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Introduction: Axillary lymph node dissection (ALND) has always been part of breast cancer (BC) treatment. However, during the past 25 years, the surgical management of the axilla has shifted towards a more conservative approach. Until now, ALND has remained the standard surgical technique when the sentinel lymph node (SLN) is macrometastatic. However, ALND may now be considered overtreatment for early-stage BC. The SINODAR-ONE trial is a prospective non-inferiority multicenter randomized study aimed at assessing the role of ALND in patients undergoing either breast-conserving surgery (BCS) or mastectomy for T1-2 BC presenting 1-2 macrometastatic SLNs. Objectives: The primary endpoint was to evaluate whether sentinel lymph node biopsy (SLNB) only was associated with clinically relevant worsening of the prognosis compared with ALND in terms of overall survival (OS). The secondary endpoint was to evaluate whether there was increased regional (lymph node recurrence) or distant recurrence in terms of recurrence-free survival (RFS) in patients with macrometastatic SLN who did not undergo ALND. Methods: Patients were randomly assigned (1:1 ratio) to either removal of ≥10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). Results: The trial started in April 2015 and ceased in April 2020, involving 889 patients. The majority of the patients (75.2%) underwent BCS; 328 of 439 patients (74.7%) in the standard treatment arm, and 333 of 440 patients (75.7%) in the experimental treatment arm. 218 patients (24.8%) underwent mastectomy. SLN status at randomization was comparable between the two groups of treatment, with a median number of two SLNs removed and a median number of one positive SLN in both arms. The median number of non-SLNs identified at definitive histopathological evaluation was 16 (interquartile range [IQR] 12–21) in the ALND group. Overall, 193 of 439 patients (44.0%) in the standard treatment arm had additional macrometastases in the removed axillary lymph nodes. However, the median number of positive non SLNs was 0 (IQR 0–1) in the ALND group. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with a 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with a 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB only arm, respectively (p = 0.936). Conclusion: The 3-year survival and relapse rates of T1-2 BC patients with 1-2 macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND in patients undergoing BCS. However, given the low number of patients treated with mastectomy, there is no certainty that ALND omission can be extended also to this sub-group. In order to collect further evidence regarding the safety of the experimental treatment in patients candidates for mastectomy, the reopening of the enrollment of these patients as part of a single-arm experimental study started in June 2022. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Testori, Valentina Errico, Alberto Bottini, Simone Di Maria Grimaldi, Giulia Caraceni, Luca Boni, Paolo Bruzzi, Bethania Fernandes, Davide Franceschini, Ruggero Spoto, Rosalba Torrisi, Marta Scorsetti, Armando Santoro, Giuseppe Canavese, Corrado Tinterri. Preservation of axillary lymph nodes in breast cancer patients undergoing mastectomy with 1-2 metastatic sentinel lymph nodes: The current status and future perspectives of the multicenter randomized clinical trial SINODAR-ONE [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-06-01.

Introduction: Patients with triple-negative (TN) or HER2-enriched ipsilateral breast cancer recurrence (IBCR) seem to be excluded from a second breast-conserving surgery (BCS) under the assumption that salvage mastectomy would provide better oncological outcomes. Objectives: The objective of this study was to describe the clinical features of these patients, to compare the two surgical alternatives (salvage mastectomy versus second BCS) in terms of oncological results, and to identify independent factors influencing prognosis and surgical treatment. Methods: We retrospectively reviewed all the consecutive patients with histologically confirmed TN or HER2-enriched IBCR. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. Results: Eighty-five patients were affected by TN or HER2-enriched IBCR, with a median age of 60 years (range, 32-87 years). The majority of patients (72.9%) were treated with salvage mastectomy. There was no significant difference in terms of DFS between patients receiving a second BCS or mastectomy (p=0.596). However, patients undergoing a second BCS had significantly better DDFS, OS, and BCSS compared to mastectomy (p=0.009; p=0.002; p=0.001, respectively). Tumor dimension < 16 mm (78.3% versus 38.7%, hazard ratio (HR)=3.602, 95% confidence interval (95% CI)=1.534-8.459, p=0.003) was found to significantly increase the probability of receiving a second BCS and positively affects recurrence and survival outcomes (DFS: HR=8.065, 95% CI=2.320-28.034, p=0.001; DDFS: HR=17.011, 95% CI=3.853-75.099, p=0.001; OS: HR: 13.881, 95% CI=2.730-70.579, p=0.002; BCSS: HR=36.773, 95% CI=4.579-295.322, p=0.001). Second BCS represents an independent protective factor for OS and BCSS (OS: HR=0.246, 95% CI=0.027-0.697, p=0.002; BCSS: HR=0.313, 95% CI=0.092-0.511, p=0.002). Conclusion: Salvage mastectomy is not always necessary and it does not seem to increase survival compared to a second BCS. This reinforces the concept that the prognosis of TN and HER2-enriched BC recurrence is mainly driven by the biology of the disease, rather than by the extent of surgery. In patients with small (< 16 mm) aggressive subtypes of IBCR, a second conservative approach can still be evaluated and offered, presenting acceptable loco-regional control and survival. Citation Format: Damiano Gentile, Andrea Sagona, Erika Barbieri, Simone Di Maria Grimaldi, Ruggero Spoto, Davide Franceschini, Stefano Vaccari, Valeriano Vinci, Ersilia Biondi, Lorenzo Scardina, Corrado Tinterri. Salvage mastectomy is not always necessary for aggressive subtypes of ipsilateral breast cancer recurrence: A single-institution retrospective study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-09.

OBJECTIVE: Patients with triple-negative (TN) or human epidermal growth factor 2 (HER2)-enriched ipsilateral breast cancer recurrence (IBCR) seem to be excluded from a second breast-conserving surgery (BCS) under the assumption that salvage mastectomy would provide better oncological outcomes. The objective of this study was to describe the clinical features of these patients, to compare the two surgical alternatives (salvage mastectomy versus second BCS) in terms of oncological results, and to identify independent factors influencing prognosis and surgical treatment. MATERIALS AND METHODS: We retrospectively reviewed all the consecutive patients with histologically confirmed TN or HER2-enriched IBCR. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. RESULTS: Eighty-five patients were affected by TN or HER2-enriched IBCR. The majority of patients (72.9%) were treated with salvage mastectomy. There was no significant difference in terms of DFS between patients receiving a second BCS or mastectomy (p = 0.596). However, patients undergoing a second BCS had significantly better DDFS, OS and BCSS compared to mastectomy (p = 0.009; p = 0.002; p = 0.001, respectively). Tumor dimension

Background: This study evaluated the outcome, toxicity and predictive factors in patients unfit for concurrent chemo-radiotherapy (CT-RT) treated with hypofractionated sequential CT-RT or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: We included patients affected by LA-NSCLC (stage IIA-IVA) treated with a total dose of 50–60 Gy in 20 fractions. The primary outcomes were local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes with prognostic factors. Results: Between 2011 and 2019, 210 patients were treated, 113 (53.8%) with sequential CT-RT and 97 (46.2%) with exclusive RT. After a median follow-up of 15.3 months, 74 patients (35.2%) had a local progression and 133 (63.3%) had a distant progression. The one-, two- and five-year LC were 73.6%, 55.3% and 47.9%, respectively. At the time of analysis, 167 patients (79.5%) died. The one-, two- and five-year OS were 64.7%, 36% and 20%, respectively. PTV volume correlated with PFS (p = 0.001) and LC (p = 0.005). Acute and late toxicity occurred in 82% and 26% of patients. Conclusions: Albeit with the known limitations of a retrospective and heterogeneous study, our work shows that hypofractionated sequential CT-RT or exclusive RT offer a good local control and toxicity profile and a promising survival rate in LA-NSCLC patients unfit for the concurrent CT-RT scheme.

Objective: The aim of this study was to evaluate clinical results and prognostic factors in a cohort of patient with oligometastatic esophagogastric adenocarcinoma treated with stereotactic radiation therapy (SRT). Methods: This retrospective study included patients affected by 1–3 metastases treated with SRT from 2013 to 2021. Local control (LC), overall survival (OS), progression-free survival (PFS), time to polymetastatic dissemination (TTPD) and time to systemic therapy change/initiation (TTS) were evaluated. Results: Between 2013 and 2021, 55 patients were treated with SRT on 80 oligometastatic sites. Median follow-up was 20 months. Nine patients had local progression. 1 and 3 years LC was respectively 92 and 78%. 41 patients experienced further distant disease progression, median PFS was 9.6 months, 1 and 3 years PFS was respectively 40 and 15%. 34 patients died, median OS was 26.6 months, 1 and 3 years OS was respectively 78 and 40%. During follow-up, 24 patients changed or initiated a new systemic therapy; median TTS time was 9 months. 27 patients experienced poliprogression, 44% after 1 year and 52% after 3 years. Median TTPD was 8 months. The best local response (LR), tyming of metastases and PS were related with prolonged PFS on multivariate analysis. LR was correlated with OS at multivariate analysis. Conclusion: SRT represents a valid treatment for oligometastatic esophagogastric adenocarcinoma. CR correlated with PFS and OS, while metachronous metastasis and a good PS correlated with a better PFS. Advances in knowledge: In selected gastroesopagheal oligometastatic patients, SRT can prolong OS Local response to SRT, metachronous timing of metastases and better PS improve PFS. Local response correlates with OS.

Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionation schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly include both patient and tumour characteristics in the physician’s decision-making process. Unfortunately, hypofractionation for breast cancer radiation therapy needed long time to enter the routine practice during the last decades despite the level-1 evidence published over time. Hereby we present the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation to harmonically boost routine clinical practice implementation following evidence-based data.

Background To analyze RapidPlan knowledge-based models for DVH estimation of organs at risk from breast cancer VMAT plans presenting arc sectors en-face to the breast with zero dose rate, feature imposed during the optimization phase (avoidance sectors AS). Methods CT datasets of twenty left breast patients in deep-inspiration breath-hold were selected. Two VMAT plans, PartArc and AvoidArc, were manually generated with double arcs from ~ 300 to ~ 160°, with the second having an AS en-face to the breast to avoid contralateral breast and lung direct irradiation. Two RapidPlan models were generated from the two plan sets. The two models were evaluated in a closed loop to assess the model performance on plans where the AS were selected or not in the optimization. Results The PartArc plans model estimated DVHs comparable with the original plans. The AvoidArc plans model estimated a DVH pattern with two steps for the contralateral structures when the plan does not contain the AS selected in the optimization phase. This feature produced mean doses of the contralateral breast, averaged over all patients, of 0.4 ± 0.1 Gy, 0.6 ± 0.2 Gy, and 1.1 ± 0.2 Gy for the AvoidArc plan, AvoidArc model estimation, RapidPlan generated plan, respectively. The same figures for the contralateral lung were 0.3 ± 0.1 Gy, 1.6 ± 0.6 Gy, and 1.2 ± 0.5 Gy. The reason was found in the possible incorrect information extracted from the model training plans due to the lack of knowledge about the AS. Conversely, in the case of plans with AS set in the optimization generated with the same AvoidArc model, the estimated and resulting DVHs were comparable. Whenever the AvoidArc model was used to generate DVH estimation for a plan with AS, while the optimization was made on the plan without the AS, the optimizer evidentiated the limitation of a minimum dose rate of 0.2 MU/°, resulting in an increased dose to the contralateral structures respect to the estimation. Conclusions The RapidPlan models for breast planning with VMAT can properly estimate organ at risk DVH. Attention has to be paid to the plan selection and usage for model training in the presence of avoidance sectors.

Background To investigate the performance of a narrow-scope knowledge-based RapidPlan (RP) model for optimisation of intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans applied to patients with pleural mesothelioma. Second, estimate the potential benefit of IMPT versus VMAT for this class of patients. Methods A cohort of 82 patients was retrospectively selected; 60 were used to "train" a dose-volume histogram predictive model; the remaining 22 provided independent validation. The performance of the RP models was benchmarked, comparing predicted versus achieved mean and near-to-maximum dose for all organs at risk (OARs) in the training set and by quantitative assessment of some dose-volume metrics in the comparison of the validation RP-based data versus the manually optimised training datasets. Treatment plans were designed for a prescription dose of 44 Gy in 22 fractions (proton doses account for a fixed relative biological effectiveness RBE = 1.1). Results Training and validation RP-based plans resulted dosimetrically similar for both VMAT and IMPT groups, and the clinical planning aims were met for all structures. The IMPT plans outperformed the VMAT ones for all OARs for the contra-lateral and the mean and low dose regions for the ipsilateral OARs. Concerning the prediction performance of the RP models, the linear regression for the near-to-maximum dose resulted in Dachieved = 1.03Dpredicted + 0.58 and Dachieved = 1.02Dpredicted + 1.46 for VMAT and IMPT, respectively. For the mean dose it resulted: Dachieved = 0.99Dpredicted + 0.34 and Dachieved = 1.05Dpredicted + 0.27 respectively. In both cases, the linear correlation between prediction and achievement is granted with an angular coefficient deviating from unity for less than 5%. Concerning the dosimetric comparison between manual plans in the training cohort and RP-based plans in the validation cohort, no clinical differences were observed for the target volumes in both the VMAT and IMPT groups. Similar consistency was observed for the dose-volume metrics analysed for the OAR. This proves the possibility of achieving the same quality of plans with manual procedures (the training set) or with automated RP-based methods (the validation set). Conclusion Two models were trained and validated for VMAT and IMPT plans for pleural mesothelioma. The RP model performance resulted satisfactory as measured by the agreement between predicted and achieved (after full optimisation) dose-volume metrics. The IMPT plans outperformed the VMAT plans for all the OARs (with different intensities for contra- or ipsilateral structures). RP-based planning enabled the automation of part of the optimisation and the harmonisation of the dose-volume results between training and validation. The IMPT data showed a systematic significant dosimetric advantage over VMAT. In general, using an RP-based approach can simplify the optimisation workflow in these complex treatment indications without impacting the quality of plans.