T.M. Janssen

Reducing interobserver variation of boost-CTV delineation in breast conserving radiation therapy using a pre-operative CT and delineation guidelines ☆

AIMS To investigate whether using a pre-operative CT scan (Preop-CT) (1) decreases interobserver variation of boost-CTV delineation in breast conserving therapy (BCT), and (2) influences the size of the delineated volumes. PATIENTS AND METHODS Thirty cT1-2N0-1 breast cancer patients underwent a CT-scan in radiation treatment position, prior to and after lumpectomy. Five observers delineated a boost-CTV, both with and without access to the Preop-CT. For each patient and for each observer pair, the conformity index (CI) and the distance between the centres of mass (COMd) for both boost volumes were calculated. In addition, all delineated volumes including the standard deviation (SD) with respect to the median delineation were calculated. RESULTS Using a Preop-CT reduced the mean COMd of the boost-CTV from 1.1cm to 1.0 cm (p<0.001). No effect was seen on the CI, but the boost-CTV volume reduced from 42 cc to 36 cc (p=0.005), implying a reduction of interobserver variation. We saw no significant change in the SD. CONCLUSION Use of a Preop-CT in BCT results in a modest but statistically significant reduction in interobserver variation of the boost-CTV delineations and in a significant reduction in the boost-CTV volume.

Target volume delineation in external beam partial breast irradiation: less inter-observer variation with preoperative- compared to postoperative delineation

The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of twenty-four breast cancer patients.

Pareto Fronts in Clinical Practice for Pinnacle

PURPOSE Our aim was to develop a framework to objectively perform treatment planning studies using Pareto fronts. The Pareto front represents all optimal possible tradeoffs among several conflicting criteria and is an ideal tool with which to study the possibilities of a given treatment technique. The framework should require minimal user interaction and should resemble and be applicable to daily clinical practice. METHODS AND MATERIALS To generate the Pareto fronts, we used the native scripting language of Pinnacle(3) (Philips Healthcare, Andover, MA). The framework generates thousands of plans automatically from which the Pareto front is generated. As an example, the framework is applied to compare intensity modulated radiation therapy (IMRT) with volumetric modulated arc therapy (VMAT) for prostate cancer patients. For each patient and each technique, 3000 plans are generated, resulting in a total of 60,000 plans. The comparison is based on 5-dimensional Pareto fronts. RESULTS Generating 3000 plans for 10 patients in parallel requires on average 96 h for IMRT and 483 hours for VMAT. Using VMAT, compared to IMRT, the maximum dose of the boost PTV was reduced by 0.4 Gy (P=.074), the mean dose in the anal sphincter by 1.6 Gy (P=.055), the conformity index of the 95% isodose (CI(95%)) by 0.02 (P=.005), and the rectal wall V(65 Gy) by 1.1% (P=.008). CONCLUSIONS We showed the feasibility of automatically generating Pareto fronts with Pinnacle(3). Pareto fronts provide a valuable tool for performing objective comparative treatment planning studies. We compared VMAT with IMRT in prostate patients and found VMAT had a dosimetric advantage over IMRT.

Beam configuration selection for robust intensity-modulated proton therapy in cervical cancer using Pareto front comparison

The Pareto front reflects the optimal trade-offs between conflicting objectives and can be used to quantify the effect of different beam configurations on plan robustness and dose-volume histogram parameters. Therefore, our aim was to develop and implement a method to automatically approach the Pareto front in robust intensity-modulated proton therapy (IMPT) planning. Additionally, clinically relevant Pareto fronts based on different beam configurations will be derived and compared to enable beam configuration selection in cervical cancer proton therapy. A method to iteratively approach the Pareto front by automatically generating robustly optimized IMPT plans was developed. To verify plan quality, IMPT plans were evaluated on robustness by simulating range and position errors and recalculating the dose. For five retrospectively selected cervical cancer patients, this method was applied for IMPT plans with three different beam configurations using two, three and four beams. 3D Pareto fronts were optimized on target coverage (CTV D(99%)) and OAR doses (rectum V30Gy; bladder V40Gy). Per patient, proportions of non-approved IMPT plans were determined and differences between patient-specific Pareto fronts were quantified in terms of CTV D(99%), rectum V(30Gy) and bladder V(40Gy) to perform beam configuration selection. Per patient and beam configuration, Pareto fronts were successfully sampled based on 200 IMPT plans of which on average 29% were non-approved plans. In all patients, IMPT plans based on the 2-beam set-up were completely dominated by plans with the 3-beam and 4-beam configuration. Compared to the 3-beam set-up, the 4-beam set-up increased the median CTV D(99%) on average by 0.2 Gy and decreased the median rectum V(30Gy) and median bladder V(40Gy) on average by 3.6% and 1.3%, respectively. This study demonstrates a method to automatically derive Pareto fronts in robust IMPT planning. For all patients, the defined four-beam configuration was found optimal in terms of plan robustness, target coverage and OAR sparing.

SPECT/CT-guided elective nodal irradiation for head and neck cancer: Estimation of clinical benefits using NTCP models

BACKGROUND AND PURPOSE The great majority of patients with lateralized head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy routinely undergo bilateral elective nodal irradiation (ENI), even though the incidence of contralateral regional failure after unilateral ENI is low. Excluding the contralateral neck from elective irradiation could reduce radiation-related toxicity and improve quality-of-life. The current study investigated the dosimetric benefits of a novel approach using lymph drainage mapping by SPECT/CT to select patients for unilateral ENI. PATIENTS AND METHODS Forty patients with lateralized cT1-3N0-2bM0 HNSCC underwent lymph drainage mapping. Two radiation plans were made; the real plan with which patients were actually treated (selective SPECT/CT-guided plan irradiating the ipsilateral neck ± any contralateral draining level); and the virtual plan (standard plan according to institutional guidelines, as if the same patient would have been treated bilaterally). Radiation doses to clinically important organs-at-risk were compared between the two plans. We used five normal tissue complication probability (NTCP) models to predict the clinical benefits of this approach. RESULTS Median dose reductions to the contralateral parotid gland, contralateral submandibular gland, glottic larynx, supraglottic larynx, constrictor muscle and thyroid gland were 19.2, 27.3, 11.4, 9.7, 12.1 and 18.4 Gy, respectively. Median NTCP reductions for xerostomia, contralateral parotid function, dysphagia, hypothyroidism and laryngeal edema were 20%, 14%, 10%, 20% and 5% respectively. CONCLUSIONS Selective SPECT/CT-guided ENI results in significant dose reductions to various organs-at-risk and corresponding NTCP values, and will subsequently reduce the incidence and severity of different troublesome radiation-related toxicities and improve quality-of-life.

The impact of margin reduction on outcome and toxicity in head and neck cancer patients treated with image-guided volumetric modulated arc therapy (VMAT)

BACKGROUND AND PURPOSE In recent decades, outcomes of patients with head and neck cancer (HNC) have improved as a result of implementing several strategies, such as chemoradiation. However, these improvements were achieved at the cost of increased toxicity. One way to reduce radiation-related toxicity is by reducing the margins. MATERIALS AND METHODS Between 2013 and 2016, 206 consecutive patients were treated with CTV-PTV margin of 5 mm and subsequently 208 patients with 3 mm margin. This study evaluates the impact of reducing clinical target volume (CTV) to planning target volume (PTV) margin on outcome and toxicity. RESULTS All patients were treated with volumetric modulated arc therapy (VMAT) with daily-image guidance using cone-beam CT (CBCT). Overall acute grade 3 toxicity was significantly lower in 3 mm-group, compared to 5 mm-group (53.8% vs. 65%, respectively, p = 0.032). The same was true for acute grade 3 mucositis (30.8% vs. 42.2%, p = 0.008) and for acute grade 3 dysphagia (feeding tube-dependence) (22.1% vs. 33.5%, p = 0.026). The incidence of ongoing feeding tube-dependence after 3 months of radiotherapy was 11.1% and 20.4%, respectively (p = 0.012). The 2-year incidence of late grade ≥2 xerostomia was 15.8% and 19.4% (p = 0.8). The 2-year loco-regional control rates of patients treated in 3 mm and 5 mm-groups were 79.9% and 79.2% (p = 1.0). The figures for disease-free survival were 71.5% and 72.7 (p = 0.6) and for overall survival were 75.2% and 75.1% (p = 0.9). CONCLUSION Reducing the CTV-PTV margin from 5 to 3 mm combined with daily CBCT-guided VMAT reduced the severity, frequency, and duration of radiation-related toxicity without jeopardizing outcome.

A robust volumetric arc therapy planning approach for breast cancer involving the axillary nodes

We quantify the robustness of a proposed volumetric-modulated arc therapy (VMAT) planning and treatment technique for radiotherapy of breast cancer involving the axillary nodes. The proposed VMAT technique is expected to be more robust to breast shape changes and setup errors, yet maintain the improved conformity of VMAT compared to our current standard technique that uses tangential intensity-modulated radiation therapy (IMRT) fields. Treatment plans were created for 10 patients. To account for anatomical variation, planning was carried out on a computed tomography (CT) with an expanded breast, followed by segment weight optimization (SWO) on the original planning CT (VMAT + SWO). For comparison purposes, tangential field IMRT plans and conventional VMAT (cVMAT) plans were also created. Anatomical changes (expansion and contraction of the breast) and setup errors were simulated to quantify changes in target coverage, target maximum, and organ-at-risk (OAR) doses. Finally, robustness was assessed by calculating the actual delivered dose for each fraction using cone-beam CT images acquired during treatment. Target coverage of VMAT + SWO was shown to be significantly more robust compared to cVMAT technique, against anatomical variations and setup errors. Sensitivity of the clinical target volume (CTV) V95% is -5%/cm of expansion for the proposed technique, which is identical to the IMRT technique and much lower than the -22%/cm for cVMAT. Results are similar for setup errors. OAR doses are mostly insensitive to anatomical variations and the OAR sensitivity to setup variations does not depend on the planning technique. The results are confirmed by dose distributions recalculated on cone-beam CT, showing that for VMAT + SWO the CTV V95% remains within 2.5% of the planned value, whereas it deviates by up to 7% for cVMAT. A practical VMAT planning technique is developed, which is robust to daily anatomical variations and setup errors.