To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and 11C-choline positron emission tomography ...(PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs).
From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months.
Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis.
In PC relapsed patients treated with ENRT and 11C-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.
•KB-model for irradiation of nodes + prostate + vesicles in post-prostatectomy patients.•The step-validation increased the confidence in using KB-optimization.•Automatic KB-model showed better/equal ...performances compared to clinical plans.•The interaction of a planner further improved planning performances.•A gEUD reduction (up to 9 Gy) was seen in both KB optimization modalities.
To develop and apply a stepping approach for the validation of Knowledge-based (KB) models for planning optimization: the method was applied to the case of concomitant irradiation of pelvic nodes and prostate + seminal−vesicles bed irradiation in post-prostatectomy patients.
The clinical VMAT plans of 52 patients optimized by two reference planners were selected to generate a KB-model (RapidPlan, v.13.5 Varian). A stepping-validation approach was followed by comparing KB-generated plans (with and without planner-interaction, RP and only-RP respectively) against delivered clinical plans (RA). The validation followed three steps, gradually extending its generalization: 20 patients used to develop the model (closed-loop); 20 new patients, same planners (open-loop); 20 new patients, different planners (wide-loop). All plans were compared, in terms of relevant dose-volume parameters and generalized equivalent uniform dose (gEUD).
KB-plans were generally better than or equivalent to clinical plans. For RPvsRA, PTVs coverage was comparable, for OARs RP was always better. Comparing only-RPvsRA, PTVs coverage was always better; bowel\bladder V50Gy and D1%, bowel\bladder\rectum Dmean, femoral heads V40Gy and penile bulb V50Gy were significantly improved. For RPvsRA gEUD reduction >1 Gy was seen in 80% of plans for rectum, bladder and bowel; for only-RPvsRA, this was found in 50% for rectum/bladder and in 70% for bowel.
An extensive stepping validation approach of KB-model for planning optimization showed better or equal performances of automatically generated KB-plan compared to clinical plans. The interaction of a planner further improved planning performances.
Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of ...complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer.
Rectal dose-volume histograms of the rectum (DVH) and clinical records of 547 prostate cancer patients (pts) pooled from five institutions previously collected and analyzed were considered. All patients were treated in supine position with 3 or 4-field techniques: 123 patients received an ICRU dose between 64 and 70
Gy, 255 patients between 70 and 74
Gy and 169 patients between 74 and 79.2
Gy; 457/547 patients were treated with conformal RT and 203/547 underwent radical prostatectomy before RT. Minimum follow-up was 18 months. Patients were considered as bleeders if showing grade 2/3 late bleeding (slightly modified RTOG/EORTC scoring system) within 18 months after the end of RT. Four NTCP models were considered: (a) the Lyman model with DVH reduced to the equivalent uniform dose (LEUD, coincident with the classical Lyman–Kutcher–Burman, LKB, model), (b) logistic with DVH reduced to EUD (LOGEUD), (c) Poisson coupled to EUD reduction scheme and (d) relative seriality (RS). The parameters for the different models were fit to the patient data using a maximum likelihood analysis. The 68% confidence intervals (CI) of each parameter were also derived.
Forty six out of five hundred and forty seven patients experienced grade 2/3 late bleeding: 38/46 developed rectal bleeding within 18 months and were then considered as bleeders The risk of rectal bleeding can be well calculated with a ‘smooth’ function of EUD (with a seriality parameter
n equal to 0.23 (CI 0.05), best fit result). Using LEUD the relationship between EUD and NTCP can be described with a TD50 of 81.9
Gy (CI 1.8
Gy) and a steepness parameter
m of 0.19 (CI 0.01); when using LOGEUD, TD50 is 82.2
Gy and
k is 7.85. Best fit parameters for RS are
s=0.49, γ=1.69, TD50=83.1
Gy. Qualitative as well as quantitative comparisons (chi-squared statistics,
P=0.005) show that the models fit the observed complication rates very well. The results found in the overall population were substantially confirmed in the subgroup of radically treated patients (LEUD:
n=0.24
m=0.14 TD50=75.8
Gy). If considering just the grade 3 bleeders (
n=9) the best fit is found in correspondence of a
n-value around 0.06, suggesting that for severe bleeding the rectum is more serial.
Different NTCP models fit quite accurately the considered clinical data. The results are consistent with a rectum ‘less serial’ than previously reported investigations when considering grade 2 bleeding while a more serial behaviour was found for severe bleeding. EUD may be considered as a robust and simple parameter correlated with the risk of late rectal bleeding.
Highlights • Application of a pixel-wise method for analysis of bladder dose surface maps (DSMs). • Extraction of spatial-dose descriptors associated with the risk of urinary toxicity. • An impact of ...trigone dose on urinary toxicity is found in the whole/HYPO populations. • A cranial extension of the 75 Gy isodose emerges for conventionally treated patients. • DSM descriptors improve the performance of models for predicting urinary toxicity.
Abstract Aims To report 5 year outcome and late toxicity in prostate cancer patients treated with image-guided tomotherapy with a moderate hypofractionated simultaneous integrated boost approach. ...Materials and methods In total, 211 prostate cancer patients, 78 low risk, 53 intermediate risk and 80 high risk were treated between 2005 and 2011. Intermediate- and high-risk patients received 51.8 Gy to pelvic lymph nodes and concomitant simultaneous integrated boost to prostate up to 74.2 Gy/28 fractions, whereas low-risk patients were treated to the prostate only with 71.4 Gy/28 fractions. Daily megavoltage computed tomography (MVCT) image guidance was applied. Androgen deprivation was prescribed for a median duration of 6 months for low-risk patients (for downsizing), 12 months for intermediate-risk and 36 months for high-risk patients. The 5 year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), overall survival and late gastrointestinal and genitourinary CTCAE.v3 toxicity were assessed. The effect of several clinical variables on both outcome and gastrointestinal/genitourinary toxicity was tested by uni- and multivariate Cox regression analyses. Results After a median follow-up of 5 years, the late toxicity actuarial incidence was: genitourinary ≥ grade 2: 20.2%; genitourinary ≥ grade 3: 5.9%; gastrointestinal ≥ grade 2: 17%; gastrointestinal ≥ grade 3: 6.3% with lower prevalence at the last follow-up visit (≥ grade 3: genitourinary: 1.9%; gastrointestinal: 1.9%). Major predictors of ≥ grade 3 genitourinary and gastrointestinal late toxicity were genitourinary acute toxicity ≥ grade 2 (hazard ratio: 4.9) and previous surgery (hazard ratio: 3.4). The overall 5 year bRFS was 93.7% (low risk: 94.6%; intermediate risk: 96.2%; high risk: 91.1%), overall survival and CSS were 88.6% (low risk: 90.5%; intermediate risk: 87.4%; high risk: 87%) and 97.5% (low risk: 98.7%; intermediate risk: 95%; high risk: 94.3%), respectively. Risk classes and androgen deprivation were not significantly correlated with either bRFS, overall survival or CSS. Twelve patients experienced a biochemical relapse but none experienced clinically proven local and/or pelvic recurrence. Conclusion A satisfactory 5 year outcome with an acceptable toxicity profile was observed. The combination of image-guided radiotherapy–intensity-modulated radiotherapy, high equivalent 2 Gy dose (EQD2) with a moderate hypofractionated approach and extensive prophylactic lymph node irradiation also leads to very good outcome in high-risk patients.
Highlights • Robustness of bladder absorbed dose relative to daily inter-fraction motion. • Systematic (SE) and random errors (RE) of bladder dose surface maps (DSM), DVH/DSH. • DSH and DVH show ...small population SE (<3.4 cm2 and <8.4 cm3 ) at the highest doses. • DSM show mean SE <1 Gy and population SE and RE (<4 and <3 Gy) at the posterior base. • Larger variations are present in the anterior and more cranial portion of bladder.
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