EP.TH.930Contemporary trends in the management of micrometastatic axillary disease in the setting of mastectomy – a 5 year single institution experience

Background Since the ACOSOG Z0011 trial, rates of axillary node clearance (ANC) for micrometastatic axillary disease have declined among women undergoing breast conservation surgery (BCS). However, for women undergoing mastectomy, it remains unclear whether omission of ANC is a safe and feasible option. Aims Identify current practice relating to management of the axilla in women with early stage, clinically node negative breast cancer, found to have micrometastatic disease on SNB, who undergo mastectomy Methods From 2013 to 2017 patients with clinical T1-T2Nmi breast cancer undergoing upfront surgery were identified from a prospective institutional database. Receipt of adjuvant radiotherapy or subsequent ANC were assessed. Patients who received neoadjuvant chemotherapy or BCS were excluded. Results 47 patients undergoing mastectomy for ESBC had micrometastasis identified on SNB. The majority of tumours had invasive ductal histology. 16/27 women underwent completion ANC (34%). Six patients had further nodal disease identified in the ANC specimen. 2 had >5 nodes positive. During the study period 31 patients (65%) received adjuvant radiotherapy. Of the patients who did not undergo ANC, 21 (67.7%) received adjuvant radiotherapy. Conclusion At this institution the majority of patients requiring mastectomy with micrometastatic disease on SNB do not undergo subsequent ANC (>60%). Although this is a small patient cohort, these data indicate the rate of residual axillary disease is low, and are in keeping with trends in the literature, and may help inform management decisions in this patient group.

Metastasis Directed Therapy and/or Systemic Therapy in Hormone-naive Oligometastatic Prostate Cancer Patient: an Emerging Dilemma

"The hormone-naive oligometastatic prostate cancer is a challenging setting for the radiation oncology community, as it represents a sort of transition scenario potentially suitable for two different approaches: a local ablative treatment alone vs a metastasisdirected treatment with the addition of hormone therapy. The choice to add androgen deprivation therapy in the oligorecurrent hormone-sensitive patient is a matter of debate, given the detrimental impact on quality of life and the number of adverse events. To date, there is no clear agreement on the optimal management of this subset of patients. As some authors highlight the attractiveness of a local approach alone, as well tolerated, easily repeatible and with very limited costs, on the other hand, other authors focus the need to cover the micrometastatic disease, often not detectable, even with the newly available imaging modalities. In this commentary, we briefly summarize the literature data in support of both therapeutic strategies."

Pancreatic Cancer Intrinsic PI3Kα Activity accelerates Metastasis and rewires Macrophage Component

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micrometastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas.We researched a gene signature that could discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events.Amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature predict PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by inhibiting tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the lipid second messenger PIP3 produced, with selective reduction of C36:2 PI-3,4,5-P3. PI3Kα inactivation prevented the accumulation of protumoural CD206-positive macrophages in the tumour-adjacent tissue.Tumour-cell intrinsic PI3Kα therefore promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution.The paper explainedPROBLEM Pancreatic cancer is one of the most lethal solid cancers characterised by rapid progression after primary tumour detection by imaging. Key signalling events that specifically drives this rapid evolution into macro-metastatic disease are so far poorly understood.RESULT With two unbiased approaches to patient data analysis, higher PI3K pathway and more specifically higher PI3Kα activation signature can now be identified in the most aggressive pancreatic cancer primary tumours, that lead to earlier patient death. Our in vitro data showed that PI3Kα is a major positive regulator of tumour cell escape from the primary tumour: tumour-intrinsic PI3Kα activity enables actin cytoskeleton remodelling to escape the pancreatic tumour. We chose to use two preclinical models of pancreatic cancer to validate that PI3Kα is a target for delaying evolution of PDAC. The first one mimicked pancreatic patient micrometastatic disease that is undetected by echography and consisted in treating mice presenting echography detected primary tumours combined with increased circulating DNA as a blood biomarker of the most aggressive tumours. The second model consisted in studying the tumour cell implantation and their early proliferation in metastatic organ after injection in blood. We treated both preclinical models with a clinically relevant PI3K α-selective inhibitor (BYL-719/Alpelisib), that is currently being tested in pancreatic cancer patients (without any patient selection). We found that PI3Kα activity drives evolution of micrometastatic disease towards macro-metastatic stage in both models: inhibition of PI3Kα delayed primary tumour and micro-metastasis evolution. Finally, PI3Kα activity increases protumoural characteristics in peritumoural immune cells via tumour cell-intrinsic cytokine production that could facilitate metastatic evolution.IMPACT Circulating tumour DNA represents a strong independent biomarker linked to relapse and poor survival in solid cancer patients. A clinical study in resected PDAC patients with micrometastatic disease characterised by high circulating tumoural DNA levels is needed to assess if PI3Kα-selective inhibitors significantly delay metastatic progression and death.Graphical AbstractPancreatic ductal adenocarcinoma requires tumour-intrinsic PI3Kα activity to accelerate inflammatory metastatic disease.Biorender illustration.

High-risk of recurrence for nodal micrometastasis with breast pathologic complete response (ypT0/Tis ypN1mi) after neoadjuvant chemotherapy.

e12524 Background: Nodal micrometastatic disease (ypN1mic) after neoadjuvant chemotherapy (nCT) for breast cancer (BC) is considered an indication for axillary lymph node disection. While pN1mic prognostic impact has been extensively studied, the prognostic impact of ypN1mic disease is uncertain and these patients are usually grouped together with nodal macrometastatic disease. Since outcomes may be difficult to evaluate in the setting of BC residual disease, our aim was to compare the prognostic meaning of ypN1mic with that of ypN0 when a pCR is obtained in the breast. Methods: We retrospectively analyzed a series of 454 BC consecutive patients treated between 2010 and 2018 with neoadjuvant chemotherapy (nCT) based on anthracyclines and taxanes (plus antiHER2 treatment when appropriate). Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients with pre-nCT sentinel lymph node biopsy or without post-nCT pathologic evaluation were excluded. Disease free (DFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox regression models. Results: 454 BC patients were included, with 106 (24%) pCR. Median follow-up was 39 months. 99 (21.8%) patients obtained a pCR both in breast and axilla (ypT0/Tis ypN0), with 4 recurrences (4%) while only 7 (1.5%) patients had isolated nodal micrometastatic disease (ypT0/Tis ypN1mic), with 2 recurrences (28%). Median DFS was not reached for the ypN0 group and was 28 months (95%CI: 21.6-34.4 months) for the ypN1mic group (HR: 16.55, 95%cI: 2.68-102.37; p = 0.003). No differences were observed for OS (p = 0.77), although 2/2 ypN1mi showed distant recurrence (2/4 for ypN0 patients). Baseline clinical and pathologic characteristics were comparable between both groups, with no differences in performance status (p = 0.45), clinical nodal stage (p = 0.48), HER2 (p = 0.32), estrogen receptors (p = 0.93), grade (p = 0.34), presence of carcinoma in situ (0.60) or clinical complete response (p = 0.42). Clinical characteristics of patients with recurrence were also similar (100%: clinically positive nodes, negative estrogen receptors, no clinical complete response). Conclusions: Residual nodal micrometastatic disease after nCT seems to be associated with a higher risk of recurrence. Although longer follow-up and larger series are needed to confirm our data, these results support the escalation of post-nCT treatment even in patients with ypN1mic and breast pCR.