Prognostic value of HPV circulating tumor DNA detection and quantification in locally advanced cervical cancer.

Background: Cervical cancers are mainly caused by an oncogenic HPV. For locally advanced stages, the standard treatment is radio-chemotherapy (RTCT) followed by brachytherapy. Nevertheless, the prognosis remains highly heterogeneous between patients. Objective: We investigated the prognostic value of HPV circulating tumor DNA (ctDNA) in locally advanced cervical cancers alongside that of Squamous Cell Carcinoma Antigen (SCC-A). Methods: This single-center retrospective study included patients treated in curative intent for an IB3 to IVA squamous cell cervical cancer. Quantification of HPV ctDNA in serum collected at diagnosis was performed using a multiplex digital PCR assay for the simultaneous detection of 8 HPV genotypes. Results: Among the 97 patients included, 76 patients (78.4%) were treated by RTCT, followed by brachytherapy for 57 patients (60%). HPV ctDNA was detected in 59/97 patients at diagnosis (60.8%). This detection was associated with lymph node invasion (p=0.04) but not with tumor stage. A high level of SCC-A at diagnosis was associated with tumor stage (p=0.008) and lymph node invasion (p=0.012). In univariate analysis, better disease-free survival (DFS) was associated with optimal RTCT regimen (p=0.002), exposure to brachytherapy (p=0.0001) and a low SCC-A at diagnosis (continuous analysis, p=0.002). Exploratory analysis revealed that 3/3 patients (100%) whose HPV ctDNA was still detectable at the end of treatment relapsed, while 6/22 patients (27.3%) whose HPV ctDNA was negative at the end of treatment relapsed. Conclusion: HPV ctDNA detection at diagnosis of locally advanced cervical squamous cell carcinomas is frequent and related to node invasion, but not to DFS. The prognostic value of HPV ctDNA detection after treatment warrants specific studies.

Treatment Response, Tumor Infiltrating Lymphocytes and Clinical Outcomes in Inflammatory Breast Cancer-Treated with Neoadjuvant Systemic Therapy.

Inflammatory breast cancer (IBC) is a rare (1%-5%), aggressive form of breast cancer, accounting for approximately 10% of breast cancer mortality. In the localized setting, standard of care is neoadjuvant chemotherapy (NACT) ± anti-HER2 therapy, followed by surgery. Here we investigated associations between clinicopathologic variables, stromal tumor-infiltrating lymphocytes (sTIL), and pathologic complete response (pCR), and the prognostic value of pCR. We included 494 localized patients with IBC treated with NACT from October 1996 to October 2021 in eight European hospitals. Standard clinicopathologic variables were collected and central pathologic review was performed, including sTIL. Associations were assessed using Firth logistic regression models. Cox regressions were used to evaluate the role of pCR and residual cancer burden (RCB) on disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). Distribution according to receptor status was as follows: 26.4% estrogen receptor negative (ER-)/HER2-; 22.0% ER-/HER2+; 37.4% ER+/HER2-, and 14.1% ER+/HER2+. Overall pCR rate was 26.3%, being highest in the HER2+ groups (45.9% for ER-/HER2+ and 42.9% for ER+/HER2+). sTILs were low (median: 5.3%), being highest in the ER-/HER2- group (median: 10%). High tumor grade, ER negativity, HER2 positivity, higher sTILs, and taxane-based NACT were significantly associated with pCR. pCR was associated with improved DFS, DRFS, and OS in multivariable analyses. RCB score in patients not achieving pCR was independently associated with survival. In conclusion, sTILs were low in IBC, but were predictive of pCR. Both pCR and RCB have an independent prognostic role in IBC treated with NACT. SIGNIFICANCE: IBC is a rare, but very aggressive type of breast cancer. The prognostic role of pCR after systemic therapy and the predictive value of sTILs for pCR are well established in the general breast cancer population; however, only limited information is available in IBC. We assembled the largest retrospective IBC series so far and demonstrated that sTIL is predictive of pCR. We emphasize that reaching pCR remains of utmost importance in IBC.

Associated Factors with Breast Nurses Unplanned Interventions in Patients Treated for an Early Breast Cancer.

Background: The presence of a breast nurse is recommended to advise and guide early breast cancer patients before and during chemotherapy/radiation therapy, and at the end of planned treatments. Nevertheless, some patients will need extra guidance. Little is known about the predisposing factors for additional requests. Aim and Objective: Determine time, reasons, and risk factors for breast nurse unplanned solicitations. Design and Methods: This monocentric retrospective study included all early breast cancer patients treated with chemotherapy during 1 year. Unplanned solicitations (in person, by phone, or by e-mail) were recorded in the medical file. They were extracted and stratified in four categories: treatment adverse events, medical condition, psychological support, and counselling. Results: 368 unplanned solicitations were observed for 265 patients, 140 patients (52.8%) asked for at least one unplanned solicitation and 57 (21.5%) asked for at least three. There was no significant difference between the four categories. Most of unplanned solicitations occurred significantly during chemotherapy, essentially after first docetaxel infusion (57% of calls). In univariate and multivariate analyses, anxiolytic treatment was significantly associated with more unplanned solicitations (OR = 2, p = 0.02), while a personal breast cancer history was associated with fewer unplanned solicitations (OR = 0.49, p = 0.05). Conclusion: Breast nurse unplanned solicitations during adjuvant or neoadjuvant chemotherapy in early breast cancers are frequent. Even if patients with anxiolytic treatment have a slightly higher risk of solicitation, no typical profile of a patient who will need extra support exists. Because of its known toxicity, the first cycle of docetaxel is associated with a clear increase in solicitations. Despite physicians' consultations, breast nurses guidance, and leaflets on supportive care and treatments side effects, optimal patient management during early breast cancer remains challenging. Further randomized studies testing more customized tools are required to improve patient support.

Place des biopsies liquides dans le diagnostic et la caractérisation moléculaire des cancers du sein: Role of liquid biopsies in the diagnosis and molecular characterization of breast cancer.

The tumor biopsy remains essential for breast cancer diagnosis and characterization. Indeed, the treatment is decided according to histological subtype, and according to the presence of targetable molecular alterations. Notably, the presence of hormone receptors, ERBB2 hyperexpression or the existence of PIK3CA or ESR1 mutations are among the alterations commonly investigated. But these biological characteristics are determined only partially by tumor biopsy, due to tumor heterogeneity or tumor plasticity that happens spontaneously or under treatment. Liquid biopsy, and in particular circulating tumor DNA and circulating tumor cells, is a non-invasive method to identify and characterize the presence of cancer in the blood. The aim of this review is to determine the value of liquid biopsy to enhance or replace the data provided by a tumor biopsy.

Lung Cancer Surgery after Treatment with Anti-PD1/PD-L1 Immunotherapy for Non-Small-Cell Lung Cancer: A Case-Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard of care for non-resectable non-small-cell lung cancer and are under investigation for resectable disease. Some authors have reported difficulties during lung surgery following ICI treatment. This retrospective study investigated the perioperative outcomes of lung resection in patients with preoperative ICI. METHODS: Patients with major lung resection after receiving ICIs were included as cases and were compared to patients who received preoperative chemotherapy without ICI. Surgical, clinical, and imaging data were collected. RESULTS: A total of 25 patients were included in the ICI group, and 34 were included in the control group. The ICI patients received five (2-18) infusions of ICI (80% with pembrolizumab). Indications for surgery varied widely across groups (p < 0.01). Major pathological response was achieved in 44% of ICI patients and 23.5% of the control group (p = 0.049). Surgery reports showed a higher rate of tissue fibrosis/inflammation in the ICI group (p < 0.01), mostly in centrally located tumours (7/13, 53.8% vs. 3/11, 27.3% of distal tumours, p = 0.24), with no difference in operating time (p = 0.81) nor more conversions (p = 0.46) or perioperative complications (p = 0.94). There was no 90-day mortality. Disease-free survival was higher in the ICI group (HR = 0.30 (0.13-0.71), p = 0.02). CONCLUSIONS: This study further supports the safety and feasibility of lung resection in patients following preoperative treatment with ICI.