Association of immune markers and Immunoscore with survival of stage III colon carcinoma (CC) patients (pts) treated with adjuvant FOLFOX: NCCTG N0147 (Alliance).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
Frank A. Sinicrope ◽  
Qian Shi ◽  
Fabienne Hermitte ◽  
Erica N Heying ◽  
Al Bowen Benson ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Stage Iii ◽  
Immune Markers ◽  
Free Survival ◽  
Resected Stage ◽  
Infiltrating Lymphocytes

3579 Background: Tumor infiltrating lymphocytes (TIL) indicate a host immune response that may influence survival. Immunoscore was developed using CD3+ and CD8+density and location in primary CC pts with pooled stages, varying treatment and follow-up. We determined if individual immune markers and/or Immunoscore are prognostic in resected stage III CC pts (N=600). Methods: CD3+ and CD8+ T-cell or CD20+ B lymphocyte density in central tumor (CT) and invasive margin (IM) was evaluated by immunostaining and quantified by image analysis. Immunoscore was calculated on a scale of I0 to I4 with high densities of CD3+ and CD8+in both CT and IM scored as I4; low densities scored as I0. Associations with disease-free survival (DFS) were evaluated by multivariable Cox regression adjusting for covariates. Results: Data for CD3+, CD8+ and CD20+ were generated (N=595). Higher density of CD3+ CT, CD3+ IM and CD8+ IM were associated with longer DFS adjusting for covariates (Table). CD3+ IM had the strongest association with DFS, and was stronger in left-sided (HRadj.=0.81, 95% CI, 0.70-0.94, padj.= 0.0049) vs right-sided (HRadj.=0.93, 95% CI, 0.85-1.0 padj.=0.52) tumors (pinteraction=0.039). Higher density of CD3+ IM was associated with older age (p=0.034), T1/2 (p<.0001), N1 (p=0.017), right-sided (p=0.013), high TILs (p=0.0008), and deficient MMR (p=0.0003). Using a prior Immunoscore risk stratification, higher scores were associated with better DFS (HR.=0.62, CI, 0.44-0.87, p=0.006) (Table). Conclusions: Densities of CD3+ and CD8+, especially at IM, are individually prognostic in FOLFOX-treated pts. Association of CD3+IM with prognosis differed by primary CC site. Immunoscore was strongly prognostic, and this result provides validation in a clinical trial cohort. [Table: see text]

scholarly journals Efficacy of Tumor-Infiltrating Lymphocytes Combined with IFN-α in Chinese Resected Stage III Malignant Melanoma

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Li ◽  
Linping Xu ◽  
Yaomei Wang ◽  
Lingdi Zhao ◽  
Daniel B. Kellner ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Surgical Excision ◽  
Stage Iii ◽  
Time Points ◽  
Measured Time ◽  
Resected Stage ◽  
Infiltrating Lymphocytes ◽  
Better Than

Background. This study aims to explore the efficacy of tumor-infiltrating lymphocytes (TIL) along with interferon-α (IFN-α) to treat stage III malignant melanoma (MM) patients in China. Methods. Between May 2010 and October 2014, 77 patients of stage III MM who underwent surgery were collected in this study. These patients were divided into two groups: patients who received TIL + IFN-α ± RetroNectin-activated cytokine-induced killer cells (R-CIK) in Arm 1 (n=27) and IFN-α ± R-CIK in Arm 2 (n=50) as adjuvant therapy. The primary endpoints were disease-free survival (DFS) time and DFS rates measured at time points of 1, 2, and 3 years. The secondary endpoints were overall survival (OS) rates measured at time points of 1, 2, 3, and 5 years as well as OS as evaluated by Kaplan-Meier. Results. Our results indicated that the median DFS and OS in Arm 1 were significantly better than those in Arm 2. The data also demonstrated that DFS rate and OS rates in Arm 1 were significantly better than those in Arm 2 at all measured time points. Conclusion. Patients who undergo surgical excision of stage III MM appear to enjoy prolonged DFS and OS when treated with TIL + IFN-α compared to IFN-α alone.

scholarly journals Efficacy of Concurrent Chemoradiotherapy In Subgroups of Stage III Nasopharyngeal Carcinoma: An Analysis Based On 10-Year Follow-Up

2021 ◽  
Author(s):  
Lei Wang ◽  
Wu Zheng ◽  
Wanqin Cheng ◽  
Dehuan Xie ◽  
Feifei Lin ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Rank Test ◽  
Free Survival ◽  
N2 Disease

Abstract PurposeTo evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT).Methods272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy (CCT) were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using Kaplan-Meier method and log-rank test.ResultsThe median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387-9.428, P=0.009), DFS (HR 2.417, 95% CI 1.291-4.423, P=0.006), and OS (HR 3.024, 95% CI 1.385-6.602, P=0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P=0.005), DFS (71.9% vs. 39.4%, P=0.001) and OS (80.0% vs. 50.5%, P=0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P>0.05). ConclusionCCRT is an effective therapy in stage III NPC, especially for patients with N2 disease but N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Association of plasma adiponectin with tumor infiltrating lymphocytes and survival in patients with stage III colon cancer (NCCTG N0147; Alliance).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3591-3591
Author(s):  
Frank A. Sinicrope ◽  
Qian Shi ◽  
Thomas C. Smyrk ◽  
Richard M. Goldberg ◽  
Steven J. Cohen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Stage Iii ◽  
Inverse Association ◽  
Plasma Adiponectin ◽  
Time To Recurrence ◽  
Infiltrating Lymphocytes

3591 Background: Adiponectin is a peptide hormone exclusively secreted by adipocytes that plays a role in immune regulation and in the host inflammatory response to cancer. We examined postsurgical adiponectin levels in relationship to tumor infiltrating lymphocytes (TILs), clinicopathological features, vitamin D status, and patient survival in participants in a phase 3 trial of adjuvant chemotherapy. Methods: Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon carcinoma who received adjuvant FOLFOX +/- cetuximab. TIL densities were determined at light microscopy in routine histopathological sections. The associations between adiponectin and 25(OH)D, TILs, other factors were evaluated by Fisher’s Exact, Chi-squared, t-test, and Kruskal-Wallis tests where appropriate. The association between adiponectin or 25(OH)D with disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS) were evaluated by multivariable Cox regression, adjusting for body mass index (BMI), race, T, N stage, performance status, tumor location, TILs, BRAF/KRAS, and mismatch repair status. Results: A statistically significant and inverse association between adiponectin level and BMI was observed with lower levels found with obesity (BMI > 30 kg/m2) [p < 0.001]. The level of adiponectin was significantly lower in men vs women (p < 0.001), in blacks vs whites or Asians (p < 0.032), and in patients with fewer regional lymph node metastases (N1 vs N2 stage, p = 0.011). A significantly lower level of adiponectin was found in patients whose tumors had high vs low TIL densities (p = 0.040), but was unrelated to 25(OH)D. Insufficiency of 25(OH)D ( < 30 ng/ml) was detected in 291 (49%) of patients and was not associated with TILs. By multivariable analysis, adiponectin was not associated significantly with patient DFS (HRadj= 0.98, 95% CI 0.74-1.29, padj= 0.88) nor with OS nor time-to-recurrence (TTR). TIL densities were significantly prognostic, but 25(OH)D was not (DFS: HRadj= 1.12, 95% CI 0.85-1.47, padj= 0.44). No significant interaction was observed for adiponectin with TILs for the association with DFS. Conclusions: Lower adiponectin levels were associated with significantly increased TIL densities in colon cancers, indicating an enhanced anti-tumor immune response. In contrast to TILs, adiponectin was not independently associated with patient outcome. Nearly one-half of stage III patients were vitamin D insufficient, although 25(OH)D was not prognostic.

scholarly journals Efficacy of concurrent chemoradiotherapy in subgroups of stage III nasopharyngeal carcinoma: an analysis based on 10-year follow-up

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lei Wang ◽  
Zheng Wu ◽  
Wanqin Cheng ◽  
Dehuan Xie ◽  
Feifei Lin ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Rank Test ◽  
Free Survival ◽  
N2 Disease

Abstract Purpose To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT). Methods A total of 272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test. Results The median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387–9.428, P = 0.009), DFS (HR 2.417, 95% CI 1.291–4.423, P = 0.006), and OS (HR 3.024, 95% CI 1.385–6.602, P = 0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P = 0.005), DFS (71.9% vs. 39.4% P = 0.001) and OS (80.0% vs. 50.5%, P = 0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P > 0.05). Conclusions CCRT is an effective therapy in stage III NPC, especially for patients with N2 disease, but IMRT alone may be adequate for N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): Results from NCCTG Intergroup Phase III Trial N0147.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA3507-CRA3507 ◽  
Author(s):  
S. R. Alberts ◽  
D. J. Sargent ◽  
T. C. Smyrk ◽  
A. F. Shields ◽  
E. Chan ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Kras Status ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Resected Stage

CRA3507 Background: FOLFOX is standard adjuvant therapy for stage III CC. Adding Cmab to FOLFOX benefits pts with metastatic CC WT KRAS tumors. N0147 assessed the potential benefit of Cmab added to FOLFOX. Methods: 21-56 days following resection and informed consent, KRAS status was centrally determined. Pts with wtKRAS CC were randomized to 12 biweekly cycles of oxaliplatin 85 mg/m2 d1, with leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 (mFOLFOX6), without (arm A) or with Cmab (arm D) 250 mg/m2 d1&8, with Cmab at 400 mg/m2, cycle 1, d1. Primary endpoint was 3-yr disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Planned accrual of 2,070 wtKRAS pts provided 90% power to detect hazard ratio (HR) of 1.33 with 2-sided α=0.05; with interim analyses after 25%, 50%, and 75% of planned events. Results: 1,760 wtKRAS pts (Arm A-858, Arm D-902) were enrolled at the time of closure; median follow-up on 1,624 pts is 15.9 months. Trial closed to accrual when preplanned interim analysis after 50% of planned events demonstrated no benefit to addition of Cmab. 3-yr DFS favored FOLFOX alone (HR 1.18, 95% CI 0.92-1.52; p=0.33). No benefit of Cmab was observed in any subgroups assessed. Any grade ≥ 3 AE, diarrhea, and failure to complete 12 cycles was significantly increased in arm D. Increased toxicity and greater differences in all outcomes were observed in pts aged ≥ 70 ( Table ). Conclusions: In this randomized phase III trial the addition of Cmab to mFOLFOX6 was of no benefit for pts with resected stage III wtKRAS CC. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

Pituitary surgery as alternative to dopamine agonists treatment for microprolactinomas, a cohort study

2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  
Keyword(s):  
Dopamine Agonists ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Pituitary Surgery ◽  
Cerebrospinal Fluid Leakage ◽  
Neurosurgical Department ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

Adjuvant therapy with alpha-interferon in radically resected stage Il and III renal cell carcinoma

1992 ◽  
Vol 59 (1_suppl) ◽  
pp. 160-162
Author(s):  
◽  
Urologico Lombardo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Alpha Interferon ◽  
Free Survival ◽  
Resected Stage

In February 1990, a multicentric randomized study was started to verify the therapeutic efficacy of adjuvant alpha-interferon in Robson's stage II and III renal cell carcinoma. Up to April 1992, 749 radical nephrectomies have been recorded by the 25 participating centers. Stage II and III patients fullfilling selection criteria were 124: 64 were assigned to Interferon therapy and 60 to control. The short follow-up does not allow any evaluation of the relapse rate. Therapy related toxicity was represented by mild fever and flu-like syndrome in 50% of cases and slight leucopenia in 5%. The recruitment of the first 200 randomized patients will end approximately within 1 year. While evaluating the hypothesis of a 20% difference in the 5 year disease-free survival between the two groups recruitment will continue up to a total of 350 cases, in order to verify the 15% hypothesis, too.

Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer

2017 ◽  
Author(s):  
Kelly McLeon
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Reference Standard ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Study Intervention ◽  
Disease Free

The landmark MOSAIC trial examined whether the addition of oxaliplatin to a postoperative adjuvant treatment regimen of fluorouracil and leucovorin affected disease-free survival from colon cancer. The MOSAIC trial established the efficacy of FOLFOX over 5-FU/LV as adjuvant treatment for stage III colon cancer and established FOLFOX4 as the reference standard for adjuvant treatment for stage III disease. This chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.

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