Relative Biological Effectiveness Values of Spot-scanning Proton Beam Therapy at Shonan Kamakura General Hospital.

BACKGROUND/AIM: This study aimed to confirm the relative biological effectiveness (RBE) values of the proton beam therapy (PBT) system installed in Shonan Kamakura General Hospital. MATERIALS AND METHODS: Clonogenic cell-survival assays were performed with a human salivary gland (HSG) cell line, a human tongue squamous-cell carcinoma cell line (SAS), and a human osteosarcoma cell line (MG-63). Cells were irradiated with proton beams and X-rays with different doses (1.8, 3.6, 5.5, and 7.3 Gy for proton beams, and 2, 4, 6, and 8 Gy for X-rays). Proton beam irradiation used spot-scanning methods and three different depths (at the proximal, center, and distal sides of the spread-out Bragg peak). RBE values were obtained from a comparison of the dose that resulted in a surviving fraction of 10% (D10). RESULTS: D10 of proton beams at the proximal, center, and distal sides and X-rays in HSG were 4.71, 4.71, 4.51, and 5.25 Gy, respectively; those in SAS were 5.08, 5.04, 5.01, and 5.59 Gy, respectively; and those in MG-63 were 5.36, 5.42, 5.12, and 6.06 Gy, respectively. The RBE10 values at the proximal, center, and distal sides in HSG were 1.11, 1.11, and 1.16 respectively; those in SAS were 1.10, 1.11, and 1.12, respectively; and those in MG-63 were 1.13, 1.12, and 1.18, respectively. CONCLUSION: RBE10 values of 1.10-1.18 were confirmed by in vitro experiments using the PBT system. These results are considered acceptable for clinical use in terms of therapeutic efficacy and safety.

Computed tomography-guided partial-breast brachytherapy using implanted catheters as fiducial markers versus co-registered magnetic resonance imaging.

PURPOSE: Partial-breast irradiation (PBI) needs accurate cavity delineation with computed tomography (CT). In perioperative PBI using multicatheter-interstitial brachytherapy (MIB), catheters implanted during surgery were enabled as fiducial markers. Magnetic resonance imaging (MRI) can also assist delineation with CT. METHODS: Patients receiving MIB-PBI were analyzed. Cavity visualization scores (CVSs) were categorized with CT. With catheter-based delineation (CBD), the relationship between cavity boundaries and catheters were used to contour the tumor bed. Co-registered MRI delineation (CMD) was also performed. The correlation between cavity volume and the excised tissue weight was compared for the two techniques. RESULTS: The association between CVS and preoperative characteristics in 159 patients showed mammographic breast density (MBD) remained correlated to CVS on multiple regression analyses; CVS = 5.2-0.61 x MBD (p < 0.0001). In 43 patients, the cavity volumes determined with CBD vs CMD were 12.8 ±â€¯6.4 cm3 vs 16.1 ±â€¯12.4 cm3 (p < 0.0001), and their plots with excised weights showed the best fitting lines were 0.29 vs 0.48 (p < 0.0001), respectively. The correlation coefficients for CBD vs CMD were 0.65 vs 0.55 (p = 0.20) in low (CVS 1-3, n = 27) and 0.72 vs 0.58 (p = 0.36) in high visualized cavities (CVS 4-5, n = 16), respectively. CONCLUSIONS: The use of implanted catheters as fiducial markers was associated with smaller cavities and greater correlations with the excised tissue weights than co-registration with MRI. This might be a useful technique, especially for patients with dense breasts on mammography.

Predicting adherence of dose-volume constraints for personalized partial-breast irradiation technique.

PURPOSE: Multicatheter interstitial brachytherapy (MIB) and external-beam (EB) radiotherapy are established partial-breast irradiation (PBI) techniques. Although EB-PBI is widely available, it requires extra irradiated margins for target uncertainties. We examined the impact of EB-PBI on dose-volume constraints as compared to MIB-PBI. METHODS AND MATERIALS: Among 653 patients receiving MIB-PBI between October 2008 and April 2020, consequent 159 patients after September 2018 were examined. Clinical target volume (CTV) included the lumpectomy cavity plus 1.0 cm. Planning target volume (PTV) for EB-PBI was defined as CTV with 1.0-cm expansion. Because the ratio of PTV to breast volume (RPB) was related to cosmesis, <25% of RPB was defined as suitable for the ipsilateral breast constraints. Preoperative breast size was classified as very small (<350 cm3), small (350-699 cm3), and medium or large (≥700 cm3). According to each category, the dose-volume constraints of the organs at risk were compared between the two PBI techniques. RESULTS: Patients including 84 very small, 59 small, and 16 moderate to large breasts were examined. Although RPB was suitable in all patients receiving MIB-PBI, it was achieved in 74 patients (46.5%) receiving EB-PBI (p < 0.0001). The suitable RPB in patients with very small, small, and moderate to large breast was 32.1%, 55.9%, and 100%, respectively (p < 0.0001). Normal-tissue constraints for the other organs could be satisfied in patients with moderate to large breasts. CONCLUSION: Although EB-PBI may be an appropriate option for patients with moderate to large breasts, MIB-PBI could still be a crucial technique, especially for patients with small breasts.

Imaging Cherenkov emission for quality assurance of high-dose-rate brachytherapy.

With advances in high-dose-rate (HDR) brachytherapy, the importance of quality assurance (QA) is increasing to ensure safe delivery of the treatment by measuring dose distribution and positioning the source with much closer intervals for highly active sources. However, conventional QA is time-consuming, involving the use of several different measurement tools. Here, we developed simple QA method for HDR brachytherapy based on the imaging of Cherenkov emission and evaluated its performance. Light emission from pure water irradiated by an 192Ir γ-ray source was captured using a charge-coupled device camera. Monte Carlo calculations showed that the observed light was primarily Cherenkov emissions produced by Compton-scattered electrons from the γ-rays. The uncorrected Cherenkov light distribution, which was 5% on average except near the source (within 7 mm from the centre), agreed with the dose distribution calculated using the treatment planning system. The accuracy was attributed to isotropic radiation and short-range Compton electrons. The source positional interval, as measured from the light images, was comparable to the expected intervals, yielding spatial resolution similar to that permitted by conventional film measurements. The method should be highly suitable for quick and easy QA investigations of HDR brachytherapy as it allows simultaneous measurements of dose distribution, source strength, and source position using a single image.

Efficacy of Single-Plane Implant Technique in Partial Breast Brachytherapy in Small-Breasted Patients.

PURPOSE: Partial-breast irradiation (PBI) using multicatheter-interstitial brachytherapy (MIB) has been supported by some randomized trials to date. However, it remains underused in Asian countries because of the population's typically smaller breasts. Single-plane implantation has been recommended in these individuals, but limited data on the clinical efficacy exist. We performed a retrospective chart review to compare the tumor control and long-term cosmesis in patients treated with the single-plane implant technique. METHODS AND MATERIALS: Patients receiving MIB-PBI between October 2008 and December 2018 were evaluated. PBI was initiated on the same day of the surgery via an intraoperative catheter implant, delivering 32 Gy by 8 fractions. Tumor control based on the rate of freedom from ipsilateral tumor recurrence (IBTR), disease-free survival, and long-term cosmesis using the Harvard scale was evaluated to compare between the single- and double-/triple-plane implant techniques. RESULTS: Five hundred sixteen patients with 526 lesions received MIB-PBI with a median follow-up of 53.1 months. Patients treated by single- and double- or triple-plane implant numbered 288 (54.8%) and 238 (45.2%), respectively. The 4-year probabilities of IBTR-free survival and disease-free survival were 97.5% and 96.5% in single-plane implant and 98.6% (P = .42) and 98.0% (P = .18) in double- or triple-plane implant MIB-PBI, respectively. Although young age (P < .05) and positive surgical margins (P < .01) were selected as independent risk factors for IBTR, single-plane implantation was not recognized as a risk factor of IBTR. Sixty-one of 69 single-plane implant patients (88.4%) and 84 of 92 double-/triple-plane implant patients (91.3%) reported excellent to good cosmetic results (P = .73). CONCLUSIONS: Although this was a retrospective study from a single institution and cosmesis was evaluated using a subjective method, this is the first report to validate single-plane implant MIB-PBI for use in small-breasted patients. Further multicenter research is required.

Moving incision for covert breast-conserving surgery may prevent early wound complications in brachytherapy-based partial-breast irradiation.

PURPOSE: Brachytherapy-based partial-breast irradiation (PBI) is a treatment option for breast-conserving therapy. Although intraoperative catheter implantation has been introduced, early wound complications are a concern. Covert operations with a moving incision are widely performed to hide surgical scars and may reduce the incision-site radiation dose. This study aimed to compare complication rates for moving incision and conventional incision in covert breast-conserving surgery. METHODS AND MATERIALS: Between October 2008 and December 2018, the medical records of all patients who underwent PBI using multicatheter interstitial brachytherapy after breast-conserving surgery were examined. Since July 2016, to hide the scar, we have performed a moving incision from above the tumor to an invisible site at our institution. The planning target volume included 1.0-1.5 cm of tissue surrounding the surgical cavity. High-dose-rate interstitial brachytherapy with a dose of 32 Gy in eight fractions was performed. The cumulative incidences of surgical site infections and symptomatic seromas ≤90 days were analyzed. RESULTS: The study included 516 consecutive patients with 526 lesions. Overall, 40 (7.6%) early wound complications were observed, in which 4 (2.6%) involved 152 moving incisions and 36 (9.6%) involved 374 conventional incisions (p = 0.01). On univariate analysis, age, tumor diameter, re-excision, planning target volume, numbers of catheters and planes, and incision type were risk factors for complications. On multivariate analysis, only incision type was a risk factor. Moving incision reduced the early complication rate by 75% (p = 0.01). CONCLUSION: Moving incision in covert breast-conserving surgery reduced the risk of early wound complications.

Catheter-based delineation of lumpectomy cavity for accurate target definition in partial-breast irradiation with multicatheter interstitial brachytherapy.

PURPOSE: In partial-breast irradiation (PBI), accurate lumpectomy cavity (LC) delineation is critical. Seroma-based delineation (SBD) using computed tomography (CT) with clips remains uncertain, causing an expansion of the LC and planning target volume (PTV). In catheter-based delineation (CBD), the implanted catheters were used as reference markers for LC delineation in multicatheter interstitial brachytherapy (MIB). MATERIAL AND METHODS: Between October 2008 and October 2018, 513 patients who underwent MIB-PBI were examined. In CBD, anatomical relations of LC to catheters were recorded. In randomly selected 22 CBD cases, the LC volume and PTV were retrospectively recontoured on SBD, and the relationship between the contribution of CBD and cavity visuality was evaluated. The LC volume and PTV before and after the introduction of CBD were compared. RESULTS: The mean LC volumes based on SBD and CBD were 19.1 cm3 and 14.1 cm3, respectively (p < 0.001). The mean PTVs based on SBD and CBD were 47.9 cm3 and 35.7 cm3, respectively (p < 0.0001). More reductions in the LC volume (5.1 cm3) (p < 0.05) and PTV (7.7 cm3) (p = 0.13) were observed in the poorly visible LC than in the visible LC. The LC volume and PTV before the introduction of CBD (n = 411) were compared with those after introduction (n = 102). Significant reductions were observed in the LC volume (5.9 cm3) (p < 0.0001) after the introduction of CBD; moreover, PTV tended to be reduced (3.9 cm3) (p = 0.17). CONCLUSIONS: CBD may help to establish the standardized procedure for MIB-PBI and prevent unnecessary radiation exposure to the normal breast tissue.

Automated source tracking with a pinhole imaging system during high-dose-rate brachytherapy treatment.

The transportation accuracy of sealed radioisotope sources influences the therapeutic effect of high-dose-rate (HDR) brachytherapy. We have developed a pinhole imaging system for tracking an Ir-192 radiation source during HDR brachytherapy treatment. Our system consists of a dual-pinhole collimator, a scintillator, and a charge-coupled device (CCD) camera. We acquired stereo-shifted images to infer the source position in three dimensions using a dual pinhole collimator with 1.0 mm diameter pinholes. The CCD camera captured consecutive images of scintillation light that corresponds to the source positions every 2 s. The system automatically tracks scintillation light points using template-matching technique and measured the source positions therefrom. By integrating a series of CCD images, we could infer the source dwell time from the pixel values in the integrated image. We investigated the tracking accuracy of our system in monitoring simulated brachytherapy as it would be performed for cervical cancer by using water as a stand-in for human tissue. Ir-192 pellet was moved through a water tank using tandem and ovoid applicators. The CCD camera captured clear images of the scintillation light produced by the underwater Ir-192 source in conditions equivalent to common clinical situations. The differences between the measured and the reference 3D source positions and dwell times were 1.5 ± 0.7 mm and 0.8 ± 0.4 s, respectively. This system has the potential to track in vivo Ir-192 source in real time and may prove a useful tool for quality assurance during HDR brachytherapy treatments in clinical settings.

Validating the efficacy of single-stage breast-conserving therapy using multicatheter partial-breast brachytherapy based on updated ASTRO guidelines.

Based on the accumulating evidence for equivalent results of partial-breast irradiation (PBI) and whole-breast irradiation (WBI) in breast-conserving therapy (BCT), the American Society for Radiation Oncology (ASTRO) updated the consensus statement (CS) to expand the range of potential candidates for PBI outside clinical trials. Of the various techniques, PBI using multicatheter interstitial brachytherapy (MCB) is the oldest and has long-term data. In this study, the efficacy of single-stage BCT using MCB-PBI achieved by an intraoperative catheter placement was validated on updated ASTRO guidelines. We retrospectively examined patients undergoing BCT using MCB-PBI or WBI. The updated CS distinguished patients aged 40-49 years with ER+, tumor ≤2 cm, and margin ≥2 mm from unsuitable patients in the previous CS. We compared the ipsilateral breast tumor recurrence (IBTR) rate in MCB-PBI with that in WBI patients with suitable or cautionary (S/C) categories on the updated CS. Between November 2007 and September 2017, 641 patients with 647 lesions underwent BCT (MCB-PBI, 407; WBI, 240). At the median follow-up time of 54.4 months, we observed 8 (1.97%; 95% CI: 0.62-3.31%) and 7 (2.92%; 95% CI: 0.79-5.05%) IBTRs, respectively. Updating the CS increased the S/C patients receiving MCB-PBI from 232 patients (57.0%) to 319 (78.4%). Comparison of clinical outcomes at the 12-month minimum follow-up between 291 MCB-PBI and 103 WBI in S/C patients showed no significant differences in the 4-year rate of IBTR-free (100% vs 98.9%; P = 0.29) and disease-free survival (98.7% vs 95.5%; P = 0.24). Overall, single-stage BCT using MCB-PBI offered similar tumor control rates, compared with WBI, on the updated ASTRO CS.

Efficacy of single-stage breast-conserving treatment using multicatheter partial breast brachytherapy evaluated by GEC-ESTRO phase 3 trial.

PURPOSE: The GEC-ESTRO has reported the equivalent outcomes of partial breast irradiation (PBI) using multicatheter interstitial brachytherapy (MCB) to whole breast irradiation (WBI) in breast-conserving therapy (BCT). We performed single-stage BCT with partial breast brachytherapy by intraoperative catheter placement. After the categorization of patients into inclusion and exclusion criteria on this trial, our databases were evaluated in order to translate it to Japanese patients. MATERIAL AND METHODS: Patients undergoing BCT were retrospectively examined between November 2007 and December 2015. The technique is an open-cavity implant with a dose of 32 Gy in 8 fractions. The 4-year clinical outcomes of MCB-PBI were evaluated in the 2 distinct categories, and the comparison of the outcomes of MCB-PBI with WBI was performed in patients with unfavorable features. RESULTS: Of a total of 501 lesions undergoing BCT, 301 lesions were treated with MCB-PBI and 200 lesions with WBI. At the median follow-up time of 52 months, the 4-year rate of ipsilateral breast tumor recurrence (IBTR)-free, disease-free (DFS), and overall survival (OS) in patients with MCB-PBI and WBI were 98.9% vs. 98.0% (p = 0.56), 97.0% vs. 95.3% (p = 0.78), and 99.6% vs. 98.2% (p = 0.38), respectively. Although in exclusion cohort treated with MCB-PBI, IBTR-free, and disease-free survival were significantly worse than in inclusion cohort, non-significantly worse outcomes was demonstrated than in exclusion cohort with WBI; IBTR-free survival (95.0% vs. 97.2%, p = 0.24), and disease-free survival (95.0% vs. 95.8%, p = 0.31). CONCLUSIONS: Single-stage BCT using MCB-PBI offered similar tumor control rates compering to WBI. However, further research is needed to define the benefit for patients with an exclusion criteria.

Impact of young age on local control after partial breast irradiation in Japanese patients with early stage breast cancer.

BACKGROUND: Partial breast irradiation (PBI) is an alternative to whole breast irradiation (WBI) for breast-conserving therapy (BCT). A randomised phase 3 trial demonstrated that PBI using multicatheter brachytherapy had an equivalent rate of local recurrence, disease-free survival, and overall survival as compared to WBI. However, limited data are available on PBI efficacy for young patients with breast cancer. METHODS: We evaluated consecutive patients with Tis-2 (≤ 3 cm) N0-1 breast cancer who underwent BCT. For PBI, patients received radiotherapy using multicatheter brachytherapy in an accelerated manner with a dose of 32 Gy in eight fractions over 5-6 days. For WBI, patients received an external beam radiation therapy that was applied to the entire breast with a total dose of 50 Gy in fractions of 2 Gy for 5 weeks. Two hundred seventy-four patients with 278 lesions received PBI; 190 patients with 193 lesions received WBI. RESULTS: Patients aged <50 years including 98 women with 99 lesions receiving PBI and 85 women with 85 lesions receiving WBI were selected. Ipsilateral breast tumor recurrence rate was 3.0 and 2.4 % by PBI and WBI, respectively (P = 0.99). There was no significant difference in 4-year probability of disease-free survival (97.6 and 91.4 % for PBI and WBI, respectively; P = 0.87). CONCLUSIONS: This is the first report of PBI efficacy in young patients in Asia. Although it is a nonrandomized retrospective chart review of a small cohort of patients with a relatively short follow-up period, PBI may be a better option than WBI following BCS in some young patients with breast cancer.

Comparison of radiation dose to the left anterior descending artery by whole and partial breast irradiation in breast cancer patients.

PURPOSE: Breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard of care for breast cancer patients. However, there is a risk of coronary events with WBI therapy. In this study, we compared the radiation dose in the left anterior descending artery (LAD) in patients receiving partial breast irradiation (PBI) with WBI. MATERIAL AND METHODS: We evaluated consecutive patients who underwent adjuvant radiotherapy after BCS between October 2008 and July 2014. Whole breast irradiation patients received 50 Gy in fractions of 2 Gy to the entire breast. Partial breast irradiation was performed using multicatheter brachytherapy at a dose of 32 Gy in eight fractions. The mean and maximal cumulative doses to LAD were calculated. The radiotherapeutic biologically effective dose of PBI was adjusted to WBI, and radiation techniques were compared. RESULTS: Of 379 consecutive patients with 383 lesions receiving radiotherapy (151 WBI and 232 PBI lesions), 82 WBI and 100 PBI patients were analyzed. In WBI patients, the mean and maximal cumulative doses for left-sided breast cancer (2.13 ± 0.11 and 8.19 ± 1.21 Gy, respectively) were significantly higher than those for right-sided (0.37 ± 0.02 and 0.56 ± 0.03 Gy, respectively; p < 0.0001). In PBI patients with left-sided breast cancer, the doses for tumors in inner quadrants or central location (2.54 ± 0.21 and 4.43 ± 0.38 Gy, respectively) were significantly elevated compared to outer quadrants (1.02 ± 0.17 and 2.10 ± 0.29 Gy, respectively; p < 0.0001). After the adjustment, the doses in PBI patients were significantly reduced in patients with tumors only in outer quadrants (1.12 ± 0.20 and 2.43 ± 0.37 Gy, respectively; p = 0.0001). CONCLUSIONS: Tumor control and dose to LAD should be considered during treatment since PBI may reduce the risk of coronary artery disease especially in patients with lateral tumors in the left breast.

[Influence of position of ionization chamber and leaf-end on verification value in IMRT verification for prostate cancer].

In IMRT for prostate cancer, MU verification is performed by the actual measurement. We have experienced a remarkable improvement in results, once succeeding in finding out the more suitable and optimal evaluation dose point in some cases even though the deviation between a designed MU score and our actual record gained at the iso-center was more than 3%. In this study, we tried to demonstrate how much influence would be given to the point dose verification by the 3D arrangement between an ion chamber and tips of the MLC. The five cases in which the bias between each actual datum and planed MU score showed that about 3% were picked up and through these MLC configurations, 8 leaf-ends around the chamber were highlighted as the influential ones. After each distance from 4 pairs, a total of 8 leaves to the axis (the mid-line) of our ion chamber were mapped. The indexes (PlanLeafScores) were computed through these distances and segmental MU scores. The ratio of these scores and results obtained at the 12 sites within 1 cm from the iso-center were carried out by single regression analysis. In all cases the ratios of planed MU values to the actual ones tended to go down in inverse proportion to the increase in PlanLeafScores (r<-0.77, p<0.002). As the dimensional arrangement between the ion chamber and the edges of the MLC were thought to determine the result of the verification. PlanLeafScores will enable us to determine the optimal evaluation of the dose point.