Radiotherapy For Early-stage Breast Cancer Research Articles

Overall survival after mastectomy versus breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer: meta-analysis.

Breast-conserving surgery with adjuvant radiotherapy and mastectomy are currently offered as equivalent surgical options for early-stage breast cancer based on RCTs from the 1970s and 1980s. However, the treatment of breast cancer has evolved and recent observational studies suggest a survival advantage for breast-conserving surgery with adjuvant radiotherapy. A systematic review and meta-analysis was undertaken to summarize the contemporary evidence regarding survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for women with early-stage breast cancer. A systematic search of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase that identified studies published between 1 January 2000 and 18 December 2023 comparing overall survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for patients with unilateral stage 1-3 breast cancer was undertaken. The main exclusion criteria were studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes, and specific breast cancer populations. The ROBINS-I tool was used to assess risk of bias, with the overall certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Studies without critical risk of bias were included in a quantitative meta-analysis. From 11 750 abstracts, 108 eligible articles were identified, with one article including two studies; 29 studies were excluded from the meta-analysis due to an overall critical risk of bias, 42 studies were excluded due to overlapping study populations, and three studies were excluded due to reporting incompatible results. A total of 35 observational studies reported survival outcomes for 909 077 patients (362 390 patients undergoing mastectomy and 546 687 patients undergoing breast-conserving surgery with adjuvant radiotherapy). The pooled HR was 0.72 (95% c.i. 0.68 to 0.75, P < 0.001), demonstrating improved overall survival for patients undergoing breast-conserving surgery with adjuvant radiotherapy. The overall certainty of the evidence was very low. This meta-analysis provides evidence suggesting a survival advantage for women undergoing breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer compared with mastectomy. Although these results should be interpreted with caution, they should be shared with patients to support informed surgical decision-making.

Abstract ED05-02: When less is more: Patient-friendly radiation courses with WBI and PBI

Abstract Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% at 5 years was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy. In this regard, strategies such as partial-breast irradiation and whole breast hypofractionation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions. Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a "one-treatment-fits-all" approach cannot be considered an appropriate option. A wide overview on the main partial and whole breast irradiation advantages, risks, timings, techniques, and available recommendations is presented, providing practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer. Citation Format: I. Meattini. When less is more: Patient-friendly radiation courses with WBI and PBI [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-02.

Radiation Oncologists’ Views on Adjuvant Radiotherapy for Early-Stage Breast Cancer in the Elderly: Comparisons between Japan and the United States

Purpose To understand perspective on breast cancer using a survey. Materials & Methods Questionnaire was distributed to 304 Japanese radiation oncologists (RadOncs) (response rate: 64.1%). Result was compared with a similar US survey. Results In a scenario with an 81-year-old patient with comorbidities, while most US RadOncs chose to tell that radiation might not be necessary, 2% of Japanese chose it. In a scenario with a healthy 65-year-old breast cancer patient with lumpectomy, while most US RadOncs chose to discuss omission of radiation, 24.5% of Japanese chose it. Conclusions Differences were observed on radiotherapy for older early-stage breast cancer.

Trends in low-value cancer care during the COVID-19 pandemic.

To assess the association between the onset of the COVID-19 pandemic and change in low-value cancerservices. In this retrospective cohort study, we used administrative claims from the HealthCore Integrated Research Environment, a repository of medical and pharmacy data from US health plans representing more than 80 million members, between January 1, 2016, and March31, 2021. We used linear probability models to investigate the relation between the onset of the COVID-19 pandemic and 4 guideline-based metrics of low-value cancer care: (1) conventional fractionation radiotherapy instead of hypofractionated radiotherapy for early-stage breast cancer; (2) non-guideline-based antiemetic use for minimal-, low-, or moderate- to high-risk chemotherapies; (3) off-pathway systemic therapy; and (4) aggressive end-of-life care. We identified patients with new diagnoses of breast, colorectal, and/or lung cancer. We excluded members who did not have at least 6 months of continuous insurance coverage and members with prevalent cancers. Among 117,116 members (median [IQR] age, 60[53-69] years; 72.4% women), 59,729 (51.0%) had breast cancer, 25,751 (22.0%) had colorectal cancer, and 31,862(27.2%) had lung cancer. The payer mix was 18.7% Medicare Advantage or Medicare supplemental and 81.2% commercial non-Medicare. Rates of low-value cancer services exhibited minimal changes during the pandemic, as adjusted percentage-point differences were 3.93 (95%CI, 1.50-6.36) for conventional radiotherapy, 0.82 (95% CI, -0.62 to 2.25) for off-pathway systemic therapy, -3.62 (95% CI, -4.97 to -2.27) for non-guideline-based antiemetics, and 2.71(95% CI, -0.59 to 6.02) for aggressive end-of-life care. Low-value cancer care remained prevalent throughout the pandemic. Policy makers should consider changes to payment and incentive design to turn the tide against low-value cancer care.

Clinical Trials of Carbon Ion Radiotherapy for Early-Stage Breast Cancer

Our institute conducted a clinical trial of curative partial breast irradiation using carbon ion radiotherapy (CIRT) to patients with stage 0 and I breast cancer since 2013. The purpose of this report is to evaluate treatment outcomes up to now. To date, we have conducted three clinical trials and one advanced medical treatment (NIRS 9404 Comprehensive Research). The first study (UMIN000010848: commonly known as Breast I trial) was 4-split irradiation for stage I low-risk patients aged 60 years or older, and the next clinical study (UMIN000029478: commonly known as Breast II trial) was for Tis-1N0M0 cases of 2 cm or less. On the other hand, 4-split irradiation using standard adjuvant drug therapy according to risk combined with whole breast irradiation by X-ray, the latest clinical trial (UMIN000046859: commonly known as Breast III trial) is a single irradiation for Tis-1N0M0 patients aged 50 years or older. be. In each phase I, the dose increase test was performed, and in phase II, treatment was performed with the recommended dose determined in phase I. Advanced medical care was provided in parallel with breast I for stage I breast cancer that was difficult or rejected to participate in breast I trial. By January 2023, 60 cases were enrolled. A total of 19 were enrolled In Breast I, 7 in Phase I, 12 in Phase II of the recommended dose of 60.0 Gy (RBE). A total of 14 were enrolled in the 9404 Comprehensive Research. A total of 17 were enrolled In Breast II, 5 cases in Phase I, 12 cases in Phase II of recommended dose 60.0 Gy (RBE). A total of 10 were enrolled in Breast III, 6 cases in Phase I, and 4 in Phase II of recommended dose 50.0 Gy (RBE). As acute adverse events, grade 2 of acute radiation dermatitis were observed in 1 case, grade 1 of acute radiation dermatitis was observed in 31 cases, and grade 1 of mastitis was observed in 6 cases. As a late adverse event, grade 3 of pneumonia of unknown causality were observed in one case, but there were no other problematic adverse events, and breast cosmetic outcome was excellent in all cases. Tumor disappearance after CIRT took 3 to 24 months. Local recurrence and axillary lymph node metastasis were observed in one high-risk case of advanced medical treatment who refused any other therapy. Two cases had ipsilateral intramammary metachronous breast cancer with different subtypes. To date, no other recurrences or metastases have been observed. CIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.

Special issue. De-escalation of loco-regional treatment in breast cancer: Time to find the balance? Partial breast irradiation.

Breast cancer is the most common cancer in women worldwide. Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy. In this regard, strategies such as partial-breast irradiation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions. Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a "one-treatment-fits-all" approach cannot be considered an appropriate option. This is a wide overview on the main partial breast irradiation advantages, risks, timings, techniques, and available recommendations. We aim to provide practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer.

Real World and Public Health Perspectives of Intraoperative Radiotherapy in Early-Stage Breast Cancer: A Multidisciplinary Analysis Beyond the Statistical Facts.

Breast conservation therapy (BCT) (usually a lumpectomy plus radiotherapy (RT)) has become a standard alternative to radical mastectomy in early-stage breast cancers with equal, if not higher, survival rates. The established standard of the RT component of the BCT had been about six weeks of Monday through Friday external beam RT to the whole breast (WBRT). Recent clinical trials have shown that partial breast radiation therapy (PBRT) to the region surrounding the lumpectomy cavity with shorter courses can result in equal local control, survival, and slightly improved cosmetic outcomes. Intraoperative RT (IORT) wherein RT is administered at the time of operation for BCT to the lumpectomy cavity as a single-fraction RT is also considered PBRT. The advantage of IORT is that weeks of RT are avoided. However, the role of IORT as part of BCT has been controversial. The extreme views go from "I will not recommend to anyone" to "I can recommend to all early-stage favorable patients." These divergent views are due to difficulty in interpreting the clinical trial results. There are two modalities of delivering IORT, namely, the use of low-energy 50 kV beams or electron beams. There are several retrospective, prospective, and two randomized clinical trials comparing IORT versus WBRT. Yet, the opinions are divided. In this paper, we try to bring clarity and consensus from a highly broad-based multidisciplinary team approach. The multidisciplinary team included breast surgeons, radiation oncologists, medical physicists, biostatisticians, public health experts, nurse practitioners, and medical oncologists. We show that there is a need to more carefully interpret and differentiate the data based on electron versus low-dose X-ray modalities; the randomized study results have to be extremely carefully dissected from biostatistical points of view; the importance of the involvement of patients and families in the decision making in a very transparent and informed manner needs to be emphasized; and the compromise some women may be willing to accept between 2-4% potential increase in local recurrence (as interpreted by some of the investigators in IORT randomized studies) versus mastectomy. We conclude that, ultimately, the choice should be that of women with detailed facts of the pros and cons of all options being presented to them from the angle of patient/family-focused care. Although the guidelines of various professional societies can be helpful, they are only guidelines. The participation of women in IORT clinical trials is still needed, and as genome-based and omics-based fine-tuning of prognostic fingerprints evolve, the current guidelines need to be revisited. Finally, the use of IORT can help rural, socioeconomically, and infrastructure-deprived populations and geographic regions as the convenience of single-fraction RT and the possibility of breast preservation are likely to encourage more women to choose BCT than mastectomy. This option can also likely lead to more women choosing to get screened for breast cancer, thus enabling the diagnosis of breast cancer at an earlier stage and improving the survival outcomes.

Abstract P2-02-03: Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis

Abstract Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p&amp;lt; 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p&amp;lt; 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.

Diffusion-Weighted MRI in the Evaluation of Early-Stage Breast Cancer Treated with a Short Preoperative Radiotherapy: Preliminary Results.

To assess tumor response with diffusion-weighted MRI (DW-MRI) after a short preoperative radiotherapy in early-stage breast cancer (BCa). This was a prospective, single-center pilot study. 3T-MRI were performed before and after radiotherapy. The longest diameter (LD) and the apparent diffusion coefficient (ADC) value of a region of interest (ROI) of the tumors were recorded. Histopathology and immunohistochemistry, including the Ki-67 index of the core biopsy and of the surgical specimen, were the reference standards. Nineteen patients with 22 early-stage BCa were included. The mean ROI ADC value was 1.093 ± 0.278 × 10-3 mm2/s before radiotherapy and 1.490 ± 0.429 × 10-3 mm2/s (p-value < 0.001) after radiotherapy. The Ki-67 index was 9.2 ± 9.1% at the percutaneous biopsy before radiotherapy and 4.9 ± 7.5% (p-value = 0.005) after radiotherapy at the surgical specimen. After neoadjuvant radiotherapy, a 4.7% decrease in LD and a 36.3% increase in ROI-ADC of the tumors were measured at MRI and a 46.7% decrease in Ki-67 index was observed at histology of the surgical specimen in comparison with the percutaneous core biopsy. In early-stage BCa, a significant increase in ROI-ADC at DWI and a significant decrease in Ki-67 index were observed after a short preoperative radiotherapy, suggesting early tumor response.

Socioeconomic Barriers to Randomized Clinical Trial Retention in Patients Treated With Adjuvant Radiation for Early-Stage Breast Cancer

Socioeconomic barriers contribute to breast cancer clinical trial enrollment disparities. We sought to identify whether socioeconomic disadvantage also is associated with decreased trial retention. We performed a secondary analysis of 253 (of 287) patients enrolled in a randomized phase 3 trial of conventionally fractionated versus hypofractionated whole-breast irradiation. The outcome of trial retention versus dropout was defined primarily based on whether the patient completed breast cosmesis outcomes assessment at 3-year follow-up, and secondarily, at 5-year follow-up. Associations of retention with severity of socioeconomic disadvantage, quantified by patients' home neighborhood area deprivation index (ADI) rank (1 [least] to 100 [most deprivation]), were tested using the Kruskal-Wallis test and multivariate logistic regression. Associations of retention with patients' use of social resource assistance were analyzed using the χ2 test. In total, 21.7% (n=55) of patients dropped out by 3 years and 36.7% (n=92) by 5 years. Median ADI was 36.5 (interquartile range, 22-57) for retained and 46.0 (interquartile range, 29-60) for dropout patients. Dropout was associated with more severe socioeconomic deprivation (ADI ≥45 vs <45) at 3 years (odds ratio, 3.63; 95% confidence interval, 1.62-8.15; P=.002) and 5 years (odds ratio, 2.55; 95% confidence interval, 1.37-4.76; P=.003). While on study, patients who ultimately dropped out were more likely to require resource assistance for practical (transportation, housing, financial) than psychological needs (distress, grief) or advance care planning (P=.03). In this study, ADI was associated with disparities in clinical trial retention of patients with breast cancer receiving adjuvant radiation treatment. Results suggest that developing multidimensional interventions that extend beyond routine social determinants needs screening are needed, not only to enhance initial clinical trial access and enrollment but also to enable robust long-term retention of socioeconomically disadvantaged patients and improve the validity and generalizability of reported long-term trial clinical and patient-reported outcomes.

Omitting radiation in early-stage breast cancer

Omitting radiation in early-stage breast cancer

IMNI PRECISION trial protocol: a phase II, open-label, non-inferior randomized controlled trial of tailoring omission of internal mammary node irradiation for early-stage breast cancer

BackgroundSince the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined.MethodsThe IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically “high risk” BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score “low risk” (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival.DiscussionThe IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC.Trial registrationClinicalTrials.gov Identifier NCT04517266. Date of registration: August 18, 2020. Status: Recruiting.

Radiation in Early-Stage Breast Cancer: Moving beyond an All or Nothing Approach.

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens' decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions.

Clinical Trials of Curative Partial Breast Irradiation for Early-Stage Breast Cancer Using Carbon Ion Radiotherapy

<h3>Purpose/Objective(s)</h3> Our institute conducted clinical trials of curative partial breast irradiation using carbon ion radiotherapy (CIRT) to patients with stage 0 and I breast cancer since 2013. The purpose of this report is to evaluate treatment outcomes up to now. <h3>Materials/Methods</h3> To date, we have conducted three clinical trials and one advanced medical treatment (NIRS9404: AMT). The first study (UMIN000010848: known as Breast I) was 4 fractions partial breast CIRT for stage I luminal patients aged 60 years or older. The AMT protocol was provided in parallel with Breast I in same manner for stage I breast cancer patients who was difficult to register due to minor variant or reject to participate in Breast I. In principle, these patients received maintenance hormone therapy. The next clinical trial (UMIN000029478: known as Breast II) enrolled patients aged 20 years and older without 2 mm or more metastasis in sentinel lymph node for all types of Tis-1N0M0, tumor size 2 cm or less. In this study, 4 fractions CIRT partial breast irradiations were combined with standard systemic therapy and x-ray whole-breast irradiation. And the latest clinical trial (UMIN000046859: known as Breast III) is a single dose of CIRT for luminal Tis-1N0M0 patients aged 50 years and older. All Breast III patients received maintenance hormone therapy. In all trials, Phase I was a dose-escalation study and Phase II was treated with the recommended dose determined in Phase I. <h3>Results</h3> By December 2021, 56 cases have been enrolled. A total of 19 were enrolled In Breast I, 7 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE), and total of 14 were enrolled in AMT. A total of 17 were enrolled In Breast II, 5 in Phase I, 12 in Phase II with a recommended dose of 60.0 Gy (RBE). A total of 6 were enrolled in Breast III, 3 in Phase I, 3 in Phase II with a recommended dose of 50.0 Gy (RBE). As acute adverse effects, acute radiation dermatitis (grade 2 in 1, Grade1 in 37), mastitis (grade 1 in 6) and myositis (grade 1 in 7) were observed. As late adverse effects, grade 3 pneumonia of unknown causality were observed in 1 case. The cosmetic results of breast were excellent in all cases. Tumor disappearance after CIRT took 3 to 24 months. Local recurrence with axillary lymph node metastasis was observed in one high-risk AMT patient who refused any systemic therapy, but no other recurrences or metastases have been observed. <h3>Conclusion</h3> CIRT for early-stage breast cancer is expected to be effective with mild adverse events, and it is considered meaningful to continue research.

Comparison of Dose Calculation Algorithms for Accelerated Partial Breast Intensity Modulated Radiation Therapy

<h3>Purpose/Objective(s)</h3> Accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) has been introduced recently as an alternative treatment to whole breast irradiation for early-stage breast cancer after lumpectomy. Plan dose volume constraints for IMRT APBI are complex, requiring a more conformal and homogenous dose distribution compared to traditional tangential beam based whole breast planning. Anisotropic Analytical Algorithm (AAA) has been widely used for photon dose calculation. An Advanced Dose Calculation algorithm (AXB) is known to achieve comparable accuracy to Monte Carlo (MC) algorithm, the golden standard dose calculation, in heterogeneous media. However, the clinical assessment of AXB has been lacking. As a preliminary study, we investigated the dosimetric differences between the AAA, AXB and MC calculations on APBI IMRT. <h3>Materials/Methods</h3> Six patients with left breast cancer who previously received APBI IMRT were analyzed for this study. All patients received 30 Gy in 5 fractions with a multi beam IMRT technique using AAA 15.6 in the planning system. The following dose volume constraints were used for acceptable plan criteria based on the APBI IMRT Florence trial and all 6 cases previously treated met these criteria: For target (lumpectomy PTV), V28.5 Gy=100%, maximum dose to target < = 105% and V105% <= 2%. For critical organs, uninvolved breast with V15 Gy < 25%, ipsilateral lung volume with V10 Gy < 20%, contralateral breast maximal dose < 1 Gy, heart with V3 Gy < 10%. For a dosimetric comparison, plans were generated with AXB 15.6, reporting dose to medium, for each corresponding AAA plan by re-optimizing with the same dose constraints. After that, AXB plans were re-calculated with MC algorithm using XVMC and compared to AXB. <h3>Results</h3> The re-calculated plans using AXB for the same monitor units with an identical beam setup from AAA plans did not meet the acceptable dose volume criteria. For re-optimized plans with AXB, target conformity index, V28.5Gy and critical organs met the criteria but maximum dose and V105% were still higher than AAA plans (107-110% vs. 104-105.5% for max dose; <i>p</i>=0.02, 2.5- 5.0% vs. 0-2% for V105; <i>p</i> <0.001). The plan comparison between AXB and MC calculations showed similarity in dose distributions and hotspot area, and minimum difference in dose volume histogram. <h3>Conclusion</h3> The present data is the first report to assess the AXB for APBI IMRT. All 6 plans needed the re-optimization for AXB from plans with AAA to comply with the dose volume constraints. However hot spot size was better with AAA plans. MC calculation confirmed the dose distribution and hot spot area produced by AXB. Therefore, the clinical use of AXB for APBI IMRT will need careful evaluation due to a discrepancy in dose distributions and hot spot sizes between AAA and AXB calculations.

Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Existing data on adding internal mammary nodal irradiation (IMNI) to the regional nodal fields are inconsistent. Methods: Randomized trials investigating the addition of IMNI to standard adjuvant radiation were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall-survival (OS), breast cancer specific-survival (BCSS), and disease-free survival (DFS) as well as distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer, and cardiovascular morbidity and mortality were also extracted. Results: Analysis included five trials comprising 10,994 patients, predominantly with higher risk, lymph node positive disease. Compared to the control group, IMNI was associated with significant improvement in OS (HR = 0.91, p = 0.004), BCSS (HR = 0.84, p < 0.001), DFS (HR = 0.89, p= 0.01), and DMFS (HR = 0.89, p = 0.02). IMNI was also associated with reduced odds for regional (OR = 0.58, p < 0.001) and loco-regional recurrence (OR = 0.85, p = 0.04). The odds for cardiotoxicity were not statistically significantly higher (OR = 1.23, p = 0.07). There were comparable odds for cardiovascular mortality (OR = 1.00, p = 1.00), non-breast cancer mortality (OR = 1.05, p = 0.74), secondary cancer (OR = 0.95, p = 0.51), and contra-lateral breast cancer (OR = 1.07, 95% 0.77–1.51, p = 0.68). Conclusions: Compared to the control group, the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness.

Melatonin supplementation for preventing cancer-related fatigue in patients receiving radiotherapy for early-stage breast cancer: A double-blind placebo-controlled phase III trial.

e24079 Background: Fatigue is common in patients undergoing radiotherapy (RT). Melatonin, an inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The effect of melatonin for prevention of fatigue and other symptoms was evaluated in a double-blind placebo-controlled trial. Methods: Early-stage or ductal carcinoma in-situ breast cancer patients ≥ 18 years, female, Eastern Cooperative Oncology Group performance status (ECOG PS) &lt; 3, hemoglobin ≥9 g/dL. RT with curative intent, randomized 1:1 to melatonin 20 mg or oral placebo, starting night before RT initiation until 2 weeks post-RT. Sample size of 142 evaluable patients in each arm for 80% power and interim analysis at mid recruitment using the unified family method rho = 0.3. Randomization stratified to RT duration (&lt; 3 weeks, ≥3 weeks) and prior chemotherapy. Primary outcome : Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue subscale after completion of RT with additional scores measured at baseline, 2 and 8 weeks post-RT. Secondary outcomes : FACIT-F subscales, Edmonton Symptom Assessment System (ESAS) and Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a. Secondary analyses reported using an F-test at a 5% significance level. Results: For this interim analysis, 85 patients screened; 80 randomized; 39 received melatonin and 38 placebo. 72 included in the analysis as 5 patients had no post baseline FACIT score. Characteristics of age, race, and ECOG PS similar in both arms. Treatment X time for FACIT-Fatigue not significant for melatonin compared to placebo (p .83). FACIT physical, emotional, and functional well-being scores not significantly different (p .35, .62, and .71) but showing a trend for social well-being (p .06). PROMIS scores not changed over time (p .34). ESAS individual symptoms of anxiety, well-being, drowsiness, poor appetite, nausea, pain, shortness of breath, sleep and tiredness not significant, except for depression (p.04). However, a decrease of 0.01 unit in depression score is not considered clinically significant. No grade 3 or 4 adverse events. No participants died during study, 2 died after study completion from breast cancer recurrence. 16 withdrew prior to study completion because of adverse events, unrelated hospitalizations, RT discontinuation, and COVID-19 precautions. Trial was stopped based on statistical analysis demonstrating no difference for primary outcome and imminent expiry of available drug. Discontinuation was approved by Data Safety Monitoring Committee. Conclusions: Melatonin did not prevent fatigue in patients with early stage breast cancer undergoing RT. Melatonin also demonstrated no benefit for other symptoms, except depression. Analysis showed little evidence of an effect, and the trial was terminated early. Clinical trial information: NCT02332928.

Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis.

BackgroundIn patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost.MethodsWe retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test.ResultsTotal 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%).ConclusionHypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Final Analysis of a Phase 2 Trial of Once Weekly Hypofractionated Whole Breast Irradiation for Early-Stage Breast Cancer

We hypothesize that 5-fraction once weekly hypofractionated (WH) whole breast irradiation (WBI) would be safe and effective after breast-conserving surgery for medically underserved patients with breast cancer. We report the protocol-specified primary endpoint of in-breast tumor recurrence (IBTR) at 5 years. After provided informed consent, patients were treated with WH-WBI after breast-conserving surgery were followed prospectively on an institutional review board-approved protocol. Women included in this study had stage 0-II breast cancer treated with negative surgical margins and met prespecified criteria for being underserved. WH-WBI was 28.5 or 30 Gy delivered to the whole breast with no elective coverage of lymph nodes. The primary endpoint was IBTR at 5 years. Secondary endpoints were distant disease-free survival, recurrence-free survival, overall survival, adverse events, and cosmesis. One hundred fifty-eight patients received WH-WBI on protocol from 2010 to 2015. Median follow-up was 5.5 years (range, 0.2-10.0 years). Stage distribution was 22% ductal carcinoma in situ, 68% invasive pN0, and 10% invasive pN1. Twenty-eight percent of patients had grade 3 tumors, 10% were estrogen receptor negative, and 24% required adjuvant chemotherapy. There were 6 IBTR events. The 5-, 7-, and 10-year risks of IBTR for all patients were 2.7% (95% confidence interval [CI], 0.89-6.34), 4.7% (95% CI, 1.4-11.0) and 7.2% (95% CI, 2.4-15.8), respectively. The 5-, 7-, and 10-year rates of distant disease-free survival were 96.4%, 96.4%, and 86.4%; the recurrence-free survival rates were 95.8%, 93.6%, and 80.7%; and the overall survival rates were 96.7%, 88.6%, and 76.7%, respectively. Improvement in IBTR-free time was seen in ductal carcinoma in situ, lobular histology, low-grade tumors, T1 stage, Her2-negative tumors, and receipt of a radiation boost to the lumpectomy bed. Postoperative WH-WBI has favorable disease-specific outcomes that are comparable to those seen with conventional and moderately hypofractionated radiation techniques. WH-WBI could improve access to care for underserved patients with stage 0-II breast cancer.

Thirty-Year Single Institution Experience of Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer

Accelerated partial breast irradiation (APBI) can reduce treatment time and spare normal breast tissue. Techniques for APBI include applicator-based, external beam radiotherapy (EBRT), intra-operative radiotherapy (IORT), and interstitial implant-based. Data comparing these various APBI modalities and associated outcomes are lacking in the literature. We conducted a single-institution retrospective analysis of patients treated with APBI to compare treatment techniques and report outcomes.Patients treated with APBI between 1990 and 2019 were included. Baseline patient characteristics, clinical and pathological features, treatment details, and clinical outcomes were retrospectively reviewed using a single-institution database. Outcomes were updated through August 2020. Statistical methods included Kruskal-Wallis test, Fisher's exact test, chi-square test of independence, and Kaplan-Meier analysis.A total of 926 APBI cases were analyzed, a majority of which were invasive ductal carcinoma (50.6%). Comparing applicator-based to EBRT, IORT, and implant-based, there was no difference in overall survival, freedom from local recurrence, or freedom from mastectomy (Table 1). 5-, 10-, and 25-year cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was 1.5% (0.87-2.5%), 3.3% (2.3-4.7%), and 5.2% (3.9-6.7%), with no difference between treatment techniques. The median follow-up time was 121.6 months (66-165.7 months). Cosmesis was good/excellent in 91%, 84%, and 93%, for applicator, EBRT, and interstitial techniques, respectively. Late toxicities assessed included pigmentary changes, telangiectasias, induration/fibrosis, and fat necrosis. The majority of late toxicities were none or Grade 1, with less than 10% of patients experiencing Grade 2 or greater toxicity.With our 30-year single-institution APBI experience using various treatment techniques, long term outcomes of both disease control and local morbidity demonstrate that the various APBI techniques are equally effective for suitable early-stage breast cancer patients. As evolving radiotherapy paradigms incorporate more shortened time-course treatments, these results affirm that APBI remains a viable alternative for such favorable patients.