biochemistry, barium esophagus (an AP and oblique view), x-ray of chest, endoscopy and endoscopic biopsy, ECG, ultrasound examination, CT scan; various nuclear isotope scans were performed as and when required in many patients as a part of their metastatic workup. The longitudinal extension and the luminal narrowing was assessed endoscopically and complemented by radiological investigations and graded into three grades with grade I representing less than 50% of luminal narrowing, grade II indicating more than 50% luminal narrowing with the endoscope negotiable beyond the lesion, and grade III representing grade II narrowing with endoscope not negotiable beyond the lesion. All patients in the re-irradiation group had initially received radiation doses of 60-65 Gy with conventional fractionation.Sixteen (47%) of these patients had recurrence/reactivation of their disease within 1 year of completion of their radical treatment, six patients (17.6%) within 1.5 years, and 12 cases (35.3%) 1.5 years after completion of their initial radiotherapy. These patients received doses of re-irradiation as per the protocol detailed in [Table - 1]. Radiation was delivered using two posterior oblique portals. Care was taken to ensure that the angles of the incident beams were different from that used in the previous radiotherapy portal arrangement and that the anterior portal was omitted. (In the usual previous radiotherapy plan the initial field arrangement consisted of two parallel opposing AP-PA portals, followed by supplement by reduced fields using three field portal arrangements: one anterior and two posterior obliques). Dilatation procedure was as described earlier. All the 35 patients in the dilatation group underwent the first dilatation procedure. For the second dilation procedure only 29 patients were available, and only ten patients were available for their third dilatation procedure. The mean duration between the first and second dilatation procedures was 35.6 ± 2.81 days and between the second and third dilatation procedure it was 36 ± 4.42 days. The majority of patients in this group either died (19/35) or developed life-threatening complications like TEF (5/35), or were lost to follow-up (11/35). The mean follow-up in these patients was 3.1 ± 1.1 months (range 1-5.83 months). In the re-irradiation group four patients were lost to follow-up within 5-9 months of completion of re-irradiation. Eighteen patients had died and 12 had survived at closure of the study. No patient in the re-irradiation group needed per-oral dilatation at any time during the course of this study. The mean overall survival period in the re-irradiation group was 7.93 ± 1.75 months (limited to 13 months) compared to 3.1 ± 1.1 months in the control group [limited to 6 months (t=2.47, P≥0.05)].Patients in the re-irradiation group showed better and more sustained improvement in their grade of dysphagia [Table - 3]. Distribution of patients vis-à-vis improvement in their performance status is detailed in [Table - 4] and the early and late toxicity profiles are shown in [Table - 5] and [Table - 6]. Discussion There have been several reported trials of re-irradiation in various recurrent malignancies, particularly in head and neck tumors, with encouraging results. [5],[7],[8],[9],[13],[14],[15],[17],[18] However, there is a dearth of literature regarding re-irradiation in recurrent/residual in-field esophageal tumors. This problem has huge dimensions and important implications in our area, and this study was undertaken keeping in view the plight of such patients and their economic constraints. Re-irradiated patients in the present study had a better quality of life, as assessed by the improvement in their performance scores and nutritional status, weight gain, and improvement in dysphagia; they also had better survival rates. In this regard, our results are consistent with the results reported in literature in recurrent tumors of various anatomical sites. [8],[10],[11],[12],[18],[19],[20],[21],[22],[23],[24] To the best of our knowledge, there is no literature available comparing the various modalities used in recurrent esophageal carcinoma. This is particularly true of use of re-irradiation with external-beam radiotherapy in this setting. Sharma et al. have used high-dose-rate intraluminal brachytherapy (HDR-ILRT), with or without external radiation, in 58 patients with advanced/recurrent esophageal carcinoma. The group included 21 patients with recurrent tumors. Overall improvement in swallowing status was seen in 22 patients (48%). Median dysphagia-free survival was 10 months. Overall complication rate was 30%, with stricture seen in 9 patients (15%), ulceration in 6 (10%), and tracheoesophageal fistula in 3 patients (5%). Complication rates were higher in the post-treatment group (38%) than in the previously untreated group (27%) (P = 0.29). The median overall survival for the entire group was 7 months. Median survival was better, although not significantly so, for the previously untreated cohort: 7.8 months vs 6 months.[25] In the present study, we re-irradiated 34 patients with recurrent/residual tumors using external-beam radiotherapy and achieved a mean survival of 7.93 ± 1.75 months, which is better than the results of Sharma et al. Pongchairerks used endoscopic laser treatment in 22 patients of stage III and IV new (untreated) cases of esophageal carcinoma. The mortality was high, with median survival of only 159.5 days. [26] Our survival results with the use of external-beam re-irradiation are better, probably because we had excluded patients with metastatic disease. Re-irradiation with radical doses of radiation compels one to think of radiation-induced toxicities, particularly the acute sequelae of such a treatment protocol. [5],[20] Computerized treatment planning system (TPS) aided us in precise tumor localization and dose computation, thereby minimizing irradiation of normal tissues. However, better results can be achieved using IMRT/conformal radiotherapy protocols. In the present study, no grade III toxicity was recorded. Patients in the dilatation group experienced retrosternal pain for about 24 h. However, complications like rupture/perforation and massive bleeding or procedure-related deaths were not seen. Three patients in the re-irradiation group developed clinical features of interstitial lung fibrosis 7-10 months after completion of re-irradiation; however, the majority of the patients were lost to follow-up (presumably died) over 12-14 months. In order to keep the morbidity of this protocol to a minimum, we ensured proper patient selection by strict adherence to the inclusion and exclusion criteria. In view of the results of this study, a trial of re-irradiation is justified in such patients. However, further studies using a large sample with conventional external-beam radiation/IMRT/conformal radiotherapy are clearly needed to establish this advantage firmly. References
Copyright 2008 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr08036t3.jpg] [cr08036t1.jpg] [cr08036t6.jpg] [cr08036t2.jpg] [cr08036t4.jpg] [cr08036t5.jpg] |
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