Hypofractionation Schedules Research Articles

A Retrospective Analysis of Toxicity and Efficacy for 2 Hypofractionated Irradiation Schedules Versus a Conventional One for Post-Mastectomy Adjuvant Radiotherapy in Breast Cancer

Introduction: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. Methods: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). Results: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi² test, p > 0.05). Conclusion: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.

Maximum surgical resection and adjuvant intensity-modulated radiotherapy with simultaneous integrated boost for skull base chordoma.

Local recurrence is common after surgical resection of clivus chordoma. We report the results of maximum surgical resection followed by intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB). We reviewed 14 consecutive clivus chordoma cases undergoing postoperative IMRT-SIB using the institutional protocol between 2005 and 2013. Total and near-total resections were achieved in 11 patients (78.6%), partial in 2 patients (14.3%), and 1 patient (7.1%) received RT for recurrent tumor after total resection. Gross residual or the high-risk area defined the planning target volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and PTV3 was PTV2 plus a 5-10mm margin. A moderate hypofractionation schedule was used: doses to PTV1, PTV2 and PTV3 were 3.9Gy, 3.15Gy and 2.8Gy through 15 fractions for the first two patients, and the rest received 2.5Gy, 2.2Gy and 1.8Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions (EQD2) was 65-68Gy for PTV1, 52-56Gy for PTV2, and 44.3-44.8Gy for PTV3. Median follow-up was 41months. Eight patients were free of disease for median 42.5months (range 23-91 months), four patients had stable disease for median 60.5months (range 39-113 months), and 1 patient showed partial response for 38months after RT. Local progression was seen in one patient who received EQD2 67.8Gy after partial resection. Estimated 5-year progression-free and overall survival rates were 92.9%. Surgery improved the neurologic deficit in six patients, and IMRT-SIB was well tolerated without lasting toxicity. Our experience suggests that maximum resection and high-dose IMRT-SIB can achieve local control without significant morbidities.

NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionation schedules in patients with low-risk prostate cancer.

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

The potential of MRI-guided online adaptive re-optimisation in radiotherapy of urinary bladder cancer

Background and purposeAdaptive radiotherapy (ART) using plan selection is being introduced clinically for bladder cancer, but the challenge of how to compensate for intra-fractional motion remains. The purpose of this study was to assess target coverage with respect to intra-fractional motion and the potential for normal tissue sparing in MRI-guided ART (MRIGART) using isotropic (MRIGARTiso), an-isotropic (MRIGARTanIso) and population-based margins (MRIGARTpop). Materials and methodsNine bladder cancer patients treated in a phase II trial of plan selection underwent 6–7 weekly repeat MRI series, each with volumetric scans acquired over a 10min period. Adaptive re-planning on the 0min MRI scans was performed using density override, simulating a hypo-fractionated schedule. Target coverage was evaluated on the 10min scan to quantify the impact of intra-fractional motion. ResultsMRIGARTanIso reduced the course-averaged PTV by median 304cc compared to plan selection. Bladder shifts affected target coverage in individual fractions for all strategies. Two patients had a v95% of the bladder below 98% for MRIGARTiso. MRIGARTiso decreased the bowel V25 with 15–46cc compared to MRIGARTpop. ConclusionOnline re-optimised ART has a considerable normal tissue sparing potential. MRIGART with online corrections for target shift during a treatment fraction should be considered in ART for bladder cancer.

Minimizing metastatic risk in radiotherapy fractionation schedules

Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor α/β values. Numerical results indicate the potential for significant reduction in metastatic risk.

Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary dissection in patients with breast cancer post-conservative surgery: impact on late toxicity.

BackgroundThe aim of the present work was to analyse the impact of mild hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after axillary dissection on late toxicity.MethodsFrom 2007 to 2012, 100 females affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were confirmed in all women. The median age at diagnosis was 60 years (range 34–83). Tumors were classified according to molecular characteristics: luminal-A 59 pts (59 %), luminal-B 24 pts (24 %), basal-like 10 pts (10 %), Her-2 like 7 pts (7 %). 82 pts (82 %) received hormonal therapy, 9 pts (9 %) neo-adjuvant chemotherapy, 81pts (81 %) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease control and treatment related toxicity were analysed in follow-up visits. The extent of lymphedema was analysed by experts in Oncological Rehabilitation.ResultsWithin a median follow-up of 50 months (range 19–82), 6 (6 %) pts died, 1 pt (1 %) had local progression disease, 2 pts (2 %) developed distant metastasis and 1 subject (1 %) presented both. In all patients the acute toxicity was mainly represented by erythema and patchy moist desquamation. At the end of radiotherapy 27 pts (27 %) presented lymphedema, but only 10 cases (10 %) seemed to be correlated to radiotherapy. None of the patients showed a severe damage to the brachial plexus, and the described cases of paresthesias could not definitely be attributed to RT. We did not observe symptomatic pneumonitis.ConclusionsIrradiation of infra-supraclavicular nodes with a mild hypofractionated schedule can be a safe and effective treatment without evidence of a significant increase of lymphedema appearance radiotherapy related.

Optimal fractionation in radiotherapy for non-small cell lung cancer – a modelling approach

ABSTRACTBackground. Conventionally fractionated radiotherapy (CFRT) has proven ineffective in treating non-small cell lung cancer while more promising results have been obtained with stereotactic body radiotherapy (SBRT). Hypoxic tumours, however, might present a challenge to extremely hypofractionated schedules due to the decreased possibility for inter-fraction fast reoxygenation. A potentially successful compromise might be found in schedules employing several fractions of varying fractional doses. In this modelling study, a wide range of fractionation schedules from single-fraction treatments to heterogeneous, multifraction schedules taking into account repair, repopulation, reoxygenation and radiosensitivity of the tumour cells, has been explored with respect to the probability of controlling lung tumours.Material and methods. The response to radiation of tumours with heterogeneous spatial and temporal oxygenation was simulated including the effects of accelerated repopulation and intra-fraction repair. Various treatments with respect to time, dose and fractionation were considered and the outcome was estimated as Poisson-based tumour control probability for local control.Results. For well oxygenated tumours, heterogeneous fractionation could increase local control while hypoxic tumours are not efficiently targeted by such treatments despite reoxygenation. For hypofractionated treatments employing large doses per fraction, a synergistic effect was observed between intra-fraction repair and inter-fraction fast reoxygenation of the hypoxic cells as demonstrated by a reduction in D50 from 53.3 Gy for 2 fractions to 52.7 Gy for 5 fractions.Conclusions. For well oxygenated tumours, heterogeneous fractionation schedules could increase local control rates substantially compared to CFRT. For hypoxic tumours, SBRT-like hypofractionated schedules might be optimal despite the increased risk of intra-fraction repair due to a synergistic effect with inter-fraction reoxygenation.

WE‐F‐304‐05: Cranial TCP/NTCP Modeling Insights and Caveats

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

WE‐F‐304‐00: Outcomes of Hypofractionated Treatments ‐ Results of the WGSBRT

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

WE‐F‐304‐04: Radiosurgery for Vestibular Schwannomas: Tumor Control Probability Analyses and Recommended Reporting Standards

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

WE‐F‐304‐01: Overview of the Working Group On Stereotactic Body Radiation Therapy (WGSBRT)

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

WE‐F‐304‐03: Optic Nerve/Chiasm Hypofractionated SRS/SRT Dose Tolerance

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

WE‐F‐304‐02: Recurrent HNC Treated with SBRT: TCP‐Based Outcome Estimates

Stereotactic Body Radiation Therapy (SBRT) was introduced clinically more than twenty years ago, and many subsequent publications have reported safety and efficacy data. The AAPM Working Group on Biological Effects of Hypofractionated Radiotherapy/SBRT (WGSBRT) extracted published treatment outcomes data from extensive literature searches to summarize and construct tumor control probability (TCP) and normal tissue complication probability (NTCP) models for six anatomical regions: Cranial, Head and Neck, Thoracic, Abdominal, Pelvic, and Spinal. In this session, we present the WGSBRT's work for cranial sites, and recurrent head and neck cancer. From literature‐based data and associated models, guidelines to aid with safe and effective hypofractionated radiotherapy treatment are being determined. Further, the ability of existing and proposed radiobiological models to fit these data is considered as to the ability to distinguish between the linear‐quadratic and alternative radiobiological models such as secondary cell death from vascular damage, immunogenic, or bystander effects. Where appropriate, specific model parameters are estimated. As described in “The lessons of QUANTEC,” (1), lack of adequate reporting standards continues to limit the amount of useful quantitative information that can be extracted from peer‐reviewed publications. Recommendations regarding reporting standards are considered, to enable such reviews to achieve more complete characterization of clinical outcomes.1 Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten Haken RK, Constine LS, Deasy JO. The lessons of QUANTEC: recommendations for reporting and gathering data on dose‐volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S155–60.Learning Objectives: Describe the techniques, types of cancer and dose schedules used in treating recurrent H&N cancers with SBRT List the radiobiological models that compete with the linear‐quadratic model in explaining the results of hypofractionated RT Describe the dose/volume metrics that are considered safe in SBRT treatment of tumors near the optic structures. Discuss the efficacy of hypofractionation and dosing schedules used in treating vestibular schwannomas Identify some difficulties in modeling TCP and NTCP for cranial tumors treated with hypofractionation. One moderator, Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA‐cleared product in commercial use, and can analyze some of this data.No others have relevant conflicts of interest.

Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits

Breast cancer and prostate cancer are the most common cancers diagnosed in women and men, respectively, in the UK, and radiotherapy is used extensively in the treatment of both. In vitro data suggest that tumours in the breast and prostate have unique properties that make a hypofractionated radiotherapy treatment schedule advantageous in terms of therapeutic index. Many clinical trials of hypofractionated radiotherapy treatment schedules have been completed to establish the extent to which hypofractionation can improve patient outcome. Here we present a concise description of hypofractionation, the mathematical description of converting between conventional and hypofractionated schedules, and the motivation for using hypofractionation in the treatment of breast and prostate cancer. Furthermore, we summarise the results of important recent hypofractionation trials and highlight the limitations of a hypofractionated treatment regimen.

Partial breast radiotherapy with simple teletherapy techniques

A prospective pilot study of partial breast irradiation (PBI) with conventional vs hypofractionated schedules was set out. The study aimed to determine efficacy, acute and late side effects, and the preference of photon vs electron irradiation based on individual features. Patients were enrolled according to internationally accepted guidelines on PBI. Conformal radiotherapy plans were generated with both photon and electron beams, and the preferred technique based on dose homogeneity and the radiation exposure of healthy tissues was applied. For electron dose verification, a special phantom was constructed. Patients were randomized for fractionation schedules of 25 × 2 vs 13 × 3Gy. Skin and breast changes were registered at the time of and ≥1 year after the completion of radiotherapy. Dose homogeneity was better with photons. If the tumor bed was located in the inner quadrants, electron beam gave superior results regarding conformity and sparing of organ at risk (OAR). If the tumor was situated in the lateral quadrants, conformity was better with photons. A depth of the tumor bed ≥3.0cm predicted the superiority of photon irradiation (odds ratio [OR] = 23.6, 95% CI: 5.2 to 107.5, p < 0.001) with >90% sensitivity and specificity. After a median follow-up of 39 months, among 72 irradiated cases, 1 local relapse out of the tumor bed was detected. Acute radiodermatitis of grade I to II, hyperpigmentation, and telangiectasia developed ≥1 year after radiotherapy, exclusively after electron beam radiotherapy. The choice of electrons or photons for PBI should be based on tumor bed location; the used methods are efficient and feasible.

English

English

Evolution of hypofractionated accelerated radiotherapy for prostate cancer - the sunnybrook experience.

Stereotactic ablative body radiotherapy (SABR) is a newer method of ultra hypo fractionated radiotherapy that uses combination of image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), to deliver high doses of radiation in a few fractions to a target, at the same time sparing the surrounding organs at risk (OAR). SABR is ideal for treating small volumes of disease and has been introduced in a number of disease sites including brain, lung, liver, spine, and prostate. Given the radiobiological advantages of treating prostate cancer with high doses per fraction, SABR is becoming a standard of care for low and intermediate-risk prostate cancer patients based upon the results from Sunnybrook and also the US-based prostate SABR consortium. This review examines the development of moderate and ultra hypo-fractionation schedules at the Odette Cancer centre, Sunnybrook Health Sciences. Moderate hypo-fractionation protocol was first developed in 2001 for intermediate-risk prostate cancer and from there on different treatment schedules including SABR evolved for all risk groups.

Cancers de prostate : quelles techniques de radiothérapie pour quelles tumeurs ? Enjeux éthiques et méthodologiques

The identification of the optimal radiation technique in prostate cancer is based on the results of dosimetric and clinical studies, although there are almost no randomized studies comparing different radiation techniques. The feasibility of the techniques depends also on the technical and human resources of the radiation department, on the cost of the treatment from the points of view of the society, the patient and the radiation oncologist, and finally on the choice of the patient. The slow evolution of prostate cancer leads to consider the biochemical failure as the main judgment criteria in the majority of the studies. A proper urinary radio-induced toxicity evaluation implies a long follow-up. Intensity-modulated radiotherapy (IMRT) combined with image-guided radiotherapy (IGRT) is recommended in case of high dose (≥76Gy) to the prostate, pelvic lymph nodes irradiation and hypofractionation schedules. For low-risk tumors, the aim of the treatment is to preserve quality of life, while limiting costs. Stereotactic body radiotherapy shows promising results, although the follow-up is still limited and phase III trials are ongoing. Focal radiation techniques are in the step of feasibility. For intermediate and high-risk tumors, the objective of the treatment is to increase the locoregional control, while limiting the toxicity. IMRT combined with IGRT leads to either a well-validated dose escalation strategy for intermediate risk tumors, or to a strategy of moderate hypofractionated schedules, which cannot be yet considered as a standard treatment. These combined radiation techniques allow finally large lymph node target volume irradiation and dose escalation potentially in the dominant intraprostatic lesion. The feasibility of simultaneous integrated boost approaches is demonstrated.

RBE of ion beams in hypofractionated radiotherapy (SBRT)

An important advantage for the application of carbon ion beams in tumour therapy is their increased relative biological effectiveness (RBE) as compared to conventional photon radiation. Since RBE among other factors depends on the dose level, the precise knowledge of the RBE dependence on the dose is of particular importance for the comparison of different fractionation schemes, involving different doses per fraction. Here we describe some general properties of the RBE vs. dose dependence, which are determined using a simple modelling approach based on the linear-quadratic model as well as a more sophisticated predictive model for the description of RBE. We show that for both approaches the systematic dependence of RBE on the cell or tissue type as characterized by the α/β-ratio of the photon linear quadratic parameters is expected to be inverted at high doses as compared to low doses.We demonstrate that this inversion is not a model specific feature, but a rather generic feature resulting from the linear-quadratic shape of dose response curves and the correlation between RBE and the photon α/β-ratio. The results are discussed with respect to other modelling approaches and to their implications for clinical applications of carbon ion beams using hypofractionated treatment schedules.

Thoracic Re-irradiation May Be an Option for Recurrent, Metastatic, or Secondary Primary Non-Small Cell Lung Cancer

Thoracic Re-irradiation May Be an Option for Recurrent, Metastatic, or Secondary Primary Non-Small Cell Lung Cancer