scholarly journals A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emmanuel M. Gabriel ◽  
Minhyung Kim ◽  
Daniel T. Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Neoadjuvant Therapy ◽  
Anticancer Agents ◽  
Intravital Microscopy ◽  
Pilot Trial ◽  
Oncologic Outcomes ◽  
Tumor Control ◽  
Systemic Delivery ◽  
Tumor Microvasculature ◽  
Lower Blood

AbstractAberrancies in the tumor microvasculature limit the systemic delivery of anticancer agents, which impedes tumor response. Using human intravital microscopy (HIVM), we hypothesized that HIVM would be feasible in patients with peritoneal carcinomatosis (PC). During cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for PC, HIVM was performed in both tumor and non-tumor areas. The primary outcome was HIVM feasibility to measure vessel characteristics. We secondarily evaluated associations between HIVM vessel characteristics and oncologic outcomes (RECIST response to neoadjuvant therapy and disease-specific survival). Thirty patients with PC were enrolled. Nineteen patients (63.3%) received neoadjuvant therapy. HIVM was feasible in all patients. Compared to non-tumor (control) areas, PC areas had a lower density of functional vessels, higher proportion of non-functional vessels, smaller lumenal diameters, and lower blood flow velocity. Qualitative differences in these vessel characteristics were observed among patients who had partial response, stable disease, or progressive disease after receiving neoadjuvant therapy. However, no statistically significant relationships were found between HIVM vessel characteristics and oncologic outcomes. These novel findings comprise the first-in-human, real-time evidence of the microscopic differences between normal and tumor-associated vessels and form the basis for our larger, ongoing clinical trial appropriately powered to determine the clinical utility of HIVM (NCT03823144).

scholarly journals 77286 Intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis

2021 ◽  
pp. 1-2
Author(s):  
Emmanuel Gabriel ◽  
Minhyung Kim ◽  
Daniel Fisher ◽  
Catherine Mangum ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Intravital Microscopy ◽  
Tumor Vasculature

scholarly journals BRAF Non-V600E Mutated Metastatic Colorectal Cancer in a Young Patient: Discussion from a Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 426-429
Author(s):  
Laure Moisset ◽  
Judith Raimbourg ◽  
Sandrine Hiret ◽  
Jonathan Dauve ◽  
Michèle Boisdron-Celle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Lymph Node ◽  
Metastatic Colorectal Cancer ◽  
Peritoneal Carcinomatosis ◽  
Young Patient ◽  
Clinical Features ◽  
Short Review ◽  
Tumor Control

We report the case of a 32-year-old man with a caecal adenocarcinoma with major lymph node extension and peritoneal carcinomatosis, presenting a BRAF-K601E mutation. A triplet (5FU plus oxaliplatin plus irinotecan) combination with bevacizumab achieved tumor control but the disease progressed immediately after cessation and the patient died 8 months after the diagnosis. A short review of BRAF non-V600E mutations shows that outcome and clinical features depend on the mutation.

The Use of Tyrosine Kinase Inhibitors in Modifying the Response of Tumor Microvasculature to Radiotherapy

2005 ◽  
Vol 4 (6) ◽  
pp. 691-698 ◽  
Author(s):  
Bo Lu ◽  
Eric T. Shinohara ◽  
Eric Edwards ◽  
Ling Geng ◽  
Jiahuai Tan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Growth Delay ◽  
Tumor Control ◽  
Angiogenic Growth Factors ◽  
Antiangiogenic Effect ◽  
Tumor Microvasculature ◽  
Rtk Inhibitors

The response of the tumor microvasculature to ionizing radiation can be modified to improve tumor control in preclinical mouse models of cancer. Recent studies have shown that a variety of cancer drugs can improve the response of cancers to radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to enhance radiation-induced destruction of tumor blood vessels. Among these compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs). Inhibition of RTKs attenuates downstream signaling from various angiogenic growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with various specificities against the receptors for VEGF, PDGF, and FGF manifest significant antiangiogenic activities as well. We have shown using tumor vascular window model and tumor growth delay assays that these compounds can enhance tumor radiation response by attacking tumor microvasculature. Furthermore, we have shown that radiation and RTK inhibitors exert their antiangiogenic effect through inhibition of the PI3K/Akt signaling pathway, which results in induction of apoptosis. Our studies have provided a basis for future clinical investigations of combining radiotherapy and RTK inhibitors.

scholarly journals CLRM-06. COMPARISON OF INDIVIDUALIZED ANTI-CANCER THERAPY REGIMENS RECOMMENDED BY A MULTIDISCIPLINARY MOLECULARLY-DRIVEN TUMOR BOARD IN A PEDIATRIC DIPG CLINICAL TRIAL (PNOC003) VERSUS THOSE SELECTED BY THE CNS-TAP TOOL

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv2-iv2
Author(s):  
Holly Roberts ◽  
Karthik Ravi ◽  
Allison Schepers ◽  
Bernard Marini ◽  
Cassie Kline ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Treatment Plan ◽  
Pilot Trial ◽  
Study Participant ◽  
Molecular Profiling ◽  
Individualized Treatment ◽  
Tumor Board ◽  
Treatment Recommendation ◽  
Patient Specific ◽  
Genomic Profiling

Abstract Genetic sequencing of diffuse intrinsic pontine gliomas (DIPG) has revealed genomic heterogeneity, fueling an interest in individualized targeted therapies. A feasibility study, PNOC003: Molecular Profiling for Individualized Treatment Plan for DIPG (NCT02274987), was completed within the Pacific Pediatric Neuro-Oncology Consortium in which a multidisciplinary tumor board reviewed molecular and genomic profiling of each participant’s tumor to make targeted therapy recommendations. Separately, our team developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which combines pre-clinical, clinical, and CNS penetration data with patient-specific genomic information to derive numeric scores for anticancer agents to objectively evaluate these therapies for use in patients with CNS tumors. We hypothesized that agents highly-scored by CNS-TAP would overlap with agents recommended by the PNOC003 tumor board. For each study participant, we retrospectively utilized the genomic profiling report to identify actionable alterations and incorporated these data into CNS-TAP to find the highest-scoring agents. We compared these CNS-TAP-recommended agents with recommendations from the tumor board for each of the 28 PNOC003 participants. Overall, 93% of patients (26/28) had at least one agent recommended by both the tumor board and CNS-TAP. Additionally, 38% of all agents (36/95) chosen by the tumor board were also selected by CNS-TAP. When only molecularly targeted anticancer agents were included in a sub-analysis, 60% of agents (34/57) were recommended by both methods. At present, we are prospectively evaluating the CNS-TAP tool within PNOC008: A Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children and Young Adults with High-Grade Glioma (NCT03739372). The CNS-TAP tool recommendations are shared during the PNOC008 molecular tumor board meetings once a consensus treatment recommendation has been reached. Subsequent analyses will focus on any adjustments in therapy decisions within the tumor board that result from the CNS-TAP tool output.

Dose prescription in SBRT for early-stage non-small cell lung cancer: are we all speaking the same language?

2020 ◽  
pp. 030089162092942
Author(s):  
Anna Merlotti ◽  
Pierluigi Bonomo ◽  
Riccardo Ragona ◽  
Marco Trovò ◽  
Filippo Alongi ◽  
...  
Keyword(s):  
Dose Distribution ◽  
Early Stage ◽  
Organs At Risk ◽  
Optimal Dose ◽  
Target Volume ◽  
Local Tumor Control ◽  
Oncologic Outcomes ◽  
Tumor Control ◽  
Distribution Data ◽  
Published Data

Introduction: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters. Methods: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers. Conclusions: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.

Optimizing trans-arterial drug delivery using mono-disperse emulsion

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 9-11
Author(s):  
Daisuke Yasui
Keyword(s):  
Anticancer Agents ◽  
Anticancer Agent ◽  
Transcatheter Arterial Chemoembolization ◽  
Human Cancer ◽  
Standard Of Care ◽  
Tumor Control ◽  
Metastatic Liver Cancer ◽  
Curative Therapy ◽  
Emulsion Droplets ◽  
Arterial Chemoembolization

Hepatocellular carcinoma is one of the most common human cancer and is the 5th cause of mortality in men and the 7th in female. Surgical resection and tumor ablation (radiofrequency or microwave) are curative therapy; however, some patients are not indicated to these treatments, mainly due to large number or size of the lesions. Transcatheter arterial chemoembolization is a standard of care for these patients. In this treatment, mixture of various anticancer agent (Doxorubicin, Cisplatin, Miriplatin) and lipophilic contrast media (Lipiodol) is administered via catheter inserted into tumor feeding arteries, followed by embolization. Tumor control can be obtained in 50-90 % of the patients and there is a room for improvement. One major cause of poor tumor control is uneven large-sized emulsion droplets, which are now used in clinical practice. The aim of this project is to improve accumulation of anticancer agents/lipiodol in the tumor by using even small-sized emulsion (mono-dispersed emulsion) which is obtained by utilizing cutting-edge technology called 'membrane emulsification'. The application can be also widened to metastatic liver cancer.

Impact of G-CSF during neoadjuvant therapy on outcomes of operable pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4126-4126
Author(s):  
Pranav Murthy ◽  
Mazen S Zenati ◽  
Samer S. AlMasri ◽  
Aatur D. Singhi ◽  
Annissa DeSilva ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Tumor Staging ◽  
Neutrophil Extracellular Trap ◽  
Oncologic Outcomes ◽  
Ductal Adenocarcinoma ◽  
Common Side Effect ◽  
Interleukin 17 ◽  
The Impact

4126 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. Neutropenia is a common side effect of cytotoxic chemotherapy, managed with administration of recombinant granulocyte-colony stimulating factor (G-CSF, Filgrastim). The interleukin 17 – G-CSF – neutrophil extracellular trap (NET) axis promotes oncogenesis and progression of PDAC, inhibiting adaptive immunity. We evaluated the impact of G-CSF administration during neoadjuvant therapy (NAT) on oncologic outcomes in patients with operable pancreatic cancer. Methods: A retrospective review of all patients with localized PDAC treated with NAT prior to pancreatic resection between 2014 – 2020 was completed at a single institution. G-CSF administration, type, and dose were collected from inpatient and outpatient medical records. Results: Of 351 patients treated, 138 (39%) received G-CSF during NAT with a median follow-up of 45.8 months. Patients who received G-CSF were younger (64.0 vs 66.7, p = 0.008), had lower BMI (26.5 vs 27.9, p = 0.021), and were more likely to receive 5-FU based chemotherapy (42% vs 28.2%, p < 0.0001), NAT dose reduction (40.6% vs 25.4%, p = 0.003), or experience febrile neutropenia (8.7% vs 3.3%, p = 0.029). No differences were observed in baseline or pathologic tumor staging. In patients who received G-CSF, 130 (94%) received Pegfilgrastim with a median cumulative dose of 12 mg (IQR 6-12). Patients who received G-CSF were more likely to have an elevated post-NAT neutrophil to lymphocyte ratio (45% vs 29.6%, p = 0.004) and systemic immune-inflammation index (39.5% vs 29.6%, p = 0.061). Receiving G-CSF was an independent predictor of perineural invasion (HR 2.4, 95 CI [1.08, 5.5], p = 0.031) and margin positive resection (HR 1.69, 95 CI [1.01, 2.83], p = 0.043). Patients who received G-CSF had decreased overall survival compared to patients who did not receive G-CSF (median OS: 29.2 vs 38.7 months, p = 0.0001). Receiving G-CSF during NAT was an independent negative predictor of progression free (HR 1.38, 95 CI [1.04, 1.83], p = 0.022) and overall survival (HR 2.02, 95 CI [1.45, 2.79], p < 0.0001). In a subset of patients with available pre- and post-NAT serum specimens (n = 28), G-CSF administration resulted in an increased number of citrullinated histone H3 complexes following NAT (+1378±1502 vs -300.7±1147 pg/ml, p = 0.007), indicative of enhanced peripheral NET formation. Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration is associated with worse oncologic outcomes and should be administered with caution. Prospective randomized as well as confirmatory clinical studies are in order.

Sign in / Sign up

Export Citation Format

Share Document