Technical Note: Dosimetric impact of spherical applicator size in Intrabeam™ IORT for treating unicentric breast cancer lesions.

To characterize the dosimetric impact of using different sizes of spherical applicators in Intrabeam™ Intraoperative Radiation Therapy (IB-IORT) to treat unicentric cancer lesions after breast-conserving lumpectomy. Using the commissioned depth dose rates, the three-dimensional dosages of the 3.5, 4.0, 4.5, and 5.0 cm spherical applicators of the IB-IORT PRS400 machine were established. Five different cancer cell infiltration depths of unicentric breast lesions were formulated by a linearly declining cancer cell density distribution from the surgical surface. The equivalent uniform dose (EUD), which is the dosage of a homogeneous dose treatment for killing the same amount of cancer cells as IB-IORT in the same target volume, was then calculated using the modified linear quadratic model (MLQ). The radiobiological response of two types of cancer cell lines and three types of normal tissues in the TARGIT-A clinical trial of 20 Gy dose was estimated. The study was carried out for an acutely responding breast cancer cell line with an α/β ratio of 10 and a slow responding breast cancer cell line with an α/β ratio of 3.85, respectively. The cancer cell density at the surgical excision surface was assumed to be 0.01%, 0.1%, 1%, and 10%, respectively. The three types of normal tissue are radiosensitive, moderate radiosensitive, and radioresistant, respectively. The therapeutic ratio (TR), which was defined by a ratio between the survival fractions of normal tissue cells respectively in IB-IORT and in homogeneous dose treatments, was calculated. The EUDs are moderately dependent on the applicator size (increasing from 1 to 10% depending on the cancer infiltrating depth when increasing diameter by 0.5 cm), not on the cancer cell radiosensitivity (differing by less than 1.30% between two cancer cell lines), and not dependent on the cancer cell population density at the surgical excision surface (differing by 0% among the tested surface densities). The EUDs decrease with the cancer cell maximum infiltrating depth. EUD of a 10 mm spherical shell target volume is about 50% of EUD of a 1 mm spherical shell. TRs are dependent on the applicator size, cancer cell infiltrating depth, and the radiosensitivities of cancer cells and normal tissue. A smaller size of applicator was found to produce a greater TR for a shallowly seated lesion (<5 mm), while a large size of applicator is better to treating a deeply seated lesion (>5 mm). The applicator size has a moderate impact on the EUDs, a greater size of applicator will deliver a greater EUD at the same cancer cell infiltrating depth, but a smaller size of applicator is seen to produce a greater TR for the shallow lesions (depth <5 mm). In addition, a greater size of applicator is preferred for treating a deeply seated lesion (depth >5 mm) because it produces a greater TR and EUD than a smaller size of applicator. IB-IORT is a preferable alternative to uniform dose treatment when treating unicentric breast cancer at smaller infiltration depths.

Saleh Y ，Zhang H 《-》

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

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.

Schwid M ，Donnelly ED ，Zhang H 《Journal of Applied Clinical Medical Physics》

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

Zhang H ，Zhong H ，Barth RF ，Cao M ，Das IJ ... -  《-》

Therapeutic analysis of high-dose-rate (192)Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions.

Zhang H ，Donnelly ED ，Strauss JB ，Qi Y ... -  《-》

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system.

Kraus-Tiefenbacher U ，Scheda A ，Steil V ，Hermann B ，Kehrer T ，Bauer L ，Melchert F ，Wenz F ... -  《Tumori J》