1887
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
oa
Quantifying cell migration distance as a contributing factor to the development of rectal toxicity after prostate radiotherapy
Rent:
Rent this article for
Access full text Article
/content/aapm/journal/medphys/41/2/10.1118/1.4852955
1.
1. Basic Clinical Radiobiology, edited by M. Joiner and A. van der Kogel, 4th ed. (Hodder Arnold, London, Great Britain, 2009).
2.
2. R. de Crevoisier, C. Fiorino, and B. Dubray, “Dosimetric factors predictive of late toxicity in prostate cancer radiotherapy,” Cancer/Radiothérapie 14, 460468 (2010).
http://dx.doi.org/10.1016/j.canrad.2010.07.225
3.
3. J. M. Michalski, H. Gay, A. Jackson, S. L. Tucker, and J. O. Deasy, “Radiation dose-volume effects in radiation-induced rectal injury,” Int. J. Radiat. Oncol., Biol., Phys. 76(Suppl. 3), S123S129 (2010).
http://dx.doi.org/10.1016/j.ijrobp.2009.03.078
4.
4. J. T. Lyman, “Complication probability as assessed from dose-volume histograms,” Radiat. Res. 104(2), S13S19 (1985).
http://dx.doi.org/10.2307/3576626
5.
5. Y. Lu et al., “A method of analyzing rectal surface area irradiated and rectal complications in prostate conformal radiotherapy,” Int. J. Radiat. Oncol., Biol., Phys. 33(5), 11211125 (1995).
http://dx.doi.org/10.1016/0360-3016(95)02030-6
6.
6. S. Li, A. Boyer, L. Yong, and G. T. Y. Chen, “Analysis of the dose-surface histogram and dose-wall histogram for the rectum and bladder,” Med. Phys. 24(7), 11071116 (1997).
http://dx.doi.org/10.1118/1.598014
7.
7. G. J. Meijer, M. van den Brink, M. S. Hoogeman, J. Meinders, and J. V. Lebesque, “Dose-wall histograms and normalized dose-surface histograms for the rectum: A new method to analyze the dose distribution over the rectum in conformal radiotherapy,” Int. J. Radiat. Oncol., Biol., Phys. 45(4), 10731080 (1999).
http://dx.doi.org/10.1016/S0360-3016(99)00270-9
8.
8. C. Fiorino et al., “Rectum contouring variability in patients treated for prostate cancer: Impact on rectum dose-volume histograms and normal tissue complication probability,” Radiother. Oncol. 63, 249255 (2002).
http://dx.doi.org/10.1016/S0167-8140(01)00469-8
9.
9. S. L. Tucker et al., “Comparison of rectal dose-wall histogram versus dose-volume histogram for modeling the incidence of late rectal bleeding after radiotherapy,” Int. J. Radiat. Oncol., Biol., Phys. 60(5), 15891601 (2004).
http://dx.doi.org/10.1016/j.ijrobp.2004.07.712
10.
10. R. Munbodh et al., “Evaluation of doses on a 2D map of the rectal wall for patients treated with imrt for prostate cancer,” Int. J. Radiat. Oncol., Biol., Phys. 66(Suppl. 3), S76 (2006).
http://dx.doi.org/10.1016/j.ijrobp.2006.07.167
11.
11. R. Munbodh, A. Jackson, J. Bauer, C. R. Schmidtlein, and M. J. Zelefsky, “Dosimetric and spatial indicators of late rectal toxicity after high-dose intensity modulated radiation therapy for prostate cancer,” Med. Phys. 35(5), 21372150 (2008).
http://dx.doi.org/10.1118/1.2907707
12.
12. R. Munbodh, A. Jackson, J. Bauer, C. R. Schmidtlein, and M. J. Zelefsky, “Spatial and anatomical indicators of rectal toxicity in IMRT of prostate cancer,” Int. J. Radiat. Oncol., Biol., Phys. 69(Suppl. 3), S10 (2007).
http://dx.doi.org/10.1016/j.ijrobp.2007.07.020
13.
13. S. L. Tucker et al., “Cluster model analysis of late rectal bleeding after IMRT of prostate cancer: A case-control study,” Int. J. Radiat. Oncol., Biol., Phys. 64(4), 12551264 (2006).
http://dx.doi.org/10.1016/j.ijrobp.2005.10.029
14.
14. E. W. Dijkstra, “A note on two problems in connexion with graphs,” Numer. Math. 1, 269271 (1959).
http://dx.doi.org/10.1007/BF01386390
15.
15. E. D. Yorke and G. J. Kutcher, “Spatial correlation in a parallel architecture NTCP model,” Proceedings of the 36th AAPM annual meeting, Anaheim CA. Med. Phys. 21, 879 (1994).
16.
16. S. M. Zhou et al., “A new three-dimensional dose distribution reduction scheme for tubular organs,” Med. Phys. 27, 17271731 (2000).
http://dx.doi.org/10.1118/1.1287050
17.
17. M. S. Hoogeman et al., “Quantification of local rectal wall displacements by virtual rectum unfolding,” Radiother. Oncol. 70, 2130 (2004).
http://dx.doi.org/10.1016/j.radonc.2003.11.015
18.
18. H. D. Thames et al., “Cluster models of dose-volume effects,” Int. J. Radiat. Oncol., Biol., Phys. 59(5), 14911504 (2004).
http://dx.doi.org/10.1016/j.ijrobp.2004.04.001
19.
19. W. D. Heemsbergen, M. S. Hoogeman, G. A. M. Hart, J. V. Lebesque, and P. C. M. Koper, “Gastrointestinal toxicity and its relation to dose distributions in the anorectal region of prostate cancer patients treated with radiotherapy,” Int. J. Radiat. Oncol., Biol., Phys. 61(4), 10111018 (2005).
http://dx.doi.org/10.1016/j.ijrobp.2004.07.724
20.
20. S. T. H. Peeters et al., “Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer,” Int. J. Radiat. Oncol., Biol., Phys. 63(4), 11421152 (2005).
http://dx.doi.org/10.1016/j.ijrobp.2005.03.060
21.
21. E. N. J. T. van Lin et al., “Reduced late rectal mucosal changes after prostate three-dimensional conformal therapy with endorectal balloon as observed in repeated endoscopy,” Int. J. Radiat. Oncol., Biol., Phys. 67(3), 799811 (2007).
http://dx.doi.org/10.1016/j.ijrobp.2006.09.034
22.
22. F. Buettner, S. Gulliford, S. Webb, M. Sydes, D. Dearnaley, and M. Partridge, “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),” Phys. Med. Biol. 54(21), 65356548 (2009).
http://dx.doi.org/10.1088/0031-9155/54/21/006
23.
23. F. Buettner, S. Gulliford, S. Webb, and M. Partridge, “Modeling late rectal toxicities based on a parametrized representation of the 3D dose distribution,” Phys. Med. Biol. 56(7), 21032118 (2011).
http://dx.doi.org/10.1088/0031-9155/56/7/013
24.
24. M. Partridge, “A radiation damage repair model for normal tissues,” Phys. Med. Biol. 53, 35953608 (2008).
http://dx.doi.org/10.1088/0031-9155/53/13/014
25.
25. R. J. Yaes and A. Kalend, “Local stem cell depletion model for radiation myelitis,” Int. J. Radiat. Oncol., Biol., Phys. 14, 12471259 (1988).
http://dx.doi.org/10.1016/0360-3016(88)90404-X
26.
26. H. R. Withers and H. Thames, “Dose fractionation and volume effects in normal tissues and tumors,” Am. J. Clin. Oncol. 11(3), 313329 (1988).
http://dx.doi.org/10.1097/00000421-198806000-00008
27.
27. M. Hauer-Jensen, “Late radiation injury of the small intestine,” Acta Oncol. 29(4), 401415 (1990).
http://dx.doi.org/10.3109/02841869009090022
28.
28. M. W. Skwarchuk and E. L. Travis, “Volume effects and epithelial regeneration in irradiated mouse colorectum,” Radiat. Res. 149, 110 (1998).
http://dx.doi.org/10.2307/3579675
29.
29. A. J. van der Kogel, “Dose-volume effects in the spinal cord,” Radiother. Oncol. 29, 105109 (1993).
http://dx.doi.org/10.1016/0167-8140(93)90234-Y
30.
30. B. Powers, H. Thames, S. Gillette, C. Smith, E. Beck, and E. Gillette, “Volume effects in the irradiated canine spinal cord: Do they exist when the probability of rectal injury is low?Radiother. Oncol. 46, 297306 (1998).
http://dx.doi.org/10.1016/S0167-8140(97)00213-2
31.
31. H. P. Bijl, P. van Luijk, R. P. Coppes, J. M. Schippers, A. W. Konings, and A. J. van der Kogel, “Unexpected changes of rat cervical spine cord tolerance caused by inhomogeneous dose distributions,” Int. J. Radiat. Oncol., Biol., Phys. 57(1), 274281 (2003).
http://dx.doi.org/10.1016/S0360-3016(03)00529-7
http://aip.metastore.ingenta.com/content/aapm/journal/medphys/41/2/10.1118/1.4852955
Loading
View: Figures

Figures

Image of FIG. 1.

Click to view

FIG. 1.

Distance maps for the region receiving at least 50 Gy to the 50 Gy isodose contour. (a) shows the spatial dose distribution on the surface of the rectum, (b) shows the minimum distance map, (50, 50) with the intensity values representing the minimum distance of points in the 50 Gy region to its boundary, and (c) illustrates the mean distance map, (50, 50) with the intensities representing the mean distance of the points to the boundary of the 50 Gy region. The corresponding dose distribution and minimum and mean distance maps on the flattened rectum in 2D are shown in (d), (e), and (f), respectively.

Image of FIG. 2.

Click to view

FIG. 2.

Distance maps for the region receiving at least 80 Gy to the 80 Gy isodose contour. (a) shows the 3D dose distribution for the part of the rectum receiving at least 80 Gy for the same patient. (b) and (c) show the minimum, (80, 80), and mean distance maps, (80, 80), for points in the 80 Gy region to the 80 Gy isodose line. The corresponding dose distributions and minimum and mean distance maps in 2D are shown in (d), (e), and (f).

Image of FIG. 3.

Click to view

FIG. 3.

DDSH, DiSH, and DSH for the minimum distance map of the region receiving at least 50 Gy to the 50 Gy isodose line illustrated in Fig. 1(b) . The DDSH is represented as an image with the intensity values in each bin or at each pixel representing the area of the rectum within the dose range and minimum distance from the 50 Gy isodose line for that bin. The marginal distribution of doses, that is the DSH, is given by the vertical bar plot and the marginal distribution of distances, the DiSH, is given by the horizontal bar plot.

Image of FIG. 4.

Click to view

FIG. 4.

Cumulative DDSH, DiSH, and DSH for the minimum distance map of the region receiving at least 50 Gy to the 50 Gy isodose line. Each bin in the cumulative DDSH represents the area in the region receiving at least 50 Gy exposed to a given minimum dose and at a given minimum distance from the 50 Gy isodose line. The cumulative distribution of doses and distances are shown as vertical and horizontal bar plots.

Image of FIG. 5.

Click to view

FIG. 5.

Isodose contours on the flattened rectum. The isodose contours for the regions receiving at least 70 Gy and 80 Gy for three different patients, P1, P2, and P3, are shown in (a), (b), and (c). The 80 Gy region was broken down into multiple smaller regions for P1 and P3. However, the total area of the 80 Gy region was similar for all three patients. That is, they had similar cumulative DSH's at these doses. The area irradiated to at least 70 Gy was the same for P1 and P3.

Image of FIG. 6.

Click to view

FIG. 6.

DiSH and cumulative DiSH for each of the patients whose isodose contours are illustrated in Fig. 5 . P1 is represented by a solid line (-), P2 by a dashed line (- -), and P3 by a solid line with dots (-.). Even though the total area of the 80 Gy region was similar for all three patients, the distribution in distances was different as illustrated by (a) the DiSH and (b) cumulative DiSH for the regions receiving at least 80 Gy to the 80 Gy isodose line. The DISH (c) and cumulative DiSH (d) for the region receiving at least 80 Gy to the 70 Gy isodose line is influenced by the area and contiguity of the region receiving at least 80 and its position relative to the 70 Gy isodose line. The DiSH and cumulative DiSH for the region receiving at least 70 Gy to the 70 Gy isodose line are shown in (e) and (f), respectively.

Image of FIG. 7.

Click to view

FIG. 7.

DDSH, DiSH, and DSH computed from the minimum distance map of the region receiving at least 50 Gy to the 50 Gy isodose line, (50, 50). The illustrated histograms were computed with a bin size of 2 mm and 2 Gy. The average 2D and marginal histograms for patients in the toxicity group are shown in (a) and the corresponding histograms for patients in the no-toxicity group are shown in (b).

Image of FIG. 8.

Click to view

FIG. 8.

Distance surface histogram for patients with toxicity (solid line) and without toxicity (dashed line). The histograms were computed from (a) (50, 50), (b) (75, 50), and (c) (75, 75). Significant differences in areas irradiated were observed for a range of distances.

Image of FIG. 9.

Click to view

FIG. 9.

ROC curves for: the area of the rectum receiving at least 50 Gy (A50, solid line), the area of the rectum receiving at least 75 Gy [A75, (−○)], the area of the rectum receiving at least 50 Gy and at a minimum distance of 2–8 mm and 14–20 mm from the 50 Gy isodose line [A5050, (- -)], the area of the rectum receiving at least 75 Gy and at a distance of 16–22 mm from the 50 Gy isodose line [A7550, [−×)], and (5) the area of the rectum receiving at least 75 Gy and at a distance of 0–4 mm and 18–24 mm from the 75 Gy isodose line [A7575, (- .)]. The respective areas under the curves were: (1) A50: 0.72, (2) A75: 0.69, (3) A5050: 0.76 (4) A7550: 0.75, and (5) A7575: 0.80.

Loading

Article metrics loading...

/content/aapm/journal/medphys/41/2/10.1118/1.4852955
2014-01-24
2014-04-16

Abstract

Spatial information is usually neglected in mathematical models of radiation-induced toxicity. In the presence of inhomogeneous dose distributions produced by intensity modulated radiation therapy (IMRT) and volumetric arc therapy, this may be a limitation. We present a model to quantify the spatial characteristics of the dose distribution on the rectum through the quantification of the distribution of distances between dose points on the surface of the rectum in three-dimensions. The method allows us to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and consequently, the development of radiation-induced toxicity in patients treated with radiation for prostate cancer.

We present a method to compute distances between dose points on the surface of the rectum in three dimensions (3D) and to generate distance maps representing the distances between specific dose regions on the rectum. We introduce the concept of the distance dose surface histogram (DDSH), which is computed from the distance maps. The DDSH is a 2D histogram of rectum area on a grid defined by pairwise combinations of dose and distance. Each bin in the DDSH quantifies the area of the rectum exposed to a given dose and at a given distance from other another dose region on the rectum. By summing across the columns and rows of the DDSH, we can generate the dose surface histogram (DSH) and distance surface histogram (DiSH) for a particular dose region. The DiSH is a marginal histogram showing the distribution of distances for the dose points in a specific dose region from another region. We computed the DDSH, DiSH, and DSH for 33 patients treated with IMRT for prostate cancer, nine of whom developed late Grade 2 or higher late rectal toxicity.

We show how even though the total area of the rectum exposed to a given dose may be the same for different patients, the distribution of distances for points receiving that dose can be different depending on the shape and contiguity of the region(s) containing those dose points. We also show that area of the rectum in the region receiving more than 75 Gy and at a distance of 16 to 22 mm from the 50 Gy isodose line was significantly correlated to the development of toxicity ( = 0.004, two sided -test). This suggests that examining the distance distribution of points in specific dose regions could provide valuable additional information in predicting the risk of a patient developing radiation-induced rectal toxicity.

We present a new method to quantify the spatial distribution of points in a given region relative to other regions on the rectum. The method provides a means to evaluate the hypothesis that distances between lower and higher dose regions on the rectum influence radiation damage repair due to the migration of normal cells into damaged areas, and may be a contributing factor to the development of radiation-induced toxicity in patients treated with radiation for prostate cancer.

Loading

Full text loading...

/deliver/fulltext/aapm/journal/medphys/41/2/1.4852955.html;jsessionid=a0iu8y3ib2cc.x-aip-live-02?itemId=/content/aapm/journal/medphys/41/2/10.1118/1.4852955&mimeType=html&fmt=ahah&containerItemId=content/aapm/journal/medphys
true
true
This is a required field
Please enter a valid email address
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Quantifying cell migration distance as a contributing factor to the development of rectal toxicity after prostate radiotherapy
http://aip.metastore.ingenta.com/content/aapm/journal/medphys/41/2/10.1118/1.4852955
10.1118/1.4852955
SEARCH_EXPAND_ITEM