Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Comparison of partial-breast irradiation and intraoperative radiation to whole-breast irradiation in early-stage breast cancer patients: a Kaplan-Meier-derived patient data meta-analysis.

PURPOSE: Partial breast irradiation (PBI) and intraoperative radiation (IORT) represent alternatives to whole breast irradiation (WBI) following breast conserving surgery. However, data is mixed regarding outcomes. We therefore performed a pooled analysis of Kaplan-Meier-derived patient data from randomized trials to evaluate the hypothesis that PBI and IORT have comparable long-term rates of ipsilateral breast tumor recurrence as WBI. METHODS: In February, 2023, PubMed, EMBASE and Cochrane Central were systematically searched for randomized phase 3 trials of early-stage breast cancer patients undergoing breast-conserving surgery with PBI or IORT as compared to WBI. Time-to-event outcomes of interest included ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and distant disease-free survival (DDFS). Statistical analysis was performed with R Statistical Software. RESULTS: Eleven randomized trials comprising 15,460 patients were included; 7,675 (49.6%) patients were treated with standard or moderately hypofractionated WBI, 5,413 (35%) with PBI and 2,372 (15.3%) with IORT. Median follow-up was 9 years. PBI demonstrated comparable IBTR risk compared with WBI (HR 1.20; 95% CI 0.95-1.52; p = 0.12) with no differences in OS (HR 1.02; 95% CI 0.90-1.16; p = 0.70) or DDFS (HR 1.15; 95% CI 0.81-1.64; p = 0.43). In contrast, patients treated with IORT had a higher IBTR risk (HR 1.46; 95% CI 1.23-1.72; p < 0.01) compared with WBI with no difference in OS (HR 0.98; 95% CI 0.84-1.14; p = 0.81) or DDFS (HR 0.91; 95% CI 0.76-1.09; p = 0.31). CONCLUSION: For patients with early-stage breast cancer following breast-conserving surgery, PBI demonstrated no difference in IBTR as compared to WBI while IORT was inferior to WBI with respect to IBTR.

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study).

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

Dose to contralateral breast from whole breast irradiation by automated tangential IMRT planning: comparison of flattening-filter and flattening-filter-free modes.

Background: The most common secondary cancer is contralateral breast (CLB) cancer after whole breast irradiation (WBI). The aim of this study was to quantify the reduction of CLB dose in tangential intensity modulated radiotherapy (t-IMRT) for WBI using flattening-filter-free (FFF) beams. Materials and methods: We generated automated planning of 20 young breast cancer patients with limited user interaction. Dose-volume histograms of the planning target volume (PTV), ipsilateral lung, heart, and CLB were calculated. The dose of PTV, the most medial CLB point, and the CLB point below the nipple was measured using an ionization chamber inserted in a slab phantom. We compared the two t-IMRT plans generated by FFF beams and flattening-filter (FF) beams. Results: All plans were clinically acceptable. There was no difference in the conformal index, the homogeneity for FFF was significantly worse. For the ipsilateral lung, the maximum dose (Dmax) was significantly higher; however, V20 showed a tendency to be lower in the FFF plan. No differences were found in the Dmax and V30 to the heart of the left breast cancer. FF planning showed significantly lower Dmax and mean dose to the CLB. In contrast to the calculation results, the measured dose of the most medial CLB point and the CLB point below the nipple were significantly lower in FFF mode than in FF mode, with mean reductions of 21.1% and 20%, respectively. Conclusions: T-IMRT planning using FFF reduced the measured out-of-field dose of the most medial CLB point and the CLB point below the nipple.

Final analysis of a Multicenter Single-Arm Confirmatory Trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up. METHODS AND MATERIALS: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity. RESULTS: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes. CONCLUSIONS: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery.

Accelerated partial breast irradiation by brachytherapy: present evidence and future developments.

Accelerated partial breast irradiation (APBI) delivers a short course of adjuvant RT after breast conserving surgery to only a limited part of the breast where the tumor was located. This procedure requires expertise, good communication, and close collaboration between specialized surgeons and attending radiation oncologists with adequate intraoperative tumor bed clip marking. However, APBI offers several intrinsic benefits when compared with whole breast irradiation (WBIR) including reduced treatment time (1 versus 4-6 weeks) and better sparing of surrounding healthy tissues. The present publication reviews the APBI level 1-evidence provided with various radiation techniques supplemented by long-term experience obtained from large multi-institutional phase II studies. Additionally, it offers an outlook on recent research with ultra-short or single-fraction APBI courses and new brachytherapy sources. Mature data from three randomized controlled trials (RCTs) clearly prove the noninferiority of APBI with 'only two techniques-1/MIBT (multicatheter interstitial brachytherapy) (two trials) and 2/intensity modulated radiotherapy (one trial)'-in terms of equivalent local control/overall survival to the previous standard 'conventionally fractionated WBIR'. However, MIBT-APBI techniques were superior in both toxicity and patient-reported outcomes (PROs) versus WBIR at long-term follow-up. Currently, in RCT-setting, alternative APBI techniques such as intraoperative electrons, 50-kV x-rays and three-dimensional conformal external beam radiotherapy (3D-CRT) failed to demonstrate noninferiority to conventionally fractionated WBIR. However, 3D-CRT-APBI compared noninferior to hypo-fractionated WBIR in preventing ipsilateral breast tumor recurrence (randomized RAPID-trial) but was associated with a higher rate of late radiation toxicity. Ultimately, MIBT remains the only APBI modality with noninferior survival/superior toxicity/PROs at 10-years and therefore should be prioritized over alternative methods in patients with breast cancer considered at low-risk for local recurrence according to recent international guidelines.

Characterization of irregular electron beam for boost dose after whole breast irradiation.

Irradiating a tumor bed with boost dose after whole breast irradiation helps reducing the probability of local recurrence. However, the success of electron beam treatment with a small area aiming to cover a superficial lesion is a dual challenge as it requires an adequate dosimetry beside a double check for dose coverage with an estimation of various combined uncertainty of tumor location and losing lateral electron equilibrium within small field dimensions. AIM OF WORK: this work aims to measure the electron beam fluence within different field dimensions and the deviation from measurement performed in standard square electron applicator beam flatness and symmetry, then to calculate the average range of the correction factor required to overcome the loss of lateral electron equilibrium. MATERIAL AND METHOD: the electron beam used in this work generated from the linear accelerator model ELEKTA Precise and dosimetry system used were a pair of PTW Pin Point ion chambers for electron beam dosimetry at standard conditions and assessment of beam quality at a reference depth of measurement, with an automatic water phantom, then a Roos ion chamber was used for absolute dose measurement, and PTW 2Darray to investigate the beam fluence of four applicators 6, 10, 14 and 20 cm2 and 4 rectangular cutouts 6 × 14, 8 × 14, 6 × 17 and 8 × 17 cm2, the second part was clinical application which was performed in a precise treatment planning system and examined boost dose after whole breast irradiation. RESULTS: revealed that lower energy (6MeV and 8MeV) showed the loss of lateral electron equilibrium and deviation from measurements of a standard applicator more than the high energy (15 MeV) which indicated that the treatment of superficial dose with 6MeV required higher monitor unit to allow for the loss of lateral electron equilibrium and higher margin as well.

Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis.

PURPOSE: There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer. METHODS: Prospective randomized trials comparing adjuvant PBI to WBI in early-stage invasive breast cancer were identified using PubMed. Odds ratios (OR), 95% confidence intervals and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmesis. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment [EBRT], intraoperative radiation treatment [IORT] or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up, patient and tumor characteristics on results. RESULTS: Nine trials comprising 14514 patients were included. While PBI was associated with increased odds of local recurrence compared to WBI (OR 1.69, P < 0.001), it was associated with reduced odds of death without breast cancer recurrence (OR 0.55, P < 0.001) and with improvement in overall survival (OS) that approached, but did not meet statistical significance (OR 0.84, P = 0.06). Subgroup analysis for PBI modality showed significant differences in the odds of local recurrence, based on method of PBI with EBRT showing the lowest magnitude of inferiority. Nodal involvement was associated with higher local recurrence risk, while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (OR 1.72, P = 0.002). Worse cosmetic outcome with PBI approached statistical significance (OR 1.23, P = 0.06). CONCLUSIONS: Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence. The balance between benefit and risk of PBI appears optimal for women with smaller hormone receptor positive tumors, without nodal involvement and treated with EBRT.

A phase II study investigating the acute toxicity of targeted intraoperative radiotherapy as tumor-bed boost plus whole breast irradiation after breast-conserving surgery in Korean patients.

BACKGROUND: There are concerns regarding local toxicity when IORT is applied in Asian women with a smaller breast volume than that of Western women. Trials are required to develop safety profiles for this technique. The aim of this trial was to evaluate acute toxicity after intra-operative radiotherapy (IORT) with low-energy X-ray plus whole breast irradiation (WBI) in Asian patients with breast cancer. METHODS: This single-arm, single-institute, phase II trial investigated acute toxicity after completion of radiotherapy (targeted IORT followed by WBI) in Korean patients treated with breast-conserving surgery (BCS). In the conventional WBI arm from the TARGIT-A trial, the incidence of acute toxicity within 6 months was 15%. To prove the non-inferiority of the acute toxicity rate, 215 patients were required. This trial is registered with ClinicalTrials.gov (NCT02213991). RESULTS: Two-hundred and fifteen women were enrolled, and 198 underwent IORT. In 33 patients, clinically significant complications during the acute period were noted. The incidence of acute toxicity was 16.7% (95% CI 11.5-21.9%). There were 29 patients with seroma needing more than 3 aspirations, 4 with wound infection, and 2 with skin breakdown. There was no difference in the rate of complications according to the tumor volume or the tumor-breast volume ratio. Advanced age and high BMI were risk factors for acute complications. CONCLUSIONS: Targeted intra-operative radiotherapy using Intrabeam® is a safe procedure for Korean patients with breast cancer with an acceptable toxicity profile in the acute period.

Accelerated partial breast irradiation-Redefining the treatment target for women with early stage breast cancer.

Following breast conserving surgery, the standard of care has been to deliver adjuvant radiation therapy directed to the whole breast (WBI) over a period of 3-7 weeks. Over the past decade, increasing data have supported the concept that treatment to the whole breast may not be required in selected patients, allowing for the emergence of partial breast irradiation (PBI). Multiple randomized trials with 5-10 years of follow-up have been published documenting the safety and efficacy associated with PBI using multiple techniques. Questions that remain to be answered include (a) what is the optimal PBI technique for each clinical scenario, (b) are there additional patients that can be effectively managed with PBI approaches, and (c) are there different techniques/dose schedules that allow for further reduction in treatment duration and/or toxicities? Partial breast irradiation represents a standard approach for appropriately selected patients. PBI provides comparable clinical outcomes to WBI while allowing for a reduction in the duration treatment and the potential for reduced toxicities. Future studies may also help to better define which patients require no radiation, PBI, hypofractionated WBI or conventional WBI, based upon patient, clinical, pathologic features as well as potentially using tumor genetics.

Automated planning of whole breast irradiation using hybrid IMRT improves efficiency and quality.

PURPOSE: To develop an automated workflow for whole breast irradiation treatment planning using hybrid intensity modulated radiation therapy (IMRT) approach and to demonstrate that this workflow can improve planning quality and efficiency when compared to manual planning. METHODS: The auto planning framework was built based on scripting with MIM and Pinnacle systems. MIM workflows were developed to automatically segment normal structures and targets, identify landmarks for beam placement, select beam energies, and set beam configurations. Pinnacle scripts were generated from the MIM workflow to create hybrid IMRT plans automatically. Each hybrid IMRT plan included two prescriptions: a three-dimensional (3D) prescription consisted of two open tangent beams, and an IMRT prescription consisted of two step-and-shoot IMRT beams. The 3D prescription delivered a full prescription dose to the maximum dose point, and the IMRT prescription was optimized to deliver a uniform dose to the entire breast while sparing dose to the normal structures. For 30 patients, the auto plans were compared with clinically accepted manual plans using the paired sample t-test. RESULTS: The auto planning process took approximately 8 min to complete. The mean dice coefficients between auto-segmentation and manual contours were 0.98, 0.94 and 0.88 for the lungs, heart, and PTVeval_Breast, respectively. The MUs of the auto plans was on average 13% higher than that of the manual plans. Auto planning improved plan quality significantly: percentage volume receiving 95% of the prescription dose (V95%) of the PTVeval_Breast increased from 91.5% to 93.2% (P = 0.001), V105% of the PTVeval_Breast decreased from 7.2% to 1.2% (P = 0.013), V20Gy of the ipsilateral lung decreased from 13.1% to 10.4% (P = 0.001) and mean heart dose for left-sided breast patients decreased from 1.2 Gy to 0.9 Gy (P < 0.001). CONCLUSION: An automated treatment planning process can make the planning process efficient with improved plan quality.

Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery.

The aim of this study was to assess tissue computed tomography (CT) number changes and corresponding dosimetric shifts in repeatedly performed simulation CT (re-sim CT) scans after conventionally fractionated irradiation in breast cancer patients. A total of 28 breast cancer patients who underwent breast-conserving surgery were enrolled in this study. All the patients had received 50.4 Gy of conventional whole-breast irradiation (WBI) and underwent re-sim CT scans for tumor bed boost. For evaluation of dosimetric shifts between initial and re-sim CT scans, electron boost plans in the same field size with the same monitor unit with source-to-skin distance of 100 cm were conducted. Dosimetric parameters (V105%, V103%, V100%, V98%, V95%, V90%: Vx% indicates volumes which receive X% of prescribed doses) between initial and re-sim CT scans were compared. The CT number data (CTmean, CTmax, CTmin) of the original and irradiated CT (re-sim CT) scans from each representative structure (lung, rib bone, soft tissue, muscle, etc.) were examined and recruited. CT numbers showed highly variable changes. Soft tissue CTmean and muscle CTmax/CTmin showed statistically and significantly increased values in the CT (re-sim CT) compared to the original CT scans. Rib bone CTmean/CTmin showed statistically and significantly decreased values in the re-sim CT compared to the original CT scans. Other CT number values showed no statistically significant changes. Among the dosimetric parameters, only V105% (p = 0.015, mean = 3.07 cc versus 1.63 cc) and V103% (p = 0.017, mean = 13.8 cc versus 11.9 cc) exhibited statistically increased values in the re-sim CT compared to the original CT scans. CT number changes after conventional WBI were different according to tissue component. For electron boost plans, the implementation of a re-sim CT might be helpfully considered because significant dosimetric factor changes were observed especially in the high-dose areas (hot spots: V105% and V103%).

Breast Cancer Patients' Preferences for Adjuvant Radiotherapy Post Lumpectomy: Whole Breast Irradiation vs. Partial Breast Irradiation-Single Institutional Study.

This study was conducted to elucidate patients with early breast cancer preference for standard whole breast irradiation (WBI) or partial breast irradiation (PBI) following lumpectomy, as well as identify important factors for patients when making their treatment decisions. Based on relevant literature and ASTRO consensus statement guidelines, an educational tool and questionnaire were developed. Consenting, eligible women reviewed the educational tool and completed the trade-off questionnaire. Descriptive statistics were calculated, as well as chi-squares and a logistic regression model. Of the 90 patients who completed the study, 62 % preferred WBI, 30 % preferred PBI, 4 % required more information, and 3 % had no preferences. Of the patients who chose WBI, 58 % preferred hypofractionated RT, whereas 25 % preferred the conventional RT regimen. The majority of patients rated recurrence rate [WBI = 55/55 (100 %), PBI = 26/26 (100 %)] and survival [WBI = 54/55 (98 %), PBI = 26/26 (100 %)] as important factors contributing to their choice of treatment preference. Financial factors [WBI = 21/55 (38 %), PBI = 14/26 (53 %)] and convenience [WBI = 36/54 (67 %), PBI = 18/26 (69 %)] were rated as important less frequently. Significantly, more patients who preferred WBI also rated standard method of treatment as important when compared to patients who preferred PBI [WBI = 52/54 (96 %), PBI = 16/26 (61 %), χ 2 = 16.63, p = 0.001]. The majority of patients with early breast cancer who were surveyed for this study preferred WBI as an adjuvant treatment post lumpectomy, yet there was a sizeable minority who preferred PBI. This was associated with the importance patients place on standard treatment. These results will help medical professionals treat patients according to patient values.

Frequency of whole breast irradiation (WBRT) after intraoperative radiotherapy (IORT) is strongly influenced by institutional protocol qualification criteria.

BACKGROUND: Accelerated partial breast irradiation (APBI) is a promising method of adjuvant radiotherapy for select patients. Intraoperative radiotherapy (IORT) is a form of APBI, and appropriate patient selection is important. AIM: The aim of our study was to analyse the influence of our protocol on the frequency of WBRT after IORT and our protocol's correlation with the reported use of WBRT according to TARGIT guidelines. We also aimed to verify how changes in our protocol influenced the frequency of WBRT. MATERIAL AND METHODS: Between April 20, 2010 and May 10, 2017, we identified 207 patients irradiated with IORT for APBI. RESULTS: Ninety-one patients (44%) met the criteria for APBI only, while 116 (56%) should have been offered additional WBRT. Retrospective analysis showed that WBRT was applied statistically significantly less frequently compared with strict protocol indications: 99 patients (47.8%) received APBI only and 108 (51.2%) underwent adjuvant WBRT (p < 0.0001). Applying the TARGIT trial guidelines, 69 patients (33.4%) should have been offered WBRT (p < 0.0001), which is twice the number of patients treated with WBRT in our study. Changing the protocol to less restrictive criteria would have statistically significantly decreased the number of patients (95, 46%) offered WBRT (p < 0.0001). CONCLUSIONS: Following international guidelines, 46% of patients should receive WBRT after IORT, which is 1.5-2 times more than for the TARGIT criteria. In our analysis, a high percentage of patients (19%) did not receive WBRT after IORT despite the protocol recommendations. The chosen protocol strongly influences the frequency of adjuvant WBRT.

Relation between Hypofractionated Radiotherapy, Toxicity and Outcome in Early Breast Cancer.

To compare adjuvant conventional radiotherapy (C-RT) to hypofractionated schedule (HF-RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C-RT (50 Gy; 2 Gy/fr) or HF-RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT-induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation-related toxicity. No increase in late toxic effects has been reported between C-RT and HF-RT schedules. Overall, the 2-year disease free survival was 94.4%. HF-RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.

Selection of patients with left breast cancer for deep-inspiration breath-hold radiotherapy technique: Results of a prospective study.

AIM: To assess prospectively which patients with left breast cancer have the dosimetric benefit from the use of deep-inspiration breath-hold radiotherapy (DIBH-RT). BACKGROUND: Improvement in selection of patients for DIBH-RT would spare time of radiotherapy staff by removing the need for preparation of two comparative treatment plans. MATERIALS AND METHODS: Thirty-one patients qualified for whole left breast irradiation underwent breath-hold training and their free-breathing (FB) and DIBH planning-CT were included in the analysis of dosimetric outcome. Mean heart dose (MHD), heart V20 Gy (V20Heart), maximum dose to LAD (LADmax), V20 for left lung (V20L.lung) were recorded from FB and DIBH plans and the differences (Δ) of these values were calculated. If relative improvement of at least 20% for any evaluated dosimetric parameter was found for the DIBH-RT, this plan was selected for treatment. Correlations of Δ of dosimetric parameters with patient-related parameters (BMI, age, PTV, cardiac contact distance [CCD], lung volume at FB) were sought. RESULTS: In 30 of 31 patients, a predefined reduction in evaluated parameters was achieved. CCD, BMI correlated positively with ΔMHD, ΔV20Heart, ΔLADmax; PTV with ΔMHD and ΔV20Heart (p < 0.05; AUC > 0.6); Lung volume correlated negatively with ΔLADmax, ΔMHD and ΔV20Heart. No specific thresholds for the lack of predefined improvement of any dosimetric parameters was identified in ROC analysis. 19/30 (63%) patients with dosimetric benefit completed their RT with DIBH. CONCLUSIONS: Despite a strong correlation between patient-related and dosimetric parameters, we cannot use the anatomical characteristics' thresholds to select patients for whom DIBH-RT will not be considered.

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.

Milestones in breast cancer treatment.

Modern treatment started in the 1880s with Halsted's mastectomy. The next milestone-a century later-was breast-conserving surgery, with equivalent survival but better esthetic outcomes than mastectomy. Sentinel node biopsy, introduced in the 1990s, was a milestone that permitted avoidance of axillary dissection if the sentinel node was disease-free. Chemotherapy was established for early breast cancer in the 1980s and its efficacy continues to improve; however side effects remain a concern, particularly since chemotherapy does not benefit most patients. External whole breast irradiation was introduced with conservative surgery, as it reduces recurrences. By the 2000s, 3-week regimens had been shown equivalent to standard 6-week regimens-easing pressure on patients and radiation centers. Intraoperative partial breast irradiation is potentially more beneficial as it permits complete local treatment in a single session; however, trials show that patients must be very carefully selected. From the 1990s irradiation technology was combined with imaging and computer technologies to produce equipment that directs radiation to more precisely defined target volumes, allowing increased dose to the target and markedly reduced dose to nearby tissues. Irradiation systems are evolving rapidly but are being implemented without data on long-term morbidity or efficacy, while costs rise steeply. The first targeted treatment was tamoxifen, a selective estrogen receptor inhibitor. Since its widespread use starting in the 1980s, tamoxifen has saved the lives or prolonged the survival of millions with estrogen-positive disease; it is cheap and has limited (but not negligible) side effects. The same cannot be said of newer targeted treatments like trastuzumab and pertuzumab, which, although effective against human epidermal growth factor receptor 2-positive cancer, come with important side effects and huge costs. Breast cancer mortality is declining in rich countries, but treatments have become more demanding and more expensive, so the outlook for the increasing numbers of women worldwide who develop the disease is uncertain.

Efficacy and safety of accelerated partial breast irradiation after breast-conserving surgery: a meta-analysis of published comparative studies.

To compare the treatment outcomes between accelerated partial breast irradiation (APBI) and conventional whole-breast irradiation (WBI) and to explore the efficacy and safety of APBI as an adjuvant treatment for early-stage breast cancer who received breast-conserving therapy. Eligible studies were identified on Medline, Embase, and the Cochrane Library updated to July 10, 2012. Comparative studies were considered for inclusion. Analyses were carried out using Stata software. Eleven comparative studies with a total of 7,097 patients were included. The meta-analysis showed that there were no statistically significant differences between group APBI and group WBI associated with the supraclavicular failure, distant metastasis, overall survival, and disease-free survival, while local recurrence (LR) and axillary failure (AF) increased in group APBI. The sensitivity analysis indicated that both the LR and AF were not statistically significant difference between the two groups. In the subgroup analysis, LR was statistically significantly higher in group APBI for patients with the age <60, large tumor size, and unknown margin status. APBI is a safe treatment modality and could become a potential option for the delivery of adjuvant radiation therapy in patients receiving breast-conserving therapy, especially for the suitable group that was classified by the American Society of Radiation Oncology Consensus Panel.