Abstract Background and purpose A radiosurgical treatment approach for early-stage breast cancer has the potential to minimize the patient’s treatment burden. The dosimetric feasibility for single ...fraction ablative radiotherapy was evaluated by comparing volumetric modulated arc therapy (VMAT) with an interstitial multicatheter brachytherapy (IMB) approach. Methods and materials The tumors of 20 patients with early-stage breast cancer were delineated on a preoperative contrast-enhanced planning CT-scan, co-registered with a contrast-enhanced magnetic resonance imaging (MRI), both in radiotherapy supine position. A dose of 15 Gy was prescribed to the planned target volume of the clinical target volume (PTVCTV ), and 20 Gy integrated boost to the PTV of the gross tumor volume (PTVGTV ). Treatment plans for IMB and VMAT were optimized for adequate target volume coverage and minimal organs at risk (OAR) dose. Results The median PTVGTV/CTV receiving at least 95% of the prescribed dose was ⩾ 99% with both techniques. The median PTVCTV unintentionally receiving 95% of the prescribed PTVGTV dose was 65.4% and 4.3% with IMB and VMAT, respectively. OAR doses were comparable with both techniques. Conclusion MRI-guided single fraction radiotherapy with an integrated ablative boost to the GTV is dosimetrically feasible with both techniques. We perceive IMB less suitable for clinical implementation due to PTVCTV overdosage. Future studies have to confirm the clinical feasibility of the single fraction ablative approach.
Treatment for locally advanced rectal cancer (LARC) consists of chemoradiation therapy (CRT) and surgery. Approximately 15% of patients show a pathological complete response (pCR). Increased ...pCR-rates can be achieved through dose escalation, thereby increasing the number patients eligible for organ-preservation to improve quality of life (QoL). A randomized comparison of 65 versus 50Gy with external-beam radiation alone has not yet been performed. This trial investigates pCR rate, clinical response, toxicity, QoL and (disease-free) survival in LARC patients treated with 65Gy (boost + chemoradiation) compared with 50Gy standard chemoradiation (sCRT).
This study follows the 'cohort multiple randomized controlled trial' (cmRCT) design: rectal cancer patients are included in a prospective cohort that registers clinical baseline, follow-up, survival and QoL data. At enrollment, patients are asked consent to offer them experimental interventions in the future. Eligible patients-histologically confirmed LARC (T3NxM0 <1 mm from mesorectal fascia, T4NxM0 or TxN2M0) located ≤10 cm from the anorectal transition who provided consent for experimental intervention offers-form a subcohort (n = 120). From this subcohort, a random sample is offered the boost prior to sCRT (n = 60), which they may accept or refuse. Informed consent is signed only after acceptance of the boost. Non-selected patients in the subcohort (n = 60) undergo sCRT alone and are not notified that they participate in the control arm until the trial is completed. sCRT consists of 50Gy (25 × 2Gy) with concomitant capecitabine. The boost (without chemotherapy) is given prior to sCRT and consists of 15 Gy (5 × 3Gy) delivered to the gross tumor volume (GTV). The primary endpoint is pCR (TRG 1). Secondary endpoints include acute grade 3-4 toxicity, good pathologic response (TRG 1-2), clinical response, surgical complications, QoL and (disease-free) survival. Data is analyzed by intention to treat.
The boost is delivered prior to sCRT so that GTV adjustment for tumor shrinkage during sCRT is not necessary. Small margins also aim to limit irradiation of healthy tissue. The cmRCT design provides opportunity to overcome common shortcomings of classic RCTs, such as slow recruitment, disappointment-bias in control arm patients and poor generalizability.
The Netherlands Trials Register NL46051.041.13. Registered 22 August 2013. ClinicalTrials.gov NCT01951521 . Registered 18 September 2013.
Accurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large ...due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy.
Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), center of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist.
Preoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p<0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p=0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range 30-153 cm3) on MRI (p<0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI.
This study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy.
International Clinical Trials Registry Platform NTR3198.
Abstract Background and purpose Breath hold is increasingly used for cardiac sparing in left-sided breast cancer irradiation. We have developed a fast automated method to verify breath hold stability ...in each treatment fraction. Material and methods We evaluated 504 patients treated with breath hold. Moderate deep inspiration breath hold was audio-guided. Medial and lateral large tangential field segments were delivered in a single breath hold and movieloops of these fields were acquired with an EPID. The thoracic wall position was automatically detected in each frame and the full range of thoracic wall motion (RTWM) was determined. If the RTWM >4 mm more than 3 times, the patient was excluded from breath hold treatment if further coaching did not yield improvement. Results Unstable breath hold was observed in 2.8% of the patients. However, this frequency dropped from 9.5% in the first 6 months to 1.6% in the subsequent 16 months. The 97% of patients with proper breath hold showed excellent stability: the average RTWM was 0.9 ± 0.5 mm. The reproducibility of the breath hold depth was confirmed by (1) the small difference between the thoracic wall positions in the medial and lateral fields within one fraction and (2) the setup errors of breath hold patients showed no significant differences with those of right-sided breast patients. Conclusions We have developed and clinically applied an imaging tool to automatically determine stability of breath holds in each treatment fraction during beam delivery.
Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated ...according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p < 0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible.
In regional radiotherapy (RT) for patients with breast cancer, lymph node (LN) targets are delineated on CT, defined by anatomical boundaries. By identifying individual LNs, MRI-based delineations ...may reduce target volumes and thereby toxicity. We optimized MRI sequences for this purpose. Our aim was to evaluate the techniques for LN delineation in RT planning.
Supine MRI was explored at 1.5 T in RT position (arms in abduction). 5 MRI techniques were optimized in 10 and evaluated in 12 healthy female volunteers. The scans included one T1 weighted (T1w), three T2 weighted (T2w) and a diffusion-weighted imaging (DWI) technique. Quantitative evaluation was performed by scoring LN numbers per volunteer and per scan. Qualitatively, scans were assessed on seven aspects, including LN contrast, anatomical information and insensitivity to motion during acquisition.
Two T2w fast spin-echo (FSE) methods showed the highest LN numbers (median 24 axillary), high contrast, excellent fat suppression and relative insensitivity to motion during acquisition. A third T2w sequence and DWI showed significantly fewer LNs (14 and 10) and proved unsuitable due to motion sensitivity and geometrical uncertainties. T1w MRI showed an intermediate number of LNs (17), provided valuable anatomical information, but lacked LN contrast.
Explicit LN imaging was achieved, in supine RT position, using MRI. Two T2w FSE techniques had the highest detection rates and were motion insensitive. T1w MRI showed anatomical information. MRI enables direct delineation of individual LNs.
Our optimized MRI scans enable accurate target definition in MRI-guided regional breast RT and development of personalized treatments.
Background
During breast-conserving surgery (BCS), surgeons increasingly perform full-thickness closure (FTC) to prevent seroma formation. This could potentially impair precision of target definition ...for boost and accelerated partial breast irradiation (APBI). The purpose of this study was to investigate the precision of target volume definition following BCS with FTC among radiation oncologists, using various imaging modalities.
Methods
Twenty clinical T1–2N0 patients, scheduled for BCS involving clip placement and FTC, were included in the study. Seven experienced breast radiation oncologists contoured the tumor bed on computed tomography (CT), magnetic resonance imaging (MRI) and fused CT–MRI datasets. A total of 361 observer pairs per image modality were analyzed. A pairwise conformity among the generated contours of the observers and the distance between their centers of mass (dCOM) were calculated.
Results
On CT, median conformity was 44 % interquartile range (IQR) 28–58 % and median dCOM was 6 mm (IQR 3–9 mm). None of the outcome measures improved when MRI or fused CT–MRI were used. In two patients, superficial closure was performed instead of FTC. In these 14 image sets and 42 observer pairs, median conformity increased to 70 %.
Conclusions
Localization of the radiotherapy target after FTC is imprecise, on both CT and MRI. This could potentially lead to a geographical miss in patients at increased risk of local recurrence receiving a radiation boost, or for those receiving APBI. These findings highlight the importance for breast surgeons to clearly demarcate the tumor bed when performing FTC.
To design a clinically reliable and efficient step-and-shoot IMRT delivery technique for the treatment of breast cancer using direct aperture optimization (DAO). Using DAO, segments are created and ...optimized within the same optimization process.
The DAO technique implemented in the Pinnacle treatment planning system, which is called direct machine parameter optimization (DMPO), was used to generate IMRT plans for twelve breast cancer patients. The prescribed dose was 50
Gy. Two DMPO plans were generated. The first approach uses DMPO only; the second technique combines DMPO with two predefined segments (DMPO
segm), having shapes identical to the conventional tangential fields. The weight of these predefined segments is optimized simultaneously with DMPO. The DMPO plans were compared with normal two-step (TS) IMRT, creating segments after optimizing the intensity.
Dose homogeneity within the target volume was 4.8±0.6, 4.3±0.5 and 3.8±0.5
Gy for the TS, DMPO and DMPO
segm plans, respectively. Comparing the IMRT plans with an idealized dose distribution obtained using only beamlet optimization, the degradation of the dose distribution was less for the DMPO plans compared with the two-step IMRT approach. Furthermore, this degradation was similar for all patients, while for the two-step IMRT approach it was patient specific.
An efficient step-and-shoot IMRT solution was developed for the treatment of breast cancer using DMPO combined with two predefined segments.
For breast boost radiotherapy or accelerated partial breast irradiation, the tumor bed (TB) is delineated by the radiation oncologist on a planning computed tomography (CT) scan. The aim of the ...present study was to investigate whether the interobserver variability (IOV) of the TB delineation is reduced by providing the radiation oncologist with additional magnetic resonance imaging (MRI) or CT scans. A total of 14 T1-T2 breast cancer patients underwent a standard planning CT in the supine treatment position following lumpectomy, as well as additional pre- and postoperative imaging in the same position. Post-lumpectomy TBs were independently delineated by four breast radiation oncologists on standard postoperative CT and on CT registered to an additional imaging modality. The additional imaging modalities used were postoperative MRI, preoperative contrast-enhanced (CE)-CT and preoperative CE-MRI. A cavity visualization score (CVS) was assigned to each standard postoperative CT by each observer. In addition, the conformity index (CI), volume and distance between centers of mass (dCOM) of the TB delineations were calculated. On CT, the median CI was 0.57, with a median volume of 22 cm3 and dCOM of 5.1 mm. The addition of postoperative MRI increased the median TB volume significantly to 28 cm3 (P<0.001), while the CI (P=0.176) and dCOM (P=0.110) were not affected. The addition of preoperative CT or MRI increased the TB volume to 26 and 25 cm3, respectively (both P<0.001), while the CI increased to 0.58 and 0.59 (both P<0.001) and the dCOM decreased to 4.7 mm (P=0.004) and 4.6 mm (P=0.001), respectively. In patients with CVS≤3, the median CI was 0.40 on CT, which was significantly increased by all additional imaging modalities, up to 0.52, and was accompanied by a median volume increase up to 6 cm3. In conclusion, the addition of postoperative MRI, preoperative CE-CT or preoperative CE-MRI did not result in a considerable reduction in the IOV in postoperative CT-guided TB delineation, while target volumes marginally increased. The value of additional imaging may be dependent on CVS.
Purpose: The aim of this paper is to quantify the importance of the reduction of positioning margins applied to the clinical target volume (CTV) on the dose distribution of the parotid gland for ...different intensity-modulated radiotherapy (IMRT) strategies for the treatment of oropharyngeal cancer.
Methods and materials: CTVs and organs at risk were delineated in the planning computed tomographic (CT) scans of three patients. Margins of 0, 3, 6 and 9
mm were applied to the CTVs in order to obtain the planning target volumes (PTVs). Three IMRT strategies were used to optimize the dose distribution.
Results: The analysis of the three IMRT strategies resulted in: (1) an optimal dose distribution in the PTV; (2) optimal dose distribution in the PTV while sparing the parotid gland and (3) more parotid gland sparing but at expense of the dose homogeneity in the PTV. The mean parotid dose increased linearly with increasing margin by approximately 1.3
Gy per mm. As a result, the normal complication probability (NTCP) for xerostomia decreased when smaller margins were applied. Reducing the margin from 6 to 3
mm resulted in an NTCP reduction of approximately 20%.
Conclusion: Reducing the CTV–PTV margin by improving the patient position accuracy may lead to a significant reduction of NTCP for the IMRT treatment of the oropharyngeal tumors and lymph nodes level II.
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