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[en] Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the tumor control probability (TCP) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules. Compared to radiotherapy with conventional fractionation schedules, simulations of hypofractionated radiotherapy may require different models for cell survival and the oxygen enhancement ratio (OER). Our TCP simulations in hypofractionated radiotherapy are based on the LQ model and the universal survival curve (USC) developed for the high doses used in SBRT. The predicted trends in local control as a function of the initial tumor volume were evaluated in SBRT for non-small cell lung cancer (NSCLC). Our results show that both LQ and USC based models cannot describe the TCP reduction for larger tumor volumes observed in the clinical studies if the tumor is considered completely oxygenated. The TCP calculations are in agreement with the clinical data if the subpopulation of radio-resistant hypoxic cells is considered with the volume that increases as initial tumor volume increases. There are two conclusions which follow from our simulations. First, the extent of hypoxia is likely a primary reason of the TCP reduction with increasing the initial tumor volume in SBRT for NSCLC. Second, the LQ model can be an acceptable approximation for the TCP calculations in hypofractionated radiotherapy if the tumor response is defined primarily by the hypoxic fraction. The larger value of OER in the hypofractionated radiotherapy compared to the conventional radiotherapy effectively extends the applicability of the LQ model to larger doses. (paper)

[en] Highlights: • SBRT for localized RCC is a promising treatment modality especially in poor surgical candidates. • Dose escalation from 48 - 60 Gy in 3 fractions was achieved with zero dose-limiting toxicities. • Local control following treatment was 90% at 3 years. • Interpretation of post-SBRT biopsies remains uncertain. • Studies comparing SBRT to percutaneous ablation for poor surgical candidates are warranted. We previously demonstrated the safety of doses up to 48 Gy in 4 fractions with stereotactic body radiotherapy (SBRT) in poor surgical candidates with localized renal cell carcinoma (RCC). In an additional expansion cohort, we aimed to assess the safety of further dose escalation to 48–60 Gy in 3 fractions.

[en] Postoperative stereotactic body radiation therapy (SBRT) for metastatic spinal tumors is increasingly being performed in clinical practice. Whereas the fundamentals of SBRT practice for intact spinal metastases are established, there are as yet no comprehensive practice guidelines for the postoperative indications. In particular, there are unique considerations for patient selection and treatment planning specific to postoperative spine SBRT that are critical for safe and effective management. The purpose of this critical review is to discuss the rationale for treatment, describe those factors affecting surgical decision making, introduce modern surgical trends, and summarize treatment outcomes for both conventional postoperative external beam radiation therapy and postoperative spine SBRT. Lastly, an in-depth practical discussion with respect to treatment planning and delivery considerations is provided to help guide optimal practice.

[en] Purpose: To assess individual volumetric tumor regression pattern in cervical cancer during therapy using serial four-dimensional MRI and to define the regression parameters' prognostic value validated with local control and survival correlation. Methods and Materials: One hundred and fifteen patients with Stage IB₂-IVA cervical cancer treated with radiation therapy (RT) underwent serial MRI before (MRI 1) and during RT, at 2-2.5 weeks (MRI 2, at 20-25 Gy), and at 4-5 weeks (MRI 3, at 40-50 Gy). Eighty patients had a fourth MRI 1-2 months post-RT. Mean follow-up was 5.3 years. Tumor volume was measured by MRI-based three-dimensional volumetry, and plotted as dose(time)/volume regression curves. Volume regression parameters were correlated with local control, disease-specific, and overall survival. Results: Residual tumor volume, slope, and area under the regression curve correlated significantly with local control and survival. Residual volumes ≥20% at 40-50 Gy were independently associated with inferior 5-year local control (53% vs. 97%, p <0.001) and disease-specific survival rates (50% vs. 72%, p = 0.009) than smaller volumes. Patients with post-RT residual volumes ≥10% had 0% local control and 17% disease-specific survival, compared with 91% and 72% for <10% volume (p <0.001). Conclusion: Using more accurate four-dimensional volumetric regression analysis, tumor response can now be directly translated into individual patients' outcome for clinical application. Our results define two temporal thresholds critically influencing local control and survival. In patients with ≥20% residual volume at 40-50 Gy and ≥10% post-RT, the risk for local failure and death are so high that aggressive intervention may be warranted.

[en] Comprehensive an up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. Examines in detail retrospective studies and prospective clinical trials for various organ sites from around the world. Written by world-renowned experts in SBRT from North America, Asia and Europe. Stereotactic body radiation therapy (SBRT) has emerged as an innovative treatment for various primary and metastatic cancers, and the past five years have witnessed a quantum leap in its use. This book provides a comprehensive and up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. It will serve as a detailed resource for this rapidly developing treatment modality. The organ sites covered include lung, liver, spine, pancreas, prostate, adrenal, head and neck, and female reproductive tract. Retrospective studies and prospective clinical trials on SBRT for various organ sites from around the world are examined, and toxicities and normal tissue constraints are discussed. This book features unique insights from world-renowned experts in SBRT from North America, Asia, and Europe. It will be necessary reading for radiation oncologists, radiation oncology residents and fellows, medical physicists, medical physics residents, medical oncologists, surgical oncologists, and cancer scientists.

[en] Background. To investigate the utility of stereotactic body radiotherapy (SBRT) in the treatment of painful renal cell carcinoma (RCC) bone metastases, and for a possible dose effect on time to symptom relief. Material and methods. Eighteen patients with 24 painful osseous lesions from metastatic RCC were treated with SBRT. The most common treatment regimens were 24 Gy in 3 fractions and 40 Gy in 5 fractions. The times from treatment to first reported pain relief and time to symptom recurrence were evaluated. Median follow-up was 38 weeks (1-156 weeks). Results. Seventy-eight percent of all patients had pain relief. Patients treated with a BED > 85 Gy achieved faster and more durable pain relief compared to those treated with a BED < 85 Gy. There was decrease in time to pain relief after a change in treatment regimen to 8 Gy x 5 fractions (BED = 86). There was only one patient with grade 1 skin toxicity. No neurological or other toxicity was observed. Conclusions. SBRT can safely and effectively treat painful RCC bony metastases. There appears to be a relationship between radiation dose and time to stable pain relief

[en] Stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage, node negative non-small cell lung cancer (NSCLC) in patients who are either medically inoperable or refuse surgical resection. SBRT has high local control rates and a favorable toxicity profile relative to other surgical and non-surgical approaches. Given the excellent tumor control rates and increasing utilization of SBRT, recent efforts have focused on limiting toxicity while expanding treatment to increasingly complex patients. We review toxicities from SBRT for lung cancer, including central airway, esophageal, vascular (e.g., aorta), lung parenchyma (e.g., radiation pneumonitis), and chest wall toxicities, as well as radiation-induced neuropathies (e.g., brachial plexus, vagus nerve and recurrent laryngeal nerve). We summarize patient-related, tumor-related, dosimetric characteristics of these toxicities, review published dose constraints, and propose strategies to reduce such complications

[en] Purpose: It has been conventionally assumed that the repair rate for sublethal damage (SLD) remains constant during the entire radiation course. However, increasing evidence from animal studies suggest that this may not the case. Rather, it appears that the repair rate for radiation-induced SLD slows down with increasing time. Such a slowdown in repair would suggest that the exponential repair pattern would not necessarily accurately predict repair process. As a result, the purpose of this study was to investigate a new generalized linear-quadratic (LQ) model incorporating a repair pattern with reciprocal time. The new formulas were tested with published experimental data. Methods: The LQ model has been widely used in radiation therapy, and the parameter G in the surviving fraction represents the repair process of sublethal damage with T_r as the repair half-time. When a reciprocal pattern of repair process was adopted, a closed form of G was derived analytically for arbitrary radiation schemes. The published animal data adopted to test the reciprocal formulas. Results: A generalized LQ model to describe the repair process in a reciprocal pattern was obtained. Subsequently, formulas for special cases were derived from this general form. The reciprocal model showed a better fit to the animal data than the exponential model, particularly for the ED50 data (reduced χ²_min of 2.0 vs 4.3, p = 0.11 vs 0.006), with the following gLQ parameters: α/β = 2.6-4.8 Gy, T_r = 3.2-3.9 h for rat feet skin, and α/β = 0.9 Gy, T_r = 1.1 h for rat spinal cord. Conclusions: These results of repair process following a reciprocal time suggest that the generalized LQ model incorporating the reciprocal time of sublethal damage repair shows a better fit than the exponential repair model. These formulas can be used to analyze the experimental and clinical data, where a slowing-down repair process appears during the course of radiation therapy.

[en] 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 clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. 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 (T_k) of accelerated repopulation and 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 with higher TCP. Using the LQ model, we achieved the best fit with onset time T_k of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T_k and (48, 1822) for K, respectively. Conclusion: This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact 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.