Robustly optimized hybrid intensity-modulated proton therapy for craniospinal irradiation.

Aim: The aim of the study was to investigate the hybrid robust optimization planning approach in intensity-modulated proton therapy (IMPT) of craniospinal irradiation (CSI). Subjects and Methods: Five IMPT-based adult CSI plans in supine position were created using Raystation treatment planning system (TPS) modelled for Proteus plus proton therapy system. A hybrid planning strategy was implemented, where clinical target volume was robustly optimized (RB) for set up uncertainties and planning target volume was optimized for target coverage using minimax algorithm in the TPS. Beam angle selection, optimization, and dose calculation approach were carefully performed to ensure optimum organ at risk (OAR) sparing, even with potential setup and range errors. The complementary dose gradients in junctions were generated using spot assignment and RB technique. Dosimetric outcomes in both nominal plan and the 16 error scenarios (±3 mm setup and 3.5% range) were analyzed using standard dose volume histogram. Results: This planning approach resulted in a homogeneous dose distribution in the target volume of CSI, including the junction regions, by explicitly reducing number of robust optimization scenarios. The proposed technique was also able to achieve excellent coverage to cribriform plate with lower lens doses and minimal dose to other OARs. Target and OAR doses in the nominal plans as well as in the worst case scenarios with setup and range errors were able to meet the predefined clinical goal. Conclusions: This proposed planning technique is efficient, robust against the uncertainties. It could be adopted in other proton therapy centers.

Challenging case of a re-irradiation in a dorsal spine primitive neuroectodermal tumor: Role of modern image-guided pencil beam proton therapy.

Extradural primary primitive neuroectodermal tumor (PNET) is a rare aggressive disease mostly occurring in young adults. We present a locally recurrent case of dorsal PNET in the fifth decade of life after a prolonged disease-free interval of 10 years. The patient received radiation therapy in fairly large fields twice in his lifetime and was planned for third-time radiation to a few overlapping paraspinal areas over a period of three decades. Keeping in mind previous irradiations, possible target volume in proximity to organs at risk (OARs) patient was planned for consolidtive radiation using the most conformal technique available, which is proton beam therapy with image guided pencil beam scanning technique. Special dose constraints for the spinal cord and other OARs were set, and proton therapy plan was generated at our institute. When compared with parallelly generated intensity-modulated radiation therapy plan with the same dose prescription and dose constraints using helical tomotherapy, intensity-modulated proton therapy plan showed superior dosimetric benefit in terms of coverage and significant sparing of OARs.

Impact of spot positional errors in robustly optimized intensity-modulated proton therapy plan of craniospinal irradiation.

We investigated the influence of random spot positioning errors (SPEs) on dosimetric outcomes of robustly optimized intensity-modulated proton therapy (RB-IMPT) plans in craniospinal irradiation (CSI). Six patients with CSI treated using the RB-IMPT technique were selected. An in-house MATLAB code was used to simulate a random SPE of 1 mm in positive, negative, and both directions for 25%, 50%, and 75% of the total spot positions in the nominal plan. The percentage dose variation (ΔD%) in the six nominal and 54 error-introduced plans was evaluated using standard dose-volume indices, line dose difference, and 3D gamma analysis method. The introduction of a random SPE of 1 mm resulted in a reduction in D99%, D98%, and D95% of both CTVs and PTVs by < 2% compared with the corresponding nominal plans. However, this leads to an increase in D1% of the lens by up to 16.9%. The line dose in the junction region showed ΔD% < 2% for the brain and upper spine and < 4% for the upper and lower spine. The 3D gamma values for 3% at 3 mm and 2% at 2 mm were above 99% and 95%, respectively, in all 54 error-introduced plans. The worst decrease in gamma values was observed for 1% at 1 mm, with values ranging from 64 to 78% for all types of SPE. The RB-IMPT plan for CSI investigated in this study is robust enough for target coverage, even if there are random SPEs of 1 mm. However, this leads to an increase in the dose to the critical organ located close to the target.

Investigating the utilization of beam-specific apertures for the intensity-modulated proton therapy (IMPT) head and neck cancer plans.

Intensity-modulated proton therapy (IMPT) planning for the head and neck (HN) cancer often requires the use of the range shifter, which can increase the lateral penumbrae of the pencil proton beam in the patient, thus leading to an increase in unnecessary dose to the organs at risks (OARs) in proximity to the target volumes. The primary goal of the current study was to investigate the dosimetric benefits of utilizing beam-specific apertures for the IMPT HN cancer plans. The current retrospective study included computed tomography datasets of 10 unilateral HN cancer patients. The clinical target volume (CTV) was divided into low-risk CTV1 and high-risk CTV2. Total dose prescriptions to the CTV1 and CTV2 were 54 Gy(RBE) and 70 Gy(RBE), respectively, with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized (patient setup uncertainty = 3 mm; range uncertainty = 3.5%) on the CTVs. For each patient, 2 sets of plans were generated: (1) without beam-specific aperture (WOBSA), and (2) with beam-specific aperture (WBSA). Specifically, both the WOBSA and WBSA of the given patient used identical beam angles, air gap, optimization structures, optimization constraints, and optimization settings. Target coverage and homogeneity index were comparable in both the WOBSA and WBSA plans with no statistical significance (p > 0.05). On average, the mean dose in WBSA plans was reduced by 12.1%, 2.9%, 3.0%, 3.8%, and 5.2% for the larynx, oral cavity, parotids, superior pharyngeal constrictor muscle, and inferior pharyngeal constrictor muscle, respectively. The dosimetric results of the OARs were found to be statistically significant (p < 0.05). The use of the beam-specific apertures did not deteriorate the coverage and homogeneity in the target volume and allowed for a reduction in mean dose to the OARs with an average difference up to 12.1%.

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India.

PURPOSE: Proton beam therapy (PBT) has been a preferred modality in pediatric malignancies requiring radiotherapy. We report our preliminary experience of treating consecutive patients younger than 25 years with image-guided pencil beam scanning PBT from the first and only center on the Indian subcontinent. METHODS: Patients were selected for PBT on the basis of a multidisciplinary tumor board decision. Patient demographic data, as well as tumor and treatment-related characteristics of the cohort, were captured. Patient and treatment-related factors and their association with acute toxicities were analyzed using univariable and multivariable analyses. RESULTS: Forty-seven patients (27 with CNS and 20 with non-CNS tumors) with a median age of 9 years (range, 2-25 years) were evaluated. Most common diagnoses were ependymoma, rhabdomyosarcoma, and glioma. Seventy-seven percent of patients traveled more than 500 km, and 70% of them lived in metropolitan cities. Forty-nine percent of patients had recurrent disease at presentation, and 15% had received a previous course of radiation. The median dose delivered was 54.8 cobalt gray equivalents (range, 40.0-70.4 cobalt gray equivalents) to a median clinical target volume of 175 mL (range, 18.7-3,083.0 mL), with 34% of patients requiring concurrent chemotherapy (CCT). Acute grade 2 and grade 3 dermatitis, mucositis, and hematologic toxicity was noted in 45% and 2%, 34% and 0%, and 38% and 30% of patients, respectively. Grade 2 fatigue was noted in 26% of patients. On multivariable analysis, for CNS tumors, both CCT and craniospinal irradiation were independently associated with ≥ 2 grade hematologic toxicity, whereas among non-CNS tumors, a clinical target volume > 150 mL was associated with ≥ 2 grade fatigue, head and neck irradiation was associated with ≥ 2 grade mucositis, and CCT was associated with grade ≥ 2 hematologic toxicity. CONCLUSION: This study demonstrates safe implementation of a PBT program for children and young adults on the Indian subcontinent. Image-guided pencil beam scanning PBT in judiciously selected patients is feasible and can be delivered with acceptable acute toxicities.

Characterization and Performance Evaluation of the First-Proton Therapy Facility in India.

PURPOSE: The purpose of this study is to evaluate the performance characteristic of volumetric image-guided dedicated-nozzle pencil beam-scanning proton therapy (PT) system. MATERIALS AND METHODS: PT system was characterized for electromechanical, image quality, and registration accuracy. Proton beam of 70.2-226.2 MeV was characterized for short- and long-term reproducibility in integrated depth dose; spot profile characteristics at different air gap and gantry angle; positioning accuracy of single and pattern of spot; dose linearity, reproducibility and consistency. All measurements were carried out using various X-ray and proton-beam specific detectors following standard protocols. RESULTS: All electro-mechanical, imaging, and safety parameters performed well within the specified tolerance limit. The image registration errors along three translation and three rotational axes were ≤0.5 mm and ≤0.2° for both point-based and intensity-based auto-registration. Distal range (R90) and distal dose fall-off (DDF) of 70.2-226.2 MeV proton beams were within 1 mm of calculated values based on the international commission on radiation units and measurements 49 and 0.0156× R90, respectively. The R90 and DDF were reproducible within a standard deviation of 0.05 g/cm2 during the first 8 months. Dose were linear from 18.5 (0.011 MU/spot) to 8405 (5 MU/spot) MU, reproducible within 0.5% in 5 consecutive days and consistent within 0.8% for full rotation. The cGy/MU for 70.2-226.2MeV was consistent within 0.5%. In-air X(Y) spot-sigma at isocenter varies from 2.96 (3.00) mm to 6.68 (6.52) mm for 70.2-226.2 MeV. Maximum variation of spot-sigma with air-gap of ±20 cm was ±0.36 mm (5.28%) and ±0.82 mm (±12.5%) along X- and Y-direction and 3.56% for full rotation. Relative spot positions were accurate within ±0.6 mm. The planned and delivered spot pattern of known complex geometry agreed with (γ%≤1) for 1% @ 1 mm >98% for representative five-proton energies at four gantry angle. CONCLUSION: The PT-system performed well within the expected accuracy level and consistent over a period of 8 months. The methodology and data presented here may help upcoming modern PT center during their crucial phase of commissioning.

Introduction of Image­Guided Pencil Beam for Skull Base Tumors in India: A Report of Two Cases and a Brief Review of the Literature.

Chordoma and chondrosarcoma are locally aggressive tumors occurring in one-third cases at the base of the skull. These tumors often recur locally with significant morbidity and mortality. The mainstay of treatment is maximal safe tumor debulking. However, in spite of gross total resection, these tumors are likely to recur. Hence, adjuvant radiation is provided to reduce the risk of local recurrence and to improve outcomes. These tumors are considered relatively radioresistant; hence, high doses of radiation are generally required during treatment. However, the presence of several important structures around the lesion poses a major challenge with respect to covering the target with the prescribed high dose. In this regard, protons, for their physical and dosimetric advantages, have become the accepted modality of treatment in these tumors. With the evolution of proton beam therapy (PBT) over the years, especially pencil beam scanning techniques; which result in an extremely high conformal intensity-modulated proton beam therapy (IMPT), robust and Monte Carlo optimization, computational algorithms, and biological modelling are the significant advances which have further enhanced the value of this technology and have improved outcomes. Herein, we would like to report our experience of two cases of skull base tumors treated with intensity-modulated proton therapy at our center along with a review of the literature.

The Role of Plan Robustness Evaluation in Comparing Protons and Photons Plans - An Application on IMPT and IMRT Plans in Skull Base Chordomas.

PURPOSE: To analyze robustness of treatment plans optimized using different approaches in intensity modulated proton therapy (IMPT) and investigate the necessity of robust optimization and evaluation in intensity modulated radiotherapy (IMRT) plans for skull base chordomas. MATERIALS AND METHODS: Two photon plans, standard IMRT and robustly optimized IMRT (RB-IMRT), and two IMPT plans, robustly optimized multi field optimization (MFO) and hybrid-MFO (HB-MFO), were created in RayStation TPS for five patients previously treated using single field uniform optimization (SFO). Both set-up and range uncertainties were incorporated during robust optimization of IMPT plans whereas only set-up uncertainty was used in RB-IMRT. The dosimetric outcomes from the five planning techniques were compared for every patient using standard dose volume indices and integral dose (ID) estimated for target and organs at risk (OARs). Robustness of each treatment plan was assessed by introducing set-up uncertainties of ±3 mm along the three translational axes and, only in protons, an additional range uncertainty of ±3.5%. RESULTS: All the five nominal plans provided comparable and clinically acceptable target coverage. In comparison to nominal plans, worst case decrease in D95% of clinical target volume-high risk (CTV-HR) were 11.1%, 13.5%, and 13.6% for SFO, MFO, and HB-MFO plans respectively. The corresponding values were 13.7% for standard IMRT which improved to 11.5% for RB-IMRT. The worst case increased in high dose (D1%) to CTV-HR was highest in IMRT (2.1%) and lowest in SFO (0.7%) plans. Moreover, IMRT showed worst case increases in D1% for all neurological OARs and were lowest for SFO plans. The worst case D1% for brainstem, chiasm, spinal cord, optic nerves, and temporal lobes were increased by 29%, 41%, 30%, 41% and 14% for IMRT and 18%, 21%, 21%, 24%, and 7% for SFO plans, respectively. In comparison to IMRT, RB-IMRT improved D1% of all neurological OARs ranging from 5% to 14% in worst case scenarios. CONCLUSION: Based on the five cases presented in the current study, all proton planning techniques (SFO, MFO and HB-MFO) were robust both for target coverage and OARs sparing. Standard IMRT plans were less robust than proton plans in regards to high doses to neurological OARs. However, robust optimization applied to IMRT resulted in improved robustness in both target coverage and high doses to OARs. Robustness evaluation may be considered as a part of plan evaluation procedure even in IMRT.

Critical neurological structure sparing radiosurgery of vestibular schwannoma: dosimetric comparison of different techniques and dose prescription methods.

AIM: To investigate potential sparing of critical neurological structures (CNSs) during radiosurgery of vestibular schwannoma (VS) employing different techniques and dose prescription methods. MATERIALS AND METHODS: Fused CT and MRI datasets of eight patients with unilateral VS representing a wide range of target volume (0.48 to 12.08 cc; mean = 3.56 cc), shape and proximity to CNSs such as cochlea, trigeminal nerve and brainstem were re-planned employing static conformal field (SCF), dynamic conformal arc (DCA) and intensity modulated radiosurgery (IMRS) techniques. For every patient, five plans were created for a fixed margin dose of 12 Gy prescribed at 80% in three plans (SCF_80%, DCA_80%, and IMRS_80%) and 50% in another two plans (SCF_50% and DCA_50%). All plans were compared using standard dosimetric indices. RESULTS: Primary goal of every plan to cover ≥99% of target volume with 12 Gy was fulfilled for all patients with minimum significant dose to target (D99) ≥11.99 Gy. Best conformity index (CI Paddick = 0.62 ± 0.12) was observed in SCF_80% and DCA_80% plans whereas; sharpest dose gradient index of 3.40 ± 0.40 was resulted from DCA_50%. All five plans resulted similar maximum dose to brainstem (11.04 ± 2.23 to 11.53 ± 1.10 Gy), cochlea (9.02 ± 1.79 to 10.15 ± 1.26 Gy) and trigeminal nerve (11.55 ± 1.38 to 12.19 ± 2.12 Gy). Among 80% prescription plans, IMRS_80% reduces mean and D5 (P < 0.05) to all CNSs. Prescription of dose at 50% isodose sharpened the dose gradient and significantly (P < 0.05) reduced mean dose and D5 to all CNSs at the cost of target conformity (P = 0.01). Mean dose to cochlea and trigeminal nerve were least at 4.53 ± 0.86 and 6.95 ± 2.02 Gy from SCF_50% and highest at 6.65 ± 0.70 and 8.40 ± 2.11 Gy from DCA_80% plans respectively. CONCLUSION: This dosimetric data provides a guideline for choosing optimum treatment option and scope of inter institutional dosimetric comparison for further improvement in radiosurgery of Vestibular Schwannoma (VS).

Evaluation of automated image registration algorithm for image-guided radiotherapy (IGRT).

The performance of an image registration (IR) software was evaluated for automatically detecting known errors simulated through the movement of ExactCouch using an onboard imager. Twenty-seven set-up errors (11 translations, 10 rotations, 6 translation and rotation) were simulated by introducing offset up to ± 15 mm in three principal axes and 0° to ± 1° in yaw. For every simulated error, orthogonal kV radiograph and cone beam CT were acquired in half-fan (CBCT_HF) and full-fan (CBCT_FF) mode. The orthogonal radiographs and CBCTs were automatically co-registered to reference digitally reconstructed radiographs (DRRs) and planning CT using 2D-2D and 3D-3D matching software based on mutual information transformation. A total of 79 image sets (ten pairs of kV X-rays and 69 session of CBCT) were analyzed to determine the (a) reproducibility of IR outcome and (b) residual error, defined as the deviation between the known and IR software detected displacement in translation and rotation. The reproducibility of automatic IR of planning CT and repeat CBCTs taken with and without kilovoltage detector and kilovoltage X-ray source arm movement was excellent with mean SD of 0.1 mm in the translation and 0.0° in rotation. The average residual errors in translation and rotation were within ± 0.5 mm and ± 0.2°, ± 0.9 mm and ± 0.3°, and ± 0.4 mm and ± 0.2° for setup simulated only in translation, rotation, and both translation and rotation. The mean (SD) 3D vector was largest when only translational error was simulated and was 1.7 (1.1) mm for 2D-2D match of reference DRR with radiograph, 1.4 (0.6) and 1.3 (0.5) mm for 3D-3D match of reference CT and CBCT with full fan and half fan, respectively. In conclusion, the image-guided radiation therapy (IGRT) system is accurate within 1.8 mm and 0.4° and reproducible under control condition. Inherent error from any IGRT process should be taken into account while setting clinical IGRT protocol.

Estimation of risk of radiation-induced carcinogenesis in adolescents with nasopharyngeal cancer treated using sliding window IMRT.

PURPOSE: To estimate the risk of radiation-induced carcinogenesis based on whole-body dose measurement on adolescent patients undergoing intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Ten adolescent patients with nasopharyngeal cancer were planed and treated to a dose of 70.2 Gy using sliding window IMRT. Peripheral dose (PD) was measured using thermoluminescent dosimeters kept at anterior, lateral and posterior positions of each axial plane at the level of xiphoid process, umbilicus and gonads of every patient. The associated risk of radiation-induced carcinogenesis was estimated based on the measured whole-body dose and using age- and sex-specific ICRP-60 nominal probability coefficient of 7.5% (boys) and 9.5% (girls) per Sv. RESULTS: In all patients, measured PD per monitor unit (MU) decreases almost exponentially with out-of-field distance and varies with gantry angle. Highest whole-body dose equivalent ranged from 0.5318 to 0.9867 Sv (mean=0.8141 Sv, SD=0.138) which was measured posteriorly at the level of xiphoid process. Whole-body dose was represented by the average dose at xiphoid process and all measurement positions ranged from 0.3661 to 0.8766 Sv (mean=0.658 Sv, SD=0.16) and 0.2267 to 0.5277 Sv (mean=0.3859 Sv, SD=0.09), respectively. The associated mean risk of radiation-induced carcinogenesis estimated based on different representation of mean whole-body dose was 6.57%, 5.3% and 3.11%, respectively. Higher mean risk of 7.32% was estimated among girls as compared to 6.25% for boys. CONCLUSIONS: Knowledge of risk of secondary malignancy is particularly important in adolescents and should be considered when choosing the optimal treatment technique and delivery system.

Whole-body PET acceptance test in 2D and 3D using NEMA NU 2-2001 protocol.

Integrated PET/CT has emerged as an integral component of oncology management because of its unique potential of providing both functional and morphological images in a single imaging session. In this work, performance of the 'bismuth germinate (BGO) crystal'-based PET of a newly installed Discovery ST PET/CT was evaluated in 2D and 3D mode for whole-body scanning using National Electrical Manufacturers Association (NEMA) NU 2-2001 protocol and the recommended phantoms. During the entire measurements, the system operates with an energy window of 375-650 keV and 11.7 ns coincidence time window. The set of tests performed were spatial resolution, sensitivity, scatter fraction (SF) and counting rate performance. The average transaxial and axial spatial resolution measured as full width at half maximum (FWHM) of the point spread function at 1 cm (and 10 cm) off-axis was 0.632 (0.691) and 0.491 (0.653) cm in 2D and 0.646 (0.682) and 0.54 (0.601) cm in 3D respectively. The average sensitivity for the two radial positions (R = 0 cm and R = 10 cm) was 2.56 (2.63) cps/kBq in 2D and 11.85 (12.14) cps/kBq in 3D. The average scatter fraction was 19.79% in 2D and 46.19% in 3D. The peak noise equivalent counting rate (NECR) evaluated with single random subtraction was 89.41 kcps at 49 kBq/cc in 2D and 60 kcps at 12 kBq/cc in 3D acquisition mode. The NECR with delayed random subtraction was 61.47 kcps at 40.67 kBq/cc in 2D and 45.57 kcps at 16.45 kBq/cc in 3D. The performance of the PET scanner was satisfactory within the manufacturer-specified limits. The test result of PET shows excellent system sensitivity with relatively uniform resolution throughout the FOV, making this scanner highly suitable for whole-body studies.

Use of peripheral dose data from uniform dynamic multileaf collimation fields to estimate out-of-field organ dose in patients treated employing sliding window intensity-modulated radiotherapy.

Peripheral doses (PD) from uniform dynamic multileaf collimation (DMLC) fields were measured for 6 MV x-rays on a Varian linear accelerator using a 0.6 cc ionization chamber inserted at 5 cm depth into a 35 x 35 x 105 cm3 plastic water phantom. PD measurements were also carried out under identical conditions for seven patients treated for head and neck and cervical cancer employing sliding window intensity-modulated radiotherapy (IMRT). The measured PD from these patient-specific intensity-modulated beams (IMBs) were compared with the corresponding data from uniform DMLC fields having similar jaws setting. The measured PD per monitor unit (PD/MU) decreases almost exponentially with out-of-field distance for all uniform DMLC and static fields. For the same strip field width of 1.2 cm, uniform DMLC fields with a larger size of 14 x 22 cm2 deliver an average of 3.51 (SD = 0.51) times higher PD/MU at all out-of-field distances compared to 6 x 6 cm2. Similar to uniform DMLC fields, PD/MU measured from different patient-specific IMBs was found to decrease almost exponentially with out-of-field distance and increase with increase in field dimension. PD per MU from uniform DMLC fields and patient-specific IMBs having similar jaws setting shows good agreement (+/-7%) except at the most proximal distance, where a variation of more than 10% (maximum 15%) was observed. Our study shows that PD data generated from uniform DMLC fields can be used as baseline data to estimate out-of-field critical organ or whole-body dose in patients treated employing sliding window IMRT if an appropriate correction factor for field dimension is applied. The whole-body dose information can be used to estimate the possible increase in risk of fatal secondary malignancy in patients treated employing sliding window IMRT.