Radiation Dose–Volume Effects in the Stomach and Small Bowel

      Published data suggest that the risk of moderately severe (≥Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.
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        • Coia L.R.
        • Myerson R.J.
        • Tepper J.E.
        Late effects of radiation therapy on the gastrointestinal tract.
        Int J Radiat Oncol Biol Phys. 1995; 31: 1213-1236
        • Vistad I.
        • Kristensen G.B.
        • Fosså S.D.
        • et al.
        Intestinal malabsorption in long-term survivors of cervical cancer treated with radiotherapy.
        Int J Radiat Oncol Biol Phys. 2009; 73: 1141-1147
        • Acker J.C.
        • Marks L.B.
        The lack of impact of pelvic irradiation on small bowel mobility: Implications for radiotherapy treatment planning.
        Int J Radiat Oncol Biol Phys. 1995; 32: 1473-1475
        • Martin J.
        • Fitzpatrick K.
        • Horan G.
        • et al.
        Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: Results of a prospective study.
        Radiother Oncol. 2005; 74: 267-274
        • Emami B.
        • Lyman J.
        • Brown A.
        • et al.
        Tolerance of normal tissue to therapeutic irradiation.
        Int J Radiat Oncol Biol Phys. 1991; 21: 109-122
        • Ishikura S.
        • Tobinai K.
        • Ohtsu A.
        • et al.
        Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I–II, diffuse large B-cell lymphoma of the stomach.
        Cancer Sci. 2005; 96: 349-352
        • Moertel C.G.
        • Frytak S.
        • Hahn R.G.
        • et al.
        Therapy of locally unresectable pancreatic carcinoma: A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.
        Cancer. 1981; 48: 1705-1710
        • Sykes A.J.
        • Kiltie A.E.
        • Stewart A.L.
        Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: A prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy.
        Support Care Cancer. 1997; 5: 500-503
        • Wong R.K.
        • Paul N.
        • Ding K.
        • et al.
        5-Hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: A placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19).
        J Clin Oncol. 2006; 24: 3458-3464
        • Brick I.B.
        Effects of million volt irradiation on the gastrointestinal tract.
        Arch Intern Med. 1955; 96: 26-31
        • Cosset J.M.
        • Henry-Amar M.
        • Burgers J.M.
        • et al.
        Late radiation injuries of the gastrointestinal tract in the H2 and H5 EORTC Hodgkin's disease trials: Emphasis on the role of exploratory laparotomy and fractionation.
        Radiother Oncol. 1988; 13: 61-68
        • Goldstein H.M.
        • Rogers L.F.
        • Fletcher G.H.
        • Dodd G.D.
        Radiological manifestations of radiation-induced injury to the normal upper gastrointestinal tract.
        Radiology. 1975; 117: 135-140
        • Cohen S.J.
        • Dobelbower Jr., R.
        • Lipsitz S.
        • et al.
        A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282.
        Int J Radiat Oncol Biol Phys. 2005; 62: 1345-1350
        • Talamonti M.S.
        • Catalano P.J.
        • Vaughn D.J.
        • et al.
        Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: A regimen with unexpected early toxicity.
        J Clin Oncol. 2000; 18: 3384-3389
        • Li C.P.
        • Chao Y.
        • Chi K.H.
        • et al.
        Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: Gemcitabine versus 5-fluorouracil, a randomized controlled study.
        Int J Radiat Oncol Biol Phys. 2003; 57: 98-104
        • Loehrer P.
        • Powell M.E.
        • Cardenes H.R.
        • et al.
        A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer.
        J Clin Oncol. 2008; (abstract 4506): 26
        • Murphy J.D.
        • Adusumilli S.
        • Griffith K.A.
        • et al.
        Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer.
        Int J Rad Oncol Biol Phys. 2007; 68: 801-808
        • Baglan K.L.
        • Frazier R.C.
        • Yan D.
        • et al.
        The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer.
        Int J Radiat Oncol Biol Phys. 2002; 52: 176-183
        • Roeske J.C.
        • Bonta D.
        • Mell L.K.
        • et al.
        A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity-modulated whole-pelvic radiation therapy.
        Radiother Oncol. 2003; 69: 201-207
        • Tho L.M.
        • Glegg M.
        • Paterson J.
        • et al.
        Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: Investigating dose-volume relationships and role for inverse planning.
        Int J Radiat Oncol Biol Phys. 2006; 66: 505-513
        • Huang E.Y.
        • Sung C.C.
        • Ko S.F.
        • et al.
        The different volume effects of small-bowel toxicity during pelvic irradiation between gynecologic patients with and without abdominal surgery: A prospective study with computed tomography-based dosimetry.
        Int J Radiat Oncol Biol Phys. 2007; 69: 732-739
        • Robertson J.M.
        • Lockman D.
        • Yan D.
        • et al.
        The dose-volume relationship of small bowel irradiation and acute grade 3 diarrhea during chemoradiotherapy for rectal cancer.
        Int J Radiat Oncol Biol Phys. 2008; 70: 413-418
        • Gunnlaugsson A.
        • Kjellen E.
        • Nilsson P.
        • et al.
        Dose-volume relationships between enteritis and irradiated bowel volumes during 5-fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer.
        Acta Oncol. 2007; 46: 937-944
        • Keys H.M.
        • Bundy B.N.
        • Stehman F.B.
        • et al.
        Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.
        N Engl J Med. 1999; 340: 1154-1161
        • Macdonald J.S.
        • Smalley S.R.
        • Benedetti J.
        • et al.
        Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction.
        N Engl J Med. 2001; 345: 725-730
        • Bosset J.F.
        • Collette L.
        • Calais G.
        • et al.
        Chemotherapy with preoperative radiotherapy in rectal cancer.
        N Engl J Med. 2006; 355: 1114-1123
        • Mak A.C.
        • Rich T.A.
        • Schultheiss T.E.
        • et al.
        Late complications of postoperative radiation therapy for cancer of the rectum and rectosigmoid.
        Int J Radiat Oncol Biol Phys. 1994; 28: 597-603
        • Hamilton C.R.
        • Horwich A.
        • Bliss J.M.
        • et al.
        Gastrointestinal morbidity of adjuvant radiotherapy in stage I malignant teratoma of the testis.
        Radiother Oncol. 1987; 10: 85-90
        • Frykholm G.J.
        • Glimelius B.
        • Pahlman L.
        Preoperative or postoperative irradiation in adenocarcinoma of the rectum: Final treatment results of a randomized trial and an evaluation of late secondary effects.
        Dis Colon Rectum. 1993; 36: 564-572
        • Peeters K.C.
        • van de Velde C.J.
        • Leer J.W.
        • et al.
        Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: Increased bowel dysfunction in irradiated patients—a Dutch colorectal cancer group study.
        J Clin Oncol. 2005; 23: 6199-6206
        • Peeters K.C.
        • Marijnen C.A.
        • Nagtegaal I.D.
        • et al.
        The TME trial after a median follow-up of 6 years: Increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.
        Ann Surg. 2007; 246: 693-701
        • Folkesson J.
        • Birgisson H.
        • Pahlman L.
        • et al.
        Swedish Rectal Cancer Trial: Long lasting benefits from radiotherapy on survival and local recurrence rate.
        J Clin Oncol. 2005; 23: 5644-5650
        • Birgisson H.
        • Pahlman L.
        • Gunnarsson U.
        • et al.
        Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy.
        Br J Surg. 2008; 95: 206-213
        • Bujko K.
        • Nowacki M.P.
        • Nasierowska-Guttmejer A.
        • et al.
        Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.
        Br J Surg. 2006; 93: 1215-1223
        • Sauer R.
        • Becker H.
        • Hohenberger W.
        • et al.
        Preoperative versus postoperative chemoradiotherapy for rectal cancer.
        N Engl J Med. 2004; 351: 1731-1740
        • Pan C.C.
        • Dawson L.A.
        • McGinn C.J.
        • et al.
        Analysis of radiation-induced gastric and duodenal bleeds using the Lyman-Kutcher-Burman model.
        Int J Radiat Oncol Biol Phys. 2003; 57: S217-S218
        • Chen M.F.
        • Tseng C.J.
        • Tseng C.C.
        • et al.
        Clinical outcome in posthysterectomy cervical cancer patients treated with concurrent Cisplatin and intensity-modulated pelvic radiotherapy: Comparison with conventional radiotherapy.
        Int J Radiat Oncol Biol Phys. 2007; 67: 1438-1444
        • Letschert J.G.
        • Lebesque J.V.
        • de Boer R.W.
        • et al.
        Dose-volume correlation in radiation-related late small-bowel complications: A clinical study.
        Radiother Oncol. 1990; 18: 307-320
        • Hoyer M.
        • Roed H.
        • Traberg Hansen A.
        • et al.
        Phase II study on stereotactic body radiotherapy of olorectal metastases.
        Acta Oncol. 2006; 45: 823-830
        • Koong A.C.
        • Christofferson E.
        • Le Q.T.
        • et al.
        Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2005; 63: 320-323
        • Schellenberg D.
        • Goodman K.A.
        • Lee F.
        • et al.
        Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer.
        Int J Radiat Oncol Biol Phys. 2008; 72: 678-686
        • Chang D.T.
        • Schellenberg D.
        • Shen J.
        • et al.
        Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas.
        Cancer. 2009; 115: 665-672
        • Hoyer M.
        • Roed H.
        • Sengelov L.
        • et al.
        Phase II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma.
        Radiother Oncol. 2005; 76: 48-53
        • Streitparth F.
        • Pech M.
        • Böhmig M.
        • et al.
        In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1479-1486


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