Comparison of intensity modulated radiotherapy plan optimisation methods for a 1.5 T MR-Linac.

PURPOSE: For the 1.5 T Elekta MR-Linac it is essential that the optimisation of a treatment plan accounts for the electron return effect on the planned dose distribution. The ability of two algorithms for the first stage fluence optimisation, pencil beam (PB) and Monte Carlo (MC), to produce acceptable plan quality was investigated. Optimisation time for each algorithm was also compared. METHODS: Ten head and neck patients, ten lung patients and five prostate patients were selected from the clinical archive. These were retrospectively planned using a research version of Monaco with both the PB and MC algorithms for the fluence optimisation stage. After full optimisation DVH parameters, optimisation time and the number of Monitor Units (MU) as a measure of plan complexity were extracted. RESULTS: There were no clinically significant differences between any of the DVH parameters studied or the total number of MUs between using PB or MC for stage 1 optimisation across the three patient groups. However, planning time increased by a factor of ten using MC algorithms for stage 1. CONCLUSION: The use of MC calculations compared to PB, for stage 1 fluence optimisation, results in increased planning time without clinical improvement in plan quality or reduction in complexity and is therefore not necessary.

A multi-institutional comparison of retrospective deformable dose accumulation for online adaptive magnetic resonance-guided radiotherapy.

Background and Purpose: Application of different deformable dose accumulation (DDA) solutions makes institutional comparisons after online-adaptive magnetic resonance-guided radiotherapy (OA-MRgRT) challenging. The aim of this multi-institutional study was to analyze accuracy and agreement of DDA-implementations in OA-MRgRT. Material and Methods: One gold standard (GS) case deformed with a biomechanical-model and five clinical cases consisting of prostate (2x), cervix, liver, and lymph node cancer, treated with OA-MRgRT, were analyzed. Six centers conducted DDA using institutional implementations. Deformable image registration (DIR) and DDA results were compared using the contour metrics Dice Similarity Coefficient (DSC), surface-DSC, Hausdorff-distance (HD95%), and accumulated dose-volume histograms (DVHs) analyzed via intraclass correlation coefficient (ICC) and clinical dosimetric criteria (CDC). Results: For the GS, median DDA errors ranged from 0.0 to 2.8 Gy across contours and implementations. DIR of clinical cases resulted in DSC > 0.8 for up to 81.3% of contours and a variability of surface-DSC values depending on the implementation. Maximum HD95%=73.3 mm was found for duodenum in the liver case. Although DVH ICC > 0.90 was found after DDA for all but two contours, relevant absolute CDC differences were observed in clinical cases: Prostate I/II showed maximum differences in bladder V28Gy (10.2/7.6%), while for cervix, liver, and lymph node the highest differences were found for rectum D2cm3 (2.8 Gy), duodenum Dmax (7.1 Gy), and rectum D0.5cm3 (4.6 Gy). Conclusion: Overall, high agreement was found between the different DIR and DDA implementations. Case- and algorithm-dependent differences were observed, leading to potentially clinically relevant results. Larger studies are needed to define future DDA-guidelines.

A margin-of-the-day online adaptive intensity-modulated radiotherapy strategy for cervical cancer provides superior treatment accuracy compared to clinically recommended margins: a dosimetric evaluation.

PURPOSE: To dosimetrically evaluate a margin-of-the-day (MoD) online adaptive intensity-modulated radiotherapy (IMRT) strategy for cervical cancer patients. The strategy is based on a single planning computed tomography (CT) scan and a pretreatment constructed IMRT plan library with incremental clinical target volumes (CTV)-to-planning target volumes (PTV) margins. MATERIAL AND METHODS: For 14 patients, 9-10 variable bladder filling CT scans acquired at pretreatment and after 40 Gy were available. Bladder volume variability during the treatment course was recorded by twice-weekly US bladder-volume measurements. A MoD strategy that selects the best IMRT plan of the day from a library of plans with incremental margins in steps of 5 mm was compared with a clinically recommended population-based margin (15 mm). To compare the strategies, for each fraction that had a recorded US bladder-volume measurement, the CT scan with the nearest bladder volume was selected from the pretreatment CT series and from the CT series acquired after 40 Gy. A frequency-weighted average of the dose-volume histograms (DVH) parameters calculated for the two selected CT scans was used to estimate the DVH parameters of the fraction of interest. RESULTS: The 15-mm recommended margin resulted in cervix-uterus underdosage in six of 14 patients. Compared with the 15-mm margin, the MoD strategy resulted in significantly better cervix-uterus coverage (p = 0.008) without a significant difference in the sparing of rectum, bladder, and small bowel. For each patient, 3-8 (median 5) plans were needed in the library of plans for the MoD strategy. The required range of the MoD was 5-45 mm (median 15 mm). Twenty-five percent of all fractions could be treated with a MoD of 5 mm and 81% of all fractions could be treated with a MoD up to 25 mm. CONCLUSIONS: Compared with a clinically recommended margin, a simple online adaptive strategy resulted in better cervix-uterus coverage without compromising organs at risk sparing.

Updating approach for lexicographic optimization-based planning to improve cervical cancer plan quality.

BACKGROUND: To investigate the capability of a not-yet commercially available fully automated lexicographic optimization (LO) planning algorithm, called mCycle (Elekta AB, Stockholm, Sweden), to further improve the plan quality of an already-validated Wish List (WL) pushing on the organs-at-risk (OAR) sparing without compromising target coverage and plan delivery accuracy. MATERIAL AND METHODS: Twenty-four mono-institutional consecutive cervical cancer Volumetric-Modulated Arc Therapy (VMAT) plans delivered between November 2019 and April 2022 (50 Gy/25 fractions) have been retrospectively selected. In mCycle the LO planning algorithm was combined with the a-priori multi-criterial optimization (MCO). Two versions of WL have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). Robust WLs have been tuned using a subset of 4 randomly selected patients. The remaining plans have been automatically re-planned by using the designed WLs. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, ranking the three competing plans. Furthermore, a previous defined global quality index has been used to gather into a single score the plan quality evaluation. RESULTS: The WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took in both cases 3 working days. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6-99.3], mCP01 99.2 [89.7-99.9], mCP02 96.9 [89.4-99.5]), while mCP02 showed a large OAR sparing improvement, especially in the rectum parameters (e.g., Rectum D50% (Gy): MP 41.7 [30.2-47.0], mCP01 40.3 [31.4-45.8], mCP02 32.6 [26.9-42.6]). An increase in plan complexity has been registered in mCPs without affecting plan delivery accuracy. In the blind comparisons, all automated plans were considered clinically acceptable, and mCPs were preferred over MP in 90% of cases. Globally, automated plans registered a plan quality score at least comparable to MP. CONCLUSIONS: This study showed the flexibility of the Lexicographic approach in creating more demanding Wish Lists able to potentially minimize toxicities in RT plans.

Fully automated volumetric modulated arc therapy technique for radiation therapy of locally advanced breast cancer.

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed. RESULTS: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V95%) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT. CONCLUSIONS: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.

iCycle: Integrated, multicriterial beam angle, and profile optimization for generation of coplanar and noncoplanar IMRT plans.

PURPOSE: To introduce iCycle, a novel algorithm for integrated, multicriterial optimization of beam angles, and intensity modulated radiotherapy (IMRT) profiles. METHODS: A multicriterial plan optimization with iCycle is based on a prescription called wish-list, containing hard constraints and objectives with ascribed priorities. Priorities are ordinal parameters used for relative importance ranking of the objectives. The higher an objective priority is, the higher the probability that the corresponding objective will be met. Beam directions are selected from an input set of candidate directions. Input sets can be restricted, e.g., to allow only generation of coplanar plans, or to avoid collisions between patient/couch and the gantry in a noncoplanar setup. Obtaining clinically feasible calculation times was an important design criterium for development of iCycle. This could be realized by sequentially adding beams to the treatment plan in an iterative procedure. Each iteration loop starts with selection of the optimal direction to be added. Then, a Pareto-optimal IMRT plan is generated for the (fixed) beam setup that includes all so far selected directions, using a previously published algorithm for multicriterial optimization of fluence profiles for a fixed beam arrangement Breedveld et al. [Phys. Med. Biol. 54, 7199-7209 (2009)]. To select the next direction, each not yet selected candidate direction is temporarily added to the plan and an optimization problem, derived from the Lagrangian obtained from the just performed optimization for establishing the Pareto-optimal plan, is solved. For each patient, a single one-beam, two-beam, three-beam, etc. Pareto-optimal plan is generated until addition of beams does no longer result in significant plan quality improvement. Plan generation with iCycle is fully automated. RESULTS: Performance and characteristics of iCycle are demonstrated by generating plans for a maxillary sinus case, a cervical cancer patient, and a liver patient treated with SBRT. Plans generated with beam angle optimization did better meet the clinical goals than equiangular or manually selected configurations. For the maxillary sinus and liver cases, significant improvements for noncoplanar setups were seen. The cervix case showed that also in IMRT with coplanar setups, beam angle optimization with iCycle may improve plan quality. Computation times for coplanar plans were around 1-2 h and for noncoplanar plans 4-7 h, depending on the number of beams and the complexity of the site. CONCLUSIONS: Integrated beam angle and profile optimization with iCycle may result in significant improvements in treatment plan quality. Due to automation, the plan generation workload is minimal. Clinical application has started.

Integrated multicriterial optimization of beam angles and intensity profiles for coplanar and noncoplanar head and neck IMRT and implications for VMAT.

PURPOSE: To quantify improved salivary gland sparing for head and neck cancer patients using intensity-modulated radiotherapy (IMRT) plans based on integrated computerized optimization of beam orientations and intensity profiles. To assess if optimized nonzero couch angles also improve VMAT plans. METHODS: Our in-house developed algorithm iCycle was used for automated generation of multicriterial optimized plans with optimized beam orientations and intensity profiles, and plans with optimized profiles for preselected beam arrangements. For 20 patients, five IMRT plans, based on one "wish-list," were compared: (i) and (ii) seven- and nine-beam equiangular coplanar plans (iCycle(7equi), iCycle(9equi)), (iii) and (iv) nine-beam plans with optimized coplanar and noncoplanar beam orientations (iCycle(copl), iCycle(noncopl)), and (v) a nine-beam coplanar plan with optimized gantry angles and one optimized couch rotation (iCycle(couch)). VMAT plans without and with this optimized couch rotation were evaluated. RESULTS: iCycle(noncopl) resulted in the best salivary gland sparing, while iCycle(couch) yielded similar results for 18 patients. For iCycle(7equi), submandibular gland NTCP values were on average 5% higher. iCycle(9equi) performed better than iCycle(7equi). iCycle(copl) showed further improvement. Application of the optimized couch angle from iCycle(couch) also improved NTCP values in VMAT plans. CONCLUSIONS: iCycle allows objective comparison of competing planning strategies. Integrated optimization of beam profiles and angles can significantly improve normal tissue sparing, yielding optimal results for iCycle(noncopl).

Fast VMAT planning for prostate radiotherapy: dosimetric validation of a deep learning-based initial segment generation method.

Objective. To develop and evaluate a deep learning based fast volumetric modulated arc therapy (VMAT) plan generation method for prostate radiotherapy.Approach. A customized 3D U-Net was trained and validated to predict initial segments at 90 evenly distributed control points of an arc, linked to our research treatment planning system (TPS) for segment shape optimization (SSO) and segment weight optimization (SWO). For 27 test patients, the VMAT plans generated based on the deep learning prediction (VMATDL) were compared with VMAT plans generated with a previously validated automated treatment planning method (VMATref). For all test cases, the deep learning prediction accuracy, plan dosimetric quality, and the planning efficiency were quantified and analyzed.Main results. For all 27 test cases, the resulting plans were clinically acceptable. TheV95%for the PTV2 was greater than 99%, and theV107%was below 0.2%. Statistically significant difference in target coverage was not observed between the VMATrefand VMATDLplans (P = 0.3243 > 0.05). The dose sparing effect to the OARs between the two groups of plans was similar. Small differences were only observed for the Dmean of rectum and anus. Compared to the VMATref, the VMATDLreduced 29.3% of the optimization time on average.Significance. A fully automated VMAT plan generation method may result in significant improvement in prostate treatment planning efficiency. Due to the clinically acceptable dosimetric quality and high efficiency, it could potentially be used for clinical planning application and real-time adaptive therapy application after further validation.

Automated Planning for Prostate Stereotactic Body Radiation Therapy on the 1.5 T MR-Linac.

PURPOSE: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac. METHODS AND MATERIALS: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [Dp]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the Dp to at least 95% of the planning target volume (PTV), V33.2 (PTV) ≥ 95%, a dose less than the Dp to the hottest cubic centimeter (V35 ≤ 1 cm3) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V32 ≤ 5%, V28 ≤ 10%, and V18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans. RESULTS: mCycle plans improved target dose coverage, with V33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans (P < .001), and rectal dose sparing, with significantly reduced V32, V28, and V18 (P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) (P < .001), whereas they were generally faster (-19%) in terms of optimization times (P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) (P = .059) and γ (2 mm, 2%) (P = .432) deliverability metrics. CONCLUSIONS: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task.

Evaluation of fully automated a priori MCO treatment planning in VMAT for head-and-neck cancer.

PURPOSE: Automated planning techniques aim to reduce manual planning time and inter-operator variability without compromising the plan quality which is particularly challenging for head-and-neck (HN) cancer radiotherapy. The objective of this study was to evaluate the performance of an a priori-multicriteria plan optimization algorithm on a cohort of HN patients. METHODS: A total of 14 nasopharyngeal carcinoma (upper-HN) and 14 "middle-lower indications" (lower-HN) previously treated in our institution were enrolled in this study. Automatically generated plans (autoVMAT) were compared to manual VMAT or Helical Tomotherapy planning (manVMAT-HT) by assessing differences in dose delivered to targets and organs at risk (OARs), calculating plan quality indexes (PQIs) and performing blinded comparisons by clinicians. Quality control of the plans and measurements of the delivery times were also performed. RESULTS: For the 14 lower-HN patients, with equivalent planning target volume (PTV) dosimetric criteria and dose homogeneity, significant decrease in the mean doses to the oral cavity, esophagus, trachea and larynx were observed for autoVMAT compared to manVMAT-HT. Regarding the 14 upper-HN cases, the PTV coverage was generally significantly superior for autoVMAT which was also confirmed with higher calculated PQIs on PTVs for 13 out of 14 patients, whereas PQIs calculated on OARs were generally equivalent. Number of MUs and total delivery time were significantly higher for autoVMAT compared to manVMAT. All plans were considered clinically acceptable by clinicians. CONCLUSIONS: Overall superiority of autoVMAT compared to manVMAT-HT plans was demonstrated for HN cancer. The obtained plans were operator-independent and required no post-optimization or manual intervention.

Analysis of the motion of oropharyngeal tumors and consequences in planning target volume determination.

PURPOSE: To determine adequate three-dimensional (3D) margins around the clinical target volume (CTV) of oropharyngeal cancers. METHODS AND MATERIALS: The CTV, bounded by implanted markers, was recorded under fluoroscopy in antero-posterior (AP) and lateral view. The peak-to-peak motion was measured in lateral, AP and cranio-caudal (CC) directions. RESULTS: During swallowing, the mean amplitude of motion measured was 9.4mm (0.9-18.5) and 4.1mm (0.6-11.4) in AP view in the CC and lateral direction, respectively; and 8.6mm (0.5-16.5) and 7.6mm (0.9-14.5) in lateral view in the CC and AP direction, respectively. In the non-swallowing period the motion was 1.5mm (0.3-3.2) and 1mm (0.4-3.6) in AP view in the CC and lateral direction, respectively; and 1.3mm (0.4-3.1) and 1.3mm (0.4-3.4) in lateral view in the CC and AP direction, respectively. This motion was believed to be due to breathing. CONCLUSION: If swallowing can be suppressed during CT acquisition, the contribution to the internal margin for this motion is negligible. Breathing related motion is also believed to be of limited clinical relevance in current practice. However, it might become of importance in future, with further reduction of margins.

Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx.

BACKGROUND AND PURPOSE: Dysphagia is a serious complaint but frequently underreported. This paper assesses for oropharyngeal cancer (OPC) the relationship between the dose received by the swallowing structures, and the findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES). MATERIALS AND METHODS: Between 2000 and 2005, 60 of 67 OPC patients local-regionally NED for at least one year following treatment responded to three types of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D. Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure. The main swallowing muscles were delineated, with the mean dose per muscle calculated using the original 3D CT-based treatment plans. Regression analysis was performed between FEES variables and the doses in the different swallowing muscles and the dysphagia related questionnaires. RESULTS: A significant relationship was found between the results of FEES and the mean dose in the superior constrictor muscle (SCM). Some of the subjective dysphagia complaints were significantly correlated with the FEES variables in this retrospectively study. CONCLUSION: A higher dose in the SCM generally results in worsening of the findings obtained by the FEES examination.

Fully automated, multi-criterial planning for Volumetric Modulated Arc Therapy - An international multi-center validation for prostate cancer.

BACKGROUND AND PURPOSE: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. MATERIAL AND METHODS: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. RESULTS: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p < 0.001) in Dmean, 4.0% (p < 0.001) in V60Gy, and 1.5% (p = 0.001) in V75Gy, and for bladder Dmean (0.9 Gy, p < 0.001). Also the clinicians' plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum Dmean and V60Gy of [-4,12] Gy and [-2,15]%, respectively. CONCLUSION: Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship.

PURPOSE/OBJECTIVE: To assess the relationship between the radiation therapy (RT) dose received by the muscular components of the swallowing (sw) apparatus and - dysphagia related - quality of life (QoL) in oropharyngeal cancer. MATERIALS/METHODS: Between 2000 and 2005, 81 patients with SCC of the oropharynx were treated by 3DCRT or IMRT, with or without concomitant chemotherapy (CHT); 43 out of these 81 patients were boosted by brachytherapy (BT). Charts of 81 patients were reviewed with regard to late dysphagia complaints; 23% experienced severe dysphagia. Seventeen patients expired. Fifty-six out of 64 (88%) responded to quality of life (QoL) questionnaires; that is, the Performance Status Scales of List, EORTC H&N35, and the M.D. Anderson Dysphagia Inventory. The superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeus muscle and the inlet of the esophagus, are considered of paramount importance for swallowing. The mean dose was calculated in the muscular structures. Univariate analysis and multivariate analysis were performed using the proportional odds model. RESULTS: Mean follow-up was 18 months (range 2-34) for IMRT, and 46 months for 3DCRT (range 2-72). At 3-years, a LRC of 84%, DFS of 78% and OS of 77% were observed. A significant correlation was observed between the mean dose in the scm and mcm, and severe dysphagia complaints (univariate analysis). A steep dose-effect relationship, with an increase of the probability of dysphagia of 19% with every additional 10 Gy, was established. In the multivariate analysis, BT (dose) was the only significant factor. CONCLUSION: A dose-effect relationship between dose and swallowing complaints was observed. One way to improve the QoL is to constrain the dose to be received by the swallowing muscles.

Fully automated treatment planning of spinal metastases - A comparison to manual planning of Volumetric Modulated Arc Therapy for conventionally fractionated irradiation.

BACKGROUND: Planning for Volumetric Modulated Arc Therapy (VMAT) may be time consuming and its use is limited by available staff resources. Automated multicriterial treatment planning can eliminate this bottleneck. We compared automatically created (auto) VMAT plans generated by Erasmus-iCycle to manually created VMAT plans for treatment of spinal metastases. METHODS: Forty-two targets in 32 patients were analyzed. Lungs and kidneys were defined as organs at risk (OARs). Twenty-two patients received radiotherapy on kidney levels, 17 on lung levels, and 3 on both levels. RESULTS: All Erasmus-iCycle plans were clinically acceptable. When compared to manual plans, planning target volume (PTV) coverage of auto plans was significantly better. The Homogeneity Index did not differ significantly between the groups. Mean dose to OARs was lower in auto plans concerning both kidneys and the left lung. One hotspot (>110% of D50%) occurred in the spinal cord of one auto plan (33.2 Gy, D50%: 30 Gy). Treatment time was 7% longer in auto plans. CONCLUSIONS: Erasmus-iCycle plans showed better target coverage and sparing of OARs at the expense of minimally longer treatment times (for which no constraint was set).

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy.

PURPOSE: To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. MATERIAL AND METHODS: Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. RESULTS: All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. CONCLUSIONS: Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible.

Intraoperative validation of CT-based lymph nodal levels, sublevels IIa and IIb: is it of clinical relevance in selective radiation therapy?

PURPOSE: The objectives of this study are to discuss the intraoperative validation of CT-based boundaries of lymph nodal levels in the neck, and in particular the clinical relevance of the delineation of sublevels IIa and IIb in case of selective radiation therapy (RT). METHODS AND MATERIALS: To validate the radiologically defined level contours, clips were positioned intraoperatively at the level boundaries defined by surgical anatomy. In 10 consecutive patients, clips were placed, at the time of a neck dissection being performed, at the most cranial border of the neck. Anterior-posterior and lateral X-ray films were obtained intraoperatively. Next, in 3 patients, neck levels were contoured on preoperative contrast-enhanced CT scans according to the international consensus guidelines. From each of these 3 patients, an intraoperative CT scan was also obtained, with clips placed at the surgical-anatomy-based level boundaries. The preoperative (CT-based) and intraoperative (surgery-defined) CT scans were matched. RESULTS: Clips placed at the most cranial part of the neck lined up at the caudal part of the transverse process of the cervical vertebra C-I. The posterior border of surgical level IIa (spinal accessory nerve [SAN]) did not match with the posterior border of CT-based level IIa (internal jugular vein [IJV]). Other surgical boundaries and CT-based contours were in good agreement. CONCLUSIONS: The cranial border of the neck, i.e., the cranial border of level IIa/IIb, corresponds to the caudal edge of the lateral process of C-I. Except for the posterior border between level IIa and level IIb, a perfect match was observed between the other surgical-clip-identified levels II-V boundaries (surgical-anatomy) and the CT-based delineation contours. It is argued that (1) because of the parotid gland overlapping part of level II, and (2) the frequent infestation of occult metastatic cells in the lymph channels around the IJV, the division of level II into radiologic sublevels IIa and IIb may not be relevant. Sparing of, for example, the ipsilateral parotid gland in selective RT can even be a treacherous undertaking with respect to regional tumor control. In contrast, the surgeon's reasoning for preserving the surgical sublevel IIb is that the morbidity associated with dissection of the supraspinal accessory nerve compartment of level II is reduced, whereas there is evidence from the surgical literature that no extra risk for regional tumor control is observed. Therefore, in selective neck dissections, the division into surgical sublevels IIa/IIb makes sense.

Comparison of VMAT and IMRT strategies for cervical cancer patients using automated planning.

BACKGROUND AND PURPOSE: In a published study on cervical cancer, 5-beam IMRT was inferior to single arc VMAT. Here we compare 9, 12, and 20 beam IMRT with single and dual arc VMAT. MATERIAL AND METHODS: For each of 10 patients, automated plan generation with the in-house Erasmus-iCycle optimizer was used to assist an expert planner in generating the five plans with the clinical TPS. RESULTS: For each patient, all plans were clinically acceptable with a high and similar PTV coverage. OAR sparing increased when going from 9 to 12 to 20 IMRT beams, and from single to dual arc VMAT. For all patients, 12 and 20 beam IMRT were superior to single and dual arc VMAT, with substantial variations in gain among the study patients. As expected, delivery of VMAT plans was significantly faster than delivery of IMRT plans. CONCLUSIONS: Often reported increased plan quality for VMAT compared to IMRT has not been observed for cervical cancer. Twenty and 12 beam IMRT plans had a higher quality than single and dual arc VMAT. For individual patients, the optimal delivery technique depends on a complex trade-off between plan quality and treatment time that may change with introduction of faster delivery systems.

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy.

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.

Curative radiotherapy for a second primary lung cancer arising after pneumonectomy -- techniques and results.

BACKGROUND AND PURPOSE: Only limited data exist on the outcome of curative radiotherapy in patients who develop a second primary lung tumour after pneumonectomy. The treatment of eight such patients is described. MATERIALS AND METHODS: The case records of patients who underwent curative radiotherapy for stage I non-small cell lung cancer after a previous pneumonectomy were reviewed. Treatment was delivered using 3D external radiotherapy to a dose of 50-70 Gy, in once-daily fractions of 2-2.5 Gy. An endobronchial brachytherapy boost was used in three patients. Original treatments were re-planned in an attempt to minimize the volume of irradiated lung. RESULTS: A complete remission was achieved in five (of six) evaluable patients, but two patients subsequently developed a local relapse. All patients survived for a minimum of 1 year after treatment. Only one patient developed significant (grade 2) radiation pneumonitis. When treatments were re-planned to optimize beam arrangements, and when customized blocks were used, the mean lung volume receiving > or = 20 Gy (calculated for 70 Gy) decreased from 24.6+/-4.1 (range, 18-31%) to 17.3+/-5.1% (range, 12-26%). Similarly, the radiation conformity index improved from 0.44+/-0.11 to 0.61+/-0.06. CONCLUSIONS: Involved-field radiotherapy can be curative in patients who develop a new lung tumour after pneumonectomy. Recent advances in defining target volumes, treatment planning and delivery are likely to improve upon these results.