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Mar 2024 DOI 10.14302/issn.2572-3030.jcgb-24-4970
Melanoma treatment has improved significantly with the development of immune checkpoint inhibition (ICI), which has greatly enhanced the survival rates of patients with metastatic melanoma. However, a significant number of patients do not respond well to ICI treatment and experience progression. This highlights the critical need for practical means to track melanoma patients' response to ICI. To address this issue, the patterns of circulating miRNAs were studied in liquid biopsies of melanoma patients. These miRNAs have the potential to provide essential information regarding the cancer stage, progression, and the presence of PD-L1 in tumor tissue. A sophisticated flow cytometric test was used to measure up to 63 different miRNAs at once. The study identified a combination of nine miRNAs that are capable of distinguishing between different stages of melanoma, particularly stage IV. Additionally, five miRNAs were pinpointed which are downregulated in patients who do not respond to ICI treatment. Furthermore, two miRNAs were found that correlate to the level of PD-L1 in tumor tissue, and low levels of miR-150-5p were linked to poorer overall survival. These findings suggest that circulating miRNAs could serve as valuable markers to predict the effectiveness of ICI, provide insights into the cancer's stage and PD-L1 status, and ultimately help physicians make better treatment decisions in the future. However, further research is needed to confirm these findings and establish their clinical usefulness.
Mar 2024 DOI 10.14302/issn.2997-2108.jcc-23-4838
Among the reproductive cancers cervical cancer has special place, because the second most frequent cause of cancer-related death among women worldwide. The studies suggested that the PI3K/mTOR/AKT signaling pathway is associated with certain reproductive tumors. A lot of research is ongoing for understanding this pathway evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that targeted PI3K/AKT. In this a single-arm study included 34 Azerbaijan population woman with HPV-negative cervical tumors. The core genes of PAM signaling pathway were analyzed using RT-PCR method. Our preliminary results suggested that tumorgenesis of HPV-negative cervical cancer patients approximately 25% associated with dysregulation of PAM signaling pathway reason which are core genes alteration. The overall survival times in the PAM-active and PAM-stable patients were not significantly varies. However, the main factor for overall survival times were treatment strategy: both PAM-active and PAM-stable patients who received radiation therapy alone had a shorter overall survival than patients who received radiation plus chemotherapy. The patients with alteration of ATK1 and mTOR genes in PAM signaling pathway had poor prognosis then patients with PIK3CA and PTEN mutation
May 2023
Background and Aim Breast cancer is the second most common cause of brain metastases after lung cancer. However, the incidence of cerebral metastases from breast cancer has increased during the last years. The purpose of this study is to determine the prognostic value of chemotherapy after whole-brain radiotherapy for patients with brain metastases from breast cancer. Methods We analyzed retrospectively 63 records of patients diagnosed with brain metastases from breast cancer and treated in the radiotherapy department at the Salah Azaiz Institute of oncology over a 5-year period between 2007 and 2011. All patients received whole-brain radiotherapy. Only 4 patients had surgical resection of the metastases before radiotherapy and 36.5% of patients received systemic treatment after irradiation. Results Overall survival was 19% at 1-year and median survival was 4,5 months. Univariate analysis indicated that systemic treatment after irradiation was correlated significantly with longer survival. (p=0,046). Conclusion Determining prognostic factors might help optimize individual treatment for metastatic breast cancer. The results of our study suggest that chemotherapy is more effective on brain metastases after irradiation. This can be explained by the fragilization of the blood-brain barrier by radiation and subsequently a better passage of cytotoxic agents.
Oct 2022 DOI 10.14302/issn.2641-5518.jcci-22-4323
Introduction Primary sarcomas of the breast are <0.1% of all malignant tumours of the breast. To date, there are 13 major breast sarcoma series in English literature. This study adds to these series characterizing primary breast sarcoma among Philippine patients. Methods All breast biopsies from the pathology records of the University of the Philippines-Philippine General Hospital (UP-PGH) were searched for breast sarcoma cases from January 2000 to December 2010. Metaplastic carcinomas and phyllodes tumors were excluded. Results There were 52 patients (45 female, 7 male) ranging in age 25-83 years (median 46 years). Majority had lump, ten cases with pain. No history of previous cancer was given. No history of prior radiation was found. Histopathological diagnoses were spindle cell sarcoma (n=13), fibrosarcoma (n=6), liposarcoma (n=6), MPNST (n=5), stromal sarcoma (n=5), angiosarcoma (n=4), MFH (n=4), leiomyosarcoma (n=3), rhabdomyosarcoma (n=3), chondrosarcoma (n=2), and synovial sarcoma (n=1). Tumors were with grade 1 (n=18), grade 2 (n=8), and grade 3 (n=10). Necrosis was noted in 6 cases. Simple mastectomy was done in 19 cases (37%), MRM in 31 cases (59%), while 2 far advanced had no surgery (3%). None had adjuvant radiotherapy or chemotherapy. The duration of follow-up for 45 patients ranged from 1 – 117 months, excluding those who were lost to follow-up. All 15 deaths were due to progressive disease. Recurrences were observed in 9 patients. The disease-free survival (DFS) and overall survival (OS) was 73%and 75%, respectively. On multivariate analysis, DFS and OS were significantly correlated with size (HR=113.63; p=0.019 and HR=77.36; p=0.037), grade (HR=20.73 ; p=0.003andHR= 39.57; p= 0.004), and having a histology of angiosarcoma (HR=35.20 ; p=0.005and HR= 50.74; p=0.007), respectively. Conclusion Sarcoma remains an important clinical entity among primary breast cancers.
Nov 2020 DOI 10.14302/issn.2766-8630.jrnm-20-3594
Purpose The purpose of this study was to assess the efficacy (overall survival, local control, progression free survival (PFS) and toxicities between two dimension (2D) and three dimension (3D) CT guided brachytherapy without using interstitial needles in cervical cancer patients. Material and Methods A retrospective case-control study was performed in Figo stage IB-IVA cervical cancer patients treated between March 1990 and August 2018. Concurrent chemoradiation using external beam radiotherapy followed by brachytherapy (BT) was the treatment method used in all patients. Clinical endpoints were overall survival, local control, progression free survival, acute toxicities and late toxicities. Results A 102 cervical cancer patients were included,52 patients have been treated with 2D and 50 patients with 3D using CT scan brachytherapy without interstitial needles. Baseline characteristics were similar between both groups. External beam was used in all patients during concurrent chemoradiation period before brachytherapy. All patients completed the treatment. Similar 3-year overall survival and local control was reported between 2D and 3D techniques. Overall 3-year survival rate was 95.7% in 2D and 91.8% in 3D brachytherapy (P value = 0.188). Local control at the 3 year follow up was 88.6% in 2D and 93.3% in 3D (P value = 0.571). Progression free survival was better in 2D rather than 3D (86.13% in 2D vs 27.4% in 3D, p value = 0.006). No grade 3 or 4 toxicity in 3D technique was observed whereas there are 1.9% of grade 3 acute GI toxicity and grade 3 late GI and GU toxicities in 2D technique (7.7% and 5.8 %). The 3D brachytherapy significantly reduced acute grade 2-3 GI side effect and grade 2-3 late GU side effect (acute GI 25% in 2D vs 4% in 3D, late GU (56% in 2D vs 16% in 3D). Conclusion Using CT guided 3D brachytherapy in treatment of cervical cancer showed similar outcomes in survival and local control but reduced toxicity compared to the 2D technique. Disease progression including metastasis was found better in the 2D brachytherapy technique. CT guided brachytherapy helped reduce dose to organs at risk and long term follow up for survival outcome and toxicities was needed.
Nov 2018 DOI 10.14302/issn.2689-5773.jcdp-18-2435
Theobjective of reviewing Hairy Cell Leukaemia may be achieved by emphasising the condition as a category of chronic lymphocytic leukaemia with hair like protrusions of the cytoplasm situated on the aberrant B cell surface. An infrequent disorder, hairy cell leukaemia contributes an estimated 2% of lymphoid malignancies with a male predominance ( M:F ::4-5:1). A majority (90%) of instances depict a mutant immunoglobulin heavy chain variable region (IGHV). The haematopoietic stem cells (HSCs) elucidate a B raf proto-oncogene( BRAF V600E gene- 7q34). An enlarged spleen may be discerned along with pancytopenia as a presenting symptom. The morphology of specific hairy cell leukaemia may be on account of an in vitro interaction of primary hairy cells with BRAF genes and MEK inhibitors, which incite a prominent MEK - ERK dephosphorylation, thereby curtailing transcriptional outpourings of the RAS- RAF- MEK-ERK pathway. Bone marrow aspiration or bone marrow trephine biopsy may be inadequate for diagnosis in 30%-50% individuals on account of extensive fibrosis and the bone marrow sections depict a characteristic interstitial infiltration of leukaemia cells.. Reticulin stains exhibit broad, dense reticulum fibres surrounding the individual or aggregates of leukaemia cells with fibrotic extensions into the abutting bone marrow. The immune reactivity of classic hairy cell leukaemia is concurrent CD19+ CD20+,CD 11c+, CD25+, CD103+ and CD123+. Immune staining for CD20+, annexin 1 and VE1 (a BRAF V600E stain) validates the diagnosis and analyses the extent of malignant bone marrow infiltration. Application of inhibitors of BRAF V600E gene is efficacious in patients resistant to standard therapy. An enlarged spleen beyond 3 centimetres of the left costal margin, a white blood cell count greater than 10000 cells/µL , circulating hairy cells in the peripheral blood greater than 5000 cells/µL and a β 2 micro-globulin level exceeding twice the normal range of 3 µg/ml delineate an inferior outcome with resistance to purine analogues (PNAs). CD38+ elucidation ensures a worse prognosis as does the lack of an IGHV mutation with a reduced overall survival,. A lack of BRAF genetic mutation in 10% -20% of hairy cell leukaemia comprises of inferior prognosis.
Feb 2018
Gastric cancer is one of the most common types of cancer in the world, usually diagnosed at an advanced stage. Despite the advances in specific anticancer agents' development, the survival rates remain modest, even in early stages. HER2 overexpression was identified on 15% - 20% of gastric cancer patients. Trastuzumab-based chemotherapy provides obvious efficacy improving outcomes of HER2 positive gastric cancer patients. We performed a meta-analysis to estimate the efficacy of the addition of trastuzumab over chemotherapy. We identified randomized controlled trials (RCTs) which compare the addition of trastuzumab therapy to chemotherapy alone reporting progression-free survival (PFS), time to progression (TTP), overall survival (OS), and/or response rates as our eligible trials. Night trials including 1101 patients were eligible for analysis. Trastuzumab therapeutic partners were cisplatin (9 RCTs), 5-fluorouracil (8 RCTs), capecitabine (6 RCTs), irinotecan (1 RCTs), docetaxel (1 RCTs), oxaliplatin (1 RCTs), and leucovorin (1 RCTs). The addition of trastuzumab agents improved OS (HR = 0.80; 95% CI = 0.72 - 0.89), PFS (HR = 0.70; 95% CI = 0.59 - 0.83), TTP (HR = 0.69; 95% CI = 0.57 - 0.83), and overall response rate (RR = 1.22; 95% CI = 0.94 - 1.59), DCR (RR = 1.19; 95% CI = 1.10 - 1.28). Our meta-analysis affirmed the efficacy of adding trastuzumab agent to chemotherapy in HER2 positive gastric cancer.
Jan 2017 DOI 10.14302/issn.2379-8572.joa-16-1399
Aim: The relation between inflammation and cancer has been known since the 19th century. However, investigations on the pathogenesis and pathophysiology of this relation have begun recently. It was demonstrated that increased neutrophil/lymphocyte ratio is a poor prognostic factor in some malignancies. The present study aimed to determine whether preoperative neutrophil/lymphocyte ratio has a prognostic value in larynx cancer. Method: Preoperative blood analyses of 139 patients, who underwent subtotal or total laryngectomy for larynx cancer between 2003 and 2013 at Marmara University School of Medicine, Department of ENT, were retrospectively evaluated. Neutrophil/lymphocyte ratio (NLR) was calculated dividing absolute neutrophil count by absolute lymphocyte count. Optimal cut-off value for NLR was determined by receiver operating characteristics (ROC) curve analysis. Statistical analyses were done using IBM SPSS statistic 22.0 (IBM SPSS, Turkey) and Med Calc 12.3.0 package programs. Results: The sensitivity of NLR in predicting advanced-stage (Stage 3 and 4) squamous-cell carcinoma of the larynx (LSSC), T4 LSSC and lymph node metastasis at different cut-off values were 66.2%, 83.9% and 73.8%, respectively and the specificity was 76.7%, 66.2% and 65.2%, respectively. Staging according to T classification revealed that NLR significantly increases with tumor stage (p<0.001). Statistically significant relation was determined between lymph node metastasis of tumor and neutrophil/lymphocyte ratio (p=0.003). Comparing overall survival (OS) and disease-free survival (DFS) between the cases with NLR <3.02 and the cases with NLR >3.02, it was demonstrated that OS and DFS are significantly lower in the cases with NLR<3.02 (p: 0.001 vs. p<0.05 for OS and p: 0.013 vs. p<0.05 for DFS) Conclusion: NLR increases with the stage of disease in LSSC. NLR is a simple, cheap, repeatable and valuable parameter that can be obtained from routine analyses, gives information about poor prognosis and survival, and is able to predict T4 LSSC, advanced-stage LSSC (stage 3-4) and lymph node metastasis.