The management of locally advanced cervical cancer relies on brachytherapy (BT) as an integral part of the radiotherapy delivery armamentarium. Occasionally, intracavitary BT is neither possible nor available. In these circumstances, post-external beam radiotherapy (EBRT) interstitial brachytherapy and/or hysterectomy may represent viable options that must be adequately executed in a timely manner. However, if these options are not applicable due to patient related or facility related reasons, a formal contingency plan should be in place. Innovative EBRT techniques such as intensity modulated and stereotactic radiotherapy may be considered for patients unable to undergo brachytherapy. Relying on provocative arguments and recent data, this review explores the rationale for and limitations of non-brachytherapy substitutes in that setting aiming to establish a formal process for the optimal execution of this alternative plan.
Clinical studies using prognostic and predictive signatures have shown that an immune signal emanating from whole tumors reflects the level of immune cell infiltration--a high immune signal linked to improved outcome. Factors regulating immune cell trafficking to the tumor, however, are not known. Previous work has shown that expression of interferon regulatory factor 5 (IRF5), a critical immune regulator, is lost in ~80% of invasive ductal carcinomas examined. We postulated that IRF5-positive and -negative breast tumors would differentially regulate immune cell trafficking to the tumor. Using a focused tumor inflammatory array, differences in cytokine and chemokine expression were examined between IRF5-positive and -negative MDA-MB-231 cells grown in three-dimensional culture. A number of cytokines/chemokines were found to be dysregulated between cultures. CXCL13 was identified as a direct target of IRF5 resulting in the enhanced recruitment of B and T cells to IRF5-positive tumor-conditioned media. The ability of IRF5 to regulate mediators of cell migration was confirmed by enzyme-linked immunosorbent assay, chromatin immunoprecipitation assay, small interfering RNA knockdown and immunofluorescence staining of human breast tumor tissues. Analysis of primary immune cell subsets revealed that IRF5 specifically recruits CXCR5(+) B and T cells to the tumor; CXCR5 is the receptor for CXCL13. Analysis of primary breast tumor tissues revealed a significant correlation between IRF5 and CXCL13 expression providing clinical relevance to the study. Together, these data support that IRF5 directly regulates a network of genes that shapes a tumor immune response and may, in combination with CXCL13, serve as a novel prognostic marker for antitumor immunity.
Background
Access to cancer care is a problem that continues to plague refugees displaced from their home countries. The turbulent political crisis in Syria, which has led to millions of refugees seeking asylum in Turkey, merits further attention. We aimed to study the rate of utilization of radiation therapy among Syrian refugees with cancer living in Turkey in an attempt to identify the contributing factors predictive of non-compliance with prescribed RT.
Methods
In this retrospective review of 14 institutional databases, Syrian refugee patients in Turkey with a cancer diagnosis from January 2015 to December 2019 who were treated with RT were identified. The demographic data, treatment compliance rates, and toxicity outcomes in these patients were surveyed. Variable predictors of noncompliance such as age, sex, diagnosis, treatment length, and toxicity were studied. The association between these variables and patient noncompliance was determined.
Results
We identified 10,537 patients who were diagnosed with cancer during the study period, of whom 1010 (9.6%) patients were treated with RT. Breast cancer (30%) and lung cancer (14%) were the most common diagnoses with up to 68% of patients diagnosed at an advanced stage (Stage III, IV). 20% of the patients were deemed noncompliant. Treatment with concurrent chemoradiotherapy (OR 1.61, 95% CI 1.06–2.46, p = 0.023) and living in a refugee camp (OR 3.62, 95% CI 2.43–5.19, p < 0.001) were associated with noncompliance. Age, sex and treatment length were not significantly associated with noncompliance.
Conclusions
Noncompliance with radiotherapy among Syrian refugees in Turkey remains an area of concern with a multitude of factors contributing to these alarming numbers. Further studies to better ascertain the finer nuances of this intricately complex problem and a global combination of efforts can pave the way to providing a solution.
Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications.
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