The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Feasibility study of a multimodal prehabilitation programme in women receiving neoadjuvant therapy for breast cancer in a major cancer hospital: a protocol.

INTRODUCTION: Neoadjuvant therapy has become a standard treatment for patients with stage II/III HER2 positive and triple negative breast cancer, and in well-selected patients with locally advanced and borderline resectable high risk, luminal B breast cancer. Side effects of neoadjuvant therapy, such as fatigue, cardiotoxicity, neurotoxicity, anxiety, insomnia, vasomotor symptoms, gastrointestinal disturbance as well as a raft of immune-related adverse events, may impact treatment tolerance, long-term outcomes, and quality of life. Providing early supportive care prior to surgery (typically termed 'prehabilitation') may mitigate these side effects and improve quality of life.During our codesign of the intervention, consumers and healthcare professionals expressed desire for a programme that 'packaged' care, was easy to access, and was embedded in their care pathway. We hypothesise that a multimodal supportive care programme including exercise and complementary therapies, underpinned by behavioural change theory will improve self-efficacy, quality of life, readiness for surgery and any additional treatment for women with breast cancer. We seek to explore cardiometabolic, residual cancer burden and surgical outcomes, along with chemotherapy completion (relative dose intensity). This article describes the protocol for a feasibility study of a multimodal prehabilitation programme. METHODS AND ANALYSIS: This is a prospective, mixed-method, feasibility study of a multi-modal programme in a hospital setting for 20-30 women with breast cancer receiving neoadjuvant therapy. Primary outcomes are recruitment rate, retention rate, adherence and acceptability. Secondary outcomes include patient reported outcome measures (PROMs), surgical outcomes, length of stay, satisfaction with surgery, chemotherapy completion rates, changes in metabolic markers and adverse events. Interviews and focus groups to understand the experience with prehabilitation and different factors that may affect feasibility of the intervention . The output of this study will be a codesigned, evidence-informed intervention assessed for feasibility and acceptability by women with breast cancer and the healthcare professionals that care for them. ETHICS AND DISSEMINATION: The study received ethics approval from the St Vincents Hospital HREC (HREC/2021/ETH12198). Trial results will be communicated to participants, healthcare professionals, and the public via publication and conferences. TRIAL REGISTRATION NUMBER: ACTRN12622000584730.

Treatment approaches and outcomes of a head and neck lymphedema service at an Australian comprehensive cancer center.

BACKGROUND: Patients treated for head and neck cancer are at high risk of developing head and neck lymphedema (HNL). We describe outcomes of HNL management at an Australian institution from 2018 to 2020. METHODS: Electronic records from Chris O'Brien Lifehouse were retrospectively reviewed from January 1, 2018 to December 31, 2020. Objective changes in HNL were assessed using The M. D. Anderson Cancer Center (MDACC) HNL rating scale and Assessment of Lymphedema of the Head and Neck (ALOHA). RESULTS: Among the 100 patients referred for management of HNL, surgery was the most frequent treatment modality (80%; 70% with neck dissection) and 69% underwent radiotherapy. Manual lymphatic drainage (MLD) was most often prescribed (96%), followed by self-MLD (93%). Small but significant improvements in ALOHA measurements were observed for 50 patients (50%). Only 5/29 (17%) patients had post-treatment improvements on the MDACC scale. CONCLUSIONS: Standardized, prospective measurement of treatment approaches and outcomes is needed to further evaluate the service.

The Clinical Utility of DCISionRT® on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery.

BACKGROUND: The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT®) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT. METHODS: The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS: Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. CONCLUSIONS: DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up.

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20% of newly diagnosed breast carcinoma cases. Historically, the incidence of axillary metastasis in DCIS has been small (1-2%) and its significance has been debated. It is widely known that serial sections of lymph nodes coupled with keratin immunohistochemistry (IHC) increases identification of micrometastasis. The advent of sentinel lymph node evaluation underscores the need to reevaluate the significance of occult micrometastases in DCIS. METHODS: Patients with DCIS and negative axillary lymph nodes from 1974 to 1992 were selected from the Saint Barnabas Medical Center Tumor Registry. All diagnoses were confirmed, and paraffin blocks were retrieved after acceptance into the study. Seven serial sections were obtained from each block and evaluated with two cytokeratin IHC stains. Clinical follow-up ranged from 10 to 28 years. RESULTS: One hundred two patients were included in the study. Micrometastases were identified in 13 patients (13%), mostly on 1 level and composed of microscopic clusters in the subcapsular sinus. Seven of these lymph node-positive patients (58%) had high-grade comedo DCIS, 4 (33%) had intermediate grades of various types of DCIS, and one had a low-grade micropapillary DCIS. The overall disease recurrence rate was 12%, but micrometasis was not detected in any of the patients who developed disease recurrence. CONCLUSIONS: Serial IHC evaluation of lymph nodes dramatically increased the identification of occult micrometastasis. However, IHC detected micrometastasis has no apparent clinical significance in DCIS, based on the current long-term clinicopathologic study. Therefore, the authors questioned the significance of occult micrometastasis, identified by IHC, in DCIS of any type and extent. Further evaluation and follow-up of lymph node micrometastases in patients with invasive tumors of various sizes are needed. The current findings would not support altering the stage of patients with DCIS and micrometastasis detected by IHC only.