Purpose Accelerated tumor repopulation has significant implications in low-dose-rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer using clinical data. Methods and Materials The linear-quadratic (LQ) model extended for tumor repopulation was used to analyze the clinical data and MRI-based 3D tumor volumetric regression data of 80 cervical cancer patients who received external beam radiotherapy (EBRT) and low dose rate (LDR) brachytherapy. The LDR dose was converted to EBRT dose in 1.8 Gy fractions using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. The patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ2 method was used to fit the TCP data with two free parameters: onset time (Tk) of accelerated repopulation and the number of clonogens (K) while other LQ model parameters were adopted from the literature, due to the limited patient data. Results Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated higher TCP. Using the LQ model, the best fit was achieved with the onset time Tk=19 days, K=139, with uncertainty ranges of (11, 22) days for Tk, and (48, 1822) for K, respectively. Conclusion This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from the clinical data using the LQ model. Our study verifies that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.

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Purpose: To introduce a method to model the 3D dose distribution of laterally asymmetric proton beamlets resulting from collimation. The model enables rapid beamlet calculation for spot scanning (SS) delivery using a novel penumbra-reducing dynamic collimation system (DCS) with two pairs of trimmers oriented perpendicular to each other. Methods: Trimmed beamlet dose distributions in water were simulated with MCNPX and the collimating effects noted in the simulations were validated by experimental measurement. The simulated beamlets were modeled analytically using integral depth dose curves along with an asymmetric Gaussian function to represent fluence in the beam's eye view (BEV). The BEV parameters consisted of Gaussian standard deviations (sigmas) along each primary axis (σ x1 ,σ x2 ,σ y1 ,σ y2 ) together with the spatial location of the maximum dose (µ x ,µ y ). Percent depth dose variation with trimmer position was accounted for with a depth-dependent correction function. Beamlet growth with depth was accounted for by combining the in-air divergence with Hong's fit of the Highland approximation along each axis in the BEV. Results: The beamlet model showed excellent agreement with the Monte Carlo simulation data used as a benchmark. The overall passing rate for a 3D gamma test with 3%/3 mm passing criteria was 96.1% between the analytical model and Monte Carlo data in an example treatment plan. Conclusions: The analytical model is capable of accurately representing individual asymmetric beamlets resulting from use of the DCS. This method enables integration of the DCS into a treatment planning system to perform dose computation in patient datasets. The method could be generalized for use with any SS collimation system in which blades, leaves, or trimmers are used to laterally sharpen beamlets. C 2015 American Association of Physicists in Medicine.

Proton GRID therapy using a PBS delivery method was successfully developed and implemented clinically. Proton GRID therapy offers many advantages over photon GRID techniques. The use of protons provides a more uniform beamlet dose within the tumor and spares normal tissues located beyond the tumor. This new PBS method will also reduce the dose to proximal organs when treating a deep-seated tumor.

Objective: Approximately 70 patients with large and bulky tumors refractory to prior treatments were treated with photon spatially fractionated GRID radiation (SFGRT). We identified 10 additional patients who clinically needed GRID but could not be treated with photons due to adjacent critical organs. We developed a proton SFGRT technique, and we report treatment of these 10 patients. Methods: Subject data were reviewed for clinical results and dosimetric data. 50% of the patients were metastatic at the time of treatment and five had previous photon radiation to the local site but not via GRID. They were treated with 15–20 cobalt Gray equivalent using a single proton GRID field with an average beamlet count of 22.6 (range 7–51). 80% received an average adjuvant radiation dose to the GRID region of 40.8Gy (range 13.7–63.8Gy). Four received subsequent systemic therapy. Results: The median follow-up time was 5.9 months (1.1–18.9). At last follow-up, seven patients were alive and three had died. Two patients who had died from metastatic disease had local shrinkage of tumor. Of those alive, four had complete or partial response, two had partial response but later progressed, and one had no response. For all patients, the tumor regression/local symptom improvement rate was 80%. 50% had acute side-effects of grade1/2 only and all were well-tolerated. Conclusion: In circumstances where patients cannot receive photon GRID, proton SFGRT is clinically feasible and effective, with a similar side-effect profile. Advances in knowledge: Proton GRID should be considered as a treatment option earlier in the disease course for patients who cannot be treated by photon GRID.