The components of progression as explanatory variables for overall survival in the RECIST database.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10602-10602
Author(s):  
Saskia Litière ◽  
Elisabeth De Vries ◽  
Lesley Seymour ◽  
Daniel J. Sargent ◽  
Lalitha Shankar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Complete Response ◽  
Tumor Type ◽  
Explanatory Variables ◽  
Best Response ◽  
Rate Of Increase ◽  
Target Disease ◽  
The Impact

10602 Background: Progressive disease (PD) according to RECIST 1.1 (Eisenhauer et al, 2009) is defined as one or more of (1) PD of measurable target lesions, (2) the presence of a new lesion (NL) or (3) the unequivocal PD of non-target disease (NT-PD). We explored the impact of these components, varying over time, on predicting overall survival (OS) in the RECIST database residing at EORTC (Bogaerts et al, 2009). Methods: Data was selected from 12 randomized clinical trials (3530 patients with breast, lung or colorectal cancer). A maximum of 5 target lesions was used to determine the sum of diameters. The following were calculated or assigned at each measurement time t: best response (BR) was best % improvement from baseline up to t (0% if no improvement - 100% if complete response (CR)); tumor growth (TG) was the weekly rate of increase from nadir to t (0 if no increase; irrespective of prior shrinkage), presence of NL (yes/no), and occurrence of NT-PD (yes/no); categories were not mutually exclusive. OS was analyzed by tumor type using a Cox regression model, adjusting for baseline sum, and including BR, TG, presence of NL and NT-PD as time dependent covariates. Results: Thirty-six percent of patients had NL, 26% had NT-PD, 11% achieved CR and 14% did not have shrinkage of target lesions, while 46% experienced TG (median strongest growth per patient of 0.5 mm/week). Regardless of tumor type, the presence of NL (Hazard Ratio (HR) ranging 1.4-2.5), NT-PD (HR 1.2-2.5) and TG (per 1mm/week increase; HR 1.1-1.4) were associated with worse OS, while achieving CR was associated with a longer OS (HR 0.2-0.8). Further analyses exploring the functional shape of the association between BR and TG, and OS are ongoing. This includes putting TG in contrast with the more usual % cutoff defining target PD. Conclusions: All three components of PD according to RECIST are independently strongly associated with OS. Quantification such as this will enable a better understanding of the role of each component (e.g. clinical aspect of NT-PD assessment) in PD evaluation. Work is ongoing to incorporate this information into an updated RECIST with enhanced prediction of subsequent survival.

The impact of the chemoradiation to surgery interval on pathological complete response: Short and long-term overall survival in esophageal cancer patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 2-2
Author(s):  
Basem Azab ◽  
Omar Picado ◽  
Caroline Ripat ◽  
Francisco Igor Macedo ◽  
Alan S Livingstone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Cox Regression ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Continuous Variable ◽  
National Cancer Data Base ◽  
Categorical Variables ◽  
Cancer Data ◽  
The Impact

2 Background: The association of the interval between neoadjuvant chemo-radiation and surgery (CRT-S), and cancer outcomes in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR), short and long overall survival (OS). Methods: Patients listed on the National Cancer Data Base from 2004 to 2013 were studied. We included patients with CRT followed by surgery in 15-90 days. All patients had reported pT, pN cancer stages and survival status. CRT-S interval was studied as continuous (weeks) and categorical variables (quintiles). Results: A total of 5181 patients were included; 81% were adenocarcinomas, 84% were males and mean age was 62 years. They were divided into CRT-S interval quintiles (15 to 37, 38 to 45, 46 to 53, 54 to 64 and 65 to 90 days) (n = 1016, 1063, 1081, 1083 and 938 patients), respectively. There was a significant increase of pCR rate across the CRT-S quintiles (18%, 21%, 24%, 25% and 29%, p < 0.001). This advantage persisted when CRT-S was measured as continuous variable in weeks (OR: 1.11, 95% CI = 1.078-1.143, p < 0.001). However, 90-day mortality significantly increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5% and 8.2%, p = 0.02) and through weeks (OR = 1.05, 95%CI = 1.005-1.106, p = 0.03). Mean OS across CRT-S quintiles was 59.2, 58.8, 55.4, 56.6 and 51.5 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval (HR 1.02, 95% 1.003-1.037, p = 0.02), especially among the last quintile (CRT-S = 65-90 days: HR 1.2, 95% CI 1.04-1.32, p = 0.009). Those with no-pCR had worse OS as time to surgery increased (p < 0.001), while pCR group had similar OS across CTR-S intervals. Conclusions: Despite higher pCR rate as CRT-S interval increasing, surgery is preferred to be done in less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. Further randomized studies are needed to consolidate our findings.

Meta-analyses of randomized trials assessing the influence of chemotherapy and prognostic factor in advanced/recurrent gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4550-4550
Author(s):  
C. Pozzo ◽  
Y. Ohashi ◽  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Meta Analysis ◽  
Performance Status ◽  
Small Sample ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
The Impact

4550 Background: Advanced or recurrent stomach cancer remains an incurable disease. Several drugs and different combinations of chemotherapy have been investigated but very often with small sample sizes making definitive conclusions difficult. The GASTRIC project is an individual-patient-data (IPD) based meta-analysis in the advanced disease setting to quantify the potential benefit of various chemotherapies. We used this large database to study the role of various prognostic factors and potential interactions with chemotherapy. Methods: All randomized clinical trials (RCT) closed to patient accrual at the end of 2004 were eligible. Radiotherapy, intraperitoneal chemotherapy, or immunotherapy was excluded. The primary endpoint was overall survival (OS). Baseline variables included sex, age, performance status (PS), diseases status at entry, prior surgery, number of organs involved at entry, location of metastasis, TNM stages, histology, operative procedures, and geographic area. The hazard ratio (HR) and 95% confidence interval (CI) was calculated by the multivariate Cox analysis to assess of the prognostic factors for their relationship to OS. Results: Fourty-nine eligible RCTs (7,120 patients) were identified. As of December 2008, IPD from 21 trials (3,619 patients) with a median follow- up of 7.3 months were available for OS. There was no statistically significant difference between 5FU-based, anthracycline-based, platinum-based, taxane-based, or irinotecan-based regimens versus any other CT. In the multivariate Cox regression analysis stratified by trial and treatment arm, PS of 2 (HR, 2.43; 95%CI, 2.02 to 2.94) compared to PS of 0, metastatic (HR, 1.29; 95%CI, 1.01 to 1.64) compared to local advanced, many number of organs, and location of metastasis (especially with peritorium; HR, 1.75; 95%CI, 1.23 to 2.48) compared to none were strongly associated with lower survival. Conclusions: Our interim results could not show an overall survival benefit in favour of 5FU-, anthracycline-, platinum-, taxane-, or irinotecan-based regimens compared with a regimen without the specific chemotherapy. We confirm the impact of PS, diseases status at entry, number of organs involved, and location of metastasis on OS. No significant financial relationships to disclose.

Achievement of Complete Response Is Important for Longer Overall Survival in Patients with Newly Diagnosed Myeloma: A Single-Institutional Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5115-5115
Author(s):  
Kanichi Iwama ◽  
Tomotaka Ugai ◽  
Hiroki Sugihara ◽  
Masayuki Yamakura ◽  
Masami Takeuchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Partial Response ◽  
Complete Response ◽  
Novel Agents ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
Female Ratio ◽  
Best Response ◽  
The Impact

Abstract Abstract 5115 INTRODUCTION. Even with the introduction of novel therapeutic agents, including thalidomide, bortezomib, and lenalidomide, multiple myeloma (MM) is an incurable disease. Deeper responses, such as complete response (CR) and very good partial response (VGPR), are major goals of treatment to obtain long-term overall response (OS) and progression-free response (PSF) in patients with MM. Recent large randomized retrospective studies also suggested improved OS and PFS in patients who achieved deeper responses. However, the prognostic impact of achieving CR or VGPR remains controversial. In addition, these studies included selected patients that may not be representative of the general population. Therefore, we analyzed cases in our database to evaluate the impact of treatment response on the outcome of consecutive patients with symptomatic MM who were treated with chemotherapeutic regimens containing novel agents over the past 6 years at our institution in Kamogawa City, Japan. PATIENTS AND METHODS. We included 97 consecutive patients treated at our institution between April 2005 and May 2011. The study population consisted of 56 male and 41 female patients with a median age of 70 years old (range: 45 −90). Due to the rapid changes in treatment modality and government approval of novel agents in myeloma during this period, initial treatment could not be uniformly categorized, but all patients received chemotherapy regimens containing at least one novel agent, including thalidomide, bortezomib, and lenalidomide. These patients were thought to be more representative of the general myeloma population. Seventy-seven (79.4%), 27 (38.6%), and 55 (56.7%) patients received bortezomib-, lenalidomide-, and thalidomide-containing regimens, respectively. Treatment responses were assessed using the International Myeloma Working Group (IMWG) criteria with minor modifications, and the best response to treatment during the course of disease was evaluated. Immunofixation test and serum free light chain measurements were performed for confirmation of CR and stringent CR. OS was calculated from the time of diagnosis until the date of death from any cause or the date on which the patient was last known to be alive. Univariate and multivariate analyses were performed for the following variables: age at diagnosis, International Staging System (ISS), and best response achieved. RESULT. The median age of patients was 71 y.o. (range: 49 −90 y.o.), and the male to female ratio was 56:41. The best responses to treatment were as follows: CR was obtained in 19 cases (19.6%), VGPR in 29 (29.9%), partial response (PR) in 34 (35.0%), and stable disease (SD) or less in 15 (15.4%). Baseline characteristics according to best response achieved in patients who achieved CR, VGPR, PR, and SD or less were similar among the patients ≥70 y.o. vs. ≤70 y.o. Patients' age has no impact on the response to treatment. With a median follow-up of 25 months, Kaplan–Meier estimated 3-year and 5-year overall survival (OS) rates were 67.2% and 35.0%, respectively. The 3- and 5-year OS were 100% in patients with CR, which were significantly superior in patients with VGPR (3-y 70%, 5-y 55.0%) and PR (3-y 60%, 5-y 23.0%). The 3- and 5-year OS were not significantly different between patients with VGPR and PR. Normalization of FLC kappa/Lambda ratio was observed in 15 of 19 (80%) patients with CR, 15 of 29 (51%) with VGPR, 4 of 34 (6.6%) in PR, and in none of 15 (0%) in SD or less. Patients who showed normalization of FLC kappa/Lambda ratio had significant OS benefit compared to those who did not. Proportional hazard Cox models showed that patients with ISS stage I/II had better 5-year OS rate compared to patients with stage III (51%; 20%, P = 0.005). However, there was no association between ISS stage and achievement of CR. CONCLUSION. The results of the present study highlighted the importance of achieving CR, not PR or VGPR, and normalization of FLC kappa/Lambda ratio for obtaining long-term OS in patients with MM regardless of age or ISS stage. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group

2009 ◽  
Vol 27 (22) ◽  
pp. 3705-3711 ◽  
Author(s):  
David A. Rodeberg ◽  
Julie A. Stoner ◽  
Andrea Hayes-Jordan ◽  
Simon C. Kao ◽  
Suzanne L. Wolden ◽  
...  
Keyword(s):  
Alternative Therapy ◽  
Prognostic Significance ◽  
Complete Response ◽  
Disease Recurrence ◽  
Radiographic Measurement ◽  
Clinical Group ◽  
Group Iii ◽  
Best Response ◽  
Pathology Reports ◽  
The Impact

Purpose Some patients with rhabdomyosarcoma (RMS) achieve less than a complete response (CR) despite receiving all planned therapy. We assessed the impact of best response at the completion of all therapy on patient outcome. Patients and Methods We studied 419 clinical group III participants who completed all protocol therapy without developing progressive disease for Intergroup Rhabdomyosarcoma Study (IRS) IV. Response (complete resolution [CR], partial response [PR; ≥ 50% decrease], or no response [NR; < 50% decrease and < 25% increase]) was determined by radiographic measurement and categorized by the best response. Results At the end of therapy, 341 participants (81%) achieved a best response of CR and 78 (19%) had a best response of PR/NR. Five-year failure-free survival was similar for participants achieving CR (80%) and PR/NR (78%). After adjustment for age, nodal status, primary site, and histology, there was no significant indication of lower risk of failure (hazard ratio [HR], 0.77; 95% CI, 0.46 to 1.27; P = .3) nor death (HR, 0.63; 95% CI, 0.36 to 1.09; P = .1) for CR versus PR/NR participants. Seventeen participants with a best response of PR/NR had surgical procedures; eight (50%) of 16 with available pathology reports had residual viable tumor and only three achieved a complete resection. Resection of residual masses was not associated with improved outcome. Conclusion CR status at the end of protocol therapy in clinical group III participants was not associated with a reduction of disease recurrence and death. Aggressive alternative therapy may not be warranted for RMS patients with a residual mass at the end of planned therapy.

Reliability-based covariate analysis for complex systems in heterogeneous environment: Case study of mining equipment

2018 ◽  
Vol 233 (4) ◽  
pp. 593-604
Author(s):  
Amin Moniri-Morad ◽  
Mohammad Pourgol-Mohammad ◽  
Hamid Aghababaei ◽  
Javad Sattarvand
Keyword(s):  
Complex Systems ◽  
Cox Regression ◽  
Reliability Evaluation ◽  
Distribution Functions ◽  
Heterogeneous Environment ◽  
Mining Equipment ◽  
Data Set ◽  
Explanatory Variables ◽  
The Impact

Operational heterogeneity and harsh environment lead to major variations in production system performance and safety. Traditional probabilistic model is dealt with time-to-event data analysis, which does not have the capability of quantifying and simulation of these types of complexities. This research proposes an integrated methodology for analyzing the impact of dominant explanatory variables on the complex system reliability. A flexible parametric proportional hazards model is developed by focusing on standard parametric Cox regression model for reliability evaluation in complex systems. To achieve this, natural cubic splines are utilized to create a smooth and flexible baseline hazards function where the standard parametric distribution functions do not fit into the failure data set. A real case study is considered to evaluate the reliability for multi-component mechanical systems such as mining equipment. Different operational and environmental explanatory variables are chosen for the analysis process. Research findings revealed that precise estimation of the baseline hazards function is a major part of the reliability evaluation in heterogeneous environment. It is concluded that an appropriate maintenance strategy potentially mitigate the equipment failure intensity.

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

Clinical relevance of clonal hematopoiesis in metastatic gastrointestinal malignancies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16082-e16082
Author(s):  
Bill Diplas ◽  
Ryan Ptashkin ◽  
Andrea Cercek ◽  
Rona Yaeger ◽  
Kelly L Bolton ◽  
...  
Keyword(s):  
Overall Survival ◽  
Genetic Alterations ◽  
Smoking History ◽  
High Status ◽  
Tumor Type ◽  
Gastrointestinal Malignancies ◽  
Clonal Hematopoiesis ◽  
Multivariate Survival ◽  
Esophagogastric Cancer ◽  
The Impact

e16082 Background: Clonal hematopoiesis (CH) represents non-random clonal selection of bone marrow-derived cells marked by somatic mutations in certain genes. The presence of CH is associated with development of atherosclerosis and leukemia, and accelerated by toxic exposures (chemotherapy, radiation, smoking) and aging (Jaiswal et al. NEJM 2017; Abelson et al. Nature 2018). The impact of these genetic alterations on cellular function is unknown, especially in the broader context of immunity and in response to cancer therapy. To determine the contribution of CH to therapeutic response and hematologic toxicity in cancer patients, we examined the outcomes of patients treated with cytotoxic and immunotherapy in relationship to CH status. Methods: We evaluated patients with metastatic colorectal cancer (CRC) or esophagogastric cancer (EGC). DNA extracted from whole blood and tumor tissue were sequenced in tandem as part of the MSK-IMPACT hybridization capture-based sequencing assay. CH was defined as any mutation with a VAF of at least 2%, present in at least 10 reads, with at least 2:1 blood:tumor reads, or 1.5:1 blood:lymph node that was not found in gnomAD with a frequency > 0.005. Additional filtering and putative driver definitions (CH-PD) were described by Bolton et al. Nature Genetics 2020. Multivariate survival analyses were performed using a Cox Proportional Hazard model correcting for CH, CH-PD, prior smoking, prior chemotherapy, prior radiation, MSI status, and age at cancer diagnosis. Results: 654 patients with EGC (n = 348) and CRC (n = 306) who began treatment between 2006 and 2020 were included in the analysis. CH was present in 34.5% and 24.4% of each group, and 17.2% and 12.9% harbored CH-PD, respectively. CH and CH-PD were both associated with older age and smoking history, and CH was also associated with prior radiation and MSI-high status (p < 0.05). Patients with CH or CH-PD receiving first-line (1L) therapy for CRC or EGC demonstrated no difference in mPFS after multivariate analysis, though 1L EGC patients with CH-PD had inferior mOS (p = 9e-5). There was no difference in pre-1L WBC, ANC, or ALC, nor in G-CSF or PEG-G-CSF doses administered during 1L therapy between patients with CH or CH-PD versus those without. Similarly, presence of CH or CH-PD had no impact on mPFS or mOS in patients receiving immune checkpoint blockade (ICB) without concurrent chemotherapy after multivariate survival analysis. Conclusions: We confirmed that the mere presence of CH is not prognostic for overall survival, but that EGC patients with CH-PD mutations have inferior overall survival, which is consistent with previous findings. Presence of CH or CH-PD was not associated with differences in baseline leukocyte counts nor need for G-CSF support, nor did it impact PFS in either tumor type, suggesting limited utility of CH in solid tumor clinical decision-making.

scholarly journals Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-Yan Meng ◽  
Xiu-Ping Zhang ◽  
Zhe Sun ◽  
Hong-Qian Wang ◽  
Wei-Feng Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Portal Vein ◽  
Tumor Thrombus ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Portal Vein Tumor Thrombus ◽  
Cox Regression Analysis ◽  
The Impact ◽  
Underlying Pathophysiology

Abstract Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

scholarly journals Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab

2014 ◽  
Vol 32 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
Suzanne L. Topalian ◽  
Mario Sznol ◽  
David F. McDermott ◽  
Harriet M. Kluger ◽  
Richard D. Carvajal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Response Duration ◽  
Advanced Melanoma ◽  
Immune Memory ◽  
Drug Discontinuation ◽  
Median Response ◽  
The Impact

PurposeProgrammed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.Patients and MethodsPatients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.ResultsMedian overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.ConclusionOverall survival following nivolumab treatment in patients with advanced treatment–refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

NF-κB in the Vascular Progression of Melanoma

2004 ◽  
Vol 22 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Mohammed Kashani-Sabet ◽  
Ladan Shaikh ◽  
James R. Miller ◽  
Mehdi Nosrati ◽  
Carlos M.M. Ferreira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Tissue Array ◽  
Matched Pair ◽  
Vascular Involvement ◽  
Tumor Vascularity ◽  
Data Set ◽  
Cox Regression Analysis ◽  
The Impact

Purpose To examine a model of melanoma progression based on vascular factors and the role of NF-κB in the vascular progression of melanoma. Patients and Methods A data set of 526 patients from the University of California San Francisco Melanoma Center with 2 years of follow-up or first relapse was studied. The impact of the presence or absence of various prognostic factors on overall survival of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. A matched-pair analysis of NF-κB expression was performed in cases with vascular involvement and increased tumor vascularity versus matched controls lacking these factors. Results Cox regression analysis of factors evaluated by the American Joint Committee on Cancer Melanoma Staging Committee reproduced the powerful impact of tumor thickness and ulceration in this data set. With the inclusion of vascular factors such as tumor vascularity and vascular involvement, ulceration was no longer significant in predicting overall survival. By multivariate analysis, vascular involvement and tumor vascularity were the strongest predictors of melanoma outcome. Tumor vascularity seems to be a precursor of both vascular involvement and ulceration. A matched-pair tissue array analysis demonstrated the significant correlation between overexpression of NF-κB–p65 and the development of vascular factors. Conclusion Vascular factors play an important role in the progression of malignant melanoma. Ulceration may be a surrogate marker for the interactions between melanoma and the tumor vasculature. NF-κB seems to play an important role in the development of these factors.

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