[Experiences of patients with cancer during the first COVID-19 lockdown: What was the impact on the patients' healthcare pathway, mental condition, and access to supportive care in cancer?] / Ressenti des patients atteints de cancer pendant le premier confinement COVID-19 : quel impact sur le parcours de soins, l'état mental et l'accès aux soins oncologiques de support ?

INTRODUCTION: The COVID-19 pandemic disrupted the organisation of the healthcare system. Very little data is available regarding the impact of the COVID-19 pandemic on patients' perceptions of their healthcare pathway. The objective of this survey was to evaluate cancer patients' perceptions of the impact of the first COVID-19 lockdown on continuity of care, their mental condition, as well as their access to Supportive Care in Cancer (SCC). METHODS: Between June 2nd and 30th, 2020, an anonymous questionnaire was sent out to the patients who visited 17 healthcare establishments in the Centre-Val de Loire region. RESULTS: Our survey questioned 861 patients, amongst which 839 were selected. The population was predominantly female (58%). Breast cancer was the most represented (27%). Approximately three patients out of four considered that their care was maintained during the lockdown. In total, 348 patients (44%) reported an altered mental status. Approximately 1/4th of patients benefited from SCC. More than half of the patients felt that SCC was not relevant to their situation, although 40% of these patients expressed mental issues. CONCLUSION: Our survey highlighted a negative impact on patients' mental condition and a low use of SCC in spite of existing needs. This demonstrates the necessity of evaluating the patients' needs and offering adequate SCC at various stages of the healthcare pathway, as well as the need for a clearly identifiable offer for the healthcare professionals and the patients.

1-year mortality in lung cancer in France according to key timepoints of care pathways.

Background: It is unclear whether delays in care affect prognosis of patients with lung cancer. The primary objective of this study was to describe the care pathway of patients diagnosed with lung cancer in a French region. Secondary objectives were to identify markers associated with 1) time from imaging to treatment and 2) with 1-year survival. Methods: In a retrospective cohort study, clinical data from multidisciplinary team meetings for all incident lung cancer cases discussed in 2018 in one French region were matched with medico-administrative data from the National Health Insurance Database. Care pathway time intervals were estimated for small cell lung cancer (SCLC), resected nonsmall cell lung cancer (NSCLC) and unresected NSCLC. Factors associated with delay in the care pathway were identified using linear regression; 1-year survival was analysed using Cox modelling. Results: A total of 685 patients were included. Median time between imaging and treatment was 49 days (interquartile range: 33-73), and was lower in cases of metastatic disease, SCLC and private care. At 1 year, 48% had died (resected NSCLC 12%). In unresected NSCLC, time from diagnostic imaging to first treatment <49 days was associated with a higher risk of death. Time intervals were similar in patients with squamous cell carcinoma versus adenocarcinoma or undifferentiated carcinoma. Discussion: Time intervals in the care pathways of lung cancer were similar to previous reports, confirming the robustness of retrospective databases. In unresectable NSCLC, rapid care was not associated with better survival.

Time interval from last visit to imaging diagnosis influences outcome in pancreatic adenocarcinoma: A regional population-based study on linked medico-administrative and clinical data.

Background: Excessive waiting time intervals for the diagnosis and treatment of patients with pancreatic cancer can influence their prognosis but they remain unclear. The objective was to describe time intervals from the medical visit to diagnostic imaging and to treatment and their prognostic impact in pancreatic cancer in one French region. Methods: This retrospective observational multicentre study included all patients with pancreatic cancer seen for the first time in 2017 in multidisciplinary team meetings (MTMs), where clinical data were collected. A probabilistic matching with the medico-administrative data from the French national healthcare database (Système National des Données de Santé) was performed to define the care pathway from clinical presentation to the beginning of treatment. Median key time intervals were estimated for both resected and unresected tumours. Factors associated with 1-year survival were studied using Cox model. Results: A total of 324 patients (88% of total patients with MTM presentation) were matched and included: male 54%, mean age 72 years ±9.2, Eastern Cooperative Oncology Group (ECOG) PS > 1 19.5%, metastatic disease at diagnosis 47.4%, tumour resection 16%. At 1 year, 57% had died (65% in the unresected group and 17% in the resected group). The median time interval from the medical visit to diagnostic imaging was 15 days [Q1-Q3: 8-44]. After imaging, median time intervals to definite diagnosis and to first treatment were 11 and 20 days, respectively. Significant prognostic factors associated with the risk of death at 1 year were ECOG PS > 1 (hazard ratio (HR) 2.1 [1.4-3.0]), metastasis (HR 2.7 [1.9-3.9]), no tumour resection (HR 2.7 [1.3-5.6]) and time interval between the medical visit and diagnostic imaging ⩾25 days (HR 1.7 [1.2-2.3]). Conclusion: Delay in access to diagnostic imaging impacted survival in patients with pancreatic cancer, regardless of whether tumour resection had been performed.

Identification of a C3'-nitrile nucleoside analogue inhibitor of pancreatic cancer cell line growth.

A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.

Synthesis and biological evaluation of novel quinazoline-4-piperidinesulfamide derivatives as inhibitors of NPP1.

The ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) was recently shown to promote mineralization of the aortic valve, hence, its inhibition represents a significant target. A quinazoline-4-piperidine sulfamide compound (QPS1) has been described as a specific and non-competitive inhibitor of NPP1. We report herein the synthesis and in vitro inhibition studies of novel quinazoline-4-piperidine sulfamide analogues using QPS1 as the lead compound. Of the 26 derivatives prepared, four compounds were found to have Ki < 105 nM against human NPP1.

Age and factors associated with access and time to post-operative adjuvant chemotherapy in colon cancer: a French epidemiological study.

BACKGROUND: Studies have shown the negative prognostic impact of increased time between colectomy and postoperative adjuvant chemotherapy (AC) in colon cancer (CC). Our aim was to investigate the role of age and non-organizational factors on access and time to AC. METHODS: All adult patients undergoing surgery for stage II or III CC in the "Région Centre-Val de Loire" in 2013, were selected. Time to AC and socio-demographic factors were collected. Logistic regression modeling was used to identify factors associated with access to AC, and a multivariate analysis performed to identify factors associated with time to AC. RESULTS: Among 404 stage II or III patients who underwent colectomy, 182 (45%; sex ratio 1.5; mean age 67.6 years; range 32-90) received AC. AC patients were younger than those without AC (67.6 vs. 77.9 years) and the difference was even greater for stage III patients (69.0 vs. 82.4). The median time to AC was 48 days, exceeding 42 days in 60% of cases. Living alone, postoperative morbidities, and emergency colectomy were independently associated with increased time to AC. Age and other factors were not associated with delayed AC. CONCLUSIONS: Emergency colectomy, postoperative morbidities, and living alone are associated with increased time to AC. Organizational measures to reduce the time to AC are therefore unlikely to have an impact. In contrast, age is not associated with increased time to AC, but to access to AC. Reasons for omitting AC in older patients requires further study.

Synthesis of novel substituted pyrimidine derivatives bearing a sulfamide group and their in vitro cancer growth inhibition activity.

The synthesis of two series of novel substituted pyrimidine derivatives bearing a sulfamide group have been described and their in vitro cancer growth inhibition activities have been evaluated against three human tumour cell lines (HT-29, M21, and MCF7). In general, growth inhibition activity has been enhanced by the introduction of a bulky substituent on the aromatic ring with the best compound having GI50<6µM for all the human tumour cell lines. The MCF7 selective compounds were evaluated on four additional human invasive breast ductal carcinoma cell lines (MDA-MB-231, MDA-MB-468, SKBR3, and T47D) and were selective against T47D cell line in all cases except one, suggesting a potential antiestrogen activity.

Styryl-N-phenyl-N'-(2-chloroethyl)ureas and styrylphenylimidazolidin-2-ones as new potent microtubule-disrupting agents using combretastatin A-4 as model.

Combretastatin A-4 (CA-4) is a well-studied and attractive molecular template to develop new antimitotics. Several thousand of modifications were performed on the ring B and the ethenyl bridge of CA-4 but only a few involved the trimethoxyphenyl moiety (TMP, ring A) often considered essential to the antiproliferative and antimicrotubule activities. In this study, we described the design, the preparation, the characterization and the biological evaluation of three new series of CA-4 analogs namely styryl-N-phenyl-N'-ethylureas (SEUs), styryl-N-phenyl-N'-(2-chloroethyl)ureas (SCEUs) and styrylphenylimidazolidin-2-ones (SIMZs) bearing a 3-Cl (series a), 3,5-Me (series b) and TMP (series c) substituents, respectively. All SCEU and SIMZ Z-isomers were active in the high and the low nanomolar range, respectively. Conversely to SEUs and their E-isomers that were significantly less active or inactive. Interestingly, the TMP moiety is giving rise to derivatives exhibiting the lowest antiproliferative activity in the SCEU series (10c) and the most active compound in the SIMZ series (12c). Moreover, SIMZ Z-isomers bearing either a 3-Cl (12a) or a 3,5-Me (12b) exhibited antiproliferative activities that are also in the same order of magnitude as 12c. All SCEU and SIMZ Z-isomers also arrested the cell cycle progression in G2/M phase, bound to the colchicine-binding site and disrupted the cytoskeleton of cancer cells. In addition to the promising and innovative microtubule-disrupting properties of SCEUs and SIMZs, these results show that the TMP moiety is not essential for the cytocidal activity of these new CA-4 analogs.