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Gastrointestinal stereotactic body radiation therapy requires detailed normal tissue planning to prevent long-term complications
Practical Radiation Oncology (2013) 3, 147–148
www.practicalradonc.org
Commentary
Gastrointestinal stereotactic body radiation therapy requires detailed normal tissue planning to prevent long-term complications Rachit Kumar MD, Joseph M. Herman MD, MSc ⁎ Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland Received 4 July 2012; accepted 9 July 2012
Stereotactic body radiation therapy (SBRT) has been gaining increasing popularity as an alternative to metastectomy for colorectal liver metastases. Furman et al 1 present their experience with a rare complication of SBRT in the treatment of hepatic metastases: gastric perforation. The authors acknowledge their error in a straightforward manner by directly addressing the fact that the stomach was not contoured as an organ at risk. Below, we briefly review previous instances of this complication reported in the literature and reported doses of stereotactic radiation associated with gastric perforation. The authors presented complication data from Rule et al 2 and Rusthoven et al. 3 Rule et al utilized a maximum point dose of 32 Gy (6.4 Gy/fraction), with a maximum volume dose of 28 Gy (5.6 Gy/fraction) to b10 mL of stomach. 2 At a median follow-up of 20 months, no grade 2 or greater gastrointestinal toxicity was seen with this dose. Rusthoven et al allowed 30 Gy in 3 fractions to the stomach as a maximum point dose. 3 Again, no grade 3 or higher gastrointestinal toxicity was reported. Data have emerged regarding gastric ulcers when utilizing abdominal SBRT. In 2007, Chang et al 4 reported a case of a large gastric ulcer of the lesser curvature in a patient who received a single fraction of SBRT for recurrent
Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401 N. Broadway, Weinberg Ste 1440, Baltimore, MD 21231. E-mail address: [email protected] (J.M. Herman).
hepatocellular carcinoma. Dose to the involved gastric wall was not reported. More recently, Onishi et al 5 reported on a case of a gastric ulcer following SBRT to an adrenal metastasis treated to 60 Gy in 10 fractions. The maximum allowed dose to the gastric wall was 61 Gy in 10 fractions. No acute toxicity was noted, but the ulcer was visible on computed tomographic scan 2.5 months after therapy. Unfortunately, the patient died of massive bleeding from the ulcer 5.5 months after the completion of radiation. The ulcer was in the 90% isodose line of the SBRT treatment volume. Kang et al 6 conducted a phase 2, nonrandomized protocol utilizing SBRT in the treatment of inoperable hepatocellular carcinoma as salvage following incomplete transarterial chemoembolization. The treatment dose ranged from 42-60 Gy in 3 fractions. This study adopted normal tissue doses for the spinal cord and liver, but no maximum dose was applied for the stomach. Two gastric ulcers were noted in this treatment group, occurring at 7 and 10 months following SBRT. The doses resulting in these lesions were 51 Gy and 54 Gy, both in 3 Gy fractions. The authors note that preexisting gastroduodenal ulcers are correlated with the development of late GI toxicity (ulcers and perforation) in the treated population. Similarly, an analysis by Hoyer et al 7 found that a gastric wall dose N30 Gy in 3 fractions (maximum point dose) was associated with a risk of visceral perforation. In 2010, the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) investigators published their dose limit recommendations for the stomach when using SBRT. 8 They recommend no more than 5 cc of the stomach should receive N 22.5 Gy, and the maximum point
1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.07.002
148
R. Kumar, J.M. Herman
dose to the stomach is b30 Gy in 3 fractions. However, the investigators acknowledge that a significant amount of research is required to understand this toxicity risk more thoroughly. We are currently evaluating the efficacy of fractionated stereotactic body radiation for unresectable pancreatic cancer. 9 We are treating patients to a dose of 33 Gy in 5 fractions (6.6 Gy per fraction). In this study, no more than 1 cc of the stomach can receive N33 Gy. Volumetric constraints include V15 b9 cc and V20 b3cc. In more than 40 patients, there was 1 patient who had a grade 4 duodenal ulcer where the tumor had invaded through the duodenal wall. Subsequently we have excluded any patients who present with invasion into the lumen of the duodenum (based on endoscopic evaluation) and have not had any further complications. In order to minimize toxicity with SBRT, radiation oncologists must be aware of the proximity and volume of bowel and stomach adjacent to the tumor. We commend Furman et al 1 in publishing these data as they contribute significantly to our field. Indeed, the widespread use of stereotactic body radiation therapy will require a greater knowledge of dose limitations to many organs, including the stomach and small bowel. The authors acknowledge their error in not completely contouring normal structures at risk, and, in doing so, suffered an unforeseen complication. In reporting their error, we not only learn from their experience, but also progress in the management of abdominal malignancies with stereotactic body radiation.
Practical Radiation Oncology: July-September 2013
References 1. Furman MJ, Whalen GF, Shah SA, Kadish SP. Gastric perforation following stereotactic body radiation therapy of hepatic metastasis from colon cancer. Pract Radiat Oncol. 2013;3(1):40-44. 2. Rule W, Timmerman R, Tong L, et al. Phase I dose-escalation study of stereotactic body radiotherapy in patients with hepatic metastases. Ann Surg Oncol. 2011;18:1081-1087. 3. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009;27:1572-1578. 4. Chang CY, Tu CH, Chiang TS, Wang HP. Acute gastric ulcer associated with gamma knife treatment (conformal stereotactic radiotherapy) of recurrent hepatocellular carcinoma. Endoscopy. 2007;39(Suppl 1):E154. 5. Onishi H, Ozaki M, Kuriyama K, et al. Serious gastric ulcer event after stereotactic body radiotherapy (SBRT) delivered with concomitant vinorelbine in a patient with left adrenal metastasis of lung cancer. Acta Oncol. 2012;51:624-628. 6. Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization [e-pub ahead of print]. Cancer. doi:10.1002/cncr.27533, accessed July 17, 2012. 7. Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases.. Acta Oncol. 2006;45:823-830. 8. Kavanagh BD, Pan CC, Dawson LA, et al. Radiation dose-volume effects in the stomach and small bowel.. Int J Radiat Oncol Biol Phys. 2010;76(Suppl 3):S101-S107. 9. Herman JM, Chang DT, Goodman KA, et al. A phase II multiinstitutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma. J Clin Oncol. 30, 2012 (suppl; abstr 4045).
www.practicalradonc.org
Commentary
Gastrointestinal stereotactic body radiation therapy requires detailed normal tissue planning to prevent long-term complications Rachit Kumar MD, Joseph M. Herman MD, MSc ⁎ Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland Received 4 July 2012; accepted 9 July 2012
Stereotactic body radiation therapy (SBRT) has been gaining increasing popularity as an alternative to metastectomy for colorectal liver metastases. Furman et al 1 present their experience with a rare complication of SBRT in the treatment of hepatic metastases: gastric perforation. The authors acknowledge their error in a straightforward manner by directly addressing the fact that the stomach was not contoured as an organ at risk. Below, we briefly review previous instances of this complication reported in the literature and reported doses of stereotactic radiation associated with gastric perforation. The authors presented complication data from Rule et al 2 and Rusthoven et al. 3 Rule et al utilized a maximum point dose of 32 Gy (6.4 Gy/fraction), with a maximum volume dose of 28 Gy (5.6 Gy/fraction) to b10 mL of stomach. 2 At a median follow-up of 20 months, no grade 2 or greater gastrointestinal toxicity was seen with this dose. Rusthoven et al allowed 30 Gy in 3 fractions to the stomach as a maximum point dose. 3 Again, no grade 3 or higher gastrointestinal toxicity was reported. Data have emerged regarding gastric ulcers when utilizing abdominal SBRT. In 2007, Chang et al 4 reported a case of a large gastric ulcer of the lesser curvature in a patient who received a single fraction of SBRT for recurrent
Conflicts of interest: None. ⁎ Corresponding author. Department of Radiation Oncology & Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401 N. Broadway, Weinberg Ste 1440, Baltimore, MD 21231. E-mail address: [email protected] (J.M. Herman).
hepatocellular carcinoma. Dose to the involved gastric wall was not reported. More recently, Onishi et al 5 reported on a case of a gastric ulcer following SBRT to an adrenal metastasis treated to 60 Gy in 10 fractions. The maximum allowed dose to the gastric wall was 61 Gy in 10 fractions. No acute toxicity was noted, but the ulcer was visible on computed tomographic scan 2.5 months after therapy. Unfortunately, the patient died of massive bleeding from the ulcer 5.5 months after the completion of radiation. The ulcer was in the 90% isodose line of the SBRT treatment volume. Kang et al 6 conducted a phase 2, nonrandomized protocol utilizing SBRT in the treatment of inoperable hepatocellular carcinoma as salvage following incomplete transarterial chemoembolization. The treatment dose ranged from 42-60 Gy in 3 fractions. This study adopted normal tissue doses for the spinal cord and liver, but no maximum dose was applied for the stomach. Two gastric ulcers were noted in this treatment group, occurring at 7 and 10 months following SBRT. The doses resulting in these lesions were 51 Gy and 54 Gy, both in 3 Gy fractions. The authors note that preexisting gastroduodenal ulcers are correlated with the development of late GI toxicity (ulcers and perforation) in the treated population. Similarly, an analysis by Hoyer et al 7 found that a gastric wall dose N30 Gy in 3 fractions (maximum point dose) was associated with a risk of visceral perforation. In 2010, the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) investigators published their dose limit recommendations for the stomach when using SBRT. 8 They recommend no more than 5 cc of the stomach should receive N 22.5 Gy, and the maximum point
1879-8500/$ – see front matter © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.prro.2012.07.002
148
R. Kumar, J.M. Herman
dose to the stomach is b30 Gy in 3 fractions. However, the investigators acknowledge that a significant amount of research is required to understand this toxicity risk more thoroughly. We are currently evaluating the efficacy of fractionated stereotactic body radiation for unresectable pancreatic cancer. 9 We are treating patients to a dose of 33 Gy in 5 fractions (6.6 Gy per fraction). In this study, no more than 1 cc of the stomach can receive N33 Gy. Volumetric constraints include V15 b9 cc and V20 b3cc. In more than 40 patients, there was 1 patient who had a grade 4 duodenal ulcer where the tumor had invaded through the duodenal wall. Subsequently we have excluded any patients who present with invasion into the lumen of the duodenum (based on endoscopic evaluation) and have not had any further complications. In order to minimize toxicity with SBRT, radiation oncologists must be aware of the proximity and volume of bowel and stomach adjacent to the tumor. We commend Furman et al 1 in publishing these data as they contribute significantly to our field. Indeed, the widespread use of stereotactic body radiation therapy will require a greater knowledge of dose limitations to many organs, including the stomach and small bowel. The authors acknowledge their error in not completely contouring normal structures at risk, and, in doing so, suffered an unforeseen complication. In reporting their error, we not only learn from their experience, but also progress in the management of abdominal malignancies with stereotactic body radiation.
Practical Radiation Oncology: July-September 2013
References 1. Furman MJ, Whalen GF, Shah SA, Kadish SP. Gastric perforation following stereotactic body radiation therapy of hepatic metastasis from colon cancer. Pract Radiat Oncol. 2013;3(1):40-44. 2. Rule W, Timmerman R, Tong L, et al. Phase I dose-escalation study of stereotactic body radiotherapy in patients with hepatic metastases. Ann Surg Oncol. 2011;18:1081-1087. 3. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009;27:1572-1578. 4. Chang CY, Tu CH, Chiang TS, Wang HP. Acute gastric ulcer associated with gamma knife treatment (conformal stereotactic radiotherapy) of recurrent hepatocellular carcinoma. Endoscopy. 2007;39(Suppl 1):E154. 5. Onishi H, Ozaki M, Kuriyama K, et al. Serious gastric ulcer event after stereotactic body radiotherapy (SBRT) delivered with concomitant vinorelbine in a patient with left adrenal metastasis of lung cancer. Acta Oncol. 2012;51:624-628. 6. Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization [e-pub ahead of print]. Cancer. doi:10.1002/cncr.27533, accessed July 17, 2012. 7. Hoyer M, Roed H, Traberg Hansen A, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases.. Acta Oncol. 2006;45:823-830. 8. Kavanagh BD, Pan CC, Dawson LA, et al. Radiation dose-volume effects in the stomach and small bowel.. Int J Radiat Oncol Biol Phys. 2010;76(Suppl 3):S101-S107. 9. Herman JM, Chang DT, Goodman KA, et al. A phase II multiinstitutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma. J Clin Oncol. 30, 2012 (suppl; abstr 4045).