Probabilistic objective functions for margin-less IMRT planning.

We present a method to implement probabilistic treatment planning of intensity-modulated radiation therapy using custom software plugins in a commercial treatment planning system. Our method avoids the definition of safety-margins by directly including the effect of geometrical uncertainties during optimization when objective functions are evaluated. Because the shape of the resulting dose distribution implicitly defines the robustness of the plan, the optimizer has much more flexibility than with a margin-based approach. We expect that this added flexibility helps to automatically strike a better balance between target coverage and dose reduction for surrounding healthy tissue, especially for cases where the planning target volume overlaps organs at risk. Prostate cancer treatment planning was chosen to develop our method, including a novel technique to include rotational uncertainties. Based on population statistics, translations and rotations are simulated independently following a marker-based IGRT correction strategy. The effects of random and systematic errors are incorporated by first blurring and then shifting the dose distribution with respect to the clinical target volume. For simplicity and efficiency, dose-shift invariance and a rigid-body approximation are assumed. Three prostate cases were replanned using our probabilistic objective functions. To compare clinical and probabilistic plans, an evaluation tool was used that explicitly incorporates geometric uncertainties using Monte-Carlo methods. The new plans achieved similar or better dose distributions than the original clinical plans in terms of expected target coverage and rectum wall sparing. Plan optimization times were only about a factor of two higher than in the original clinical system. In conclusion, we have developed a practical planning tool that enables margin-less probability-based treatment planning with acceptable planning times, achieving the first system that is feasible for clinical implementation.

Implementation of endoscopic ultrasound for lung cancer staging.

BACKGROUND: EUS-guided FNA is currently advocated in lung cancer staging guidelines as an alternative for surgical staging to prove mediastinal metastases. To date, training requirements for chest physicians to obtain competency in EUS for lung cancer staging are unknown. OBJECTIVE: To test a training and implementation strategy for EUS for the diagnosis and staging of lung cancer. DESIGN: Prospective national multicenter implementation trial. Nine (chest) physicians from 5 hospitals participated in a dedicated EUS educational program (investigation of 50 patients) for the diagnosis and staging of lung cancer. EUS outcomes of trainees were compared with those of the training center. SETTING: Four general hospitals, the national cancer center (implementation centers), and a tertiary referral center (expert center). PATIENTS: This study involved 551 consecutive patients with (suspected) lung cancer, all candidates for surgical staging, who underwent EUS in 1 of the 5 implementation centers (n = 346) or the single expert center (n = 205). Surgical-pathological staging was the reference standard in case no mediastinal metastases were found. RESULTS: EUS had a sensitivity of 83% versus 82% and accuracy of 89% versus 88% for mediastinal nodal staging (implementation center vs expert center). Surgery was spared because of EUS findings in 51% versus 54% of patients. A single complication occurred in each group. LIMITATION: Surgical-pathological verification of mediastinal nodes was not available in all patients staged negative at EUS. CONCLUSION: Chest physicians who participate in a dedicated training and implementation program for EUS in lung cancer staging can obtain results similar to those of experts for mediastinal nodal staging.

Relating dose outside the prostate with freedom from failure in the Dutch trial 68 Gy vs. 78 Gy.

PURPOSE: For prostate cancer patients at risk for subclinical spread of the disease, we investigated whether incidental dose outside the target was associated with tumor control. METHODS AND MATERIALS: We selected 352 intermediate-risk (mainly T2b-T3a) and high-risk (mainly T3b) patients treated in a randomized trial. Target volume was prostate (68-78 Gy) and seminal vesicles (50-78 Gy). Failure (clinical or biochemical) was evaluated at 4 years. To compare three-dimensional dose distributions, an automated mapping procedure was introduced. Between patients, these maps provide an approximate identification of corresponding anatomical locations. Maps of the dose difference between patients with and without failure were constructed. Univariate and multivariate analyses were performed including the dose in selected points. RESULTS: Dose differences were mainly found in the obturatorial region for the high-risk patients, and in the presacral region for the intermediate risk group (>7 Gy, p < 0.01). Univariate hazard ratios per 10 Gy for selected dose points were 0.83 (p = 0.01, obturatorial) and 0.72 (p = 0.002, presacral). These hazard ratios were stable under multivariate analysis correcting for established prognostic factors, hospital, and dose to the prostate. CONCLUSIONS: Patients without failure have received on average a higher dose to regions where regional cancer spread could be expected.

Nonviable tumor tissue should not upstage Wilms' tumor from stage I to stage II: a report from the SIOP 93-01 nephroblastoma trial and study.

In SIOP trials, Wilms' tumors were labeled as stage II by the presence of nonviable and/or viable tumor in the renal sinus and/or perirenal fat. The aim of this study was to determine if this approach was justified. Stage II Wilms' tumors were reviewed to establish whether staging was due to viable or nonviable tumor, and this was related to clinical outcome. One hundred sixty-nine patients were included: 40 had stage II due to the presence of nonviable tumor and 129 due to viable tumor. Postoperatively, 29 patients were undertreated: 7 with nonviable and 22 with viable stage II tumors. No undertreated patient with nonviable stage II relapsed or died (event-free survival [EFS] and overall survival [OS] 100%), whereas 3 of 22 with viable stage II relapsed, and 2 of them died (EFS 86%, OS 91%). Of 140 correctly treated patients, only 1 of 33 nonviable stage II patients relapsed and died (EFS and OS 97%); 8 of 107 patients with viable stage II relapsed (EFS 92%), and 3 of them died (OS 97%). The presence of nonviable tumor in the renal sinus and/or perirenal fat does not predict an adverse outcome in Wilms' tumors, and alone it does not warrant designation to stage II.