Principal component analysis-based pattern analysis of dose-volume histograms and influence on rectal toxicity

PURPOSE: The variability of dose-volume histogram (DVH) shapes in a patient population can be quantified using principal component analysis (PCA). We applied this to rectal DVHs of prostate cancer patients and investigated the correlation of the PCA parameters with late bleeding. METHODS AND MATERIALS: PCA was applied to the rectal wall DVHs of 262 patients, who had been treated with a four-field box, conformal adaptive radiotherapy technique. The correlated changes in the DVH pattern were revealed as "eigenmodes," which were ordered by their importance to represent data set variability. Each DVH is uniquely characterized by its principal components (PCs). The correlation of the first three PCs and chronic rectal bleeding of Grade 2 or greater was investigated with uni- and multivariate logistic regression analyses. RESULTS: Rectal wall DVHs in four-field conformal RT can primarily be represented by the first two or three PCs, which describe approximately 94% or 96% of the DVH shape variability, respectively. The first eigenmode models the total irradiated rectal volume; thus, PC1 correlates to the mean dose. Mode 2 describes the interpatient differences of the relative rectal volume in the two- or four-field overlap region. Mode 3 reveals correlations of volumes with intermediate doses ( approximately 40-45 Gy) and volumes with doses >70 Gy; thus, PC3 is associated with the maximal dose. According to univariate logistic regression analysis, only PC2 correlated significantly with toxicity. However, multivariate logistic regression analysis with the first two or three PCs revealed an increased probability of bleeding for DVHs with more than one large PC. CONCLUSIONS: PCA can reveal the correlation structure of DVHs for a patient population as imposed by the treatment technique and provide information about its relationship to toxicity. It proves useful for augmenting normal tissue complication probability modeling approaches.     

Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer

BACKGROUND: We sought to identify the bladder dose-volume factors associated with an increased risk of late urinary toxicity among prostate cancer patients treated with radiotherapy. METHODS AND MATERIALS: This retrospective analysis included data from 128 prostate cancer patients treated on protocol with 2 Gy/fraction to 46 Gy followed by a boost to 78 Gy. The endpoint for this analysis was Grade 1 or greater late genitourinary (GU) toxicity occurring within two years of treatment. The Lyman-Kutcher-Burman, mean dose, threshold dose, and hottest volume models were fitted to the toxicity data using the maximum likelihood method. RESULTS: Model fits based on dose-volume histograms tended to fit the toxicity data better than models based on dose-wall histograms. The hottest volume (hotspot) model was found to be the best-fitting model investigated. The best fit was for the hottest 2.9% of bladder (95% CI, 1.1-6.8%). This model has an area under the receiver operating characteristic curve of 0.74. The hotspot model separated the patients into clinically meaningful subgroups with approximately 25% of the patients who received <78 Gy to the hottest 2.9% of bladder had GU toxicity at eight years compared with approximately 50% when the dose was > or =78 Gy (p = 0.002). CONCLUSION: This provides the first evidence supporting that bladder "hotspots" are related to GU toxicity within two years after external beam radiotherapy for prostate cancer. Confirming data are needed from other investigators. Particular attention should be given to hotspots higher than 78 Gy in bladder in radiation treatment planning.     

Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

PURPOSE: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade > or = 2 rectal bleeding. METHODS AND MATERIALS: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD, (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. RESULTS: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. CONCLUSIONS: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse.     

Acute small bowel toxicity and preoperative chemoradiotherapy for rectal cancer: investigating dose-volume relationships and role for inverse planning

PURPOSE: The relationship between volume of irradiated small bowel (VSB) and acute toxicity in rectal cancer radiotherapy is poorly quantified, particularly in patients receiving concurrent preoperative chemoradiotherapy. Using treatment planning data, we studied a series of such patients. METHODS AND MATERIALS: Details of 41 patients with locally advanced rectal cancer were reviewed. All received 45 Gy in 25 fractions over 5 weeks, 3-4 fields three-dimensional conformal radiotherapy with daily 5-fluorouracil and folinic acid during Weeks 1 and 5. Toxicity was assessed prospectively in a weekly clinic. Using computed tomography planning software, the VSB was determined at 5 Gy dose intervals (V5, V10, etc.). Eight patients with maximal VSB had dosimetry and radiobiological modeling outcomes compared between inverse and conformal three-dimensional planning. RESULTS: VSB correlated strongly with diarrheal severity at every dose level (p<0.03), with strongest correlation at lowest doses. Median VSB differed significantly between patients experiencing Grade 0-1 and Grade 2-4 diarrhea (p相似文献   

Impact of knee support and shape of tabletop on rectum and prostate position

PURPOSE: To evaluate the impact of different tabletops with or without a knee support on the position of the rectum, prostate, and bulb of the penis; and to evaluate the effect of these patient-positioning devices on treatment planning. METHODS AND MATERIALS: For 10 male volunteers, five MRI scans were made in four different positions: on a flat tabletop with knee support, on a flat tabletop without knee support, on a rounded tabletop with knee support, and on a rounded tabletop without knee support. The fifth scan was in the same position as the first. With image registration, the position differences of the rectum, prostate, and bulb of the penis were measured at several points in a sagittal plane through the central axis of the prostate. A planning target volume was generated from the delineated prostates with a margin of 10 mm in three dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each planning target volume. Dose-volume histograms were calculated for all rectal walls. RESULTS: The shape of the tabletop did not affect the rectum and prostate position. Addition of a knee support shifted the anterior and posterior rectal walls dorsally. For the anterior rectal wall, the maximum dorsal shift was 9.9 mm (standard error of the mean [SEM] 1.7 mm) at the top of the prostate. For the posterior rectal wall, the maximum dorsal shift was 10.2 mm (SEM 1.5 mm) at the middle of the prostate. Therefore, the rectal filling was pushed caudally when a knee support was added. The knee support caused a rotation of the prostate around the left-right axis at the apex (i.e., a dorsal rotation) by 5.6 degrees (SEM 0.8 degrees ) and shifts in the caudal and dorsal directions of 2.6 mm (SEM 0.4 cm) and 1.4 mm (SEM 0.6 mm), respectively. The position of the bulb of the penis was not influenced by the use of a knee support or rounded tabletop. The volume of the rectal wall receiving the same dose range (e.g., 40-75 Gy) was reduced by 3.5% (SEM 0.9%) when a knee support was added. No significant differences were observed between the first and fifth scan (flat tabletop with knee support) for all measured points, thereby excluding time trends. CONCLUSIONS: The rectum and prostate were significantly shifted dorsally by the use of a knee support. The rectum shifted more than the prostate, resulting in a dose benefit compared with irradiation without knee support. The shape of the tabletop did not influence the rectum or prostate position.     

肺癌不同放射治疗技术剂量学比较研究

目的：应用三维治疗计划系统评价肺癌不同的照射方法，以明确肺癌三维适形放射治疗的优势。方法：选用13例ⅢA、ⅢB期非小细胞肺癌病例，采用Cadplan 6.0.8三维治疗计划系统设计放射治疗计划，每例均做3个计划，分别为常规、常规加适形和适形放射治疗计划，计划的总剂量均为66Gy。用剂量体积直方图（DVH）比较靶区剂量和正常组织的受照射剂量的差异。结果：3种治疗计划均能满足靶区剂量要求，剂量变化差异无显著性意义。常规、常规加适形和适形放射治疗计划的照射适形指数分别为0．13、0．24和0．35；全肺接受≥20Gy照射的体积百分比的均数分别为32％、26％、34％和22％；心脏平均剂量的均数分别为18．15和12Gy。结论：肺癌常规放射治疗设野方法基本能满足靶区的剂量学要求，然而正常组织的受照剂量明显高于其他2种治疗计划。三维适形放射治疗的主要优势在于减少正常组织的受照剂量。     

Long term rectal function after high-dose prostatecancer radiotherapy: Results from a prospective cohort study

Purpose

To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors.

Materials and methods

Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ?6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated.

Results

Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2–G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p = 0.016) ?G1 lrb was significantly associated with V75Gy (OR = 1.07). In multivariate analysis, ?G1 linc was associated with V40Gy (OR = 1.015), use of antihypertensive medication (OR = 0.38), abdominal surgery before RT (OR = 4.7), haemorrhoids (OR = 2.6), and G2–G3 acute faecal incontinence (OR = 4.4), a nomogram to predict the risk of long-term ?G1 linc was proposed.Importantly, the prevalence of ?G1 linc was significantly correlated with the mean incontinence score during the first 3 years after RT (OR = 16.3).

Conclusions

Long-term (median: 7 years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3 years after RT. Linc was associated with several risk factors.     

Comparison between the ideal reference dose level and the actual reference dose level from clinical 3D radiotherapy treatment plans

Purpose

Retrospective study of 3D clinical treatment plans based on radiobiological considerations in the choice of the reference dose level from tumor dose-volume histograms.

Methods and materials

When a radiation oncologist evaluates the 3D dose distribution calculated by a treatment planning system, a decision must be made on the percentage dose level at which the prescribed dose should be delivered. Much effort is dedicated to deliver a dose as uniform as possible to the tumor volume. However due to the presence of critical organs, the result may be a rather inhomogeneous dose distribution throughout the tumor volume. In this study we use a formulation of tumor control probability (TCP) based on the linear quadratic model and on a parameter, the F factor. The F factor allows one to write TCP, from the heterogeneous dose distribution (TCP{(ε_j,D_j)}), as a function of TCP under condition of homogeneous irradiation of tumor volume (V) with dose D (TCP(V,D)). We used the expression of the F factor to calculate the “ideal” percentage dose level (iDL_r) to be used as reference level for the prescribed dose D delivery, so as to render TCP{(ε_j,D_j)} equal to TCP(V,D).The 3D dose distributions of 53 clinical treatment plans were re-evaluated to derive the iDL_r and to compare it with the one (D_tpL) to which the dose was actually administered.

Results

For the majority of prostate treatments, we observed a low overdosing following the choice of a D_tpL lower than the iDL_r. While for the breast and head-and-neck treatments, the method showed that in many cases we underdosed choosing a D_tpL greater than the iDL_r. The maximum difference between the iDL_r and the D_tpL was −3.24% for one of the head-and-neck treatments.

Conclusions

Using the TCP model, the probability of tumor control is compromised following an incorrect choice of D_tpL; so we conclude that the application of the F factor is an effective tool and clinical aid to derive the optimal reference dose level from the dose-volume histogram (DVH) of each treatment plan.     

Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: a radiobiologic analysis

PURPOSE: To quantify the mitigation of geometric uncertainties achieved with the application of various patient setup techniques during the delivery of hypofractionated prostate cancer treatments, using tumor control probability (TCP) and normal tissue complication probability. METHODS AND MATERIALS: Five prostate cancer patients with approximately 16 treatment CT studies, taken during the course of their radiation therapy (77 total), were analyzed. All patients were planned twice with an 18 MV six-field conformal technique, with 10- and 5-mm margin sizes, with various hypofractionation schedules (5 to 35 fractions). Subsequently, four clinically relevant patient setup techniques (laser guided and image guided) were simulated to deliver such schedules. RESULTS: As hypothesized, the impact of geometric uncertainties on clinical outcomes increased with more hypofractionated schedules. However, the absolute gain in TCP due to hypofractionation (up to 21.8% increase) was significantly higher compared with the losses due to geometric uncertainties (up to 8.6% decrease). CONCLUSIONS: The results of this study suggest that, although the impact of geometric uncertainties on the treatment outcomes increases as the number of fractions decrease, the reduction in TCP due to the uncertainties does not significantly offset the expected theoretical gain in TCP by hypofractionation.     

Spatial heterogeneity of the volume effect for radiation pneumonitis in mouse lung

: In a previous study to determine the effect of partial voume irradiation on damage and morbidity from pneumonitis in mouse lung, a critical determinant of the volume effect was the spatial location of the irradiated subvolume within the ling. The goals of the present study were to (a) define the dose-volume effect curves for radiation pneumonitis in mouse lung, (b) defined the threshold volume, and (c) further investigate the special heterogeneity of the radiosensitivity of mouse lung.

: eight fractional volumes ranging from 94% to 17% of the lungs of C3Hf/Kam mice were irradiated with single doses ranging from 12 to 22 Gy, depending on the volume irradiated. The fractional volumes irradiated were determined from computed tomographic scans of mouse lung. To determine the effect of location of irradiated subvolume, equivalent volumes in the base and the apex were irradiated by shielding the prescribed adjacent volume in the apex or base respectively. Dose-response curves of breathing rate at 22 weeks and lethality at 28 weeks were constructed for each subvolume irradiated in the apex or base and fitted by logit analysis, and ED₅₀s and LD₅₀s with 95% confidence limits obtained, respectively. Lungs from dead mice or mice sacrificed when moribund were examined for histologic signs of pneumonitis.

: Irradiation of any of the eight subvolumes in the base yielded a consistently lower isoeffect dose for both assays of radiation pneumonitis than if the same irradiated subvolume was lovated in the apex. Plots of isoeffect dose for breathing rate as s function of subvolume irradiated in the base or apex showed that these curves were non linear but exhibited a plateau between irradiated volumes of 70% and 80% in both the apex and base. A similar curve was obtained for lethality and volume irradiated in the base. A threshold volume, i.e., irradiation of that volume that should produce no changes in breating rate or mortality, was dependent on the location of the irradiated subvolume.

: The response of mouse ling to partial volume irradiation is heterogeeous and is critically dependent on the specific location of the irradiated subvolume in the ling, i.e., a given subvolume in the base is consistently more sensitive than the same subvolume in the apex using either breathing rate or lethality as assays of radiation pneumonitis. We suggest that this heterogeneity is due to the antomy of the tracheobronchial tree, i.e., to the distribution of non-gas exchange-conducting airways in the irradiated volume. These data have implications for the modeling of dose-volume effects in the lung and the prediction of normal tissue complication probabilities for radiation pneumonitis in humans.     

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

PURPOSE: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. RESULTS: Anal dosimetric variables were associated with RTOG/EORTC Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D(mean). Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus. CONCLUSION: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.     

Reduction of dose delivered to the rectum and bulb of the penis using MRI delineation for radiotherapy of the prostate

PURPOSE: The prostate volume delineated on MRI is smaller than on CT. The purpose of this study was to determine the influence of MRI- vs. CT-based prostate delineation using multiple observers on the dose to the target and organs at risk during external beam radiotherapy. MATERIALS AND METHODS: CT and MRI scans of the pelvic region were made of 18 patients and matched three-dimensionally on the bony anatomy. Three observers delineated the prostate using both modalities. A fourth observer delineated the rectal wall and the bulb of the penis. The planning treatment volume (PTV) was generated from the delineated prostates with a margin of 10 mm in three-dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each PTV. Dose-volume histograms were calculated of all PTVs, rectal walls, and penile bulbs. The equivalent uniform dose was calculated for the rectal wall using a volume exponent (n = 0.12). RESULTS: The equivalent uniform dose of the CT rectal wall in plans based on the CT-delineated prostate was, on average, 5.1 Gy (SEM 0.5) greater than in the plans based on the MRI-delineated prostate. For the MRI rectal wall, this difference was 3.6 Gy (SEM 0.4). Allowing for the same equivalent uniform dose to the CT rectal wall, the prescribed dose to the PTV could be raised from 78 to 85 Gy when using the MRI-delineated prostate for treatment planning. The mean dose to the bulb of the penis was 11.6 Gy (SEM 1.8) lower for plans based on the MRI-delineated prostate. The mean coverage (volume of the PTV receiving > or =95% of the prescribed dose) was 99.9% for both modalities. The interobserver coverage (coverage of the PTV by a treatment plan designed for the PTV delineated by another observer in the same modality) was 97% for both modalities. The MRI rectum was significantly more ventrally localized than the CT rectum, probably because of the rounded tabletop and no knee support on the MRI scanner. CONCLUSIONS: The dose delivered to the rectal wall and bulb of the penis is significantly reduced with treatment plans based on the MRI-delineated prostate compared with the CT-delineated prostate, allowing a dose escalation of 2.0-7.0 Gy for the same rectal wall dose. The interobserver coverage was the same for CT and MRI delineation of the prostate. A statistically significant difference in position between the CT- and MRI-delineated rectum was observed, probably owing to a different tabletop and use of knee support.