Scheduled Cycles Research Articles

Real-world outcomes of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: the JSCCR-TRIPON study.

FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Out of 104 patients who met the criteria, the median age was 58years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8months (95% CI, 10.6-15.0) and 27.9months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

Determinants of clinic absenteeism in a chemotherapy service of a cancer center located at Rio de Janeiro, Brazil.

Clinic absenteeism promotes higher waiting lists for medical procedures and public resources waste. The present work aimed to identify the reasons for clinic absenteeism from each cycle of the antineoplastic chemotherapy treatment, as well as to determine the socio-demographic, clinical and treatment profiles of this population. This observational prospective work evaluated pediatric and adult patients which missed their chemotherapy cycle between May and October 2023 in a Cancer Center located in Rio de Janeiro, Brazil. Clinic absenteeism rate was calculated, and socio-demographic profile was described. Reasons for absenteeism, treatment protocol and most used drugs were also identified. This work analyzed data from 69 patients, the majority above 60 years old. Approximately 60% were male, 33.3% had little to no education and 63.8% lived outside the center city. Absenteeism average monthly rate was 1.73% for adults and 0.87% for children. The most related non-attendance reasons were patient feeling too ill to attend their chemotherapy session, failure to remember the cycle day and lack of means of transportation. Most prevalent neoplasms were from the digestive tract (46%). Fluorouracil, irinotecan, oxaliplatin and gemcitabine were the most discarded drugs due to absenteeism. Older patients and the ones residing far away from the Center tend to miss the scheduled chemotherapy cycles. However, most reasons for absenteeism could be avoided by confirmation calls or text messages. These procedures implementation could lead to a lower absenteeism rate and less resource waste.

Synchronous timing of return to breeding sites in a long-distance migratory seabird with ocean-scale variation in migration schedules

BackgroundMigratory birds generally have tightly scheduled annual cycles, in which delays can have carry-over effects on the timing of later events, ultimately impacting reproductive output. Whether temporal carry-over effects are more pronounced among migrations over larger distances, with tighter schedules, is a largely unexplored question.MethodsWe tracked individual Arctic Skuas Stercorarius parasiticus, a long-distance migratory seabird, from eight breeding populations between Greenland and Siberia using light-level geolocators. We tested whether migration schedules among breeding populations differ as a function of their use of seven widely divergent wintering areas across the Atlantic Ocean, Mediterranean Sea and Indian Ocean.ResultsBreeding at higher latitudes led not only to later reproduction and migration, but also faster spring migration and shorter time between return to the breeding area and clutch initiation. Wintering area was consistent within individuals among years; and more distant areas were associated with more time spent on migration and less time in the wintering areas. Skuas adjusted the period spent in the wintering area, regardless of migration distance, which buffered the variation in timing of autumn migration. Choice of wintering area had only minor effects on timing of return at the breeding area and timing of breeding and these effects were not consistent between breeding populations.ConclusionThe lack of a consistent effect of wintering area on timing of return between breeding areas indicates that individuals synchronize their arrival with others in their population despite extensive individual differences in migration strategies.

Ideal frozen embryo transfer regime.

This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published research on different endometrial preparation methods for frozen embryo transfer (FET). While the artificial-FET cycle provides advantages in scheduling and implantation, it falls short in ensuring optimal obstetric outcomes. In contrast, natural-FET ensures embryo implantation conditions if ovulation is correctly identified. Supplementing with exogenous progesterone shields against low corpus luteum progesterone secretion, crucial for positive obstetric outcomes. In mNC-FET, ovulation is hCG-triggered, closely resembling natural cycles and reducing monitoring visits for enhanced patient convenience.Letrozole is a recommended option for anovulatory patients, preserving endometrial thickness. It is cost-effective, less likely to induce multifollicular development than gonadotropins, and better tolerated.In a novel approach, the natural-proliferative-phase-FET initiates progesterone in an unmediated ovulatory cycle at 7 mm endometrial thickness, combining the benefits of a natural proliferative endometrium with the convenience of scheduled artificial cycles. The artificial cycle offers scheduling advantages, but may compromise obstetric outcomes. Natural FET relies on accurate ovulation timing for successful implantation. mNC-FET simplifies the process using hCG induction, minimizing clinic visits for improved convenience. Letrozole is highlighted as a cost-effective and well tolerated option in anovulatory patients. A recent innovative approach combines elements of natural and artificial cycles, showing promise for FET procedures.

270. PERIOPERATIVE CHEMOTHERAPY FOR OPERABLE GASTRO-ESOPHAGEAL JUNCTION OR GASTRIC CANCER: FLOT VERSUS ANTHRACYCLINE TRIPLETS

Abstract Background Since the FLOT4-AIO study (2019) showed improved survival in patients treated with neoadjuvant fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) compared to those treated with neoadjuvant anthracycline triplets, FLOT became standard of care in the Netherlands and most Western countries. The aim of this study was to compare the overall survival (OS), pathological response and surgical outcomes of FLOT chemotherapy to anthracycline triplets in the Netherlands, using real-world population level data. Methods Patients diagnosed with resectable (cT2-4a/cTxN0–3/NxM0) gastro-esophageal junction and gastric carcinoma between 2015–2020 were selected from the Netherlands’ Cancer Registry. Patients were included if they received neoadjuvant FLOT or anthracycline triplets whether this was followed by resection or not. OS was calculated from start of neoadjuvant therapy, analyzed using cox regression analysis and adjusted for sex, age, comorbidities, performance status, cT-stage/cN-stage and tumor grade. Secondary outcomes included the pathological complete response (pCR), proportion of patients that fully completed neoadjuvant chemotherapy (100% of scheduled cycles permitting dose reductions), proportion of patients that underwent (radical) surgical resection and proportion receiving adjuvant therapy. Results 778 included patients were treated with FLOT and 913 with anthracycline triplets. Patients treated with FLOT underwent more staging diagnostic laparoscopies (DLS) (73.5% vs. 44.1%, p < 0.0001). Adjusted OS was better after neoadjuvant FLOT (HR = 0.84, 95% CI 0.72–0.98, p = 0.03). 3-year and 5-year OS were 56.4% and 46.6% after FLOT and 52.7% and 45.5% after anthracycline triplets, respectively. A higher proportion of patients treated with FLOT fully completed neoadjuvant chemotherapy (78.5% vs. 73.1%, p = 0.009) and had R0 resections (86.2% vs. 85.2%, p = 0.007). No statistically significant differences were seen in the proportions of patients that underwent resection, received adjuvant therapy, or had pCR. Conclusion Real-world population level data showed better OS of patients treated with FLOT chemotherapy compared to anthracycline triplets. No statistically significant difference was observed in pCR or resection rates. Thus, not every outcome as described in the FLOT4-AIO trial could be reproduced in a real-world population, despite improved staging with DLS in the FLOT group. Divergent baseline characteristics and less intensive neoadjuvant treatments in real-world patients compared to patients in clinical trials may contribute to this discrepancy.

Early Wearing-Off Effect of OnabotulinumtoxinA in Chronic Migraine: A Prospective Real-Life Study.

Chronic migraine (CM) is a significant public health problem that affects 2.2% of the global population. Onabotulinumtoxin A (OnabotA) is a safe and effective prophylactic treatment for patients with CM. The standard injection interval for OnabotA is 12 weeks. Nevertheless, some patients experience a wearing-off effect (WOE) in the weeks preceding the next scheduled cycle. The objectives of this study are to determine the prevalence of early WOE, to analyze variables that could be clinical predictors and to specify which interval is the most appropriate to define the existence of this phenomenon. This is a prospective single-center study of consecutive adult patients with CM who, after failing previous prophylactic therapies, started OnabotA treatment following the PREEMPT protocol between June and December of 2021. A total of 59 patients (93.2% female, age 44 ± 12 years) were included. A total of 37 patients (64.9%) fulfilled medication overuse criteria. Of the total patients, 40.6% reported WOE and this was more frequent after the first cycle (35.6%). Depression and anxiety disorder was a statistically significant clinical predictor of WOE (OR 3.4; CI 95% 1.22-10.84; p = 0.028). A better cut-off point to consider WOE seems to be at 10 weeks. Early WOE is common in patients on OnabotA treatment for CM. Individualizing the standard 12-week injection, using total doses of 195 U, and managing psychiatric comorbidities with pharmacological and non-pharmacological strategies may improve treatment outcomes and reduce OnabotA WOE.

Tough Decision Making in Pembrolizumab-Associated Acute Interstitial Nephritis: A Case Report

Pembrolizumab is an immune checkpoint inhibitor used as a cancer therapy. The incidence of immune related adverse events in patients receiving immune checkpoint inhibitors can be as high as 59%–85%. Renal adverse effects are uncommon, but the incidence of kidney toxicity related to pembrolizumab is rising as the use of this agent becomes more frequent. We present an uncommon case of biopsy-proven acute interstitial nephritis secondary to pembrolizumab in a patient with metastatic squamous cell carcinoma at the time of his fourth scheduled cycle. Despite the good initial tumor response, pembrolizumab had to be suspended and the patient started on corticosteroids with an initial good response. On his own initiative, the patient stopped prednisolone early, leading to a rebound acute kidney injury. Pembrolizumab was not reintroduced for the risk of further renal function worsening. His clinical status declined due to the progression of the neoplastic disease, and he was referred for palliative care. This case illustrates the importance of systematizing some key points in the approach to acute interstitial nephritis secondary to pembrolizumab: the role of the differential diagnosis of acute kidney injury in a patient under an immune checkpoint inhibitor, the role of glucocorticoids and the controversy about rechallenging this drug after a related acute interstitial nephritis.

Identifying cause-and-effect relationships of manufacturing errors using sequence-to-sequence learning

In car-body production the pre-formed sheet metal parts of the body are assembled on fully-automated production lines. The body passes through multiple stations in succession, and is processed according to the order requirements. The timely completion of orders depends on the individual station-based operations concluding within their scheduled cycle times. If an error occurs in one station, it can have a knock-on effect, resulting in delays on the downstream stations. To the best of our knowledge, there exist no methods for automatically distinguishing between source and knock-on errors in this setting, as well as establishing a causal relation between them. Utilizing real-time information about conditions collected by a production data acquisition system, we propose a novel vehicle manufacturing analysis system, which uses deep learning to establish a link between source and knock-on errors. We benchmark three sequence-to-sequence models, and introduce a novel composite time-weighted action metric for evaluating models in this context. We evaluate our framework on a real-world car production dataset recorded by Volkswagen Commercial Vehicles. Surprisingly we find that 71.68% of sequences contain either a source or knock-on error. With respect to seq2seq model training, we find that the Transformer demonstrates a better performance compared to LSTM and GRU in this domain, in particular when the prediction range with respect to the durations of future actions is increased.

An investigation into the causes of abnormal waste of Ortho-K lenses.

PurposeTo investigate the reasons for wasting orthokeratology (OK) lenses due to breakage or loss, provide more comprehensive guidelines for the clinical care of lenses and minimize time and costs for patients due to excessive broken and lost lenses.MethodsA survey was administered to clinic outpatients who had broken or lost their OK lenses before the regularly scheduled replacement cycle (1–1.5 years). The association between the frequency of OK lens breakage and daily care was assessed using Fisher's exact test and multivariable ordered logistic regression analysis.ResultsA total of 306 valid questionnaires were collected. Among the subjects, 141 were male, and 165 were female, with a mean age of 10.57 ± 2.00 years (range: 6–18 years). In the investigation of the causes of OK lens waste, 81.4% of the patients reported lens breakage, 13.1% lost their lenses, and 5.6% of patients experienced both fragmentation and lens loss. More than half of the patients (52.90%) used incorrect lens cleaning techniques. In further analysis of the relationship between the frequency of OK lens fragmentation within a year and daily care habits, a significant difference was observed between the caregiver (P = 0.03) and whether the lenses were cleaned promptly after removal (P < 0.001). Mothers as daily caregivers of OK lenses had a lower frequency of fragmentation in a year compared to nanny or grandparents (P = 0.014, OR = 0.33, 95% CI = 0.13, 0.80). The failure to clean the lenses according to eye care practitioners' guidance was a risk factor for the frequent breakage of OK lenses (P < 0.001. OR = 5.29, 95% CI = 3.15, 8.89).ConclusionsThe causes of OK lens waste were mainly attributed to caregivers, care practices and some unexpected situations that can be avoided through optometrists' reminders. Regardless of the reasons for noncompliant behavior leading to breakage or loss of OK lenses, all of the complications can probably be addressed by better and more frequent reinforcement of care procedures by practitioners. Better clinical guidance measures and more frequent reminders could prevent a large proportion of abnormal waste of OK lenses.

Evaluation of cytokine profile in cervicovaginal lavage specimens of women having asymptomatic reproductive tract infections

Reproductive tract infections (RTIs) such as vaginal candidiasis and bacterial vaginosis (BV) are common among sexually active women and can be both symptomatic or asymptomatic. The microbiota of the reproductive tract triggers immune response at the cervicovaginal interface resulting in secretion of cytokines during the course of these RTIs. The objective of this study was to evaluate the cytokine profile in cervicovaginal lavage of women having asymptomatic vaginal infections. Measurement of vaginal cytokines was done for various interleukins including IL-1β, IL-6, IL-8, IL-10, IL-12/IL23p40, IL-17A, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) by ProcartaPlex™ Multiplex Immunoassay. Women having vaginal Candida infection had increased concentration of IL-1β (p=.01), IL-6 (p=.007), IL-8 (p=.327), IL-12/IL23p40 (p=.049) and IFN-γ (p=.125). The results of our study suggest that evaluation of these cytokines could be explored as an additional measure to determine host inflammatory response in women having asymptomatic vaginal candidiasis. Impact Statement What is already known on this subject? Studies assessing the vaginal cytokine profile to assess the vaginal milieu in various cohorts such as post-menopausal women, pregnant women, women with history of preterm birth, CIN and scheduled IVF cycle are being undertaken. Variable cytokine response has been reported in literature in women with symptomatic bacterial vaginosis and Candida infection. However, much less is known about vaginal cytokine profile in asymptomatic infection. What do the results of this study add? The results of the study show increased concentration of the pro-inflammatory cytokines IL-1β, IL-6 IL-8, IL-12/IL23p40 and interferon gamma (IFN-γ) in women having asymptomatic Candida, vaginal leucocytosis and raised vaginal pH. What are the implications of these findings for clinical practice and/or further research? Evaluation of vaginal cytokine profile (IL-1β, IL-6 IL-8, IL-1β, IL-12/IL23p40 and IFN-γ) could be explored as an additional measure to determine inflammation in asymptomatic women. Vaginal cytokines (IL-1β, IL-6 IL-8, IL-1β, IL-12/IL23p40 and IFN-γ) could be used further for development of a point of care test.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients.

The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p = 0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p = 0.013), the oocyte maturity rate (79.42 versus 47.87%) (p = 0.041), the fertilization rate (65.68 versus 34.54%) (p = 0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p = 0.003) were higher in the GnRH antagonist group than in the control group. The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

The Omission of High-Dose Cytarabine during Consolidation Therapy of Ph-Positive ALL Patients Treated with Nilotinib and Low-Intensity Chemotherapy Results in an Increased Risk of Relapses Despite Non-Inferior Levels of Late BCR-ABL1 MRD Response. First Results of the Randomized Graaph-2014 Study

The Omission of High-Dose Cytarabine during Consolidation Therapy of Ph-Positive ALL Patients Treated with Nilotinib and Low-Intensity Chemotherapy Results in an Increased Risk of Relapses Despite Non-Inferior Levels of Late BCR-ABL1 MRD Response. First Results of the Randomized Graaph-2014 Study

Intermittent Fasting Inhibits High-Fat Diet-Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction.

Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.

Evaluating Pembrolizumab Interference with Monoclonal Protein Detection By Immunofixation and By MALDI-TOF Mass Spectrometry (MASS-FIX)

Introduction: Pembrolizumab is a humanized IgG1-κ monoclonal antibody (mAb) targeting the PD-1 receptor that is currently evaluated in clinical trials for the treatment of multiple myeloma (MM). Similar to other mAbs (e.g. daratumumab), it is important to know if pembrolizumab is identified by immunofixation (IFE) and whether it interferes with the detection of endogenous M-protein of patients with MM. Methods: Waste serum of patients with solid malignancies treated with pembrolizumab per routine clinical practice or on clinical trials was collected prior to their next scheduled treatment cycle (trough). All patients had received at least 4 cycles of therapy to allow the drug to reach steady-state. Samples were tested for the presence of a monoclonal protein using both IFE (Sebia Inc.) and nanobody enrichment coupled to MALDI-TOF mass spectrometry (MASS-FIX), as previously described (Mils JR, et al, Clinical Chemistry, 2016). IFE gels and MASS-FIX mass spectra were independently interpreted by the authors (TVK, MAW, AD, DLM). Two samples containing pembrolizumab at 0.05 g/dL and 0.025 g/dL, respectively and one normal serum were used as controls. Results: Of 32 patients, 20 were male. Median age was 62 years. The most common indications for treatment were metastatic melanoma (n=17) and colorectal cancer (n=6). Median dose of the drug was 200mg and all patients received one dose every three weeks. No patients had a detectable IgG kappa band or peak by IFE or MASS-FIX. One patient had a small IgG lambda band on IFE that was not detected by MASS-FIX and one patient had a small IgM lambda peak on MASS-FIX that was not detected by IFE. Pembrolizumab controls were barely detectable by IFE at 0.05 or 0.025 g/dL but were detectable by MASS-FIX. Conclusions: Pembrolizumab, at standard doses, should not interfere with monoclonal protein detection by IFE or MASS-FIX. MASS-FIX can identify monoclonal peaks from Pembrolizumab at low serum concentrations better than IFE. [Display omitted] DisclosuresDispenzieri:Celgene, Millenium, Pfizer, Janssen: Research Funding.

Dose intensity and treatment duration of bortezomib in transplant-ineligible newly diagnosed multiple myeloma.

Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy. We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib. Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48weeks (range 1-57), cumulative bortezomib dose was 41.8mg/m2 (2.6-67.6) and median dose intensity was 1.0mg/m2 /wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86weeks (95%CI 77-104) and 209weeks (95% CI 157-259) respectively. Patients who progressed <60days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6mg/m2 than the remaining individuals, 45.5 (P=.023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P=.00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P=.00002), patients with at least 50weeks of treatment (P=.02) and patients receiving a cumulative dose of at least 49mg/m2 (P=.05). Achievement of a VGPR (HR 0.23; 95%CI 0.12-0.46; P=.00002) and a cumulative dose of 49mg/m2 (HR 0.46, 95%CI 0.27-0.78; P=.003) were statistically independent prognostic factors for PFS. Toxicity-related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN. Biweekly full-dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.

Efficacy and safety of 177Lu-DOTATATE in patients (pts) with advanced pancreatic neuroendocrine tumors (pNETs): Data from the NETTER-R international, retrospective registry.

4116 Background: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is indicated in somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumours. The NETTER-R registry builds upon the existing evidence for pts with advanced pNETs, who have limited therapeutic options. Methods: NETTER-R is a retrospective registry of pts with unresectable or metastatic, well-differentiated, SSTR-positive, progressive pNETs treated with 177Lu-DOTATATE in the UK, France and Spain. Pts who received ≥1 administration of 177Lu-DOTATATE were included. The primary endpoint was progression-free survival (PFS) based on RECIST v1.1. Secondary endpoints included overall survival (OS), safety and tumour response. Results: A total of 110 pts with pNETs were identified. Median age was 58.0 years (range 28–89) and 52.7% were male. At baseline, 96.4% of pts had progressive disease. The Ki-67 index was ≤2% in 23.6%, 3–20% in 66.4% and &gt;20% in 2.7% of pts (7.3% missing). Metastases were present in the liver in 95.5% and bone in 29.1% of pts. Nearly all pts (90.9%) had received at least one prior anticancer therapy (somatostatin analogues: 70.0%, chemotherapy: 61.8%, protein kinase inhibitors: 38.2%). The majority of pts (70.0%) received all four scheduled cycles of 177Lu-DOTATATE. The cumulative activity was 26.6–32.6 GBq in 65.5% of pts (&lt;26.6 GBq: 31.8%, ≥32.6 GBq: 2.7%). 12 pts were re-treated after disease progression and received 1–4 additional cycles of 177Lu-DOTATATE. By RECIST v1.1, evaluable in 62 pts, median PFS was 24.8 months (95% CI 17.5–34.5) and objective response rate was 40.3% (95% CI 28.1–53.6); all responses were partial. The response rate, including radiological, clinical, metabolic and biomarker assessments, evaluable in 100 pts, was 54.0% (95% CI 43.7–64.0), including 2 pts with complete response. Over a median follow-up of 24.5 months (range 2.0–123.4), median OS in 110 pts was 41.4 months (95% CI 28.6–50.2). 71.8% (n=79/110) of pts had at least one treatment-emergent adverse event (TEAE). The most frequent were nausea (28.2%) and fatigue (22.7%), predominantly grade 1/2 in severity. No TEAEs led to treatment discontinuation. Grade 3 anaemia and lymphopenia occurred in 1 (0.9%) and 4 (3.6%) pts, respectively. No grade ≥3 thrombocytopenia or neutropenia were reported. Renal TEAEs occurred in 6 pts (5.5%; grade 1: n=1, grade 2: n=2, grade 3: n=3). Grade 3 renal events were transient (≤24 days) and did not lead to treatment modification. No acute leukaemia or myelodysplastic syndrome were reported within the follow-up. Conclusions: In a real-world population of pts with advanced pNETs, 177Lu-DOTATATE was well tolerated with a safety profile consistent with the NETTER-1 trial. With limited follow-up, the OS and PFS compared favourably with cohorts of progressive pNET patients treated with other systemic agents.

Predictive factors of poor blood collecting flow during leukocyte apheresis for cellular therapy.

Leukocyte apheresis is necessary in various cellular therapies. However, maintenance of a stable flow rate during leukocyte apheresis is often difficult, even in patients or donors without major problems. Despite this, predictive methods and evidence regarding the reality of the situation are limited. We conducted a retrospective analysis involving adult patients who required leukocyte apheresis for the treatment of neoplasms using WT1-pulsed dendritic cell vaccine. Monocytes were separated from apheresis products to obtain dendritic cells. All the patients were pre-evaluated based on laboratory and chest X-ray findings and subjected to an identical apheresis procedure. The occurrence of poor blood collecting flow during leukocyte apheresis was monitored, and the frequency, clinical information, and associated risk factors were analyzed. Among 160 cases, poor blood collecting flow was observed in 53 cases (33.1%) in a median time of 54 min (range, 2-127 min) post-initiation of leukocyte apheresis. Owing to difficulty in obtaining higher collecting flow, a longer procedure time was required, and in some cases, the scheduled apheresis cycles could not be completed. Consequently, the number of harvested monocytes was low. Multivariable analysis indicated that female patients have an increased risk of poor inlet flow rate. Furthermore, prolonged QT dispersion (QTD) calculated using Bazett's formula was found to be a risk factor. Although the patients did not present any major problems during leukocyte apheresis, poor blood collecting flow was observed in some cases. Sex and pre-evaluated QTD might be useful predictors for these cases; however, further prospective evaluation is necessary.

Hospital-acquired malnutrition in paediatric patients: a multicentre trial focusing on prevalence, risk factors, and impact on clinical outcomes.

Alteration of nutrient metabolism during hospital stay may cause a deterioration in patients' nutritional status. The aim of this study was to determine the prevalence and possible risk factors for nutritional deterioration in hospitalized children. A multicentre prospective study was conducted among the patients aged 1 month to 18 years in tertiary-care hospitals, between December 2018 and May 2019. Demographic data, illness, and nutritional assessment on the first and the last day of admission were collected. There were 623 patients enrolled in this study with the median age of 4.3 years. Two thirds of the patients had at least one underlying disease. Eighty-eight percent of the patients were admitted with mild medical conditions including a scheduled cycle of chemotherapy or immunosuppressive drugs, minor infection, and non-invasive procedures. The prevalence of nutritional deterioration (reduction in body mass index ≥ 0.25 Z-score) was 24% and was associated with a significantly higher rate of nosocomial infection (24% vs. 11%, p < 0.001) compared to patients without hospital-acquired malnutrition. Risk factors included moderate to severe medical conditions (AOR 1.90, 95% CI 1.09-3.31, p = 0.024), pneumonia (AOR 1.85, 95% CI 1.05-3.28, p = 0.034), seizure (AOR 2.82, 95% CI 1.28-6.19, p = 0.01), and surgery (AOR 2.98, 95% CI 1.60-5.56, p = 0.001). Nutritional management showed a significant reduction in the incidence of hospital-acquired malnutrition and a trend towards a 60% decrease in infectious complications in patients with moderate to severe medical conditions.Conclusions: Approximately one fourth of paediatric patients developed malnutrition during hospitalization. Nutritional screening, assessment, and treatment should be implemented to improve the outcomes of hospitalized paediatric patients. What is Known: • Malnutrition at admission has a negative impact on outcomes of patients, including prolonged hospitalization, increased costs of care, and a higher rate of nosocomial infection. What is New: • Hospital-acquired malnutrition can occur regardless of prior nutritional status and is predominantly related to illness severity. • Malnourished patients with nutritional intervention experience an improvement in their nutritional status as well as a lower risk of developing hospital morbidity during hospitalization.

Prognostic Value of 18F-Choline PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Radium-223.

We aimed to investigate the role of positron emission computed tomography (PET/CT) with 18F-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (223Ra-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with 18F-choline before 223Ra-therapy were retrospectively evaluated. The following PET-derived parameters were calculated: number of lesions, maximum and mean standardized uptake values (SUVmax, SUVmean), lean body mass corrected SUV peak (SULpeak), metabolic tumor volume (MATV), and total lesion activity (TLA). After 223Ra-therapy, all patients underwent regular follow-up until death. The predictive power of clinical and PET-derived parameters on overall survival (OS) was assessed by Kaplan–Meier analysis and the Cox proportional hazard method. All the patients showed 18F-choline-avid lesions at baseline PET/CT. Among the enrolled subjects, eleven (55%) completed all the six scheduled cycles of 223Ra-therapy; seven (35%) were responders according to imaging and biochemical parameters. Mean OS was 12.7 ± 1.4 months: by Kaplan–Meier analysis, number of lesions, PSA level and TLA were significantly correlated with OS. In multivariate Cox analysis, TLA remained the only significant predictor of survival (p = 0.003; hazard ratio = 7.6, 95% confidence interval = 1.9–29.5 months). 18F-choline PET may be useful for patients’ stratification before 223Ra-therapy. In particular, high metabolically active tumor burden (i.e., TLA) was predictive of poor outcome.

Abstract 253: Trajectory of Ventricular Fibrillation Prognostic Status During Cardiopulmonary Resuscitation

Background: Resuscitation from out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) typically involves continuous CPR cycles interrupted every 2 minutes for rhythm analysis and potential defibrillation. Quantitative measures of the VF ECG waveform have been proposed to guide therapy for VF arrest because they are associated with myocardial energetics, are dynamic over the course of resuscitation, and predict outcome. However, while VF waveform measures have until recently have required CPR interruption to accurately gauge prognostic status, CPR interruptions are associated with a lower chance of survival. We used a novel waveform measure previously-validated during active CPR to estimate the course of VF status through the 2-minute CPR cycle between consecutive shocks. Methods: We conducted an observational study of patients with VF OHCA who experienced recurrent VF for at least 90 seconds following initial shock. We used the continuous defibrillator ECG to calculate the VF waveform measure as a function of predicted probability of survival-with-intact-neurologic-status at 1-s intervals over the course of resuscitation between shocks. Results: We collected 499 VF ECG segments (≥90 seconds) during CPR from 313 patients. The trajectory of the average prognostic VF measure had a 3-phase time-dependent pattern (Fig. 1). During CPR, the slope of the measure decreased during the initial 25 s of VF (slope = -12%/min) and was relatively flat during the subsequent 65-s interval of VF (slope = +1%/min). Furthermore, slope decreased sharply following the cessation of CPR for rhythm analysis, charge, and shock (slope = -23%/min). Conclusion: On average, a novel VF waveform measure assessed during the scheduled cycle of CPR and rhythm analysis between consecutive shocks was characterized by a period of decline, stabilization, and then decline. Whether these changes in VF status can be used to improve care for individual patients is uncertain.