Rectum motion and morbidity prediction: Improving correlation between late morbidity and DVH parameters through use of rectum planning organ at risk volumes

Abstract Background and purpose. The rectum is a major dose-limiting organ at risk (OR) in radiotherapy (RT) of prostate cancer. Methods to predict adverse effects in the rectum are therefore important but their precision often limited, not the least by the internal motion of this organ. In this study late rectal morbidity is investigated in relation to the internal motion of the rectum by applying the ‘Planning organ at Risk Volume’ (PRV) concept. Materials and methods: Late rectal morbidity was analysed in 242 prostate cancer patients treated to 70 Gy with conformal RT to either the prostate, the prostate and seminal vesicles or the whole pelvis (initial 50 Gy only). Late rectal morbidity was classified by the late gastro-intestinal (GI) RTOG toxicity scoring system. Cumulative dose-volume histograms (DVHs) were derived for the rectum OR and six rectum PRVs i.e. the OR expanded with six different margins (narrow/intermediate/wide in anterior direction or in both anterior and posterior direction). The difference in rectum dose-volume parameters between patients with Grade 0–1 vs. Grade 2 or higher morbidity was investigated by logistic regression and permutation tests. Results: Late Grade 2 or higher morbidity was observed in 25 of 242 (10%) patients. The logistic regression analysis and the permutation tests reached significance (p ≤ 0.05) for only one dose level of the rectum OR (40 Gy). For the PRVs, several dose levels were found to be significant (p-value range: 0.01–0.046), most pronounced for the PRV with narrow margins of 6 mm anterior and 5 mm posterior with five intermediate (38–42 Gy) and ten high (62–71 Gy) dose levels. Conclusions: The statistical methods applied displayed consistently a small though significant difference in DVH parameters between patients with vs. without Grade 2 or higher late rectal morbidity for intermediate and high dose levels. The difference became most evident when using a PRV with narrow margins.

[1]  C. Grau,et al.  Image-guided adaptive radiotherapy – integration of biology and technology to improve clinical outcome , 2008, Acta oncologica.

[2]  A. Hanlon,et al.  Late GI and GU complications in the treatment of prostate cancer. , 1997, International journal of radiation oncology, biology, physics.

[3]  W. Sauerbrei,et al.  Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. , 1994, Journal of the National Cancer Institute.

[4]  The contribution, history, impact and future of physics in medicine , 2009, Acta oncologica.

[5]  H. von der Maase,et al.  Dose-volume histograms associated to long-term colorectal functions in patients receiving pelvic radiotherapy. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[6]  J. Petersen,et al.  The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy , 2009, Acta oncologica.

[7]  C. Moore,et al.  Rectal motion can reduce CTV coverage and increase rectal dose during prostate radiotherapy: A daily cone-beam CT study. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[8]  L. Muren,et al.  Acute morbidity related to treatment volume during 3D-conformal radiation therapy for prostate cancer. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  M. Sormani,et al.  Dosimetric predictors of diarrhea during radiotherapy for prostate cancer , 2007, Strahlentherapie und Onkologie.

[10]  Marcel van Herk,et al.  Margins for geometric uncertainty around organs at risk in radiotherapy. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[11]  Y. Kvinnsland,et al.  Testing the new ICRU 62 'Planning Organ at Risk Volume' concept for the rectum. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  F. Gao,et al.  Comparison of Four Modalities for Distant Metastases Staging in Endemic Nasopharyngeal Carcinoma , 2007 .

[13]  R. Jeraj Future of Physics in Medicine and Biology , 2009, Acta oncologica.

[14]  P. Koper,et al.  Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer. , 2005, International journal of radiation oncology, biology, physics.

[15]  Icru Prescribing, recording, and reporting photon beam therapy , 1993 .

[16]  M. Sydes,et al.  A comparison of dose-volume constraints derived using peak and longitudinal definitions of late rectal toxicity. , 2010, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  M. Goitein,et al.  Fitting of normal tissue tolerance data to an analytic function. , 1991, International journal of radiation oncology, biology, physics.

[18]  Steve Webb,et al.  Dose-volume constraints to reduce rectal side effects from prostate radiotherapy: evidence from MRC RT01 Trial ISRCTN 47772397. , 2010, International journal of radiation oncology, biology, physics.

[19]  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.

[20]  James A. Purdy,et al.  Three-dimensional conformal therapy or standard irradiation in localized carcinoma of prostate: preliminary results of a nonrandomized comparison. , 2000, International journal of radiation oncology, biology, physics.

[21]  M. Herk Will IGRT live up to its promise , 2008 .

[22]  J. Bailar,et al.  The histology and prognosis of prostatic cancer. , 1967, The Journal of urology.

[23]  R Mohan,et al.  Clinically relevant optimization of 3-D conformal treatments. , 1992, Medical physics.

[24]  Steve Webb,et al.  Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397) , 2009, Physics in medicine and biology.

[25]  J. Deasy,et al.  Radiation dose-volume effects in radiation-induced rectal injury. , 2010, International journal of radiation oncology, biology, physics.

[26]  R. Katz Dose. , 2020, Radiation research.

[27]  D. Yan,et al.  A model to accumulate fractionated dose in a deforming organ. , 1999, International journal of radiation oncology, biology, physics.

[28]  C. Ling,et al.  Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response. , 2000, International journal of radiation oncology, biology, physics.

[29]  L. Muren,et al.  Late gastrointestinal morbidity after three-dimensional conformal radiation therapy for prostate cancer fades with time in contrast to genitourinary morbidity. , 2008, International journal of radiation oncology, biology, physics.

[30]  Lei Dong,et al.  Fit of a Generalized Lyman Normal-Tissue Complication Probability (NTCP) Model to Grade ≥ 2 Late Rectal Toxicity Data From Patients Treated on Protocol RTOG 94-06 , 2007 .

[31]  Melvin L. Griem,et al.  Prescribing, Recording, and Reporting Photon Beam Therapy , 1994 .

[32]  M. Yano,et al.  Factors predictive of tumor recurrence and survival after initial complete response of esophageal squamous cell carcinoma to definitive chemoradiotherapy. , 2010, International journal of radiation oncology, biology, physics.

[33]  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.

[34]  T. Pajak,et al.  Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) , 1995, International journal of radiation oncology, biology, physics.

[35]  F Foppiano,et al.  Fitting late rectal bleeding data using different NTCP models: results from an Italian multi-centric study (AIROPROS0101). , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[36]  J J Shuster,et al.  Re: Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. , 1994, Journal of the National Cancer Institute.

[37]  Ludvig Paul Muren,et al.  On the use of margins for geometrical uncertainties around the rectum in radiotherapy planning. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[38]  G J Kutcher,et al.  Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms. , 2001, International journal of radiation oncology, biology, physics.