A method for assessing tumor response to therapy and more precisely guiding treatment decisions so as to improve survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13122-e13122
Author(s):  
Julia Wilkerson ◽  
Laleh Amiri-Kordestani ◽  
Ravi A. Madan ◽  
Bamidele Adesunloye ◽  
Sen Hong Zhuang ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Treatment Decisions ◽  
Response To Therapy ◽  
Phase Iii ◽  
Categorical Variables ◽  
Percentage Increase ◽  
Pre Treatment ◽  
Cancer Multiple ◽  
Over Time

e13122 Background: The response of tumors to chemotherapy is monitored using imaging data or tumor markers and this quantitative data provides a rich source for an objective response assessment and treatment decisions. Responses are usually assessed as categorical variables based on percentage increase or decrease in tumor size. Methods: We have developed mathematical equations that describe efficacy as a continuous variable, enabling the extraction of the appropriate rate constants for tumor growth and regression (decay), designated g and d, respectively. Both are used to describe the rates of tumor growth and regression for the fraction of tumor that is growing despite treatment and the fraction dying as a result of therapy, respectively. Results: Using data from randomized phase III trials in kidney and breast cancer, multiple myeloma, and medullary thyroid carcinoma; as well as phase II trials in prostate cancer we have shown that: (1) values of g but not those of d are strongly correlated (negatively) with patient survival; (2) g can be discerned early in treatment, before growth is demonstrated clinically, providing an early efficacy measure; (3) g typically does not change over time, even over years, suggesting resistance is intrinsic and predictable and does not worsen over time; (4) effective therapies both increase d, and reduce g; and (5) in every cancer studied, the evidence suggests tumor growth reverts to its pre-treatment rate when chemotherapy is discontinued. Conclusions: The observation that g remains stable allows one to predict the most likely outcome of continued therapy. The evidence indicates that the increase in g occurring after treatment discontinuation is due to a resumption of a pre-treatment growth rate and not a change in biology. Our hypothesis is that if a favorable growth rate that slows tumor growth can be identified, survival might be improved if therapies that achieve this favorable growth rate are continued despite crossing conventional disease progression boundaries. We plan a prospective test of this model to provide a more informed decision and better survival outcome by maximizing the benefit obtained from approved therapies.

Predictive value of tumor growth rate during previous treatment for tumor response to regorafenib (REGO) and trifluridine/tipiracil (TFTD) in metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 766-766
Author(s):  
Takeshi Kawakami ◽  
Toshiki Masuishi ◽  
Yasuyuki Kawamoto ◽  
Katsuhiro Omae ◽  
Tetsuhito Muranaka ◽  
...  
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Treatment Period ◽  
Tumor Response ◽  
Previous Treatment ◽  
Target Lesion ◽  
Tumor Growth Rate ◽  
Long Duration ◽  
Pre Treatment ◽  
Slow Growing

766 Background: Although REGO and TFTD have been recognized as standard salvage treatments for patients (pts) with refractory mCRC, it is still unclear which drug should be used first. Tumor growth rate (TGR) during the pre-treatment period is associated with survival in lung and laryngeal cancer treated with chemoradiotherapy. However, little is known about the association between TGR during the pre-treatment period and tumor response to REGO and TFTD. Methods: We retrospectively analyzed the data of consecutive mCRC pts who were treated with REGO or TFTD at three institutions. We classified pts into slow-growing (SG) or rapid-growing (RG) groups according to TGR, and appearance of new lesions (NL+) or their absence (NL–) during the pre-treatment period. TGR was calculated as follows: TGR = (D1 − D0)/100D0 (CT1 − CT0), where CT1 is the date of computed tomography (CT) at progressive disease, CT0 is the date of CT before CT1, and Dn is the sum of target lesion diameters at CTn (according to RECIST version 1.1). SG was defined as NL– with a low TGR ( < 0.33), and RG was defined as NL− with a high TGR (≥0.33) or NL+, irrespective of TGR. Results: A total of 244 pts (RG/SG: 133/111, REGO/TFTD: 132/112) were eligible. The proportion of RG pts with a long duration from first-line chemotherapy and SG pts with elevated ALP was higher in the REGO group, while the proportion of SG pts with poor PS was higher in the TFTD group. The disease control rate (DCR) was similar in both groups (REGO 29% vs TFTD 23%, p = 0.556) among RG pts, while the DCR of TFTD was significantly better than REGO in SG pts In a multivariate analysis of predictive factors for DCR, drug selection was an independent factor for DCR in SG pts (odds ratio 3.51; 95% CI 1.33-9.27; p = 0.011). In RG group, DCRs of NL+ pts were worse than that of NL- pts (16% vs 36% in REGO group, p = 0.109; 9% vs. 31% in TFTD group, 0.108). Conclusions: TGR during the pre-treatment period would be helpful in selecting between REGO and TFTD, especially for pts with slow-growing tumors. Pts with appearance of new lesions may not benefit from either REGO or TFTD as salvage treatment.

Determining the rate of tumor growth and decay in patients with metastatic breast cancer as an early efficacy endpoint: A study assessing ixabepilone efficacy.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 246-246
Author(s):  
L. Amiri-Kordestani ◽  
I. Jawed ◽  
J. Wilkerson ◽  
W. D. Stein ◽  
S. E. Bates ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Phase Ii ◽  
Tumor Regression ◽  
Single Agent ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Phase Iii ◽  
Second Line ◽  
Significant Difference ◽  
Previously Treated

246 Background: Early efficacy assessment in drug development should help find new cancer therapies. We have developed a novel method to analyze tumor response to therapy by quantifying the rate of tumor regression (d) and growth (g). We have shown g is slower when pts are on effective therapy and that g correlates with survival (Stein et al, Oncologist 2008). We utilized this method to evaluate a phase III trial of capecitabine (CAP) ± IXA in second line therapy (Tomas et al, JCO 2007) and a three-cohort phase II trial in second and subsequent lines of therapy in pts with MBC consisting of (1) Daily X 5 IXA given to taxane (TAX)-naïve patients (Denduluri et al, JCO 2007); (2) Daily X 5 IXA in pts previously treated with TAX (Low et al, JCO 2005); and (3) Daily X 3 IXA in pts previously treated with TAX (Denduluri et al, Invest New Drug 2007). Methods: Using tumor measurements assessed by RECIST and a two-phase mathematical equation we determined d and g. Results: In the phase III study g was superior to PFS identifying a significant difference between the arms very early—before the 200th pt had enrolled. In an individual patient the g values could be estimated as early as the 3rd evaluation, long before tumor growth was observed clinically. IXA + CAP in second line (g = 0.0018) was more effective than CAP (g = 0.0023) at reducing g, and more effective (p=0.0085) than single agent IXA in the Phase II study (g = 0.0027). Single agent IXA was comparably effective (p=0.814) in reducing the g of tumors previously exposed to a TAX (g = 0.0032) as in reducing the g of TAX-naïve tumors (g = 0.0035), consistent with its development as an agent active in TAX-refractory disease. Unlike differences in g, the d of single agent IXA (0.118) was comparable to that of IXA+CAP (0.0074) suggesting differences were primarily driven by effect on the growth of residual tumor. Conclusions: Unlike PFS, an incremental measure of efficacy, g is a continuous variable and can more accurately assess differences between treatments. Because calculations of g are indifferent to assessment intervals, estimating a tumor’s g allows comparison of efficacy across trials.

Does Pre-treatment Metabolic Tumor Growth Rate (MTGR) Predict Progression in Lung Cancer?

2009 ◽  
Vol 75 (3) ◽  
pp. S446
Author(s):  
D.V. Eastham ◽  
C.H. Chapman ◽  
A.K. Rao ◽  
B. Narasimhan ◽  
A. Quon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Rate ◽  
Tumor Growth ◽  
Tumor Growth Rate ◽  
Pre Treatment

Relationship between tumor burden to growth rate and treatment outcomes of nivolumab for patients with head and neck squamous carcinoma.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 68-68
Author(s):  
Chiaki Suzuki ◽  
Naomi Kiyota ◽  
Yoshinori Imamura ◽  
Junpei Rikitake ◽  
Satoshi Sai ◽  
...  
Keyword(s):  
Growth Rate ◽  
Head And Neck ◽  
Small Sample Size ◽  
Squamous Carcinoma ◽  
Small Sample ◽  
Phase Iii ◽  
Tumor Growth Rate ◽  
Cytotoxic Treatment ◽  
Pre Treatment ◽  
Clinical Records

68 Background: Nivolumab improved overall survival (OS) in the treatment of platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) in a phase III clinical trial. However, Kaplan-Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3-6 months, suggesting that patients with initial resistance to immunotherapy may have better outcomes with cytotoxic treatment. Here, we explored suitable conditions and candidates of predictive factors for nivolumab for R/M HNSCC. Methods: We retrospectively reviewed the clinical records of 28 consecutive patients with HNSCC from 2014-2018. Tumor size was evaluated by computed tomography according to RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3Log (Dt/D0)/t, where D0 and Dt are the sum of the longest diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1 t defined as the 4-week interval between tumor evaluations. Results: After exclusion of 2 patients with unevaluable responses, 26 patients were included in the study. Median follow-up time for survivors was 9.5 months. Median SumTLs at baseline was 43.2 mm (range, 10.1-135.3). Median Gr was 0.22 (range, 0.05-0.76). Median OS and PFS was 7.9 months (95% CI, 5.8 to 34.5) and 3.7 months (95% CI, 2.1 to 12.9), respectively. Patients with progression within 3 months showed significantly worse survival (HR 6.33, 95% CI 2.08-21.67, p=0.001). Moreover, higher Gr and bigger SumTLs appeared to be associated with poorer outcomes. We therefore explored the association between prognosis and the ratio of SumTLs to Gr (SumTLs/Gr). The cut off value of SumTLs/Gr was calculated by ROC analysis. Pre-treatment SumTLs/Gr > 212 was associated with significantly worse OS (HR 8.87, 95% CI 2.33-58.29, p<0.001) and PFS (HR 2.86, 95% CI 1.10-8.33, p=0.03). Conclusions: Although retrospective with a small sample size, these results suggest that pre-treatment SumTLs/Gr > 212 was significantly associated with inferior OS and PFS in R/M HNSCC patients treated with nivolumab. R/M HNSCC patients with pre-treatment SumTLs/Gr > 212 might be unsuitable for treatment with nivolumab.

Analysis of tumor growth rate for radioiodine (RAI)-refractory differentiated thyroid cancer patients receiving placebo and/or sorafenib in the phase III DECISION study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 6015-6015 ◽  
Author(s):  
Christian Kappeler ◽  
Dennis P. Healy ◽  
Christoph Baumer ◽  
Gerold Meinhardt ◽  
Rossella Elisei ◽  
...  
Keyword(s):  
Growth Rate ◽  
Thyroid Cancer ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Differentiated Thyroid Cancer ◽  
Phase Iii ◽  
Tumor Growth Rate

Small Choroidal Melanoma: Correlation of Growth Rate with Pathology

2021 ◽  
pp. 1-10
Author(s):  
Vishal Raval ◽  
Shiming Luo ◽  
Emily C. Zabor ◽  
Arun D. Singh
Keyword(s):  
Growth Rate ◽  
Retinal Pigment ◽  
Choroidal Melanoma ◽  
Case Series ◽  
Subretinal Fluid ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Basal Diameter ◽  
Orange Pigment ◽  
Rpe Atrophy

<b><i>Purpose:</i></b> The aim of the study was to evaluate equivalence of growth rate and pathologic confirmation in small choroidal melanoma (SCM). <b><i>Design:</i></b> This study is a case series. <b><i>Subjects, Participants, and Controls:</i></b> A total of 61 patients with a choroidal melanocytic tumor of size 5.0–16.0 mm in the largest basal diameter and 1.0–2.5 mm in thickness were classified into the pathology-confirmed group (<i>n</i> = 19), growth-confirmed group (<i>n</i> = 30), and with combined observations (<i>n</i> = 12). <b><i>Methods:</i></b> Distribution of clinical variables (age, gender, laterality, tumor dimensions, tumor location, and presence of orange pigment, subretinal fluid, drusen, and retinal pigment epithelial [RPE] atrophy) between the groups was analyzed. Patient and disease characteristics were summarized as the median and interquartile range for continuous variables and the frequency and percentage for categorical variables. Comparisons were made using the Wilcoxon rank sum test for continuous variables and either Fisher’s exact test or the χ<sup>2</sup> test for categorical variables with a <i>p</i> value threshold of 0.05 for statistical significance. Growth rate (change in basal dimension/12 months) diagnostic of SCM was quantified. <b><i>Main Outcome Measures:</i></b> The primary aim of this study was to test the hypothesis that “growth” was diagnostic of SCM with the secondary aim of quantifying the malignant “growth rate” (growth rate of SCM). <b><i>Results:</i></b> The clinical characteristics among all 3 groups were similar except more patients with symptoms (68 vs. 20 vs. 42%, <i>p</i> = 0.004) and juxtapapillary location (<i>p</i> = 0.03) were in the pathology group than in the growth-confirmed group. Those in the combined and growth-confirmed groups had more patients with drusen (11 vs. 60 vs. 50%, <i>p</i> = 0.003) and RPE atrophy (11 vs. 23 vs. 67%, <i>p</i> = 0.003), respectively, than in the pathology group. The median time to detect growth was 9 months (range 3–26 months). The mean growth rate in basal dimension was 1.8 mm/12 months (range, 0.0–7.4 mm; [95% CI: 1.32–2.28]). <b><i>Conclusions and Relevance:</i></b> Choroidal melanocytic lesions exhibiting a defined growth rate can be clinically diagnosed as SCM without a need for biopsy.

scholarly journals CTNI-01. EFFECT OF STEREOTACTIC RADIOSURGERY COMPARED TO WHOLE-BRAIN RADIOTHERAPY FOR LIMITED BRAIN METASTASIS ON LONG TERM COGNITION AND QUALITY OF LIFE: A POOLED ANALYSIS OF RANDOMIZED CLINICAL TRIALS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii40-ii41
Author(s):  
Joshua Palmer ◽  
Brett Klamer ◽  
Karla Ballman ◽  
Paul Brown ◽  
Jane Cerhan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Randomized Clinical Trials ◽  
Whole Brain Radiotherapy ◽  
Pooled Analysis ◽  
Cognitive Outcomes ◽  
Phase Iii ◽  
Brain Radiotherapy ◽  
Over Time

Abstract PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of &gt;1 standard deviation from baseline in &gt;2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of &gt;2 cognitive scores with &gt;2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in &gt;1 and &gt;2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in &gt;3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in &gt;1 CM at every time point. SRS had fewer patients with a 2 SD decline at &gt;2 and &gt;3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p&lt; 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p&lt; 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

scholarly journals Hepatocellular Carcinoma Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE): Outcome Analysis Using a Model Based On Pre-Treatment CT Texture Features

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 956
Author(s):  
Marcello Andrea Tipaldi ◽  
Edoardo Ronconi ◽  
Elena Lucertini ◽  
Miltiadis Krokidis ◽  
Marta Zerunian ◽  
...  
Keyword(s):  
Texture Analysis ◽  
Clinical Data ◽  
Transarterial Chemoembolization ◽  
Prognostic Value ◽  
Texture Features ◽  
Response To Therapy ◽  
Survival Prediction ◽  
Ct Examination ◽  
Drug Eluting ◽  
Pre Treatment

(1) Introduction and Aim: The aim of this study is to investigate the prognostic value, in terms of response and survival, of CT-based radiomics features for patients with HCC undergoing drug-eluting beads transarterial chemoembolization (DEB-TACE). (2) Materials and Methods: Pre-treatment CT examinations of 50 patients with HCC, treated with DEB-TACE were manually segmented to obtain the tumor volumetric region of interest, extracting radiomics features with TexRAD. Response to therapy evaluation was performed basing on post-procedural CT examination compared to pre-procedural CT, using modified RECIST criteria for HCC. The prognostic value of texture analysis was evaluated, investigating the correlation between radiomics features, response to therapy and overall survival. Three models based on texture and clinical variables and a combination of them were finally built; (3) Results: Entropy, skewness, MPP and kurtosis showed a significant correlation with complete response (CR) to TACE (all p < 0.001). A predictive model to identify patients with a high and low probability of CR was evaluated with an ROC curve, with an AUC of 0.733 (p < 0.001). The three models built for survival prediction yielded an HR of 2.19 (95% CI: 2.03–2.35) using texture features, of 1.7 (95% CI: 1.54–1.9) using clinical data and of 4.61 (95% CI: 4.24–5.01) combining both radiomics and clinical data (all p < 0.0001). (4) Conclusion: Texture analysis based on pre-treatment CT examination is associated with response to therapy and survival in patients with HCC undergoing DEB-TACE, especially if combined with clinical data.

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.

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