Reirradiation to the abdomen for gastrointestinal malignancies
© Haque et al; licensee BioMed Central Ltd. 2009
Received: 6 July 2009
Accepted: 18 November 2009
Published: 18 November 2009
Reirradiation to the abdomen could potentially play a role in palliation of symptoms or local control in patients with gastrointestinal malignancies. Our goal was to retrospectively determine rates of toxicity, freedom from local progression and overall survival in gastrointestinal cancer patients treated with reirradiation to the abdomen.
Between November 2002 and September 2008, 13 patients with a prior history of abdominal radiotherapy (median dose 45 Gy) were treated with reirradiation for recurrent or metastatic gastrointestinal malignancies. The median interval between the two courses of radiotherapy was 26 months. Patients were treated with a hyperfractionated accelerated regimen, using 1.5 Gy fractions twice daily, with a median dose of 30 Gy (range 24-48 Gy). Concurrent chemotherapy was administered to 8 (62%) patients.
The 1-year rate of freedom from local progression was 50%, and the median duration of freedom from local progression was 14 months. The 1-year rate of overall survival was 62%, and the median duration of overall survival was 14 months. One patient developed grade 3 acute toxicity (abdominal pain and gastrointestinal bleeding), requiring hospitalization during radiotherapy; subsequently, that patient experienced a grade 4 late toxicity (gastrointestinal bleeding). No other patients developed grade 3-4 acute or late toxicity or required hospitalization during radiotherapy.
Hyperfractionated accelerated reirradiation to the abdomen was well-tolerated with low rates of acute and late toxicity. Reirradiation could play a role in providing a limited duration of local control in gastrointestinal cancer patients with a history of prior abdominal radiotherapy.
Multiple studies have demonstrated the safety and efficacy of reirradiation at various sites of the body, including head and neck, brain, breast, lung and pelvis [1–15]. Among gastrointestinal malignancies, many studies have shown the safety and efficacy of pelvic reirradiation for rectal cancer [11–15]. However, to the best of our knowledge, no studies to date have evaluated the safety and efficacy of reirradiation to the abdomen for gastrointestinal malignancies. Reirradiation to the abdomen could potentially play a role in palliation of symptoms or local control. Hence, the goal of this study was to retrospectively determine rates of toxicity, freedom from local progression and overall survival in gastrointestinal cancer patients treated with reirradiation to the abdomen.
Materials and methods
Between November 2002 and September 2008, 13 patients with gastrointestinal cancer and a history of prior abdominal radiotherapy underwent reirradiation, with a hyperfractionated accelerated approach, at the University of Texas M.D. Anderson Cancer Center. The hospital and radiotherapy records of these patients were reviewed. The M. D. Anderson Institutional Review Board approved this study.
Patient and Treatment Characteristics
Median (Range) or Number of Patients (%)
Age at Retreatment (years)
Prior Radiotherapy Dose
30 Gy (10-12 fractions)
35 Gy (14 fractions)
45 Gy (25 fractions)
50.4 Gy (28 fractions)
Retreatment Interval (months)
Indication for Retreatment
Palliation of Pain
Palliation of Bleeding
Definitive (Not candidate for other treatments)
Consolidation after Chemotherapy
Prior radiotherapy records were obtained and reviewed in all cases at the time of retreatment. The median dose of prior radiotherapy was 45 Gy (range 30-50.4 Gy). The prior radiotherapy dose was 30 Gy in 2.5-3 Gy fractions in 2 patients, 35 Gy in 2.5 Gy fractions in 2 patients, 45 Gy in 1.8 Gy fractions in 4 patients and 50.4 Gy in 1.8 Gy fractions in 5 patients. Prior radiation was given with a definitive intent in 9 patients and for palliation in 4 patients. The median interval between the two courses of radiotherapy was 26 months (range 5-83 months).
At the time of reirradiation, 8 (62%) patients had recurrent disease and 5 (38%) patients had metastatic disease. Prior to reirradiation, patients had received a median of 2 (range 0-4) different regimens of chemotherapy, not including concurrent chemotherapy given with radiation. Reirradiation was administered for palliation of pain in 5 patients, palliation of bleeding in 4 patients, definitive treatment in 3 patients who were not candidates for other therapies, and consolidative treatment after chemotherapy in 1 patient.
Patient-specific Retreatment Characteristics
Tumor Size (cm)*
Retreatment Dose (Gy)
Retreatment Interval (months)
7 × 7 × 5
Kidneys V20 0%, 38%, Liver V30 0%, Max. cord dose 15 Gy
10 × 4 × 2
Kidneys V20 0%, 0%, Liver V30 5%, Max. cord dose 20 Gy
5 × 5 × 6
Kidneys V20 0%, 0%, Liver V30 25%, Max. cord dose 3 Gy
Kidneys V20 0%, 0%, Liver V30 58%, Max. cord dose 42 Gy
10 × 9 × 10
Kidneys V20 0%, 2%, Max. cord dose 12 Gy
5 × 3 × 3
Kidneys V20 0%, 0%, Liver V30 0%, Max. cord dose 32 Gy
7 × 3 × 10
Max. cord dose 12 Gy
4 × 3 × 3
Kidneys V20 7%, 21%, Max. cord dose 23 Gy
Kidneys V20 22%, 32%, Max. cord dose 39 Gy
8 × 6 × 5
Kidneys V20 7%, 17%, Liver V30 5%, Max. cord dose 27 Gy
Kidneys V20 9%, 23%, Liver V30 22%, Max. cord dose 43 Gy
6 × 6 × 6
Kidney V20 0%, Liver V30 0%, Max. cord dose 12 Gy
Kidney V20 0%, Liver V30 12%, Max. cord dose 39 Gy
9 × 10 × 17
Max. cord dose 7 Gy
9 × 6 × 8
Kidneys V20 0%, 0%, Liver V30 20%, Max. cord dose 18 Gy
Kidneys V20 14%, Liver V30 72%, Max. cord dose 46 Gy
6 × 4 × 6
Kidneys V20 0%, 0%, Liver V30 0%, Max. cord dose 17 Gy
Kidneys V20 8%, 24%, Liver V30 33%, Max. cord dose 46 Gy
5 × 6 × 5
Kidneys V20 5%, 8%, Liver V30 4%, Max. cord dose 23 Gy
Kidneys V20 18%, 20%, Liver V30 42%, Max. cord dose 38 Gy
Follow-up information was obtained from hospital records and radiation therapy department records. Follow-up information was also obtained from the M. D. Anderson Tumor Registry, which collects information on patients annually through letters, phone calls, and Bureau of Vital Statistics records. The median follow-up interval was 8 (range 3-26) months.
Acute and late toxicity was graded using the Common Terminology Criteria for Adverse Events version 3.0 . Local progression was defined as any radiographic progression within the treated field. The rates of freedom from local progression and overall survival were estimated by Kaplan-Meier methods . All time intervals were calculated from the date of completion of reirradiation.
Local Control and Survival
Only 1 patient (8%) developed grade 3 acute toxicity (abdominal pain and bleeding from gastrojejunal anastomosis) during chemoradiation; this patient required hospitalization for 4 days and termination of radiation therapy before completion of the prescribed course. No other patient developed grade 3-4 acute toxicity or was hospitalized for acute toxicity. Only one patient developed grade 2 acute toxicity (duodenal ulceration and stricture); radiation therapy was stopped early in this patient to prevent progression of the ulcer. The remaining 11 patients completed their prescribed course of radiation therapy.
The patient with grade 3 acute toxicity subsequently developed grade 4 late toxicity (bleeding from the gastrojejunal anastomosis), two months after completion of reirradiation. The gastrojejunal anastomosis had received a cumulative maximum dose of 63 Gy in this patient. The patient was initially treated with endoscopic clips, epinephrine and coagulation, and then required a surgical revision of gastrojejunostomy. This patient had no subsequent episodes of gastrointestinal bleeding. No other patient developed grade 3-4 late toxicity.
We have hereby reported the first study on reirradiation to the abdomen for gastrointestinal cancers. Patients treated with reirradiation had a limited overall survival, with a median survival of 14 months, which reflects the poor prognosis of patients with recurrent or metastatic abdominal malignancies. Reirradiation provided local control for a limited duration, with a median duration of freedom from local progression of 14 months. However, this duration of local control was clinically significant, taking into consideration the limited life expectancy in these patients. Reirradiation provided these patients durable local control that lasted for the majority of their remaining life without significant increase in morbidity.
Reirradiation was well-tolerated with only one patient experiencing grade 3-4 acute and late toxicity. In addition, one patient developed grade 2 acute toxicity. These toxicity events involved gastrointestinal bleeding or ulceration. Patients treated with reirradiation may have a higher risk of developing gastrointestinal bleeding and ulceration, compared to patients not exposed to prior radiation therapy. Hence, we need to be cognizant about the risk of bleeding and ulceration in patients treated with abdominal reirradiation, especially around the duodenum or jejunal anastomosis.
We used a hyperfractionated accelerated regimen to deliver radiation therapy, with 150 cGy fractions, given twice daily. We recently reported outcomes in 50 rectal cancer patients treated with pelvic reirradiation with an identical regimen, with a total dose of 30-39 Gy . Pelvic reirradiation was well-tolerated, with grade 3 acute toxicity occurring in 4% and grade 3-4 late toxicity occurring in 26% of patients. The median duration of freedom from local progression was 21 months and the median overall survival was 26 months. Rectal cancer patients likely had superior outcomes because of more favorable tumor biology compared to abdominal cancers, and because many of the rectal cancer patients underwent surgical resection in addition to radiation therapy. Nevertheless, we have now demonstrated in two separate sites of the body that reirradiation can be safely administered using a hyperfractionated accelerated approach, with 150 cGy twice daily fractions.
This study had several limitations. The number of patients was small, and there was considerable heterogeneity in tumor type and site of reirradiation. Hence, it is difficult to draw firm conclusions regarding the local control and survival outcomes in this study. Moreover, since patients received systemic therapy in addition to radiation therapy, it is difficult to surmise how much radiation contributed to the overall outcomes. Toxicity rates were assessed based on a review of hospital and departmental records, and therefore, may have been underestimated. The median follow-up interval was relatively short, and any patients who achieve long-term survival after reirradiation could potentially have higher rates of late toxicity. In spite of these limitations, this study shows that abdominal reirradiation could be a potential treatment option in selected patients with gastrointestinal malignancies. Of note, only 13 patients were treated with this approach in a period of about 6 years at a large institution. Careful patient selection clearly plays an important role in determining who might benefit from this treatment.
In conclusion, our study showed that abdominal reirradiation was well-tolerated with low rates of acute and late toxicity. Abdominal reirradiation appeared to provide local control, albeit with a limited duration. We suggest that abdominal reirradiation could have many potential applications in selected patients with recurrent or metastatic gastrointestinal cancers. Reirradiation may help in palliation of symptoms, such as pain or bleeding. In patients with isolated areas of disease that are refractory to chemotherapy, reirradiation could help achieve local control. In patients that have a good response to chemotherapy, reirradiation could have a consolidative role. Further studies are warranted to evaluate the role of abdominal reirradiation in these settings. Further studies are also needed to confirm the safety of abdominal reirradiation.
This study was supported in part by grant CA16672 from the National Cancer Institute, Department of Health and Human Services.
- Tanvetyanon T, Padhya T, McCaffrey J, Zhu W, Boulware D, Deconti R, Trotti A: Prognostic factors for survival after salvage reirradiation of head and neck cancer. J Clin Oncol 2009, 27: 1983-1991. 10.1200/JCO.2008.20.0691View ArticlePubMedGoogle Scholar
- Sulman EP, Schwartz DL, Le TT, Ang KK, Morrison WH, Rosenthal DI, Ahamad A, Kies M, Glisson B, Weber R, Garden AS: IMRT reirradiation of head and neck cancer-disease control and morbidity outcomes. Int J Radiat Oncol Biol Phys 2009, 73: 399-409.View ArticlePubMedGoogle Scholar
- Popovtzer A, Gluck I, Chepeha DB, Teknos TN, Moyer JS, Prince ME, Bradford CR, Eisbruch A: The Pattern of Failure After Reirradiation of Recurrent Squamous Cell Head and Neck Cancer: Implications for Defining the Targets. Int J Radiat Oncol Biol Phys 2009, 74: 1342-1347.PubMed CentralView ArticlePubMedGoogle Scholar
- Janot F, de Raucourt D, Benhamou E, Ferron C, Dolivet G, Bensadoun RJ, Hamoir M, Gery B, Julieron M, Castaing M, Bardet E, Gregoire V, Bourhis J: Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. J Clin Oncol 2008, 26: 5518-5523. 10.1200/JCO.2007.15.0102View ArticlePubMedGoogle Scholar
- Langer CJ, Harris J, Horwitz EM, Nicolaou N, Kies M, Curran W, Wong S, Ang K: Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol 2007, 25: 4800-4805. 10.1200/JCO.2006.07.9194View ArticlePubMedGoogle Scholar
- Henke G, Paulsen F, Steinbach JP, Ganswindt U, Isijanov H, Kortmann RD, Bamberg M, Belka C: Hypofractionated reirradiation for recurrent malignant glioma. Strahlenther Onkol 2009, 185: 113-119. 10.1007/s00066-009-1969-9View ArticlePubMedGoogle Scholar
- Paulino AC, Mai WY, Chintagumpala M, Taher A, Teh BS: Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys 2008, 71: 1381-1387.View ArticlePubMedGoogle Scholar
- Fokas E, Wacker U, Gross MW, Henzel M, Encheva E, Engenhart-Cabillic R: Hypofractionated Stereotactic Reirradiation of Recurrent Glioblastomas: A Beneficial Treatment Option after High-Dose Radiotherapy? Strahlenther Onkol 2009, 185: 235-240. 10.1007/s00066-009-1753-xView ArticlePubMedGoogle Scholar
- Wurschmidt F, Dahle J, Petersen C, Wenzel C, Kretschmer M, Bastian C: Reirradiation of recurrent breast cancer with and without concurrent chemotherapy. Radiat Oncol 2008, 3: 28. 10.1186/1748-717X-3-28PubMed CentralView ArticlePubMedGoogle Scholar
- Cetingoz R, Arican-Alicikus Z, Nur-Demiral A, Durmak-Isman B, Bakis-Altas B, Kinay M: Is re-irradiation effective in symptomatic local recurrence of non small cell lung cancer patients? A single institution experience and review of the literature. J Buon 2009, 14: 33-40.PubMedGoogle Scholar
- Valentini V, Morganti AG, Gambacorta MA, Mohiuddin M, Doglietto GB, Coco C, De Paoli A, Rossi C, Di Russo A, Valvo F, Bolzicco G, Dalla Palma M: Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study. Int J Radiat Oncol Biol Phys 2006, 64: 1129-1139.View ArticlePubMedGoogle Scholar
- Mohiuddin M, Lingareddy V, Rakinic J, Marks G: Reirradiation for rectal cancer and surgical resection after ultra high doses. Int J Radiat Oncol Biol Phys 1993, 27: 1159-1163.View ArticlePubMedGoogle Scholar
- Mohiuddin M, Marks GM, Lingareddy V, Marks J: Curative surgical resection following reirradiation for recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1997, 39: 643-649.View ArticlePubMedGoogle Scholar
- Mohiuddin M, Marks G, Marks J: Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer 2002, 95: 1144-1150. 10.1002/cncr.10799View ArticlePubMedGoogle Scholar
- Lingareddy V, Ahmad NR, Mohiuddin M: Palliative reirradiation for recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1997, 38: 785-790. 10.1016/S0360-3016(97)00058-8View ArticlePubMedGoogle Scholar
- Das P, Delclos M, Skibber J, Rodriguez-Bigas M, Feig B, Chang G, Eng C, Bedi M, Krishnan S, CH C: Hyperfractionated Accelerated Radiotherapy for Rectal Cancer in Patients with Prior Pelvic Irradiation. Int J Radiat Oncol Biol Phys 2009, 69: S277-S277.View ArticleGoogle Scholar
- Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse Events, version 3.0. Department of Health and Human Services, National Institutes of Health, National Cancer Institute 2003.
- Kaplan E, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958, 53: 457-481. 10.2307/2281868View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.