Valérie Seegers

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but may induce pseudoprogression (PP), an atypical response pattern that may mimic progressive disease (PD). Although iRECIST criteria were developed to characterize such atypical responses, distinguishing PP from PD when progression is first observed remains challenging. We aimed to characterize patients with clinically suspected PP and explore clinical and biological factors associated with subsequent classification as PP versus PD. Methods: We conducted a retrospective single-center study including patients with metastatic cancer treated with ICIs at the Institut de Cancérologie de l’Ouest (ICO) in whom PP was clinically suspected. Clinical, biological, treatment, and outcome data were collected at ICI initiation, PP suspicion, and subsequent PP/PD classification. Associations with PP versus PD were explored using univariable and multivariable logistic regression. Results: Among 123 patients with clinically suspected PP, 56 were subsequently classified as PP and 67 as PD. The most frequent primary tumors were lung (38%), kidney (24%), and bladder (11%) cancers. Median time from ICI initiation to PP suspicion was 79 days. ECOG performance status of 0 at ICI initiation was more frequent in the PP than in the PD group (55% vs. 32%; p = 0.046). At PP suspicion, median LDH levels were lower in the PP than in the PD group (189 vs. 232.5 U/L; p = 0.003). After multivariable adjustment, higher LDH levels at PP suspicion remained associated with PD (adjusted OR 2.78 per 100 U/L increase; 95% CI, 1.19–6.52; p = 0.019). Conclusions: In patients with clinically suspected PP, LDH may provide complementary information but cannot reliably distinguish PP from PD when considered alone. Confirmatory imaging therefore remains essential for treatment decision-making.

OBJECTIVES: Guidelines recommend targeting a mean arterial pressure (MAP) greater than or equal to 65 mm Hg in septic shock. Although experts advocate for individualized targets, no validated bedside tool exists. An increased renal resistive index (RRI) is associated with acute kidney injury, and increasing MAP can reduce RRI. This study investigated the physiologic impact of a higher MAP on renal function based on RRI evolution during a transient high MAP target test. DESIGN: Prospective physiologic and randomized study. SETTING: Medical ICU of a university hospital. Patients: Patients in the early phase of septic shock (norepinephrine ≥ 0.05 µg/kg/min base within 9 hr of initiation, with or without lactate > 2 mmol/L) without chronic kidney disease or immediate need for renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a standardized 2-hour MAP test (65–70 followed by 80–85 mm Hg) with RRI measured at each period. RRI responders were defined by an RRI decrease greater than or equal to 0.05 during the MAP test. Following the MAP test, patients were randomized according to the “low” (65–70) or “high” (80–85 mm Hg) MAP target for 5 days, stratified by RRI response during the MAP test. Eighty patients were randomized; 23 (29%) were RRI responders. Among RRI responders, the higher MAP target was not associated with improved renal outcomes (i.e., diuresis, Kidney Disease: Improving Global Outcomes stage, need for renal replacement therapy, or serum creatinine). RRI nonresponders had higher urine output with a high MAP target, whereas no other renal parameter differed significantly; these findings should be considered exploratory. CONCLUSIONS: In early septic shock, a decrease in RRI during a MAP test did not identify patients who would benefit from higher MAP targets to improve renal function. Conversely, the absence of an RRI decrease during the MAP test may help identify patients in whom increasing MAP is associated with increased urine output.

Background: The CAPTRANE trial evaluated the efficacy of randomly assigned high-concentration capsaicin patch (HCCP) versus daily oral pregabalin (PGB) in adults with chronic neuropathic pain (DN4 ≥ 4) post-breast cancer surgery. The objective of its 4-month open-label extension following patient’s self-selection of their second treatment (HCCP, PGB, or none) was to explore efficacy and safety of various strategies. Methods: The study was conducted in France between March 2019 and November 2022. At each clinic visit, we assessed pain intensity (NRS, 0–10), painful area (cm²), mood (HADS), and quality of life (EQ-5D-5L). Standard statistical tests were used. Results: Data from 116 patients (all females; 76% aged < 65 years) were collected. At Month 2, 71% (46/65) of HCCP-treated patients received a second HCCP application and none switched to PGB, whereas 27% (14/51) continued on PGB and 49% (25/51) of PGB-treated patients switched to HCCP. At Month 6, NRS scores had decreased in HCCP-treated patients, including PGB/HCCP-treated patients, with a reduction of −2.0 [−4.0; 0.0] and −3.0 [−4.0; −2.0] in the HCCP/HCCP and PGB/HCCP group, respectively (median[interquartile]). Adverse events aligned with those expected with HCCP and PGB; none were serious. Conclusions: This first study to examine switching between PGB and HCCP treatments for chronic intercostobrachial neuropathic pain after breast cancer surgery showed patients’ preference for HCCP, confirmed the benefit of repeated HCCP applications, and indicated that HCCP could be preceded by PGB without compromising efficacy or safety. These findings suggest that HCCP may be used early in this population, and PGB initiated before HCCP to relieve patients waiting for HCCP application.

Background/Objectives: CAPTRANE evaluated the efficacy and tolerability of high-concentration capsaicin patch (HCCP) vs. oral pregabalin for the treatment of postsurgical neuropathic pain (PSNP) following breast cancer surgery. The study was designed with the aim of demonstrating noninferiority of one HCCP against daily pregabalin. Methods: This was a multicenter, randomized, parallel-arm, open-label study conducted across nine centers in France. The primary endpoint was a change from baseline in the Numeric Pain Rating Scale (NPRS) score after 2 months. Results: Recruitment challenges resulted in the randomization of 140 patients (versus 644 planned); the per-protocol population comprised 107 patients (HCCP: n = 65; pregabalin: n = 42). Baseline characteristics were similar between the two groups. In the per-protocol analysis, the mean (standard deviation) change versus baseline in NPRS score was −1.926 (2.554) with HCCP and −1.634 (2.498) with pregabalin. The prespecified analysis showed that HCCP was not inferior to pregabalin: the lower bound of the 90% confidence interval for the between-arm difference was −0.889 and the upper bound was +0.260 (i.e., below the predefined clinical threshold of +0.4). Patient-reported outcomes showed no statistically significant differences between treatments. The painful area size decreased significantly more with HCCP. Tolerability profiles differed, with HCCP mostly causing application-site reactions. While >50% of patients switched from pregabalin to HCCP, none switched from HCCP to pregabalin. Conclusions: This comparative study in PSNP post breast cancer surgery, evaluating a single treatment of HCCP, shows a noninferior reduction in pain intensity, a superior reduction in painful area size, and a patient preference for HCCP compared with pregabalin. Despite limitations, it contributes valuable initial data for PSNP management in breast cancer care.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

In a multicenter prospective cohort of cancer patients (CP; n = 840) and healthcare workers (HCWs; n = 935) vaccinated against COVID-19, we noticed the following: i/after vaccination, 4.4% of HCWs and 5.8% of CP were infected; ii/no characteristic was associated with post-vaccine COVID-19 infections among HCWs; iii/CP who developed infections were younger, more frequently women (NS), more frequently had gastrointestinal, gynecological, or breast cancer and a localized cancer stage; iv/CP vaccinated while receiving chemotherapy or targeted therapy had (NS) more breakthrough infections after vaccination than those vaccinated after these treatments; the opposite was noted with radiotherapy, immunotherapy, or hormonotherapy; v/most COVID-19 infections occurred either during the Alpha wave (11/41 HCW, 20/49 CP), early after the first vaccination campaign started, or during the Omicron wave (21/41 HCW, 20/49 CP), more than 3 months after the second dose; vi/risk of infection was not associated with values of antibody titers; vii/the outcome of these COVID-19 infections after vaccination was not severe in all cases. To conclude, around 5% of our CPs or HCWs developed a COVID-19 infection despite previous vaccination. The outcome of these infections was not severe.

Geriatric assessment (GA) can predict and improve treatment tolerance and estimate overall survival in older patients with cancer. Several international organizations promote GA; however, data related to its implementation in daily clinical practice are still limited. We aimed to describe GA implementation in patients over 75 years old with metastatic prostate cancer treated with docetaxel as first-line treatment, and with positive G8 screening test or frailty criteria. This retrospective real-world study included 224 patients treated from 2014 to 2021 in four French centers, including 131 patients with a theoretical indication of GA. Among the latter, 51 (38.9%) patients had GA. The main barriers to GA were the lack of systematic screening (32/80, 40.0%), unavailability of geriatric physician (20/80, 25.0%), and absence of referral despite a positive screening test (12/80, 15.0%). With GA performed in only one-third of the patients with a theoretical indication in daily clinical practice, mostly due to an absence of screening test, the use of GA is currently sub-optimal.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute’s Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

In this prospective, real-life cohort study, we followed 523 cancer patients (CP) and 579 healthcare workers (HCW) from two cancer centers to evaluate the biological and clinical results of the COVID-19 vaccination campaign. Seventy percent of the CP and 90% of the HCW received an mRNA vaccine or the AZD1222 vaccine. Seropositivity was high after the first vaccine among HCW and poor among CP. The second dose resulted in almost 100% seropositivity in both cohorts. Antibody response was higher after the second injection than the first in both populations. Despite at least two doses, 8 CP (1.5%) and 14 HCW (2.4%) were infected, corresponding either to a weak level of antibody or a new strain of virus (particularly the Omicron variant of concern). Sixteen CP and three HCW were hospitalized but none of them died from COVID-19. To conclude, this study showed that two doses of COVID-19 vaccines were crucially necessary to attain sufficient seropositivity. However, the post-vaccination antibody level declines in individuals from the two cohorts and could not totally prevent new SARS-CoV-2 infections.