Number Of Treatment Cycles Research Articles

Perioperative adebrelimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: A single-arm, open-label, multicenter study.

421 Background: Neoadjuvant programmed cell death 1 (PD-1) inhibitors combined with chemotherapy have shown promising results in treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, relatively little attention has been focused on programmed cell death ligand 1 (PD-L1) blockades. This study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab (anti-PD-L1 antibody) plus chemotherapy followed by adjuvant adebrelimab for resectable LA-ESCC. Methods: In this single-arm, multicenter study, patients (pts) with newly diagnosed, locally advanced resectable thoracic ESCC (cT1b-2, N+ or cT3-4a, N0/+) received 2 cycles of neoadjuvant chemoimmunotherapy with adebrelimab (1200 mg), paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ) every 3 weeks, followed by esophagectomy and 16 doses of adebrelimab. The primary endpoints were safety and pathological complete response (pCR) rate. Secondary endpoints included surgery completion rate, R0 resection rate, major pathological response (MPR) rate, event-free survival (EFS) and disease-free survival (DFS). The trial was registered at Chinese Clinical Trial Registry, identifier: ChiCTR2300069179. Results: Between May 2023 and January 2024, 36 pts met inclusion criteria, with a median age of 65 years (range: 42-73). Of these, 66.7% (24/36) were classified as stage III-IVa. As of August 1, 2024, the median number of treatment cycles for all pts was 7 (interquartile range, 2-12). The neoadjuvant therapy completion rate was 91.7% (33/36). Thirty-two pts underwent minimally invasive esophagectomy, resulting in an overall surgical resection rate of 88.9% and an R0 resection rate of 90.6%. The pCR rate was 15.6% (5/32) and the MPR rate was 31.2% (10/32). The EFS and DFS outcomes were not mature. During the preoperative treatment period, 35 pts (97.2%) experienced any grade of treatment-related adverse events (TRAEs). Grade 3 or 4 TRAEs occurred in 7 pts (19.4%), and there were no grade 5 TRAEs. The most common grade 3/4 adverse events included neutropenia (11.1%), leukopenia (5.6%), diarrhea (5.6%) and hyponatremia (5.6%). Surgical complications of grade 3/4 were reported in 7 pts (21.9%), with anastomotic fistula (6.3%) being the most common. No perioperative deaths occurred. Conclusions: Neoadjuvant adebrelimab combined with chemotherapy and adjuvant adebrelimab demonstrated encouraging clinical efficacy and manageable safety in pts with LA-ESCC. Further study is warranted. Clinical trial information: ChiCTR2300069179.

Efficacy and safety of trifluridine/tipiracil and bevacizumab (FTD/TPI+BEV) in patients with metastatic colorectal cancer (mCRC) in real-world practice.

204 Background: In Sunlight trial, the combination of FTD/TPI + BEV showed a significant improvement in Overall Survival (OS) and Progression-Free Survival (PFS), along with better Objective Response Rate (ORR) and Disease Control Rate (DCR), compared to FTD/TPI alone, in patients with mCRC progressing after two chemotherapy regimens. The BeTAS trial aimed to evaluate the effectiveness and safety of the FTD/TPI + BEV combination in real-world practice. Methods: This was a retrospective, observational, multicenter study of mCRC patients treated with FTD/TPI+BEV in routine clinical practice across 11 Spanish university hospitals. It included patients with mCRC who were refractory or intolerant to standard therapies. Results: A total of 208 patients treated with FTD/TPI+BEV between July 2019 and December 2023 were included. The median age was 69 years (range 33 to 88 years), with 59.8% being male. 15.3% had an ECOG performance status of 2, 55.9% had RAS mutations, 30.3% had three or more metastatic sites, and 81.2% had liver metastases. Additionally, 19.8% had a time from diagnosis of first metastasis of less than 18 months, and 55.3% were categorized in Tabernero's Unfavorable Prognostic Subgroup. Most patients (81.3%) received FTD/TPI+BEV as third-line therapy, with 90.5% having previously received anti-VEGF therapy. The median number of treatment cycles was 4 (range 1 to 31 cycles). The ORR was 4.6%, and the DCR was 50%. The median PFS was 4.9 months (95% CI, 4.0-5.7 months), and the median OS was 11.1 months (95% CI, 9.5-12.8 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.2%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: Our series confirms the efficacy and safety of FTD/TPI + BEV in routine clinical practice, even in a population with poor prognosis and an extensive history of previous treatments.

Real-world data of durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: A Thailand multicenter observational study.

607 Background: Currently, durvalumab plus gemcitabine and cisplatin is a standard of care for patients with advanced biliary tract cancer (BTC). We aimed to evaluate efficacy and tolerability of durvalumab plus gemcitabine and cisplatin in real world experience in Thailand where there is high incidence of liver-fluke related cholangiocarcinoma (CCA). Methods: This is an observation study of patients with advanced BTC participating in the early access program of durvalumab since August 2023. Data were collected and analyzed for efficacy and toxicity. Results: Fifty patients participated the early access program in 14 centers across Thailand. Median follow-up time was 8.5 months. Median number of treatment cycles was 8.8 (1-16) cycles. Thirty six (72%) patients were alive and 8 (16%) patients were still on treatment. The mean age was 63 years, 60% were male and 92% were ECOG 0-1. There were 68% intrahepatic cholangiocarcinoma (CCA), 28% extrahepatic CCA and 8% gallbladder cancer. There were 29.5% objective response rate and 79.5% disease control rate. Median progression free survival (PFS) was 6.0 (95%CI 4.49-7.50) months. Eight (16%) patients were still on treatment with PFS more than 10 months. Grade 3 or 4 adverse events (AEs) were reported in 50% of patients. Most AEs were related to chemotherapy, there were 10% immune related AEs. Conclusions: In this real-world experience, durvalumab plus gemcitabine and cisplatin was efficacious and tolerable in Thai patients with advanced BTC.

Prevalence and predictive factors of chemotherapy-induced peripheral neuropathy in cancer patients: A cross-sectional single-center study in Pakistan.

Chemotherapy-induced peripheral neuropathy is a debilitating pain condition resulting from cancer treatment and is known to be associated with a decrease in health-related quality of life. This single-center cross-sectional study, conducted at Institute of Nuclear Medicine Oncology and Radiotherapy (INOR), Abbottabad, Pakistan, assessed the prevalence and severity of chemotherapy-induced peripheral neuropathy and its impact on quality of life in cancer patients undergoing chemotherapy. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CIPN20 questionnaires. Subscales are scored from 0 to 100, with higher scores indicating greater symptom severity. A total of 154 patients participated, with a mean age of 48.57 years (SD 14.22); 33.8% were male and 66.2% were female. The prevalence of sensory CIPN was 36.4%. The mean scores for the sensory, motor, and autonomic subscales of the QLQ-CIPN20 were 23.2 (SD 19.1), 16.6 (SD 15.8), and 14.8 (SD 17.2), respectively. CIPN symptom severity was negatively correlated with global health status/quality of life and physical, role, emotional, cognitive, and social functioning. There was no significant association with age, sex, body surface area, height, weight, or type of chemotherapeutic agent used. However, symptom severity increased with the number of treatment cycles completed (e.g., sensory, p = 0.003). CIPN was prevalent in this healthcare center and significantly impacted function and quality of life. These findings highlight the importance of developing strategies to mitigate CIPN and the need for routine screening of CIPN.

Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial.

To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). IMPROVE (ClinicalTrials.gov identifier: NCT04425239) was an open-label, multicenter, randomized phase II noncomparative trial. Patients with unresectable RAS/BRAF wt mCRC were randomly assigned (1:1) to receive FOLFIRI plus PAN continuously until progression (arm A) or intermittently, with treatment-free intervals (arm B) until progression on treatment, toxicity, or death. The primary end point was progression-free survival on treatment (PFSot) at 12 months. Assuming a null hypothesis of median PFSot time ≤7 months and target PFSot ≥10 months, 65 patients per arm were needed to achieve 80% power and 10% type I error, according to the binomial test. Between May 2018 and June 2021, 69 patients were randomly assigned to arm A and 68 to arm B. The median number of treatment cycles was 13 in arm A and 16 in arm B. At a median follow-up of 43.2 months (IQR, 35.0-50.5), median PFSot was 11.2 and 17.5 months with 12-month PFSot rates of 45.7% and 58.5%, for arms A and B, respectively. The overall response rates were 68.1% and 61.2%, and median overall survival rates were 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 skin PAN-related adverse events was 30.3% in arm A and 17.9% in arm B. Intermittent FOLFIRI plus PAN after the induction phase was feasible, and the primary end point was met with reduced toxicity while allowing patients more time off treatment.

CTNI-73. ASSESSMENT OF MOLECULAR ALTERATIONS IN NEWLY DIAGNOSED GBM MGMT-UNMETHYLATED PATIENTS TREATED WITH VAL-083

Abstract Glioblastoma (GBM) commonly features molecular alterations in the TERT, EGFR, PTEN, and TP53 genes, which contributes to uncontrolled cell growth, evasion of apoptosis, and enhanced tumor cell survival. VAL-083 is a bi-functional DNA-targeting agent which rapidly induces inter-strand DNA cross-links at N7 and O6-guanine inducing double-strand breaks causing cell death independently of MGMT DNA repair and DNA mismatch repair deficiency. VAL-083 was evaluated in an open-label, biomarker-driven, phase 2 trial in MGMT-unmethylated, bevacizumab-naïve GBM patients. The molecular profile of tumors from a newly diagnosed GBM patient subgroup who received VAL-083 alone after chemo-radiation with concurrent TMZ, was determined in order to correlate with clinical outcomes. Thirty-four (34/36, 94.4%) patients who received 30 mg/m2 VAL-083 (days 1-3 of 21-day cycle) had available next-generation sequencing data on their primary tissue. Patient median age was 54.8 years (5-95pth: 29.8-66.0), median KPS was 90 (5-95pth: 80-100) and 58.8% were males. The median number of cycles of VAL-083 was 7.5 (5-95pth: 1-12). There were 5 dose reductions due to toxicity. The median time to progression (PFS) and overall survival (OS) were 9.2 mo (95%CI: 7.6-10.2) and 16.5 mo (95%CI: 13.3-19.0), respectively. The mean number of molecular alterations was 3.9 (5-95pth 1-8). Six (17.6%) patients had gene fusions. The most common molecular alterations were TERT promoter (91.2%), EGFR amplification (amp) (52.9%), PTEN (50.0%), EGFR (20.6%), and TP53 (20.6%). Additional alterations (in ≥2 patients; 6%) included EGFR-EGFR (EGFRvIII), BRCA2, CDKN2A/B, CDK4/6 amp, MDM2/4 amp, NF1, NOTCH1, PIK3R1 and RB1. While TP53 mutations showed a trend as predictors for time to progression (P 0.027), this was not observed with OS. None of the molecular alterations were predictors of number of treatment cycles or dose reductions. No specific molecular alterations were identified that predicted either improved or poorer patient outcome, during treatment with VAL-083. Clinicaltrials.gov identifier: NCT02717962.

Evaluating N-acetylcysteine as a Protective Agent Against Chemotherapy-induced Neuropathy in Breast Cancer: A Triple-blind, Randomized Clinical Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant clinical issue that affects patients' quality of life and can limit the dosing of chemotherapeutic agents. N-acetylcysteine (NAC) has been proposed as a potential chemoprotective agent against CIPN due to its antioxidant properties. This study aimed to investigate the efficacy of oral NAC in preventing and controlling taxane-induced neuropathy in patients with breast cancer. This randomized, triple-blind, placebo-controlled trial included 80 breast cancer patients undergoing taxane-based chemotherapy. Participants were divided into 2 groups: an intervention group receiving 1200mg of oral NAC in divided doses per day and a placebo group. Patients were evaluated for neuropathy grade and functional status at 1 and 12 weeks postintervention. Our analysis revealed no significant difference in the incidence and severity of neuropathy between the intervention and placebo groups at 1 (P=0.328) and 12 weeks (P=0.569) postchemotherapy. Baseline characteristics such as age, number of treatment cycles, and disease stage were similar between groups, indicating a homogeneous population. Oral NAC at a dose of 1200mg per day did not significantly reduce the incidence or severity of taxane-induced neuropathy. These findings suggest that the oral bioavailability of NAC may be insufficient to exert a protective effect and that future studies should consider alternative dosing strategies or routes of administration. The need for further research to optimize NAC's chemoprotective role in CIPN remains evident.

Hypogammaglobulinemia and severe infections in Multiple Sclerosis patients on anti-CD20 agents: a multicentre study

BackgroundHypogammaglobulinemia (HG) is a known side effect of treatment with anti-CD20 monoclonal antibodies, and it is associated with the risk of infections. ObjectivesAim of this retrospective multicentre study was to assess the frequency of HG in Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder patients treated with Ocrelizumab or Rituximab and its association with the occurrence of severe infections (SI). Furthermore, predictors of HG and SI were sought. MethodsWe included 556 patients (190M, 366F, mean age: 47 years) with a mean follow-up of 28 months (range 12-90 months). ResultsIgG HG occurred in 20% and IgM HG in 34% of patients. At multivariable analysis, the risk of IgG HG was influenced by an older age (≥50 years) (OR 1.64, 95%CI: 1.06-2.54, p=0.027), and by the number of treatment cycles (OR: 1.20, 95%CI: 1.09-1.33, p<0.001).A total of 25 SI occurred (100 person-years rate: 1.8), with a disease phenotype other than relapsing-remitting (OR 1.50, 95%CI: 1.02-2.20; p=0.039) and IgG HG (OR 2.65, 95%CI: 1.15-6.12; p=0.022) increasing its risk. ConclusionsIgG and IgM HG occurred in a considerable proportion of patients. IgG HG increased the risk of SI, which were, nevertheless, relatively infrequent. Our results highlight the importance of monitoring immunoglobulin levels during treatment with anti-CD20 agents, to personalize treatment strategies.

Evaluating the Effectiveness of Nivolumab in Metastatic Lung Cancer Among Patients Aged 65 and Older.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predominantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly patients, particularly those aged 65 and above, remain underexplored due to their underrepresentation in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients receiving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3, 54.1, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusions: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846). This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5mg/kg) and nab-paclitaxel (260mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival. Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached). Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.

Application of Laser-Induced Breakdown Spectroscopy to quantify the changes in plasma characteristics in calcite-precipitated soils

The changes in calcium carbonate precipitation of modified soil by Enzyme Induced Calcite Precipitation (EICP) were investigated using Laser-Induced Breakdown Spectroscopy (LIBS). This experiment enabled elemental composition analysis of the soil samples. The plasma electron density and temperature were also extracted from the collected spectra of distinct soil samples i.e., W1 and W2 treated with EICP. The type of the crystal of CaCO3 deposited during the treatment process was investigated using scanning electron microscopy (SEM) and X-ray diffraction (XRD) tests. This research was conducted by utilizing an Nd: YAG laser with a wavelength of 532 nm, a pulse duration of 6 ns, and an energy of 25 mJ, from where the plasma temperature and electron density of modified soil throughout several treatment cycles were analyzed. The spectra were collected from different locations within the sample and the spectral range considered for the study was 370 nm-800 nm. The plasma electron density and plasma temperature determined using LIBS spectral data increase with the increase in the treatment cycle. With the increase in the treatment cycle, the deposition of CaCO3 was found to increase and correspondingly plasma temperature increased by 220 % for soil W1 and 117.3 % for soil W2. A similar rise in plasma electron density was noticed at the highest cycle of the treatment process; plasma electron density is augmented by 106.4 % for W1 and 21.50 % for W2. This investigation of the LIBS spectral data information indicates a positive correlation between the number of treatment cycles and the plasma temperature, meaning that as the treatment cycles rise, the plasma temperature also increases indicating a larger deposition of CaCO3. The findings are valuable in the domain of geotechnical engineering, where lasers are extensively employed for the examination of the soil profile and can prove to be a useful method for the characterization of the modified soils.

Immunogenicity of Botulinum Toxin Type A in Different Clinical and Cosmetic Treatment, a Literature Review.

Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions. This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation. A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine's evidence hierarchy. The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A. This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy.

Factors affecting peripheral neuropathy induced by nanoparticle albumin-bound paclitaxel in patients with pancreatic cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity limiting the use of nab-paclitaxel (Nab-P) in treating patients with pancreatic cancer. The aim of this study was to identify the factors affecting CIPN using patient-reported outcome measures and the minimally invasive volumetric absorptive microsampling (VAMS) technique. The maximum concentrations of paclitaxel (Cmax) were measured from 81 VAMS samples collected from 44 participants with pancreatic cancer. The association between CIPN development and demographic, clinical and pharmacokinetic factors was determined using univariable and multivariable logistic regression. The association between CIPN severity and the factors was evaluated using Spearman's rank correlation. The impact of Cmax and the number of treatment cycles on the severity was assessed using multivariable linear regression. The development of CIPN was significantly associated with cumulative dose (odds ratio 1.005, 95% confidence interval [CI] 1.003-1.007), treatment cycles (3.47, 2.25-5.85), alkaline phosphate (0.992, 0.985-0.998) and age (1.092, 1.020-1.179), with an area under the receiver operating characteristic curve of 0.89 (95% CI 0.83-0.95). The severity of CIPN significantly worsened with increasing cumulative dose (coefficient 0.58, 95% CI 0.44-0.69), treatment cycles (0.57, 0.44-0.68) and age (0.18, 0.00-0.35). The severity of CIPN was predictable from treatment cycles (P = .0002) and Cmax (P = .01). The higher the cumulative dose of Nab-P, treatment cycles and age, the more frequently and severely do the patients experience CIPN. In predicting the severity of CIPN using Cmax, minimally invasive VAMS is a feasible alternative to venous blood sampling.

Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: a retrospective analysis using US claims data

BackgroundThe randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines.MethodsPatients with CRC in the Optum’s de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group.Results703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1).ConclusionsFollowing inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients

IntroductionTreating older adults with chemotherapy remains a challenge, given their under-representation in clinical trials and the lack of robust treatment guidelines for this population. Moreover, older patients, especially those with...

Awareness of Food, Supplement, and Drug Interactions among Oncology Patients on Oral Chemotherapy

Abstract Background Food-drug interactions (FDIs) are very common, but under-reported due to a lack of proper history or lack of knowledge and limited research. Our study highlights the knowledge gap among oncology patients treated with capecitabine regarding food-oral chemotherapy interactions. Method A cross-sectional study was conducted among 110 breast and colon cancer patients, purposively sampled from the chemotherapy outpatient clinic from June 2021 to December 2021. A structured questionnaire and interviews were used to collect data, we asked them about the information they had received from the doctor and the way they were taking the medicine. Data were analyzed using SPSS, and the p-value of p &amp;lt; 0.05 was considered significant. Results Regarding the sociodemographic and clinical data of participants, their ages widely ranged from 20-83 years old, and their mean age was 54.78±13.18. The majority of participants were females 81(73.6%), non-employed 86(78.2%), colon cancer 72(65.5%) and received ≤4 cycles 66 (60%). Still, there is poor awareness concerning FDI among oncology patients and most participants were unaware of the possible interactions of capecitabine with grapefruits, vitamins, herbs, and antioxidants, but the majority 92 (83.6%) were taking their medication correctly concerning meal recommendations and only 18(16.4% )were not taking capecitabine within 30 minutes of meals. The current study showed that patients’ knowledge was not associated with age, sex, education, marital status, or occupation. The main factors that affected knowledge in the current study were the cancer site and the number of treatment cycles, as colon cancer patients and those who have received four or fewer cycles had better doctor-patient communication. Conclusion There is a lack of awareness about interactions between oral chemotherapy and various nutrients and supplements among patients in the current study. Patient education and better doctor-patient communication are recommended to ensure optimal oral chemotherapy intake and patient safety.

P-371 It’s worth the freeze: outcomes from thawing electively cryopreserved oocytes are comparable in patients with reduced vs normal ovarian reserve at the time of cryopreservation

Abstract Study question For patients coming back to use oocytes derived from elective cryopreservation, does their initial ovarian reserve predict thaw survival, embryos’ developmental milestones and pregnancy success? Summary answer Thaw survival, fertilization rate, embryo development and pregnancy success rates do not vary significantly according to AMH level at initial cryopreservation. What is known already Increasing numbers of patients are electing to cryopreserve oocytes for future use. AMH (Anti Mullerian Hormone) is an ovarian reserve marker often assessed prior to initiation of treatment that predicts response to fertility treatment and the resulting oocyte yield. However, it is not known whether oocytes derived from a patient with compromised ovarian reserve (perhaps over multiple treatment cycles) will fare as well as that of a patient with normal ovarian reserve and a higher per cycle oocyte yield. Our study seeks to shed light on whether a lower initial AMH level negatively impacts the prognosis of the thawed oocytes. Study design, size, duration We included in our retrospective study all oocyte thaw cycles resulting from electively cryopreserved oocytes since 1996 at a single academically affiliated fertility center. 325 patients completed a total of 510 thaw cycles. 315 cycles were excluded from analysis for no AMH information. 6376 oocyte cryopreservation cycles were performed over that timeframe. The primary outcomes were laboratory statistics including oocyte survival, fertilization and embryo blastulation rates, while the secondary outcome was cumulative live birth rates. Participants/materials, setting, methods AMH categories of &amp;lt; 1, 1-2 and &amp;gt; 2 were selected to stratify reduced, low-normal, and normal ovarian reserves, respectively. 70.7% inseminated oocytes with partner sperm while the remaining 29.3% used donor sperm. Mean age at time of oocyte cryopreservation was 36.5 (range 27.5 to 46.2) while mean age at time of oocyte thaw was 39.2 (range 27.7 to 47.5). The statistical analysis was performed using ANOVA for mean comparisons and chi-squared for pregnancy data. Main results and the role of chance Average oocyte yield per cryopreservation cycle was significantly different across AMH groups (7.7 oocytes in AMH &amp;lt; 1, 10.5 oocytes in AMH 1-2, and 17.2 oocytes in AMH &amp;gt; 2, p &amp;lt; 0.01). The number of treatment cycles completed was highest in patients with AMH &amp;lt; 1 at 1.26 cycles. Oocyte survival (mean 89.0%), fertilization rate (mean 75.3%), and blastocyst conversion rate (mean 62.4%) did not vary significantly across AMH groups. Time to oocyte use was not significantly impacted by AMH at the time of initial testing. Those with reduced AMH &amp;lt; 1 came back earlier to utilize the oocytes (787 days), vs 1141 days for patients with AMH 1-2 and 1021 days for patients with AMH &amp;gt; 2. However, this difference was not statistically significant, p = 0.4. The rate of PGT-A euploid embryos did not vary between groups (38.8% in AMH &amp;lt; 1, 45.3% in AMH 1-2, 53.0% in AMH &amp;gt; 2, p = 0.07). Clinical pregnancy, miscarriage rate, and live birth rate in the first transfer cycle was not impacted by AMH. Total cumulative live birth rate was not correlated with AMH (31.6% in AMH &amp;lt; 1, 44.4% in AMH 1-2, 47.8% in AMH &amp;gt; 2, p = 0.48). Limitations, reasons for caution This data was collected at a single fertility center and thus has limited generalizability. 8.0% of patients came back to utilize their oocytes, which varies widely across the published literature. 60.6% of patients did not have AMH assessed as part of their pre-treatment testing and were excluded from analysis. Wider implications of the findings Although reduced ovarian reserve impacts oocyte yield, many studies find no impact on resulting oocyte quality, embryo development and pregnancy success rates. Those with compromised AMH have comparable oocyte thaw outcomes to those with normal ovarian reserve, though more oocyte cryopreservation cycles may be needed to achieve a successful outcome. Trial registration number N/A

Patient organ dose during multicycle radiation dosimetry in Lutetium −177 radionuclide therapy

Precise patient radiation dosimetry during theranostic procedures allows clinicians to tailor therapeutic procedures to each patient. Organ dose measurement aids in adjustment of the administered activity or number of treatment cycles to maximize tumor cell destruction while minimizing damage to healthy tissues. This study was aimed at quantifying patient organ doses during Lu-177 DOTATATE and Lu-177 PSMA theranostic procedures. Nine patients underwent Lu-177 radionuclide therapy, usually four cycles with 6–8 GBq administered activity per cycle. The typical dose is 7.5 GBq as a fixed activity. Using quantitative dosimetry, physicians can estimate the next dose cycle according to patient condition. The average dose per activity for critical organs were low, at 1.76, 1.96, 0.25, 0.5, and 2.43 mSv/MBq for the right kidney, left kidney, liver bladder, and spleen, respectively. The doses for the left and right kidneys, liver, urinary bladder, and spleen were lower than those in previously published studies. Wide variations were observed in patient organ doses for Lu-177 DOTATATE and Lu-177 PSMA procedures. Further studies are recommended to ensure organ safety during theransotic procedures, to minimize the radiogenic risks to healthy organs.

Irinotecan plus raltitrexed as second‑line chemotherapy for metastatic colorectal cancer: A retrospective study.

The present study evaluated the efficiency, prognostic factors for and the safety of irinotecan combined with raltitrexed (TOMIRI) in patients with metastatic colorectal cancer (CRC). Outcome data of patients who received TOMIRI as first-, second- and third- or later-line treatment regimens were assessed to compare the efficacy of this regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Kaplan-Meier curves and univariate and multivariate analyses were performed to evaluate efficacy. From January 2017 to December 2019, TOMIRI was administered as a first-line treatment in 23 patients, second-line treatment in 164 patients and third- or later-line treatment in 18 patients. Irinotecan and 5-fluorouracil (FOLFIRI) was administered to another 50 patients, who served as the control group. The median PFS was 9, 7 and 6 months and the median OS was 37, 21 and 17 months for first-, second- and third- or later-line treatments, respectively. The ORRs of the included patients were 21.7, 13.4 and 11.1%, respectively, and the DCRs were 91.3, 81.7 and 66.7%, respectively. Compared with FOLFIRI, TOMIRI as a second-line chemotherapy treatment was associated with longer survival of the patients with CRC. Further analysis demonstrated that pathologic tumor-node-metastasis category, carcinoembryonic antigen, carbohydrate antigen 19-9, treatment cycles, targeted therapy, treatment of local metastases and first-line PFS were prognostic factors for second-line treatment. Among these, the number of treatment cycles was of vital importance. Hepatic dysfunction was the most commonly reported grade 1-2 (55.1%) and grade 3-4 (7.3%) adverse event. Neutropenia (12.2%), thrombocytopenia (10.2%), anemia (27.3%), proteinuria (38.1%) and hematuria (21.0%) were also common grade 1-2 adverse events. In conclusion, TOMIRI may be recommended as an effective and safe second-line treatment for metastatic CRC in the clinic.

Minimum number of mature oocytes needed to obtain at least one euploid blastocyst according to female age in in vitro fertilization treatment cycles

To find a useful tool for estimating the minimum number of metaphase II (MII) oocytes needed to obtain at least one euploid blastocyst according to female age. Retrospective analysis of invitro fertilization (IVF) treatment cycles with preimplantational genetic testing for aneuploidies (PGT-A) performed over 5 years in IVIRMA Valencia (Spain), January 2017-March 2022. Approval from the Institutional Review Board of IVI Valencia (2204-VLC-040-CR). Private infertility clinic in Spain. Eligible patients were undergoing their first IVF-PGT-A treatment cycle, in which at least one MII oocyte was obtained, regardless of oocyte and semen origin. Oocyte donation cycles were included in the donor group (≤34 years old). Treatment cycles from women with their own oocytes were selected only when the oocytes were aged ≥35 years (patient group). Only trophoectoderm biopsies performed on days 5 or 6 of development and analyzed using next-generation sequencing were included. Preimplantational genetic testing for aneuploidy cycles because of a known abnormal karyotype were excluded. Not applicable. Number of MII oocytes needed to obtain one euploid blastocyst according to female age. A total of 2,660 IVF-PGT-A treatment cycles were performed in the study period in the eligible population (patients group = 2,462; donors group =198). The mean number of MII oocytes needed to obtain one euploid blastocyst increased with age, as did the number of treatment cycles that did not get at least one euploid blastocyst. An adjusted multivariate binary regression model was designed using 80% of the patient group sample (n = 2,462; training set). A calculator for the probability of obtaining at least one euploid blastocyst was created using this model. The validation of this model in the remaining 20% of the patient group sample (n = 493; validation set) showed that it could estimate the event of having at least one euploid blastocyst with an accuracy of 72.0%. Our results show a preliminary model capable of predicting the number of MII oocytes needed to obtain at least one euploid blastocyst according to female age, calculated with the largest database of IVF-PGT-A treatment cycles ever used for this purpose, including only treatment cycles using next-generation sequencing on trophoectoderm biopsies. Once this model has been properly validated, it could help with decision-making for both clinicians and patients coming to an infertility clinic.