Fractionated Grid Therapy Research Articles

A Novel 3D MLC-Based Forward Planning Technique for Spatial Fractionated GRID Therapy

A Novel 3D MLC-Based Forward Planning Technique for Spatial Fractionated GRID Therapy

Dosimetry modeling of focused kV x‐ray radiotherapy for wet age‐related macular degeneration

Wet (neovascular) age-related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti-VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet-AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation-based radiotherapy device uses fixed 4mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting-edge polycapillary x-ray optics. Simulation of the polycapillary optics was achieved via Monte Carlo (MC)-based three-dimensional (3D) geometric ray tracing. Phase-space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall ~0.2mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4-based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including ±0.75mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball. The simulated CNV treatments by 60-kVp focused x-ray beams show highly conformal delivery of dose to the lesion plus margin (0.75mm) with sharp dose fall-offs and controllable spatial modulation patterns. The 90%-10% isodose penumbra is <0.5mm. With a prescription dose of 16Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75-mm linear displacements and 5-degree gaze angle rotation of the eyeball. Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques.

A novel, yet simple MLC-based 3D-crossfire technique for spatially fractionated GRID therapy treatment of deep-seated bulky tumors.

PurposeTreating deep‐seated bulky tumors with traditional single‐field Cerrobend GRID‐blocks has many limitations such as suboptimal target coverage and excessive skin toxicity. Heavy traditional GRID‐blocks are a concern for patient safety at various gantry‐angles and dosimetric detail is not always available without a GRID template in user’s treatment planning system. Herein, we propose a simple, yet clinically useful multileaf collimator (MLC)‐based three‐dimensional (3D)‐crossfire technique to provide sufficient target coverage, reduce skin dose, and potentially escalate tumor dose to deep‐seated bulky tumors.Materials/methodsThirteen patients (multiple sites) who underwent conventional single‐field cerrobend GRID‐block therapy (maximum, 15 Gy in 1 fraction) were re‐planned using an MLC‐based 3D‐crossfire method. Gross tumor volume (GTV) was used to generate a lattice pattern of 10 mm diameter and 20 mm center‐to‐center mimicking conventional GRID‐block using an in‐house MATLAB program. For the same prescription, MLC‐based 3D‐crossfire grid plans were generated using 6‐gantry positions (clockwise) at 60° spacing (210°, 270°, 330°, 30°, 90°, 150°, therefore, each gantry angle associated with a complement angle at 180° apart) with differentially‐weighted 6 or 18 MV beams in Eclipse. For each gantry, standard Millenium120 (Varian) 5 mm MLC leaves were fit to the grid‐pattern with 90° collimator rotation, so that the tunneling dose distribution was achieved. Acuros‐based dose was calculated for heterogeneity corrections. Dosimetric parameters evaluated include: mean GTV dose, GTV dose heterogeneities (peak‐to‐valley dose ratio, PVDR), skin dose and dose to other adjacent critical structures. Additionally, planning time and delivery efficiency was recorded. With 3D‐MLC, dose escalation up to 23 Gy was simulated for all patient's plans.ResultsAll 3D‐MLC crossfire GRID plans exhibited excellent target coverage with mean GTV dose of 13.4 ± 0.5 Gy (range: 12.43–14.24 Gy) and mean PVDR of 2.0 ± 0.3 (range: 1.7–2.4). Maximal and dose to 5 cc of skin were 9.7 ± 2.7 Gy (range: 5.4–14.0 Gy) and 6.3 ± 1.8 Gy (range: 4.1–11.1 Gy), on average respectively. Three‐dimensional‐MLC treatment planning time was about an hour or less. Compared to traditional GRID‐block, average beam on time was 20% less, while providing similar overall treatment time. With 3D‐MLC plans, tumor dose can be escalated up to 23 Gy while respecting skin dose tolerances.ConclusionThe simple MLC‐based 3D‐crossfire GRID‐therapy technique resulted in enhanced target coverage for de‐bulking deep‐seated bulky tumors, reduced skin toxicity and spare adjacent critical structures. This simple MLC‐based approach can be easily adopted by any radiotherapy center. It provides detailed dosimetry and a safe and effective treatment by eliminating the heavy physical GRID‐block and could potentially provide same day treatment. Prospective clinical trial with higher tumor‐dose to bulky deep‐seated tumors is anticipated.

TU‐CD‐304‐08: Feasibility of a VMAT‐Based Spatially Fractionated Grid Therapy Technique

Purpose:Grid therapy (GT) uses spatially modulated radiation doses to treat large tumors without significant toxicities. Incorporating 3D conformal‐RT or IMRT improved single‐field GT by reducing dose to normal tissues spatially through the use of multiple fields. The feasibility of a MLC‐based, inverse‐planned multi‐field GT technique has been demonstrated. Volumetric modulated arc therapy (VMAT) provides conformal dose distributions with the additional potential advantage of reduced treatment times. In this study, we characterize a new VMAT‐based GT (VMAT‐GT) technique with respect to its deliverability and dosimetric accuracy.Methods:A lattice of 5mm‐diameter spheres was created as the boost volume within a large treatment target. A simultaneous boost VMAT (RapidArc) plan with 8Gy to the target and 20Gy to the boost volume was generated using the Eclipse treatment planning system (AAA‐v11). The linac utilized HD120 MLC and 6MV flattening‐filter free beam. Four non‐coplanar arcs, with couch angles at 0, 45, 90 and 317° were used. Collimator angles were at 45 and 315°. The plan was mapped to a phantom. Calibrated Gafchromic EBT3 films were used to measure the delivered dose.Results:The VMAT plan generated a highly spatially modulated dose distribution in the target. D95%, D50%, D5% for the spheres and the targets in Gy were 18.9, 20.6, 23 and 8.0, 9.6, 14.8, respectively. D50% for a 1cm ring 1cm outside the target was 3.0Gy. The peak‐to‐valley ratio of this technique is comparable to previously proposed techniques, but the MUs were reduced by almost 50%. Film dosimetry showed good agreement between calculated and delivered dose, with an overall gamma passing rate of &gt;98% (3% and 1mm). The point dose differences at sphere centers varied from 2–8%.Conclusion:The deliverability and dose calculation accuracy of the proposed VMAT‐GT technique demonstrates that ablative radiation doses are deliverable to large tumors safely and efficiently.

Dosimetric evaluation of multi-pattern spatially fractionated radiation therapy using a multi-leaf collimator and collapsed cone convolution superposition dose calculation algorithm

Purpose: In this paper, we present an alternative to the originally proposed technique for the delivery of spatially fractionated radiation therapy (GRID) using multi-leaf collimator (MLC) shaped fields. We employ the MLC to deliver various pattern GRID treatments to large solid tumors and dosimetrically characterize the GRID fields. Methods and materials: The GRID fields were created with different open to blocked area ratios and with variable separation between the openings using a MLC. GRID designs were introduced into the Pinnacle 3 treatment planning system, and the dose was calculated in a water phantom. Ionization chamber and film measurements using both Kodak EDR2 and Gafchromic EBT film were performed in a SolidWater ® phantom to determine the relative output of each GRID design as well as its spatial dosimetric characteristics. Results: Agreement within 5.0% was observed between the Pinnacle 3 predicted dose distributions and the measurements for the majority of experiments performed. A higher magnitude of discrepancy (15%) was observed using a high photon beam energy (18 MV) and small GRID opening. Skin dose at the GRID openings was higher than the corresponding open field by a factor as high as three for both photon energies and was found to be independent of the open-to-blocked area ratio. Conclusion: In summary, we reaffirm that the MLC can be used to deliver spatially fractionated GRID therapy and show that various GRID patterns may be generated. The Pinnacle 3 TPS can accurately calculate the dose of the different GRID patterns in our study to within 5% for the majority of the cases based on film and ion chamber measurements. Disadvantages of MLC-based GRID therapy are longer treatment times and higher surface doses.

SU‐EE‐A1‐05: Dosimetric Evalualtion of a Commercial Compensator for Spatially Fractionated Radiation Therapy

Purpose: Spatially fractionated GRID therapy is utilized to treat large tumors by irradiating the volume through isolated small openings. The technique has shown high efficacy for bulky tumors, but it is used at relatively few facilities. In this study, we exploit the use of a prototype brass GRID, which could make GRID therapy more attractive to physicians and more widely available to patients. Method and Materials: A prototype GRID compensator was constructed by milling divergent holes of 1 cm diameter at the isocenter in a cube of brass. The GRID block is manufactured so that it can irradiate a maximum field size of 25×25cm2. Measurements for the characterization of the dosimetric properties of the GRID were performed using a Varian 23Ex linac, in a solid water phantom at 100cm SSD, for both 6MV and 18MV. Radiographic films were placed perpendicular to the beam axis to obtain lateral profiles, and parallel to the beam axis to find the percent depth doses (PDDs). A pinpoint ion chamber under the central hole was used to find the output factors. Results: The profiles have an obvious peak and valley pattern, with transmissions under the solid portion of the block of approximately 15% for 6MV and 30% for 18MV. The PDDs are less penetrating than their open‐field counterparts, for both 6MV and 18MV when compared against the 10×10cm2 open field. Conclusion: This prototype brass GRID compensator is a viable alternative to the cerrobend compensators or MLC‐based fields currently in use. Its ease of creation and use give it decided advantages. We believe this compensator can be put to clinical use, and will allow more centers to offer GRID therapy to their patients.Research sponsored by .decimal corporation.

Fractionated Grid Therapy in Treating Cervical Cancers: Conventional Fractionation or Hypofractionation?

To evaluate the conventionally fractionated and hypofractionated grid therapy in debulking cervical cancers using the linear quadratic (LQ) model. A Monte Carlo technique was used to calculate the dose distribution of a commercially available grid in a 6-MV photon beam. The LQ model was used to evaluate the therapeutic outcome of both the conventionally fractionated (2 Gy/fraction) and hypofractionated (15 Gy/fraction) grid therapy regimens to debulk cervical cancers with different LQ parameters. The equivalent open-field dose (EOD) to the cancer cells and therapeutic ratio (TR) were defined by comparing grid therapy with the open debulking field. The clinical outcomes from 114 patients were used to verify our theoretical model. The cervical cancer and normal tissue cell survival statistics for grid therapy in two regimens were calculated. The EODs and TRs were derived. The EOD was only a fraction of the prescribed dose. The TR was dependent on the prescribed dose and the LQ parameters of both the tumor and normal tissue cells. The grid therapy favors the acutely responding tumors inside radiosensitive normal tissues. Theoretical model predictions were consistent with the clinical outcomes. Grid therapy provided a pronounced therapeutic advantage in both the hypofractionated and conventionally fractionated regimens compared with that seen with single fraction, open debulking field regimens, but the true therapeutic advantage exists only in the hypofractionated grid therapy. The clinical outcomes and our study indicated that a course of open-field radiotherapy is necessary to control tumor growth fully after a grid therapy.

TU‐EE‐A2‐02: Fractionated Grid Therapy in Treating Cervical Cancers: Hypo‐Fractionation Or Conventional Fractionation?

Purpose: To evaluate the hypo‐fractionated and conventionally fractionated grid therapy in treating cervical cancers. Material and methods: A Monte Carlo technique was employed to calculate dose distribution of a commercially available grid. Based on the previously validated Monte Carlo technique, our new study has considered the divergence of all holes and thus improved the accuracy of grid geometry description in the simulations. The linear‐quadratic (LQ) model is used to evaluate the therapeutic outcome of both the hypo‐fractionated (fewer fractions and higher dose/fraction, herein 15 Gy/fraction) and conventionally fractionated (2Gy/fraction) regimens using grid therapy to treat cervical tumors that were represented by different radio‐biological responses. Results: The dose profiles and 2D dose distributions at dmax (d=1.5 cm) and 5 cm depths in water were obtained. An excellent agreement of dose profiles between calculated and measured was confirmed. The tumor cell and normal tissue survival statistics of grid therapy for two types of treatment regimens were calculated using the 2‐D dose distributions at the depth of 5 cm, and the therapeutic ratios and equivalent open field doses were obtained. Conclusions: The consideration of the divergence of grid holes has improved the Monte Carlo simulation results. In both the hypo‐fractionated and conventionally fractionated regimens, the therapeutic ratio depends not only on the single α/β value, but also on the individual α and β values. There is a significant therapeutic advantage of grid therapy for treating the studied cervical cancer cells because of their large α/β values, and the normal tissue sparing effect for the hypo‐fractionation regimen with few fractions is comparable to the conventional fractionation regimen with many fractions. For the radiosensitive normal tissues, both regimens give almost the same results, but for the radio‐resistant normal tissue the conventional fractionation regimen is preferred to spare them.

SU-FF-T-249: Fractionated Grid Therapy in Treating Cervical Cancers

Purpose: To evaluate the potential therapeutic advantage of external beam grid therapy in treating cervical cancer in comparison of conventional open field radiotherapy.Method and Materials: A Monte Carlo technique was employed to calculate 2‐dimensinal dose distribution of a commercially available grid, and the linear‐quadratic (LQ) model was applied to study the therapeutic advantage of using grid therapy for treating cervical cancers. A list of cervical cancer cell lines with known LQ parameters were used to calculate the radiotherapy response. Acutely responding normal muscle with α/β value of 3.1 Gy was used to evaluate the outcomes of between the open and grid field irradiations. The normal muscle tissue with three different sensitivities was assumed according to their response to a 2Gy open field. The therapeutic ratio based on sparing normal cells has been defined and calculated. The treatment regimens with 2Gy per fraction and 5 to 20 fractions were used in the calculations. Results: The survival fractions of normal tissues as well as tumor cells in the open and grid field are calculated. An appreciable therapeutic advantage has been demonstrated. Therapeutic ratio up to 9.5 for radio‐sensitive normal muscles was found. However, the radio‐resistant muscle does not show apparent advantage benefiting from the grid therapy. The results of data analysis showed that the therapeutic outcome depends not only on the single value α/β, but also on the individual α and β values of both the tumor and normal tissue cells. Conclusion:Monte Carlo technique was proven to be able to provide the dosimetric characteristics for grid therapy. The grid therapy in this study was found to be advantageous for treating the acutely responding cervical tumors (α/β>6), but not for slow responding ones (α/β⩽6). The acutely responding tumors and radio‐sensitive normal tissues are more suitable for using the grid therapy.

Spatially fractionated (GRID) radiation for palliative treatment of advanced cancer

To evaluate the use of single large doses spatially fractionated radiation (GRID) therapy either alone or in combination with conventional radiation in the palliative treatment of advanced cancer. Sixty-one patients with advanced cancer who had exhausted conventional approaches to palliative treatment with surgery, chemotherapy and/or radiotherapy were treated with high dose GRID therapy using high energy photons. Seventy-two symptomatic areas of disease were irradiated. A 50:50 GRID (open to closed areas) was utilized and a single fraction of 1,000–2,000 cGy to dmax was delivered to the open areas using a single field with either 6 MV or 25 MV photons. Follow-up ranged from 2 weeks to 28 months. Short follow-up times in some patients was due to their end stage disease. Patients were analyzed for palliation of symptoms and normal tissue morbidity. Sixty-four of 72 treatments were evaluable for palliative response. The results of treatment indicated a 27% (17/64) complete palliative response. A partial response was obtained in 64% (41/64). Overall response rate was 91%. Pain was the primary reason for treatment. Twenty-eight percent complete pain relief and 62% partial pain relief was achieved with GRID therapy. Symptoms related to large tumor masses were completely relieved in 19% and partially relieved in 71%. No acute morbidity was observed in spite of the large single doses delivered. Eight patients who were followed 12 to 28 months have shown no late morbidity. The use of spatially fractionated GRID therapy to deliver large single doses of radiation for palliative treatment has proven effective, especially for patients with short life expectancies. Further optimization of the GRID radiation distribution and maximum tolerable doses need to be established. Radiat Oncol Invest 1996;4:41–47. © 1996 Wiley-Liss, Inc.