Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

Grid therapy is a treatment technique that has been introduced for patients with advanced bulky tumors. The purpose of this study is to investigate the effect of the radiation sensitivity of the tumors and the design of the grid blocks on the clinical response of grid therapy. The Monte Carlo simulation technique is used to determine the dose distribution through a grid block that was used for a Varian 2100C linear accelerator. From the simulated dose profiles, the therapeutic ratio (TR) and the equivalent uniform dose (EUD) for different types of tumors with respect to their radiation sensitivities were calculated. These calculations were performed using the linear quadratic (LQ) and the Hug‐Kellerer (H‐K) models. The results of these calculations have been validated by comparison with the clinical responses of 232 patients from different publications, who were treated with grid therapy. These published results for different tumor types were used to examine the correlation between tumor radiosensitivity and the clinical response of grid therapy. Moreover, the influence of grid design on their clinical responses was investigated by using Monte Carlo simulations of grid blocks with different hole diameters and different center‐to‐center spacing. The results of the theoretical models and clinical data indicated higher clinical responses for the grid therapy on the patients with more radioresistant tumors. The differences between TR values for radioresistant cells and radiosensitive cells at 20 Gy and 10 Gy doses were up to 50% and 30%, respectively. Interestingly, the differences between the TR values with LQ model and H‐K model were less than 4%. Moreover, the results from the Monte Carlo studies showed that grid blocks with a hole diameters of 1.0 cm and 1.25 cm may lead to about 19% higher TR relative to the grids with hole diameters smaller than 1.0 cm or larger than 1.25 cm (with 95% confidence interval). In summary, the results of this study indicate that grid therapy is more effective for tumors with radioresistant characteristics than radiosensitive tumors.PACS number(s): 87.55.‐x

Section: Discussionmentioning

confidence: 99%

Is grid therapy useful for all tumors and every grid block design?

Gholami

Nedaie

Longo

et al. 2016

“…We estimate the uncertainty from the breast IB‐IORT scatter dosimetric correction is at the same level, also 7%. The cell culture study indicated the uncertainties of the cell radiosensitivity parameters of α and β could be up to 20% 17. We assume those components are not correlated, thus the total uncertainty of the EUD and TR is estimated to be 31%.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, using EUD, 3D dose distribution of IB‐IORT, and normal cell population function f n (x i ) (f n (x i ) = 1‐f c (x i )), the average survival fractions of the three types of normal tissues (radiosensitive, moderate radiosensitive, and radioresistant) were, respectively, calculated in the EUD and IB‐IORT fields. The therapeutic ratio (TR) of this procedure was then defined17 and calculated by comparing the normal cell survival fractions between the IB‐IORT and EB‐IORT (namely EUD) with the equation of

T R = \frac{{\bar{S F}}_{n o r m a l} false(I B - I O R T false)}{{\bar{S F}}_{n o r m a l} false(E B - I O R T false)}

…”

Section: Methodsmentioning

confidence: 99%

“…Based on the literature of modeling the radioresponse of melanoma and cervical cancer cells,17, 20 an acute responding and a slow responding breast cancer cell lines were chosen. The acute responding breast cancer cell line has an α / β ratio of 10, which is standard for squamous cell carcinomas.…”

Section: Methodsmentioning

confidence: 99%

“…All the MLQ parameters for the five modeled cells are shown in Table 1. A value of 0.15 for δ and 0.693 for λ was chosen for all normal tissues and cancer cells 15, 17…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic analysis of Intrabeam‐based intraoperative radiation therapy in the treatment of unicentric breast cancer lesions utilizing a spherical target volume model

Schwid

Donnelly

Zhang

2017

Self Cite

It is postulated that the outcomes in treating breast cancer with intraoperative radiotherapy (IORT) would be affected by the residual cancer cell distribution within the tumor bed. The three‐dimensional (3D) radiation doses of IntrabeamTM (IB) IORT with a 4‐cm spherical applicator at the energy of 50 and 40 kV were calculated. The modified linear quadratic model (MLQ) was used to estimate the radiobiological responses of the cancer cells and interspersed normal tissues with various radiosensitivities. By comparing the average survival fraction of normal tissues in IB‐IORT and uniform dose treatment for the same level of cancer cell killing, the therapeutic ratios (TRs) were derived. The equivalent uniform dose (EUD) was found to increase with the prescription dose and decrease with the cancer cell infiltrating distance. For 50 kV beam at the 20 Gy prescription dose, the EUDs are 18.03, 16.49 and 13.56, 11. 29, and 9.28 Gy respectively, for 1.5, 3.0, 6.0, 9, and 15.0 mm of the cancer cell infiltrating distance into surrounding tissue. The dose rate of 50 kV is at least 1.87× higher than that of 40 kV beam. The EUDs of 50 kV beam are up to 15% higher than that of the 40 kV beam. The TR increases with the prescription dose, but decreases with the distance of cancer cell infiltration distance. Average TRs of 50 kV beam are up to 30% larger than that of 40 kV beam. In conclusion, IB‐IORT can provide a possible therapeutic advantage on sparing more normal tissue compared with the External Beam IORT (EB‐IORT) for shallowly populated unicentric breast lesion. Our data suggest that IB‐IORT dose size should be adjusted based on the individual patient's cancer cell infiltrating distance for delivering an effective dose, one dose‐fits‐all regimen may have undertreated some patients with large cancer infiltrating distance.

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

Pokhrel

Halfman

Sanford

et al. 2020

Purpose Treating 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/methods Thirteen 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. Results All 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. Conclusion The 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.