Search

Purpose: To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor., Methods and Materials: Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor γ (fixing α/β = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population., Results: The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/β values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/β = 5 Gy, best-fit values for γ were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for γ (0.6-1.0 Gy/d), with comparable goodness of fit for α/β values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including γ were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC = 0.73)., Conclusions: The unexpected impact of moderate hypofractionation on severe incontinence and hematuria after postprostatectomy radiation therapy may be explained by a bladder α/β value <1 Gy or, radiobiologically more plausible, by introducing a time factor likely to represent a previously hypothesized consequential component of late effect., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The aim of this paper was the application of the failure mode and effects analysis (FMEA) approach to assess the risks for patients undergoing radiotherapy treatments performed by means of a helical tomotherapy unit. FMEA was applied to the preplanning imaging, volume determination, and treatment planning stages of the tomotherapy process and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system; and 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. A total of 74 failure modes were identified: 38 in the stage of preplanning imaging and volume determination, and 36 in the stage of planning. The threshold of 125 for RPN was exceeded in four cases: one case only in the phase of preplanning imaging and volume determination, and three cases in the stage of planning. The most critical failures appeared related to (i) the wrong or missing definition and contouring of the overlapping regions, (ii) the wrong assignment of the overlap priority to each anatomical structure, (iii) the wrong choice of the computed tomography calibration curve for dose calculation, and (iv) the wrong (or not performed) choice of the number of fractions in the planning station. On the basis of these findings, in addition to the safety strategies already adopted in the clinical practice, novel solutions have been proposed for mitigating the risk of these failures and to increase patient safety.

Purpose: To report planning and acute toxicity data of the first 60 patients treated within a Phase I-II study with moderate hypofractionation by image-guided helical tomotherapy., Methods and Materials: Various clinical target volumes (CTVs) were defined: CTV1-pelvic nodes; CTV2-upper portion of seminal vesicles; CTV3-lower portion of SV; CTV4-prostate; overlap between planning target volume (PTV) 4 and rectum. Different doses to each PTV were simultaneously delivered in 28 fractions. For 31 low-risk patients: 56.0, 61.6, and 71.4 Gy for PTV2-4, respectively; for 20 intermediate-risk patients: 51.8, 61.6, 65.5, and 74.2 Gy for PTV1-4, respectively; for 9 high-risk patients: 51.8 and 65.5 Gy for PTV1-2 and 74.2 Gy for PTV3-4. For all patients, the dose to overlap was 65.5 Gy., Results: The mean fraction of rectum receiving more than 65 Gy (V65) and rectal Dmax were 10% and 70.8 Gy respectively. In cases of pelvic node irradiation, the intestinal cavity (outside PTV) receiving > 45 and 50 Gy was 86 and 12 cc, respectively. A homogeneous dose distribution within each PTV was guaranteed. Acute genitourinary toxicity according to RTOG scoring system was as follows: 21/60 (35%) Grade 1, 12/60 (20%) Grade 2, 2/60 (3%) Grade 3. Acute rectal toxicities were: 18/60 (30%) Grade 1. Twelve (20%) patients showed Grade 1 upper intestinal toxicity (uGI). No patients experienced > or = Grade 2 acute rectal or uGI side effects., Conclusions: This study shows excellent results with regard to acute toxicity. Further research is necessary to assess definitive late toxicity and tumor control outcome.

Purpose: To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT)., Methods: The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP)., Results: Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role., Conclusion: The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.

Simple Summary: Studies comparing performances of machine learning (ML) methods in building predictive models of toxicity in RT are rare. Thanks to the availability of a large cohort (n = 1314) of breast cancer patients homogeneously treated with tangential fields, different ML approaches could be compared. This work shows how more complex models typically achieve higher performances. At the same time, for this test case, the importance is given mainly by a few variables, and toxicity can be predicted by simpler models with similar performances. The availability of more individually characterizing features (here partially missing) is expected to have a likely much higher impact than the choice of the best-performing ML/DL approach. Purpose. Different ML models were compared to predict toxicity in RT on a large cohort (n = 1314). Methods. The endpoint was RTOG G2/G3 acute toxicity, resulting in 204/1314 patients with the event. The dataset, including 25 clinical, anatomical, and dosimetric features, was split into 984 for training and 330 for internal tests. The dataset was standardized; features with a high p-value at univariate LR and with Spearman ρ > 0.8 were excluded; synthesized data of the minority were generated to compensate for class imbalance. Twelve ML methods were considered. Model optimization and sequential backward selection were run to choose the best models with a parsimonious feature number. Finally, feature importance was derived for every model. Results. The model's performance was compared on a training–test dataset over different metrics: the best performance model was LightGBM. Logistic regression with three variables (LR3) selected via bootstrapping showed performances similar to the best-performing models. The AUC of test data is slightly above 0.65 for the best models (highest value: 0.662 with LightGBM). Conclusions. No model performed the best for all metrics: more complex ML models had better performances; however, models with just three features showed performances comparable to the best models using many (n = 13–19) features. [ABSTRACT FROM AUTHOR]

Purpose. To verify the possibility of using Helical Tomotherapy to safely escalate dose to single or multiple highly radioresistant dominant intra-prostatic lesions (DILs) as assessed by functional magnetic resonance imaging (MRI). Material. In seven intermediate/high risk patients, T2WI, T1WI and DWI MRI imaging showed evidence of one DIL in four patients and two DILs in three patients in the peripheral zone of the prostate. The planning strategy was to deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4 Gy/28 fractions (EQD2=75 Gy) to the remaining portion of PTV. A higher priority was assigned to rectal constraints relative to DIL coverage. Rectal NTCP calculations were performed using the most recently available model data. Results. The median dose to DIL could safely be escalated to at least 100 Gy (EQD2,α/β=10=113 Gy) without violating safe constraints for the organs at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and 5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder, urethra and femoral heads were always respected. Conclusions. IGRT by Helical Tomotherapy may permit the safe escalation of EQD2,α/β=10 to at least 113 Gy to DILs without significantly increasing rectal NTCP compared to plans without dose escalation. A Phase I-II clinical study is warranted. [ABSTRACT FROM AUTHOR]