Radiomics models to predict bone marrow metastasis of neuroblastoma using CT

Background:Bone marrow is the leading site for metastasis from neuroblastoma and affects the prognosis of patients with neuroblastoma.However,the accurate diagnosis of bone marrow metastasis is limited by the high spatial and temporal heterogeneity of neuroblastoma.Radiomics analysis has been applied in various cancers to build accurate diagnostic models but has not yet been applied to bone marrow metastasis of neuroblastoma.Methods:We retrospectively collected information from 187 patients pathologically diagnosed with neuroblastoma and divided them into training and validation sets in a ratio of 7:3.A total of 2632 radiomics features were retrieved from venous and arterial phases of contrastenhanced computed tomography(CT),and nine machine learning approaches were used to build radiomics models,including multilayer perceptron(MLP),extreme gradient boosting,and random forest.We also constructed radiomics‐clinical models that combined radiomics features with clinical predictors such as age,gender,ascites,and lymph gland metastasis.The performance of the models was evaluated with receiver operating characteristics(ROC)curves,calibration curves,and risk decile plots.Results:The MLP radiomics model yielded an area under the ROC curve(AUC)of 0.97(95%confidence interval[CI]:0.95–0.99)on the training set and 0.90(95%CI:0.82–0.95)on the validation set.The radiomics‐clinical model using an MLP yielded an AUC of 0.93(95%CI:0.89–0.96)on the training set and 0.91(95%CI:0.85–0.97)on the validation set.Conclusions:MLP‐based radiomics and radiomics‐clinical models can precisely predict bone marrow metastasis in patients with neuroblastoma.

Machine‐learning radiomics to predict bone marrow metastasis of neuroblastoma using magnetic resonance imaging

Background: Neuroblastoma is one common pediatric malignancy notorious forhigh temporal and spatial heterogeneities. More than half of its patients developdistant metastases involving vascularized organs, especially the bone marrow. It isthus necessary to have an economical, noninvasive method without muchradiation for follow‐ups. Radiomics has been used in many cancers to assistaccurate diagnosis but not yet in bone marrow metastasis in neuroblastoma.Methods: A total of 182 patients with neuroblastoma were retrospectivelycollected and randomly divided into the training and validation sets. Fivehundredand seventy‐two radiomics features were extracted from magneticresonance imaging, among which 41 significant ones were selected via T‐testfor model development. We attempted 13 machine‐learning algorithms andeventually chose three best‐performed models. The integrative performanceevaluations are based on the area under the curves (AUCs), calibration curves,risk deciles plots, and other indexes.Results: Extreme gradient boosting, random forest (RF), and adaptiveboosting were the top three to predict bone marrow metastases in neuroblastoma while RF was the most accurate one. Its AUC was 0.90(0.86–0.93), F1 score was 0.82, sensitivity was 0.76, and negative predictivevalue was 0.79 in the training set. The values were 0.82 (0.71–0.93), 0.80,0.75, and 0.92 in the validation set, respectively.Conclusions: Radiomics models are likely to contribute more to metastaticdiagnoses and the formulation of personalized healthcare strategies in clinics.It has great potential of being a revolutionary method to replace traditionalinterventions in the future.

Esophageal squamous cell carcinoma with dural and bone marrow metastases

Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis.The most common sites of visceral metastasis are the lung,liver and bone,but brain and bone marrow involvement is exceedingly rare.Herein,we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs,dysphagia and body weight loss.Esophageal squamous cell carcinoma with regional lymph node,liver and bone metastases was diagnosed.He underwent concurrent chemoradiotherapy and got a partial response.Four months later,he complained of headache,diplopia and severe hearing impairment in the left ear.There was no evidence for bacterial,fungal,tuberculous infection or neoplastic infiltration.Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull.Dural metastasis was diagnosed and he received whole brain irradiation.In addition,laboratory examination revealed severe thrombocytopenia and leucopenia,and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma.This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases.We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

Bone marrow metastatic neuroendocrine carcinoma with unknown primary site:A case report and review of the literature

BACKGROUND Metastatic neuroendocrine carcinoma(NEC) of bone marrow is uncommon.Here,we report a case of bone marrow metastatic NEC with an unknown primary site.CASE SUMMARY A 73-year-old Chinese woman was admitted to our hospital because marked chest distress and asthma lasting 1 d on March 18,2018.She was initially diagnosed with pulmonary infection,cardiac insufficiency,thrombocytopenia and severe anemia.Following treatment with antibiotic therapy,diuresis and blood transfusion,the patient’s symptoms greatly improved.After bone marrow examinations,the patient was diagnosed with bone marrow metastatic NEC,bone marrow necrosis(BMN) and secondary myelofibrosis(MF).Further imaging workup did not show the primary tumor,we presumed that the primary site might regress spontaneously or merely be unexplored due to lack of positron emission tomography with gallium peptide.Everolimus(10 mg/d) was added to the treatment and the best supportive and symptomatic therapies were also administered.Unfortunately,the patient’s condition continued to deteriorate and she died on May 15,2018.CONCLUSION Bone marrow invasion of NEC is rare and our patient who suffered from bone marrow metastatic NEC as well as secondary BMN and MF had an extremely poor prognosis.Bone marrow biopsy plays an important role in the diagnosis of solid tumors invading bone marrow.

Occult colon cancer with sepsis as the primary manifestation identified by bone marrow puncture:A case report

BACKGROUND Bone marrow metastasis is common in liver and lung cancer,but there are few reports on bone marrow metastasis in colon cancer.To date,there are no such reports from China's Mainland,and reports of bone marrow metastasis with septic shock as the main manifestation are even rarer.CASE SUMMARY A 71-year-old woman with sepsis as the first symptom presented with high fever,low blood pressure and high inflammation indicators.Computed tomography(CT)examination revealed mild inflammation of the lungs and no obvious abnormalities in the abdomen.Blood culture suggested Escherichia coli,Aeromonas hydrophila and Aeromonas caviae infection.Antibiotic treatment significantly improved the patient’s sepsis symptoms;however,her thrombocytopenia(TCP)could not be corrected despite repeated platelet transfusions.Many malignant cells were ultimately found following a bone marrow puncture smear,and further positron emission tomography/CT(PET/CT)examination confirmed that the malignant tumor in the ascending colon was accompanied by multiple metastases,including the liver and bones.Colon adenocarcinoma was confirmed by autopsy.CONCLUSION Patients with advanced colon cancer may not have typical clinical symptoms,and sepsis may be the first symptom.When patients have severe TCP that cannot be explained by sepsis of intestinal origin,it is necessary to be aware of the possibility of bone marrow metastasis of intestinal tumors.As such patients often cannot tolerate endoscopy,bone marrow biopsy smears or biopsy tests for specialized cells can help obtain a diagnosis,especially in less developed countries where PET/CT is scarce.

Chromosome band 11q23 deletion predicts poor prognosis in bone marrow metastatic neuroblastoma patients without MYCN amplification

Background:Interphase fluorescence in situ hybridization(FISH)of bone marrow cells has been confirmed to be a direct and valid method to assess the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog(MYCN)amplification in patients with bone marrow metastatic neuroblastoma.MYCN amplification alone,however,is insufficient for pretreatment risk stratification.Chromosome band 11q23 deletion has recently been included in the risk stratification of neuroblastoma.In the present study,we aimed to evaluate the biological characteristics and prog-nostic impact of 11q23 deletion and MYCN amplification in patients with bone marrow metastatic neuroblastoma.Methods:We analyzed the MYCN and 11q23 statuses of 101 patients with bone marrow metastatic neuroblastoma using interphase FISH of bone marrow cells.We specifically compared the biological characteristics and prognostic impact of both aberrations.Results:MYCN amplification and 11q23 deletion were seen in 12(11.9%)and 40(39.6%)patients.The two mark-ers were mutually exclusive.MYCN amplification occurred mainly in patients with high lactate dehydrogenase(LDH)and high neuron-specific enolase(NSE)levels(both P<0.001),and MYCN-amplified patients had more events(tumor relapse,progression,or death)than MYCN-normal patients(P=0.004).11q23 deletion was associated only with age(P=0.001).Patients with MYCN amplification had poorer outcomes than those with normal MYCN(3-year event-free survival[EFS]rate:8.3±8.0%vs.43.8±8.5%,P<0.001;3-year overall survival[OS]rate:10.4±9.7%vs.63.5%±5.7%,P<0.001).11q23 deletion reflected a poor prognosis only for patients with normal MYCN(3-year EFS rate:34.3±9.5%vs.53.4±10.3%,P=0.037;3-year OS rate:42.9±10.4%vs.75.9±6.1%,P=0.048).Those with both MYCN amplification and 11q23 deletion had the worst outcome(P<0.001).Conclusions:Chromosome band 11q23 deletion predicts poor prognosis only in bone marrow metastatic neuroblastoma patients without MYCN amplification.Combined assessment of the two markers was much superior to single-marker assessment in recognizing the patients at a high risk of disease progression.

Thrombocytopenia with multiple splenic lesions-histiocytic sarcoma of the spleen without splenomegaly: A case report

BACKGROUND Histiocytic sarcoma(HS)of the spleen is reported to be a rare and lethal disease.The clinicopathological features of splenic HS have not been well described.The objective of this paper is to describe the diagnosis and treatment of a case of this rare disease and provide a review of the literature.CASE SUMMARY In this article,we discuss the case of a 40-year-old Hispanic female who presented with progressive thrombocytopenia and multiple hypoechoic lesions in the spleen without splenomegaly.Positron emission tomography-computed tomography showed increased activity in cervical lymph nodes,as well as multiple bone and splenic lesions with positive uptake.Two bone marrow biopsies and fine-needle aspiration of the cervical lymph node were inconclusive.Laparoscopic splenectomy was performed,and gross examination showed a 110.1 g spleen with multiple rubbery,nodular lesions within the subcapsular sinus and splenic parenchyma.The microscopic findings showed multinodular histiocyte proliferation with atypia and multilobulated nuclei,which were positive for CD163,CD4,and CD68 by immunohistochemical analysis.The final pathologic diagnosis was difficult and was found to be low-grade HS of the spleen,after consultations with two renowned hematopathology institutions.At the patient’s five-month follow-up visit,her bone marrow metastasis had progressed.She is waiting to be enrolled in a clinical trial.CONCLUSION Pathologic diagnosis of splenic HS can be challenging.Low-grade differentiation may be associated with a slow progressive disease.