scholarly journals An algorithm for thoracic re-irradiation using biologically effective dose: a common language on how to treat in a “no-treat zone”

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Eric D. Brooks ◽  
Xiaochun Wang ◽  
Brian De ◽  
Vivek Verma ◽  
Tyler D. Williamson ◽  
...  

Abstract Background Re-irradiation (re-RT) is a technically challenging task for which few standardized approaches exist. This is in part due to the lack of a common platform to assess dose tolerance in relation to toxicity in the re-RT setting. To better address this knowledge gap and provide new tools for studying and developing thresholds for re-RT, we developed a novel algorithm that allows for anatomically accurate three-dimensional mapping of composite biological effective dose (BED) distributions from nominal doses (Gy). Methods The algorithm was designed to automatically convert nominal dose from prior treatment plans to corresponding BED value maps (voxel size 2.5 mm3 and α/β of 3 for normal tissue, BED3). Following the conversion of each plan to a BED3 dose distribution, deformable registration was used to create a summed composite re-irradiation BED3 plan for each patient who received two treatments. A proof-of-principle analysis was performed on 38 re-irradiation cases of initial stereotactic ablative radiotherapy (SABR) followed by either re-SABR or chemoradiation for isolated locoregional recurrence of early-stage non-small cell lung cancer. Results Evaluation of the algorithm-generated maps revealed appropriate conversion of physical dose to BED at each voxel. Of 14 patients receiving repeat SABR, there was one case each of grade 3 chest wall pain (7%), pneumonitis (7%), and dyspnea (7%). Of 24 patients undergoing repeat fractionated radiotherapy, grade 3 events were limited to two cases each of pneumonitis and dyspnea (8%). Composite BED3 dosimetry for each patient who experienced grade 2–3 events is provided and may help guide development of precise cumulative dose thresholds for organs at risk in the re-RT setting. Conclusions This novel algorithm successfully created a voxel-by-voxel composite treatment plan using BED values. This approach may be used to more precisely examine dosimetric predictors of toxicities and to establish more accurate normal tissue constraints for re-irradiation.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi-tao Dai ◽  
Li Ma ◽  
Ting-ting Cao ◽  
Lian Zhu ◽  
Man Zhao ◽  
...  

AbstractTo perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm3 (5.736–49.246 cm3). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20–70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs.


2017 ◽  
Vol 52 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Chih-Yen Tu ◽  
Te-Chun Hsia ◽  
Hsin-Yuan Fang ◽  
Ji-An Liang ◽  
Su-Tso Yang ◽  
...  

AbstractBackgroundStereotactic ablative radiotherapy (SABR) is a promising option for non-operated early-stage non-small cell lung cancer (NSCLC) compared to conventional fractionated radiotherapy (CFRT). However, results from conclusive randomized controlled trials are not yet available. The aim of our study was to explore the effectiveness of SABR vs. CFRT for non-operated early-stage NSCLC.Patients and methodsWe used a comprehensive population-based database to identify clinical stage I non-operated NSCLC patients in Taiwan diagnosed from 2007 to 2013 who were treated with either SABR or CFRT. We used inverse probability weighting and the propensity score as the primary form of analysis to address the nonrandomization of treatment. In the supplementary analyses, we constructed subgroups based on propensity score matching to compare survival between patients treated with SABR vs. CFRT.ResultsWe identified 238 patients in our primary analysis. A good balance of covariates was achieved using the propensity score weighting. Overall survival (OS) was not significantly different between those treated with SABR vs. CFRT (SABR vs. CFRT: probability weighting adjusted hazard ratio [HR] 0.586, 95% confidence interval 0.264–1.101, p = 0.102). However, SABR was significantly favored in supplementary analyses.ConclusionsIn this population-based propensity-score adjusted analysis, we found that OS was not significantly different between those treated with SABRvs. CFRT in the primary analysis, although significance was observed in the supplementary analyses. Our results should be interpreted with caution given the database (i.e., nonrandomized) approach used in our study. Overall, further studies are required to explore these issues.


2017 ◽  
Vol 52 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Chih-Yen Tu ◽  
Te-Chun Hsia ◽  
Hsin-Yuan Fang ◽  
Ji-An Liang ◽  
Su-Tso Yang ◽  
...  

Abstract Background Stereotactic ablative radiotherapy (SABR) is a promising option for non-operated early-stage non-small cell lung cancer (NSCLC) compared to conventional fractionated radiotherapy (CFRT). However, results from conclusive randomized controlled trials are not yet available. The aim of our study was to explore the effectiveness of SABR vs. CFRT for non-operated early-stage NSCLC. Patients and methods We used a comprehensive population-based database to identify clinical stage I non-operated NSCLC patients in Taiwan diagnosed from 2007 to 2013 who were treated with either SABR or CFRT. We used inverse probability weighting and the propensity score as the primary form of analysis to address the nonrandomization of treatment. In the supplementary analyses, we constructed subgroups based on propensity score matching to compare survival between patients treated with SABR vs. CFRT. Results We identified 238 patients in our primary analysis. A good balance of covariates was achieved using the propensity score weighting. Overall survival (OS) was not significantly different between those treated with SABR vs. CFRT (SABR vs. CFRT: probability weighting adjusted hazard ratio [HR] 0.586, 95% confidence interval 0.264–1.101, p = 0.102). However, SABR was significantly favored in supplementary analyses. Conclusions In this population-based propensity-score adjusted analysis, we found that OS was not significantly different between those treated with SABR vs. CFRT in the primary analysis, although significance was observed in the supplementary analyses. Our results should be interpreted with caution given the database (i.e., nonrandomized) approach used in our study. Overall, further studies are required to explore these issues.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Michael Mayinger ◽  
Roman Ludwig ◽  
Sebastian M. Christ ◽  
Riccardo Dal Bello ◽  
Alex Ryu ◽  
...  

Abstract Purpose To assess the effects of daily adaptive MR-guided replanning in stereotactic body radiation therapy (SBRT) of liver metastases based on a patient individual longitudinal dosimetric analysis. Methods Fifteen patients assigned to SBRT for oligometastatic liver metastases underwent daily MR-guided target localization and on-table treatment plan re-optimization. Gross tumor volume (GTV) and organs at risk (OARs) were adapted to the anatomy-of-the-day. A reoptimized plan (RP) and a rigidly shifted baseline plan (sBP) without re-optimization were generated for each fraction. After extraction of DVH parameters for GTV, planning target volume (PTV), and OARs (stomach, duodenum, bowel, liver, heart) plans were compared on a per-patient basis. Results Median pre-treatment GTV and PTV were 14.9 cc (interquartile range (IQR): 7.7–32.9) and 62.7 cc (IQR: 42.4–105.5) respectively. SBRT with RP improved PTV coverage (V100%) for 47/75 of the fractions and reduced doses to the most proximal OARs (D1cc, Dmean) in 33/75 fractions compared to sBP. RP significantly improved PTV coverage (V100%) for metastases within close proximity to an OAR by 4.0% (≤ 0.2 cm distance from the edge of the PTV to the edge of the OAR; n = 7; p = 0.01), but only by 0.2% for metastases farther away from OAR (> 2 cm distance; n = 7; p = 0.37). No acute grade 3 treatment-related toxicities were observed. Conclusions MR-guided online replanning SBRT improved target coverage and OAR sparing for liver metastases with a distance from the edge of the PTV to the nearest luminal OAR < 2 cm. Only marginal improvements in target coverage were observed for target distant to critical OARs, indicating that these patients do not benefit from daily adaptive replanning.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 316-316
Author(s):  
S. F. Petit ◽  
B. Wu ◽  
M. Kazhdan ◽  
A. Dekker ◽  
P. Simari ◽  
...  

316 Background: Due to the low dose tolerance of the organs at risk (OARs) in the abdomen the tumor dose for pancreatic cancer patient is restricted to 50-60 Gy in 1.8-2.0 Gy fractions when combined with chemotherapy. The goal of this study was to develop a system that can determine the minimal radiation dose to the OARs of each individual patient that is achievable while maintaining adequate tumor coverage. This could guide treatment planners to spare the OARs to the fullest extent. When the minimal doses to the OAR are achieved, the total plan can be upscaled until the normal tissue dose constraints are met, allowing for an increase in tumor dose without increased normal tissue toxicity. Methods: The minimal achievable dose to the OARs depends on its proximity to the planning target volume (PTV). The overlap volume histogram (OVH) was used to describe the spatial relation of each OAR to the PTV. A database of 33 patients, treated with IMRT, was queried to find the lowest achieved dose to an organ for any of the prior patients with less favorable PTV-OAR configurations than the current patient. This minimal dose must also be achievable for the OAR of the new patient. For 25 randomly chosen patients the lowest achievable dose to the liver and kidneys was predicted this way. Then the patients were replanned to verify if this dose could be achieved. The new plans were compared to the original clinical plans. Results: After replanning the predicted achievable dose to the liver was realized within 1 and 2 Gy for more than 86% and 96% of the patients respectively. For the kidneys these numbers were 83% and 96%. The average improvement in terms of mean dose was 1.4 Gy (range 0 – 4.6 Gy) for the liver and 1.7 Gy (range 0 – 6.3 Gy) for the kidneys. This would have allowed an increase in PTV dose of on average 5 Gy (range 0-13 Gy) based on the liver and 8.5 Gy (range 0-38 Gy) based on the kidneys compared to the original plan, without an increase in dose to the bowel, cord, and stomach. Conclusions: The lowest achievable dose to the OARs could accurately be predicted for pancreatic cancer patients within seconds. This can guide dosimetrists to spare the OARs or increase the PTV dose by 5 Gy without increased toxicity. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9035-9035
Author(s):  
Joe Y. Chang ◽  
Steven H. Lin ◽  
Luyang Yao ◽  
Saumil Gandhi ◽  
Zhongxing X. Liao ◽  
...  

9035 Background: Stereotactic Ablative Radiotherapy (SABR) provides > 95% local control and has become standard care of medically inoperable stage I NSCLC. However, cumulatively about 40% of patients develop recurrence in the regional lymph nodes, distant organs, or secondary lung cancer. Combined immunotherapy and SABR (I-SABR) may reduce these recurrences by stimulating stronger cancer specific immune response. Methods: This is an ongoing phase II randomized study (SABR vs. I-SABR) to evaluate the efficacy and toxicity of I-SABR in medically inoperable, early stage (T1-T3: < 7 cm, including multi-primary tumors), isolated recurrence NSCLC without lymph node or distant metastasis. The primary objective is event-free survival (any recurrence and/or death). Secondary objectives include rates of ≥Grade 2 toxicity. 4-D CT image guided SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) was delivered to all patients. Patients randomized to I-SABR received additional concurrent Nivolumab (240 mg, every two weeks for total of 7 doses or 480 mg every four weeks for total of 4 doses). 140 patients are anticipated to enroll. We report here interim analysis of toxicity. Results: 92 patients (median age: 72, range: 57 to 90) were enrolled and randomized (47 to SABR; 45 to I-SABR). With median follow up of 14.5 months (range 2 to 28 months), there were no treatment-related grade 4/5 adverse events. For the I-SABR arm, there was one case of possible related grade 3 dyspnea, skin rash and 2 cases of probable grade 3 fatigue. There were possible/probable treatment related 2 cases of grade 2 pneumonitis, fatigue, pruritus and 1 case of grade 2 hyperthyroidism and arthralgia. No patients discontinued treatment due to adverse effects. For the SABR arm, there were possible treatment related 1 case of grade 2 fatigue and pneumonitis. All symptoms resolved with or without treatment. Conclusions: Combined Nivolumab immunotherapy and SABR (I-SABR) appear to be well-tolerated in this fragile patient population with no grade 4/5 toxicity. All toxicities were tolerable and resolved. The major barrier for patient enrollment and/or randomization is patient’s perception of potential toxicities and additional clinic visits. Continued enrollment and additional follow up are needed to validate these findings. Clinical trial information: NCT03110978.


1999 ◽  
Vol 17 (2) ◽  
pp. 517-517 ◽  
Author(s):  
Michael J. Zelefsky ◽  
Kent E. Wallner ◽  
C. Clifton Ling ◽  
Adam Raben ◽  
Timothy Hollister ◽  
...  

PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival outcome and incidence of late toxicity for patients with early-stage prostate cancer treated at a single institution with either three-dimensional conformal radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine-125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer, defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score of 6 or lower, and stage less than or equal to T2b, were selected for this analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and 145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64 years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median implant dose was 150 Gy. Prostate-specific antigen relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up times for the 3D-CRT and TPI groups were 36 and 24 months, respectively. RESULTS: Eleven patients (8%) in the 3D-CRT group and 12 patients (8%) in the TPI group developed a biochemical relapse. The 5-year PSA relapse-free survival rates for the 3D-CRT and the TPI groups were 88% and 82%, respectively (P = .09). Protracted grade 2 urinary symptoms were more prevalent among patients treated with TPI compared with 3D-CRT. Grade 2 urinary toxicity, which was manifest after the implant and persisted for more than 1 year after this procedure, was observed in 45 patients (31%) in the TPI group. In these 45 patients, the median duration of grade 2 urinary symptoms was 23 months (range, 12 to 70 months). On the other hand, acute grade 2 urinary symptoms resolved within 4 to 6 weeks after completion of 3D-CRT, and the 5-year actuarial likelihood of late grade 2 urinary toxicity for the 3D-CRT group was only 8%. The 5-year actuarial likelihood of developing a urethral stricture (grade 3 urinary toxicity) for the 3D-CRT and TPI groups was 2% and 12%, respectively (P < .0002). Of 45 patients who developed grade 2 or higher urinary toxicity after TPI, the likelihood of resolution or significant improvement of these symptoms at 36 months from onset was 59%. The 5-year likelihood of grade 2 late rectal toxicity for the 3D-CRT and TPI patients was similar (6% and 11%, respectively; P = .97). No patient in either group developed grade 3 or higher late rectal toxicity. The 5-year likelihood of posttreatment erectile dysfunction among patients who were initially potent before therapy was 43% for the 3D-CRT group and 53% for the TPI group (P = .52). CONCLUSION: Both 3D-CRT and TPI are associated with an excellent PSA outcome for patients with early-stage prostate cancer. Urinary toxicities are more prevalent for the TPI group and subsequently resolve or improve in most patients. In addition to evaluating long-term follow-up, future comparisons will require detailed quality-of-life assessments to further determine the impact of these toxicities on the overall well-being and quality of life of the individual patient.


2021 ◽  
Author(s):  
Michael Mayinger ◽  
Roman Ludwig ◽  
Sebastian M. Christ ◽  
Riccardo Dal Bello ◽  
Alex Ryu ◽  
...  

Abstract Purpose: To assess the effects of daily adaptive MR-guided replanning in stereotactic body radiation therapy (SBRT) of liver metastases based on a patient individual longitudinal dosimetric analysis. Methods: Fifteen patients assigned to SBRT for oligometastatic liver metastases underwent daily MR-guided target localization and on-table treatment plan re-optimization. Gross tumor volume (GTV) and organs at risk (OARs) were adapted to the anatomy-of-the-day. A reoptimized plan (RP) and a rigidly shifted baseline plan (sBP) without re-optimization were generated for each fraction. After extraction of DVH parameters for GTV, planning target volume (PTV), and OARs (stomach, duodenum, bowel, liver, heart) plans were compared on a per-patient basis.Results: Median pre-treatment GTV and PTV were 14.9 cc (interquartile range (IQR): 7.7 – 32.85) and 62.7 cc (IQR: 42.4 – 105.5) respectively. SBRT with RP improved PTV coverage (V100%) for 47/75 of the fractions and reduced doses to the most proximal OARs (D1cc, Dmean) in 33/75 fractions compared to sBP. RP significantly improved PTV coverage (V100%) for metastases within close proximity to an OAR by 4.0 % (≤ 0.2 cm distance; n = 7; p = 0.01), but only by 0.2% for metastases farther away from OAR (> 2 cm distance; n = 7; p = 0.37). No acute grade 3 treatment-related toxicities were observed.Conclusion: MR-guided online replanning SBRT improved target coverage and OAR sparing for liver metastases with a distance of more < 2 cm to the nearest luminal OAR. Only marginal improvements in target coverage were observed for target distant to critical OARs, indicating that these patients do not benefit from daily adaptive replanning.


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