Did the COVID-19 pandemic delay treatment for localized breast cancer patients? A multicenter study.

BACKGROUND: Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level. OBJECTIVE: To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized breast cancer (BC) during the COVID-19 pandemic. METHODS: We used data from the PAPESCO-19 multicenter cohort study, which included patients from 4 French comprehensive cancer centers. We measured the delay to first treatment as the number of days between diagnosis and the first treatment regardless of whether this was neoadjuvant chemotherapy or surgery. COVID-19 pandemic exposure was estimated with a composite index that considered both the severity of the pandemic and the level of lockdown restrictions. We ran generalized linear models with a log link function and a gamma distribution to model the association between delay and the pandemic. RESULTS: Of the 187 patients included in the analysis, the median delay to first treatment was 42 (IQR:32-54) days for patients diagnosed before and after the start of the 1st lockdown (N = 99 and 88, respectively). After adjusting for age and centers of inclusion, a higher composite pandemic index (> = 50 V.S. <50) had only a small, non-significant effect on times to treatment. Longer delays were associated with factors other than the COVID-19 pandemic. CONCLUSION: We found evidence of no direct impact of the pandemic on the actual delay to treatment among patients with localized BC.

Correlation between changes in nutritional status and tumor response in patients receiving immunotherapy for lung cancer (NUTIMMUNO study).

Malnutrition is a common condition in lung cancer, and it is an independent prognostic factor. The main objective of this study was to determine whether an early improvement at 3 months in the nutritional status (NS) of patients undergoing immune checkpoint inhibitor (ICI) is associated with a tumor response to treatment at 6-month follow-up. The clinical data of 106 patients initiating ICI for bronchopulmonary non-small cell lung cancer (NCSLC) were retrospectively reviewed. NS was defined according to the HAS 2019 recommendation, depending on BMI, percentage of weight loss, and albuminemia. NS was assessed at baseline (M0) and 3 months (M3) after ICI treatment initiation according to 3 categories: well-nourished, malnourished, and very malnourished. The NS evolution of the 92 patients who were still alive at 3 months was determined. The proportion of patients with malnutrition at M0 and M3 was 39.6% and 43.3%. Median follow-up was 18.7 months. OS and PFS were longer for patients in the M0 well-nourished group than in the malnourished and very malnourished groups. Patients who remained well-nourished had a significantly better ICI success rate at 6 months than patients who remained malnourished or improved or deteriorated their NS. OS was significantly longer for remaining well-nourished patients compared to the amelioration group and the degradation group. PFS was not significantly modified between the 4 evolution groups. Maintaining good NS during the first months of ICI treatment leads to better OS and objective response rate than remaining malnourished or early deteriorating NS. However, an early improvement in NS does not seem to predict a good tumor response to treatment and not a better OS either.

Intrathecal cervical analgesia for cancer pain: a 12-year follow-up study in a comprehensive cancer center.

BACKGROUND: Intrathecal analgesia plays a key role for patients suffering refractory cancer pain. Nevertheless, intrathecal drug delivery systems (IDDS), requiring a cervical catheter tip implantation, have been poorly described in medical literature. AIMS: A monocentric retrospective follow-up study was designed to evaluate results of cervical IDDS for cancer pain. PATIENTS AND METHODS: From January 2010 to December 2022, all intrathecal-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed in the cervical vertebral canal. Post-implant assessment of pain was determined using a numeric rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly. Pain scores were compared using the Wilcoxon's signed rank test. RESULTS: Ninety-eight patients were included in this study; all received intrathecal treatments. Implanted patients suffered from severe pain (mean presurgical maximum numerical rating score 8.02±0.24 despite a mean 562.56±127.72 mg of oral morphine equivalent daily dose). Mean survival time after intrathecal treatment start was 208.48±67 days. Intrathecal drug delivery systems provided pain relief compared with initial pain score with a significant statistical difference after 1 week, 1 month, 2 and 3 months (p<0.01). A 50% reduction in initial pain level was achieved in 93% of cases during the first week of intrathecal implant. CONCLUSIONS: Results suggest that long-term intrathecal treatment using a multidrug regimen for cancer-related pain through cervical intrathecal catheters was suitable and safe in our study population. We demonstrated a clinically and statistically significant pain reduction in patients using mainly a percutaneous lumbar approach.

COVID-19 Infection despite Previous Vaccination in Cancer Patients and Healthcare Workers: Results from a French Prospective Multicenter Cohort (PAPESCO-19).

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.

Intrathecal Catheter for Chemotherapy in Leptomeningeal Carcinomatosis From HER2-Negative Metastatic Breast Cancer.

PURPOSE: Most oncological treatments for leptomeningeal metastasis (LM) do not cross the blood-brain barrier (BBB). One therapeutic option is intrathecal (IT) chemotherapy. Both the brain-implanted Omaya reservoir and lumbar puncture (LP) are classic routes for IT chemotherapy delivery. An intrathecal catheter (IC) connected to a subcutaneous port is a recently developed option for the management of chemotherapy infusions. It is essential to evaluate the efficacy and safety of chemotherapy infusion using such device. METHODS: We conducted a retrospective monocentric study within Institut de cancerologie de l'Ouest at Angers, including all patients with advanced breast cancer (aBC) with LM implanted with an IT device for IT chemotherapy between January 2013 and May 2020. The primary endpoint was overall survival (OS) and secondary endpoints included surgical feasibility, patient safety, and progression-free survival (PFS). The catheter was inserted through an LP, the tip was positioned at the right level and connected to a subcutaneous port implanted under the skin of the anterior thoracic wall. IT chemotherapy is painless and easy for qualified nurses to administer on an outpatient basis. RESULTS: Thirty women underwent the implantation. No failures occurred during the procedure. A total of 77% of patients reported no complications after implantation. Only three complications required surgical treatment. The median number of IT chemotherapy courses per patient was 8 (range, 2-27). The tolerance profile for iterative IT chemotherapy was manageable in ambulatory care. With a median follow-up of 76.5 months (95% confidence interval [CI], 11.6-not available), the median OS was 158 days (95% CI, 87-235), and the median PFS was 116 days (95% CI, 58-174). CONCLUSION: Infusing chemotherapy using an implanted catheter is an efficient option for managing IT chemotherapy with a good tolerance profile. Patient-reported outcomes for the evaluation of IT chemotherapy toxicity are currently being developed.

Correction: Bienfait et al. Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center. Cancers 2023, 15, 349.

In the original publication [...].

Geriatric Assessment Implementation before Chemotherapy in MEtastatic Prostate Cancer, Results from the Real-Life Study GAMERS.

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.

Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center.

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.

Postoperative prophylactic intermittent noninvasive ventilation versus usual postoperative care for patients at high risk of pulmonary complications: a multicentre randomised trial.

BACKGROUND: Pulmonary complications are an important cause of morbidity and mortality after surgery. We evaluated the clinical effectiveness of noninvasive ventilation (NIV) in preventing postoperative acute respiratory failure. METHODS: This is an open, multicentre randomised trial that included patients at high risk of postoperative pulmonary complications after elective or semi-urgent surgery with an Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score ≥45. Patients were randomly assigned to intermittent prophylactic face-mask NIV for 6-8 h day-1 or usual postoperative care. The primary outcome was in-hospital acute respiratory failure within 7 days after surgery. Patients who underwent surgery and postoperative extubation were included in the modified intended-to-treat analysis. Results are presented as n (%) and odds ratios (ORs) with 95% confidence intervals. RESULTS: Between November 2017 and October 2019, 266 patients were randomised and 253 included in the main analysis. Of these, 203 (80.2%) were male with a mean age of 68 (11) yr and an ARISCAT score of 53 (6); 237 subjects (93.7%) underwent cardiac or thoracic surgery. There were 125 patients allocated to prophylactic NIV and 128 to usual care. Unplanned treatment termination occurred in 58 subjects in the NIV group, which was linked to NIV discomfort for 36 subjects. There was no difference in the incidence of the primary outcome of postoperative acute respiratory failure between treatment groups (NIV: 30 of 125 subjects [24.0%] vs usual care: 35 of 128 subjects [27.3%]; OR 0.97 [0.90-1.04]; P=0.54). CONCLUSIONS: Prophylactic NIV was difficult to implement after high-risk surgery because of low patient compliance. Prophylactic NIV did not prevent acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03629431 and EudraCT 2017-001011-36.

Unresolved early post-operative pain trajectory predicts moderate-to-severe persistent pain after breast cancer surgery-An observational cohort study.

BACKGROUND: Modelling acute post-operative pain trajectories may improve the prediction of persistent pain after breast cancer surgery (PPBCS). This study aimed to investigate the predictive accuracy of early post-operative pain (EPOP) trajectories in the development of PPBCS. MATERIALS & METHODS: This observational study was conducted in a French Comprehensive Cancer Centre and included patients who underwent breast cancer surgery from December 2017 to November 2018. Perioperative and follow-up data were obtained from medical records, and anaesthesia and perioperative charts. EPOP was defined as pain intensity during the first 24 h after surgery, and modelled by a pain trajectory. K-means clustering method was used to identify patient subgroups with similar EPOP trajectories. The prevalence of moderate-to-severe PPBCS (numeric rating scale ≥4) was evaluated until 24 months after surgery. RESULTS: A total of 608 patients were included in the study, of which 18% (n = 108) and 9% (n = 52) reported mild and moderate-to-severe PPBCS, respectively. Based on EPOP trajectories, we were able to identify a low (64%, n = 388), resolved (30%, n = 182), and unresolved (6%, n = 38) pain group. Multivariate analysis identified younger age, axillary lymph node dissection, and unresolved EPOP trajectory as independent risk factors for moderate-to-severe PPBCS development. When compared to patients reporting mild PPBCS, moderate-to-severe PPBCS patients experienced significantly more neuropathic pain features, pain-related interference, and delayed opioid cessation. CONCLUSION: EPOP trajectories can distinguish between resolved and unresolved acute pain after breast cancer surgery, allowing early identification of patients at risk to develop significant PPBCS.

COVID-19 Vaccination Campaign in Cancer Patients and Healthcare Workers-Results from a French Prospective Multicenter Cohort (PAPESCO-19).

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.

Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial.

BACKGROUND: In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. METHODS: The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling. RESULTS: We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. CONCLUSION: Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality.

COVID-19 Infections in Cancer Patients Were Frequently Asymptomatic: Description From a French Prospective Multicenter Cohort (PAPESCO-19).

Background: Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors. Methods: We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [PAtients et PErsonnels de Santé des Centres de Lutte Contre le Cancer pendant l'épidémie de COvid-19] study). This analysis used data recorded between June 17, 2020 and November 30, 2020 in CPs (first 2 waves, no variants). At inclusion and quarterly, CPs reported the presence of predefined COVID-19 symptoms and had a blood rapid diagnostic test; a reverse transcription polymerase chain reaction (RT-PCR) was done in case of suspected infection. Results: A total 878 CPs were included; COVID-19 prevalence was similar in both CPs (8%) and HCWs (9.5%); of the 70 CPs (8%) who were COVID (+), 29 (41.4%) were and remained asymptomatic; 241/808 of the COVID (-) (29.8%) were symptomatic. 18 COVID (+) were hospitalized (2% of CPs), 1 in intensive care unit (ICU) and 1 died (0.1% of CPs and 2.4% of symptomatic COVID [+] CPs). Only the inclusion center was associated with clinical presentation (in Nancy, Angers, Nantes, and Clermont-Ferrand: 65.4%, 35%, 28.6%, and 10% CPs were asymptomatic, respectively). Conclusions: Seroprevalence of COVID-19 in CPs was similar to that observed in HCWs; mortality related to COVID-19 among CPs was 0.1%. More than 40% of COVID (+) CPs were asymptomatic and one third of COVID (-) CPs had symptoms. Only geographic origin was associated with the presence or absence of symptoms. Social distancing and protective measures must be applied in CPs at home and when hospitalized.

Impact of Iron-Deficiency Management on Quality of Life in Patients with Cancer: A Prospective Cohort Study (CAMARA Study).

BACKGROUND: Iron deficiency (ID) is very common in patients with solid tumors and may cause symptoms such as fatigue. However, its impact on clinical outcomes is poorly described. The aim of this prospective monocentric cohort study was to evaluate the evolution of quality of life (QoL) of these patients after iron supplementation. METHODS: We included patients treated for a solid tumor, which were diagnosed with a functional (ferritin <800 ng/mL) or absolute (ferritin <300 ng/mL) ID (transferrin saturation coefficient <20%). The primary endpoint was patients' QoL evolution between baseline and intermediate visit, 15-30 days after initial intravenous iron supplementation, assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Secondary endpoints were the same assessment between baseline, intermediate, and final visit at 6 months and the evolution of functional capacities. RESULTS: From 02/2014 to 12/2016, 248 patients were enrolled, of whom 186 were included in the analyses, including 140/186 (75.3%) with absolute ID. Anemia was detected in 141/174 (81.0%) patients at baseline. The FACT-An scores improved significantly between inclusion and intermediate visit (P = .001) and also between the 3 times of evaluation (P < .001). The most improved dimensions were those assessing physical, emotional well-being, and fatigue. Patients who performed the functional tests in all 3 phases had a significant improvement in performance on the majority of tests. CONCLUSION: The supplementation of ID was associated with an improvement of the QoL and functional capacities in patients with cancer. A randomized control trial is necessary to confirm our results. Our findings underline the importance of supportive care, including screening for ID, in oncology. CLINICAL TRIAL REGISTRATION NUMBER: NCT03625661.

High flow nasal cannula improves breathing efficiency and ventilatory ratio in COPD patients recovering from an exacerbation.

BACKGROUND AND STUDY PURPOSE: High flow nasal cannula (HFNC) may improve CO2 elimination by washing out CO2 from the upper airways. This study aimed at assessing the effect of HFNC on minute ventilation and ventilatory ratio (VR), a surrogate of dead space, in patients hospitalized for acute hypercapnic COPD exacerbation. METHODS: Physiological study comparing HFNC at 40 L/min to low flow oxygen. Variations of tidal volume (VT) and minute ventilation between the two treatments were estimated from chest plethysmography. Respiratory rate (RR) and arterial blood gases were measured. Variations in VR were calculated. Data were compared using Wilcoxon tests. RESULTS: Recordings performed in 10 patients. Minute ventilation was reduced with HFNC by -16.2 [-30.9-0.4] % (p = 0.049). VT was not different but RR was lower during HFNC. PaCO2 was lower with HFNC compared to standard oxygen: 48.7 [46.4-58.1] vs 50.7 [48.4-57.5] mmHg (p = 0.020). VR decreased by -18.0 [-34.7 - -4.0] % (p = 0.020) with HFNC. CONCLUSIONS: In patients recovering from acute COPD exacerbation, the use of HFNC reduced RR, minute ventilation, PaCO2 and VR compared to standard oxygen. These changes are consistent with a decrease in physiologic dead space with HFNC.

Peripheral Neuropathic Pain Following Breast Cancer: Effectiveness and Tolerability of High-Concentration Capsaicin Patch.

PURPOSE: Data supporting the use of high-concentration capsaicin patches (HCCPs) in breast cancer (BC) patients and BC survivors (BCSs) with peripheral neuropathic pain (PNP) are limited. This observational study evaluated the effectiveness and safety of HCCP applications in BCSs/BC patients with PNP. PATIENTS AND METHODS: Data from all patients treated with HCCP in the pain department of a French comprehensive cancer centre were collected from 01-Jan-2014 to 14-Oct-2020. Independent pain specialists completed the Clinical Global Impression of Change (CGIC) for each included patient based on data extracted from patient's electronic medical record compiled by the treating pain specialist after each HCCP application. RESULTS: Patients (N=279; mean age: 59.2 years; previous history of PNP medication: 54.5%) received on average 4.1 repeated HCCP applications (1141 HCCP applications); 68.8% received HCCP as an add-on to systemic therapy and 27.9% as first-line therapy. PNP was most frequently caused by surgery (62.4%) followed by chemotherapy (11.8%) and radiotherapy (6.5%). A complete or important analgesic effect was reported at least once by 82.3% of patients. A 6.0% reported no effect at all. For post-surgical PNP existing for <12 months and >10 years an important or complete effect was observed for 70.7% and 56.0% of applications. For chemotherapy- or radiotherapy-induced PNP, this important or complete effect was observed for 52.7% and 52.3% of applications, respectively. HCCP application was associated with site reactions in 54.4% of patients (mainly burning sensation or pain, 45.9%, or erythema, 30.8%) and high blood pressure in 7.2%. CONCLUSION: This real-world chart review provides important effectiveness and safety information to clinicians when considering topical options to treat PNP in BCSs/BC patients.

Serum phosphate level and its kinetic as an early marker of acute kidney injury in tumor lysis syndrome.

INTRODUCTION: Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied. METHODS: In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development. RESULTS: One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence. CONCLUSION: This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Prognostic Value of Metabolic, Volumetric and Textural Parameters of Baseline [18F]FDG PET/CT in Early Triple-Negative Breast Cancer.

(1) Background: triple-negative breast cancer (TNBC) remains a clinical and therapeutic challenge primarily affecting young women with poor prognosis. TNBC is currently treated as a single entity but presents a very diverse profile in terms of prognosis and response to treatment. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose ([18F]FDG) is gaining importance for the staging of breast cancers. TNBCs often show high [18F]FDG uptake and some studies have suggested a prognostic value for metabolic and volumetric parameters, but no study to our knowledge has examined textural features in TNBC. The objective of this study was to evaluate the association between metabolic, volumetric and textural parameters measured at the initial [18F]FDG PET/CT and disease-free survival (DFS) and overall survival (OS) in patients with nonmetastatic TBNC. (2) Methods: all consecutive nonmetastatic TNBC patients who underwent a [18F]FDG PET/CT examination upon diagnosis between 2012 and 2018 were retrospectively included. The metabolic and volumetric parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG) and the textural features (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) of the primary tumor were collected. (3) Results: 111 patients were enrolled (median follow-up: 53.6 months). In the univariate analysis, high TLG, MTV and entropy values of the primary tumor were associated with lower DFS (p = 0.008, p = 0.006 and p = 0.025, respectively) and lower OS (p = 0.002, p = 0.001 and p = 0.046, respectively). The discriminating thresholds for two-year DFS were calculated as 7.5 for MTV, 55.8 for TLG and 2.6 for entropy. The discriminating thresholds for two-year OS were calculated as 9.3 for MTV, 57.4 for TLG and 2.67 for entropy. In the multivariate analysis, lymph node involvement in PET/CT was associated with lower DFS (p = 0.036), and the high MTV of the primary tumor was correlated with lower OS (p = 0.014). (4) Conclusions: textural features associated with metabolic and volumetric parameters of baseline [18F]FDG PET/CT have a prognostic value for identifying high-relapse-risk groups in early TNBC patients.

A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial).

INTRODUCTION: Resistance to trastuzumab in breast cancer is an ongoing challenge. Clinical and biological effects of co-targeting HER2 and mammalian target of rapamycin (mTOR) in patients with HER2-positive early operable breast cancer via the addition of everolimus to preoperative trastuzumab were evaluated in a phase II randomised study. METHODS: Patients were randomised 1:1 to receive trastuzumab (4 mg/kg initial dose then 2 mg/kg weekly for 5 weeks) alone or combined with everolimus (10 mg/day for 6 weeks) and then underwent surgery. Tumours were assessed by clinical examination and echography at the baseline and on treatment. The primary end-point was the clinical response rate at 6 weeks. Pathological response and safety were also evaluated. Baseline and surgery tumour samples were assessed by immunohistochemistry and multiplex immunoanalysis for predictive downstream effectors of the PI3K/AKT/mTOR and MAP kinase (MAPK) pathways. RESULTS: Eighty-two patients were enrolled, 41 per arm. The clinical response rates were 34.1% and 43.9% with trastuzumab alone and combined with everolimus, respectively. Pathological response rates were 43.6% and 47.5%, respectively. Addition of everolimus increased toxicity, notably mucositis (82.5% versus 5.0%) and rash (57.5% versus 10.0%), but grade III/IV events were rare. No correlation between response to treatments and baseline candidate biomarkers was identified, except for PIK3CA mutations which were found to predict trastuzumab resistance. Significant changes were seen in several MAPK pathway effectors after combination therapy. CONCLUSIONS: The addition of everolimus did not improve the efficacy, but induced MAPK signalling. Combination therapy to overcome pathway cross-talk should be considered to maximise the effectiveness of trastuzumab in this setting. ClinicalTrial.gov Identifier NCT00674414.

Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19 versus non-COVID-19 pulmonary acute respiratory distress syndrome.

BACKGROUND: Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation. METHODS: 135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS. RESULTS: The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28-44] vs 32 [26-38] ml cmH2O-1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666). CONCLUSIONS: For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients. TRIAL REGISTRATION: clinicaltrials.gov NCT04385004.