Prognosis of local invasive relapses after carcinoma in situ of the breast: a retrospective study from a population-based registry.

PURPOSE: The prognosis of local invasive recurrence (LIR) after prior carcinoma in situ (CIS) of the breast has not been widely studied and existing data are conflicting, especially considering the specific prognosis of this entity, compared to de novo invasive breast cancer (de novo IBC) and with LIR after primary IBC. METHODS: We designed a retrospective study using data from the specialized Côte d'Or Breast and Gynecological cancer registry, between 1998 and 2015, to compare outcomes between 3 matched groups of patients with localized IBC: patients with LIR following CIS (CIS-LIR), patients with de novo IBC (de novo IBC), and patients with LIR following a first IBC (IBC-LIR). Distant relapse-free (D-RFS), overall survival (OS), clinical, and treatment features between the 3 groups were studied. RESULTS: Among 8186 women initially diagnosed with IBC during our study period, we retrieved and matched 49 CIS-LIR to 49 IBC, and 46 IBC-LIR patients. At diagnosis, IBC/LIR in the 3 groups were mainly stage I, grade II, estrogen receptor-positive, and HER2 negative. Metastatic diseases at diagnosis were higher in CIS-LIR group. A majority of patients received adjuvant systemic treatment, with no statistically significant differences between the 3 groups. There was no significant difference between the 3 groups in terms of OS or D-RFS. CONCLUSION: LIR after CIS does not appear to impact per se on survival of IBC.

A phase I study of the combination of atezolizumab, tiragolumab, and stereotactic body radiation therapy in patients with metastatic multiorgan cancer.

BACKGROUND: Immunotherapy targeting the PD-1/PD-L1 pathway is a standard of care in a number of metastatic malignancies, but less than a fifth of patients are expected to respond to ICIs (Immune Checkpoint Inhibitors). In a clinical trial, combining the anti-TIGIT (T cell immunoreceptor with Ig and ITIM domains) Mab (monoclonal antibody) tiragolumab with atezolizumab improved outcomes in non-small cell lung cancer. In preclinical models, SBRT (Stereotactic Body Radiation Therapy) could increase expression levels of the inhibitory co-receptors TIGIT and PD-L1. We aim to assess the combination of tiragolumab with atezolizumab and SBRT in metastatic, previously treated by ICIs, non-small cell lung cancer, head and neck cancer, bladder cancer, and renal cell cancer. METHODS: This phase I study (ClinicalTrials.gov NCT05259319) will assess the efficacy and safety of the combination of atezolizumab with tiragolumab and stereotactic body radiation therapy in patients with histologically proven metastatic non-small cell lung cancer, renal cell cancer, bladder cancer, and head and neck cancer previously treated. First part: 2 different schedules of SBRT in association with a fixed dose of atezolizumab and tiragolumab will be investigated only with metastatic non-small cell lung cancer patients (cohort 1). The expansion cohorts phase will be a multicentric, open-label study at the recommended scheme of administration and enroll additional patients with metastatic bladder cancer, renal cell cancer, and head and neck cancer (cohort 2, 3 and 4). Patients will be treated until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal in the absence of progression or intolerance. The primary endpoint of the first phase is the safety of the combination in a sequential or concomitant scheme and to determine the expansion cohorts phase recommended scheme of administration. The primary endpoint of phase II is to evaluate the efficacy of tiragolumab + atezolizumab + SBRT in terms of 6-month PFS (Progression-Free Survival). Ancillary analyses will be performed with peripheral and intratumoral immune biomarker assessments. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov: NCT05259319, since February 28th, 2022.

Omitting axillary lymph node dissection after positive sentinel lymph node in the post-Z0011 era: Compliance with NCCN and ASCO clinical guidelines and Z0011 criteria in a large prospective cohort.

PURPOSE: In the ACOSOG Z0011 trial, patients with primary breast cancer and 1-2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. METHODS: Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-François Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. RESULTS: Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR)=6.1; 95% confidence interval (CI): 1.4-26.7; P=0.02)) and only one SLN removed (OR=9.1; 95%CI: 2.2-33.3; P=0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR=5.1; 95%CI: 1.2-22.2; P=0.03) was associated with the failure to perform completion ALND when recommended. CONCLUSION: Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

[Para-aortic lymph node staging in grade IB2 and above cervical cancers: Comparison of 18FDG PET-CT with para-aortic lymphadenectomy, using data from the Côte d'Or gynaecological cancer registry from 2003 to 2016]. / Stadification ganglionnaire lombo-aortique dans les cancers du col de stade supérieur ou égal à IB2: comparaison des performances du PETscan au 18FDG et du curage lombo-aortique à partir des données du registre des cancers gynécologiques de Côte d'Or de 2003 à 2016.

INTRODUCTION: Current guidelines (ASCO, ESTRO, and ESGO) recommend para-aortic lymphadenectomy (PAL) for lymph node staging in patients with a negative initial PET-CT in locally advanced cervical cancer (LACC), with the aim to determine the radiation fields for radiochemotherapy. The main goal of this study was to compare overall survival (OS) in two groups, which differed according to the para-aortic lymph node staging technique used: imaging alone versus imaging and PAL. Secondary objectives were to determine recurrence-free survival (RFS), the proportion of false negatives on PET-CT, and surgery-related complications. METHODS: We conducted a retrospective, observational study on data from the Côte d'Or gynaecological cancer registry collected from 2003 to 2016, and compared two groups of LACC with different techniques for staging para-aortic lymph nodes: PET-CT alone (iN group) (n=99) and PET-CT associated with PAL (pN group) (n=35) for a total of 134 patients. RESULTS: OS (HR=1.04 (95% CI: 0.53-2.03); P=0.9) and RFS (HR=0.65 (95% CI: 0.29-1.45); P=0.29) were similar in both groups. There were 11.4% of false negatives in PET-CT, and 2.9% of patients who underwent PAL experienced complications. The staging method, iN or pN, had no impact on the time to the implementation of concomitant radiochemotherapy. CONCLUSION: For lymph node staging in LACC, PAL after a PET-CT as compared with PET-CT staging alone, had no significant impact on OS or RFS.

[Strategies in case of metastatic sentinel lymph node in breast cancer]. / Stratégies en cas de positivité du ganglion sentinelle dans les cancers du sein.

Management strategy of micro or macro metastatic sentinel lymph node(s) (SLNs) in breast cancer has dramatically changed over the past ten years and the publication of five randomized trials results: ACOSOG Z0011, IBCSG 23-01, and AATRM comparing axillary lymph node dissection (ALND) versus SLNs biopsy alone; and AMAROS and OTOASOR comparing ALND versus axillary radiotherapy. Despite methodological limitations of several of these trials, notably ACOSOG Z0011, the international recommendations (ASCO, NCCN) and the expert consensus of St Gallen do not recommend the performance of a complementary ALND in case of macro or micro metastatic SLN, if all ACOSOG Z0011 inclusion criteria are met. Moreover, in the context of a mastectomy, with one or two positive SLN and a wall irradiation indication, an axillary radiotherapy can be proposed as an alternative to ALND. Additionally, ALND is also indicated in extracapsular involvement or when three or more SLNs are metastatic. This change in strategy led to a significant decrease on the number of ALNDs performed and resulted on the abandon of SLNs extemporaneous examination. In France, there are no national recommendations on axillary management in the context of SLN involvement. Moreover, a multitude of different local guidelines, led to very heterogeneous practices in our country. The next evolution on axillary management strategy will be the implementation of a SLNs procedure after neoadjuvant chemotherapy (NAC) for patients with lymph node involvement proven before NAC and for whom NAC has allowed axillary downstaging.