Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses.

OBJECTIVE: The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients. METHODS: A systematic review with meta-analyses was conducted on related articles from PubMed, EBSCOhost, Scopus, and Cochrane databases with last updated search on October 31, 2020. A total of 7 studies regarding c-Met overexpression and overall survival (OS) and/or progression free survival (PFS) are included in this study. RESULTS: All studies used immunohistochemistry to examine the expression of c-Met protein. The results showed that the positive rate of c-Met overexpression was detected in approximately 33,9% - 60,5% of GBM patients. c-Met overexpression was related to worse OS (HR: 1,74; 95% CI: 1,482-2,043; Z=6,756; p<0,001) and PFS (HR: 1,66; 95% CI: 1,327-2,066; Z=4,464; p<0,001) in GBM patients. Low heterogeneity of subjects was found in both OS and PFS analyses, I2 values were 7,8% and 0,0%, respectively. CONCLUSION: In conclusion, c-Met overexpression is significantly related to shorter OS and PFS in GBM patients, so c-Met can be considered as a potential prognostic indicator in GBM.

Relationship of Adherence to Cervical Cancer Treatment Guideline Towards Patients' Five-year Survival: Systematic Review of Follow-up Trials.

Cervical cancer is the one of the most common gynecology malignancies in the world. National Comprehensive Cancer Network (NCCN) guidelines on cervical cancer are widely adopted as national guidelines and clinical practice guidelines. These guidelines are constantly being updated but their effectiveness has not been questioned. Therefore, we conducted a systematic review to assess outcomes with/without guideline adherence in the published studies. This systematic review was conducted according to PRISMA statement. Searching with strategy on PubMed, ProQuest, Scopus, and Wiley databases resulted in three studies that met all criteria, thus assessed further with Newcastle-Ottawa scale, and assessed qualitatively. All three studies adopt NCCN guidelines. We found that the proportion of adherence to cervical cancer treatment guidelines was low, ranging from 42% to 54%, with violations occurring at various clinical stages. One study stated that early stage cervical cancer was more likely to receive guideline adherence (adjusted OR=5.48; 95%CI: 1.94-15.5; p=0.001) than advanced stage. There was a higher five-year survival of cervical cancer patients in the guideline-adhering group than in the nonadhering group. In all three studies, survival in the adherent group was reported as big as 88%, 79%, and 93%, respectively, compared to nonadherent group with 56%, 78%, and 88.1%respectively (p<0.05). One study stated that adherence to guidelines could reduce cervical cancer mortality on stage I and II by 0.22 times (p<0.05). As the conclusion, adherence to guidelines increases survival rates. In the early stages, there are differences in survival.

Tackling Resistance to Cancer Immunotherapy: What Do We Know?

Cancer treatment has evolved tremendously in the last few decades. Immunotherapy has been considered to be the forth pillar in cancer treatment in addition to conventional surgery, radiotherapy, and chemotherapy. Though immunotherapy has resulted in impressive response, it is generally limited to a small subset of patients. Understanding the mechanisms of resistance toward cancer immunotherapy may shed new light to counter that resistance. In this review, we highlighted and summarized two major hurdles (recognition and attack) of cancer elimination by the immune system. The mechanisms of failure of some available immunotherapy strategies were also described. Moreover, the significance role of immune compartment for various established cancer treatments were also elucidated in this review. Then, the mechanisms of combinatorial treatment of various conventional cancer treatment with immunotherapy were discussed. Finally, a strategy to improve immune cancer killing by characterizing cancer immune landscape, then devising treatment based on that cancer immune landscape was put forward.

Ensuring safety and sustainability of radiotherapy services during the COVID-19 pandemic in resources constrain country: An Indonesian experience.

The global COVID-19 pandemic has placed a significant burden on the healthcare sector, overwhelming health services in affected countries worldwide. As healthcare facilities reorganize their services to adapt to this challenging problem, it is important that the sustainability of essential oncology services, including radiotherapy, is maintained. This article describes the Indonesian experience in ensuring sustainability of radiotherapy services during the pandemic, highlighting various important adjustments which were made to allow radiotherapy centers nationwide to continue operating while protecting staff and patients from the risk of disease transmission. As the backlog of patients waiting to start treatment will inevitably grow, some insight on how to proactively manage this issue will also be described.

Patterns of Care and Outcome Analysis of Nasopharyngeal Carcinoma: An Indonesian Single Institution Study.

BACKGROUND: Nasopharyngeal cancer is endemic to Southeast Asia. However, there is limited clinical evidence of nasopharyngeal cancer in Indonesia, which has the largest population in Southeast Asia. METHODS: Patterns of care and treatment outcomes in 428 patients with newly-diagnosed and pathologically-confirmed nasopharyngeal cancer were retrospectively analyzed. RESULTS: Concurrent chemo-radiotherapy (CCRT) was the first-line treatment for stages I-IVB diseases. The 2-year overall survival (OS) of all patients were 100.0%, 100.0%, 93.8%, 86.2%, 82.9%, and 62.4% for stages I, II, III, IVA, IVB, and IVC, respectively. The 2-year OS of CCRT-treated patients were 100.0%, 100.0%, 92.6%, 82.4%, and 78.3% for stages I, II, III, IVA, and IVB, respectively. CONCLUSION: The patterns of care and treatment outcomes were potentially consistent with world standards, needing future validation. This is the largest study of newly diagnosed nasopharyngeal cancer in Indonesia, a huge disease burden, providing an important basis for the clinical management of this disease.

Deep learning-assisted literature mining for in vitro radiosensitivity data.

BACKGROUND AND PURPOSE: Integrated analysis of existing radiosensitivity data obtained by the gold-standard clonogenic assay has the potential to improve our understanding of cancer cell radioresistance. However, extraction of radiosensitivity data from the literature is highly labor-intensive. To aid in this task, using deep convolutional neural networks (CNNs) and other computer technologies, we developed an analysis pipeline that extracts radiosensitivity data derived from clonogenic assays from the literature. MATERIALS AND METHODS: Three classifiers (C1-3) were developed to identify publications containing radiosensitivity data derived from clonogenic assays. C1 uses Faster Regions CNN with Inception Resnet v2 (fRCNN-IRv2), VGG-16, and Optical Character Recognition (OCR) to identify publications that contain semi-logarithmic graphs showing radiosensitivity data derived from clonogenic assays. C2 uses fRCNN-IRv2 and OCR to identify publications that contain bar graphs showing radiosensitivity data derived from clonogenic assays. C3 is a program that identifies publications containing keywords related to radiosensitivity data derived from clonogenic assays. A program (iSF2) was developed using Mask RCNN and OCR to extract surviving fraction after 2-Gy irradiation (SF2) as assessed by clonogenic assays, presented in semi-logarithmic graphs. The efficacy of C1-3 and iSF2 was tested using seven datasets (1805 and 222 publications in total, respectively). RESULTS: C1-3 yielded sensitivity of 91.2% ±â€¯3.4% and specificity of 90.7% ±â€¯3.6%. iSF2 returned SF2 values that were within 2.9% ±â€¯2.6% of the SF2 values determined by radiation oncologists. CONCLUSION: Our analysis pipeline is potentially useful to acquire radiosensitivity data derived from clonogenic assays from the literature.

Robustness of Clonogenic Assays as a Biomarker for Cancer Cell Radiosensitivity.

Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF2 (surviving fraction after 2 Gy irradiation) and for D10 (dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF2 and D10 have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF2 and D10 as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons.

Mutational analysis of uterine cervical cancer that survived multiple rounds of radiotherapy.

Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naïve tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in PIK3CA and KRAS, and putative inactivating mutations in SMAD4, as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in KMT2A, TET1, and NLRP1 as acquired mutation signatures observed only in recurrent tumors after radiotherapy. Comprehensive mining of published in vitro genomics data pertaining to radiosensitivity revealed that simultaneous mutations in KRAS and SMAD4, which have not been described previously in uterine cervical cancer, are associated with cancer cell radioresistance. The association between this mutation signature and radioresistance was validated by isogenic cell-based experiments. These results provide proof-of-principle for the analytical pipeline employed in this study, which explores clinically relevant mutation signatures for radioresistance, and demonstrate that this approach is worth pursuing with larger cohorts in the future.

Inter-assay precision of clonogenic assays for radiosensitivity in cancer cell line A549.

Clonogenic assays are the gold standard for determining radiosensitivity, which governs tumor response to radiation therapy. Although multiple studies of clonogenic assays on cancer cell lines have been published, the robustness of this technique has not been examined by comparative analysis of data from different studies. To address this issue, we investigated the inter-assay precision of clonogenic assays by analyzing in-house and published data on A549, a cell line frequently studied in this context. The coefficients of variation for SF2, the surviving fraction after 2 Gy irradiation, and D10, the radiation dose that reduces survival to 10%, were below 30% for both in-house data obtained from 20 independent experiments performed under consistent experimental settings (i.e., radiation type, dose rate, and timing of cell seeding) and data collected from 192 publications using diverse experimental settings. Multivariate analyses of the published data revealed that timing of cell seeding significantly affected SF2. These data indicate that SF2 and D10 of clonogenic assay have acceptable inter-assay precision, and that timing of cell seeding influences the inter-assay precision of SF2. These results provide a rationale for combined analysis of published clonogenic assay data, which may help to discover robust biological properties associated with tumor radiosensitivity.

DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells.

Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs.