A phase 2 prospective noninferiority trial evaluating a novel 9 fraction course of whole breast radiation and simultaneous lumpectomy boost.

Tis and T1-3N0 patients enrolled to receive 3420 cGy radiation to the breast with 3960 cGy to the lumpectomy cavity. The primary endpoint was averaged photographic cosmetic scores at 24 months with a hypothesis of >70% good to excellent cosmetic breast scoring 24 months after completing radiation, assuming a baseline excellent/good cosmetic scoring of 80% with an 80% power, α = 0.1.

From 2018 to 2020, with institutional review board approval, 103 patients were enrolled. Patients had mostly invasive ductal carcinoma (75%), tumor size ≤ 2cm (88%), negative margins (92%), no lympho-vascular invasion (80%), and estrogen receptor positive (85%). Patients had a mean age of 59.5 years (33-82). With a mean follow-up of 51 months, there were no local recurrences and 1 patient with both regional (axilla) and distant (brain) recurrence. Twenty-four-month post-radiation therapy (RT) cosmetic photos were 68% excellent/good, and 32% fair/poor. The null hypothesis was not rejected with one-sided 95% exact binomial confidence interval of 59.1% (59.1%-100%). There were no reported late ≥grade 3 radiation toxicity events and only 4 patients with late grade 2 events. Patient-reported outcomes utilizing the Breast-Q survey revealed breast satisfaction in 85% of women.

We demonstrate an effective novel 9 fraction whole breast + lumpectomy boost radiation schedule. This trial uses one of the shortest published radiation schedules for a lumpectomy boost. Although we did not meet our prespecified cosmetic endpoint, no significant cosmetic change from baseline was seen in 80% of patients. We demonstrate excellent local control, and patient-reported satisfaction with low RT-related toxicity. We hope to move this concept forward in a randomized trial against the 5-day United Kingdom (UK) Fast Forward regimen, inclusive of a simultaneous lumpectomy cavity boost.

To evaluate whether hypofractionated radiotherapy (HF-RT) in node-negative intact breast cancer significantly increased after guideline updates, trial publications, and COVID-19.

Patients with node-negative breast cancer undergoing lumpectomy and adjuvant RT were identified in the National Cancer Database. Receiving ≥25 and <50 Gy in 5-20 fractions defined HF-RT. Receiving 50 to 66 Gy in >20 fractions defined conventional RT (CF-RT). Patient characteristics were compared with X 2 testing. Joinpoint analysis identified when fractionation significantly changed. Variables associated with HF-RT were identified by univariate and multivariate (MVA) logistic regression. Two-sided P -value <0.05 was significant.

Patients meeting criteria totaled 236,336; 54.8% received CF-RT and 45.2% HF-RT. HF-RT and 5-fraction RT significantly increased after 2015 and 2019, respectively ( P <0.05). On MVA, HF-RT was positively associated with: age older than or equal to 65 years (OR 2.14, P <0.001); private insurance (OR 1.27, P =0.03); treatment in Midwest (OR 1.66, P <0.001) or Western United States (US) (OR 3.77, P <0.001); distance ≥50 miles (OR 1.16, P =0.001); later year of diagnosis (OR 1.44, P <0.001); and partial breast irradiation (OR 2.08, P <0.001). HF-RT was negatively associated with: community (OR 0.49, P <0.001) or integrated network (0.55, P <0.001) centers; grade 2 (OR 0.83, P <0.001) or 3 (OR 0.49, P <0.001), hormone receptor negative (OR 0.66, P <0.001), and HER2+ (OR 0.74, P <0.001) disease; positive surgical margins (OR 0.61, P <0.001); and presence of lympho-vascular invasion (OR 0.86, P <0.001).

HF-RT in node-negative intact breast cancer increased after 2015, coinciding with US and European guideline updates. Five-fraction RT increased after 2019, coinciding with COVID-19 and FAST-Forward trial results.

The Early Breast Cancer Trialists' Collaborative Group's 2023 meta-analysis of radiation therapy to regional nodes in early breast cancer demonstrated a significant improvement in overall survival (OS) without an associated improvement in locoregional recurrence in the trials comparing internal mammary node (IMN) irradiation versus none. We aimed to study cases with IMN relapse (IMNR) and controls without IMNR to examine the link between IMNR and OS.

Patients treated curatively between 2005 and 2014, who subsequently developed IMNR, were identified in a population-based database. The IMNR cases were matched 1:2 to controls without IMNR using patient and tumor characteristics. The internal mammary vessels in the first 3 intercostal spaces were outlined on planning computed tomography scans as the IMN clinical target volume, and the mean equivalent doses in 2-Gy fractions to the IMNs were calculated. Multivariable Fine and Gray competing-risk regression and Cox regression were used to evaluate the effect of the baseline patient, tumor, and treatment variables, including therapeutic IMN irradiation with ≥40 Gy on IMNR and OS.

Seventy cases were matched with 140 controls. Median follow-up was 9.1 years, median tumor size was 25 mm, and N-stages were: 37% N0, 33% N1, and 30% N2-3. The medians of the IMN doses were 4.1 Gy for cases and 13.7 Gy for controls (P < .001). On multivariable analysis, worse IMNR was associated with mastectomy (hazard ratio [HR], 2.11; P = .02), and better IMNR was associated with therapeutic IMN irradiation (HR, 0.36; P = .009); worse OS was associated with larger tumor size (HR, 1.02; P = .006), ≥10 positive axillary nodes (HR, 3.15; P = .04), and triple-negative subtype (HR, 2.92; P = .03), and better OS was associated with therapeutic IMN irradiation (HR, 0.49; P = .02).

We demonstrated that therapeutic IMN irradiation with ≥40 Gy was associated with both a lower risk of IMNR and improved OS.

Breast cancer (BC) is the most prevalent cancer in women and radiotherapy (RT) is an integral part of its treatment. High-level evidence guides clinical decisions, but given the abundance of guidelines, a need to navigate within the evidence has been identified by the board of the Scientific Association of Swiss Radiation Oncology (SASRO). A pilot project was initiated aiming to create an overview of recent clinically relevant evidence for BC RT, to make it easily available to (radiation) oncologists and radiation oncologists in training.

A panel of 10 radiation oncology experts for BC RT, one expert in BC surgery, and one expert in BC medical oncology critically reviewed the relevant literature. The panel comprehensively represented different geographical regions of Switzerland as well as university, cantonal, and private institutions. We sought to create a consensual overview of the most relevant questions in BC RT today, accompanied by the most recent and relevant available evidence.

From January 2023 to January 2024, the panel met four times to review and work on an initial draft. The final draft was reviewed and accepted by all panelists. We hereby publish this work to make it available to international audiences. After publication, the work will be made available to all SASRO members on the SASRO website. This work is to be updated every 2 years.

The identified need was addressed with a successful pilot project and will be further expanded upon in other tumor pathologies.

To determine the dosimetric effects of set-up errors on boost coverage, and compares skin toxicity of sequential and simultaneous boost techniques for left-sided breast cancer.

This retrospective study included 23 early-stage breast cancer cases. Single isocenter HFWBI-SIB(s-SIB), single isocenter HFWBI-SB(s-SB) and dual isocenter HFWBI-SB(d-SB) were planing. Rotations of 0.5°, 1°, and 2° coupled with translationals of 0.5 mm, 1.0 mm, and 2.0 mm were applied along three orthogonal axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using GEE univariate analysis to determine how PTV coverage was related to 1/CIRTOG, PTVboost volume, PTVboost separation to isocenter. The relationship between the high-dose regions within the PTVbreast and Ratio_V was evaluated using univariate analysis.

The s-SIB had optimal target coverage and lower high-dose volume, but it increased the risk of compromised coverage to tumor bed. For the s-SB technique, V95 exceeded 95% under all setup errors. At 2.0° coupled with 2.0 mm, s-SIB and d-SB exhibited V95 values below 95% in 34.8% and 8.7% of cases, respectively. At other setup errors, both s-SIB and d-SB demonstrated V95 values greater than 95%. Notably, high-dose regions such as V105%, V107%, and V110% within the PTVbreast across the three techniques displayed a significant correlation with Ratio_V.

Simultaneous-integrated boost for early-stage breast cancer can reduce skin toxicity compared to sequential techniques but with the risk of compromising tumor bed coverage.

IntroductionRadiotherapy treatment plans traditionally rely on physical indices like Dose-volume histograms and spatial dose distributions. While these metrics assess dose delivery, they lack consideration for the biological effects on tumors and healthy tissues. To address this, radiobiological models like tumor control probability (TCP) and Normal tissue complications probability (NTCP) are increasingly incorporated to evaluate treatment efficacy and potential complications. This study aimed to assess the predictive power of radiobiological models for TCP in breast cancer radiotherapy and provide insights into the model selection and parameter optimization.MethodsIn this retrospective observational study, two commonly used models, the Linear-Poisson and Equivalent uniform dose (EUD)-based models, were employed to calculate TCP for 30 patients. Different radiobiological parameter sets were investigated, including established sets from literature (G1 and G2) and set with an optimized "a" parameter derived from clinical trial data (a1 and a2). Model predictions were compared with clinical outcomes from the START trials.ResultsThe Linear-Poisson model with es lished parameter sets from the literature demonstrated good agreement with clinical data. The standard EUD-based model (a = -7.2) significantly underestimated TCP. While both models exhibited some level of independence from the specific parameter sets (G1 vs. G2), the EUD-based model was susceptible to the "a" parameter value. Optimization suggests a more accurate "a" value closer to -2.57 and -5.65.ConclusionThis study emphasizes the importance of clinically relevant radiobiological parameters for accurate TCP prediction and optimizing the "a" parameter in the EUD-based model based on clinical data (a1 and a2) improved its predictive accuracy significantly.

Objectives: Few studies have analyzed surgical site infections associated with hypofractionated RT. The purpose of this study was to identify risk factors for surgical site infections with a particular focus on volumetric parameters that reflect the size of the volumes treated, including tumors, surgical cavities, and breasts. Methods: A total of 145 early breast cancer patients who were surgically staged 0-II undergoing hypofractionated RT on the whole breast were retrospectively reviewed. Tumor size (cm) was measured from surgical pathology. Surgical cavity volume (cc) and breast volume (cc) were calculated by segmenting each axial slice of simulation CT. The cavity-to-breast ratio (%) was calculated as surgical cavity volume/breast volume × 100. Results: The incidence of surgical site infection was 4.8% at a median of 6.3 months after the completion of RT. In univariate analysis, tumor size (OR 2.01, p = 0.025), surgical cavity volume (OR 1.03, p = 0.013), cavity-to-breast ratio (OR 1.29, p = 0.005), and BMI (OR 1.23, p = 0.014) were significantly associated with surgical site infection. In multivariate analysis, the cavity-to-breast ratio (OR 1.24, p = 0.039) remained significantly associated with surgical site infection. Conclusions: This study highlights the importance of volumetric parameters, specifically the cavity-to-breast ratio, as significant predictors of surgical site infection in a pure cohort of early breast cancer patients undergoing breast-conserving surgery and hypofractionated RT. Tailored approaches, including the use of prophylactic antibiotics, prophylactic aspiration, and close follow-up, may reduce the morbidity associated with surgical site infection and prevent the potential compromise of tumor outcomes.

Recent advancements in the treatment of early-stage breast cancer have significantly shifted the radiotherapy landscape. Traditionally, the standard of care included lumpectomy followed by endocrine therapy and 3-5 weeks of adjuvant radiation targeting the entire unilateral breast. This review summaries modern trials, emphasizing data reported since 2019 that have changed radiation treatment paradigms. Ultra-hypofractionated treatment regimens have enabled radiation oncologists to deliver the total radiation dose in as few as 5 treatments over 1 week for select patients. Partial breast irradiation, treating only the breast tissue nearest to the lumpectomy cavity, has also emerged as an effective and well-tolerated treatment. Furthermore, a growing body of evidence supports the safety of omitting radiation completely for certain older adults with low-risk disease. Ongoing research in areas such as precision cancer care, treatment de-escalation, and toxicity prevention and management reflects a broader shift toward shared decision-making in medicine and individually tailored treatment paradigms. As research progresses, treatment options will continue to evolve. Advances in radiation oncology will give the oncology team a growing array of tools to custom treatment plans to individual patient risks and toxicity concerns. Knowledge of radiation advances should be used to facilitate shared decisions with patients about the balance of treatment efficacy, toxicity, and quality of life, with the ultimate goal of promoting high-quality, personalized, and patient-centered cancer care.

Breast cancer radiotherapy has evolved significantly, driven by decades of research into fractionation schedules aimed at optimizing treatment efficacy and minimizing toxicity. Initial trials such as NSABP B-06 and EBCTCG meta-analyses established the benefits of adjuvant whole-breast irradiation in reducing local recurrence and improving survival rates. The linear-quadratic (LQ) model provided a framework to understand tissue response to radiation, highlighting the importance of the α/β ratio in determining fractionation sensitivity. The present scoping review aimed to identify and describe hypofractionation regimens for whole breast radiotherapy and evaluate dose differences using the LQ model across proposed α/β ratios. A comprehensive PubMed search for clinical trials published since 2010 on hypo-fractionated regimens was performed. Studies discussing α/β ratios for breast cancer have been also searched. Data on dose, fractions and α/β ratios were collected, and biologically effective dose (BED) and equivalent dose in 2 Gy fractions were calculated. The coefficient of variation for BED varied with α/β ratios, showing the lowest variability for an α/β ratio of ~3 without tumor repopulation and increased with repopulation (BED-kT; k is a constant that depends on the repopulation rate of the tumor, and T is the total treatment time in days). Significant differences in BED variances were observed across α/β ratios (F-statistic 219.6, P<0.0001). START trials (P, A, and B) established α/β ratios of 3-4 Gy for breast cancer and normal tissues, confirming that hypofractionation is as effective as standard fractionation with potentially fewer late toxicities. Subsequent trials, such as FAST and FAST-Forward, demonstrated that ultra-hypofractionation is equivalent in tumor compared with conventional regimens. Further research is needed to gain a stronger understanding of radiobiological properties of breast cancer cells. Advances in radiotherapy technologies and the integration of biomarkers, radiomics and genomics are transforming treatment, moving towards precision medicine.

To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes.

Systematic review and meta-analysis.

Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023).

Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions).

Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively.

Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence.

The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics.

From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF.

MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings.

PROSPERO CRD42023460249.

To compare the dosimetric advantages and disadvantages between hybrid intensity-modulated radiation therapy (h-IMRT) and the volumetric modulated arc therapy (VMAT) technique in hypofractionated whole-breast irradiation (HF-WBI) for early-stage breast cancer (BC).

The dose distribution of h-IMRT and VMAT plans was compared in 20 breast cancer patients. This comparison included evaluation of dosimetric parameters using dose volume histograms (DVHs) for the planning target volume (PTV) and organs-at-risk (OARs). Additionally, the study examined the normal tissue complication probability (NTCP), the second cancer complication probability (SCCP) and the tumor control probability (TCP) based on different models.

Significant differences were detected between the two plans, in terms of Machine units (MUs), the control points, 95 % volume (V95 %), dose homogeneity index (DHI) and conformity index (CI). The endpoint of grade II radiation pneumonitis and cardiac death due to ischemic heart disease were assessed. In h-IMRT plan, the NTCP values were marginally lower for radiation pneumonitis and slightly higher for cardiac death compared to VMAT plan, as determined by the Lyman-Kutcher-Burman model. The Schneider model was employed to predict the SCCP for both the bilateral lungs and contralateral breast, the results demonstrate that the h-IMRT plan outperforms the VMAT plan, with statistical significance. Additionally, the LQ-Poisson model was employed to forecast the TCP of the PTV, showing that the h-IMRT plan outperformed the VMAT plan (P > 0.05).

The h-IMRT technique, offering superior dose coverage and better therapeutic efficacy with fewer side effects as calculated by models, is more suitable for HF-WBI compared to the VMAT technique.

We aimed to update the trend of hypofractionated whole-breast irradiation (HF-WBI) use over time in the US and examine factors associated with lack of HF-WBI adoption for patients with early-stage invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) undergoing a lumpectomy.

Among patients who underwent a lumpectomy, we identified 928,034 patients with early-stage IBC and 330,964 patients with DCIS in the 2004 to 2020 National Cancer Database. We defined HF-WBI as 2.5-3.33 Gy/fraction to the breast and conventionally fractionated WBI as 1.8-2.0 Gy/fraction. We evaluated the trend of HF-WBI utilization using a generalized linear model with the log link and binomial distribution. Factors associated with HF-WBI utilization were assessed using multivariable logistic regression in patients diagnosed between 2018 and 2020.

Among patients with IBC, HF-WBI use has significantly increased from 0.7% in 2004 to 63.9% in 2020. Similarly, HF-WBI usage among patients with DCIS has also increased significantly from 0.4% in 2004 to 56.6% in 2020. Black patients with IBC were less likely than White patients to receive HF-WBI (adjusted odds ratio [AOR] 0.81; 95% CI, 0.77-0.85). Community cancer programs were less likely to administer HF-WBI to patients with IBC (AOR, 0.80; 95% CI, 0.77-0.84) and to those with DCIS (AOR, 0.87; 95% CI, 0.79-0.96) than academic/research programs. Younger age, positive nodes, larger tumor size, low volume programs, and facility location were also associated with lack of HF-WBI adoption in both patient cohorts.

HF-WBI utilization among postlumpectomy patients has significantly increased from 2004 to 2020 and can finally be considered standard of care in the US. We found substantial disparities in adoption within patient and facility subgroups. Reducing disparities in HF-WBI adoption has the potential to further alleviate health care costs while improving patients' quality of life.

Technology advances in cancer care have paralleled rapidly increasing expenditures in radiation therapy. The use and costs of shorter cancer radiation therapy offer potential utility in clinical practice. We evaluate use and expenditures of Medicare Advantage (MA) beneficiaries receiving hypofractionated whole breast irradiation (HF-WBI) compared with conventionally fractionated whole breast irradiation (CF-WBI) in the United States and examine the relationship of patient characteristics with HF-WBI use.

We performed a retrospective analysis of radiation therapy in MA beneficiaries using private employer-sponsored insurance claims for a pooled cross-sectional evaluation from 2009 to 2017. The study population included female MA beneficiaries with early-stage breast cancer treated with lumpectomy and whole breast irradiation.

A total of 9957 women received HF-WBI, and 18,920 received CF-WBI. Older age, greater distance from home to treatment facility, and a higher proportion of college graduates in the community of residence were associated with increased HF-WBI use. Mean insurer-paid radiation therapy expenditures were significantly lower for HF-WBI versus CF-WBI (adjusted difference, $4113; 95% CI, $4030-$4,197). Mean patient out-of-pocket expenditure for HF-WBI was $426 less than that of CF-WBI. Across US states, geographic variation existed in the ratio of costs for HF-WBI relative to CF-WBI (range, 0.41-0.87).

HF-WBI use among MA beneficiaries with breast cancer has dramatically increased over time, surpassing CF-HBI as the dominant form of radiation therapy. HF-WBI clinical adoption has outpaced any continual cost decrease, despite wide variation across US states for this shorter radiation therapy treatment. As MA enrollment continues to expand, identifying the drivers of HF-WBI use and the sources of variation in costs of HF-WBI will help direct the quality of cancer care delivered to Medicare beneficiaries.

Hypofractionated radiation therapy (RT) was recommended for several cancer sites to reduce outpatient visits during the COVID-19 pandemic. This study aimed to identify the impact of the pandemic on hypofractionated RT for breast cancer in Japan.

The monthly number of courses for hypofractionated and conventional RTs was counted using sample data sets from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, a nationwide database accumulating insurance claims data comprehensively. Changes in the number of hypofractionated and conventional RTs were estimated using an interrupted time-series analysis.

The number of hypofractionated RT courses gradually increased before the pandemic in contrast to that of conventional RT courses, which gradually decreased. However, conventional RT remained outnumbered by hypofractionated RT throughout the observation period. After the outbreak of the pandemic, the use of hypofractionated RT significantly increased in April 2020 (1312 courses; 95% CI, 801-1823) but decreased in October 2020 (-601; 95% CI, -1111 to -92). Subgroup analysis by age and the number of beds in medical institutions revealed similar trends.

Although conventional RT for breast cancer has been gradually replaced by hypofractionated RT, it remains predominant. The use of hypofractionated RT increased briefly early in the COVID-19 pandemic; however, this increase was not sustained, unlike in other countries. Considering the benefits of hypofractionated RT for breast cancer, its use should be encouraged in Japan.

This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS.

Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities.

The survival analysis after propensity score matching confirmed that patients who received IORT (n = 2200) had a better 5-year OS than those who received EBRT (n = 2200) (p = 0.015). However, the two groups did not differ significantly in 5-year BCSS (p = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT.

In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.

Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors.

This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot.

Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P < 0.001), and tumor bed planning target volume (PTV-TB) (P = 0.002) were significantly correlated with higher rates of acute skin toxicity.

Hypofractionated WBI demonstrated similar acute skin adverse reactions compared to conventional WBI. These findings indicate that hypofractionated radiotherapy offers comparable tolerance, equivalent curative effect, convenience, and economic benefits, supporting its clinical promotion.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy.

A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions.

The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma in situ. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy.

The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation.

This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS. A total of 2904 participants will be recruited and randomized in a 1:1 ratio into the HFRTsib and CFRTseq groups. All patients will receive whole breast irradiation, and those with positive axillary nodes will receive additional RNI, including internal mammary irradiation. The prescribed dose for the HFRTsib group will be 40 Gy in 15 fractions, combined with a SIB of 48 Gy in 15 fractions to the tumor bed. The CFRTseq group will receive 50 Gy in 25 fractions, with a sequential boost of 10 Gy in 5 fractions to the tumor bed.

This trial intends to assess the effectiveness and safety of SIB combined with HFRT in early breast cancer patients following BCS. The primary endpoint is locoregional control, and the results of this trial are expected to offer crucial evidence for utilizing HFRT in breast cancer patients after BCS.

This trial was registered at ClincalTrials.gov (NCT04025164) on July 18, 2019.

The addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme.

We included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis.

Between 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4-11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%.

Adjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects.

Breast cancer requires evaluating treatment plans using dosimetric and biological parameters. Considering radiation dose distribution and tissue response, healthcare professionals can optimize treatment plans for better outcomes.

This study aimed to evaluate the effects of the different Dose Calculation Algorithms (DCAs) and Biologically Model-Related Parameters (BMRPs) on the prediction of cardiopulmonary complications due to left breast radiotherapy.

In this practical study, the treatment plans of 21 female patients were simulated in the Monaco Treatment Planning System (TPS) with a prescribed dose of 50 Gy in 25 fractions. Dose distribution was extracted using the three DCAs [Pencil Beam (PB), Collapsed Cone (CC), and Monte Carlo (MC)]. Cardiopulmonary complications were predicted by Normal Tissue Complication Probability (NTCP) calculations using different dosimetric and biological parameters. The Lyman-Kutcher-Burman (LKB) and Relative-Seriality (RS) models were used to calculate NTCP. The endpoint for NTCP calculation was pneumonitis, pericarditis, and late cardiac mortality. The ANOVA test was used for statistical analysis.

In calculating Tumor Control Probability (TCP), a statistically significant difference was observed between the results of DCAs in the Poisson model. The PB algorithm estimated NTCP as less than others for all Pneumonia BMRPs.

The impact of DCAs and BMRPs differs in the estimation of TCP and NTCP. DCAs have a stronger influence on TCP calculation, providing more effective results. On the other hand, BMRPs are more effective in estimating NTCP. Consequently, parameters for radiobiological indices should be cautiously used s to ensure the appropriate consideration of both DCAs and BMRPs.

This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer.

In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed.

During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed.

Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis.

For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT.

Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0-III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted.

Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51-68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5-128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869-1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT.

In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC.

Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC.

Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions.

Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.

To evaluate the organ at risk (OAR) dose and its characteristic variation with different clinically usable prescription doses (RxD) for breast and chest wall radiotherapy in patients with early-stage left-sided breast cancer.

In total, 145 patients with early-stage breast cancers (T1N0M0-T2N0M0) on the left side were treated with radiotherapy after a modified radical mastectomy or breast conservation surgery, with a mean age of 45.1 ± 21.6 years. The patient received 4050 cGy of field-in-field (three-dimensional conformal radiotherapy) treatment limited to the breast or chest wall, excluding the supraclavicular node, axillary node and internal mammary chain, over 15 fractions. Additional plans of 5000 cGy/25 fractions, 4500 cGy/20 fractions and 2600 cGy/5 fractions were created with no or minor changes to the original plan. Mathematical modelling was used to study the distinctive change in the dose-volume characteristics for various OARs as a function of the RxD. OAR dosages, both absolute and normalised, were expressed in terms of the RxD. The mathematical (functional) relationship between OAR doses and different prescription levels was deduced by the least squares fit method.

The left lung mean dose, V5Gy (%), V10Gy (%) and V20Gy (%) and the heart mean dose, V10Gy (%) and V20Gy (%) were evaluated. The dose-volume parameters showed a parabolic variation (x2) with the RxD. Prescription normalised OAR doses showed a linear relationship with the RxD; relative dose increased with diminishing RxD. Normalised lung and heart mean doses exhibited saturation (linear relationship) with RxD variation. Paired sample t-test results between RxD versus all evaluated parameters were found to be statistically significant (P = 0.004). The Pearson correlation coefficient between different prescription levels for left lung mean dose (range 0.942-1.0), heart mean dose (range 1.0-1.0), left lung V5Gy (%) (range 0.987-1.0), left lung V10Gy (%) (range 0.991-0.999), heart V10Gy (%) (range 0.998-1.0).

The functional form of absolute OAR dose-volume parameters versus RxD is parabolic and the RxD normalised OAR dose-volume parameter versus RxD is a straight line with a negative slope as RxD increases. This indicates an increase in the relative OAR dose-volume parameters if the RxD is reduced. This study is the first of its kind to compare the OAR doses as a function of clinically used degenerate prescription levels. These data will help to comprehend the OAR doses while adopting a new dose fractionation regimen and reviewing the radiotherapy treatment plans.

Accelerated partial breast irradiation (APBI) is one of the standard treatment options in early-stage node negative breast cancer in selected patients. However, the optimal dose fractionation schedule still represents a challenge. We present the 12-year follow up results of clinical and cosmetic outcomes of once daily APBI with external beam radiation therapy which provides an APBI radiation dose equivalent to the whole breast radiation with a boost.

From July 2008 to August 2010, we enrolled 34 patients with T1, T2 (< 3cm) N0 to receive once daily APBI with three dimensional conformal radiation therapy (3D-CRT) to a total dose of 49.95 Gy over 15 single daily fractions over 3 weeks at 3.33 Gy per fraction. Ipsilateral breast tumor recurrence (IBTR), acute toxicity, late toxicity and cosmesis was analyzed. The median follow-up for all patients is 144 months (12 years).

The median age of the patients was 61 years (range 46-83). Nine patients had ductal carcinoma in situ (DCIS) and 25 patients had invasive cancer. The median size of the tumor with DCIS pathology was 0.5 cm, while median size of the tumor with invasive cancer pathology was 1.0 cm. All of the patients had negative margins and negative nodes. Two IBTR was observed (5.8%). One patient had DCIS at recurrence and other had invasive recurrence. Two patients died due to non-cancer cause. The 12-year actuarial ipsilateral breast recurrence free survival was 93.5% and the 12-year actuarial overall survival was 93.2%. Late Grade 2 toxicity was observed in 6 patients and late grade 3 toxicity was seen in 1 patient. 91% of the patients had excellent to good cosmesis.

This novel APBI dosing schema is based on an equivalent dose compared to whole breast radiation plus a tumor bed boost. This once daily APBI scheme is well-tolerated and demonstrates good to excellent cosmetic outcome and low rates of late complications on long term follow-up.

Proton radiotherapy may be a compelling technical option for the treatment of breast cancer due to its unique physical property known as the "Bragg peak." This feature offers distinct advantages, promising superior dose conformity within the tumor area and reduced radiation exposure to surrounding healthy tissues, enhancing the potential for better treatment outcomes. However, proton therapy is accompanied by inherent challenges, primarily higher costs and limited accessibility when compared to well-developed photon irradiation. Thus, in clinical practice, it is important for radiation oncologists to carefully select patients before recommendation of proton therapy to ensure the transformation of dosimetric benefits into tangible clinical benefits. Yet, the optimal indications for proton therapy in breast cancer patients remain uncertain. While there is no widely recognized methodology for patient selection, numerous attempts have been made in this direction. In this review, we intended to present an inspiring summarization and discussion about the current practices and exploration on the approaches of this treatment decision-making process in terms of treatment-related side-effects, tumor control, and cost-efficiency, including the normal tissue complication probability (NTCP) model, the tumor control probability (TCP) model, genomic biomarkers, cost-effectiveness analyses (CEAs), and so on. Additionally, we conducted an evaluation of the eligibility criteria in ongoing randomized controlled trials and analyzed their reference value in patient selection. We evaluated the pros and cons of various potential patient selection approaches and proposed possible directions for further optimization and exploration. In summary, while proton therapy holds significant promise in breast cancer treatment, its integration into clinical practice calls for a thoughtful, evidence-driven strategy. By continuously refining the patient selection criteria, we can harness the full potential of proton radiotherapy while ensuring maximum benefit for breast cancer patients.

This study aims to evaluate the long-term treatment outcome of conventional and hypofractionation radiotherapy in postmastectomy cancer breast patients.

A total of 140 postmastectomy breast cancer patients were included in this retrospective study, who were treated from 2012 to 2014 with chemotherapy and various fractionation radiotherapy schedules. Radiotherapy treatment records for study group-I received radiotherapy 4256 cGy in 16 fractions over 3½ weeks, group-II patients received 4005 cGy in 15 fractions over 3 weeks, and conventional radiotherapy group-III received 5000 cGy in 25 fractions over 5 weeks.

The median follow-up of patients from all groups was 60 months (range 9 to 111 months). There were 39 cases with disease failure, 13 (26%) in group I (42.56 Gy), 16 (40%) in group II (40.05 Gy), and 10 (20%) in group III (50 Gy). There were 4 locoregional recurrences (LRRs), two isolated, and 11 distant failures in group I, 3 LRRs (1 isolated LRR) and 15 distant failures in group II, and only one LRR and 9 distant failures in group III. The disease-free survival (DFS) were 74%, 60%, and 80%, respectively, in groups I, II, and III (P =0.044).

The long-term results of this study show that hypofractionation radiotherapy in postmastectomy cases is well tolerated and acute and late side effects are also comparable to conventional fractionation. In our study, locoregional and distant failure seems slightly higher with hypofractionation schedules than in other studies, highlighting the need for more studies with long-term follow-up in postmastectomy patients.

FAST-Forward aimed to identify a 5-fraction schedule of adjuvant radiotherapy delivered in 1 week that was non-inferior in terms of local cancer control and as safe as the standard 15-fraction regimen after primary surgery for early breast cancer. Published acute toxicity and 5-year results are presented here with other aspects of the trial.

Multicentre phase III non-inferiority trial. Patients with invasive carcinoma of the breast (pT1-3pN0-1M0) after breast conservation surgery or mastectomy randomised (1 : 1 : 1) to 40 Gy in 15 fractions (3 weeks), 27 Gy or 26 Gy in 5 fractions (1 week) whole breast/chest wall (Main Trial). Primary endpoint was ipsilateral breast tumour relapse; assuming 2% 5-year incidence for 40 Gy, non-inferiority pre-defined as < 1.6% excess for 5-fraction schedules (critical hazard ratio = 1.81). Normal tissue effects were assessed independently by clinicians, patients and photographs.

Two acute skin toxicity sub-studies were undertaken to confirm safety of the test schedules. Primary endpoint was proportion of patients with grade ≥ 3 acute breast skin toxicity at any time from the start of radiotherapy to 4 weeks after completion. Nodal Sub-Study patients had breast/chest wall plus axillary radiotherapy testing the same three schedules, reduced to the 40 and 26 Gy groups on amendment, with the primary endpoint of 5-year patient-reported arm/hand swelling.

A sequential hypofractionated or simultaneous integrated boost has not been studied.

Ninety-seven UK centres recruited 4096 patients (1361:40 Gy, 1367:27 Gy, 1368:26 Gy) into the Main Trial from November 2011 to June 2014. The Nodal Sub-Study recruited an additional 469 patients from 50 UK centres. One hundred and ninety and 162 Main Trial patients were included in the acute toxicity sub-studies.

Acute toxicity sub-studies evaluable patients: (1) acute grade 3 Radiation Therapy Oncology Group toxicity reported in 40 Gy/15 fractions 6/44 (13.6%); 27 Gy/5 fractions 5/51 (9.8%); 26 Gy/5 fractions 3/52 (5.8%). (2) Grade 3 common toxicity criteria for adverse effects toxicity reported for one patient. At 71-month median follow-up in the Main Trial, 79 ipsilateral breast tumour relapse events (40 Gy: 31, 27 Gy: 27, 26 Gy: 21); hazard ratios (95% confidence interval) versus 40 Gy were 27 Gy: 0.86 (0.51 to 1.44), 26 Gy: 0.67 (0.38 to 1.16). With 2.1% (1.4 to 3.1) 5-year incidence ipsilateral breast tumour relapse after 40 Gy, estimated absolute differences versus 40 Gy (non-inferiority test) were -0.3% (-1.0-0.9) for 27 Gy (p = 0.0022) and -0.7% (-1.3-0.3) for 26 Gy (p = 0.00019). Five-year prevalence of any clinician-assessed moderate/marked breast normal tissue effects was 40 Gy: 98/986 (9.9%), 27 Gy: 155/1005 (15.4%), 26 Gy: 121/1020 (11.9%). Across all clinician assessments from 1 to 5 years, odds ratios versus 40 Gy were 1.55 (1.32 to 1.83; p < 0.0001) for 27 Gy and 1.12 (0.94-1.34; p = 0.20) for 26 Gy. Patient and photographic assessments showed higher normal tissue effects risk for 27 Gy versus 40 Gy but not for 26 Gy. Nodal Sub-Study reported no arm/hand swelling in 80% and 77% in 40 Gy and 26 Gy at baseline, and 73% and 76% at 24 months. The prevalence of moderate/marked arm/hand swelling at 24 months was 10% versus 7% for 40 Gy compared with 26 Gy.

Five-year local tumour incidence and normal tissue effects prevalence show 26 Gy in 5 fractions in 1 week is a safe and effective alternative to 40 Gy in 15 fractions for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.

Ten-year Main Trial follow-up is essential. Inclusion in hypofractionation meta-analysis ongoing. A future hypofractionated boost trial is strongly supported.

FAST-Forward was sponsored by The Institute of Cancer Research and was registered as ISRCTN19906132.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/01/47) and is published in full in Health Technology Assessment; Vol. 27, No. 25. See the NIHR Funding and Awards website for further award information.

With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in the contralateral breast for long-term survivors of breast cancer. Individually estimated radiation absorbed doses to the four quadrants and areola central area of the contralateral breast were estimated for 2,132 women treated with radiation therapy for local/regional breast cancers at age <55 years diagnosed between 1985 and 2008. The two inner quadrant doses and two outer quadrant doses were averaged. Trends in dose to each of the three areas of the contralateral breast were evaluated in multivariable models. The population impact of reducing contralateral breast dose on the incidence of radiation-associated CBC was assessed by estimating population attributable risk fraction (PAR) in a multivariable model. The median dose to the inner quadrants of the contralateral breast was 1.70 Gy; to the areola, 1.20 Gy; and to the outer quadrants, 0.72 Gy. Ninety-two percent of patients received ≥1 Gy to the inner quadrants. For each calendar year of diagnosis, dose declined significantly for each location, most rapidly for the inner quadrants (0.04 Gy/year). Declines in dose were similar across subgroups defined by age at diagnosis and body mass index. The PAR for CBC due to radiation exposure >1 Gy for women <40 years of age was 17%. Radiation dose-reduction measures have reduced dose to the contralateral breast during breast radiation therapy. Reducing the dose to the contralateral breast to <1 Gy could prevent an estimated 17% of subsequent radiation-associated CBCs for women treated under 40 years of age. These dose estimates inform CBC surveillance for the growing number of breast cancer survivors who received radiation therapy as young women in recent decades. Continued reductions in dose to the contralateral breast could further reduce the incidence of radiation-associated CBC.

The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system.

The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models.

The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose).

The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.

The present study attempts to evaluate the acute and subacute toxicities of hypofractionated volumetric modulated arc therapy (HFX-VMAT) in patients with early breast cancer (EBC). It is a retrospective analysis of 23 patients treated with HFX-VMAT after breast-conserving surgery between September 2021 and February 2022. A total dose of 50.05 to 52.55 Gy was delivered, consisting of 40.05 Gy to the ipsilateral whole breast in 15 fractions of 2.67 Gy and a tumor bed boost dose of 10-12.5 Gy in 4-5 fractions. The primary endpoint was acute/subacute radiation pneumonitis (RP). The secondary endpoint was poor cosmesis, indicating acute/subacute radiation dermatitis. Chest computed tomography (CT) and the Common Terminology Criteria for Adverse Events v.5.0 were used to assess acute and subacute RP and dermatitis, respectively, during radiotherapy (RT) and at 3- and 6-months post-RT. The median follow-up duration was 3.8 months (range, 2.3-4.2). A total of seven patients developed RP. None of these patients presented RP-related symptoms; the diagnosis was based on radiologic findings observed on follow-up chest CT. Among the seven patients with RP, five had right-sided, and two had left-sided breast tumors (71.4 vs. 28.6%; P=0.026). Grade 1 erythema was observed in 19 patients (82.6%) and grade 2 erythema in four (17.4%). The mean target dose, D_105% (the dose received by 105% of the target volume), homogeneity index, mean lung dose, ipsilateral lung V₂₀ (the percentage volume receiving 20 Gy), and V₃₀ (the percentage volume receiving 30 Gy) for ipsilateral whole breast RT were significantly associated with RP (P=0.039, 0.047, 0.018, 0.015, 0.018 and 0.003, respectively.). HFX-VMAT showed tolerable acute/subacute toxicities. Therefore, HFX-VMAT is an effective and safe treatment option for EBC.

The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer.

Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions.

A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules.

Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.

Breast cancer is the most prevalent cancer in women, and the second leading cause of cancer death in women in the United States. Radiation therapy is an important component in the multimodal management of breast cancer, including early stage and locally advanced breast cancers, as well as metastatic cases. Breast cancer radiation therapy has seen significant advancements over the past 20 years. This article discusses the latest advances in the radiotherapeutic management of breast cancer, especially focusing on the technological advances in radiation treatment planning and techniques that have exploited the understanding of radiation biology.