Introduction
Peritoneal carcinomatosis is considered a late‐stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC) can be an ...effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS‐HIPEC using only preoperatively known variables.
Methods
Adult patients with peritoneal carcinomatosis and who underwent CRS‐HIPEC were included from a large, single‐center, prospectively maintained dataset (2001–2020). TO was defined as a hospital length of stay ≤14 days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90 days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user‐friendly risk calculator was then developed.
Results
A total of 1954 CRS‐HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n = 258) achieved TO following CRS‐HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery.
Conclusion
This is a data‐driven study to predict the probability of achieving TO after CRS‐HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.
Teclistamab is a BCMA/ CD3 bispecific T cell engager, FDA approved in relapsed/refractory multiple myeloma (RRMM) after 4 prior lines of therapy, based on the results of MajesTEC-1 study. Early ...toxicities of teclistamab include CRS and ICANS. To mitigate the risk of CRS/ICANS, teclistamab is administered in a step-up dosing approach. 48h inpatient observation after each of the 3 step-up doses is recommended, although not mandated by FDA. Based on our outpatient CAR-T program experience, we implemented an outpatient teclistamab step-up dosing administration program.
To evaluate safety of outpatient teclistamab administration.
Retrospective review of toxicity outcomes of patients treated in outpatient teclistamab program at Fox Chase.
Comprehensive Cancer Center, BMT program.
Eligible patients were required to stay within 1h from Fox Chase with a caregiver during the observation period (days 1-10). Patients and caregivers received education on CRS and ICANS. Teclistamab was administered on days 1, 3, and 8. Safety monitoring protocol included daily evaluation in the outpatient clinic, home monitoring of vital signs, and 8 pm physician phone call on days 1-5 and 8-10, within 48h window after each step-up dose. CBC, CMP, CRP, ferritin were monitored at each visit. Patients with CRS/ ICANS of any grade were admitted for observation and management.
Between 12/2022-5/2023, 18 patients completed outpatient teclistamab step-up dosing. The median age was 66y (46-81). 12(66.7%) patients did not have CRS/ICANS. 5(27.8%) patients had grade 1 CRS, of which 1(5.6%) had concurrent grade 1 ICANS. 1(5.6%) patient had grade 2 CRS. Of the 6 CRS events, 3(50%) occurred after the first dose and 3(50%) after the second dose. 5 of 6 patients with CRS received 1 dose of tocilizumab, and the patient with concurrent ICANS also received dexamethasone, with prompt resolution of symptoms. All patients completed step-up dosing with no recurrent CRS/ICANS.
Outpatient teclistamab step-up dosing administration with close monitoring and prompt hospitalization for toxicity management is safe and feasible in heavily pre-treated RRMM patients. This approach allows a significant reduction of inpatient stay, resulting in significant healthcare resource savings and improvement of patients’ experience.
Open cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is still considered the golden standard of treatment, but for well-selected patients, minimally invasive ...surgery is showing promising results in reducing overall morbidity and hospital stay with no apparent consequences on long-term outcomes. One area where minimally invasive modalities bring evident benefits is risk-reducing CRS plus HIPEC where usually the overall bulk of resections being made are procedures where laparoscopy already is the golden standard of treatment. We present a case series of three patients with type II low-grade appendiceal mucinous neoplasm (LAMN) who, after reviewing the pathological and radiological findings, were selected for risk-reducing laparoscopic CRS and HIPEC. One of the patients was converted to open surgery due to discrepancies between the intraoperative findings and the preoperative radiological assessment. The median follow-up was 17 months with no recurrence found. A review of the Pubmed database was performed and was in congruence with our experience: The role of laparoscopic CRS plus HIPEC in well selected patients surpasses diagnostic or palliative purposes and is an important option especially when speaking about risk reducing surgeries with several benefits concerning morbidity and noninferiority in long-term oncological outcomes.
Modulation of the dysbiotic gut microbiome with "healthy" bacteria via a stool transplant or supplementation is increasingly practiced, however this approach has not been explored in the nasal ...passages. We wished to verify whether
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bacteria could be safely applied via irrigation to the nasal and sinus passages in individuals with chronic rhinosinusitis (CRS) with previous undergone endoscopic sinus surgery, and whether this was accompanied by bacterial community flora modification.
Prospective open-label pilot trial of safety and feasibility.
Academic tertiary hospital center.
Twenty-four patients with CRS refractory to previous medical and surgical therapy received a 14-day course of BID sinus irrigations containing 1.2 × 10
CFU live
. Patients were monitored for safety using questionnaire, sinus endoscopy, otoscopy, UPSIT-40 smell testing, and endoscopically-obtained conventional sinus culture and a swab for 16S microbiome profiling.
All 24 patients receiving at least one treatment successfully completed treatment.
probiotic treatment was safe, with no major adverse events or new infections. Treatment was associated with improvement in sinus symptoms, QOL, and mucosal scores, which remained improved during the subsequent 14-day observation period. Microbiome changes associated with treatment were limited to an increase of the pathobiont
, a bacteria identified as potentially beneficial in the upper airways. Subgroup analysis suggested differences in microbiomes and responses for CRSsNP and CRSwNP phenotypes, but these did not attain significance.
Intranasal irrigation of live
bacteria to patients with refractory chronic rhinosinusitis was safe, and was associated with effects on symptoms, mucosal aspect and microbiome composition. Intranasal bacteria may thus find a role as a treatment strategy for CRS.
www.ClinicalTrials.gov. identifier: NCT04048174.
The objective of this study is to assess the correlation between the pre-operative CA125 Elimination rate constant K(KELIM) score and the intraoperative chemo-response score (CRS) in patients with ...advanced high grade serous ovarian cancer(HGSC) treated with neoadjuvant chemotherapy(NACT).
This is a retrospective cohort study of patients with Stage III-IV HGSC treated with NACT from March 2010 to December 2019 at Princess Margaret Cancer Center, Toronto, Canada. KELIM scores were calculated based on the tool devised by You et al. available online. CRS was assessed using an established 3-tier scoring system. An association analysis was performed to determine if the KELIM score assessed during NACT can predict CRS score at the time of interval cytoreductive surgery(ICS).
172 patients were included in this analysis. Patients with CRS 1–2 had a lower median Platinum Free Interval(PFI) (9.24 vs 13.64 months, p = 0.005), lower median progression free survival(PFS) (14.99 vs 20.29 months, p = 0.003) and lower 5-year overall survival(OS) (63.8% vs 69.7%, p = 0.54) compared to patients with CRS3. Among patients with CRS 1–2(n = 115), 68.7% had KELIM <1, while 56.2% of patients with CRS3 had KELIM ≥1(56.2%), p = 0.0017, suggesting a correlation between the KELIM and CRS scores. Furthermore, patients with KELIM ≥1 and CRS3 had significantly higher PFS compared to other groups(median PFS 28.27 months vs 17.66 months for KELIM ≥1/CRS 1/2; 17.13 months for KELIM <1/CRS 3; and 14.53 months for KELIM <1/CRS 1–2, p = 0.003).
The biochemical KELIM score correlated with the surgical pathologic CRS score and may predict pathological response to chemotherapy. This information can be utilized to tailor and personalize treatment in patients with advanced ovarian malignancy.
•The KELIM score is predictive of chemotherapy response in patients with advanced ovarian cancer who are treated with NACT.•The KELIM score correlates with the pathologic CRS score.•The combination of the KELIM and CRS scores can be used to personalize treatment for patients with advanced ovarian cancer.
In response to the urgent need for the development of low-orbit 5th Generation Mobile Networks (5G) protocol standards, R16 protocol standards and terminal baseband chips based on 5G low-orbit ...broadband satellite communication systems, a Primary Synchronization Signal (PSS) detection algorithm of " two blocks combined and divided into two cross-correlation" is proposed for coarse frequency offset estimation based on the analysis of the Low Earth Orbit (LEO)-5G system's PBCH link structure and downlink time-frequency synchronization overall architecture. The frequency offset is further estimated through Secondary Synchronization Signal (SSS) correlation, and combined with Cell-Specific Reference Signal (CRS) pilot signal to determine the precise synchronization LEO-5G downlink synchronization algorithm with Field Programmable Gate Array (FPGA). The feasibility and effectiveness of the algorithm were verified by simulation using Vivado and Matlab. The results show that the synchronization algorithm has good rea
In response to the urgent need for the development of low-orbit 5th Generation Mobile Networks (5G) protocol standards, R16 protocol standards and terminal baseband chips based on 5G low-orbit ...broadband satellite communication systems, a Primary Synchronization Signal (PSS) detection algorithm of " two blocks combined and divided into two cross-correlation" is proposed for coarse frequency offset estimation based on the analysis of the Low Earth Orbit (LEO)-5G system's PBCH link structure and downlink time-frequency synchronization overall architecture. The frequency offset is further estimated through Secondary Synchronization Signal (SSS) correlation, and combined with Cell-Specific Reference Signal (CRS) pilot signal to determine the precise synchronization LEO-5G downlink synchronization algorithm with Field Programmable Gate Array (FPGA). The feasibility and effectiveness of the algorithm were verified by simulation using Vivado and Matlab. The results show that the synchronization algorithm has good rea
Colorectal cancer (CRC) patients with peritoneal metastasis (CRC-PM) have a worse prognosis than those with liver and lung metastases. Cytoreductive surgery (CRS) followed by hyperthermic ...intraperitoneal chemotherapy (HIPEC) is an effective locoregional treatment for CRC-PM. To date, the prognostic analysis of CRS/HIPEC mostly focuses on clinical and pathological characteristics; however, genetic characteristics, such as RAS/BRAF mutation status, are not sufficient. This study aimed to systematically assess the correlation between RAS/BRAF status and PM risk, as well as the prognostic efficacy of CRS/HIPEC for CRC.
This study was written in accordance with the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We searched PubMed, EMBASE, and the Cochrane library with the following keywords: “Peritoneal Neoplasms,” “raf Kinases” and “ras Proteins”. The fixed-effects model and inverse variance method were used for analysis. Odds ratios (OR) and 95 % confidence intervals (CI) were used to reflect the risk of PM associated with RAS/BRAF mutations. Hazard ratios (HR) and 95 % CI were used to evaluate the effects of RAS/BRAF mutations on the prognosis of CRS/HIPEC.
Eighteen articles included 5567 patients. In the risk analysis of PM, patients with BRAF mutation were more likely to have PM than those with wild-type BRAF (OR = 2.28, 95 % CI = 1.73–3.01, P < 0.001, I2 = 0 %). In contrast, there was no significant difference in the effect of RAS mutation and wild-type on PM of CRC (OR = 1.28, 95 % CI = 0.99–1.66, P = .06, I2 = 0 %). In a prognostic analysis of CRS/HIPEC, RAS mutation predicted poor overall survival (HR = 1.68, 95 % CI = 1.39–2.02, P < 0.001, I2 = 1 %) and disease-free survival (HR = 1.61, 95 % CI = 1.34–1.94, P < 0.001, I2 = 42 %). The results for BRAF mutation was consistent with the prognostic impact of RAS mutation's overall survival (HR = 2.57, 95 % CI = 1.93–3.44, P < 0.001, I2 = 0 %) and disease-free survival (HR = 1.90, 95 % CI = 1.40–2.56, P < 0.001, I2 = 82 %).
BRAF mutation, rather than RAS mutation, was a high-risk factor for CRC-PM. And both BRAF and RAS mutations negatively affected the prognosis of CRS/HIPEC in CRC-PM patients. Our results could provide suggestions for the selection of comprehensive treatment for CRC-PM with RAS/BRAF mutations.
To describe the outcome of CAR-T therapy in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Retrospective analysis of CAR-T therapy outcome in DLBCL, in a single center. The chimeric ...antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas.
Between November 2020 and December 2022, a total of 25 patients with relapsed or refractory DLBCL to ≥2 lines of therapy received an infusion and were included in the analysis. Of the 25 patients, 64% were male, the median age was 48 (20-73), and ECOG was 0-1. The disease subtype includes germinal center B-cell (GCB) 52% (n=12) and activated B-cell (ABC) 48% (n=12); the disease stage was III (44%, n=11) and IV (52%, n=13). All patients received at least 2 lines of therapy; 52% received ≥ 3 lines. Relapsed after autologous stem cell transplantation in 24% (n=6). Three patients (12%) have CNS involvement which was controlled at the infusion time. All patients received lymphodepletion (LD) therapy with fludarabine and cyclophosphamide (Flu/Cy). 20% (n=5) required bridging therapy before LD.
Overall response rate (ORR), complete responses (CR), partial responses (PR). The respective toxicities include cytokine release syndrome (CRS) and neurologic events namely ICANS.
The best ORR was 52%; 32% of the patients had CR, and 20% had PR. The disease progression (DP) was 48%. The 2 years overall survival was 72% with 69.2% for GCB subtype. Overall progressive free survival (PFS) was 44%, and the best PFS was observed in GCB subtype 53.8%. Day-90 PET/CT ORR 44% (CR/PR) 36%/8%. DP at day 90 was 36%. The main toxicities post CAR-T cell infusion including cytokines release syndrome (CRS) was 88% with 12% grade ≥ 3, and the neurotoxicity (NT) namely was 24% with 20% grade ≥ 3. Tocilizumab was used in 60%. Two patients died from disease progression within 30 days after infusion.
In this single-center retrospective analysis of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, the rates of durable responses were like the real-world data and JULIET NCT02445248 trial outcome using tisagenlecleucel therapy
Complementary resistive switches (CRS), which consist of two anti-serially connected bipolar switching ReRAM cells, can reduce sneak path currents in passive crossbar arrays. However, the high ...operation current restrains the implementation of the CRS device. In this article, we present low current operation (<300 A) of vertically stacked, 4F2-compatible Ta2O5-based CRS devices exhibiting two terminals. Two types of devices, either offering a nano- or a micrometer scale bottom cell (BC), are considered. The top cell (TC) in both configurations is designed of micrometer size. A novel three-step electroforming procedure for the vertical CRS device having no access to the middle electrode is exemplified and compared to the conventional forming procedure using three-terminal CRS devices. This three-step electroforming procedure provides adjustment of the maximum switching current in the nano-BC CRS: a low-level current compliance during forming enables low current CRS operation in subsequent switching cycles. Further, the nano-BC CRS shows the stable switching up to 104 cycles whereas the micro-BC CRS endures up to 106 cycles.
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