scholarly journals Circulating stromal cells in resectable pancreatic cancer correlates to pathological stage and predicts for poor clinical outcomes

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Kirby P. Gardner ◽  
Mohammed Aldakkak ◽  
Cha-Mei Tang ◽  
Susan Tsai ◽  
Daniel L. Adams
Keyword(s):  
Pancreatic Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Treatment ◽  
Pathological Stage ◽  
Resectable Pancreatic Cancer ◽  
Free Survival ◽  
Standard Of Care Treatment ◽  
Advanced Pathological Stage ◽  
Worse Prognosis

AbstractPancreatic cancer (PC) is notoriously difficult to diagnosis and properly stage resulting in incorrect primary treatment. Diagnostic and prognostic biomarkers are desperately needed to more accurately stage patients and select proper treatments. Recently, a newly discovered circulating stromal cell, i.e. cancer associated macrophage-like cell (CAML), was found to accurately identify solid cancers and predict for worse prognosis. In this pilot study, blood samples were procured from 63 PC patients prior to start of therapeutic intent. CAMLs were found in 95% of samples tested, with ≥12 CAMLs/7.5 mL and ≥50 µm CAMLs both predicting for advanced pathological stage and progression free survival. These data suggest that CAML assessment prior to treatment of PC predicts patients with under-staged disease and with more aggressive PC less likely to respond to standard of care treatment.

scholarly journals NIMG-07. LACUNARITY AND FRACTAL DIMENSION ACT AS PRETREATMENT IMAGING BIOMARKERS FOR SURVIVAL IN GLIOBLASTOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi162-vi163
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Haylye White ◽  
Maciej Mrugala ◽  
Leland Hu ◽  
...  
Keyword(s):  
Fractal Dimension ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Imaging Biomarkers ◽  
Free Survival ◽  
Patient Cohort ◽  
Biological Phenomena ◽  
Microenvironmental Factors ◽  
Standard Of Care Treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of only 15 months with standard of care treatment. Lacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, another morphological measure of the complexity of pixel arrangement, of segmented necrotic regions on gadolinium-enhanced T1 weighted (T1gd) MRI have previously been shown to distinguish both overall survival (OS) and progression free survival (PFS) in GBM (n = 95). In our larger patient cohort (n = 389), we sought to validate or refute previously published results connecting morphological metrics and patient survival. We identified pretreatment necrotic regions of our retrospective first-diagnosis GBM patient cohort using segmented T1gd MRI enhancing regions. We calculated lacunarity and fractal dimension across all T1gd MRI slices with enhancing tumor, and used the median lacunarity and fractal dimension values for our analysis. We find that a lacunarity threshold can significantly distinguish OS (14 months vs 19 months median, log-rank p = 0.015, n = 389) and a fractal dimension threshold can significantly distinguish PFS (8 months vs 11 months median, log-rank p = 0.015, n = 123). We believe that morphological metrics such as lacunarity and fractal dimension could play a role in standard-of-care prognostic considerations at tumor presentation. This link between morphological and survival metrics could be driven by underlying biological phenomena or microenvironmental factors that should be further explored.

scholarly journals Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis

2019 ◽  
Vol 111 (8) ◽  
pp. 782-794 ◽  
Author(s):  
Quisette P Janssen ◽  
Stefan Buettner ◽  
Mustafa Suker ◽  
Berend R Beumer ◽  
Pietro Addeo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Free Survival ◽  
Patient Level ◽  
Grade Iii

Abstract Background FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

scholarly journals FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592095329
Author(s):  
Changhoon Yoo ◽  
Inhwan Hwang ◽  
Tae Jun Song ◽  
Sang Soo Lee ◽  
Jae Ho Jeong ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Significant Proportion ◽  
Progression Free Survival ◽  
Conversion Surgery ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Free Survival

Background: Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC. Methods: This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status. Results: With median follow-up duration of 40.3 months [95% confidence interval (CI), 36.7–43.8] in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5–11.7) and 18.1 (95% CI, 16.0–20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3–66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5–37.9%). PFS and OS did not differ between BRPC and LAPC groups [median PFS, 11.1 months (95% CI, 8.8–13.5) versus 10.1 months (95% CI, 8.4–11.8), p = 0.47; median OS, 18.4 months (95% CI, 16.1–20.8) versus 17.1 months (95% CI, 13.2–20.9), p = 0.50]. Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS. Conclusion: FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.

scholarly journals Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sébastien Thureau ◽  
Vincent Marchesi ◽  
Marie-Hélène Vieillard ◽  
Lionel Perrier ◽  
Albert Lisbona ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Stereotactic Body Radiation Therapy ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Standard Of Care Treatment

Abstract Background Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. Methods This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. Discussion The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. Trials registration ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study

scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

scholarly journals Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy

2021 ◽  
Vol 10 (8) ◽  
pp. 1609
Author(s):  
Zainab L. Rai ◽  
Roger Feakins ◽  
Laura J. Pallett ◽  
Derek Manas ◽  
Brian R. Davidson
Keyword(s):  
Pancreatic Cancer ◽  
Mechanism Of Action ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Standard Of Care ◽  
Locally Advanced Pancreatic Cancer ◽  
Animal Data ◽  
Standard Of Care Treatment ◽  
Apoptosis And Necrosis

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

2021 ◽  
pp. 107815522110386
Author(s):  
Angela Chen ◽  
Vincent H Ha ◽  
Sunita Ghosh ◽  
Carole R Chambers ◽  
Michael B Sawyer
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Free Survival ◽  
Colony Stimulating Factors ◽  
Median Progression Free Survival ◽  
Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

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