New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

The potential for liquid biopsies in the precision medical treatment of breast cancer

Currently the clinical management of breast cancer relies on relatively few prognostic/predictive clinical markers(estrogen receptor, progesterone receptor, HER2), based on primary tumor biology. Circulating biomarkers, such as circulating tumor DNA(ctDNA) or circulating tumor cells(CTCs) may enhance our treatment options by focusing on the very cells that are the direct precursors of distant metastatic disease, and probably inherently different than the primary tumor's biology. To shift the current clinical paradigm, assessing tumor biology in real time by molecularly profiling CTCs or ctDNA may serve to discover therapeutic targets, detect minimal residual disease and predict response to treatment. This review serves to elucidate the detection,characterization, and clinical application of CTCs and ctDNA with the goal of precision treatment of breast cancer.

Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases

Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is(limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Genomic medicine and cancer clinical trial in Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.

Treatment of gastric cancer

The authors focused on the current surgical treatment of resectable gastric cancer,and significance of periand post-operative chemo or chemoradiation.Gastric cancer is the 4thmost commonly diagnosed cancer and the second leading cause of cancer death worldwide.Surgery remains the only curative therapy,while perioperative and adjuvant chemotherapy,as well as chemoradiation,can improve outcome of resectable gastric cancer with extended lymph node dissection.More than half of radically resected gastric cancer patients relapse locally or with distant metastases,or receive the diagnosis of gastric cancer when tumor is disseminated;therefore,median survival rarely exceeds12 mo,and 5-years survival is less than 10%.Cisplatin and fluoropyrimidine-based chemotherapy,with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients,is the widely used treatment in stageⅣpatients fit for chemotherapy.Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance

Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer

The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.

Treatment of esophagogastric junction carcinoma:An unsolved debate

The incidence of esophagogastric junction adenocarcinoma(AEG) is increasing worldwide. Barrett's esophagus(BE) associated with dysplasia is the main risk factor for the development of cancer. Currently, screening programs to individuate and eradicate BE represent the best way to reduce AEG cancer. Several endoscopic approaches are here discussed. Surgicalstrategies for different types of AEG cancer are now fairly standardized, and multidisciplinary strategies u s i n g c h e m o t h e ra py o r c h e m o ra d i o t h e ra py m ay improve the outcome of these patients. Here we briefly discuss the keypoints, main topics, and critical issues, according to accumulating evidence and taking into account our own experience.

Potential role of metabolomics in diagnosis and surveillance of gastric cancer

Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics' role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool.

Clinical management of advanced gastric cancer: The role of new molecular drugs

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States.Surgery represents the main approach for this disease but,notwithstanding the advances in surgical techniques,we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates.Despite the development of new drugs has significantly improved the effectiveness of chemothera-py,the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor.Recently,several molecular target agents have been investigated;in particular,trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients.New molecules targeting vascular epithelial growth factor,mammalian target of rapamycin,and anti hepatocyte growth factor-c-Met pathway are also under investigation,with interesting results.Anyway,it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results.In this paper we review the actual"scenario"of targeted treatments,also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma,discussing their efficacy and potential applications in clinical practice.

Role of liver biopsy in hepatocellular carcinoma

The role of liver biopsy in the diagnosis of hepatocellular carcinoma(HCC)has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis.In fact,in the diagnostic algorithm for this tumor,histology is currently relegated to controversial cases.Furthermore,the risk of complications,such as tumor seeding and bleeding,as well as inadequate sampling have further limited the use of liver biopsy for HCC management.However,there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and,as the information content of the tissue sample increases,the advantages of liver biopsy might modify the current risk/benefit ratio.We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC.As the potentiality of precision medicine comes to the management of HCC,it will be crucial to have rapid pathways to define prognosis,and even treatment,by identifying the patients who could most benefit from target-driven therapies.All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.

Biological subtypes of breast cancer: Prognostic and therapeutic implications

Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.

Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

Despite advances in the management of patients with locally advanced,non-metastatic rectal adenocarcinoma(LARC),prognosis remains largely unsatisfactory due to a high rate of distant relapse.In fact,currently available neoadjuvant protocols,represented by fluoropyrimidine-based chemo-radiotherapy(CT-RT)or short-course RT,together with improved surgical techniques,have largely reduced the risk of local relapse,with limited impact on distant recurrence.Available results of phaseⅢtrials with additional cytotoxic agents combined with standard CT-RT are disappointing,as no significant reduction in the risk of recurrence has been demonstrated.In order to improve the control of micrometastatic disease,integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach.In particular,the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models,and thusmay represent a suitable companion in the neoadjuvant treatment of LARC.Preliminary results of phase?Ⅰ-Ⅱclinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection:treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.

Treatment of locally advanced rectal cancer:Controversies and questions

Rectal cancers extending through the rectal wall, or involving locoregional lymph nodes (T3/4 or N1/2), have been more difficult to cure. The confines of the bony pelvis and the necessity of preserving the autonomic nerves makes surgical extirpation challenging, which accounts for the high rates of local and distant relapse in this setting. Combined multimodality treatment for rectal cancer stage Ⅱ and Ⅲ was recommended from National Institute of Health consensus. Neoadjuvant chemoradiation using fluoropyrimidine-based regimen prior to surgical resection has emerged as the standard of care in the United States. Optimal time of surgery after neoadjuvant treatment remained unclear and prospective randomized controlled trial is ongoing. Traditionally, 6-8 wk waiting period was commonly used. The accuracy of studies attempting to determine tumor complete response remains problematic. Currently, surgery remains the standard of care for rectal cancer patients following neoadjuvant chemoradiation, where-as observational management is still investigational. In this article, we outline trends and controversies associated with optimal pre-treatment staging, neoadjuvant therapies, surgery, and adjuvant therapy.

Primary prevention of colorectal cancer:Myth or reality?

Colorectal cancer incidence has been rising strongly in parallel with economic development.In the past few decades,much has been learned about the lifestyle,dietary and medication risk factors for this malignancy.With respect to lifestyle,compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk.Although there is controversy about the role of specific nutritional factors,consideration of dietary pattern as a whole appears useful for formulating recommendations.Though quite often recommended,the role for many supplements,including omega-3,vitamin D,folate,and vitamin B6,remains unsettled.Only calcium and vitamin D supplementation appear to add a modest benefit,particularly in those with a low daily intake.With regard to chemoprevention,medications such as aspirin and nonsteroidal antiinflammatory drugs,and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk,though their utility is affected by their side effect profile.However,the role of agents such as statins,bisphosphonates and antioxidants have yet to be determined.Ultimately,primary prevention strategies focusing on modifying environmental,lifestyle risk factors,and chemopreventive drugs are options that have already been tested,and may impact on colon cancer incidence.

Clinical and molecular characteristics of East Asian patients with von Hippel–Lindau syndrome

Background: Von Hippel–Lindau(VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome.Methods: To create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non?English language articles identi?fied through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction.Results: Of 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common(40.9%, 63/154), followed by large/complete deletions(32.5%, 50/154) and nonsense mutations(11.7%, 18/154). Compared with a previously reported study of both East Asian and non?East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients(40.9% vs. 52.0%; P = 0.012 and 8.4% vs. 13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients(32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher.Conclusions: Evidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.

Neoadjuvant chemotherapy for colorectal liver metastases:A contemporary review of the literature

Colorectal carcinoma(CRC)is one of the leading causes of cancer-related deaths worldwide,and up to 50%of patients with CRC develop colorectal liver metastases(CRLM).For these patients,surgical resection remains the only opportunity for cure and long-term survival.Over the past few decades,outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy,as well as improvements in operative technique and perioperative care.Chemotherapy in the modern era of oxaliplatin-and irinotecancontaining regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents.The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery.Consequently,the use of neoadjuvant strategies is becoming progressively more established.For patients with CRLM,the primary advantage of neoadjuvant chemotherapy(NCT)is the potential to down-stage metastatic disease in order to facilitate hepatic resection.On the other hand,the routine use of NCT for patients with resectable metastases remains controversial,especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy.Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk,reserving NCT for patients with borderline resectable or unresectable disease and high operative risk.Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability.In light of the growing number of treatment options available to patients with metastatic CRC,it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

Single dose dexamethasone prophylaxis of postembolisation syndrome after chemoembolisation in hepatocellular carcinoma patient:A randomised,double-blind,placebo-controlled study

BACKGROUND Even in the immuno-oncology era,transcatheter arterial chemoembolisation(TACE)is the most effective way to treat intermediate stage hepatocellular carcinoma(HCC).Postembolisation syndrome(PES)is the most common side effect from TACE and there is still no standard prevention guideline.AIM To evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with HCC.METHODS This study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic metastasis.Patients were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before TACE.The primary outcome was a negative result of PES at 48 h after TACE,which was defined as score<2 of Southwest Oncology Group toxicity coding criteria using fever,nausea,vomiting and pain to calculated.And the secondary end point was duration of admission between two groups.RESULTS One hundred patients were randomly assigned 1:1.Under intention-to-treat analysis,49 patients were randomly assigned to the dexamethasone and 51 to the placebo groups.Both groups were similar for baseline characteristics.The negative PES rate was significantly higher in the dexamethasone group than in the placebo group(63.3%vs 29.4%;P=0.005).Mean Southwest Oncology Group toxicity coding PES was 2.14(95%CI:1.41-2.8)vs 3.71(95%CI:2.97-4.45)between the dexamethasone and placebo groups,respectively.Cumulative incidence of fever was significantly lower in dexamethasone group with P<0.001,pain,nausea and vomiting were also lower in the dexamethasone group compared with the placebo group(P=0.16,P=0.11,and P=0.49).The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes mellitus.CONCLUSION Single dose dexamethasone was effective at preventing PES among patients with HCC treated with TACE.The study showed no adverse events of special interest related to dexamethasone.

Heavily calcified gastrointestinal stromal tumors:Pathophysiology and implications of a rare clinicopathologic entity

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended andthe patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis(longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature.