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We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post‐treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC‐AUC > 0.65, and all models had overall ROC‐AUC > 0.95. Predicted response scores significantly distinguished (P 50% showed a statistically significant reduction (log‐rank P

Purpose Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established. Materials and methods Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy. Results Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response. Conclusion The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

Background In this study, we observe the patterns initial palliative treatment for premenopausal patients with HR-positive/HER2-negative MBC and determine if nonadherence to clinical guidelines are associated with worse clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) in the South Korean population. Methods A retrospective review was performed for premenopausal patients diagnosed with HR-positive/HER2-negative MBC between October 1997 and May 2016 who received palliative systemic treatments at a large tertiary medical center. Survival outcomes were analyzed according to the palliative treatment received prior to disease progression. Results The review identified a total of 272 premenopausal patients meeting study criteria, whose median age was 39 years. Endocrine therapy was the initial treatment in 137 patients (Group 1) with chemotherapy as initial treatment in 135 patients. In the latter group, chemotherapy was continued in 78 patients (Group 2), whereas chemotherapy was switched to endocrine treatment in 57 patients prior to any disease progression (Group 3). Both PFS and OS were significantly longer for chemotherapy-endocrine therapy (median PFS 18.2 months and OS 85.2 months) than for chemotherapy-alone (median PFS 12.6 months and OS 45.5 months) or endocrine therapy-alone (median PFS 7.0 months and OS 57.3 months) (all p values

Objectives Several studies have demonstrated the promise of continuation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) beyond progression in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). The aim of the present study is to clarify the efficacy of continuation of gefitinib in patients with NSCLC beyond progression. Materials and methods A total of 50 patients with EGFR-mutant NSCLC who progressed based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria during gefitinib treatment were eligible. The primary endpoint was progression-free survival-2 (PFS2; time from first gefitinib dose to off-gefitinib progression). Secondary endpoints were PFS1 (time from first gefitinib dose to RECIST 1.1 progression); the difference between PFS2 and PFS1 (PFS2-PFS1); overall survival (OS); and safety. Patients received gefitinib 250 mg/d orally until symptomatic progression or at the investigator’s discretion. Results Between January 2016 and March 2017, 50 patients were enrolled in this study. One patient withdrew consent, leaving a total of 49 patients to be evaluated. The median PFS2-PFS1 was 5.1 months (95% CI, 2.5–7.8), and the median PFS2 was 27.7 months (95% CI, 21.6–33.9). Twelve patients (24.4%) continued gefitinib therapy for 14 months (median value, range 7.2–20.3 months) after RECIST 1.1 progression. The median OS was not reached. Patients were classified by the characteristics of progression at the time of enrollment. PFS2-PFS1 was significantly shorter in patients with pleural metastasis or pleural effusion compared with the other types of progression (1.8 months vs. 7.1 months, p-value = 0.005). Conclusion In patients with EGFR-mutant NSCLC who experience progression, it is beneficial to maintain gefitinib treatment with local treatment such as radiotherapy until symptomatic progression. However, in patients with pleural metastasis or effusion, continuation of gefitinib beyond progression should be carefully determined on a case by case basis.

Introduction ROS1-rearranged NSCLC is classified as a distinct molecular subset of NSCLC with a therapeutic target. ROS1 rearrangement is most often identified in never-smokers with adenocarcinoma and EGFR and ALK receptor tyrosine kinase gene (ALK) wild type. Treatment with tyrosine kinase inhibitors (TKIs), which target the ROS1 kinase domain, is considered the standard of care. TKIs have been shown to have a robust and durable response. However, information regarding the clinical outcomes of TKI treatment, including brain metastasis, remains limited. Methods We identified 103 consecutive cases of ROS1-positive NSCLC by using break-apart fluorescence in situ hybridization (n = 84), next-generation sequencing (n = 23), or both (n = 3). Information regarding fusion breakpoints was available for eight patients. Clinical data, including patient characteristics, incidence of brain metastasis, response to chemotherapy, or to TKIs, were retrospectively analyzed. Results The median patient age was 56 years, and 58.9% of the patients were female. Most of the patients (75.7%) were never-smokers. Adenocarcinoma was predominant (98.1%), and two cases with pleomorphic carcinoma were identified. Sixty percent of patients had an extrathoracic metastatic lesion, and 22% had an intracranial lesion at the initial presentation or at the time of recurrence. The median time to development of brain metastases was 12.0 months (range 2.1–84.1). The most common fusion partner was CD74 molecule gene (CD74), followed by syndecan 4 gene (SDC4), ezrin gene (EZR), tropomyosin 3 gene (TPM3), TRK-fused gene (TFG), zinc finger CCHC-type containing 8 gene (ZCCHC8), sacrolemma associated protein gene (SLMAP), and myosin VC gene (MYO5C). All of these fusion partners preserved the tyrosine kinase domain of ROS1. The median overall survival time was 52.1 months (95% confidence interval [CI]: 23.6–not reached). In the 90 patients who were treated with pemetrexed-based chemotherapy, the overall response rate and progression-free survival time were 53.3% and 8.0 months (95% CI: 6.4–11.7), respectively. The overall response rate and progression-free survival time were 70.7% and 12.7 months (95% CI: 8.1–21.8), respectively, for the 50 patients treated with TKIs. Brain metastasis was more often observed during TKI treatment (15.5%) than during pemetrexed-based chemotherapy (6.7%). Conclusions ROS1-positive NSCLC has distinct clinical characteristics, with an effective and durable response to both TKIs and pemetrexed-based chemotherapies. Regardless, given its novel characteristics and distinct clinical responses to conventional chemotherapies and TKIs, the treatment strategy for ROS1-positive NSCLC remains to be further developed.

Background: We designed a single-arm, open-label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplementation in patients with refractory colorectal cancer (CRC) that failed to respond to standard treatments including 5-fluorouracil, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1 every 3 weeks, with folic acid and vitamin B12 supplementation. Treatment was continued until disease progression or intolerable toxicity. Between June 2016 and October 2016, 24 patients were enrolled in this study. Results: One patient withdrew consent, leaving a total of 23 patients for evaluation. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). There was no patient with complete response (CR) or partial response (PR). However, stable disease was observed in 10 patients (43.4%) and maintained more than 6 months in 7 of 10 patients. The median progression-free survival was 1.6 months (95% CI, 1.1-2.0) and the median overall survival was 9.8 months (95% CI, 5.9-13.6). Grade 3 treatment-related adverse events occurred in one patient with elevated liver enzymes and hematologic adverse event of grade 2 anemia was observed in one patient. There were no cases of dose reduction or treatment-related deaths and all toxicities were manageable. Conclusions: Pemetrexed monotherapy showed moderate disease control and acceptable toxicity profile as salvage therapy for refractory CRC.

OBJECTIVES For patients with locally advanced oesophageal cancer, improved complete pathological response after neoadjuvant chemoradiation (nCRT) and the detrimental effects on the quality of life related to oesophagectomy have led to the need for a reliable method to select patients who have achieved complete pathological response and do not need surgery. The reliability of 18F-fluorodeoxyglucose positron emission–computed tomography (PET-CT) for predicting the pathological response after nCRT was evaluated. METHODS Patients with locally advanced oesophageal cancer who were treated with nCRT and oesophagectomy from July 2010 to February 2017 were analysed. On the post-nCRT PET-CT, a complete metabolic response was defined as all tumourous lesions demonstrating maximum standardized uptake value (SUVmax) ≤2.5. To minimize the effect of radiation-induced oesophagitis, complete metabolic response was also defined as no viable lesion distinguishable from the background with diffuse uptake. The sensitivity, specificity, positive predictive value and negative predictive value were analysed for SUVmax, [X]ΔSUVmax and %ΔSUVmax. RESULTS A total of 158 patients with oesophageal squamous cell carcinoma were analysed. The rate of complete pathological response was 27.8%, and that of complete metabolic response was 7.6%. The sensitivity, specificity, positive predictive value and negative predictive value based on SUVmax ≤2.5 and visual normalization were 95%, 14%, 74% and 50%, respectively. Analysis for [X]ΔSUVmax and %ΔSUVmax using the optimal cut-off values determined by the receiver operating characteristic curves did not show an improved predictive efficacy. CONCLUSIONS PET-CT is not a reliable tool for predicting pathological response. Patients diagnosed with resectable oesophageal cancer who underwent neoadjuvant therapy should not be exempt from surgery based on PET-CT results.

Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year. Several studies recommend the same regimens of chemotherapy as used for circulating AML to treat isolated MS. We focused on the diagnosis of MS in this study. The correct diagnosis of MS is important for adequate treatment. In conclusion, MS should be considered in the differential diagnosis of intestinal tumor. (Korean J Gastroenterol 2016;68:148-151)

Extranodal natural killer/T-cell lymphoma (ENKTL) is associated with Epstein-Barr virus (EBV) infection, a common cause of hemophagocytosis. As interleukin-18 (IL18) is related with hemophagocytosis, we measured serum IL18 and IL18-related cytokines of newly diagnosed patients with ENKTL (N = 114) to investigate the role as a biomarker for hemophagocytosis and determine the prognosis of ENKTL. The median value of serum IL18 was 20.5 pg/mL (1.23-2021.81 pg/mL). The high IL18 group (≥20.5 pg/mL) was associated with stage III/IV, the presence of hemophagocytosis and poor treatment outcome. Serum IL18 showed significant positive correlations with TNFα, IFNγ, and IP10. Overall survival was significantly different between the high and low IL18 groups (p < .001), and high serum IL18 was independently prognostic for survival in the multivariate analysis. In conclusion, serum IL18 levels may be associated with the hemophagocytosis and poor survival outcomes in patients with ENKTL.

PURPOSE We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance. Materials and Methods A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2-, luminal B and HR+/HER2+, HR-/HER2+ and HER2-enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS. RESULTS In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation-related discordant breast cancer including the VHL gene in the HR+/HER2- group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01). CONCLUSION A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.

Purpose This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). Materials and methods From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status. Results Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression. Conclusion EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

e17000Background: The results from randomized phase III trials showed that 3-weekly docetaxel added to androgen-deprivation therapy (ADT) has a significant impact on survival of patients with mCNPC...

10113Background: Iron deficiency anemia (IDA) are common complications in cancer patients. Evidence on intravenous (IV) iron for treatment of chemotherapy-induced anemia (CIA) is emerging. Herein, ...

840 Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplement in refractory colorectal (CRC) patients who failed standard treatments, including 5-FU, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1, every 3 weeks, with folic acid and vitamin B12 supplementation. Patients began vitamin supplementation with B12 intramuscular injection (1000 mcg) every 9 weeks starting 1 week before the first pemetrexed dose, and patients received daily oral folic acid (1 mg) starting at least 5 days before the first pemetrexed dose. Treatment was continued until disease progression or intolerable toxicity was observed. Results: Between June 2016 and October 2016, 24 patients were enrolled in this study. One patient withdrew content, leaving a total of 23 patients to be evaluated. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). No complete response and no partial response were observed among the patients. Stable disease was observed in 10 patients (43.4%), and 7 patients had a response duration of 2 months or more. The median PFS was 1.6 months (95% CI, 1.1 to 2.0) and the median OS was 9.8 months (95% CI, 5.9 to 13.6). Only one patient experienced treatment-related toxicity of grade 3 or more. Neither hematologic toxicities nor dose reduction due to treatment-related toxicities were observed. There was no treatment-related death. Conclusions: Pemetrexed monotherapy showed moderate disease control and an acceptable toxicity profile as salvage therapy for refractory CRC. Clinical trial information: NCT02588781.