A narrative review for radiation oncologists to implement preoperative partial breast irradiation.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454).

Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study - a phase I/II clinical trial protocol.

BACKGROUND: Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients. METHODS: This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate. DISCUSSION: The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale. TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov ( NCT04679454 ).

Mastectomy alone for pT1-2 pN0-1 breast cancer patients: when postmastectomy radiotherapy is indicated.

PURPOSE: To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy. METHODS: Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray's test tested difference. Kaplan-Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed. RESULTS: 1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2 years (9.2 years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival. CONCLUSIONS: Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

Prognostic significance of neutrophil-to-lymphocyte ratio in HPV status era for oropharyngeal cancer.

AIM: To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. PATIENTS AND METHODS: A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. RESULTS: Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR <3 and ≥3, respectively. CONCLUSION: A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.

Correction to: Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

Unfortunately, the denomination of the IEO was incorrectly published in the affiliation of this original.

Radioablation +/- hormonotherapy for prostate cancer oligorecurrences (Radiosa trial): potential of imaging and biology (AIRC IG-22159).

BACKGROUND: Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are: 1. Compare SBRT +/- ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL). 2. Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses. METHODS: This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3 years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed: 1. Randomized clinical study (3 years for accrual and 2 years for follow-up and data analysis); 2. Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria; 3. Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling. We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed. DISCUSSION: Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria. So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness. TRIAL REGISTRATION: The RADIOSA study was prospectively registered at clinicaltrials.gov ( NCT03940235 , May 2019).

Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

PURPOSE: To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT). METHODS AND MATERIALS: We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS. CONCLUSIONS: A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Tools to Guide Radiation Oncologists in the Management of DCIS.

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

Ultra-hypofractionated whole breast adjuvant radiotherapy in the real-world setting: single experience with 271 elderly/frail patients treated with 3D and IMRT technique.

PURPOSE: The purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT). METHODS: From July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1-T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases. RESULTS: A total of 271 patients were included in the study. Median age was 76 (46-86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early-late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm3 was reported as predictive for moderate-severe (≥ G2) acute toxicity. CONCLUSIONS: Weekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique.

The POLO (Partially Omitted Lobe) approach to safely treat in-breast recurrence after intraoperative radiotherapy with electrons.

OBJECTIVES: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). METHODS: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. RESULTS: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. CONCLUSION: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. ADVANCES IN KNOWLEDGE: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

Ten-year results of hypofractionated whole breast radiotherapy and intraoperative electron boost in premenopausal women.

AIM: To evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women. METHODS AND MATERIALS: Women aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed. RESULTS: 481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5-6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8-83.5), BCSS 97.5 % (95 % CI, 95.5-98.6 %), OS 96.5 % (95 % CI, 94.3-97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases. CONCLUSIONS: ELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable.

Comparing TomoHelical and TomoDirect in postmastectomy hypofractionated radiotherapy after immediate breast reconstruction.

BACKGROUND: Postmastectomy radiotherapy (PMRT) with TomoHelical™ (TH) or TomoDirect™ (TD) allows a uniform target coverage. In this study, we compare treatment plans using TD and TH in the setting of hypofractionated PMRT and immediate breast reconstruction. MATERIAL AND METHODS: The TD-treatment plans of breast cancer patients treated between May 2016 and August 2019 were retrospectively selected. All the TD plans were re-planned on TH with the same prescription dose (40.05 Gy/15 fractions) and according to our dose/volume constraints. Data about the 2 treatment plans were compared with a focus on PTV coverage and all the organs at risk (OARs) constraints. RESULTS: Fifty patients for a total number of 100 treatment plans (50 with TD and 50 re-planned with TH) were analyzed. All the median value in the TD PTV CHEST WALL plans fulfilled the predefined planning objectives, even though TH emerged as best for target coverage with statistically significant difference for V90%. TD provided the lowest V95% for the PTV SVC, but the median value was near to the recommended value of 90% (89.8 % vs 98.6% for TD and TH, respectively). Overall, TD reached the best OARs sparing. The main statistically significant differences with TH were for contralateral breast, ipsilateral and contralateral lung. All the other dose values for TH were higher than TD, but they fulfilled the recommended/acceptable predefined planning objectives. CONCLUSIONS: In the setting of PMRT, TD compared to TH reached an acceptable target volume coverage, with an optimal sparing of OARs.

Predictors of positive axillary non-sentinel lymph nodes in breast cancer patients with positive sentinel lymph node biopsy after neoadjuvant systemic therapy.

AIM: To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. RESULTS: Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23-56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. CONCLUSIONS: Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

Implant risk failure in patients undergoing postmastectomy 3-week hypofractionated radiotherapy after immediate reconstruction.

AIM: To evaluate reconstruction failure (RF) rate in patients receiving implant-based immediate breast reconstruction (IBR) and hypofractionated (HF) postmastectomy radiation therapy (PMRT). MATERIALS AND METHODS: Stage II-III breast cancer patients, treated with HF-PMRT using intensity modulated radiotherapy were stratified in two groups according to IBR: single-stage direct-to-implant (DTI-group) and two-stage expander and implant (TE/I-group). Irradiated patients were matched with non-irradiated ones who underwent the same IBR during the same period. Prescription dose was 40.05 Gy/15 fractions to chest wall and infra/supraclavicular nodal region. Primary endpoint was RF defined as the need of major revisional surgery (MaRS) for implant removal or conversion to autologous reconstruction. Secondary endpoint was the rate of minor revisional surgeries (MiRS) including implant repositioning or substitution with another implant. RESULTS: One hundred and seven irradiated patients (62 in TE/I-group, 45 in DTI-group) were matched with 107 non-irradiated subjects. Median follow-up was 4.2 years (0.1-6.1) In the TE/I setting, MaRS was performed in 8/62 irradiated patients (12.9%) of the irradiated TE/I group compared to 1/62 (1.6%) non-irradiated subjects (p = 0.015). In the DTI setting, MaRs occurred in 3/45 irradiated patients (6.7%) compared to 1/45 non-irradiated ones (2.2%) (p = 0.35). Overall MaRS rate was 10.3% in the irradiated group. MiRS was performed in 35.6% and 31.1% of the irradiated and non-irradiated DTI-groups (p = 0.65), respectively, and in 12.9% and 8.1% of the irradiated and non-irradiated TE/I groups (p = 0.38), respectively. CONCLUSIONS: Compared to the non-irradiated counterparts, the TE/I group showed higher rate of RF, while no statistically significant difference was observed for the DTI group. The use of hypofractionation and IMRT to implant-based IBR did not seem to increase the risk of RF which appeared to be in line with the literature.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Workload of breast image-guided intensity-modulated radiotherapy delivered with TomoTherapy.

OBJECTIVE: To report treatment times (door to door) of adjuvant treatments of breast cancer (BC) with intensity-modulated radiotherapy (IMRT). METHODS: Treatment times of 62 patients with BC on the TomoTherapy Hi-Art System were collected for the analysis. Patients underwent either locoregional radiotherapy (postmastectomy radiotherapy [PMRT]) with helical modality (TomoHelical) or whole breast radiotherapy (RT) with simultaneous integrated boost (WBRT-SIB) with direct modality (TomoDirect). Door-to-door time was broken down into different steps, which were crucial to RT session. RESULTS: A total of 594 treatment fractions were monitored. Median treatment time was 22.4 minutes (17.2-30.8) for PMRT and 14.4 minutes (10.9-23.5) for WBRT-SIB. The mean beam-on time accounted for 61.36% of the overall treatment time for PMRT compared to 57% for WBRT-SIB. The beam-on time was a much more time-consuming process. CONCLUSION: This treatment times analysis on the use of IMRT for BC might be useful to organize and improve the workflow efficiency in RT facilities.

Long-Term Results and Reconstruction Failure in Patients Receiving Postmastectomy Radiation Therapy with a Temporary Expander or Permanent Implant in Place.

BACKGROUND: This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant. METHODS: Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap. RESULTS: The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09). CONCLUSIONS: Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Breast Adjuvant Radiotherapy Amid the COVID-19 Crisis in a Hub Cancer Center, Lombardy, Italy.

INTRODUCTION: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here. METHODS: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables. RESULTS: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant (p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions. CONCLUSION: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals.

Phase II prospective trial "Give Me Five" short-term high precision radiotherapy for early prostate cancer with simultaneous boost to the dominant intraprostatic lesion: the impact of toxicity on quality of life (AIRC IG-13218).

As part of the AIRC IG-13218 (NCT01913717), we analyzed data from patients with low- and intermediate-risk prostate cancer treated with extreme hypofractionated radiotherapy (RT) and simultaneous boost to the intraprostatic lesion. The aim of the study is to identify clinically meaningful information through the analysis of validated questionnaires testing gastrointestinal (GI) and genitourinary (GU) RT-related toxicity and their impact on quality of life (QoL). At the end of RT treatment, clinical assessment and prostate-specific antigen (PSA) measurements were performed every 3 months for at least 2 years and GI and GU toxicities were evaluated contextually. QoL of enrolled patients was assessed by International Prostate Symptoms score (IPSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), EORTC QLQ prostate specific (QLQ-PR25), and sexual activity by International Index of Erectile Function (IIEF-5). Patients' score changes were calculated at the end of RT, at one month after RT and at 12 and 24 months. Sixty-five prospectively enrolled patients were analyzed. Extensive analysis of different QoL assessments showed that patients' tolerance was satisfactory across all the considered time points, with no statistically significant change of QoL from baseline compared to that before RT. Overall survival and biochemical progression-free survival at 2-years were of 98% and 97%, respectively. Despite the toxicity of extreme hypofractionation was low and tumor control was encouraging, a longer follow-up is necessary to confirm our findings. The increasing dose to the dominant intraprostatic lesion does not worsen the RT toxicity and consequently does not affect patients' QoL, thus questioning the possibility of an even more escalated treatment.

Comparison of Outcomes and Toxicity Between Extreme and Moderate Radiation Therapy Hypofractionation in Localized Prostate Cancer: A Propensity Score Analysis.

PURPOSE: To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups. METHODS AND MATERIALS: Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival. RESULTS: Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P < .001 and P < .002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups. CONCLUSIONS: EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa.