PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. METHODS AND MATERIALS: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally. All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade ≥3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy. A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life. RESULTS: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P=.012). The incidence of grade ≥3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively. Compared with patients treated without IG-IMRT (n=48), those treated with IG-IMRT (n=35) had a significantly lower incidence of grade ≥3 neutropenia (8.6% vs 27.1%; 2-sided χ(2)P=.035) and nonsignificantly lower incidence of grade ≥3 leukopenia (25.7% vs 41.7%; P=.13) and any grade ≥3 hematologic toxicity (31.4% vs 43.8%; P=.25). CONCLUSIONS: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes. Positron emission tomography IG-IMRT reduces the incidence of acute neutropenia.

• MeSH
• adenokarcinom diagnostické zobrazování   patologie   terapie   MeSH
• brachyterapie metody   MeSH
• celková dávka radioterapie MeSH
• chemoradioterapie metody   MeSH
• cisplatina terapeutické užití   MeSH
• gastrointestinální trakt účinky záření   MeSH
• incidence MeSH
• kostní dřeň * MeSH
• léčba šetřící orgány metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory děložního čípku diagnostické zobrazování   patologie   terapie   MeSH
• neutropenie epidemiologie   prevence a kontrola   MeSH
• protinádorové látky terapeutické užití   MeSH
• radiosenzibilizující látky terapeutické užití   MeSH
• radioterapie řízená obrazem metody   MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• spinocelulární karcinom diagnostické zobrazování   patologie   terapie   MeSH
• studie proveditelnosti MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

PURPOSE: To demonstrate an efficient method for training and validation of a knowledge-based planning (KBP) system as a radiation therapy clinical trial plan quality-control system. METHODS AND MATERIALS: We analyzed 86 patients with stage IB through IVA cervical cancer treated with intensity modulated radiation therapy at 2 institutions according to the standards of the INTERTECC (International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer, National Clinical Trials Network identifier: 01554397) protocol. The protocol used a planning target volume and 2 primary organs at risk: pelvic bone marrow (PBM) and bowel. Secondary organs at risk were rectum and bladder. Initial unfiltered dose-volume histogram (DVH) estimation models were trained using all 86 plans. Refined training sets were created by removing sub-optimal plans from the unfiltered sample, and DVH estimation models… and DVH estimation models were constructed by identifying 30 of 86 plans emphasizing PBM sparing (comparing protocol-specified dosimetric cutpoints V10 (percentage volume of PBM receiving at least 10 Gy dose) and V20 (percentage volume of PBM receiving at least 20 Gy dose) with unfiltered predictions) and another 30 of 86 plans emphasizing bowel sparing (comparing V40 (absolute volume of bowel receiving at least 40 Gy dose) and V45 (absolute volume of bowel receiving at least 45 Gy dose), 9 in common with the PBM set). To obtain deliverable KBP plans, refined models must inform patient-specific optimization objectives and/or priorities (an auto-planning "routine"). Four candidate routines emphasizing different tradeoffs were composed, and a script was developed to automatically re-plan multiple patients with each routine. After selection of the routine that best met protocol objectives in the 51-patient training sample (KBPFINAL), protocol-specific DVH metrics and normal tissue complication probability were compared for original versus KBPFINAL plans across the 35-patient validation set. Paired t tests were used to test differences between planning sets. RESULTS: KBPFINAL plans outperformed manual planning across the validation set in all protocol-specific DVH cutpoints. The mean normal tissue complication probability for gastrointestinal toxicity was lower for KBPFINAL versus validation-set plans (48.7% vs 53.8%, P<.001). Similarly, the estimated mean white blood cell count nadir was higher (2.77 vs 2.49 k/mL, P<.001) with KBPFINAL plans, indicating lowered probability of hematologic toxicity. CONCLUSIONS: This work demonstrates that a KBP system can be efficiently trained and refined for use in radiation therapy clinical trials with minimal effort. This patient-specific plan quality control resulted in improvements on protocol-specific dosimetric endpoints.

• MeSH
• klinické zkoušky jako téma normy   MeSH
• kostní dřeň MeSH
• kritické orgány * MeSH
• léčba šetřící orgány metody   normy   MeSH
• lidé MeSH
• močový měchýř MeSH
• nádory děložního čípku patologie   radioterapie   MeSH
• pánevní kosti MeSH
• plánování radioterapie pomocí počítače metody   normy   MeSH
• radioterapie s modulovanou intenzitou metody   normy   MeSH
• rektum MeSH
• řízení kvality * MeSH
• střeva MeSH
• tumor burden MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• validační studie MeSH