فهرست مطالب
International Journal of Cancer Management
Volume:11 Issue: 11, Nov 2018
- تاریخ انتشار: 1397/09/05
- تعداد عناوین: 10
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Page 1Context: One of the most important achievements in cancer research is the development of cancer immunotherapy. However, only a subset of patients respond to immunotherapy modalities, and few patients respond for a durable time. Here, we review the possible genomic mechanisms of response and resistance to these therapies, which can lead to the selection of responders, who may benefit most from immunotherapy. Evidence Acquisition: We searched PubMed, Scopus, and Web of Science Core Collection with the following keywords: “Immunotherapy, Resistance, Response, Programmed cell death 1 receptor, CTLA-4, Cancer immunity, Tumor Genomics, and Somatic Mutations”.ResultsT cells that specifically recognize cancer-associated antigens, are responsible for the immune system response against cancer. Nonsynonymous mutations, which are transcribed and translated into polypeptides, may generate new epitopes (neoepitopes), which can lead to their presentation on major histocompatibility (MHC) class I molecules and subsequently recognized by the adaptive immune system. Despite the unprecedented durable responses, the majority of patients treated with cancer immunotherapies do not respond to the therapy (primary resistance), and some patients relapse after an initial response (acquired resistance). Resistance to immunotherapy can be a result of tumor cell intrinsic or extrinsic factors. There is correlation between tumor mutation burden (TMB) and response to immunotherapy. In addition, mismatch repair deficient tumors harbor considerably more somatic mutations compared to mismatch repair proficient tumors and respond better to anti-programmed cell death protein 1 (anti-PD1) therapy. Mutations in other DNA repair genes may also affect immunotherapy response.ConclusionsNeoantigen specific T cells constitute a major “active component” for the success of cancer immunotherapies. The genetic damage that confers tumorigenic growth, can also be targeted by the immune machinery to inhibit cancer development and progression. With further validation of experiments, genomics-based approaches can allow to select patients most likely to achieve durable responses to immunotherapy modalities.Keywords: Cancer Genomics, Immunotherapy, Cancer Immunosurveillance, Tumor Mutation Burden
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Page 2BackgroundInvasive lobular carcinoma (ILC) differs from invasive ductal carcinoma (IDC) in genomic profile, clinicopathologic behavior, and response to treatment. Despite favorable profile, ILC is susceptible to recurrence. Thus, most of studies did not include ILC in intraoperative radiotherapy (IORT) trials or considered it as a cautionary criteria, especially in accelerated partial breast irradiation (APBI).ObjectivesIn this study, we compared treatment outcome between breast cancer patients with ILC and IDC treating with breast conserving surgery and intraoperative electron radiotherapy (IOERT).MethodsA total of 191 patients with early breast cancer treated with breast conserving surgery and IOERT were included in the study. This study compared outcome of 42 ILC patients with 135 IDC patients. Fourteen patients were mixed type. ILC was a suitable criterion, as well. Local recurrence and disease-free survival were endpoints of study.ResultsMedian follow-up was 23.17 month and 21.17 month for IDC and ILC, respectively. Univariate analysis was done according to age, pathologic, and biologic factors and multivariate analysis was according molecular subtype. There were 3 patients with local recurrence. Two patients were in the IDC group and another one was the ILC group. There was no significant difference between two groups. The 4-year disease-free survival (DFS) was 95.45% and 97.40% for ILC and IDC, respectively.ConclusionsIn this study, there was no significant difference in in-breast tumor recurrence (IBTR) and DFS between two groups. It was seem lobular carcinoma can be used for APBI and it may be a suitable criterion as the IDC.Keywords: Breast Cancer, Intra Operative Radiotherapy, Lobular Carcinoma, APBI, IOERT, Radical Dose
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Page 3BackgroundOne of the most important limiting factors affecting the efficacy of treatment using monoclonal antibodies (mAbs) is their immunogenicity to the patients that may influence the diagnostic and therapeutic process.ObjectivesThis study determined the unwanted immunologic response to the presence of antibody against some theraputic agents made following taking mAbs in patients with malignancy.MethodsBlood samples were collected from patients with cancer, including 32 patients with lymphoma or leukemia, 43 patients with breast cancer, and 23 patients with adenocarcinoma (colon or ovarian cancer) while receiving treatment with Rituximab, Trastuzumab, and Bevacizumab, respectively. Serum levels of human antibodies against the mentioned mAbs were determined by the standard sandwich ELISA method designed in the research.ResultsThe presence of human antibodies against the mentioned mAbs was detected in 4 out of 32 (12.5%) Rituximab-treated patients and 7 out of 43 (16.3%) Trastuzumab-treated patients with a mean ± SD titer of 2.33 ± 0.37 AU/mL and 1.2 ± 0.21 AU/mL, respectively. The probability for the presence of anti-mAb in patients treated with Rituximab alone was significantly higher than patients, who took concomitantly Rituximab and once or more chemotherapeutic agents (26.6% vs. 0.0%; P < 0.02). None of Bevacizumab-treated patients, as was anticipated, developed antibody against the administrated mAb.ConclusionsThe results of this study indicates the production of antibody against therapeutic mAbs Rituximab and Trastuzumab in a number of treated patients and this may influence their efficacy of treatment. The production of the human anti-mAb may be suppressed by chemotherapeutic drugs in Rituximab-treated patients and this phenomenon may be considered as a bonus effect during treatment. Bevacizumab did not show immunogenicity in the treated patients.Keywords: Immunogenicity, Malignant Patients, Monoclonal Antibody, Rituximab, Trastuzumab, Bevacizumab
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Page 4BackgroundCompassion can help people regulate their emotional responses to cancer-induced bodily changes. However, compassion effects on levels of anxiety and depression among breast cancer patients is largely unknown.ObjectivesThe present study aimed at investigating the effectiveness of compassion-focused interventions on anxiety and depression levels among patients with breast cancer in Ahvaz, Iran.MethodsThis study was a randomized controlled trial with pre- and post-tests. Respondent-driven sampling was used to sample from women, who visited clinical oncology ward in Golestan Hospital in Ahvaz. The primary sample consisted of 30 patients with breast cancer. They, then, were randomly allocated to two experimental and control groups. Compassion-focused therapy (CFT) was provided to the experimental group for 8 weeks, and the control group only received motivational enhancement therapy (MET). The data were analyzed in two stages of pre- and post-test, using Chi-square test and covariance analysis through SPSS software.ResultsAfter adjusting for pre-test scores, the primary outcomes showed that compassion-focused interventions had a significant effect on the reduction of depression symptoms; also, secondary outcomes showed that this intervention was associated with a significant decrease in anxiety levels (all < 0.001). However, according to the findings, the interventions had greater positive impacts on the anxiety levels.ConclusionsThese findings can confirm the efficacy of psychological interventions in patients with cancer in planning future interventions and linking medical and psychiatric therapies.Keywords: Compassion-Focused Interventions, Anxiety, Depression, Breast Cancer
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Page 5BackgroundAssessment of efficacy of preoperative magnetic resonance imaging (pMRI) is important to improve the diagnosis and treatment results in patients with breast cancer (BC).ObjectivesWe designed this study to determine the role of pMRI in surgical planning for patients suffering from BC.MethodsWe, cross sectionally, observed 98 women with BC referring to an educational hospital in Tehran from January 2014 to December 2015. Data pertaining age, pathological type of BC, preoperative imaging findings, and surgical planning were gathered. The frequency of plan alteration was determined according to pMRI findings and analyzed, using appropriate statistical analyses (descriptive statistics, independent t-test, Chi-square, and Fisher’s exact tests).ResultsInitial surgical plan of 23 patients (23.47%) was changed. Pathological diagnosis of BC (P = 0.460), size of lesion (P = 0.696), laterality (P = 0.139), and lymph node involvement (P = 0.094) did not seem to alter the surgical plan. On the contrary, younger age (P = 0.049), more lesions (P = 0.002), pMRI enhancement curve washout pattern (P = 0.020), and multifocality (P < 0.001) of lesions in pMRI seemed to change surgical treatment plan. Yet, neither ultrasonography nor mammography findings did alter the plan (P > 0.050).ConclusionspMRI findings, including multiple lesions and multifocal involvement showing enhancement pattern suggestive for malignancy, may change surgical planning in about a quarter of women suffering from BC, particularly the younger ones, but MRI is not mere criterion for determining and usage of it should be limited to necessary subjects because when it is done without strict parameters, it will cause over diagnosis and over treatment.Keywords: Magnetic Resonance Imaging, Breast Cancer, Surgical Procedure
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Page 6BackgroundColorectal cancer is a highly prevalent cancer around the world and Iran. There are different criteria that can affect the survival rate of this disease. Surgical margin status is one of these criteria; there are still challenges about how it can change the surveillance of the disease.ObjectivesIn this study, we assessed the relativity between surgical margin status and the stage of disease in Iranian patients suffering from colorectal cancer.MethodsThis is an observational cross-sectional study. A total of 797 patients with colorectal cancer were included and a checklist of demographic, clinical, and pathological data was filled for each one. Based on the pathology result of the biopsy, the patients were divided into different histological groups. Surgical margin status was defined individually. To declare the relativity between surgical margin status and independent variables, we used Spearman’s rho test.ResultsThe stage of the disease and its histological type and grade were significantly correlated. There was also a significant correlation between histological grade and type of the disease.ConclusionsSurgical margin status and stage of the disease are challenging prognostic factors in disease recurrence and survival. The patients who participated in this study had meanly higher age and stage of diagnosis than earlier studies either global or local. It can be due to a lack of a systematic program for early detection of CR cancer in Iran that emphasizes the necessity of GI screening systems.Keywords: Neoplasm, Colorectal Tumor, Iran
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Page 7BackgroundOxidative stress is associated with the development of a large variety of malignancies.ObjectivesThis study was conducted to evaluate the acetylcholinesterase (AChE) and arylesterase (ARE) activities, malondialdehyde (MDA), and total antioxidant capacity (TAC) plasma levels in two groups of patient with breast cancer and benign breast diseases compared to healthy volunteers.MethodsThe present study was composed of two groups of patients with malignant breast tumors (MBT) and benign breast diseases (BBD), and a control group (CON). Enzyme activities and antioxidants markers were measured, using spectrophotometry.ResultsIn both case groups, MBT and BBD, ARE was found to show lower activity compared to CON group (P = 0.004 and P = 0.014, respectively). Lower activity of AChE was found in both MBT and BBD compared to CON subjects (P = 0.003 and P = 0.034, respectively). The mean plasma levels of MDA in both groups of patients MBT and BBD were higher than those in CON (P < 0.001 for both comparisons). No significant differences were detected between groups regarding the mean levels of TAC.ConclusionsThe results obtained from the current study indicate that healthy subjects show a different redox status than patients with MBT and BBD. Our data suggest that erythrocyte AChE may be considered as an indicator of oxidative stress along with other factors in patients with breast tumors. Thus, consuming antioxidant supplements can be helpful for the prevention of breast diseases.Keywords: Acetylcholinesterase, Arylesterase, Breast Cancer, Malondialdehyde, Oxidative Stress, Total Antioxidant Capacity
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Page 8BackgroundAstrocytomas (sub-group of gliomas) are central neuron system malignant diseases, which are originated from astrocytes. There are several documents about molecular mechanism of astrocytomas and many related genes are introduced. Here, gene expression profile alteration for grade III relative to grade II of astrocytoma is analyzed via protein-protein interaction (PPI) network to screen and introduce critical differentially expressed genes (DEGs).MethodsThe significant DEGs were extracted from gene expression omnibus (GEO) database and included in a PPI network by Cytoscape software. The common significant DEGs and central nodes of the network were selected and enriched by ClueGO to find related biological terms.ResultsTwenty critical genes including zinc finger protein 765 (ZNF765), zinc finger protein 540 (ZNF540), Zeste white 10 (ZW10) ZW10 interacting kinetochore protein (ZWINT), collagen type XVIII alpha 1 chain (COL18A1), protamine 2 (RRM2), kinesin family member 23 (KIF23), minichromosome maintenance 10 (MCM10), anaphase promoting complex subunit 7 (ANAPC7), NADPH oxidase activator 1 (NOXA1), ryanodine receptor 2 (RYR2), myozenin 3 (MYOZ3), myosin binding protein C (MYBPC2), fast type, keratin 17 (KRT17), zinc phosphodiesterase ELAC protein 2 (ELAC2), Abelson helper integration site 1 (AHI1), latent transforming growth factor beta binding protein 1 (LTBP1), kaptin (actin binding protein) (KPTN), BEN domain containing 3 (BEND3), cysteine and histidine rich 1 (CYHR1), and hyaluronoglucosaminidase 2 (HYAL2) were identified. Eight class of biological terms related to the critical genes were determined and discussed.ConclusionsA wide range of the introduced significant genes indicates that there are several possible therapeutic ways to challenge astrocytoma.Keywords: Astrocytoma, Gene, Protein, Grade, Network
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Page 9BackgroundPromoting hope, resulting in more positive health outcomes for patients with breast cancer and social support, is an important aspect of caring for people with this disease. Few studies have addressed how women with breast cancer to become hopeful with social support.ObjectivesThis study aimed at explaining the perception of Iranian women with breast cancer regarding the role of social support in promoting their hope.MethodsThis qualitative study was conducted with conventional content analysis method through in-depth semi-structured interviews held with 17 breast cancer women selected through purposive sampling at Shohada-e Tajrish Hospital in Tehran (capital of Iran). The data were collected from July 2016 to December 2017. The Graneheim &Lundman method was used for analyzing and interpreting the data, while the criteria of the Guba and Lincoln method were used to ensure the trustworthiness of these data.ResultsSupportive network as a theme and three major groups were obtained from the data analysis as follow. Family support (spousal support and first-degree relatives’ support), community support (peer support group and governmental/non-governmental organizations support), and the healthcare provider’s support. Accordingly, received support from the three support networks leads to promoting hope in women with breast cancer.ConclusionsThe promotion of hope in women with breast cancer requires the development of the supportive network. Nurses should design and implement appropriate programs based on this support network, which includes family support, community support, and the healthcare provider’s support.Keywords: Promotion of Hope, Social Support, Breast Cancer, Qualitative Research, Iran
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Page 10BackgroundIndividuals with breast cancer may experience multiple types of recurrence and a terminal event during their life. Follow-up may be interrupted for several reasons, including patients lost to follow-up or end of a study. Death is considered as a dependent terminal event.ObjectivesThe main objective was to model the dependency between (locoregional and metastaticrelapses and death in breast cancer patients.MethodsThis retrospective cohort study was conducted in Cancer Research Center, Shahid Beheshti University of Medical Sciences on 342 patients with BC. Patients were followed up to 20 years from January 1996 until February 2015. This study considers the analysis of diseases recurrence and survival for joint modeling of three correlated evens: Local recurrence, metastasis, and death. The aims are to detect the effects of relapses on death and the correlation between local and distant recurrences. We propose a joint frailty model for multiple recurrent events with a terminal event.ResultsAccording to all obtained results of the fitted models, the risk of local and metastatic relapses or death increased for women with positive lymph node (N+) or for women with a grade higher than I. Also, it was found that if the association between these 3 times to events are not taken into account, we may lose a significant association. The variable HR+ was significantly correlated with the hazards of two types of recurrences, and death for both reduced and proposed models (P < 0.05).ConclusionsWe concluded that the risk of locoregional recurrences is correlated with the risk of metastatic and the risk of metastatic relapse is also correlated with death. In this special setting, it can be difficult to get an independence between locoregional and distant recurrences. Also, these results should be considered with caution, with the few number of recurrences.Keywords: Breast Cancer, Disease Recurrence, Survival Analysis, Frailty Model