scholarly journals Change in Tumor Size by RECIST Correlates Linearly With Overall Survival in Phase I Oncology Studies

2012 ◽  
Vol 30 (21) ◽  
pp. 2684-2690 ◽  
Author(s):  
Rajul K. Jain ◽  
J. Jack Lee ◽  
Chaan Ng ◽  
David Hong ◽  
Jing Gong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Anticancer Agents ◽  
Tumor Size ◽  
Continuous Variable ◽  
Phase I Trials ◽  
Management Options ◽  
Cox Models ◽  
Kaplan Meier ◽  
The Relationship

Purpose RECIST is used to quantify tumor changes during exposure to anticancer agents. Responses are categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Clinical trials dictate a patient's management options based on the category into which his or her response falls. However, the association between response and survival is not well studied in the early trial setting. Patients and Methods To study the correlation between response as quantified by RECIST and overall survival (OS, the gold-standard survival outcome), we analyzed 570 participants of 24 phase I trials conducted between October 2004 and May 2009, of whom 468 had quantifiable changes in tumor size. Analyses of Kaplan-Meier estimates of OS by response and null Martingale residuals of Cox models were the primary outcome measures. All analyses are landmark analyses. Results Kaplan-Meier analyses revealed strong associations between change in tumor size by RECIST and survival (P = 4.5 × 10−6 to < 1 × 10−8). The relationship was found to be near-linear (R2 = 0.75 to 0.92) and confirmed by the residual analyses. No clear inflection points were found to exist in the relationship between tumor size changes and survival. Conclusion RECIST quantification of response correlates with survival, validating RECIST's use in phase I trials. However, the lack of apparent boundary values in the relationship between change in tumor size and OS demonstrates the arbitrary nature of the CR/PR/SD/PD categories and questions emphasis placed on this categorization scheme. Describing tumor responses as a continuous variable may be more informative than reporting categoric responses when evaluating novel anticancer therapies.

Ifosfamide (IFO) and doxorubicin (DOX) dose-intensities seem related to overall survival in adult soft-tissue sarcoma (STS) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9581-9581
Author(s):  
G. F. Almeida ◽  
G. Castro ◽  
I. M. Snitcovsky ◽  
A. C. Bassani ◽  
M. E. Diz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Size ◽  
Rank Test ◽  
Lower Grade ◽  
Chi Square ◽  
Outpatient Unit ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
The Relationship ◽  
Palliative Setting

9581 Background: IFO/DOX dose intensities (DI) seem to impact on the outcome of STS. We explored retrospectively the relationship between DI and overall survival (OS) in STS. Methods: From Jan/00 to Jun/05, 70 untreated STS pts received IFO/DOX, 32 as neo/adjuvant and 38 in the palliative setting at our outpatient unit. Filgrastin was not mandatory. Median age 47 y (17–74 y), 44 male; mean tumor size 13.6 cm in the neo/adjuvant and 16.5 cm in the palliative group (p=0.202, t-test). Most frequent histologies: leiomyo (16 pts), synovial (13), malignant fibrous histiocytoma (8) and liposarcoma (8). 28 pts had lower/ 9 upper limb tumors, 9 retroperitoneal, 9 trunk, 6 mediastinal, 5 visceral and 4 head and neck. Kaplan-Meier survival curves were considered from diagnosis and compared by log-rank test. Results: For the 70 pts, the mean DI for IFO and DOX were 2.5±0.9 mg/m2/wk and 18.8±6.0 mg/m2/wk, respectively. There was no difference between neo/adjuvant and palliative IFO/DOX DI (p=0.314/p=0.247, respectively). With 19-mo median f-up, the median OS (mOS) was 43 mo in the neo/adjuvant group with an advantage for pts submitted to conservative surgeries (46.5 mo vs. 16.8 mo; HR 0.185, 95%CI 0.003–0.399, p=0.007) as well as in those diagnosed with tumors with less than 3 mitoses/10 HPF (48.3 mo vs. 18.8 mo; HR 0.272, 95%CI 0.058–0.871, p=0.031). No differences in mOS related to tumor size, margin status or primary sites were found. According to IFO DI, the mOS were 46.5 mo, not reached (NR), 14.5 mo and 43 mo for pts in the 1st and subsequent DI quartiles (chi-square test for trend, p=0.004). In the median f-up of 9.8 mo, pts in the palliative setting presented mOS 21.8 mo, superior in the lower grade subgroup (NR vs. 11.1 mo; HR 0.130, 95%CI 0.076–0.746, p=0.014) and in the STS not from extremities (40.9 mo vs. 10.8 mo; HR 2.152, 95%CI 0.959–5.137, p=0.063). According to IFO DI quartiles, we also found a direct correlation between mOS (11.3 mo, 19 mo, 45.1 mo, and NR) and DI (p=0.052), and similar trend was shown for DOX DI, with 11.3 mo, 10.3 mo, NR, and 40.9 mo mOS for the 1st, 2nd, 3rd and 4th quartiles (p=0.018). Conclusions: In these STS adult pts, we have found a relationship between IFO and DOX DI and OS. Further evaluations of more intensive chemotherapy schedules are warranted. No significant financial relationships to disclose.

scholarly journals Eight-Gene Metabolic Signature Related with Tumor-Associated Macrophages Predicting Overall Survival for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Junyu Huo ◽  
Yunjin Zang ◽  
Hongjing Dong ◽  
Xiaoqiang Liu ◽  
Fu He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Survival Analysis ◽  
Risk Score ◽  
Risk Group ◽  
Cancer Genome ◽  
Metabolic Reprogramming ◽  
Tumor Associated Macrophages ◽  
Kaplan Meier ◽  
The Relationship

Abstract Background: In recent years, the relationship between tumor associated macrophages (TAMs) and solid tumors has become a research hotspot. The study aims at exploring the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma(HCC), in order to provide a new way of treatment for HCC.Materials and methods: The study selected 343 HCC patients with complete survival information(survival time >= 1month) in the Cancer Genome Atlas (TCGA) as the study objects. Kaplan-Meier survival analysis assisted in figuring out the relationship between macrophage infiltration level and overall survival (OS), and Pearson correlation test to identify metabolic reprogramming genes(MRGs) related to tumor macrophage abundance. Lasso regression algorithm were conducted on prognosis related MRGs screened by Univariate Cox regression analysis and Kaplan-Meier survival analysis to construct the riskscore, another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) were used for external validation regarding the prognostic signature.Results: A risk score composed of 8 metabolic genes can accurately predict the OS of training cohort(TCGA) and testing cohort(ICGC). It is important that the risk score could widely used for people with different clinical characteristics, and is an independent predictor independent of other clinical factors affecting prognosis. As expected, high-risk group exhibited an obviously higher macrophage abundance relative to low-risk group, and the risk score presented a positive relation to the expression level of three commonly used immune checkpoints(PD1,PDL1,CTLA4).Conclusion: Our study constructed and validated a novel eight‑gene signature for predicting HCC patients’ OS, which possibly contributed to making clinical treatment decisions.

Association of low RKIP expression with poor prognosis in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu
Keyword(s):  
Overall Survival ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Tnm Stage ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Nsclc Patients

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.

scholarly journals Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
External Beam Radiation ◽  
Rank Test ◽  
Beam Radiation ◽  
Kaplan Meier ◽  
Target Volumes ◽  
The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

Abstract 2753: Change in tumor size by RECIST correlates linearly with progression-free and overall survival in phase I studies

2010 ◽  
Author(s):  
Rajul K. Jain ◽  
J. Jack Lee ◽  
David Hong ◽  
Jing Gong ◽  
Aung Naing ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Tumor Size ◽  
Phase I Studies

scholarly journals Cardiac troponin I elevation and overall survival among cancer patients receiving investigational compounds during phase I trials

2016 ◽  
Vol 214 ◽  
pp. 364-369
Author(s):  
Antoine Hollebecque ◽  
Emilie Lanoy ◽  
Frederic Troallen ◽  
Laurie Soulat-Dufour ◽  
Christophe Massard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Cancer Patients ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Cardiac Troponin I ◽  
Phase I Trials

Multi-Institutional Phase I Trials of Anticancer Agents

2008 ◽  
Vol 26 (12) ◽  
pp. 1926-1931 ◽  
Author(s):  
Afshin Dowlati ◽  
Sudhir Manda ◽  
Joseph Gibbons ◽  
Scot C. Remick ◽  
Lauren Patrick ◽  
...  
Keyword(s):  
Phase I ◽  
Anticancer Agents ◽  
Maximum Tolerated Dose ◽  
National Institutes Of Health ◽  
Cytotoxic Agents ◽  
Phase I Trials ◽  
Tumor Type ◽  
Targeted Agents ◽  
Phase I Studies ◽  
Number Of Patients

Purpose Physicians involved in the conduct of phase I studies of novel anticancer agents have raised concerns about the emergence of multi-institutional phase I trials and about using the optimal biologic dose (OBD) as an alternative to the maximum-tolerated dose (MTD) as the primary end point in early drug development. We sought to determine the factors associated with multi-institutional phase I studies and OBD determination. Patients and Methods We reviewed all published phase I trials between January 1998 and June 2006 from two major clinical cancer journals. The following components from each trial were determined: number of participating sites, sponsor, nation where study was conducted, MTD or OBD established, number of patients accrued, mechanism of action of the studied agent, accrual time, and tumor type. Results We identified 463 trials. Fifty-six percent were performed in single institutions. Only 30% reported accrual time. The number of patients enrolled on single institution studies was significantly lower than on multi-institutional studies (P < .05), but there was no difference in accrual time. There was no association between the number of institutions and the sponsor or the mechanism of drug action. National Institutes of Health–sponsored trials enrolled fewer patients per trial than pharmaceutical-sponsored trials (P < .05). Although 99% of trials with cytotoxic agents determined an MTD, only 64% of trials with targeted agents did. Conclusion Multi-institutional phase I studies do not decrease the time to study completion and result in an increase in number of patients per trial. One third of trials with targeted agents failed to determine an MTD.

Patterns of peri-operative systemic therapy in liver-limited metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14048-e14048
Author(s):  
Trenton Tyler Kellock ◽  
Daniel John Renouf ◽  
Caroline Speers ◽  
Winson Y. Cheung
Keyword(s):  
Overall Survival ◽  
Hepatic Resection ◽  
Systemic Therapy ◽  
Liver Surgery ◽  
Median Overall Survival ◽  
Operative Therapy ◽  
Liver Lesion ◽  
Kaplan Meier ◽  
Improved Outcomes ◽  
The Relationship

e14048 Background: Treatment for liver-limited mCRC is increasingly multi-disciplinary, frequently involving systemic therapy and surgery. Our aims were to 1) explore the use and choice of systemic therapy pre- and post-liver resection and 2) examine if specific regimens were associated with improved outcomes. Methods: All patients diagnosed with liver-limited mCRC in British Columbia, Canada from 2006 to 2007 were reviewed. Summary statistics were used to describe surgical and systemic treatment patterns. Kaplan-Meier methodology was used to characterize the relationship between systemic regimen and survival. Results: Among 374 patients, 42% were aged >/=70 years, 60% were men, 24/39/37% were ECOG 0/1/2+, 80% had primary tumor surgery, and 68% received prior adjuvant chemotherapy. For liver metastases, 95 (26%) were offered hepatic resection. Compared to those who did not receive liver surgery, resected patients were younger (median 60 vs 69), had better function (ECOG 0/1 88 vs 55%), largest liver lesion was smaller (median 3 vs 4 cm), and had fewer total lesions (median 1 vs 4) (all p<0.05). Patients who underwent liver surgery also had improved median overall survival (12.0 vs 9.4 months, p<0.05) than those who did not. Among resected patients, 47% received pre-operative chemotherapy: FOLFOX (28%, median 7 cycles), FOLFIRI (18%, median 9 cycles), or capecitabine (1%, median 6 cycles) while 74% received post-operative treatment: FOLFOX (26%, median 3 cycles), FOLFIRI (37%, median 9 cycles), or capecitabine (11%, median 8 cycles). About 15% and 31% of patients also received bevacizumab as part of their pre- and post-operative regimens, respectively. Median overall survival did not differ significantly based on choice of chemotherapy backbone: FOLFOX (13.9 months), FOLFIRI (11.5 months), and capecitabine (10.9 months) (p=0.44) or receipt of bevacizumab: yes (14.5 months) vs no (11.1 months) (p=0.57) Conclusions: In this retrospective cohort of liver-limited mCRC patients, hepatic resection was associated with improved survival. Among those offered peri-operative therapy, FOLFOX, FOLFIRI, and capecitabine, either alone or in combination with bevacizumab, appear to be reasonable options.

Association of mucin production and survival in colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Mucin Production ◽  
Kaplan Meier ◽  
The Relationship ◽  
Disease Free

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.

Real-world evidence for carfilzomib dosing intensity on overall survival and treatment progression in multiple myeloma patients

2021 ◽  
pp. 107815522110152
Author(s):  
Noopur Raje ◽  
Rohan Medhekar ◽  
Sumeet Panjabi ◽  
Dionne M Hines ◽  
Xin Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Patient Outcomes ◽  
Medical Records ◽  
Single Agent ◽  
Subsequent Treatment ◽  
Cox Models ◽  
Kaplan Meier ◽  
Risk Of Mortality ◽  
Real World Evidence

Introduction Carfilzomib dosing as a single agent or in combination with dexamethasone (Kd) has evolved from the initial 27 mg/m2 twice-weekly (legacy dose), to more recently approved doses of 56 mg/m2 twice-weekly and 70 mg/m2 once-weekly (optimized doses). The objective of this study was to evaluate the overall survival (OS), and time to next treatment (TTNT) among multiple myeloma patients treated with Kd optimized vs legacy doses. Methods A retrospective analysis of patients receiving Kd between 01/01/2013–07/31/2017 was conducted using IQVIA’s oncology electronic medical records database. Kd dose was estimated based on body surface area. OS was measured from the Kd-initiation date until death. TTNT was defined as the time from Kd-initiation until the start of subsequent treatment. Kaplan-Meier analysis and Cox models were used to evaluate OS and TTNT. Results Of the 1,469 patients evaluated, 129 (8.8%) received optimized dose and 1,340 (91.2%) received legacy dose. Risk of mortality was 64% lower for patients receiving the optimized doses (HR: 0.36, 95% CI: 0.178–0.745). Patients receiving the optimized doses had significantly longer TTNT compared to patients receiving the legacy dose (median TTNT: 17.5 months [95% CI: 14.8-NE] and 13.2 months, [95% CI: 12.4–14.4], respectively; p = 0.023), and 33% lower risk of progressing to the subsequent treatment (HR: 0.67, 95% CI: 0.48–0.93). Conclusions Patient outcomes could be improved if eligible MM patients are treated with the optimized, recently approved Kd doses (56 mg/m2 twice-weekly and 70 mg/m2 once-weekly).

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