Ano-rectal wall dose-surface maps localize the dosimetric benefit of hydrogel rectum spacers in prostate cancer radiotherapy.
ABSTRACT: Background and purpose:To evaluate spatial differences in dose distributions of the ano-rectal wall (ARW) using dose-surface maps (DSMs) between prostate cancer patients receiving intensity-modulated radiation therapy with and without implantable rectum spacer (IMRT+IRS; IMRT-IRS, respectively), and to correlate this with late gastro-intestinal (GI) toxicities using validated spatial and non-spatial normal-tissue complication probability (NTCP) models. Materials and methods:For 26 patients DSMs of the ARW were generated. From the DSMs various shape-based dose measures were calculated at different dose levels: lateral extent, longitudinal extent, and eccentricity. The contiguity of the ARW dose distribution was assessed by the contiguous-DSH (cDSH). Predicted complication rates between IMRT+IRS and IMRT-IRS plans were assessed using a spatial NTCP model and compared against a non-spatial NTCP model. Results:Dose surface maps are generated for prostate radiotherapy using an IRS. Lateral extent, longitudinal extent and cDSH were significantly lower in IMRT+IRS than for IMRT-IRS at high-dose levels. Largest significant differences were observed for cDSH at dose levels >50?Gy, followed by lateral extent at doses >57?Gy, and longitudinal extent in anterior and superior-inferior directions. Significant decreases (p?=?0.01) in median rectal and anal NTCPs (respectively, Gr 2 late rectal bleeding and subjective sphincter control) were predicted when using an IRS. Conclusions:Local-dose effects are predicted to be significantly reduced by an IRS. The spatial NTCP model predicts a significant decrease in Gr 2 late rectal bleeding and subjective sphincter control. Dose constraints can be improved for current clinical treatment planning.
Project description:<h4>Background and purpose</h4>For the first time, delivered dose to the rectum has been calculated and accumulated throughout the course of prostate radiotherapy using megavoltage computed tomography (MVCT) image guidance scans. Dosimetric parameters were linked with toxicity to test the hypothesis that delivered dose is a stronger predictor of toxicity than planned dose.<h4>Material and methods</h4>Dose-surface maps (DSMs) of the rectal wall were automatically generated from daily MVCT scans for 109 patients within the VoxTox research programme. Accumulated-DSMs, representing total delivered dose, and planned-DSMs, from planning CT data, were parametrised using Equivalent Uniform Dose (EUD) and 'DSM dose-width', the lateral dimension of an ellipse fitted to a discrete isodose cluster. Associations with 6 toxicity endpoints were assessed using receiver operator characteristic curve analysis.<h4>Results</h4>For rectal bleeding, the area under the curve (AUC) was greater for accumulated dose than planned dose for DSM dose-widths up to 70Gy. Accumulated 65Gy DSM dose-width produced the strongest spatial correlation (AUC 0.664), while accumulated EUD generated the largest AUC overall (0.682). For proctitis, accumulated EUD was the only reportable predictor (AUC 0.673). Accumulated EUD was systematically lower than planned EUD.<h4>Conclusions</h4>Dosimetric parameters extracted from accumulated DSMs have demonstrated stronger correlations with rectal bleeding and proctitis, than planned DSMs.
Project description:Recently, a new radiotherapy delivery technique has become clinically available--volumetric modulated arc therapy (VMAT). VMAT is the delivery of IMRT while the gantry is in motion using dynamic leaf motion. The perceived benefit of VMAT over IMRT is a reduction in delivery time. In this study, VMAT was compared directly with IMRT for a series of prostate cases. For 10 patients, a biologically optimized seven-field IMRT plan was compared with a biologically optimized VMAT plan using the same planning objectives. The Pinnacle RTPS was used. The resultant target and organ-at-risk dose-volume histograms (DVHs) were compared. The normal tissue complication probability (NTCP) for the IMRT and VMAT plans was calculated for 3 model parameter sets. The delivery efficiency and time for the IMRT and VMAT plans was compared. The VMAT plans resulted in a statistically significant reduction in the rectal V25Gy parameter of 8.2% on average over the IMRT plans. For one of the NTCP parameter sets, the VMAT plans had a statistically significant lower rectal NTCP. These reductions in rectal dose were achieved using 18.6% fewer monitor units and a delivery time reduction of up to 69%. VMAT plans resulted in reductions in rectal doses for all 10 patients in the study. This was achieved with significant reductions in delivery time and monitor units. Given the target coverage was equivalent, the VMAT plans were superior.
Project description:BACKGROUND: To evaluate the safety of focal dose escalation to regions with standardized uptake value (SUV) >2.0 using intensity-modulated radiation therapy (IMRT) by comparison of radiotherapy plans using dose-volume histograms (DVHs) and normal tissue complication probability (NTCP) for postoperative local recurrent rectal cancer METHODS: First, we performed conventional radiotherapy with 40 Gy/20 fr. (CRT 40 Gy) for 12 patients with postoperative local recurrent rectal cancer, and then we performed FDG-PET/CT radiotherapy planning for those patients. We defined the regions with SUV > 2.0 as biological target volume (BTV) and made three boost plans for each patient: 1) CRT boost plan, 2) IMRT without dose-painting boost plan, and 3) IMRT with dose-painting boost plan. The total boost dose was 20 Gy. In IMRT with dose-painting boost plan, we increased the dose for BTV+5 mm by 30% of the prescribed dose. We added CRT boost plan to CRT 40 Gy (summed plan 1), IMRT without dose-painting boost plan to CRT 40 Gy (summed plan 2) and IMRT with dose-painting boost plan to CRT 40 Gy (summed plan 3), and we compared those plans using DVHs and NTCP. RESULTS: D(mean) of PTV-PET and that of PTV-CT were 26.5 Gy and 21.3 Gy, respectively. V50 of small bowel PRV in summed plan 1 was significantly higher than those in other plans ((summed plan 1 vs. summed plan 2 vs. summed plan 3: 47.11 +/- 45.33 cm3 vs. 40.63 +/- 39.13 cm3 vs. 41.25 +/- 39.96 cm3 (p < 0.01, respectively)). There were no significant differences in V30, V40, V60, D(mean) or NTCP of small bowel PRV. CONCLUSIONS: FDG-PET-guided IMRT can facilitate focal dose-escalation to regions with SUV above 2.0 for postoperative local recurrent rectal cancer.
Project description:PURPOSE:Comparing radiation treatment plans by using the same safety margins and dose objectives for all techniques, to ascertain the optimal radiation technique for the stereotactic body radiotherapy (SBRT) of low-risk prostate cancer. MATERIAL AND METHODS:Treatment plans for 27 randomly selected patients were compared using intensity-modulated (IMRT) techniques as Sliding Window (SW), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT), as well as Cyber Knife (CK) system. The target dose was calculated to 36.25 Gy delivered in five fractions over 1 week. Dosimetric indices for target volume and organs at risk (OAR) as well as normal tissue complication probability (NTCP) of late rectal and urinary bladder toxicities were analyzed. RESULTS:The CK provided lower homogeneity in the target volume, but higher values for most of the conformity indices compared to the IMRT approaches. The SW demonstrated superior rectum sparing at medium-to-high dose range (V18 Gy - V32.6 Gy) compared to other techniques (p < 0.05). The whole urinary bladder experienced the best shielding by SW and VMAT at the medium dose (V18 Gy, p < 0.05 versus CK), however we obtained no relevant differences between techniques at the high dose. Generally, the CK demonstrated significantly superior rectum and bladder exposure at V18 Gy as compared to HT, SW, and VMAT. For the rectum, mean NTCP values were significantly superior for HT (NTCP = 2.3%, p < 0.05), and for urinary bladder, the NTCP showed no significant advantages for any technique. CONCLUSION:No absolute dosimetric advantage was revealed to choose between CK or IMRT techniques for the SBRT of low-grade prostate cancer. Using the same safety margins and dose objectives, IMRT techniques demonstrated superior sparing of the rectum and bladder at a medium dose compared to CK. Comparing different IMRT approaches SW displayed superior rectum sparing at a medium-to-high dose range, whereas both SW and RA revealed superior bladder sparing compared to HT. HT demonstrated a significantly lower NTCP outcome compared to CK or IMRT techniques regarding the rectum. Radiation plans can be optimized further by an individual modification of dose objectives independent of the treatment plan strategy.
Project description:AIM:To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. METHODS:A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ? 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. RESULTS:Sixteen patients (20.3%) developed acute grade?2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1-0.16), slope m=0.09 (0.08-0.11), and threshold dose TD50=56.8 (53.7-59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ?2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the remainder (p=0.01). CONCLUSIONS:Patient specific characteristics strongly influence the likelihood of acute grade ? 2 rectal toxicity in radiation therapy for prostate cancer.
Project description:Purpose: To determine whether there are differences in bone marrow tolerance to chemoradiotherapy (CRT) between two chemotherapy regimens according to FOWARC protocol and how chemotherapy regimens affect radiation dose parameters and normal tissue complication probability (NTCP) modelings that correlate with acute hematologic toxicity (HT) in rectal cancer patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. Materials and Methods: One hundred and twenty-eight rectal cancer patients who received IMRT from a single institution were recruited from Chinese FOWARC multicenter, open-label, randomized phase III trial. We assessed HT in these patients who were separated into two groups: Oxaliplatin (L-OHP) + 5- fluorouracil (5FU) (FOLFOX, 70 of 128) and 5FU (58 of 128). The pelvic bone marrow (PBM) was divided into three subsites: lumbosacral spine (LSS), ilium (I), and lower pelvic (LP). The endpoint for HT was grade ?3 (HT3+) and grade ?2 (HT2+) leukopenia, neutropenia, anemia and thrombocytopenia. Logistic regression was used to analyze the association between HT2+/HT3+ and dosimetric parameters. Lyman-Kutcher-Burman (LKB) model was used to calculate NTCP. Results: Sixty-eight patients experienced HT2+: 22 of 58 (37.9%) 5FU and 46 of 70 (65.7%) FOLFOX (p = 0.008), while twenty-six patients experienced HT3+: 4 of 58 (6.9%) 5FU and 22 of 70 (31.4%) FOLFOX (p = 0.016). PBM and LP dosimetric parameters were correlated with HT2+ in the 5FU group but not in the FOLFOX group. No PBM dosimetric parameters were correlated with HT3+ in both groups. For PBM, NTCP at HT3+ was 0.32 in FOLFOX group relative to 0.10 in 5FU subset (p < 0.05). Conclusion: Patients receiving FOLFOX have lower BM tolerance to CRT than those receiving 5FU. Low-dose radiation to the PBM is predictive for HT2+ in patients who received 5FU. NTCP modeling in FOLFOX group predicts much higher risk of HT3+ than 5FU group.
Project description:<h4>Background</h4>The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model.<h4>Methods</h4>For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison.<h4>Result</h4>The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P?=?0.007), duodenum (1.87% vs. 5.02%, P?=?0.004), and stoduo (5.67% vs. 7.81%, P?=?0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ?NTCP <sub>IMRT - ro-IMPT</sub> (using parameter from Pan et al. for gastric bleed) of ?5 to <?10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCP<sub>ro-IMPT</sub>/NTCP<sub>IMRT</sub>) reduction was noted (0.16-0.81) for all GI-OARs except for duodenum (>?1) with endpoint grade???3 GI toxicity (using parameters from Holyoake et al.).<h4>Conclusion</h4>With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.
Project description:<h4>Background and purpose</h4>To determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).<h4>Methods and materials</h4>Two groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5-25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.<h4>Results</h4>PMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05).<h4>Conclusion</h4>Whilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.
Project description:To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system.Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle(3)). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1-5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC).In total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 ± 1.2 vs. MCO: 3.6 ± 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57-0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 ± 4.5 Gy vs. 12.9 ± 4.0 Gy, p < 0.001), and to reduced dose to the contra-lateral parotid gland (28.1 ± 11.8 Gy vs. 23.0 ± 11.2 Gy, p < 0.002). Consequently, NTCP estimates for xerostomia reduced by 8.4 ± 7.4% (p < 0.003). The hands-on time of the conventional IMRT planning was approximately 205 min. The time to create an MCO-plan was on average 43 ± 12 min.MCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve.
Project description:OBJECTIVE:To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose. METHODS:The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose-volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan. RESULTS:Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1?±?0.6 vs 72.7?±?0.3?Gy; p?<?0.001) and decreased for the rectum (38.2?±?2.5 vs 43.5?±?2.5?Gy; p?<?0.001) and the bladder (29.1?±?9.0 vs 36.9?±?9.3?Gy; p?<?0.001) for the boosted plan. The prostate TCP was increased (80.1?±?1.3 vs 75.3?±?0.9?Gy; p?<?0.001) and rectal NTCP lowered (3.84?±?3.65 vs 9.70?±?5.68?Gy; p?=?0.04) in the boosted plan. The bladder NTCP was negligible for both plans. CONCLUSION:Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found. ADVANCES IN KNOWLEDGE:The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.