Image_1_Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature.tif

BackgroundCancer of unknown primary (CUP) is a malignant and aggressive tumor whose primary origin is still unknown despite thorough evaluation. CUP can be life-threatening with a median overall survival of less than 1 year based on empirical chemotherapy. Gene detection technology advances the driver gene detection of malignant tumors and the appropriate precise therapy. Immunotherapy has ushered in a new era in cancer therapy, changing the way advanced tumors, including CUP, are treated. Combined with comprehensive clinical and pathological investigations, molecular analysis of the original tissue and detection of potential driver mutations may provide therapeutic recommendations for CUP.Case presentationA 52-year-old female was admitted to hospital for dull abdominal pain, with peripancreatic lesions below the caudate lobe of the liver and posterior peritoneal lymph nodes enlargement. Conventional biopsy under endoscopic ultrasonography and laparoscopic biopsy both revealed poorly differentiated adenocarcinoma based on immunohistochemical series. To help identify tumor origin and molecular characteristics, 90-gene expression assay, tumor gene expression profiling with Next-generation sequencing (NGS) method and Immunohistochemical expression of PD-L1 were employed. Although no gastroesophageal lesions discovered by gastroenteroscopy, the 90-gene expression assay yielded a similarity score and prompted the most likely primary site was gastric/esophagus cancer. NGS revealed high TMB (19.3mutations/Mb) but no druggable driver genes identified. The Dako PD-L1 22C3 assay IHC assay for PD-L1 expression revealed a tumor proportion score (TPS) of 35%. Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C>T mutation at exon 7 and Janus kinase 1(JAK1), the patient received immunochemotherapy instead of immunotherapy alone. She was successfully treated with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance, which achieved a complete response (CR) maintained for 2 years without severe adverse events.ConclusionsThis case highlights the value of multidisciplinary diagnosis and individual precision treatment in CUP. Further investigation is needed as an individualized treatment approach combining immunotherapy and chemotherapy based on tumor molecular characteristics and immunotherapy predictors is expected to improve the outcome of CUP therapy.</p

Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

<div><p>Backgrounds</p><p>It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.</p><p>Methods</p><p>Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.</p><p>Results</p><p>A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20–0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35–0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38–0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.</p><p>Conclusions</p><p>For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.</p></div

Direct comparison of EGFR exon 19 deletions versus EGFR exon 21 L858R mutations in TKI therapy cohort in terms of HR for PFS. CI = confidence interval; EGFR = epidermal growth factor receptor; HR = Hazard ratio; PFS = progression-free survival; TKI = tyrosine kinase inhibitor.

<p>Direct comparison of EGFR exon 19 deletions versus EGFR exon 21 L858R mutations in TKI therapy cohort in terms of HR for PFS. CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p

MOESM1 of A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

Additional file 1. Questionnaire for survey of the clinical features and management of bone metastatic disease in China

Geometric distribution of indirect comparisons.

<p>Solid lines between regimens represented the existence of direct comparisons. Chemo  =  chemotherapy; EGFR  =  epidermal growth factor receptor; TKI  =  tyrosine kinase inhibitor.</p

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Direct comparison of TKI versus chemotherapy in EGFR exon 19 deletions cohort in terms of HR for PFS. CI = confidence interval; EGFR = epidermal growth factor receptor; HR = Hazard ratio; PFS = progression-free survival; TKI = tyrosine kinase inhibitor.

<p>Direct comparison of TKI versus chemotherapy in EGFR exon 19 deletions cohort in terms of HR for PFS. CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p

Flow chart of patients’ selection.

<p>Flow chart of patients’ selection.</p

Direct comparison of TKI versus chemotherapy in EGFR exon 21 L858R mutations cohort in terms of HR for PFS. CI = confidence interval; EGFR = epidermal growth factor receptor; HR = Hazard ratio; PFS = progression-free survival; TKI = tyrosine kinase inhibitor.

<p>Direct comparison of TKI versus chemotherapy in EGFR exon 21 L858R mutations cohort in terms of HR for PFS. CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p

Profile summarizing the trial flow.

<p>CI  =  confidence interval; EGFR  =  epidermal growth factor receptor; HR  =  Hazard ratio; PFS  =  progression-free survival; TKI  =  tyrosine kinase inhibitor.</p