PMEPA1 gene isoforms to indicate disease progression in solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16580-e16580 ◽  
Author(s):  
Shashwat Sharad ◽  
Zsã³fia Sztupinszki ◽  
Zoltan Szallasi ◽  
Inger L. Rosner ◽  
Shiv Srivastava ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Disease Progression ◽  
Solid Tumors ◽  
Progression Free Survival ◽  
Overall Survival Rate ◽  
Free Survival ◽  
Gene Isoforms

e16580 Background: Dysfuncitons of androgen and TGF-β signaling play important roles in prostate tumorigenesis. PMEPA1 gene has been defined as an androgen and TGF-β responsive gene which inhibits androgen and TGF-β signaling via negative feed-back loops. Our previous data has established that PMEPA1 distinct isoforms ( PMEPA1-a and PMEPA1-b) with disparities within N-terminus protein sequences navigate different androgen/TGF-β signaling regulations. In this study, the roles of PMEPA1 isoforms in disease progressions were investigated in solid tumors of prostate (CaP), breast, lung and colon. Methods: RNA seq data from total 2479 solid tumor samples in the TCGA dataset were used to study the correlation between expressions of PMEPA1 isoforms and disease progression including Gleason score, pathology stages, progression free survival rate (PFS) and overall survival rate (OS). The cohort is composed of 482 prostate, 1049 breast, 499 lung and 449 colon cancer patients. Results: In CaP, the TCGA data analysis showed that lower transcript level of PMEPA1-b isoform associated with higher Gleason scores and lower progression free survival rate (PFS) (P = 0.014) and worse overall survival rate (OS) (P < 0.01). The ratio of mRNA levels of PMEPA1-a versus PMEPA-b indicated higher Gleason score, lower PFS rate (P = 0.0063) and worse OS rate (P = 0.0042). In contrast, higher expression of both PMEPA1-a and PMEPA- b associated with lower PFS (P = 0.023 and 0.028, respectively) in breast cancer. And the enhanced ratio of PMEPA1-a/ b was also found to indicate lower PFS (P = 0.016) and worse OS (P = 0.016) in breast cancer. Similarly, the increased transcript levels of PMEPA1-a and PMEPA1-b isoforms significantly associated with lower PFS and worse OS rates in lung and colon cancer. The expression of PMEPA1 isoforms was not found to associate with pathology stages of diseases. Conclusions: Our data establish the biomarker potential of PMEPA1 gene isoforms ( a and b) indicating more aggressive disease progressions in 4 solid tumors, further underscoring the PMEPA1 isoform specific biological functions to differentiate regulation of androgen and TGF-β signaling in cancer cells.

scholarly journals Experience of Hepatocellular Cancer Therapy with Multikinase Inhibitors in the Republic of Bashkortostan

2020 ◽  
Vol 10 (3) ◽  
pp. 183-189
Author(s):  
Sh. Kh. Gantsev ◽  
O. N. Lipatov ◽  
K. V. Menshikov ◽  
D. S. Tursumetov ◽  
Kh. S. Saydulaeva
Keyword(s):  
Overall Survival ◽  
Chronic Hepatitis ◽  
Survival Rate ◽  
Survival Rates ◽  
Elevated Serum ◽  
Malignant Neoplasm ◽  
Progression Free Survival ◽  
Control Group ◽  
Overall Survival Rate ◽  
Free Survival

Introduction. Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. During the early stages, HCC is asymptomatic, which makes X-ray examination a particularly important diagnostic tool. According to WHO data, the mortality rate from HCC was 782,000 in 2018. HCC is associated with a number of risk factors: a high viral load, liver cirrhosis, detected HBeAg and elevated serum HBsAg levels. Inhibitors of tyrosine kinase receptors increase the overall survival and progression-free survival rates in patients with metastatic HCC. In this article, we conduct an analysis of results of the REFLECT study obtained for Russian patients by the Republican Clinical Oncological Dispensary, Ufa.Materials and methods. The experimental group included 9 patients (52.9%) receiving Lenvatinib. The control group included 8 patients (47.1%)) underwent therapy with Sorafenib at a dose of 800 mg per day 7 (41.17%) patients had a history of chronic hepatitis, of which hepatitis B and chronic hepatitis C was confirmed in 6 and 1 cases, respectively.Results and discussion. Over the period from 2017 up to the present, progression-free survival was observed in three patients (17.6%), of which 2 and 1 received Lenvatinib and Sorafenib, respectively. Overall survival was 10.5 months. The median overall survival rate in the experimental and control groups was 9.8 and 11.2 months, respectively. These parameters are considered comparable, provided that the sample was small.Conclusions. The use of Lenvatinib demonstrated the efficacy comparable to that of Sorafenib in terms of the overall survival rate in patients with inoperable HCC. Lenvatinib allowed statistically and clinically significant improvement in the progression-free survival and time to progression to be achieved. 

Efficacy of immunotherapy with PD-1 inhibitor in colorectal cancer: a meta-analysis

2020 ◽  
Vol 9 (18) ◽  
pp. 1285-1292
Author(s):  
Shengqi He ◽  
Dongqing Hu ◽  
Haixia Feng ◽  
Ye Xue ◽  
Jin Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Objective Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Overall Survival Rate ◽  
Free Survival

Aim: PD-1 inhibitors have a leading role among immunotherapy while its efficacy on colorectal cancer (CRC) patients did not reach consensus and the small sample size remains as a limitation. Therefore, we undertook a meta-analysis on the effects of the monotherapy anti-PD-1 inhibitors in treating metastatic colorectal cancer (mCRC). Materials & methods: We searched databases to identify studies on efficacy of anti-PD-1 inhibitor on CRC. Objectives were objective response rate, progression-free survival rate, disease control rate and overall survival rate with their 95% CI. Results: The overall survival rate at 1-year was 64.2% (95% CI: 0.46–0.83). Disease control rate was 56.5% (CI: 0.27–0.86) and the objective response rate as 19.7% (CI: 0.08–0.32). The 1-year-progression-free survival rate was 38.4% (CI: 0.12–0.66). Sensitivity analysis and subgroup analysis were also conducted. Conclusion: The monotherapy anti-PD-1 inhibitors are effective in treating mCRC and could be a new option for dMMR mCRC patient in first-line treatment.

scholarly journals Efficacy and Toxicity of Folfoxiri for Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 7 (24) ◽  
pp. 4244-4249
Author(s):  
Trinh Le Huy ◽  
My Hanh Bui ◽  
Toi Chu Dinh ◽  
Hoang Thi Hong Xuyen
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Overall Survival Rate ◽  
Free Survival ◽  
Colorectal Cancer Patients

BACKGROUND: In recent times, scientists have found new treatments for colorectal cancer patients. AIM: The study is to evaluate the efficacy and toxicity of triplet combination chemotherapy of 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) for patients with metastatic colorectal cancer in stage IV. METHODS: Uncontrolled clinical trial carried on 39 stage IV colorectal cancer patients. RESULTS: The overall response rate of the treatment was 79.4%. The average progression-free survival was 13.4 ± 9 months. The overall survival rate at 12th month and 24th month were 90% and 76%, respectively. The proportion of granulocytopenia was 48.9%, no grade 3 or 4. Side effect beyond hematology was most seen in hepatic toxicity with 52.5%, mainly at grade 1. Vomiting was 18.3%, all at grade 1. Other adverse event was very low at percentage. CONCLUSIONS: The triplet combination FOLFOXIRI chemotherapy improves the outcome of patients with metastatic colorectal cancer regarding rate of response, overall survival rate and progression-free survival, and the level of toxicity was acceptable.

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 Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

scholarly journals Could Primary Tumor Resection Improve Survival in Metastatic Breast Cancer?

2021 ◽  
Vol 9 (07) ◽  
pp. 422-428
Author(s):  
Rafaela Aparecida Dias de Oliveira ◽  
Lyvia Aparecida Dias de Oliveira ◽  
Marília Davoli Abella Goulart ◽  
Maria Clara Faustino Linhares
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Systemic Therapy ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Tumor Resection ◽  
Free Survival

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size.  Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.

scholarly journals A Cross Sectional Study on Loco-Regional Recurrences and Overall Survival Rate among Patients with Stage II (T2N0M0) Glottis Carcinoma Treated with Chemoradiation and Surgery

2021 ◽  
Vol 8 (04) ◽  
pp. 219-223
Author(s):  
Niharika Darasani
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Squamous Cell ◽  
Stage Ii ◽  
Overall Survival Rate ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Tertiary Teaching ◽  
Voice Preservation ◽  
Disease Specific

BACKGROUND Single modality treatment for stage I and stage II squamous cell carcinomas of glottis region gave excellent results. Since a long time these are treated either with definitive radiation therapy or surgical excision with endoscopes. There was not much difference with regard to voice preservation, local recurrence and disease-free survival period. Our aim was to study the clinical presentation and management protocol of glottis carcinoma in a tertiary hospital and observe the final outcome of stage II (T2N0M0) glottis carcinoma and specific factor for survival in patients treated with surgery, radiotherapy and concurrent chemoradiation. METHODS 43 patients of glottis carcinoma stage II (T2N0M0) attending a tertiary teaching hospital between May 2015 and April 2017 were included in the study. Demography and smoking status of subjects were recorded. Staging of the disease was according to American Joint Committee on Cancer (AJCC) Staging System 7th edition. Paraglottic space infiltration was taken as a criteria to upgrade the staging. The overall survival rate, recurrence free survival, disease specific survival rate and laryngeal function preservation rate were calculated. RESULTS Out of 43 patients, males were 90.69 % and 09.30 % were females. Male to female ratio was 10.57 : 1. Mean age was 58.62 ± 2.35 years. 67.44 % were current smokers, 27.90 % were former smokers and 02.32 % were non-smokers. The overall survival scores and disease specific survival was 100 % with 11.62 % locoregional recurrences. The voice preservation was 86.04 %. Radiotherapy was used in 72.09 %, chemoradiation in 18.60 % patients and 11.62 % patients underwent surgery. 11.62 % patients presented with locoregional recurrence during 24 months of follow up. 02.32 % patients had to undergo tracheostomy. CONCLUSIONS The overall survival scores and disease specific survival were 100 % with 11.62 % loco-regional recurrence. Voice preservation was 86.04 %. Proactive prevention rather than escalation of treatment protocol gives better prognosis. KEYWORDS Glottis, Larynx, Supra Glottis, Sub Glottis, Squamous Cell Carcinoma, Chemo Radiation and Trans Oral Laryngeal Surgeries

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