Reducing variability among treatment machines using knowledge‐based planning for head and neck, pancreatic, and rectal cancer

PURPOSE: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans. METHODS: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types. RESULTS: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy. CONCLUSIONS: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine

Low incidence of late recurrence in patients with intermediate-risk prostate cancer treated by intensity-modulated radiation therapy plus short-term androgen deprivation therapy

Objectives: This study evaluated the long-term outcomes of intensity-modulated radiation therapy (IMRT) combined with short-term neoadjuvant androgen deprivation therapy (ADT) in patients with intermediate-risk (IR) prostate cancer (PCa). Materials and methods: Patients with IR PCa treated with IMRT at our institution between September 2000 and November 2010 were analyzed retrospectively. The treatment consisted of IMRT (70–78 Gy in 35–39 fractions) combined with 6 months of neoadjuvant ADT. Salvage ADT was initiated when the prostate-specific antigen level was > 4.0 ng/mL Results: In total, 106 consecutive patients with IR PCa (median age: 70 years old) were analyzed. The median follow-up period was 8.0 years. The overall survival, PCa-specific survival, biochemical failure, and clinical failure rates were 99.0%, 100.0%, 6.8%, and 1.9% at 5 years and 89.1%, 100.0%, 11.3%, and 2.9% at 10 years, respectively. Late recurrence (> 5 years) was observed in three cases (2.8%). The cumulative incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicities (grade 2/3) were 10.5% and 5.8% at 5 years, and 14.7% and 5.8% at 10 years, respectively. No patient developed grade 4/5 GU toxicities or grade 3–5 GI toxicities. Conclusion: IMRT at a dose up to 78 Gy combined with short-term neoadjuvant ADT resulted in excellent long-term disease-free outcomes with acceptable morbidities among patients with IR PCa. In addition, the incidence of late recurrence was very low. Further investigation is warranted to confirm our findings

Clinical significance of IDC-P as predictive factor after intensity-modulated radiation therapy

The clinical significance of intraductal carcinoma of the prostate (IDC-P) in men with nonmetastatic prostate cancer (PCa) treated with high-dose external-beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC-P in men who received intensity-modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high-risk (H-R) and very high–risk (VH-R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re-reviewed biopsy cores for the presence of IDC-P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6-month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H-R and VH-R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow-up period was 8.4 years. The 10-year PCa-specific survival, biochemical failure (BF), clinical failure, and castration-resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC-P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC-P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC-P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC-P was correlated with a significantly higher incidence of disease progression in men with H-R and VH-R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC-P as an independent predictive factor for survival outcomes

限局性前立腺がんに対する3週間での高度寡分割強度変調放射線治療のパイロット試験

京都大学0048新制・課程博士博士(医学)甲第21653号医博第4459号新制||医||1035(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 鈴木 実, 教授 富樫 かおり, 教授 森田 智視学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Highly hypofractionated intensity-modulated radiation therapy for nonmetastatic prostate cancer with a simultaneous integrated boost to intraprostatic lesions: a planning study

PURPOSE: The purpose of this planning study was to develop an acceptable technique for highly hypofractionated intensity-modulated radiation therapy using simultaneous integrated boost technique (SIB-hHF-RT) for nonmetastatic National Comprehensive Cancer Network high-risk prostate cancer. MATERIALS AND METHODS: We created SIB-hHF-RT plans for 14 nonmetastatic prostate cancer patients with MRI-detectable intraprostatic lesions (IPLs) and without intestines locating close to the seminal vesicle and prostate. We prescribed 57 Gy for IPLs and 54 Gy for the remainder of planning target volume (PTV) in 15 fractions. The IPLs were contoured based on magnetic resonance imaging, and PTV was generated by adding 6-8-mm margins to the clinical target volume. For the dose-volume constraints of organs at risk (OARs), the same constraints as 54 Gy plans were used so as not to increase the toxicity. RESULTS: All created plans fulfilled the dose-volume constraints of all targets and OARs. The median estimated beam-on time was 108.5 s. For patient-specific quality assurance, the global gamma passing rates (3%/2 mm) with 10% dose threshold criteria were greater than 93% in all cases and greater than 95% in 11 cases. CONCLUSION: SIB-hHF-RT plans were developed that fulfill the acceptable dose-volume constraints and pass patient-specific quality assurance. We believe these plans can be applied to selected patients with nonmetastatic prostate cancer

Evaluation of different set-up error corrections on dose-volume metrics in prostate IMRT using CBCT images.

We investigated the effect of different set-up error corrections on dose-volume metrics in intensity-modulated radiotherapy (IMRT) for prostate cancer under different planning target volume (PTV) margin settings using cone-beam computed tomography (CBCT) images. A total of 30 consecutive patients who underwent IMRT for prostate cancer were retrospectively analysed, and 7-14 CBCT datasets were acquired per patient. Interfractional variations in dose-volume metrics were evaluated under six different set-up error corrections, including tattoo, bony anatomy, and four different target matching groups. Set-up errors were incorporated into planning the isocenter position, and dose distributions were recalculated on CBCT images. These processes were repeated under two different PTV margin settings. In the on-line bony anatomy matching groups, systematic error (∑) was 0.3 mm, 1.4 mm, and 0.3 mm in the left-right, anterior-posterior (AP), and superior-inferior directions, respectively. ∑ in three successive off-line target matchings was finally comparable with that in the on-line bony anatomy matching in the AP direction. Although doses to the rectum and bladder wall were reduced for a small PTV margin, averaged reductions in the volume receiving 100% of the prescription dose from planning were within 2.5% under all PTV margin settings for all correction groups, with the exception of the tattoo set-up error correction only (≥ 5.0%). Analysis of variance showed no significant difference between on-line bony anatomy matching and target matching. While variations between the planned and delivered doses were smallest when target matching was applied, the use of bony anatomy matching still ensured the planned doses

Monitoring of mechanical errors and their dosimetric impact throughout the course of non-coplanar continuous volumetric-modulated arc therapy

Abstract Background Volumetric-modulated Dynamic WaveArc therapy (VMDWAT) is a non-coplanar continuous volumetric modulated radiation therapy (VMAT) delivery technique. Here, we monitored mechanical errors and their impact on dose distributions in VMDWAT using logfiles throughout the course of treatment. Methods Fifteen patients were enrolled (2 skull base tumor patients and 13 prostate cancer patients). VMDWAT plans were created for the enrolled patients. The prescribed dose for the skull base tumor was set as 54 Gy at 1.8 Gy per fraction, and that for the prostate cancer was set as 72 to 78 Gy at 2 Gy per fraction. We acquired logfiles to monitor mechanical errors and their impact on dose distribution in each fraction. The root mean square error (RMSE) in the multi-leaf collimator (MLC), gantry angle, O-ring angle and monitor unit (MU) were calculated using logfiles throughout the course of VMDWAT for each patient. The dosimetric impact of mechanical errors throughout the course of VMDWAT was verified using a logfile-based dose reconstruction method. Dosimetric errors between the reconstructed plans and the original plans were assessed. Results A total of 517 datasets, including 55 datasets for the 2 skull base tumor patients and 462 datasets for the 13 prostate cancer patients, were acquired. The RMSE values were less than 0.1 mm, 0.2°, 0.1°, and 0.4 MU for MLC position, gantry angle, O-ring angle, and MU, respectively. For the skull base tumors, the absolute mean dosimetric errors and two standard deviations throughout the course of treatment were less than 1.4% and 1.1%, respectively. For prostate cancer, these absolute values were less than 0.3% and 0.5%, respectively. The largest dosimetric error of 2.5% was observed in a skull base tumor patient. The resultant dosimetric error in the accumulated daily delivered dose distribution, in the patient with the largest error, was up to 1.6% for all dose-volumetric parameters relative to the planned dose distribution. Conclusions MLC position, gantry rotation, O-ring rotation and MU were highly accurate and stable throughout the course of treatment. The daily dosimetric errors due to mechanical errors were small. VMDWAT provided high delivery accuracy and stability throughout the course of treatment. Trial registration UMIN000023870. Registered: 1 October 2016

A pilot study of highly hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer

The purpose of this pilot study was to evaluate the feasibility of highly hypofractionated intensity-modulated radiation therapy (IMRT) in 15 fractions over 3 weeks for treating localized prostate cancer based on prostate position-based image-guided radiation therapy. Twenty-five patients with National Comprehensive Cancer Network (NCCN) very low- to unfavorable intermediate-risk prostate cancer were enrolled in this study from April 2014 to September 2015 to receive highly hypofractionated IMRT (without intraprostatic fiducial markers) delivering 54 Gy in 15 fractions over 3 weeks. Patients with intermediate-risk disease underwent neoadjuvant androgen suppression for 4–8 months. Twenty-four patients were treated with highly hypofractionated IMRT, and one was treated with conventionally fractionated IMRT because the dose constraint of the small bowel seemed difficult to achieve during the simulation. Seventeen percent had very low- or low-risk, 42% had favorable intermediate-risk, and 42% had unfavorable intermediate-risk disease according to NCCN guidelines. The median follow-up period was 31 months (range, 24–42 months). No Grade ≥3 acute toxicity was observed, and the incidence rates of Grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. No Grade ≥2 late toxicity was observed. Biochemical relapse was observed in one patient at 15 months, and the biochemical relapse-free survival rate was 95.8% at 2 years. A prostate-specific antigen bounce of ≥0.4 ng/ml was observed in 11 patients (46%). The highly hypofractionated IMRT regimen is feasible in patients with localized prostate cancer and is more convenient than conventionally fractionated schedules for patients and health-care providers

Long-term safety of high-dose whole pelvic IMRT for high-risk localized prostate cancer through 10-year follow-up

[Background] The aim of this study was to evaluate the long-term efficacy and safety of whole pelvic intensity-modulated radiation therapy with a simultaneous-integrated boost (WP-SIB-IMRT) for locally advanced prostate cancer (LAPCa). [Methods] All patients with cT3–4N0M0 prostate cancer treated with WP-SIB-IMRT between February 2006 and September 2009 at our institution were analyzed retrospectively. The prescribed dose was 78 Gy to the prostate and 58.5 Gy to the prophylactic pelvic lymph nodal area in 39 fractions delivered using the simultaneous-integrated boost technique. All patients received short-term neoadjuvant androgen-deprivation therapy alone (median 8.3 months). Propensity-score matching (PSM) analysis was performed to evaluate the additional benefit of prophylactic whole pelvic radiation therapy (WPRT), using the cohort of 203 LAPCa patients treated with prostate-only IMRT (PO-IMRT). [Results] In total, 47 consecutive patients were analyzed. The median estimated risk of pelvic lymph node involvement was 57.5%. The median follow-up period was 10.5 years. The 10 year prostate cancer-specific survival and biochemical failure (BF) rates were 92.2 and 54.8%, respectively. The 10 year cumulative incidence rates of ≥ grade 2 late genitourinary and gastrointestinal toxicities were 21.6 and 17.2%, respectively. From a total of 250 patients, PSM analysis identified 76 patients with similar characteristics, and no significant difference in BF rates was observed between WP-SIB-IMRT and PO-IMRT cohorts (p = 0.261). [Conclusions] WP-SIB-IMRT for LAPCa was safe over long-term observation, although no clear benefit of WPRT was observed among our small and highly selected cohort. Regarding the additional efficacy of WPRT, further investigations are needed