Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy Radiation Therapy in ≥PT2, pN0 Patients With a Comprehensive Tumor Control Probability Model

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• 作者：Claudio Fiorino ; PhD^&lowast ; ; ^{fiorino.claudio@hsr.it" class="auth_mail" title="E-mail the corresponding author} ; Sara Broggi ; PhD^&lowast ; ; Nicola Fossati ; MD^&dagger ; ; Cesare Cozzarini ; MD^&Dagger ; ; Gregor Goldner ; MD^§ ; ; Thomas Wiegel ; MD^‖ ; Wolfgang Hinkelbein ; MD^¶ ; ; R. Jeffrey Karnes ; MD^# ; Stephen A. Boorjian ; MD^# ; Karin Haustermans ; MD^&lowast ; &lowast ; ; Steven Joniau ; MD^&dagger ; &dagger ; ; Federica Palorini ; PhD^&lowast ; ; Shahrokh Shariat ; MD^&Dagger ; &Dagger ; ; Francesco Montorsi ; MD^&dagger ; ; Hein Van Poppel ; MD^&dagger ; &dagger ; ; Nadia Di Muzio ; MD^&Dagger ; ; Riccardo Calandrino ; PhD^&lowast ; ; Alberto Briganti ; MD^&dagger ;
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：96
• 期：2
• 页码：333-340
• 全文大小：396 K

文摘

To fit the individual biochemical recurrence-free survival (bRFS) data from patients treated with postprostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model.

Methods and Materials

Considering pre-RT prostate-specific antigen (PSA) as a surrogate of the number of clonogens, bRFS may be expressed as a function of dose-per-fraction–dependent radiosensitivity (α_eff), the number of clonogens for pre-RT PSA = 1 ng/mL (C), and the fraction of patients who relapse because of clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data from 894 node-negative, ≥pT2, pN0 hormone-naive patients treated with adjuvant (n=331) or salvage (n=563) intent were available: 5-year bRFS data were fitted grouping patients according to GS (<7:392, =7:383, >7:119).

Results

The median follow-up time, pre-RT PSA, and dose were 72 months, 0.25 ng/mL, and 66.6 Gy (range 59.4-77.4 Gy), respectively. The best-fit values were 0.23 to 0.26 Gy⁻¹ and 10⁷ for α_eff and C for the model considering a linear dependence between K and PSA. Calibration plots showed good agreement between expected and observed incidences (slope: 0.90-0.93) and moderately high discriminative power (area under the curve [AUC]: 0.68-0.69). Cross-validation showed satisfactory results (average AUCs in the training/validation groups: 0.66-0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS. bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of the maximum) declined by about 2.7% and 4.5% for each increment of 0.1 ng/mL for GS <7 and ≥7, respectively.

Conclusions

Individual data were fitted by a TCP model, and the resulting best-fit parameters were radiobiologically consistent. The model suggests that relapses frequently result from clonogens outside the irradiated volume, supporting the choice of lymph-node irradiation, systemic therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0 ng/mL; GS ≥7: PSA >0.3 ng/mL). Early RT should be preferred over delayed RT; the detrimental effect of PSA increase can never be fully compensated by increasing the dose, especially for patients with GS ≥7.