Difference In Disease-free Survival Research Articles

Evaluation of tumor infiltrating lymphocites (TILs) and survival in patients with resected non-small cell lung cancer.

e20010 Background: Due to the prognosis of non-small cell lung cancer (NSCLC), even at initial stages we need to characterise better our patients in order to know their prognosis. The purpose of our study is to find some prognostic factors to help us to choose the best therapeutic approach. We found some data about histology and tumor lymphocytic infiltration. Methods: We followed outcome of 94 patients diagnosed of initial stage NSCLC that underwent surgery in our institution between 2010-2013, for more than 5 years, and related survival with findings in tumor samples. Results: Tumor samples were classified in order to establish 4 variables related to tumor lymphocitic inflltration (TILs, as it was established by Brambilla et al): absent, mild, moderate and intense. 20 (21.3%) patients were considered TILs intense, 36 (38.3%) moderate, 33 (35.1%) mild and 5 absent (5.3%). We found some significative differences in disease free survival (DFS, more favorable for TILs absent group), but none for overall survival (OS). Conclusions: TILs and tumor stage could be part of an immunoscore to classify initial stage NSCLC, this score should be validated in future studies [Table: see text]

Abstract P1-15-24: Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy

Abstract Background: Among patients with locally advanced breast cancer (LABC), preoperative systemic treatment is the standard of care; approximately 80% of the patients treated with neoadjuvant chemotherapy present partial or complete clinical response, however there are patients who progress during this therapy or at the end of it, the tumors remain inoperable, this confers a worse prognosis, with an increase in the rates of metastasis and decrease overall survival. The benefit of concomitant chemoradiotherapy in local control is controversial. The objective of this trial is to analyze the efficacy of local control and survival in patients with locally advanced breast cancer who received systemic treatment plus chemoradiotherapy or radiotherapy alone preoperatively. Patients and Methods Prospective, randomized, open label trial; patients with LABC whom after neoadjuvant chemotherapy based con anthracyclines and taxanes have disease progression or inoperable disease. Arm A (standard) received radiotherapy (RT) 50 Gy in 25 fractions or chemoradiotherapy (CRT)(gemcitabine 100 mg/m2 plus cisplatin 30 mg/m2) weekly during radiation. The primary endpoint was local recurrence. Secondary end points included systemic recurrence, overall survival and -surgical complications. Statistical analysis was done with SPSS v 20.0, groups comparison was done with X2, survival was analyzed with Kaplan-meier method and comparison among groups with log-rank. Proportional Cox model associate clinical variables with recurrence and death. Local ethics committee approves the trial. Results: 78 patients were included, median follow-up was 116 months (110-121) at this time, 37 patients had recurrence (local, systemic or both) of which 18 were treated with CRT vs 19 RT alone (51.4 vs 44.2%, p=0.34). Higher rates of local recurrence were in RT alone 63.1% vs 38.9% with chemoradiotherapy with significance difference (p=0.004). There were no differences in disease free survival (p=0.542) and overall survival was found (p=0.303), 57.1 vs 53.5% respectively. Proportion of surgical complications were similar 71.4% for CRT vs 69.8% for RT (p=0.848). However hematological and gastrointestinal toxicity were more prevalent in patients treated with CRT p<0.005 Conclusion: Chemoradiotherapy it´s a feasible option to reduce the risk of local recurrence, however without any additional benefit to improve the recurrence-free survival or overall survival. Surgical complications are still the same. Citation Format: Ramos M, Arce C, Lara F, Alvarado A, Castañeda N. Randomized phase II trial to evaluate chemoradiotherapy vs radiotherapy among non-responders breast cancer patients treated with chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-24.

A matched survival analysis of patients treated with neoadjuvant FOLFIRINOX prior to pancreatic surgery: prognosis changes with downstaging of disease

Background: There is a paucity of data relating to the oncological behaviour of pancreatic tumours following neoadjuvant FOLFIRINOX. Methods: Patients with pancreatic adenocarcinoma who received neoadjuvant FOLFIRINOX chemotherapy (FOLFIRINOX group) in a single centre were matched by age, sex, type of surgery, performance status and post-operative histological stage with a group who did not receive neoadjuvant therapy prior to pancreatic surgery (MATCH group). Statistical methods included Kaplan-Meier survival estimates with log-rank test and Cox proportional hazard regression. Co-variates included: age, sex, performance status, type of surgery, PV resection, Ca19-9, presentation & pre-op radiological stage, histological stage, tumour differentiation, lymphovascular or perineural invasion, and neoadjuvant radiation therapy. Results: Fourteen patients in the FOLFIRINOX group (median age 60; 8F) were identified from a prospectively managed database and were matched 1:1 using described criteria. Mean overall survival for FOLFIRINOX and MATCH were 37.4 (95% CI 20.3 -54.4) and 40.8 (95% CI 29.4 - 52.2) months respectively (p=0.459). There was no difference in disease free survival (22.2. v 29.8; p=0.259). Cox regression analysis identified only margin status (p=0.008) as a prognostic indicator for overall survival. Conclusion: In this series prognosis following neoadjuvant FOLFIRINOX appears similar to the stage of disease achieved following treatment rather than at presentation.

A matched survival analysis of patients treated with neoadjuvant FOLFIRINOX prior to pancreatic surgery: prognosis changes with downstaging of disease

Background: There is a paucity of data relating to the oncological behaviour of pancreatic tumours following neoadjuvant FOLFIRINOX. Methods: Patients with pancreatic adenocarcinoma who received neoadjuvant FOLFIRINOX chemotherapy (FOLFIRINOX group) in a single centre were matched by age, sex, type of surgery, performance status and post-operative histological stage with a group who did not receive neoadjuvant therapy prior to pancreatic surgery (MATCH group). Statistical methods included Kaplan-Meier survival estimates with log-rank test and Cox proportional hazard regression. Co-variates included: age, sex, performance status, type of surgery, PV resection, Ca19-9, presentation & pre-op radiological stage, histological stage, tumour differentiation, lymphovascular or perineural invasion, and neoadjuvant radiation therapy. Results: Fourteen patients in the FOLFIRINOX group (median age 60; 8F) were identified from a prospectively managed database and were matched 1:1 using described criteria. Mean overall survival for FOLFIRINOX and MATCH were 37.4 (95% CI 20.3 -54.4) and 40.8 (95% CI 29.4 - 52.2) months respectively (p=0.459). There was no difference in disease free survival (22.2. v 29.8; p=0.259). Cox regression analysis identified only margin status (p=0.008) as a prognostic indicator for overall survival. Conclusion: In this series prognosis following neoadjuvant FOLFIRINOX appears similar to the stage of disease achieved following treatment rather than at presentation.

Prognostic Value of Transferrin Receptor-1 (CD71) Expression in Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the commonest childhood cancer. Transferrin receptor 1 (CD71) is a trans-membrane glycoprotein which has important role in iron homeostasis by acting as a gatekeeper regulating iron uptake from transferrin and is an attractive target for anti-cancer agents, particularly those that aim to induce lethal iron deprivation in malignant hematopoietic cells. To assess the prognostic value of Transferrin receptor -1 (CD71) in children with newly diagnosed ALL. This study was carried out on 75 patients with newly diagnosed ALL. Transferrin receptor-1 expression was analyzed on the bone marrow blasts by flow cytometry at time of diagnosis with positive CD71 expression is considered when ≥20% of malignant cells express this marker while negative expression is considered when <20% of malignant cells express this marker. Transferrin receptor-1 positive expression was detected in 45 patients (60%) while negative expression was found in the remaining 30 patients (40%). CD71 expression was significantly higher on T- ALL patients compared with B-ALL patients. Positive CD71 expression at diagnosis was significantly associated with bad clinical and laboratory prognostic factors as lymphadenopathy, higher white blood cell count, higher hemoglobin level, lower platelets count, and higher blast cells in peripheral blood and bone marrow and higher lactate dehydrogenase levels'. There were significant differences in disease free survival (DFS) and overall survival (OS) between positive and negative CD71 expression groups with significantly shorter DFS and OS in positive CD71 expression group compared to negative group. 'Positive Transferrin receptor -1 (CD71) expression in patients with ALL is adverse prognostic factor and should be taken in consideration in designing future therapeutic strategies based on patient- specific risk factors'.

Clinical feature of who grade 2 and 3 pancreas neuroendocrine tumor

Introduction: This study aimed to evaluate clinicopathologic outcome of WHO grade 2 and 3 Pancreas NET and clarify the risk factor for survival and recurrence of WHO grade 2 and 3 pancreas NET. Methods: We retrospectively reviewed database of 126patients who underwent curtive intent surgery for pancreas NET at a single institute from January 2000 through december 2016. WHO grade 2(n = 29) and grade 3(n = 30) patients were included in this study. Clinicopathologic characteristics and overal survival, disease free survival rates were analyzed. Results: There were no significant difference in clinical characteristics between WHO grade 2 and 3 groups except age(p = 0.023). There was no significant difference in overall survival(p = 0.078), but there was significant difference in disease free survival(p = 0.012). Tumor location was the prognostic factor for overall survival in multivariate analysis(P=0.022). Poorly differentiation(P < 0.001), Positive resection margin(P = 0.007), Metastasis(P < 0.001) were risk factor for recurrence. Conclusions: Tumor location, differentiation, resection margin, metastasis are better prognostic factor than WHO grade for grade 2,3 Pancreas NET.

SCOT: Tumor sidedness and the influence of chemotherapy duration on DFS.

558 Background: Patients with R-sided tumours who develop metastatic disease have a worse prognosis compared to patients with L-sided tumours. The latter may also have a greater benefit from treatment with EGFR inhibitors. In general, registry studies and meta-analyses have shown that patients with loco-regional R-sided tumours have a worse overall survival (OS). This has recently been confirmed by the PETACC8 study but only after they had relapsed. There was not a significant difference in disease free survival (DFS). Methods: The SCOT study showed that 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) was non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. Here we divide the population into left and right-sided tumours to see whether sidedness had an impact on DFS. We also evaluated whether sidedness impacted on the 3 vs. 6-months comparison in SCOT. Results: 6088 patients with Stage III/high risk Stage II cancers or the colon or rectum were randomised between March 27, 2008 and November 29, 2013 from 244 centres (164 UK, 32 Australia, 19 Spain, 14 Sweden, 10 Denmark and 5 New Zealand). In February 2017 (3-years FU) information on sidedness was available for 3219 patients (1207 R-sided, 2012 L-sided). Characteristics: Right: median age: 65, Male: 53%, T4 41%, Stage II: 17%; Left: median age: 65, Male: 66%, T4 24%, Stage II: 21%). Patients with R-sided tumours had a significantly worse DFS (3-year DFS right: 73% (se=1%), left: 80% (se=1%). HR 1.401 (95% CI 1.216-1.615; p=0.000004). Adjusting for T and N-stage reduced the HR to 1.215 (95% ci 1.051-1.404, p=0.009). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR (3 month/6 month) 1.049 (0.849 -1.296) L: 0.910 (0.753-1.099). Test for homogeneity, p=0.327). Further sub-set analysis was limited due to cohort size. Conclusions: This is the first study to show that unselected patients with R-sided tumours had a worse DFS compared to L-sided tumours. This implies that prognosis is influenced primarily by greater recurrence rather than the contributing factors that influence OS. Tumour sidedness did not impact on the 3-months vs. 6-months comparison in SCOT. Clinical trial information: ISRCTN59757862.

Tumor–stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

Background: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor–stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy.Material and methods: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors were sampled and analyzed by conventional microscopy. Patients were divided into stroma-high (>50%, i.e. TSR low) and stroma-low (≤50%, i.e. TSR high) for the comparison with clinical data.Results: A low TSR was found in 47% of the surgically resected primary tumors and correlated to a significantly higher T- and N-category compared, to tumors with a high TSR (p < .01). A low TSR was also significantly associated with disease recurrence (p = .008), translating into significant differences in disease free survival (DFS) and overall survival, p < .002. The 5-year DFS rate for patients with a low TSR was 55%, compared to 94% in the group of patients with a high TSR.Conclusions: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting patients for post-operative treatment.

232P - Pregnancy associated breast cancer spotlights

Background: Pregnancy associated breast cancer (PABC) is a rare entity of breast cancer. It is defined as breast cancer occurring during pregnancy or within 12 months from end of pregnancy. Though rare, it represents a very challenging situation to both the physician and patient. This retrospective study is an attempt to focus on PABC cases presenting at our institute regarding their personal, disease characteristics and type of treatment received. Methods: This is a retrospective study conducted at Kasr-Al-Ainy oncology center “NEMROCK”. The files of female patients diagnosed with breast cancer under the age of 40 in the period from January 2005 to December 2014 were retrospectively reviewed. A comparison has been conducted between PABC cases and non-pregnant cases concerning personal and disease characteristics, modality of treatment and outcomes. Results: This study included a total of 175 patients 40 years old or younger, among them 40 were PABC cases. Twenty five percent of PABC presented with distant metastasis at first presentation while only 11.6% of the non-pregnant patients presented with metastasis (P value 0.039). Time from onset of symptoms till breast cancer diagnosis was more than 6 months in 55.6% of PABC cases in comparison to 36.3% in non-pregnant cases (P value 0.043). Concerning treatment; 32.4% of PABC cases received neoadjuvant chemotherapy while 20.7% of non-pregnant patients received it (P value 0.027). There was no statistical difference in personal and disease characteristics between pregnant and non-pregnant patients including family history, pathological subtypes, stage, grade and biological subtypes. There was no statistically significant difference in disease free survival between PABC cases and non-pregnant ones (P value 0.497). Conclusions: PABC is associated with a late diagnosis. Although PABC patients present at later stages than non-pregnant ones and the use of neoadjuvant treatment is higher in pregnant cases, the outcome of patients with PABC is comparable to that of non-PABC of matched age. Legal entity responsible for the study: Kasr alainy department of oncology Funding: None Disclosure: All authors have declared no conflicts of interest.

Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I–IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB (p < 0.05). We present a novel and effective model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

Analysis of racial differences in histologic subtype and survival in renal cell carcinoma at an urban academic cancer center.

e16571 Background: Black patientswithrenal cell carcinoma (RCC) have a unique distribution of histological subtypes and historic worse survival compared to white patients. Little is known about RCC in Hispanics. We investigated histologic and survival differences between racial groups treated for RCC at the Montefiore-Einstein Cancer Center (MECC) in Bronx, NY. Methods: We included via the Cancer Registry 1010 patients who underwent RCC resection at MECC between 2000 and 2015. Demographics, clinical characteristics and pathology reports were collected. Logistic regression and Cox proportional hazards models were built to evaluate the association of histology and survival with clinically and statistically significant risk factors in Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (H) patients. Results: 233 patients were NHW (23.1%), 383 NHB (37.9%), 174 H (17.2%), and 220 other race (21.8%). Median age was 61 (range 22, 91). 58% were male. Histology was 529 (52%) clear cell (CC), 255 (25%) papillary (P), 100 (10%) chromophobe, and 126 (12.5%) other. P was more common in NHB (60.5%) compared to NHW (17%) and less common in H (6.3%) patients (P &lt; 0.0001). On multivariate logistic analysis, patients with P vs. CC were more likely to be NHB (OR 5.06; 95% CI 2.92, 8.76; P &lt; 0.0001) and less likely to have a body mass index &gt; 30 (BMI, OR 0.49; 95% CI 0.32, 0.76, P = 0.001) adjusting for age, race, gender, hypertension (HTN), and end stage renal disease (ESRD). Adjusting for above covariates there were no significant differences for C vs. CC. There was no difference in disease free survival (DFS) for NHB vs. NHW (HR 0.93; 95% CI 0.44, 1.94; P = 0.841) or H vs. NHW (HR 1.29; 95% CI 0.62, 2.71; P = 0.495) patients adjusting for age, gender, histology, ESRD, and BMI. There was no difference in overall survival (OS) for NHB vs. NHW (HR 0.97; 95% CI 0.57, 1.65; P = 0.908) or H vs. NHW (HR 1.37; 95% CI 0.79, 2.38; P = 0.256) patients adjusting for the same covariates. Conclusions: In this cohort of patients with RCC, P histology and lower BMI were significantly associated with NHB race. Unlike historic cohorts there was no significant difference in DFS or OS in NHB compared to NHW patients.

A retrospective study on multifocal and multicentric vs. unifocal breast cancer. Preliminary results

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, but they still remain a controversial subject for many senologists in regards to the best treatment options. Conservatory approach is reserved preponderantly to unifocal localization of the invasive breast carcinoma while in MF and MC the radically techniques are still the main option. The real impact of MC and MF breast cancers on survival is still unknown, but it is presumed to be worse. MF and MC breast cancers are currently over treated by radical mastectomy (RM). The AMAROS trial and also the Z0011 trial recently demonstrated that less surgery does not necessarily mean less local control or worse survival outcomes. About 450 women that underwent surgery for breast cancers stages I-III were included in this monocentric retrospective study; clinical and pathological data were obtained from the database of the Institute of Oncology ”Prof. Dr. Alexandru Trestioreanu” Bucharest. Our primary objective was to see if there is any difference in disease free survival in early breast cancer patients primary treated by conservative surgery according to unifocal (UF) vs. MF vs. MC feature of the invasive component. Our secondary objectives were to identify if there is any correlation between the conservative or radical type of surgery and other clinical and histologcal characterstics; if there is any differences in survival between UF vs. MF vs. MC breast carcinoma. Median follow-up was of 51 months. MC and MF cancers were present in 38 patients (8.4%) and 13 (2.9%) respectively and most of them were treated with mastectomy (6 MF and 19 MC) rather than with breast conservative surgery (BCS). In the entire data analyzed there was no statistical difference between event free survival (EFS) in the subgroup that underwent BCS vs. radical surgery (RS): 21 events (16.4%) vs. 53 events (16.61% ) (p=0.957), median EFS 99.79 mo 95% CI [92.67-106.91] mo vs. 98.19 95% CI [92.81-103.56] mo (p=0.773). We found a significant correlation between recurrence and a family history of cancer (p=0.035), the tumor/node/metastasis (p<0.001), type of surgery (p= 0.035). Relapse rate wasn’t significantly different whatever the type of surgery done. Median EFS wasn’t different between patients that underwent BCS and those that underwent RS. BCS is a reasonable option in selected UF/MC/MF cancers, particularly in younger women with small breast tumors.

Subgroup efficacy evaluation of the AE37 HER2 vaccine in breast cancer patients in the adjuvant setting.

3088 Background: AE37 is a Ii-Key hybrid of the HER2 peptide AE36 (HER2776-790), which stimulates peptide-specific T cells. We have completed the active phase of a prospective, randomized, multi-center, phase II trial of the AE37 vaccine in the adjuvant setting. The primary analysis, performed after a median follow up (f/u) of 25 months (mo), did not show a significant difference in disease free survival (DFS) between vaccinated and control patients (pts). However, demonstrating the efficacy of cancer vaccines may require more time than other therapies, especially in malignancies with relatively late recurrences like breast cancer. Here, we present updated efficacy data after extended f/u in subgroups of pts stratified by clinicopathologic characteristics. Methods: Clinically disease-free, node positive or high-risk node negative pts with any level of HER2 expression were randomized to receive AE37 + GM-CSF (VG) or GM-CSF alone (CG) following standard of care therapy. Pts received 6 monthly intradermal inoculations during the primary vaccine series (PVS) followed by 4 boosters administered every 6 mo. Kaplan Meier and log rank analyses were performed from the time of the first inoculation in pts who completed at least the PVS, according to stage, node status, tumor size, HER2 expression and ER/PR status. Results: There were no clinicopathologic differences between groups in the 298 enrolled pts (VG = 153, CG = 145). The vaccine is safe and well tolerated. After a median f/u of 55 mo, there was a trend toward improved DFS in the VG among stage IIB/III pts (VG, n = 73, DFS 82% vs CG, n = 61, 67%, HR = 0.48, p = 0.06) and those with low HER2 expression (HER2 LE, VG, n = 68, 89% vs CG, n = 66, 51%, HR = 0.47, p = 0.1). Improved DFS in the VG was documented in patients with both stage IIB/III disease and HER2 LE (VG, n = 39, 90% vs CG, n = 38, 32%, HR 0.3, p = 0.02) and triple negative (TNBC) pts (VG, n = 21, 89% vs CG, n = 21, 0%, HR 0.26, p = 0.05). Conclusions: The AE37 vaccine is safe and well tolerated and has statistically significant efficacy in stage IIB/III pts with HER2 LE and in TNBC pts. This justifies further evaluation in a phase III study enrolling stage IIb/III pts not eligible for trastuzumab treatment and the very high risk TNBC group. Clinical trial information: NCT00524277.

Minimally invasive approach to intrahepatic cholangiocarcinoma: technical notes for a safe hepatectomy and lymphadenectomy

Background: Despite the improvements of laparoscopic (LPS) technologies and their extensive application to the treatment of liver diseases, minimally invasive approach to intrahepatic cholangiocarcinoma (ICC) is still poorly widespread. The aim of the present study is to investigate the extension and the diffusion of laparoscopy applied to surgical treatment of ICC. Methods: We reviewed studies dealing with the LPS treatment of ICC and LPS lymphadenectomy (LND) for ICC. Data regarding conversion rate, morbidity and LND were extracted, synthesized and analyzed. Additionally, we described technical notes for a safe liver resection and LND. Results: We identified 11 studies encompassing liver resections for ICCs. Among a total of 1,882 cases included, there were 101 (5.5%) patients treated laparoscopically who were affected by ICC. The observed conversion rate was comparable to that of other LPS advanced procedures; laparoscopy was not responsible for increased morbidity and LND was demonstrated being feasible without causing any increasing in the post-operative complications. Furthermore, no differences in disease free survival and on the 3-year overall survival were observed. Conclusions: Few are the cases of ICC that are nowadays tackled laparoscopically. Hepatic resection and LPS LND for ICC are feasible and safe; as more, laparoscopy granted both short and long term results that were comparable to open surgery, extending the applicability of minimally invasive surgery.

Abstract PD2-07: 10-year follow-up and biomarker discovery for adjuvant endocrine therapy; results of the TEAM trial

Abstract Optimal endocrine therapy for postmenopausal, hormone-receptor positive (HR+) early breast cancer remains a point of discussion. The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial showed no significant differences for disease free survival (DFS) and overall survival (OS) at 5 years between exemestane monotherapy and sequential treatment (tamoxifen followed by exemestane). We now report disease related outcomes at 10 years of follow-up (FU), and an explorative analysis to assess the predictive value of clinicopathological and immune-related biomarkers. In the TEAM trial, postmenopausal women with HR+ positive early breast cancer were randomly assigned to exemestane alone or sequential therapy. For this analysis, TEAM patients from countries that completed 10 years of FU were included. The primary endpoint was DFS at ten years, analyzed by intention to treat. Secondary outcomes were OS and cumulative incidence of relapse. An explorative per protocol analysis for relapse free survival (RFS) was performed to identify predictive pathological and immunological biomarkers, including centrally determined ER (ER-poor 0-6 vs ER-rich 7-8) and PR (0-4 vs 5-8) Allred scores, and the immunological markers CD8, FoxP3, classical HLA class 1 and HLA-G which were described earlier (Engels et al, Breast Cancer Treat Res, 2015). In total, 6120 patients were eligible for the current analysis, 3075 patients with exemestane monotherapy and 3045 patients randomized to sequential treatment. Median follow up was 9.83 years. DFS was 66.8% in the exemestane group and 66.8% in the sequential group (hazard ratio (HR) 0.96, 95% CI 0.88-1.05, p=0.389). OS was 74% in the exemestane, and 73% in the sequential group, respectively (HR 0.98, 95% CI 0.89-1.09, p=0.737). The cumulative incidence of relapse was 20% and 22% in the exemestane and sequential groups, respectively (HR 0.88, 95% CI 0.79-0.99, p=0.031). In the explorative per protocol analysis (n=4041), Allred score were available for 2996 patients; immunological markers for 1754 patients. Patients with above median numbers of FoxP3-positive T-cells showed a benefit of exemestane monotherapy for RFS (HR 0.56, 95% CI 0.42-0.75, p&amp;lt;0.001) in contrast to patients with low numbers of FoxP3-positive cells (HR 1.0, 95% CI 0.77-1.32, p=0.97, p-value for interaction 0.004). A high tumor differentiation grade was associated with more benefit for exemestane monotherapy (grade 1/2 HR 0.78, 95% CI 0.65-0.94, p=0.01, grade 3/4 HR 0.61, 95% CI 0.49-0.75, p&amp;lt;0.001), with a borderline significant interaction (p=0.07). ER Allred score showed a borderline significant treatment by marker effect interaction (ER-rich HR 0.69 (95% CI 0.58-0.81, p&amp;lt;0.001); ER-poor HR 0.94 (95% CI 0.65-1.34, p=0.71, p for interaction 0.12). After ten years of follow up, both exemestane monotherapy and sequential therapy remain appropriate options for postmenopausal HR+ early breast cancer patients. Interestingly, the number of regulatory T-cells was a predictive factor for the benefit of exemestane monotherapy, which implies a role of the local immune system in endocrine therapy. Furthermore, data suggested that patients with a higher differentiation grade or ER-rich tumor derive more benefit from exemestane monotherapy. Citation Format: Blok EJ, Derks MGM, Kuppen PJK, Meershoek-Klein Kranenbarg EM, Engels CC, Liefers G-J, Putter H, Seynaeve CM, Kroep JR, Nortier JWR, Rea DW, Hasenburg A, Markopoulos CJ, Paridaens R, Bartlett JMS, van de Velde CJH. 10-year follow-up and biomarker discovery for adjuvant endocrine therapy; results of the TEAM trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD2-07.

OA19.06 Adjuvant Chemotherapy Decisions Based on Molecular Risk Status Improves Outcomes in Early Stage, Non-Small Cell Lung Cancer

A clinically certified, 14-gene quantitative PCR expression assay has been found to assess mortality risk more accurately than clinicopathologic criteria in early-stage, non-squamous, non-small cell lung cancer (NSCLC). Clinically validated molecular stratification may provide a more informative approach to identify early stage NSCLC patients who are most likely to benefit from chemotherapy than current National Comprehensive Cancer Network (NCCN) high-risk clinicopathologic features. Prospective molecular risk-stratification by the 14-gene quantitative PCR expression assay was performed on 91 consecutive patients with stage I-IIA non-squamous NSCLC after complete surgical resection at a single institution. Information from molecular risk profiling was used in conjunction with pathologic stage and NCCN criteria to make adjuvant chemotherapy recommendations. Fisher’s exact test was used to compare recurrence rates, and Kaplan-Meier analysis and log-rank tests were used to evaluate differences in disease free survival. Median age was 69 years, 57% were female and median follow up was 23±2 months. Among all patients, 33 (36%) met NCCN high-risk criteria for adjuvant chemotherapy and 27 (30%) were molecular high risk. Recommendations for adjuvant chemotherapy were discordant in 18 (55%) of NCCN high-risk patients and in 12 (44%) who were molecular high-risk. Twelve (44%) of molecular high-risk patients agreed to receive adjuvant chemotherapy. Whereas recurrence was observed in 33% of molecular high-risk patients who did not receive adjuvant chemotherapy, none of the molecular high-risk patients who underwent chemotherapy recurred (log-rank p=0.001). This prospective single-institution study demonstrates the clinical utility of molecular testing of early-stage NSCLC to supplement pathologic stage and NCCN guidelines in making adjuvant chemotherapy recommendations. Molecular risk scores better differentiated prospective recurrence rates than did NCCN risk criteria. This study provides preliminary evidence that molecular testing followed by adjuvant chemotherapy in molecularly high-risk patients may prevent a significant number of recurrences and improve outcomes.

Neoadjuvant chemotherapy with methotrexate/vinblastine/doxorubicin/cisplatin vs. gemcitabine/cisplatin for muscle-invasive bladder cancer: a review and meta-analysis

Objective To systematically assess the efficacy of neoadjuvant chemotherapy (NAC) with methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) vs. gemcitabine/cisplatin (GC) for muscle-invasive bladder cancer (MIBC). Methods Randomized controlled trials (RCTs) or non-RCTs regrading the efficacy of NAC with MVAC vs. GC for MIBC were retrieved in Pubmed, Cochrane library, Sciverse, CNKI, VIP and Wanfang database from databases establishment to May 2016. According to the including and exclusion criterion, two reviewers independently reviewed the trials, conducted the Meta-analysis with RevMan 5.3 soft ware. Results A total of 13 non-randomized clinical controlled trials were eligible for the study including 1690 cases. The pooled results showed that MVAC group had a lower down staging rate (RR=0.77, 95%CI 0.61-0.97, P=0.03) and complete response rate (RR=0.70, 95%CI 0.53-0.93, P=0.01). Statistically significant were observed. However, there was no significant difference in disease free survival (RR=0.88, 95%CI 0.60-1.29, P=0.53). Conclusion Compared with MVAC, NAC with GC had higher down staging rate and complete response rate. Therefore, NAC with GC should be considered as a preferable option for MIBC. Key words: Muscle invasive bladder cancer; Methotrexate/vinblastine/doxorubicin/cisplatin (MVAC); Gemcitabine/cisplatin (GC); Neoadjuvant chemotherapy; Meta analysis

Abstract 2263: Prognostic significance of REV3like and TYMS gene expression in blood samples from non-small cell lung patients treated with platinum-based chemotherapy plus pemetrexed

Abstract BACKGROUND: Pemetrexed is an effective antineoplastic agent as monotherapy (second line and maintenance setting) or in platinum-based combination regimes (first-line). Pemetrexed inhibits three key enzymes in the folate metabolic pathway: thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyl transferase (GARFT). As a consequence, pemetrexed interferes with the synthesis of both pyrimidine and purine, thereby effectively inhibiting both DNA and RNA synthesis. The aim of this study was to investigate the impact of the PBMC (peripheral blood mononuclear cells) expression levels of AEG1, BRCA1, REV3like, ant TYMS mRNA in the clinical outcome in NSCLC patients treated with Pemetrexed-based therapy. MATERIAL AND METHODS: This is a prospective, observational cohort study, of consecutively selected patients. We included patients with non-squamous NSCLC, stage IV, treated with platinum-based chemotherapy plus Pemetrexed. Blood samples from each patient were collected at the beginning of treatment. Quantitative reverse transcription (qRT)-PCR was performed with the use of the TaqMan gene expression assay (Applied Biosystems) according to the manufacturer's instructions. Amplifications were carried out on the Applied Biosystem 7500 RT-PCR system, and relative gene expression values were calculated by the ΔΔCt method (Sequence Detection System 2.0.5). Results from analysis, done in triplicate, are expressed relative to expression levels of GAPDH. RESULTS: We here present preliminary results of 16 patients included in the study: median age was 63.4 (range 52-82); 12 were males. Histological subtypes were 13 adenocarcinomas, and 3 large cell carcinomas. Pemetrexed was combined with Carboplatin in 9 patients and Cisplatin in 7 patients. Best response obtained was partial response in 7 patients, stable disease in 3 patients, and progression in 5 patients. We found significant differences in the REV3like expression levels between patients with PR&amp;SD and patients with PD (0.69 ± 0.14 vs 0.44 ± 0.07; P = 0.003). In addition there were statistically significant differences in disease free survival (3 ± 0.74 vs 13 ± 1.89, P = 0.035; 12 ± 2.32 vs 3 ± 2.19, P = 0.003, months), and overall survival (10 ± 5.21 vs not reached, P = 0.026; not reached vs 12 ± 2.38, P = 0.007, months) between patients with mRNA levels of REV3like and TYMS under mean value of the cohort and patients with levels over mean value of the our cohort. CONCLUSIONS: This study supports the value of the PBMC expression profiling of the REV3like and TYMS genes in the prognosis of NSCLC treated with platinum-based chemotherapy plus Pemetrexed. Citation Format: Maria Teresa Agullo-Ortuño, C.Vanessa Díaz-García, José A. López-Martín, Elena Prieto-García, Santiago Ponce, Jon Zugazagoitia, Lara Iglesias-Docampo, Ana B. Enguita, Luis Paz-Ares, Juan A. Nuñez-Sobrino. Prognostic significance of REV3like and TYMS gene expression in blood samples from non-small cell lung patients treated with platinum-based chemotherapy plus pemetrexed. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2263.

PWE-090 Are Cancers of The Colon Biologically Different Compared to Rectal Cancer?

Introduction Emerging evidence suggests that tumour biology of rectal cancers differs from colonic cancer. This study aimed to determine which clinic-pathological factors affect lymph node yield (LNY) and survival in colonic (CC) compared to rectal cancer (RC). Methods Patients [a1] with stage I-III disease undergoing curative surgery, between 2006 and 2012, were included. Multivariate linear/logistic regression and Kaplan Meier survival analysis with SPSS version 21 were performed. Results 726 patients (M:F-398: 328, median age-70 years(63–78 yrs) were included (median follow up-58 months-(37–78 months)); 205 patients had RC. Male gender and younger age were associated with RC. A higher LNY was detected with RC compared to CC (median LNY:20 (14–27.5) versus 18 (12–25), p = 0.013). No differences in locoregional recurrence or distant metastases were found (CC 40/521 versus RC 13/205, p = 0.635 and CC 98/521 versus RC 36/205, p = 0.750 respectively). Overall survival (OS) was better in CC compared to RC (mean OS 114 months versus 90 months, p = 0.004); no difference in disease free survival (DFS) was observed. An inadequate LNY ( Conclusion An inadequate LNY is related to aspects of the primary tumour and is a marker of poor prognosis for CC patients only. No survival differences are observed for RC patients with an inadequate LNY compared to those with >12 lymph nodes questioning the prognostic significance of number of lymph nodes retrieval in RC. Disclosure of Interest None Declared

Abstract P3-13-06: The efficacy and long term results of intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ

Abstract Introduction Breast conserving surgery (BCS) is a standard procedure for early breast cancer and resection margin state is the most important risk factor of local recurrence. Re-operation is generally conducted in 20∼40% after initial BCS to achieve negative margins, especially in breast cancer with carcinoma in situ components. In this study, we analyzed the long-term follow up results and efficacy of BCS using intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ (DCIS) patients. Methods Between 2004 and 2006, 1016 patients were diagnosed with primary breast cancer and received breast cancer surgery. Among them, BCS was attempted as an initial operation for 523 patients. Superior, inferior, medial and lateral margin of resected specimen were evaluated according to the intraoperative frozen section analysis. If tumor cells existed less than 2mm from resected specimen margin, intraoperative further resection was done and if the further resection was impossible, initial BCS was converted to mastectomy. All medical records and pathologic reports were reviewed retrospectively. Results Of the 523 patients who had to undergo BCS, 13.3% (70/523) were converted to mastectomy during initial BCS. The number of the patients who had either only DCIS or invasive carcinoma c carcinoma in situ component was 372 (71.1%, 372/523) and 17.2% (64/372) were converted to mastectomy. One hundred fifty one (28.9%, 151/523) patients had only invasive carcinoma and 3.97% (6/151) were converted to mastectomy. In this study, we analyzed 94 patients who had to undergo BCS with DCIS. The rate of intraoperative conversion to mastectomy was 13.8% (13/94) and 81 patients had successful BCS with 0∼3 times of intraoperative frozen section analysis. There were no differences between patients who had BCS and final mastectomy in clinicopathologic characteristics such as physical examination of tumor, age of patients, DCIS subtypes, nuclear polymorphism, presence of necrosis, ER, PR, HER2 and Ki67. After permanent biopsy was reported, in 5 patients, resected specimen had tumor cells within less than 2mm from resected margin, not inked margin. They had no reoperations and no recurrences. Mean follow up period was 76.6 months. One locoregional and 3 local recurrences in BCS patients and 1 local recurrence in mastectomy patients were found. There was no difference in disease free survival between two groups (95.1% vs 92.3%, p=0.659). In these DCIS patients, reoperation rate was 0%. Conclusion Intraoperative frozen section analysis during BCS to access resection margin helps to avoid reoperations and increase intraoperative success rate of BCS in DCIS. It also shows oncological safe long term results. Further studies are needed to resolve the problem with cost-effectiveness of intraoperative frozen section analysis. Citation Format: Choi JE, Yeu KJ, Park JY, Kang SH, Lee SJ, Bae YK. The efficacy and long term results of intraoperative frozen section analysis to access resection margin in ductal carcinoma in situ. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-06.