Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

[The quality manager in radiation therapy: Evolution of the role, presentation of a French national Survey]. / Le responsable qualité en radiothérapie : évolution du rôle, présentation d'une enquête nationale.

PURPOSE: Review the role of the quality manager 15 years after ASN Decision 2008-DC-103 and 10 years after the creation of the Association française de la qualité et sécurité en radiothérapie (AFQSR), taking into account the new regulatory framework introduced by ASN Decisions 2021-DC-708 and 2019-DC-660. MATERIALS AND METHODS: a survey was drawn up and distributed to members of the French association for quality and safety in radiotherapy. RESULTS: The role of the quality manager in radiotherapy is one of the pillars of the quality/safety approach introduced by ASN Decision 2008-DC-103. CONCLUSION: The hierarchical position of the quality manager needs to be better defined, as does the notion of authority. The time and resources allocated to the function and to the quality/safety approach also need to be adapted, as these are the main factors of tension identified by the survey. The publication of ASN Decision 2019-DC-660 has extended the scope of the quality manager to include imaging in several centers.

[Radiation TherapisTs Radiographer (RTTs) and risk management in radiotherapy: An international survey]. / Manipulateurs en électroradiologie et gestion des risques en radiothérapie : présentation des résultats d'une enquête internationale.

PURPOSE: In order to study the role perception and the effective involvement of Radiation TherapisTs (RTTs) in risk management in radiotherapy, a survey was developed and distributed in five countries (France, Switzerland, Belgium, Ireland, the Netherlands). MATERIALS AND METHODS: The article presents the results of this survey and the comparison between the different countries. RESULTS: Overall, the results of the survey show a good involvement and perception of the RTTs around the risk management approach, although training in this area has yet to be systematized. CONCLUSION: Although with differences in the results between the participating countries, the survey seems to highlight the deployment of preventive actions that are evaluated as not very effective by the respondents and by the international scientific literature.

[Experience feedback committees (CREX) in French radiotherapy departments in 2019]. / Comités de retour d'expérience (CREX) dans les centres de radiothérapie français en 2019.

Ten years after the beginning of CREX in radiotherapy departments we wanted to know about users' feeling. We sent a survey to 168 centers in the whole country and a hundred of them answer. The time, top management's involvement and professionals' training seem to be the key success factors. Systemic analysis methods and mainly the Orion© one are not identified as an issue. The main challenge for the next years will be the effectiveness check of actions.

[Implementation of the tracer patient audit in a private radiation therapy centre]. / Mise en place de l'audit patient traceur au sein d'un centre privé de radiothérapie.

The "tracer patient" audit is an evaluation method introduced by the French health authority in the V2014 certification. This is not mandatory in private radiotherapy centres. In our continuous quality improvement approach and in order to improve the management of patient care, the management of our radiation therapy centre has decided to use this method to evaluate our medical practice and to engage healthcare professionals at the core of this approach.

Human pancreatic adenocarcinomas express parathyroid hormone-related protein.

PTH-related protein (PTHrP) is expressed in many common malignancies such as breast and prostate cancer and can regulate their growth. Little is known, however, about the role of PTHrP in pancreatic adenocarcinoma. To study PTHrP in pancreatic exocrine cancer, we studied its expression in pancreatic cancer cell lines and surgical specimens. Eight human pancreatic adenocarcinoma cell lines were evaluated: AsPC-1, BxPC-3, Capan-1, CFPAC-1, MIA PaCa-2, PANC-1, PANC-28, and PANC-48. Murine monoclonal antibodies to the amino-terminal (1-34), mid-region (38-64), and carboxyl-terminal peptides (109-141) of PTHrP were used to identify cellular PTHrP and secreted PTHrP, including Western blotting and immunocytochemical staining for PTHrP from each cell line. Cellular PTHrP was detected in all cell line extracts by both Western blotting and immunoassay. CFPAC-1, derived from a pancreatic liver metastasis, had the highest concentration of PTHrP, and MIA PaCa-2, derived from primary pancreatic adenocarcinoma, had the lowest. PTHrP was localized by immunocytochemical staining in the cytoplasm in all but one cell line, and both nuclear and cytoplasmic immunostaining were observed in the MIA PaCa-2 and PANC-1 cells. Secretion of PTHrP into cell medium was also observed for each cell line and paralleled intracellular PTHrP levels. Evidence for differential processing of PTHrP expression was provided by studies demonstrating different patterns of PTHrP among the cell lines when assessed by PTHrP immunoassays directed against different PTHrP peptides. In specific, PTHrP secretion measured by a PTHrP-(38-64) assay was highest for BxPC-3, whereas the highest levels of secreted PTHrP-(109-141) occurred in CFPAC-1 and PANC-1. Growth of AsPC-1 cells was stimulated in a dose-dependent manner by PTHrP-(1-34). Immunostaining from archival tissue of patients with pancreatic adenocarcinoma revealed strong PTHrP expression in all 14 specimens. All patients were eucalcemic preoperatively. These results demonstrate that PTHrP is commonly expressed in pancreatic cancer. Our data suggest that PTHrP may have growth-regulating properties in pancreatic adenocarcinoma cells, but further studies are required.

Antimetastatic efficacy of adjuvant gemcitabine in a pancreatic cancer orthotopic model.

Gemcitabine is a promising new agent that has been recently studied for palliation of advanced (stage IV) unresectable pancreatic cancer. We hypothesized that adjuvant gemcitabine would reduce recurrence and metastases following surgical resection of pancreatic cancer. To test this hypothesis, we evaluated gemcitabine on a green fluorescent protein (GFP) transductant of the human pancreatic cancer cell line BxPC-3 (BxPC-3-GFP) using surgical orthotopic implantation (SOI) in nude mice. GFP enabled high resolution fluorescent visualization of primary and metastatic growth. Five weeks after SOI, the mice were randomized into three groups: Group I received exploratory laparotomy only. Group II underwent surgical resection of the pancreatic tumor without further treatment. Group III underwent tumor resection followed by adjuvant treatment with gemcitabine, 100 mg/kg every three days for a total of four doses, starting two days after resection. The mice were sacrificed at thirteen weeks following implantation and the presence and location of recurrent tumor was recorded. Gemcitabine reduced the recurrence rate to 28.6% compared to 70.6% with resection only (P = 0.02) and reduced metastatic events 58% in the adjuvant group compared to resection only. This study, demonstrating that gemcitabine is effective as adjuvant chemotherapy post-pancreatectomy, suggests this new indication of the drug clinically.

Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models.

Pancreatic cancer is a highly metastatic disease that responds poorly to currently-available treatment. In order to better visualize and understand the chronology and specificity of metastatic targeting of pancreatic cancer, two human pancreatic cancer cell lines, expressing green fluorescent protein (GFP), were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tumor fragments were transplanted by surgical orthotopic implantation (SOI) to the nude mouse pancreas for fluorescence visualization of the chronology of pancreatic tumor growth and metastatic targeting. BxPC-3-GFP tumors developed rapidly in the pancreas and spread regionally to the spleen and retroperitoneum as early as six weeks. Distant metastases in BxPC-3-GFP were rare. In contrast, MIA-PaCa-2-GFP grew more slowly in the pancreas but rapidly metastasized to distant sites including liver and portal lymph nodes. Regional metastases in MIA-PaCa-2-GFP were rare. These studies demonstrate that pancreatic cancers have highly specific and individual 'seed-soil' interactions governing the chronology and sites of metastatic targeting.