Retrospective cohort study on the safety and efficacy of cetuximab for metastatic colorectal cancer patients: HGCSG0901—Analysis of predictive markers.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 683-683
Author(s):  
Kazuteru Hatanaka ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Takahiro Kogawa ◽  
Hiraku Fukushima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Skin Toxicity ◽  
Kras Mutations ◽  
Free Survival ◽  
Egfr Expression ◽  
Kras Status ◽  
Expression Status

683 Background: The anti-EGFR antibody Cetuximab (Cmab) do not provide therapeutic effect to patients with KRAS mutations. It has been reported that there is no correlation between the staining intensity of EGFR and efficacy of Cmab. Moreover, the previous studies have suggested that the intensity of skin toxicity that occurs after the administration is a predictive marker of Cmab. Methods: Of 269 cases registered in the multi-institutional retrospective study (HGCSG0901) treated with Cmab, 252 patients for 3rd line or after treatment line were analyzed. Each degree of skin toxicity, KRAS mutation status and EGFR expression status, respectively, were analyzed for response rates, progression-free survival (PFS) and overall survival (OS). The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each regimen in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status: wild type (WT)/mutant type (MT): 135/32, EGFR status: positive/negative: 210/38, Skin toxicity: Grade 0/1/2/3: 31/50/128/43. Analysis of KRAS status: Response rate: WT 23.7%/MT 6.3% (p=0.028), Progression-free survival: WT 4.8 months /MT 2.1 months (p<0.001), Overall survival: WT 9.9 months/MT 5.3 months (p=0.003). There was a significant correlation between the degree of skin toxicity and efficacy. However, EGFR expression status showed no differences in efficacy. Conclusions: Here, we reported the results of efficacy analysis for each predictive marker of Cmab. As with previous reports, patients with KRAS mutations did not benefit from Cmab. Degree of skin toxicity was a useful indicator of effectiveness after starting treatment, whereas EGFR status was not effective predictor in daily practice setting.

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer (mCRC): Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial—Comparison of the efficacy of KRAS status.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 536-536
Author(s):  
Michio Nakamura ◽  
Satoshi Yuki ◽  
Masayoshi Dazai ◽  
Yoshimitsu Kobayashi ◽  
Takashi Kato ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Rank Test ◽  
Wild Type ◽  
Target Number ◽  
Mutant Type ◽  
Free Survival ◽  
Kras Status

536 Background: Mutations of the KRAS gene were identified as a predictive marker in mCRC for anti-EGFR antibody. Previously reported data suggest that the longer overall survival (OS) observed with bevacizumab (BV) treatment in mCRC is independent of alterations in the KRAS status. We analized efficacy of BV combined irinotecan and S-1 (IRIS/Bev) in mCRC relative to KRAS status. Methods: In the retrospective analysis (n=53) of patients who participated in the Phase II trial of IRIS/Bev, additional statistical analyses were done with data from KRAS mutational analyses. In this trial, eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival (PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRASin terms of PFS and OS. All statistical tests were performed using SPSS. Results: The target number of 53 patients was enrolled as of March 2009. KRAS status was assessed in 43 patients (wild = 27, mutant = 16). Response rate was 63.0% with wild-type and 68.8% with mutant-type KRAS, that was not significant (p=0.752). The median Progression-free survival was 17.1 months with wild-type and 22.7 months with mutant-type KRAS, that was not significant (p=0.531). And median OS was 49.0 months with wild-type and 38.0 months with mutant-type KRAS, that was not significant(p=0.906) as well. Conclusions: IRIS/Bev provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab: TRICOLORE study) is already started. Comparison of the efficacy of KRAS status is also planned in this study. Clinical trial information: NCT00569790.

scholarly journals PD-1 Expression Status on CD8+ Tumour Infiltrating Lymphocytes Associates With Survival in Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Peiwen Fan ◽  
Xi Li ◽  
Yaning Feng ◽  
Hongchao Cai ◽  
Danning Dong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cellular Expression ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Expression Status

Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

Pilot study of plasma KRAS as a prognostic biomarker in localized pancreas ductal adenocarcinoma (PDAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 294-294
Author(s):  
Benjamin A. Krantz ◽  
Erika Gedvilaite ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Daoqi You ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Disease Status ◽  
Ductal Adenocarcinoma ◽  
Kras Mutations ◽  
Free Survival ◽  
Risk Of Death ◽  
System Disease ◽  
Droplet Pcr

294 Background: Validated predictive and prognostic biomarkers are needed in PDAC. Such biomarkers could predict response and resistance early in treatment. As 95% of PDAC harbor KRAS mutations (mKRAS), plasma mKRAS has utility as a biomarker. We explored the prognostic value of mKRAS in a PDAC cohort at Memorial Sloan Kettering. Methods: 10 mL of whole blood was collected at diagnosis of localized PDAC and early interval CT scan (approx. 8 weeks). DNA was extracted with QIAamp DNA kits (Qiagen, Valencia, CA). Single locus, if tissue KRAS known, or multiplex (G12A, G12C, G12D, G12R, G12S, G12V, G13D) digital droplet PCR (ddPCR) was performed with QX200 (BioRad, Hercules, CA) ddPCR system. Disease status was determined by radiographic, CA19-9 and clinical evaluation. Results: N = 18 enrolled (median age: 65 [range 34-85]). Median time between baseline (B) and interval (I) blood was 2.53 months (range 0.9-6). One had locally recurrent disease, 2 AJCC stage IIa, 1 IIb and 14 III. Three had tissue KRAS G12D mutation, 6 G12V and 9 unknown. Eight had gemcitabine-based treatment, 10 5-FU-based and 5 radiation. See table. mKRAS and CA19-9 at B were not associated with progression free survival (PFS) or overall survival (OS). mKRAS detection at I was associated with shorter PFS/OS (P < 0.01), but CA19-9 was not. mKRAS change from B to I was also associated with PFS/OS. For every 1 copy/mL increase in the change of mKRAS from B to I, the risk of death or progression/death increased by nearly 2 fold after controlling for baseline value (p = 0.01 for OS, p = 0.03 for PFS). Four patients, all undetectable mKRAS at I, went to surgery; 2/4 resected. Conclusions: In this pilot, 59% of localized PDAC patients had detectable mKRAS at B. mKRAS detection at I and change from B to I were associated with PFS/OS supporting that mKRAS early in treatment may be a useful prognostic and predictive marker in localized PDAC. We have initiated a large prospective trial to evaluate the predictive and prognostic potential of plasma mKRAS in advanced PDAC. [Table: see text]

Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity andKRASstatus in patients receiving panitumumab monotherapy

Cancer ◽  
2009 ◽  
Vol 115 (7) ◽  
pp. 1544-1554 ◽  
Author(s):  
Marc Peeters ◽  
Salvatore Siena ◽  
Eric Van Cutsem ◽  
Alberto Sobrero ◽  
Alain Hendlisz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Reported Outcomes ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Free Survival ◽  
Patient Reported

Mutational Aberrations Detected in Mucinous Epithelial Ovarian Cancer of Asian Women

2018 ◽  
Vol 28 (3) ◽  
pp. 428-436 ◽  
Author(s):  
Wen Yee Chay ◽  
Li Lian Kwok ◽  
Wen Ning Tiong ◽  
Sai Sakktee Krisna ◽  
Kiat Hon Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Kras Mutation ◽  
Sanger Sequencing ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Double Negative ◽  
Double Positive ◽  
Kras Mutations ◽  
Free Survival ◽  
Significant Difference

BackgroundMucinous epithelial ovarian cancers (mEOCs) respond poorly to conventional chemotherapy and have a poor prognosis in advanced stages. The genomic landscape for mEOC in the Asian settings is ill defined. We seek to identify various mutational aberrations present in mEOC and correlate them with clinical outcomes.MethodsA total of 199 cases of mEOC were identified from a prospectively maintained gynecologic oncology tumor database. DNA was extracted and analyzed for KRAS mutations by using Sanger sequencing. Further MassArray sequencing was performed on 45 samples. Clinicopathologic correlation was performed with the results obtained.FindingsKRAS mutation status was evaluable in 124 cases. Fifty-five percent (68/124) were KRAS negative, whereas 45% (56/124) harbored a KRAS mutation, lower than that in Western populations. Successful ascertainment of both KRAS and HER2 statuses by Sanger sequencing occurred for 105 cases. The proportion of the double-positive subtype (HER2+ and KRAS positive) was 8% (8/105); double-negative subtype (HER2− and KRAS negative), 34% (36/105); and cases with mutation in either KRAS or HER2, 58% (61/105). The KRAS mutation rate was 44%, 50%, and 29% among Chinese, Indians, and Malays, respectively. There was no significant difference in overall survival (P = 0.952) or progression-free survival (P = 0.635) between KRAS-positive and KRAS-negative patients. Similar results were observed for progression-free survival (P = 0.206) and overall survival (P = 0.440) when outcomes were examined between the 4 groups based on KRAS and HER2 mutation. Patients in the double-negative mutation subgroup had higher risk for death/progression compared with patients in the other 3 mutation subgroups. Further MassARRAY multiplexed profiling was performed in patients with sufficient DNA material (n = 45) and yielded KRAS mutations (n = 16), PDGFRA mutations (n = 3), PIK3CA (n = 1) and KIT (n = 1), and HRAS, FGFR, MET, and NRAS (n = 1 each).ConclusionsOur study provides further knowledge about the mutational aberrations in mEOC in Asian populations. Neither the presence of KRAS mutation nor their correlation with HER2 mutations influenced outcomes.

Complex carbohydrates as a predictive marker in metastatic colorectal cancer (mCRC) cancer patients treated with a vascular endothelial growth factor (VEGF) inhibitor and chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15134-e15134
Author(s):  
Petra Martin ◽  
David William Fennelly ◽  
Pauline Rudd ◽  
Diarmuid O'Donoghue ◽  
Kieran Sheahan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Sialic Acid ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Free Survival ◽  
Complex Carbohydrates

e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as a key driver in oncopathology. Elevated levels of sialic acid sugars affect tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Changes in sialylation can be associated with malignant transformation and with progression and poor prognosis of carcinomas, which can be explained by the recognition of malignant cells by selectins, causing interactions of tumor cells with platelets, leukocytes and endothelium facilitating metastasis. Secreted or proteolytically released carcinoma mucins bearing unusual forms of sialylation can be detected in the bloodstream and are used as diagnostic and prognostic aids. Bevacizumab directly binds VEGF (a glycoprotein) to inhibit angiogenesis. The aim of this study was to analyze the pool of asparagine-linked complex carbohydrates (i.e. the N-glycome), of whole serum to identify sugars that are associated with survival in mCRC patients treated with a VEGF and chemotherapy. Methods: We used our recently developed high-throughput automated platform to precisely measure the levels of complex serum carbohydrates in patients (n = 68) with metastatic colorectal cancer samples of patients who went on to receive bevacizumab and chemotherapy. Survival analysis was performed using the R package ‘survival’. Results: We observed several sialic-acid bearing glycans that correlated with overall survival and progression free survival. A complex tetra-antennary, highly sialylated glycan, known as A4G4S4, correlated with reduced overall survival probability (p = 0.0007, hazard ratio = 1.86). High levels of a sialylated tri-antennary glycan, called A3G3S3 demonstrated significantly reduced progression-free survival (p = 0.002). Conclusions: We believe that sialylated glycans could be excellent predictive markers of response to therapy and warrant further evaluation in clinical trials. Tri and tetra-antennary sialyated glycoproteins were associated with poorer survival in our patient cohort, suggesting that glycans could be key drivers of pathobiology.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

scholarly journals IMMU-08. MODELING UPFRONT GLIOBLASTOMA SURGICAL RESECTION AND STEROID USE REVEALS IMMUNOSUPPRESSIVE CHANGES AND SUGGESTS THAT PERIPHERAL LYMPHOCYTE COUNTS ARE ASSOCIATED WITH TUMOR VOLUME AND PROGNOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii106-ii106
Author(s):  
Balint Otvos ◽  
Tyler Alban ◽  
Matthew Grabowski ◽  
Defne Bayik ◽  
Robert Winkelman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Surgical Resection ◽  
Cd8 T Cells ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Peripheral Lymphocyte ◽  
Steroid Use ◽  
Free Survival ◽  
Steroid Administration

Abstract Glioblastoma (GBM) and its treatment produces systemic immunosuppression, which is being targeted by immunotherapies. However, it remains unclear how surgical resection and steroids specifically in GBM alter the immune system. To further explore this issue, immunocompetent C57Bl/6 mice were intracranially inoculated with syngeneic glioma cells (GL261 and CT-2A) and growth of tumors was evaluated by MRI. Host immune cell populations were analyzed during surgical resection and steroid administration. Mice with surgically resected tumors had a longer median survival compared to mice subjected to tumor biopsies, and had increased bone marrow sequestration of both CD4 and CD8 T cells with corresponding decreased blood lymphocytes. Furthermore, physiologic doses of dexamethasone administered perioperatively decreased tumor edema, but increased the number and proliferative capacity of both marrow and circulating MDSCs while generating no survival benefit. Independent of therapy or dexamethasone, intracranial tumor volume correlated linearly with decreased CD4 and CD8 T cells in peripheral blood, and increased T cell sequestration within the bone marrow. We validated these parameters in steroid-naïve newly diagnosed GBM patients and observed decreased lymphocytes correlated linearly with increased tumor volume. When initial lymphocyte counts in both steroid-naïve and steroid-administered patients were used in univariate and multivariate models predicting progression-free survival and overall survival, decreased initial lymphocyte counts were an independent predictor of decreased progression free survival and decreased overall survival, with steroid use and initial tumor size falling out of significance during stepwise selection. Taken together, tumor volume is linearly correlated with marrow sequestration of lymphoid cells, but both surgery and steroid administration further suppress active immune responses along lymphoid and myeloid lineages. Furthermore, decreasing peripheral lymphocyte counts at diagnosis of GBM indicate an immune system less able to mount responses to the tumor and portent a worse progression free and overall survival.

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