Median OS Of Patients Research Articles

P-177 Overall survival of patients with left-sided metastatic colorectal cancer in real life: Experience from University Hospital for Tumors in Zagreb, Croatia

According to 2016 Eurostat cancer statistics, Croatia has the second-highest standardised death rate for colorectal cancer (CRC) among the EU Member States. In light of that fact, we tried to analyse the reasons behind this bad result in our cohort of patients. Available real-world data suggest that median OS of patients with left-sided mCRC is 22 to 25 months. Overall, around 750 patients are treated each year due to mCRC in Croatia. Of that, 70-75% are left-sided tumors. We present survival results of patients treated for left-sided mCRC in our institution.

NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR-mutations.

9506 Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-small-cell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95% CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively. Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences. Clinical trial information: UMIN000017069 .

Clinicopathological features of de novo CD5-positive diffuse large B-cell lymphoma

Objective: To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5(+)DLBCL). Methods: Fifty seven cases of de novo CD5(+)DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results: Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients' genders, clinical stage, the level of serum LDH,β2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence (P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients (P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression (P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients (P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression (P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5(+)DLBCL (P<0.05). Conclusions: Bcl-2 protein expression has no effect on the prognosis in de novo CD5(+)DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5(+)DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.

Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis

To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

Expression of CCR7 and Tim-3 in Childhood Patients with Acute Lymphoblastic Leukemia and Their Predictive Value for Prognosis

To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.

1q21 Gain May Challenge the Role of t(4;14) As an Adverse Prognostic Marker of Multiple Myeloma

In the era of bortezomib, traditional prognostic markers in multiple myeloma (MM) may be suspect. The outcome of patients with t(4;14) is largely improved by bortezomib based treatment. Whether the outcome of patients with t(4;14) is still homogeneously inferior remains unknown. In this long follow-up non-randomized clinical trial, we observed no significant difference in the PFS and OS of t(4;14) positive or negative patients in the bortezomib arm. Interestingly, t(4;14) was highly correlated with the presence of 1q21 gain. In t(4;14)-positive patients, the median OS of patients with and without 1q21 gain was 38.8 and 57.2 months (P=0.034), respectively. In t(4;14)-negative patients, the median OS of the two subgroups was 43.0 and 89.4 months (P&lt;0.001), respectively. In contrast, no statistical difference in PFS or OS was observed in 1q21 gain patients with versus without t(4;14) aberration. We then discovered that 1q21 gain facilitated the acquisition of new chromosome abnormalities and contributed to the genomic instability, evidenced by the strong correlation between 1q21 gain and complex karyotypes or the acquisition of more than two cytogenetic aberrations. Moreover, 1q21 gain and/or del(17p) were powerful enough to discriminate the high-risk patients. The combination of 1q21 gain with International Staging System (ISS) was useful to divide MM patients with respect to their survival. Finally, although bortezomib might benefit patients with 1q21 gain, it could not completely overcome its adverse effects, suggesting the necessity of more effective therapies for these patients. Figure Disclosures Zhan: BIPHARM LLC: Consultancy, Other: % Allocation of Profit. Anderson:Gilead Sciences: Other: Advisory Board; Janssen: Other: Advisory Board; OncoPep: Other: Scientific founder ; Sanofi-Aventis: Other: Advisory Board; C4 Therapeutics: Other: Scientific founder .

PB2176 DIAGNOSIS AND MANAGEMENT OF SYSTEMIC AL AMYLOIDOSIS IN REAL WORLD

Background:Light‐chain (AL) amyloidosis is the most common form of systemic amyloidosis, accounting for 70% of patients with amyloidosis. It is characterized by deposition of a misfolded monoclonal light‐chain that is secreted from a malignant plasma cell clone, and interferes with an organ's normal function. Clinical features depends on organs involved. To continue improving patient prospects, early and accurate diagnosis and meticulous treatment choices are essential. Immunohistochemistry of abdominal fat aspirates is the most widely available method for amyloid typing, and it has to be done by a highly specialized pathologist, combined with clinical data and genotyping, it may lead to accurate amyloidosis classification. Delayed diagnosis remains a major obstacle to initiating effective therapy.Aims:To describe retrospectively the diagnosis and management in our hospital, of twenty five patients with biopsy‐proven systemic AL amyloidosis (included between 05/2011‐01/2019).MethodsMedian age at diagnosis was 64 years (range 45‐84). 44% patients were male and 56% female. At baseline evaluation, λ free light chains was shown in 92%, median bone marrow plasma cells was 10.9% (5 patients had associated MM), 12% had unfavorable genetic. Mayo stage was distributed as follows: I (8%), II (20%), III (28%), IV (44%). 20 pts (80%) had cardiac involved and 12 (60%) had typical pattern of delayed gadolinium enhancement in magnetic resonance. Median left ventricle thickness was 16.7 mm.Results:The histological diagnosis was in 28% by renal biopsy, 20% minor salivary gland, 16% fat aspiration, 8% cardiac, and proceeds with mass spectroscopy in 2 patients. Fat aspiration was performed in 15 pts (60%), but only 4 (26%) were positive. 44% received one regimen of treatment [0‐6 lines]. Bortezomib and lenalidomide were the most used drugs in first and second line (80% and 32% respectively). 20% underwent ASCT (only 2 directly). 16% received doxycycline. The hematologic and organic response for each line and PFS is shown in table 1. Median PFS was decreasing with Mayo stage (1‐2 stage: 16 month, 3: 9.7 months, 4: 7 months. Median OS was 4 years [95% CI 1.5‐6.4] with median follow up of 7.8 years, and median OS in patients achieving RC/VGPR was 4.9 years [95% CI 1.7‐8].Summary/Conclusion:1) Our series PFS and OS are worse comparing with literature, in real world AL amyloidosis is still diagnosed late, in advance Mayo stage (72%), and cardiac involvement. 2) The fat aspiration is not the diagnosis tool in the most cases. 3) Early diagnosis is the key to managing the disease and improves de survival of these patients. 4) It could be recommendable to start therapy, if clinical‐analytic suspicious is high, although without histological confirmation, but it has to be provided in further studies.image

Deregulation of lncRNA-AC078883.3 and microRNA-19a is involved in the development of chemoresistance to cisplatin via modulating signaling pathway of PTEN/AKT.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used in the NSCLC treatment for over 30 years, and its effects are impaired by drug resistance. This study aimed to investigate the potential role of lncRNA-AC078883.3 in the development of chemoresistance against cisplatin. Real-time PCR, Western blot analysis, Immunohistochemistry (IHC) assay, bioinformatic analysis, and luciferase assay were collaboratively used to establish the lncRNA-AC078883.3/miR-19a/PTEN/AKT pathway. Also, the effect of cisplatin on cell proliferation was observed via an MTT assay. Furthermore, Cox regression and Kaplan-Meier analyses were used to study whether lncRNA-AC078883.3 is involved in the survival of NSCLC. Compared with the Cisplatin-Sensitive group, the Cisplatin-Resistance group exhibited lower levels of lncRNA-AC078883.3 and PTEN and higher levels of miR-19a and p-Akt. The growth rate of A549 and H460 cells and the IC 50 of DPP in the Cisplatin-Resistance group were higher than those in the Cisplatin-S group. miR-19a contains a putative binding site of lncRNA-AC078883.3, which enabled the luciferase activity of wild-type lncRNA-AC078883.3 to be reduced by miR-19a. In addition, by directly targeting PTEN 3'-untranslated region (UTR), miR-19a repressed the luciferase activity of wild-type PTEN 3'-UTR. The median OS of patients with reduced lncRNA-AC078883.3 expression was longer than that of patients with higher lncRNA-AC078883.3 expression. Finally, compared with low lncRNA-AC078883.3-expression patients, the high lncRNA-AC078883.3-expression patients were associated with lower miR-19a expression and higher PTEN expression. Therefore, we suggested for the first time that the low expression of lncRNA-AC078883.3 contributed to the development of chemoresistance against cisplatin.

Impact of facility patient volume on overall survival in patients with muscle invasive bladder cancer undergoing trimodality bladder preservation therapy.

e16039 Background: There is an association between higher hospital and urologist case volume and improved survival outcomes for patients with bladder cancer. Limited data on facility volume and outcomes exists following trimodality bladder preservation with TURBT followed definitive chemoradiation (CRT). Methods: The National Cancer Database was queried for patients from 2004-2013 with urothelial bladder cancer (cT2-4aN0M0) receiving definitive CRT after TURBT. High-volume bladder preservation case volume (BPCV) was defined as facilities in the &gt; 70th percentile of trimodality bladder preservation cases per ten years examined. We compared OS between high- and low-BPCV using Cox proportional hazard models. CRT was defined as &gt; = 5040cGy pelvic RT with chemotherapy given within 21 days. Propensity matching was performed to match high- and low-volume centers. Results: A total of 666 treatment facilities treating 1,635 patients with bladder preservation were identified with a median follow-up of 26 months (range 2-136 months). A 70th percentile cutoff identified 497 patients that received treatment at 64 high-volume facilities. Median OS of patients treated at high BPCV centers was 37.0 months (95% CI, 27.9-33.6) versus 32.3 months (95% CI, 27.3-46.7) for patients treated at low BPCV centers (P = 0.004). High BPCV facilities were independently associated with a decreased hazard of death (HR, 0.86, 95% CI, 0.75-0.98; P = 0.031). When BPCV was analyzed as a continuous variable, an increasing number of bladder preservation cases per institute was also independently associated with improved OS (HR: 0.98, 95% CI, 0.97-0.99; P = 0.044). In the propensity score matched cohort, median OS of patients treated at high BPCV was 36.1 months (95% CI, 26.5-45.8) versus 28.1 months (95% CI, 23.9-32.3) for patients treated at a low BPCV facility (P = 0.016). Conclusions: In this observational cohort, treatment at a high BPCV facility was associated with improved OS. Causal factors for this finding may include greater institutional expertise in multidisciplinary bladder cancer care and potential advantages in treatment technology.

Clinical features and treatment outcome of elderly multiple myeloma patients with impaired renal function.

BackgroundRenal impairment (RI) is a most common complication of multiple myeloma (MM), which is associated with an increased risk of early death and worse survival.MethodsWe retrospectively analyzed clinical features and outcomes of 77 MM patients over 70 years old and compared the differences between with and without RI groups.ResultsThe percentage of elder MM patients with RI was 61%. Hemoglobin level was a protective factor (OR = 0.954, P = 0.033), while creatinine and hypertension were hazards (OR = 1.288, P < 0.001 and OR = 30.12, P = 0.008). And the percentages of patients with mild‐to‐moderate RI and moderate‐to‐severe RI were 40.4% and 59.6%. Complete remission (CR) rate was higher in patients treated with bortezomib (33.3%) than those with non‐bortezomib treatment (3.33%) (P = 0.007). Meanwhile, CRrenal was higher in patients with bortezomib (58.3%) than non‐bortezomib treatment (22.2%) (P = 0.025). The median OS of the patients with RI treated with bortezomib was longer than those with non‐bortezomib regimens (15.0 vs 6.0 months, P = 0.001). The same result was observed in the patients with moderate‐to‐severe RI (13.0 vs 6.0 months, P = 0.007). The median OS of the patients with RI receiving the bortezomib regimens (15 months) was longer than those with non‐bortezomib regimens (6.0 months) (P = 0.001).ConclusionHemoglobin is a protective factor in elder patients with RI, while creatinine and hypertension were hazards. The median OS of elderly patients with RI was worse, and bortezomib can improve the CR rate in these patients.

Unique profiles of targetable genomic alterations and prognosis in young Chinese patients with lung adenocarcinoma

ObjectiveLung adenocarcinoma in young patients is a rare entity, and the targetable genomic alterations (GAs) are poorly studied. In other cancers, it has been demonstrated that young age defines unique disease biology. Here, the association of young age with GAs and prognosis is studied in a large cohort of Chinese patients. MethodsWe retrospectively screened 1000 consecutive patients, and identified 181 patients aged 40 years or younger. GAs were identified by next-generation sequencing (NGS) assay. The clinical and genetic characteristics were analyzed. ResultsAmong younger group, 167(92.3%) patients were diagnosed withadvanced-stage adenocarcinoma, 98(54.1%) were female, 27(14.9%) were smokers, and the median age was 35 years. Targetable GAs which were significantly more common in the younger population (P < 0.001), were associated with young age (P < 0.05). The frequency of ALK translocations, EGFR and KRAS mutations was 37.6%, 34.3% and 6.1%, respectively. Younger patients had a higher prevalence of rare GAs including HER2, ROS1 and MET (P < 0.05). Prognosis for younger patients was similar (median OS of patients with GAs, 23.91 vs 23.67 months, P > 0.05) or better than that for older population (median OS of patients without GAs, 44.28 vs 41.88 months, P < 0.05) according to GAs. Therapy modality was an independent prognostic factor (P < 0.05), and 83% of death rate decreased if given preferred therapy. ConclusionYounger patients with lung adenocarcinoma had unique prevalence of targetable GAs. Comprehensive genotyping including NGS is recommended for personalized therapy and prognosis evaluation in this population.

Proposed Modification of the 8th Edition of the AJCC Staging System for Gastric Cancer

Background: The American Joint Committee on Cancer (AJCC) staging system has been the standardized staging system for malignancies since the first edition in 1987. The 8th edition of gastric cancer was released in 2016, and is expected to be used in clinical practice in 2018. The aim of this study was to improve this new gastric cancer staging system. Methods: We conducted median overall survival analyses in a cohort of 8359 gastric cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2014) via Kaplan–Meier curves and log-rank tests, and proposed a modified staging system based on median OS. The concordance index (C-index) was conducted to evaluate the predictive accuracy. Results: Using the 8th AJCC staging system, the median OS of patients at the same stage varied widely between the different substages, especially in stage III. Despite the definitions of T, N, and M, substages in the modified staging system were regrouped based on median OS. The C-index of stage III patients with the modified staging system [0.579, 95% confidence interval (CI) 0.564–0.593] was higher than the 8th AJCC staging system (0.567, 95% CI 0.552–0.581). Moreover, we divided these patients into two groups according to their examined lymph node counts (≥15 or 1–14), and studied the effectiveness of the modified staging system in the two groups. Conclusions: The modified 8th AJCC staging system for gastric cancer proposed in this study generates better prognostic stratifications and may be evaluated for further update.Abbreviations:AJCCAmerican Joint Committee on CancerOSOverall SurvivalSEERSurveillance, Epidemiology, and End Results

Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

Central Nervous System Relapse in Patients with Extranodal NK/T-Cell Lymphoma, Nasal Type

Introduction: Extranodal NK/T cell lymphoma (ENKTL), nasal type is an uncommon, unique subset of non-Hodgkin lymphoma. Its clinical outcome has improved significantly with introduction of non-anthracycline based chemotherapy and radiotherapy. Yet little is known about central nervous system (CNS) involvement of ENKTL, nasal type.Methods: A total of 168 patients with ENKTL-nasal type were included in this study. All patients were diagnosed between 2003.1 and 2016.6 in Asan Medical Center, Seoul, Korea. Patients with secondary CNS involvement at diagnosis and patients with aggressive NK-cell leukemia were excluded. CNS involvement was confirmed by pathology or MRI of affected organ. Cox regression analysis was performed to identify possible risk factors for CNS involvement.Results: Out of 168 patients, 109 patients were male and 59 patients were female. Median age at diagnosis was 52 years (range: 16-83). The number of patients with stage I/II disease was 112 (66.7%) and stage III/IV was 56 (33.3%). The number of patients with low, intermediate, high prognostic index of natural killer cell lymphoma (PINK) was 70 (41.7%), 55 (32.7%), 43 (25.6%) each. Thirty (17.8%) out of 168 received anthracycline-based chemotherapy for first line treatment, either CHOP or CHOP-like regimen, and 123 patients (73.2%) had non-anthracycline based chemotherapy. Ninety two patients (54.8%) received sequential radiotherapy or concurrent chemoradiation.During the 63 months of median follow-up, 9 patients (5.4%) developed CNS relapse. Among those 9 patients, 4 had leptomeningeal involvement, 3 had brain parenchymal disease, and the remaining 2 had both leptomeningeal and brain parenchymal involvement.Median time from diagnosis to CNS relapse was 5.0 months (95% confidence interval (CI): 4.6-5.3). Median OS after CNS metastasis was 3.4 months (1.6-5.1). Significant differences in OS were noted between the two groups, with median OS in patients with CNS relapse of 8.9 months (7.8-10.1) and 58 months (19.6-96.4) in patients without CNS relapse. (p<0.001)After univariate analysis, eastern cooperative oncology group (ECOG) performance status≥2 (hazard ratio (HR) 9.7 [95% CI: 1.1-84.3] p=0.039), stage III/IV (HR 5.8 [1.5-23.5], p=0.013), lung or pleural involvement (HR 12.5 [3.3-47.5], p<0.001), peritoneal involvement (HR 46.2 [4.1-521.5], p=0.002), PINK≥2 (HR 6.2 [1.2-32.2], p=0.03) were associated with increased CNS relapse. First-line treatment regimens including etoposide or high-dose methotrexate (MTX) were associated with decreased incidence of CNS relapse. (HR 0.24 [0.06-0.88], p=0.032). Due to the small number of CNS events, multivariate analysis was not available. No association was found with age, sex, serum lactate dehydrogenase level, number of involved extranodal sites, international prognostic index, non-nasal or nasal type and Ki-67 labeling index.Conclusions: Our study demonstrated that CNS relapse or progression in ENKTL-nasal type is rare (5.4%) but its clinical course is poor. CNS event usually occurred in the early course of the disease and we suggest that CNS evaluations should be considered in highly selected patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hematopoeitic Cell Transplant - Comorbidity Index (HCT-CI) Score Is a Useful Tool for Predicting Induction Mortality and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia Patients

Intro:Assessment of induction mortality risk in acute myeloid leukemia (AML) patients is challenging. Hematopoietic cell transplant comorbidity index (HCT-CI) score was designed for risk assessment of patients undergoing an allogeneic transplant. However, it is often used in clinical practice to assess induction mortality risk in AML patients. We analyzed the predictive power of the score to assess induction mortality risk as well as overall survival in AML patients at our institution.Methods:Between Jan 2009 and March 2013, 101 consecutive newly diagnosed AML patients treated at our institution were included for analysis. All patients received bolus HiDAC (3gm/m2) on day 1-5 and high dose mitoxantrone (80mg/m2) on day 2. The median age was 65 years (range18-90). The total number of patients in the age group <60, 60-69 and ≥70 were 30(29.7%), 35(34.6%) and 36(35.6%) respectively. HCT-CI scores were calculated before induction chemotherapy. Kaplan Meir curve was used to calculate OS and PFS. 4-week induction mortality was calculated from the date of the induction chemotherapy. The patient cohort was divided into those with HCT-CI scores of > or ≤3.Results:The number of patients with the HCT-CI score of 0,1,2 and 3 were 8,13,17 and 13 respectively. 50% of our patients (51 patients) had a score of 4 or more on the HCT-CI index. The 4 and 8-week mortality in our cohort was 3/101 (2.9%) and 7/99 (7%) respectively. 4-week induction mortality in <60, 60-69 and ≥70 years of age groups were 0/30(0%), 1/35(2.8%) and 2/36(5.5%) respectively. Similarly, in above age groups, 8-week induction mortality were 0/29(0%), 2/34(5.8%) and 5/36(13.8%) respectively. The median OS in patients with an HCT-CI score ≤3 was 87 months versus 11.5 months in those with a score >3 (log-rank, p=0.0046, Fig1). 2-yr NRM rate for patients with HCT-CI score ≤3 and >3 was 47% and 71%, respectively (p=0.01, Fig2). Hazard ratio for overall mortality in patients with HCT-CI score >3 is 1.793 with p=0.023, 95% CI = (1.083 - 2.971). HR for 8-week mortality in patients with an HCT-CI score >3 is 2.035 (p=0.412), although not statistically significant due to a low number of events. However, by Cox multivariable regression analysis HCT-CI retained a significant impact on 8-week mortality (HR=1.24, p= 0.03) and overall survival (HR=1.144, p= 0.006).Conclusion:An HCT-CI score is a valuable tool in the assessment of the induction mortality in newly diagnosed AML patients and can be used for risk assessment of overall mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Molecular characteristics of colorectal cancer in a Middle Eastern population in a single institution.

BACKGROUNDThe few studies of the molecular biology of colorectal cancer (CRC) in Middle Eastern populations have included only small samples of patients.OBJECTIVEEvaluate the frequency and prognostic effect of RAS, BRAF, PIK3CA, PTEN, and EGFR somatic mutations as well as mismatch repair (MMR) deficiency in Lebanese Middle Eastern patients.DESIGNRetrospective single-center descriptive study.SETTINGLebanese Middle Eastern patients in a tertiary medical center.METHODSWe included all patients diagnosed with CRC between January 2010 and December 2015, in whom RAS mutational status and the expression of MLH1 and MSH2 proteins were available.MAIN OUTCOME MEASURESGenetic mutations detected by direct sequencing while MMR protein expression was evaluated by immunohistochemistry.SAMPLE SIZE645 patients.RESULTSRAS, BRAF, EGFR, PI3KCA, and PTEN mutation rates were 38.5%,12.9%, 0%, 11.1% and 0% respectively. The MMR deficiency rate was 20.6%. No factor was associated with RAS mutation whereas MMR-deficient tumors were less likely to be metastatic at diagnosis. Among patients with wild-type RAS females fared better than males (median overall survival [OS]=1734 vs 1079 days respectively, P=.015) even after adjustment for confounding factors by Cox regression analysis. This finding was not reproduced in the RAS-mutated group. The median OS of patients with MMR-deficient tumors was not reached, while the median OS was 2475 days in patients who had maintained expression of both MLH1 and MSH2.CONCLUSIONThe RAS mutation rate was similar to Western and East Asian countries, but not for the BRAF mutation and MMR deficiency. We also found a prognostic effect for sex in the RAS wild-type group, a finding worthy of further exploration.LIMITATIONSRetrospective, single center and small sample size. Expression of MSH6 and PMS2 not analyzed.

P3.17-001 The Prognostic Analysis of Postoperative Radiotherapy for Esophageal Squamous Cell Carcinoma with Different Status of Lymph Node Metastasis

Lymph node metastasis is a significant prognostic factor in patients with resected esophageal cancer. Although the role of postoperative radiotherapy has not been confirmed, a large number of studies have shown that postoperative radiotherapy can improve the local control and survival, especially for stage III and lymph node positive patients. This study retrospectively analyzed the prognostic factors of postoperative radiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), and evaluated the prognostic value of different status of lymph node metastasis. Data from 121 patients with locally advanced ESCC who underwent radical resection and received postoperative radiotherapy from 2006 to 2013 were reviewed retrospectively. OS and DFS were estimated using Kaplan-Meier. Univariate analysis and multivariate analysis were performed to investigate prognostic factors by the Log-rank test and the Cox regression model. The effects of different status of lymph node metastasis on OS and recurrence patterns were compared. The median DFS of all patients was 22.57 months, and median OS was 32.90 months. Multivariate analysis showed that Karnofsky Performance Status, length of tumor and positive lymph nodes ratio (LNR) were independent prognostic factors of DFS and OS. For patients with lymph nodes metastasis, LNR has better prognostic value for OS (AUC=0.673, P =0.04) compared with the number of positive lymph nodes (AUC=0.584 P=0.31). The median OS of patients with LNR≤ 15% and LNR>15% were 33.43 and 19.20 months, P =0.04. Patients without lymph node skip metastasis (NSM) had better OS than that with NSM, but the difference was not statistically significant. Among the patients with both LNR>15% and NSM, OS was significantly worse than other lymph node positive patients, with median OS of 14.33 vs. 32.50 months, P=0.02. The analysis of the treatment failure patterns showed that more distant metastases were observed in patients with LNR>15%, while more local and regional recurrences were observed with LNR≤15%. The status of lymph node metastasis was related to the prognosis of postoperative radiotherapy for locally advanced ESCC. LNR has better prognostic value for OS, treatment failure patterns varied in different LNR. The patients with both high LNR and NSM have significantly poorer prognosis.

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.

The Prognosis of Small Cell Lung Cancer in Patients with Pulmonary Fibrosis.

The purpose of this study was to assess the prognosis of small cell lung cancer (SCLC) based on the underlying pulmonary disease. A total of 204 patients with SCLC were reviewed and categorized into three groups: normal, emphysema and fibrosis. The median overall survival duration (OS) in patients with normal lungs (n=57), with emphysema (n=105) and fibrosis (n=42) was 21.3, 16.4 and 10.8 months (p=0.063). In limited-stage disease (LD), the median OS in patients with fibrosis (7.4 months) was shorter than normal (52.7 months) or emphysema patients (26.4 months) (p=0.034). In extensive-stage disease (ED), the median OS in patients with fibrosis (12.7 months) was not significantly different from normal (11.4 months) or emphysema patients (13.5 months) (p=0.600). Patients with fibrosis had a poorer prognosis than normal or emphysema patients in LD-SCLC, but the coexistence of pulmonary fibrosis did not affect the prognostic outcomes in ED-SCLC.

Prognostic value of immunohistochemical factors in esophageal small cell carcinoma (ESCC): Analysis of clinicopathologic features of 73 patients.

37 Background: Esophageal small cell carcinoma (ESCC) is a very rare but aggressive disease with poor prognosis. The objective of this study was to describe immunohistochemical and clinicopathological features of patients with ESCC in Chinese population, and to clarify how the utilization of different marker combinations affects prognostic outcome. Methods: We retrospectively reviewed a total of 73 patients with ESCC. The tumor samples obtained were immunohistochemically analysed of neuron specific enolase enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), and Thyroid Transcriptional Factor-1 (TTF-1). The positivity of these four factors and their correlation with clinical characteristics was described. The relation between positive expression of them and survival was also analysed. Results: The median age at the time of diagnosis was 57 (ranging from 36 to 77 years). 55 patients were male (75.3%) and 18 patients (24.7%) were female. Immunological reactivity of the samples was Syn 68.5%, TTF-1 46.6%, NSE 90.4%, CgA 43.8%. There were sixteen cases with four biomarkers positive (21.9%), twenty-six cases with three biomarkers positive (35.6%), fourteen cases with two biomarkers positive (19.2%), and twelve cases with only one biomarker positive (16.4%). Five cases (6.8%) were all negative. The expression of NSE was insignificantly associated with primary tumor location (P = 0.01). The 2-year and 3-year cancer-specific survivals were 24.8% and 19.9%, respectively. The median OS was 13.5 months. Although not statistically significant, expression of any factor was tended to positively affect survival. And the median OS of patients without expression of four factors was significant worse than those with at least one factor of positive expression (6.1 months vs 15.3 months, P = 0.002). Conclusions: Chinese ESCC patients have a poor prognosis even after local or systemic treatment. Relatively high percentages of positive labeling of Syn, CgA, NSE and TTF-1 implicated their diagnostic value in ESCC. More important, these four biomarkers might be probable favourable prognostic factors for ESCC.