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.

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.

Fully automated volumetric modulated arc therapy plan generation for prostate cancer patients.

PURPOSE: To develop and evaluate fully automated volumetric modulated arc therapy (VMAT) treatment planning for prostate cancer patients, avoiding manual trial-and-error tweaking of plan parameters by dosimetrists. METHODS AND MATERIALS: A system was developed for fully automated generation of VMAT plans with our commercial clinical treatment planning system (TPS), linked to the in-house developed Erasmus-iCycle multicriterial optimizer for preoptimization. For 30 randomly selected patients, automatically generated VMAT plans (VMATauto) were compared with VMAT plans generated manually by 1 expert dosimetrist in the absence of time pressure (VMATman). For all treatment plans, planning target volume (PTV) coverage and sparing of organs-at-risk were quantified. RESULTS: All generated plans were clinically acceptable and had similar PTV coverage (V95% > 99%). For VMATauto and VMATman plans, the organ-at-risk sparing was similar as well, although only the former plans were generated without any planning workload. CONCLUSIONS: Fully automated generation of high-quality VMAT plans for prostate cancer patients is feasible and has recently been implemented in our clinic.

Automated generation of IMRT treatment plans for prostate cancer patients with metal hip prostheses: comparison of different planning strategies.

PURPOSE: To compare IMRT planning strategies for prostate cancer patients with metal hip prostheses. METHODS: All plans were generated fully automatically (i.e., no human trial-and-error interactions) using iCycle, the authors' in-house developed algorithm for multicriterial selection of beam angles and optimization of fluence profiles, allowing objective comparison of planning strategies. For 18 prostate cancer patients (eight with bilateral hip prostheses, ten with a right-sided unilateral prosthesis), two planning strategies were evaluated: (i) full exclusion of beams containing beamlets that would deliver dose to the target after passing a prosthesis (IMRT remove) and (ii) exclusion of those beamlets only (IMRT cut). Plans with optimized coplanar and noncoplanar beam arrangements were generated. Differences in PTV coverage and sparing of organs at risk (OARs) were quantified. The impact of beam number on plan quality was evaluated. RESULTS: Especially for patients with bilateral hip prostheses, IMRT cut significantly improved rectum and bladder sparing compared to IMRT remove. For 9-beam coplanar plans, rectum V60 Gy reduced by 17.5% ± 15.0% (maximum 37.4%, p = 0.036) and rectum D mean by 9.4% ± 7.8% (maximum 19.8%, p = 0.036). Further improvements in OAR sparing were achievable by using noncoplanar beam setups, reducing rectum V 60Gy by another 4.6% ± 4.9% (p = 0.012) for noncoplanar 9-beam IMRT cut plans. Large reductions in rectum dose delivery were also observed when increasing the number of beam directions in the plans. For bilateral implants, the rectum V 60Gy was 37.3% ± 12.1% for coplanar 7-beam plans and reduced on average by 13.5% (maximum 30.1%, p = 0.012) for 15 directions. CONCLUSIONS: iCycle was able to automatically generate high quality plans for prostate cancer patients with prostheses. Excluding only beamlets that passed through the prostheses (IMRTcut strategy) significantly improved OAR sparing. Noncoplanar beam arrangements and, to a larger extent, increasing the number of treatment beams further improved plan quality.

Toward fully automated multicriterial plan generation: a prospective clinical study.

PURPOSE: To prospectively compare plans generated with iCycle, an in-house-developed algorithm for fully automated multicriterial intensity modulated radiation therapy (IMRT) beam profile and beam orientation optimization, with plans manually generated by dosimetrists using the clinical treatment planning system. METHODS AND MATERIALS: For 20 randomly selected head-and-neck cancer patients with various tumor locations (of whom 13 received sequential boost treatments), we offered the treating physician the choice between an automatically generated iCycle plan and a manually optimized plan using standard clinical procedures. Although iCycle used a fixed "wish list" with hard constraints and prioritized objectives, the dosimetrists manually selected the beam configuration and fine tuned the constraints and objectives for each IMRT plan. Dosimetrists were not informed in advance whether a competing iCycle plan was made. The 2 plans were simultaneously presented to the physician, who then selected the plan to be used for treatment. For the patient group, differences in planning target volume coverage and sparing of critical tissues were quantified. RESULTS: In 32 of 33 plan comparisons, the physician selected the iCycle plan for treatment. This highly consistent preference for the automatically generated plans was mainly caused by the improved sparing for the large majority of critical structures. With iCycle, the normal tissue complication probabilities for the parotid and submandibular glands were reduced by 2.4% ± 4.9% (maximum, 18.5%, P=.001) and 6.5% ± 8.3% (maximum, 27%, P=.005), respectively. The reduction in the mean oral cavity dose was 2.8 ± 2.8 Gy (maximum, 8.1 Gy, P=.005). For the swallowing muscles, the esophagus and larynx, the mean dose reduction was 3.3 ± 1.1 Gy (maximum, 9.2 Gy, P<.001). For 15 of the 20 patients, target coverage was also improved. CONCLUSIONS: In 97% of cases, automatically generated plans were selected for treatment because of the superior quality. Apart from the improved plan quality, automatic plan generation is economically attractive because of the reduced workload.

On the beam direction search space in computerized non-coplanar beam angle optimization for IMRT-prostate SBRT.

In a recent paper, we have published a new algorithm, designated 'iCycle', for fully automated multi-criterial optimization of beam angles and intensity profiles. In this study, we have used this algorithm to investigate the relationship between plan quality and the extent of the beam direction search space, i.e. the set of candidate beam directions that may be selected for generating an optimal plan. For a group of ten prostate cancer patients, optimal IMRT plans were made for stereotactic body radiation therapy (SBRT), mimicking high dose rate brachytherapy dosimetry. Plans were generated for five different beam direction input sets: a coplanar (CP) set and four non-coplanar (NCP) sets. For CP treatments, the search space consisted of 72 orientations (5° separations). The NCP CyberKnife (CK) space contained all directions available in the robotic CK treatment unit. The fully non-coplanar (F-NCP) set facilitated the highest possible degree of freedom in selecting optimal directions. CK(+) and CK(++) were subsets of F-NCP to investigate some aspects of the CK space. For each input set, plans were generated with up to 30 selected beam directions. Generated plans were clinically acceptable, according to an assessment of our clinicians. Convergence in plan quality occurred only after around 20 included beams. For individual patients, variations in PTV dose delivery between the five generated plans were minimal, as aimed for (average spread in V(95): 0.4%). This allowed plan comparisons based on organ at risk (OAR) doses, with the rectum considered most important. Plans generated with the NCP search spaces had improved OAR sparing compared to the CP search space, especially for the rectum. OAR sparing was best with the F-NCP, with reductions in rectum D(Mean), V(40Gy), V(60Gy) and D(2%) compared to CP of 25%, 35%, 37% and 8%, respectively. Reduced rectum sparing with the CK search space compared to F-NCP could be largely compensated by expanding CK with beams with relatively large direction components along the superior-inferior axis (CK(++)). Addition of posterior beams (CK(++) → F-NCP) did not lead to further improvements in OAR sparing. Plans with 25 beams clearly performed better than 11-beam plans. For CP plans, an increase from 11 to 25 involved beams resulted in reductions in rectum D(Mean), V(40Gy), V(60Gy) and D(2%) of 39%, 57%, 64% and 13%, respectively.

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).

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.

Does atlas-based autosegmentation of neck levels require subsequent manual contour editing to avoid risk of severe target underdosage? A dosimetric analysis.

BACKGROUND AND PURPOSE: To investigate the dosimetric impact of not editing auto-contours of the elective neck and organs at risk (OAR), generated with atlas-based autosegmentation (ABAS) (Elekta software) for head and neck cancer patients. MATERIALS AND METHODS: For nine patients ABAS auto-contours and auto-contours edited by two observers were available. Based on the non-edited auto-contours clinically acceptable IMRT plans were constructed (designated 'ABAS plans'). These plans were then evaluated for the two edited structure sets, by quantifying the percentage of the neck-PTV receiving more than 95% of the prescribed dose (V(95)) and the near-minimum dose (D(99)) in the neck PTV. Dice coefficients and mean contour distances were calculated to quantify the similarity of ABAS auto-contours with the structure sets edited by observer 1 and observer 2. To study the dosimetric importance of editing OAR auto-contours a new IMRT plan was generated for each patient-observer combination, based on the observer's edited CTV and the non-edited salivary gland auto-contours. For each plan mean doses for the non-edited glands were compared with doses for the same glands edited by the observer. RESULTS: For both observers, edited neck CTVs were larger than ABAS auto-contours (p≤ 0.04), by a mean of 8.7%. When evaluating ABAS plans on the PTVs of the edited structure sets, V(95) reduced by 7.2%±5.4% (1 SD) (p<0.03). The mean reduction in D(99) was 14.2 Gy (range 1-54 Gy). Even for Dice coefficients >0.8 and mean contour distances <1mm, reductions in D(99) up to 11Gy were observed. For treatment plans based on observer PTVs and non-edited auto-contoured salivary glands, the mean doses in the edited glands differed by only -0.6 Gy±1.0 Gy (p=0.06). CONCLUSIONS: Editing of auto-contoured neck CTVs generated by ABAS is required to avoid large underdosages in target volumes. Often used similarity measures for evaluation of auto-contouring algorithms, such as dice coefficients, do not predict well for expected PTV underdose. Editing of salivary glands is less important as mean doses achieved for non-edited glands predict well for edited structures.

Clinical validation of atlas-based auto-segmentation of multiple target volumes and normal tissue (swallowing/mastication) structures in the head and neck.

PURPOSE: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images. METHODS AND MATERIALS: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas. RESULTS: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a "minor deviation, editable" or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min. CONCLUSION: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

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.

Can errors in reconstructing pre-chemotherapy target volumes contribute to the inferiority of sequential chemoradiation in stage III non-small cell lung cancer (NSCLC)?

Concurrent chemo-radiotherapy (CT-RT) has been shown to be superior to sequential CT-RT for stage III non-small cell lung cancer (NSCLC). Pre-chemotherapy gross tumor volumes (GTV) are commonly contoured for sequential CT-RT and, as significant inter-clinician variability exists in defining GTV's for lung cancer, we postulated that the poorer local control observed with sequential CT-RT may partly be due to the larger errors in defining GTV after chemotherapy-induced tumor regression. Pre-and post-chemotherapy CT scans for RT planning (RTP) were performed in ten patients who received induction chemotherapy for NSCLC. Image registration of pre- and post-chemotherapy RTP scans was performed for all patients. GTV's were first contoured in the conventional manner by two clinicians, i.e. by visual reconstruction from hard copies of the pre-chemotherapy diagnostic CT scans ('GTV-visual'). A 'GTV-match' was then contoured after image-registration, and the 'gold standard' volume was considered to be the overlap of the 'GTV-match' generated by both clinicians. The 'GTV-match' was on average 31-40% larger than 'GTV-visual'. The mean percentage of the 'gold standard', which was not covered by the 'GTV-visual' was similar for both clinicians, i.e. 26.3+/-12.5 and 28.0+/-15.0%. The inter-clinician agreement in contouring improved after image registration. These data suggest that conventional visual contouring of pre-chemotherapy GTV's may fail to treat the actual pre-chemotherapy tumor volume, and thus confound studies evaluating optimal sequencing of chemo-radiotherapy in NSCLC.

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.