scholarly journals Tumor growth rate during re-challenge chemotherapy with previously used agents as salvage treatment for metastatic colorectal cancer: A retrospective study

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257551
Author(s):  
Masashi Ishikawa ◽  
Atsuo Takashima ◽  
Yusuke Nagata ◽  
Ryoichi Sawada ◽  
Masahiko Aoki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Rate ◽  
Retrospective Study ◽  
Tumor Growth ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Chemotherapeutic Agents ◽  
Salvage Treatment ◽  
Tumor Growth Rate ◽  
Tumor Shrinkage

Background In clinical practice, the same chemotherapeutic agents are occasionally reused (re-challenge) after failure of all available standard chemotherapy options for metastatic colorectal cancer (mCRC). However, the benefits of re-challenge chemotherapy (Re-Cx) are unclear. This retrospective study evaluated the efficacy of Re-Cx, focusing on the tumor growth rate (TGR). Methods The study included mCRC patients with measurable lesions who received Re-Cx from November 2011 to October 2018 at National Cancer Center Hospital. Re-Cx was defined as re-administration of agents which had been used in prior lines of chemotherapy and discontinued due to disease progression. We compared the TGR immediately after initiating Re-Cx regimens with that observed at the time of disease progression during prior chemotherapy (Prior-Cx) immediately before Re-Cx. Results Of the 25 patients who received Re-Cx, five patients received two Re-Cx regimens. Therefore, a total of 30 cases of Re-Cx were analyzed in this study. The regimens of Re-Cx were oxaliplatin based (19 cases), irinotecan based (8 cases), and others (3 cases). Although the objective response rate to Re-Cx was 0%, the disease control rate was 60% (18 cases), and 40% (12 cases) showed some tumor shrinkage. We compared the effects of Re-Cx and Prior-Cx by the TGR and found that the TGR of Re-Cx was slower than that recorded in Prior-Cx in 26 of 30 cases (87%). In particular, the ratio of% TGR <0, which indicates tumor shrinkage, was obtained in 13 of 30 cases (43.3%). The median progression-free survival and overall survival after Re-Cx were 3.8 and 6.57 months, respectively. Conclusion We found that Re-Cx may have some anti-tumor efficacy as salvage treatment for mCRC and these results also suggested the clinical benefits of Re-Cx.

scholarly journals Radioembolization for Metastatic Colorectal Cancer

2021 ◽  
Author(s):  
David Guez ◽  
Patrick D. Sutphin ◽  
Suvranu Ganguli
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Salvage Treatment ◽  
Review Article ◽  
Prognostic Indicators ◽  
Common Site ◽  
First Line ◽  
Resistance To Therapy ◽  
Duration Of Response ◽  
Dominant Disease

AbstractThe liver is the most common site of metastatic disease in colorectal cancer, and, in the setting of liver-dominant disease, a chief contributor to mortality. Chemotherapy is the backbone of treatment for metastatic colorectal cancer; however, the duration of response is limited and resistance to therapy inevitably develops. Radioembolization represents a targeted treatment to the liver which has been studied in first-line, second-line, and in salvage treatment. Therapeutic rationale, outcomes, and prognostic indicators are presented in this systematic review article.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Guideline-recommended incorporation of biomarker testing results in metastatic colorectal cancer therapy

2020 ◽  
Vol 17 (3) ◽  
pp. 185-194
Author(s):  
Jared Freml ◽  
Thomas Delate ◽  
Jesus Hermosillo-Rodriguez
Keyword(s):  
Colorectal Cancer ◽  
Retrospective Study ◽  
Cancer Therapy ◽  
Metastatic Colorectal Cancer ◽  
Small Proportion ◽  
Biomarker Testing ◽  
Over Time

Aim: To describe pharmacogenomic tumor testing among patients with metastatic colorectal cancer. Methods: This was a retrospective study of patients with metastatic colorectal cancer diagnosed between 1 January 2014 and 30 June 2018. Patients were assessed for pharmacogenomic testing and appropriateness of chemotherapy use. Results: Overall, 112/167 (67.1%) patients had at least one of the three recommended pharmacogenomic tests and 41/167 (24.6%) had all tests. Twenty-four patients were treated with cetuximab with 8/167 (4.7%) identified as being treated with a RAS variant (n = 3) or incomplete testing (n = 5); thus, not in accordance with guidelines. Conclusion: Uptake of testing was variable but increased over time; however, a small proportion of patients received cetuximab with a variant or not all recommended tests being performed.

scholarly journals Tumor growth characteristics of the Walker 256 AR tumor, a regressive variant of the rat Walker 256 A tumor

2010 ◽  
Vol 53 (5) ◽  
pp. 1101-1108 ◽  
Author(s):  
Fernando Guimarães ◽  
Alessandra Soares Schanoski ◽  
Tereza Cristina Samico Cavalcanti ◽  
Priscila Bianchi Juliano ◽  
Ana Neuza Viera-Matos ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Wistar Rats ◽  
Tumor Regression ◽  
Growth Characteristics ◽  
Tumor Growth Rate ◽  
Continuous Growth ◽  
Tumor Bearing ◽  
Walker 256 ◽  
Complete Tumor

The present study aimed at characterizing the subcutaneous development of the Walker 256 (W256) AR tumor, a regressive variant of the rat W256 A tumor. Wistar rats were injected subcutaneously with 4x10(6) W256 A or W256 AR tumor cells. The development of tumors was evaluated daily by percutaneous measurements. None of the W256 A tumors (n=20) regressed, but 62% of the W256 AR tumor-bearing rats (n=21) underwent complete tumor regression within 35 days. Continuous growth of AR tumors was characterized by an increase of the tumor growth rate from day 12, which reached values above 1.0 g/day, and were significantly higher (p<0.05) than those of the regressive AR tumors. Immunosuppression by irradiation before subcutaneous injection of AR cells completely abrogated tumor regression and was associated with severe metastatic dissemination. Daily evaluation of the tumor growth rate enabled the discrimination, in advance, between continuously growing tumors and those that regressed later on.

Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 481-491 ◽  
Author(s):  
Alexander E. Ropper ◽  
Xiang Zeng ◽  
Hariprakash Haragopal ◽  
Jamie E. Anderson ◽  
Zaid Aljuboori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Growth Rate ◽  
Neural Stem Cells ◽  
Tumor Growth ◽  
Rat Model ◽  
Weight Bearing ◽  
Tumor Growth Rate ◽  
Intramedullary Spinal Cord ◽  
Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P &lt;.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

scholarly journals Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules

2010 ◽  
Vol 6 (3) ◽  
pp. e1000712 ◽  
Author(s):  
Samuel Bernard ◽  
Branka Čajavec Bernard ◽  
Francis Lévi ◽  
Hanspeter Herzel
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Tumor Growth Rate
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