Search

Introduction: Colorectal carcinoma is one of the cancers with a high disease burden globally. Previous observational studies have found a connection between colorectal cancer incidence with sunlight exposure and vitamin D levels. Subsequent studies investigated this relationship further and found various anti-tumoral pathways regulated by vitamin D in colorectal tissue. This paper aims to elucidate the actions of those pathways in preventing the malignant transformation of the colorectal cell by reviewing relevant literature. Methods: A search was conducted on several medical literature electronic databases for original research studying the effects of vitamin D treatment on colorectal adenoma and colorectal cancer and its underlying anti-tumoral mechanism. A total of 122 studies were included for evaluation. Results: Twenty-seven studies passed for analysis. These in vitro and in vivo study reveals that vitamin D treatment can suppress cell proliferation, induce apoptosis, maintain cellular differentiation, reduce the pro-inflammatory response, inhibit angiogenesis, and hinder metastatic progression in colorectal cancer and colorectal adenoma cells by regulating associated gene transcription or directly prevents activation of selected signalling pathways. Five studies have also shown that adding calcium to vitamin D treatment increases the anti-tumoral activity of vitamin D through cross-talk between both of their pathways. Conclusion: Vitamin D could potentially impede colorectal cancer transformation and growth through interaction with various signalling pathways and regulating gene transcription. Further clinical studies are needed to confirm whether vitamin D can be used as the basis of targeted colorectal cancer therapy using its inherent anti-tumoral properties.

Aims: This study was done to assess the survival of patients with glioblastoma multiform and to identify factors that can affect patient survival. Materials and methods: From January 2015 to December 2019, 55 patients with histopathologically confirmed glioblastoma multiform and received adjuvant radiation/chemoradiation in our department were retrospectively analyzed. Results: The median overall survival (OS) for entire cohort was 13 months and 1-year OS and 2-year OS rate were 52.7% and 3.6% with the mean follow-up period was 12 months. In univariate analysis, age (≤50 years vs >50 years, p=0.02), performance status (≥90 vs 70-80 vs 20.4cm3, p=0.001) and time to initiate adjuvant therapy (6 weeks, p=0.01) were significantly affect overall survival. In multivariate analysis, RTOG RPA classification and involvement of parietal lobes were independent prognostic factors for overall survival. Conclusions: RTOG RPA classification that consisted of age and performance status is an independent prognostic factor for the clinical outcome of GBM. Besides this well-known factor, we also identified the involvement of parietal lobe gives a strong negative influence on survival of GBM patients.

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

Cancer is the leading cause of death in children worldwide. Pediatric cancer is challenging to detect early because it generally appears with signs and symptoms that are not typical. The increase in cancer cases in pediatric must be followed by an increase in cancer management in all fields of scientific disciplines. Radiation oncology, as one of the areas of science, has an essential role in definitive, adjuvant, palliative, and prophylactic cancer in pediatric. Apart from these uses, radiation management is a significant contributor to the complications of pediatric cancer survivors. Complications that arise can be in the form of growth retardation, tissue changes, secondary cancer, neurocognitive changes, infertility, or other hormonal dysfunction and preterm labor. An increase in radiation techniques followed the development of treatment machines able to reduce radiation-related morbidity and mortality rates. In pediatric radiotherapy, the entire process from the pre-procedure anesthesia to radiotherapy requires special attention. Psychological issues are also worth observing. This study will briefly discuss these matters and the management of some of the most common pediatric cancers in Dr. Cipto Mangunkusumo Hospital.

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

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

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.

Diffuse Intrinsic Pontine Gliomas (DIPG) is a rare and highly aggressive central nervous system tumour arising from glial cells which occur mostly in children. It remains a potentially deadly cancer despite treatment, with the highest mortality rate, in which most children die within 1-year of diagnosis. Radiation therapy might improve the clinical symptoms, but the results are temporary, with tumor progression typically occurring months post radiation, whereas chemotherapy remains controversial. Here we present a case report of a patient with DIPG Indonesia and how we diagnose and currently treat it. An eight years-old boy presented with decrease level of consciousness with headache, limb weakness, slurred speech, double vision, hemifacial weakness, paraplegia, and disequilibrium which worsened two weeks prior to admission. He was initially noted to have a medially inverted left eye two months prior to admission. On physical examination, there was a N.VI and N.VII palsy, hyperreflexia, paraplegia, and nystagmus. Head MRI demonstrated a solid with minimal enhancement after contrast administration in the left pons region extending into mesencephalon with cystic component and flat floor of fourth ventricle sign, causing hydrocephalus, suggestive diffuse intrinsic pontine glioma. He was given fractionated focal intensity modulated radiation therapy (IMRT) to the tumor along with 5 mm margins with a total dose of 54 Gy. 1.8 Gy fractions, given once daily for 5 days per week over a period of 6 weeks. Supportive care in the form of corticosteroids is used to treat the peri-tumoral edema. There was a short period of motoric improvement. But then the disease progressed with the latest head CT showed hydrocephalus formation with increased size of mass. He is treated with chemotherapy using Temozolomide, and currently alive after 3 months post diagnosis. Keywords: childhood brain tumour, Diffuse Intrinsic Pontine Glioma, radiation therapy

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% ± 3.4% and specificity of 90.7% ± 3.6%. iSF2 returned SF2 values that were within 2.9% ± 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.

In the current big data era, massive genomic cancer data are available for open access from anywhere in the world. They are obtained from popular platforms, such as The Cancer Genome Atlas, which provides genetic information from clinical samples, and Cancer Cell Line Encyclopedia, which offers genomic data of cancer cell lines. For convenient analysis, user-friendly tools, such as the Tumor Immune Estimation Resource (TIMER), which can be used to analyze tumor-infiltrating immune cells comprehensively, are also emerging. In clinical practice, clinical sequencing has been recommended for patients with cancer in many countries. Despite its many challenges, it enables the application of precision medicine, especially in medical oncology. In this review, several efforts devoted to accomplishing precision oncology and applying big data for use in Indonesia are discussed. Utilizing open access genomic data in writing research articles is also described.

Highlights: • Status of Radiotherapy Centers in Indonesia. • Radiotherapy adjustment during COVID-19 outbreak in Indonesia. • Strategies for RT Centers in Indonesia to Cope with Backlog during and after COVID-19 Pandemic., 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.

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.

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

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.

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.

学位記番号：医博甲1751

Studi retrospektif ini bertujuan untuk mengetahui perbandingan respon terapi radiasi antara teknik konvensional 2D dengan pengecilan lapangan radiasi teknik 2D, 3DCRT atau brakiterapi pada pasien kanker nasofaring stadium dini (stadium I – IIa). Dari 20 sampel didapatkan respon komplit pada 17 pasien (85%) dan respon parsial pada 3 pasien (15%) (p=0.219). Efek samping akut yaitu dermatitis radiasi grade 3-4 adalah 5% (p=0.435), mukositis grade 3-4 adalah 15% (p=0.510) dan xerostomia grade 3-4 adalah 0% (p=0.517). Secara statistik tidak didapatkan perbedaan bermakna tetapi secara klinis mempunyai kesan ada kecenderungan bahwa dengan pengecilan lapangan radiasi teknik brakiterapi dan 3D-CRT lebih baik dalam hal efek samping akut mukositis dibanding teknik 2D

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-naive 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.

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., PD-L1 is upregulated in many cancers due to exogenous cellular stress. Here the authors show that PD-L1 is upregulated in response to DNA double strand breaks via STAT and IRF1 signalling.