Search

Background: For patients who are node positive at presentation and are found to have a complete nodal tumour response (ypN0) post-neoadjuvant chemotherapy (NACT), we do not yet know whether local axillary therapy can be modified based on the response to NACT. ATNEC addresses whether axillary treatment can be de-escalated, post-surgery, in T1-3N1M0 breast cancer patients who have no residual nodal disease post-NACT. Methods: Design: ATNEC is a phase III, randomized (1:1), multi-centre trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to ypN0, ATNEC randomizes patients to axillary treatment (nodal radiotherapy [ART] or axillary nodal clearance [ANC]) vs. no further axillary treatment. Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria: • Age ≥ 18 • Male or female • T1-3N1M0 breast cancer at diagnosis (pre-NACT) • FNA or core biopsy confirmed axillary nodal metastases at presentation • ER and HER2 status evaluated on primary tumour • Received standard NACT as per local guidelines • Imaging of the axilla to assess response to NACT • Dual tracer SNB post-NACT and at least 3 nodes removed (sentinel nodes and marked node). o If a single tracer is used, the patient is eligible if the involved node is marked pre-NACT and at least 3 nodes removed (including the marked node) o If axillary node sampling is performed following failed localization of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node). o If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node of the 3 removed nodes. • No evidence of nodal metastases post-NACT (ypN0) Exclusion criteria: • Bilateral invasive breast cancer • SNB prior to NACT • Previous ipsilateral axillary nodal surgery • Previous cancer within last 5 years or concomitant malignancy Aims: To assess whether omitting further axillary treatment (ART or ANC) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who post NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease-free survival, and whether lymphoedema is reduced at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomization, avoid bias from exclusions and preserve statistical power. Radiotherapy Quality Assurance: ATNEC has in-built radiotherapy QA coordinated by National Radiotherapy Trials QA (RTTQA) group. The RTQA monitors trial protocol compliance ensuring clinical outcomes reflect differences in randomization schedules rather than departures from the protocol. ATNEC is the only trial in the UK that offers QA for IMC radiotherapy. Screening Data: ATNEC collects screening data to monitor acceptance rates and reasons why patients decline the trial to identify ways to improve recruitment. Screening data until 30-Jun-22 shows that 69% of eligible patients were approached (244/354) and, of those approached, 45% were consented (109/244). For the 81 patients who declined, the most common reasons were; preference for axillary treatment (31%), preference for no axillary treatment (10%), no reason documented (23%) and ineligibility (21%). ClinicalTrials.gov: NCT04109079 Target accrual: 1900 Target sites: 100 Trial Status: Recruiting. As of 30-Jun-22: 52 sites open, 158 patients enrolled, 54 randomised. ATNEC is open to new sites and international collaboration. Citation Format: Amit Goyal, Sophie Nicholls, Andrea Marshall, Natalie Hammonds, Duncan Wheatley, Beatrix Elsberger, Janice Rose, Helen-Teresa Edwards, Roeum Butt, Abeer Shaaban, Shama Puri, Samreen Ahmed, Tara Homer, Luke Vale, Julie Bruce, Sophie J. Gasson, Helen Higgins, Janet A. Dunn. ATNEC: A multicentre, randomized trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the axillary lymph nodes after neoadjuvant chemotherapy [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 OT1-09-02.

Background: For patients who are node positive to start at presentation and are found to have a complete nodal tumour response (ypN0) post neoadjuvant chemotherapy (NACT), we do not yet know whether local axillary therapy can be modified based on the response to NACT. ATNEC randomised trial specifically address axillary management following NACT in patients with proven axillary node metastases. Methods: Design: ATNEC is a phase III, randomised (1:1), multi-centre trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to benign (ypN0), ATNEC randomly assigns patients to axillary treatment (nodal radiotherapy or axillary nodal clearance) vs. no axillary treatment (without further surgery). Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Stratification: Institution, type of surgery (breast conserving surgery [BCS] vs mastectomy), receptor status (triple negative vs HER2 positive vs ER status positive and/or PR status positive and HER2 negative). Inclusion criteria:. • Age ≥ 18. • Male or female. • T1-3N1M0 breast cancer at diagnosis (pre-NACT). • FNA or core biopsy confirmed axillary nodal metastases at presentation. • ER and HER2 status evaluated on primary tumour. • Received standard NACT as per local guidelines. • Imaging assessment of the axilla at completion of NACT. • Dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node). o If a single tracer is used, the patient is eligible if the involved node is marked before NACT and at least 3 nodes removed (including the marked node). o If axillary node sampling is performed following failed localisation of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node). o If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node and at least 3 nodes removed. • No evidence of nodal metastases post NACT (ypN0). Exclusion criteria:. • Bilateral invasive breast cancer. • SNB prior to NACT. • Previous ipsilateral axillary nodal surgery. • Previous cancer within last 5 years or concomitant malignancy. Radiotherapy Quality Assurance: ATNEC has in-built radiotherapy QA programme that is coordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900 Number of sites: 100 Trial Status: Recruiting. Trial is open to new sites. Disclaimer: This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (Reference - HTA NIHR128311). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Citation Format: Amit Goyal, Sophie Cramp, Andrea Marshall, Duncan Wheatley, Natalie Hammonds, Shama Puri, Tara Homer, Luke Vale, Roeum Butt, Romaana Mir, Janice Rose, Helen Teresa Edwards, Samreen Ahmed, Abeer Shaaban, Beatrix Elsberger, Julie Bruce, Sophie Gasson, Valerie Speirs, Jacqui Shaw, Helen Higgins, Janet Dunn. ATNEC: A multi-centre, randomised trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the lymph glands after neoadjuvant chemotherapy (clinicaltrials.gov: nct04109079) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-01.

Objectives: Radiologist input in peer review of head and neck radiotherapy has been introduced as a routine departmental approach. The aim was to evaluate this practice and to quantitatively analyse the changes made. Methods: Patients treated with radical-dose radiotherapy between August and November 2020 were reviewed. The incidence of major and minor changes, as defined by The Royal College of Radiologists guidance, was prospectively recorded. The amended radiotherapy volumes were compared with the original volumes using Jaccard Index (JI) to assess conformity; Geographical Miss Index (GMI) for undercontouring; and Hausdorff Distance (HD) between the volumes. Results: In total, 73 out of 87 (84%) patients were discussed. Changes were recommended in 38 (52%) patients: 30 had ≥1 major change, eight had minor changes only. There were 99 amended volumes: The overall median JI, GMI and HD was 0.91 (interquartile range [IQR]=0.80–0.97), 0.06 (IQR = 0.02–0.18) and 0.42 cm (IQR = 0.20–1.17 cm), respectively. The nodal gross-tumour-volume (GTVn) and therapeutic high-dose nodal clinical-target-volume (CTVn) had the biggest magnitude of changes: The median JI, GMI and HD of GTVn was 0.89 (IQR = 0.44–0.95), 0.11 (IQR = 0.05–0.51), 3.71 cm (IQR = 0.31–6.93 cm); high-dose CTVn was 0.78 (IQR = 0.59–0.90), 0.20 (IQR = 0.07–0.31) and 3.28 cm (IQR = 1.22–6.18 cm), respectively. There was no observed difference in the quantitative indices of the 85 ‘major’ and 14 ‘minor’ volumes (p = 0.5). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and can help avoid gross error in contouring. Advances in knowledge: The major and minor classifications may benefit from differentiation with quantitative indices but requires correlation from clinical outcomes.

Background: POSNOC is a UK-ANZ multicentre, non-inferiority, randomised trial comparing systemic therapy alone with systemic therapy plus Axillary Treatment (Axillary radiotherapy or ALND) for women with ≤2 macrometastases at SNB. The primary outcome is axillary recurrence within 5 years. This paper describes screening, recruitment and compliance data. Methods: Sites were requested on a monthly basis to upload screening data and provide reasons for non-recruitment of eligible patients into the trial. Sites entered in the online database whether the patients were compliant with their randomisation allocation. Results: The study opened in July 2014 and completed target recruitment of 1900 women (24% of those screened) in July 2021, at 95 sites in the UK and 20 sites in Australia and New Zealand. The reason for non-enrolment was unknown in 1300 women. Of the remaining 4774 women with known reasons, who were screened but not randomised, the most common reasons for non-recruitment were due to either patients (n=2219, 46.5%) or their clinicians (n=782, 16.4%) favouring axillary treatment, or patients (n=490, 10.3%) or their clinicians (n=170, 3.6%) not wishing to have axillary treatment. Over the course of the study, there was an increase in the proportion of patients wanting axillary treatment and declining the trial (Mean % patients declined 2015 – 17.9%, 2021 – 39.1%). Mean number of participants recruited per site per month was 0.24 (SD 0.18) overall, 0.25 (SD 0.19) in the UK, and 0.19(SD 0.15) in ANZ. The mean was < 0.3 in 79 sites and >0.9 in only one site. Recruitment rate remained consistent throughout the study (mean 25.3 per month) except for during the first 6 months of recruitment (5.7) and during the COVID pandemic Apr-Sep 2020 (7.5). Of 89 (4.8%) participants non-compliant with allocation, n=45 (50.6%) received systemic therapy alone and n=44 (49.4%) received systemic therapy plus axillary treatment. There was no fluctuation in the direction of non-compliance during the study duration. There was increasing uptake of axillary radiotherapy to treat the axilla instead of ALND over the course of the study in patients receiving axillary treatment (Number who had ART of all who had axilla treatment2014-2017 - 248/454 (54.6 %); 2018-2021 – 315/449 (70.2%)). Conclusion: Recruitment and compliance with randomised allocation remained consistent over a seven-year period. POSNOC with in-built radiotherapy QA will provide definitive data on axillary management in patients undergoing mastectomy or BCS with ≤2 macrometastases on SNB. Citation Format: Amit Goyal, Cydney Bruce, Shabina Sadiq, Mickey Lewis, Alan Montgomery, G Bruce Mann, Heath Badger, Kathryn Monson, Valerie Jenkins, Lesley Fallowfield, Malcolm Reed, David Dodwell, Patricia Fairbrother, Tara Homer, Luke Vale, Roeum Butt, Elizabeth Miles, Shelley Dowey, Lucy Matthews, Hugh Jarrett, Juliet Jackson, Arfan Ali. Recruitment, clinical equipoise, patient acceptance and compliance in the UK-ANZ POSNOC trial [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 P5-01-07.

TPS615 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40-70% of patients. This raises questions about the benefit of further axillary treatment in patients with no evidence of residual nodal disease (ypN0) post NACT. Methods: Design: ATNEC is a phase 3, randomized (1:1), multi-center UK trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to benign (ypN0), ATNEC randomly assigns patients to axillary treatment (nodal radiotherapy [ART] or axillary nodal clearance [ALND]) vs no further axillary treatment. Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative).Inclusion criteria: Age ≥ 18; Male or female; T1-3N1M0 breast cancer at diagnosis (pre-NACT); FNA or core biopsy confirmed axillary nodal metastases at presentation; ER and HER2 status evaluated on primary tumor; Received standard NACT as per local guidelines; Imaging of the axilla to assess response to NACT;Dual tracer SNB post-NACT and at least 3 nodes removed (sentinel nodes and marked node): If a single tracer is used, the patient is eligible if the involved node is marked pre-NACT and at least 3 nodes removed (including the marked node), If axillary node sampling is performed following failed localization of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node), If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node and at least 3 nodes removed; No evidence of nodal metastases post NACT (ypN0). Exclusion criteria: Bilateral invasive breast cancer; SNB prior to NACT; Previous ipsilateral axillary nodal surgery; Previous cancer within last 5 years or concomitant malignancy. Aims: To assess whether omitting further axillary treatment (ALND & ART) for patients with early-stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease-free survival, and reduces lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomization, avoid bias from exclusions and preserve statistical power. Radiotherapy Quality Assurance: Study has in-built radiotherapy QA program that will be coordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1,900 Status: Recruiting. As of 11-Feb-2022, 39 sites open, 87 patients enrolled, 31 randomized. Clinical trial information: NCT04109079.