NIMG-33. VOLUMETRIC TUMOR MEASUREMENTS ARE SUPERIOR TO 2D BIDIRECTIONAL MEASUREMENTS IN THE EVALUATION OF IDH INHIBITION IN DIFFUSE GLIOMAS: EVIDENCE FROM A PROSPECTIVE PHASE I TRIAL OF IVOSIDENIB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi136-vi136
Author(s):  
Benjamin Ellingson ◽  
Grace Kim ◽  
Matt Brown ◽  
Jihey Lee ◽  
Noriko Salamon ◽  
...  
Keyword(s):  
Growth Rate ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Phase I ◽  
Growth Rates ◽  
Tumor Growth Rate ◽  
Low Grade ◽  
Measurement Variability ◽  
3D Measurements ◽  
Volumetric Measurements

Abstract Since IDH mutant (mIDH) low-grade gliomas (LGGs) progress slowly and patients have a relatively long survival, testing of new therapies in clinical trials based solely on survival can take more than 20 years. Guidance on therapeutic evaluation using LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to the best approach for evaluating LGGs in clinical trials including use of volumetric (3D) measurements, which would theoretically allow for more accurate measurements of irregular shaped lesions and allow readers to better assess areas of change within these tumors. A total of 21 (out of 24) non-enhancing, recurrent mIDH LGGs with imaging pre- and post-treatment enrolled in a phase I, multicenter, open-label study to assess the safety and tolerability of oral ivosidenib (NCT02073994) were included in this exploratory ad hoc analysis. 2D bidirectional and 3D volumetric measurements were centrally evaluated by one of 3 radiologists at an imaging CRO using a paired read and forced adjudication paradigm. The effects of 2D vs. 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were then quantified. 3D volumetric measurements had significantly longer estimates of PFS (P=0.0181), more stable (P=0.0063) and considerably lower measures of tumor growth rate (P=0.0037), the highest inter-reader agreement (weighted Kappa=0.7057), and significantly lower reader discordance rates (P=0.0002) with comparable recommended LGG RANO 2D approaches. In summary, 3D volumetric measurements are better for determining response assessment in LGGs due to longer PFS and more stable measures of tumor growth rates (i.e. less “yo-yo-ing” of measurements over time causing fewer erroneous calls of progression and more accurate growth rates), highest inter-reader agreement, and lowest reader discordance rates. Future studies will focus on validating this in a larger cohort and determining whether these measurements better reflect clinical benefit.

scholarly journals Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials

2013 ◽  
Vol 20 (1) ◽  
pp. 246-252 ◽  
Author(s):  
Charles Ferté ◽  
Marianna Fernandez ◽  
Antoine Hollebecque ◽  
Serge Koscielny ◽  
Antonin Levy ◽  
...  
Keyword(s):  
Growth Rate ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Phase I ◽  
Antitumor Drug ◽  
Tumor Growth Rate ◽  
Phase I Clinical Trials ◽  
Early Indicator ◽  
Drug Activity

scholarly journals RTHP-28. TTFIELDS TREATMENT AFFECTS TUMOR GROWTH RATES: A POST-HOC ANALYSIS OF THE PIVOTAL PHASE 3 EF-14 TRIAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi215-vi215
Author(s):  
Noa Urman ◽  
Gitit Lavy-Shahaf ◽  
Shay levi ◽  
Ze’ev Bomzon
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Growth Rates ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Local Tumor Control ◽  
Tumor Growth Rate ◽  
Tumor Control ◽  
Pivotal Phase ◽  
Tumor Treating Fields

Abstract INTRODUCTION The pivotal EF-14 trial showed that Tumor Treating Fields (TTFields) extend Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients. This leads to the hypothesis that TTFields therapy leads to local control of tumors, yielding a significant decrease in tumor growth rates. Here we present an analysis testing this hypothesis in biopsy-only patients who participated in the EF-14 trial. METHODS Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1c MRIs at baseline and at progression. Tumor growth rate was calculated as: growth_rate=(ln(v0)-ln(v1))/dt. (v0- tumor volume at baseline), v1- Tumor volume at progression, dt- days to progression), which models tumor volume as increasing exponentially over time. Median growth rates in the treatment and control arms were compared. RESULTS The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p< 0.008 Wilcoxon rank-sum) DISCUSSION AND CONCLUSIONS This study shows that tumor growth rates are slower in patients treated with TTFileds+Temozolomide (TMZ) than in patients treated with TMZ alone. This analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection since a large portion of the tumor has been removed. The negative median growth rate for patients in the treatment arm may indicate that a significant number of TTFields-treated patients a decrease in tumor volume was observed, suggesting that TTFields enhances local tumor control. References: [1] Stupp, Roger, et al. Jama 318.23 (2017): 2306–2316.[[2 Stensjøen, Anne Line, et al. Neuro-oncology 17.10 (2015): 1402–1411.

A Comparison of Growth Rates of Acoustic Neuromas: Nonsurgical Patients vs. Subtotal Resection

1993 ◽  
Vol 109 (3) ◽  
pp. 482-487 ◽  
Author(s):  
Seth I. Rosenberg ◽  
Herbert Silverstein ◽  
Michael A. Gordon ◽  
John M. Flanzer ◽  
Thomas O. Willcox ◽  
...  
Keyword(s):  
Growth Rate ◽  
Elderly Patients ◽  
Tumor Growth ◽  
Brain Stem ◽  
Growth Rates ◽  
Tumor Growth Rate ◽  
Subtotal Resection ◽  
Average Growth ◽  
Patients Âgés ◽  
Acoustic Neuromas

A conservative approach to the management of acoustic neuromas in elderly patients has been used since 1971. Elderly patients without symptoms of brain stem compression are initially treated by observation and yearly radiographic imaging. A translabyrinthine radical-subtotal resection is performed if brain stem compression is present or if tumor is growing rapidly. Twenty-three patients, ages 65 to 86 years, had initial nonsurgical management of their tumors. Growth rates could be determined for 16 patients. Thirteen patients not requiring surgery had an average tumor growth rate of 0.6 mm/yr. Three patients with an average growth rate of 6.8 mm/yr eventually required surgery. No patient whose tumor was < 15 mm at initial evaluation has experienced brain stem symptoms or demonstrated rapid tumor growth. Twenty-four patients ages 65 to 86 years underwent planned subtotal tumor excision. Eighteen patients followed postoperatively for more than 1 year demonstrated an average rate of regrowth of tumor of 0.7 mm/yr. (OTOLARYNGOL HEAD NECK SURG 1993;109:482-7.)

Tumor growth rate as an early indicator of the efficacy of anti-PD-1 immunotherapy in advanced melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21050-e21050 ◽  
Author(s):  
Bixia Tang ◽  
Zhihong Chi ◽  
Xinan Sheng ◽  
Lu Si ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Growth Rate ◽  
Clinical Trials ◽  
Tumor Growth ◽  
Objective Response ◽  
Antibody Therapy ◽  
Progression Free Survival ◽  
Tumor Growth Rate ◽  
Imaging Data ◽  
Pretreatment Period ◽  
Tumor Measurements

e21050 Background: As immunotherapeutics take longer time to show clinical efficacy compared with chemotherapy and targeted therapy, it is critical to select patients with low tumor growth rate (TGR) prior immunotherapy as to get sufficient time for immunotherapeutics to play functions. However, which threshold of TGR before immunotherapy may be associated with good outcome remains unknown. Methods: Medical records from patients with advanced refractory melanoma prospectively treated in clinical trials (NCT02836795 and NCT03013101) of anti-PD-1 antibody toripalimab were analyzed. TGR was computed during the pretreatment period (reference) and the treatment period (treatment). Associations between TGR and objective response at the first evaluation, progression free survival (PFS), overall survival (OS) were computed. Results: We analyzed a total of 142 patients enrolled in these two clinical trials. Excluded for no measurable lesions in pretreatment period or incomplete imaging data through the pretreatment/treatment periods, a total of 90 patients could be explored for the relationship of TGR and the efficacy of anti-PD-1 antibody. TGR and hyperprogression were defined as Champiat S. used to make. The distribution of TGR is as follows: median 63.7 (range: -51~720). A total of 15 (16.7%), 41 (45.6%), 34 (37.8%) and 0 patients exhibited PR, SD, PD, CR, respectively. An association between lower TGR (TGR ≤55) and objective response was observed (P≤0.001). Among evaluable patients at week 8, 83.9% (13+34/56) and 26.5% (2+7/34) showed PR/SD from baseline tumor measurements for the group of TGR≤55 and TGR > 55, respectively. Median PFS was 5.5 0.9m in the group of TGR≤55 compared 1.8 0.4m in the group of TGR > 55 (P≤0.001). Median OS was not reached in the group of TGR≤55 group and was 15.9 1.8m in the group of TGR > 55 (p = 0·02). Two patients were confirmed pseudoprogression in the follow-up. The TGR of these two patients was lower than 55. Five patients experienced hyperprogression. The TGR of each patient was 9, 12, 54, 56, 78, respectively. Conclusions: Melanoma patients with TGR≤55 prior anti-PD-1 antibody therapy are more likely to benefit from this regimen. However, it could not predict patients who may develop hyperprogression after anti-PD-1 antibody therapy. Clinical trial information: NCT02836795 and NCT03013101.

scholarly journals Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults

2020 ◽  
Vol 22 (7) ◽  
pp. 993-1005 ◽  
Author(s):  
Alexandre Roux ◽  
Arnault Tauziede-Espariat ◽  
Marc Zanello ◽  
Sophie Peeters ◽  
Gilles Zah-Bi ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Growth Rates ◽  
Progression Free Survival ◽  
World Health ◽  
Tumor Growth Rate ◽  
Who Grade ◽  
Spontaneous Tumor ◽  
Grade Ii ◽  
Grade Iii

Abstract Background We quantified the spontaneous imaging growth rate of oligodendrogliomas. We assessed whether (i) it discriminates between World Health Organization (WHO) grade II and grade III oligodendrogliomas, and (ii) grade III oligodendrogliomas with neo-angiogenesis are associated with more fast growth rates (≥8 mm/y). Methods This work employed a retrospective bicentric cohort study (2010–2016) of adult patients harboring a newly diagnosed supratentorial oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (WHO 2016 classification), with a minimum of 2 available MRIs before any treatment (minimum 6-week interval) to measure the spontaneous tumor growth rate. Results We included 108 patients (age 44.7 ± 14.1 y, 60 males). The tumor growth rate was higher in grade III oligodendrogliomas with neo-angiogenesis (n = 37, median 10.4 mm/y, mean 10.0 ± 6.9) than in grade III oligodendrogliomas with increased mitosis count only (cutoff ≥6 mitoses, n = 18, median 3.9 mm/y, mean 4.5 ± 3.2; P = 0.004), and higher than in grade II oligodendrogliomas (n = 53, median 2.3 mm/y, mean 2.8 ± 2.2; P &lt; 0.001). There was increased prevalence of fast tumor growth rates in grade III oligodendrogliomas with neo-angiogenesis (54.1%) compared with grade III oligodendrogliomas with increased mitosis count only (11.1%; P &lt; 0.001), and in grade II oligodendrogliomas (0.0%; P &lt; 0.001). The tumor growth rate trends did not differ between centers (P = 0.121). Neo-angiogenesis (P &lt; 0.001) and mitosis count at ≥9 (P = 0.013) were independently associated with tumor growth rates ≥8 mm/year. A tumor growth rate ≥8 mm/year was the only predictor independently associated with shorter progression-free survival (P = 0.041). Conclusions The spontaneous tumor growth rate recapitulates oligodendroglioma aggressiveness, permits identification of grade III oligodendrogliomas preoperatively when ≥8 mm/year, and questions the grading by mitosis count.

scholarly journals P04.07 Correlation of 18F-fluorethyl-L-tyrosine (18F-FET) uptake in positron emission tomography (PET) and MRI growth rate in low-grade glioma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii30-iii30
Author(s):  
M Mueller ◽  
M Kamp ◽  
M Sabel ◽  
G Stoffels ◽  
N Galldiks ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Malignant Transformation ◽  
Growth Patterns ◽  
Low Grade Glioma ◽  
Tumor Growth Rate ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
The Mean

Abstract BACKGROUND Low-grade gliomas (LGGs, WHO grade II) are a heterogeneous group of tumors of the central nervous system with diverse behavior in histopathology, genetics and growth patterns. Therefore, different therapeutic strategies are discussed ranging from watchful waiting to radical resection and adjuvant radio-/chemotherapy. For a better evaluation of tumor progression or malignant transformation, the O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) uptake in PET or the tumor growth rate assessed on MRI are used depending on the neurooncological center. Here, we correlated both methods. MATERIAL AND METHODS Inclusion criteria for this retrospective study were (1) newly diagnosed and neuropathologically confirmed low-grade glioma; (2) at least two MRIs at initial diagnosis and follow-up for calculation of the tumor growth rate (using IDS7 by Sectra AB, Sweden, 2018); (3) and an additional preoperative 18F-FET PET scan. RESULTS From 2008 to 2018, 34 patients were identified (mean age 39.7 years; 68% diffuse astrocytoma). The mean tumor growth rate on MRI was 0.091 cm3/d. The average mean 18F-FET uptake was 1.42; the average maximum 18F-FET uptake was 2.18. The Pearson correlation coefficient between the tumor growth rate and the mean and maximum 18F-FET uptake was r=0.19, and r=0.10. In the group of diffuse astrocytomas, the mean growth rate in tumors with a mean 18F-FET uptake of >1.5 was significantly higher than the mean growth rate of those with a mean 18F-FET uptake of ≤1.5 (p<0.1). CONCLUSION Data suggest that astrocytic LGGs with increased 18F-FET uptake may show a more aggressive behaviour, with a potentially higher risk for an earlier tumor progression or malignant transformation. For further elucidation of a correlation between the tumor growth rate and the 18F-FET uptake, larger prospective studies are needed. In the future, the combination of both methods in the management of low-grade gliomas could help to detect tumor progression as well as tumor malignization more precisely.

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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