Anatomical and clinical predictors of acute bowel toxicity in whole pelvis irradiation for prostate cancer with Tomotherapy.

PURPOSE Assessing predictors of acute bowel toxicity after whole-pelvis irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on prostate/prostate bed. METHODS AND MATERIALS In the period March 2005-April 2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT Tomotherapy. Median dose to the pelvic nodes was 51.8 Gy/28 fractions while concomitantly delivering 65.5-74.2 Gy to prostate/prostatic bed. The impact of many anatomical and clinical parameters on ≥ Grade 2 acute bowel toxicity was investigated by logistic analyses. RESULTS Only 15/178 patients (8.4%) experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate analysis were nodal CTV (CTVN ≥ 380 cc; OR: 3.7, p=0.017), treatment duration (< 40 days; OR: 6.2, p=0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p=0.015). A multivariate analysis including only pre-treatment variables revealed an independent role of CTVN and age; if including treatment-related factors the best predictors were age, treatment duration and Grade 2 rectal toxicity. This last was correlated with the overlap between PTVN and loops (OVPN ≥ 51 cc; OR: 14.4, p=0.0003) that is representative of the volume of loops receiving the prescribed dose (51.8 Gy, 1.85 Gy/fr). CONCLUSIONS Acute bowel toxicity after WPRT Tomotherapy is mild, relatively rare and associated to larger CTVN and older age. While efforts to further reduce it do not appear to be relevant, the pre-treatment assessment of "high-risk" patients may help physicians in better managing symptoms. A prospective validation would be very important in confirming these results and in better refining dose-volume bowel effects including symptoms milder that the ones here investigated and retrospectively assessed.

[1]  O. Odland,et al.  Intensity-modulated radiotherapy of pelvic lymph nodes in locally advanced prostate cancer: planning procedures and early experiences. , 2008, International journal of radiation oncology, biology, physics.

[2]  J. Ajani,et al.  Recommended guidelines for the treatment of cancer treatment-induced diarrhea. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Tahuanty A Pena,et al.  To bleed or not to bleed... , 2010, Chest.

[4]  M. Gallucci,et al.  Analysis of toxicity in patients with high risk prostate cancer treated with intensity-modulated pelvic radiation therapy and simultaneous integrated dose escalation to prostate area. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[5]  W. Hop,et al.  Irradiation of true pelvis for bladder and prostatic carcinoma in supine, prone or Trendelenburg position. , 1983, International journal of radiation oncology, biology, physics.

[6]  C. Fiorino,et al.  Clinical and dosimetric predictors of late rectal toxicity after conformal radiation for localized prostate cancer: results of a large multicenter observational study. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[7]  D. Brizel,et al.  Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  W. Stenson Prostaglandins and epithelial response to injury , 2007, Current opinion in gastroenterology.

[9]  R K Valicenti,et al.  Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  G. Sanguineti,et al.  Is IMRT needed to spare the rectum when pelvic lymph nodes are part of the initial treatment volume for prostate cancer? , 2006, International journal of radiation oncology, biology, physics.

[11]  Issam El-Naqa,et al.  RTOG GU Radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. , 2009, International journal of radiation oncology, biology, physics.

[12]  C. Fiorino,et al.  IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  C. Fiorino,et al.  Predictors of acute bowel toxicity in patients treated with IMRT whole pelvis irradiation after prostatectomy. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  N. Green The avoidance of small intestine injury in gynecologic cancer. , 1983, International journal of radiation oncology, biology, physics.

[15]  C. De Wagter,et al.  Late radiotherapy-induced lower intestinal toxicity (RILIT) of intensity-modulated radiotherapy for prostate cancer: the need for adapting toxicity scales and the appearance of the sigmoid colon as co-responsible organ for lower intestinal toxicity. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  Steve Webb,et al.  Clinical implementation of dynamic and step-and-shoot IMRT to treat prostate cancer with high risk of pelvic lymph node involvement. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  S. Hancock,et al.  Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients. , 2007, International journal of radiation oncology, biology, physics.

[18]  T. Kinsella,et al.  Minimization of small bowel volume within treatment fields utilizing customized "belly boards". , 1990, International journal of radiation oncology, biology, physics.

[19]  D P Dearnaley,et al.  Reduction of small and large bowel irradiation using an optimized intensity-modulated pelvic radiotherapy technique in patients with prostate cancer. , 2000, International journal of radiation oncology, biology, physics.

[20]  G. Sanguineti,et al.  Acute toxicity of whole-pelvis IMRT in 87 patients with localized prostate cancer , 2008, Acta oncologica.

[21]  J. Kountouras,et al.  Recent advances in the management of radiation colitis. , 2008, World journal of gastroenterology.

[22]  M. Zelefsky,et al.  Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy. , 2005, International journal of radiation oncology, biology, physics.

[23]  J. Bourhis,et al.  Glucagon-like peptide-2 improves both acute and late experimental radiation enteritis in the rat. , 2007, International journal of radiation oncology, biology, physics.

[24]  M. Sormani,et al.  Comparison of three strategies to delineate the bowel for whole pelvis IMRT of prostate cancer. , 2008, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[25]  G. Sanguineti,et al.  Does Treatment of the Pelvic Nodes with IMRT Increase Late Rectal Toxicity over Conformal Prostate-Only Radiotherapy to 76 Gy? , 2006, Strahlentherapie und Onkologie.

[26]  R W de Boer,et al.  Dose-volume correlation in radiation-related late small-bowel complications: a clinical study. , 1990, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[27]  D. Dearnaley,et al.  The impact of introducing intensity modulated radiotherapy into routine clinical practice. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  J. Rodier,et al.  Prevention of radiation enteritis by an absorbable polyglycolic acid mesh sling. A 60‐case multicentric study , 1991, Cancer.

[29]  F. Fazio,et al.  Dose-volume relationships for acute bowel toxicity in patients treated with pelvic nodal irradiation for prostate cancer. , 2009, International journal of radiation oncology, biology, physics.

[30]  F. Fazio,et al.  Evidence of limited motion of the prostate by carefully emptying the rectum as assessed by daily MVCT image guidance with helical tomotherapy. , 2008, International journal of radiation oncology, biology, physics.

[31]  G. Sanguineti,et al.  Dose-volume effects for normal tissues in external radiotherapy: pelvis. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[32]  B. Aslim,et al.  Effects of probiotics on radiation-induced intestinal injury in rats. , 2006, Nutrition.

[33]  F. Fazio,et al.  Phase I-II study of hypofractionated simultaneous integrated boost with tomotherapy for prostate cancer. , 2009, International journal of radiation oncology, biology, physics.

[34]  John C Roeske,et al.  A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity-modulated whole-pelvic radiation therapy. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[35]  F. Fazio,et al.  Physics aspects of prostate tomotherapy: Planning optimization and image-guidance issues , 2008, Acta oncologica.

[36]  Manuela Gariboldi,et al.  To bleed or not to bleed. A prediction based on individual gene profiling combined with dose-volume histogram shapes in prostate cancer patients undergoing three-dimensional conformal radiation therapy. , 2009, International journal of radiation oncology, biology, physics.

[37]  F. Fazio,et al.  Significant reduction of acute toxicity following pelvic irradiation with helical tomotherapy in patients with localized prostate cancer. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[38]  R Martinez-Monge,et al.  Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in three-dimensional radiation therapy planning. , 1999, Radiology.

[39]  M. Uysal,et al.  The effect of selenium and/or vitamin E treatments on radiation-induced intestinal injury in rats. , 2000, Life sciences.