Naoko Takeda

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.

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.

Efficacy of reduced dose of pegfilgrastim in Japanese breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide therapy

Background This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Methods Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. Results From November 2013 to March 2016, 97 patients with stage I–III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n = 41; epirubicin and cyclophosphamide group, n = 56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P = 0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P = 0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P = 0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P = 0.16). Conclusions Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients.

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

Abstract 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.

Abstract P3-12-19: Impact of young age on local control after partial-breast irradiation in early-stage breast cancer

Background: Although the rate of breast-conserving surgery (BCS) increased, the receipt of adjuvant radiotherapy after BCS decreased especially for young patients. The long-term daily visit to radiation facilities must be the most relevant barriers to receiving radiation therapy. The use of partial-breast irradiation (PBI) is considered an alternative option. However, there are limited data to be seen how safe PBI is as an option of adjuvant radiation therapy in young patients compared with whole-breast irradiation (WBI). In this report, we reviewed our single-institution experience with PBI compared with WBI in young breast cancer patients. Methods: We evaluated 443 consecutive patients with T≤3-cm N0–1 breast cancer who underwent breast-conserving therapy (BCT) between November 2007 and May 2015. 268 patients received PBI using interstitial multicatheter brachytherapy. The interstitial brachytherapy was performed in an accelerated fashion with a dose of 32 Gy in eight fractions over 5-6 days. 185 patients received WBI with a dose of 50 Gy in fractions of 2 Gy. Patients with risk factors such as positive margins and young age received a subsequent 10 Gy boost to the tumor bed, and the regional nodal irradiation was added in patients with ≥ 4 positive nodes. Patients who underwent neoadjuvant chemotherapy were excluded from the analysis. Our primary objective was to assess outcome rates of ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS), and overall survival (OS), and compare the patterns of treatment failures between the cohorts. Results: Patients aged Conclusions: We observed equivalent IBTR rates between PBI and WBI cohorts in young breast cancer patients. If there are no differences in survival between the two radiotherapy regimens, PBI may be a better option than WBI after BCS in such a population. To our knowledge, this is the first report describing that the efficacy of PBI after BCS is comparable with WBI in young breast cancer patients in Asia. However, our data are limited by our short median follow-up with small number of patients. The application of PBI should still be carefully considered until mature Phase III trial data are available. Citation Format: Sato K, Mizuno Y, Fuchikami H, Takeda N, Kato M. Impact of young age on local control after partial-breast irradiation in early-stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-19.

Abstract P1-15-22: Comparison of cardiac dose between accelerated partial-breast irradiation and whole-breast irradiation in breast cancer patients

[Background] Breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI) has now become the standard treatment for early-stage breast cancer. However, WBI is associated with an increased risk of coronary events, especially in patients with preexisting cardiac risk factors. In radiotherapy (RT), the highest dose is likely delivered to the left anterior descending artery (LAD), which is the typical site for ischemic heart disease. We initiated a prospective, observational study on accelerated partial-breast irradiation (APBI) using multicatheter brachytherapy after BCS. In this study, we compared the radiation dose to LAD between patients receiving APBI and those receiving WBI. [Methods] The study participants included a cohort selected from consecutive patients who underwent BCS followed by RT since November 2007. In the WBI group, patients received 50 Gy in fractions of 2 Gy to the entire breast. APBI was initiated on the day of primary surgery in the form of multicatheter brachytherapy, at a dose of 32 Gy in 8 fractions. The planned target volume was defined as the estimated tumor volume plus a 20-mm margin. Dose distribution analysis was performed on the basis of postoperative CT using dose–volume histograms. LAD was outlined from its origin to each visible end using the planning CT images. First, the mean and maximal total doses to LAD were calculated. Second, the radiotherapeutic biologically effective dose of APBI was adjusted to that of WBI for comparisons between the two different RT schedules. [Results] Of the 359 consecutive patients who underwent BCS followed by RT, we retrospectively reviewed 182 patients for radiation dose to LAD. The 82 patients receiving WBI were randomly selected; 42 patients had right breast cancer and 40 had left breast cancer. We selected 100 consecutive APBI patients with left breast cancer treated between September 2009 and December 2013 because the LAD dose is considered to be virtually zero in right breast cancer patients. In the WBI patients, the mean and maximal total LAD dose were significantly higher in left breast cancer patients (2.1 ± and 8.2 ± 1.2 Gy, respectively) than in right breast cancer patients (0.4 ± 0.02 and 0.6 ± 0.03 Gy, respectively; p [Conclusions] Our results show that APBI may decrease the risk of coronary artery disease, especially in patients with outer quadrant tumors in the left breast. Although APBI should be carefully interpreted until mature phase-III data are available, the risk of ipsilateral breast tumor recurrences and LAD dose must be considered together while administering RT after BCS. Citation Format: Kazuhiko Sato, Yoshio Mizuno, Hiromi Fuchikami, Naoko Takeda, Takahiro Shimo, Jun Kubota, Yuko Inoue, Hiroshi Seto, Masahiro Kato. Comparison of cardiac dose between accelerated partial-breast irradiation and whole-breast irradiation in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-22.