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1/12/26

ABSTRACT

BACKGROUND: Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM.

METHODS: Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS.

RESULTS: We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively.

CONCLUSIONS: Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

PMID:37621684 | PMC:PMC10446765 | DOI:10.3389/fonc.2023.1231600

05:27

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PubMed articles on: Cancer & VTE/PE

Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis

JCO Clin Cancer Inform. 2023 Aug;7:e2300060. doi: 10.1200/CCI.23.00060.

ABSTRACT

PURPOSE: Recent studies have suggested that machine learning (ML) could be used to predict venous thromboembolism (VTE) in cancer patients with high accuracy.

METHODS: We aimed to evaluate the performance of ML in predicting VTE events in patients with cancer. PubMed, Web of Science, and EMBASE to identify studies were searched.

RESULTS: Seven studies involving 12,249 patients with cancer were included. The combined results of the different ML models demonstrated good accuracy in the prediction of VTE. In the training set, the global pooled sensitivity was 0.87, the global pooled specificity was 0.87, and the AUC was 0.91, and in the test set 0.65, 0.84, and 0.80, respectively.

CONCLUSION: The prediction ML models showed good performance to predict VTE. External validation to determine the result's reproducibility is necessary.

PMID:37616550 | DOI:10.1200/CCI.23.00060

05:27

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PubMed articles on: Cancer & VTE/PE

No evidence for a genetic causal effect of breast cancer on venous thromboembolism: a mendelian randomization study

J Thromb Thrombolysis. 2023 Aug 24. doi: 10.1007/s11239-023-02871-1. Online ahead of print.

ABSTRACT

Active cancer is known to contribute to venous thromboembolism (VTE), but the cause-and-effect association of breast cancer on VTE is not yet clear. In order to investigate the possible causal relationships, we used a Mendelian randomization analysis. Data for generically predicted breast cancer were identified based on the BCAC consortium. A meta-analysis of genome-wide association study (GWAS) comprising 1,500,861 participants for VTE as well as data from the FinnGen study for VTE, DVT and PE was used for the causal-effect estimation. Our primary method was inverse-variance weighted (IVW), and our supplementary methods included weighted median and MR-Egger. We also carried out sensitivity analysis for the study. No evidence of causal-effect was detected of overall breast cancer on VTE in both the GWAS meta-analysis (OR=1.01, 95%CI:0.98-1.04, p = 0.495) and the FinnGen consortium (OR=1.00,95%CI:0.96-1.04, p = 0.945). In addition, the presence of ER-positive or ER-negative disease did not significantly influence the incidence of VTE and its subtypes. In conclusion, no genetic cause-and-effect of breast cancer on VTE risk was detected in the large MR analysis.

PMID:37615800 | DOI:10.1007/s11239-023-02871-1

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07:38

Cardiotoxicity News

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PubMed articles on: Cardio-Oncology

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab

In Vivo. 2023 Sep-Oct;37(5):2139-2146. doi: 10.21873/invivo.13311.

ABSTRACT

BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T).

PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity.

RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06).

CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

PMID:37652487 | DOI:10.21873/invivo.13311

07:38

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PubMed articles on: Cardio-Oncology

A framework for assessing the impact of cardiac and respiratory motion for STereotactic Arrhythmia Radioablation (STAR) using a digital phantom with a 17-segment model - A STOPSTORM.eu consortium study

Int J Radiat Oncol Biol Phys. 2023 Aug 29:S0360-3016(23)07853-7. doi: 10.1016/j.ijrobp.2023.08.059. Online ahead of print.

ABSTRACT

The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the impact of cardiorespiratory motion on STAR. The 4D XCAT phantom was expanded with the 17-segment left ventricular (LV) model which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D-CT scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of VT patients: 6, 2, and 1 mm in the Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D-respiratory CT scans used for radiotherapy planning. The average volume of the 17 segments was 6 cm3 (1-9 cm3). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24-79%) compared to individual segment volumes, whereas envelopes increased by 126% (79-167%) if also respiratory motion was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68-75% of the motion envelope. The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the impact of (cardio)respiratory motion and motion management strategies for VT patients.

PMID:37652302 | DOI:10.1016/j.ijrobp.2023.08.059