Aims: The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients. Materials and methods: We systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. Results: The combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50-0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate. Conclusion: Our meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration. (c) 2023 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Preoperative chemoradiotherapy (CRT) may enhance antitumor immunity by increasing T-cell activation and tumor infiltration. These effects could possibly sensitize tumour cells to immunecheckpoint inhibitors and other immunotherapies. We investigated the immunologic alterations occurring after preoperative CRT for locally advanced rectal cancer (LARC). The multicenter randomized STAR-01 study compared the preoperative CRT regimen with 50.4 Gy in 28 daily fractions with concomitant infused fluorouracil at the dose of 225 mg/m2/d with the same regimen plus oxaliplatin given weekly at the dose of 60 mg/m2 in patients with LARC. Pre- and/or postoperative specimens were available for 305 patients from this trial (109 paired pre- and post-treatment samples). The immunoistochemical evaluation was performed with a panel of immune cells and associated factors such as CD3, CD20, CD4/CD8, PD-1. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) were also assessed. Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) was evaluated on pre-treatment tumour biopsies. After therapy we observed a decreased CD4/CD8 ratio (P<.0001) and reduced expression levels of CD20 (P<.0001). The expression level of CD3+ and PD-1+ cells after therapy did not change significantly. The relative increase of lymphocytes CD8+ within the CD4/CD8 ratio evaluated on post-operative samples was significantly associated with pathological complete response after CRT (P<.0001), event-free survival (EFS) [hazard ratio (HR)=1.77, 95% confidence interval (CI)=1.08 to 2.89, P=.0227] and overall survival (OS) [HR=2.01, 95% CI=1.19 to 3.4, P=.0087] adjusted for treatment arm and adjuvant chemotherapy. Our data indicate that CRT may induce an enrichment of CD8+ T lymphocytes and this translates in a better response to CRT and survival. Data on MSI status will be presented at the meeting.

The prognosis of biliary tract cancer (BTC) remains dismal. Recently, the phase 3 randomized TOPAZ-1 trial has established a novel standard of care as first line, demonstrating a survival prolongation when the anti-programmed death-ligand 1 (PD-L1) durvalumab is added to the gemcitabine plus cisplatin backbone. FOLFOX is considered the recommended second-line treatment, based on the results of the ABC-06 trial. Recent studies investigated the activity of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV), providing conflicting results. In the final analysis results of the phase IIb NIFTY trial, the combination of nal-IRI + 5-FU/LV demonstrated longer median PFS (4.2 versus 1.7 months, p=0.004), OS (8.6 versus 5.3 months, p=0.02) and objective response rate (ORR; 12.5 versus 3.5%) compared to 5-FU/LV alone in patients who progressed to first-line gemcitabine plus cisplatin (21, 22). Results of the phase II NALIRICC trial have been presented at the ESMO Congress 2022. In previously treated BTC patients the addition of nal-IRI to 5-FU/LV failed to improve PFS (2.64 versus 2.30 months) and OS (6.90 versus 8.21 months). We performed a meta-analysis aiming to evaluate survival outcomes and response rates in these two randomized trials investigating the activity of nal-IRI in previously treated BTC patients. We retrieved all potentially relevant results through PubMed/Medline, Cochrane library and EMBASE and abstracts presented at the main international oncological meetings. Hazard Ratio (HR) and 95% Confidence Intervals (95%CI) for progression-free survival (PFS) and overall survival (OS), and Odds Ratio (OR) and 95% CIs for objective response rate (ORR) were extracted. Results from two studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. A total of 274 BTC patients were available for the meta-analysis. 137 patients received the combination therapy and 137 received 5-FU/LV alone. The combination therapy significantly decreased the risk of progression (HR 0.70; 95%CI 0.50-0.97) compared with 5-FU/LV alone. Furthermore, longer OS (HR 0.84; 95%CI 0.53-1.31) and higher ORR (RR 3.15; 95%CI 1.20-.25) were observed in the doublet arm. FOLFOX is considered the optimal option in the all-comer BTC patients in the second-line setting. However, the control arm of the pivotal arm was the active symptom control alone. Furthermore, not all patients are eligible to this therapy and not all benefit from it. Our meta-analysis supports the role of nal-IRI plus 5-FU/LV in the second-line setting in BTC patients. Further studies are warranted in order to find the best place for this promising combination therapy.

Preoperative chemoradiotherapy can enhance antitumor immunity through increasing T-cell activation and tumor infiltration. These effects could potentially sensitize tumors to immunotherapies, including checkpoint inhibitors. We explored whether preoperative therapy for locally advanced rectal cancer induces immunologic changes. We analyzed by immunohistochemistry 55 locally advanced rectal cancers from the STAR-01 cohort. Paired pre- and post-operative specimens were available for 25 out of 55 patients. The multicenter STAR-01 study enrolled patients treated with preoperative chemoradiation with or without oxaliplatin. The immunoistochemical analysis was performed with a panel of immune cells and associated factors as CD3, CD20, CD4/CD8, PD1 and FoxP3. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) was also evaluated. Response to preoperative chemoradiotherapy was assessed according to tumor regression grade (TRG sec. Ryan –AJCC Eight ed.). The expression level of CD3+, CD20+, FoxP3+ and PD1+ cells were not significantly different after therapy. The TILs and RILs immunosuppressive cells were higher in better responder (TRG0), although we did not find any statistical significance given the small sample size. Decreasing CD4/CD8 ratio on post-operative samples was significantly associate with TRG 0 (p <0.01). The increase of lymphocyte CD8+ was related to a good pathological response after chemoradiotherapy. Our data suggest that chemoradiotherapy may induce an enrichment of CD8+ T lymphocytes in good responders. The new frontier of best treatment could be the use of specific immune cells (T lymphocytes) to activate the system's response immune against disease.

Background: STAR-01 is a randomized phase III trial investigating the effect of adding oxaliplatin (OXA) to preoperative (preop) 5-fluorouracil (FU)-based pelvic chemoradiation (CRT) in patients (pts) with resectable locally advanced rectal cancer (LARC).Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or nodal involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq x 6) (Arm B). Surgery was scheduled 6-8 weeks after completing CRT and 4 months of adjuvant FU monotherapy were advised in both arms. Overall survival (OS) was the primary endpoint. The cumulative incidence of distant metastases was a protocol-planned secondary end-point, particularly relevant to directly test the study hypothesis of a systemic effect of weekly oxaliplatin added to preoperative FU-based chemoradiation.Results: From November 2003 through August 2008, 739 (arm A: 377, arm B: 362) eligible patients were enrolled at 41 Italian institutions. We previously reported safety and tumor response results showing a higher rate of moderate to severe acute toxicity in patients receiving OXA without any difference in pCR. However, a significant reduction in early distant metastases was observed in patients receiving preoperative OXA combined to FP-based standard CRT (6-month incidence of distant relapse: 6.2 vs 2.2% in arm A vs B). With a median follow up of 8.9 years (IQR 8.1-9.9), 162 treatment failures (80 local and 189 at distant sites) and 248 deaths were observed. Rates of metastases at distant sites were 8% vs 5% at 1-y, 22% vs 19% at 3-y, 26 % vs 23 % at 5-y and 28% vs 24 % at 7-y. Overall, the relative risk of developing metastases at distant sites in patients receiving preoperative OXA was 0.86, 95% CI 0.65-1.14. There were 136 deaths in Arm A vs 112 in arm B (HR 0.82, CI 0.64-1.05, p = 0.114). The corresponding 5- and 10-year OS rates were 77.6 vs 80.4 % and 62.3 vs 67.4 % (Arm A vs B).Conclusions: Although statistical significance is not reached, these results suggest a small, but sustained, impact on the development of distant metastases supporting the study hypothesis of a systemic effect of weekly OXA concomitant to preoperative chemoradiation. This difference is paralleled by a smaller than planned reduction in the relative risk of death with a 3-6% absolute long-term benefit. Further investigation with pooled analyses of similar studies testing OXA in combination with FP-based preop CRT is warranted and planned. Background: STAR-01 is a randomized phase III trial investigating the effect of adding oxaliplatin (OXA) to preoperative (preop) 5-fluorouracil (FU)-based pelvic chemoradiation (CRT) in patients (pts) with resectable locally advanced rectal cancer (LARC). Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or nodal involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq x 6) (Arm B). Surgery was scheduled 6-8 weeks after completing CRT and 4 months of adjuvant FU monotherapy were advised in both arms. Overall survival (OS) was the primary endpoint. The cumulative incidence of distant metastases was a protocol-planned secondary end-point, particularly relevant to directly test the study hypothesis of a systemic effect of weekly oxaliplatin added to preoperative FU-based chemoradiation. Results: From November 2003 through August 2008, 739 (arm A: 377, arm B: 362) eligible patients were enrolled at 41 Italian institutions. We previously reported safety and tumor response results showing a higher rate of moderate to severe acute toxicity in patients receiving OXA without any difference in pCR. However, a significant reduction in early distant metastases was observed in patients receiving preoperative OXA combined to FP-based standard CRT (6-month incidence of distant relapse: 6.2 vs 2.2% in arm A vs B). With a median follow up of 8.9 years (IQR 8.1-9.9), 162 treatment failures (80 local and 189 at distant sites) and 248 deaths were observed. Rates of metastases at distant sites were 8% vs 5% at 1-y, 22% vs 19% at 3-y, 26 % vs 23 % at 5-y and 28% vs 24 % at 7-y. Overall, the relative risk of developing metastases at distant sites in patients receiving preoperative OXA was 0.86, 95% CI 0.65-1.14. There were 136 deaths in Arm A vs 112 in arm B (HR 0.82, CI 0.64-1.05, p = 0.114). The corresponding 5- and 10-year OS rates were 77.6 vs 80.4 % and 62.3 vs 67.4 % (Arm A vs B). Conclusions: Although statistical significance is not reached, these results suggest a small, but sustained, impact on the development of distant metastases supporting the study hypothesis of a systemic effect of weekly OXA concomitant to preoperative chemoradiation. This difference is paralleled by a smaller than planned reduction in the relative risk of death with a 3-6% absolute long-term benefit. Further investigation with pooled analyses of similar studies testing OXA in combination with FP-based preop CRT is warranted and planned.

Background: The outcomes of IBC pts who received NC could be different by Subtypes. Methods: We retrospectively reviewed the clinical records of 228 pts treated with NC for stage II-III IBC from 2000 to 2014. For each pt we recorded baseline tumor size, type of NC, type of surgery (S), pathological response (pCR defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS). IHC subtypes were defined according to ER and PgR expression, Ki-67 level, and HER2 status: Luminal A (LA): ER and PR + ,HER2-ve and Ki67< 20%(4.8%) Luminal B (LB): ER and/or PR + ,HER2-ve and Ki67 = 20%(27.2%) Luminal HER2 (LHER2): ER and/or PR + ,HER2+ and any Ki67(25.4%) HER2 positive (HER2+): neg ER and PR, HER2+ and any Ki67(11.4%) TN: ER-and PR-ve, HER2-ve and any Ki67(17.5%) Unknown in 33 cases(13.6%) pCR and OS outcomes also on the basis of both pre- and post- NC Ki67 levels were assessed Results: Median age was 50 yrs (r. 25-75). The NC consisted of an anthracyclines (A)?taxanes (T) in all HER2- (151 pts), associated with weekly carboplatin (C) in a few cases (9) of TN and of T + trastuzumab (H) ± A (32 ) or C (36 pts) in HER2+ disease. Only 8 pts did not receive S: 5 for distant progression disease (PD) and 3 because still on NC. Quadrantectomy was performed in 127 pts (56%) pCR was achieved in 52 pts (23%) with further 4 pts showing a RT =1 mmTable: A22Relationship between pCR and Sub, ki67 and PDLA (%)LB (%)LHER2 (%)HER2 +TN (%)Median Ki67PD (%)pCR08.231.052.036.447.45.8No pCR10091.869.048.063.638.134.3p Value<0.0001< 0.0001<0.0001 Open table in a new tab All but 21 HER2+ pts (89) received H obtaining pCR in 39.7% of cases regardless chemotherapy type (A-based 35.5% vs C- 43.7%). Seven of 9 pts receiving C addition underwent S with pCR in all but 2 cases. The median Fup was 52 ms (r.1-182 ms). The 5y-RFS and OS were higher in whom achieved pCR than those did no (RFS 93.8 vs 67.8%;p = 0.001 and OS 95.8 vs 76.0%;p = 0.007). Median Ki67 in pretreated core biopsy was 40 compared to 30% in post-NC RT. Pts with high (>30%) post-NC PI showed significantly higher risk for relapse (5y-RFS 49.3%;p = 0.001) and death (5yOS 56.4%;p = 0.007) compared with pts with <15% (RFS 93.6 and OS 89.6%) or >15-30 Ki67 levels (RFS 73.0 and OS 82.6%) . Conclusions: The pCR rate was significantly higher in aggressive subtypes HER2+ and TN than luminals. Pts achieving pCR showed better RFS and OS compared to no pCR pts. Interestingly high pre-NC PI seems to predict the possibility obtaing pCR, while post-NC PI seem to be of prognostic value in pts who do not receive pCR.

Background: Patients affected by LACC (stage Ib2-IV) could be equally treated with neoadjuvant CT followed by surgery or with radical cCTRT. The standard CT is based on wCDDP given concurrently to RT. The present report is aimed to describe the toxicities and the clinical outcomes of pts treated with wCDDP plus RT for LACC. Patients and methods: From May 2001 to November 2014, we treated a consecutive series of 87 patients. The treatment consisted of whole pelvic external RT (plus RT boost in patients with parametrial invasion) and brachytherapy (B) in selected cases, with good clinical response to external RT. CDDP was given weekly at the dose of 40 mg/sqm, starting on day 1 of RT. Acute and late toxicities were evaluated according to NCIC and LENT-SOMA criteria respectively. Results: Major pts characteristics were: median age 55 yrs (range 30-79); median PS 0 (range 0-2); FIGO stage: Ib2 in 7 pts, IIa in 7, IIb in 28, IIIa in 3, IIIb in 26, IVa in 8, IVb (without visceral metastasis) in 8. Histology: squamous in 77 pts, adenocarcinoma in 8, mixed (squamous and adenocarcinoma) in 1, and undifferentiated in 1. Pts treated with external RT alone (39 pts) received a median total dose of 63 Gy (range 43.-67), which was 74.4 Gy (range 50-85) in pts receiving also B (48 pts). The treatment was completed in 71% of the pts. The median number of delivered CT courses was 5 (range 1-8): one patient received only 1 course of wCDDP due to gastrointestinal toxicity. Out of the 372 administered courses of wCDDP, 3 were at reduced dose due to patient compliance, 9 due to haematological toxicities, 10 due to non-hematological toxicities, 11 due to age; admistration of therapy was delayed due to haematological and non-haematological toxicities in 10 and 4 courses, respectively. Grade 3-4 toxicities consisted of anemia (1 pt), neutropenia (4 pts), nausea (2 pts), diarrhoea (2 pts), constipation (1 pt), fatigue (1 pt). No grade late toxicity 3-4 was observed. The response was evaluable in 78 pts with a rate was 88.4% (54 CR and 15 PR). After a median follow-up of 34 mos, the 2-year OS and DFS were 79.9% and 69.2% respectively, with median OS and DFS not reached. Conclusions: Our experience confirms the good activity and tolerability of this combined CT-RT treatment in LACC, according to the literature data.

e15591 Background: The prognosis of CC is related to both primary tumor stage, size, and histologic grade and to the lymph nodes status. Recently, the use of PET in CC staging is increasing. Furthermore, it has been hypothesized that some PET parameters such as tumor uptake of fluorine-18-labeled fluorodeoxyglucose (18FDG) measured as maximum standardized uptake value (SUVmax) and tumor volume may be associated with aggressive biological characteristics of cancer cells, in patients with CC. The present report is aimed to evaluate the prognostic role of PET in CC patients treated with chemotherapy (CT) alone or concurrent chemo/radiotherapy (CT/RT). Methods: Between January 2007 and November 2010, a consecutive series of 24 pts with CC was treated with CT or CT/RT. All pts underwent a baseline 18FDG PET (Siemens Biograph 64 True Point). PET scan was performed at 1 hour after injection of 4 MBq/Kg of 18FDG. For each assessment we evaluated SUVmax, while metabolic tumor volume (cervix and lymph node) was measured by an automated contouring program with a fixed threshold of SUV max = 2.5. For each pt we also recorded traditional prognostic factors (histology, tumor grade, smoking status, age, and stage). Progression Free Survival (PFS) and Overall Survival (OS) were calculated by Kaplan-Meier methods. Results: Major pts characteristics were: median age 54 yrs (range 33-77); median PS 0 (range 0-2); smokers 17 and no smokers 7; FIGO stage: Ib2 in 2 pts, IIa in 1, IIb 4, IIIb in 7, IVa in 4, IVb in 6; squamous histotype 21 pts and adenocarcinoma 3. No statistically significant relationship was found between PET parameters and traditional prognostic factors, excepting for stage with earlier stages (I-III) having a lower tumor volume compared to patients with IV stage (58.77 vs 136.5 mm3 p = 0.031). Similarly, PFS and OS were not influenced by PET parameters. Conclusions: From our preliminary data, PET parameters are not able to distinguish pts with different prognosis. Anyway, PET may increase our ability of tumor measuring. Larger samples are need to definitively assess the prognostic value of PET in CC.

165 Background: Responder pts to first-line DOC, who have stopped the treatment in absence of progression, usually experience a disease progression within few months. In recent years, ReC with DOC has emerged as a therapeutic option for these pts, able to achieve again a response. The available data usually report on the clinical outcome of pts who have received one or two ReCs, but it is unclear whether more ReCs may be offered to these pts and if there is a maximum number of affordable ReCs. Methods: We retrospectively reviewed the clinical record of the pts with CRPC treated in our Department with DOC from March, 2002 to September, 2010. We selected pts who received multiple ReCs until the appearance of a true resistance to DOC: we consider as DOC-resistant pts showing a clinical and/or biochemical progression during DOC treatment. Results: We have identified a consecutive series of 26 pts, who have received a median number of 2 ReCs (range 2- 6). The median age was 68 yrs (range 58-82 yrs). The ReC consisted of DOC q 3 wks in 7 cases, DOC + estramustine q 3 wks in 38, weekly DOC + estramustine in 23. Multiple ReCs were well tolerated with no more than grade 1 hematological and non-hematological toxicities. To date, 11 pts are still DOC-sensitive (after 2-6 ReCs, median 2) and are receiving ReCs or are in the off-therapy period after ReCs. After a median follow-up of 30 months, 14 pts are dead and 12 alive. The median survival is 40 mos and the projected 3-years overall survival is 54%. Conclusions: In our experience multiple DOC ReCs may be administered in DOC-sensitive pts with CRPC. This may provide a long-term disease control with remarkable survival rate compared to those of DOC pivotal studies (19 mos) and a second line treatment may be retarded until the appearance of a true DOC-resistance. [Table: see text] No significant financial relationships to disclose.

e15126 Background: ReC with DOC is an option for CRPC pts, who have responded to first-line DOC and have stopped the treatment without progression. The possibility of obtaining a new response by a DOC ReC is usually considered on the basis of the response to the previous treatment. We attempt to identify if there are additional factors able to predict ReC response. METHODS From March, 2002 to December, 2010, a consecutive series of 45 CRPC pts received at least one ReC after first-line DOC, for a total of 91 ReC courses (median 2, range 1-7). ReCs consisted of 4-6 DOC cycles and were proposed until the appearance of a true resistance to DOC: we consider as DOC-resistant pts showing a clinical and/or biochemical progression during DOC treatment. For each ReC course, we recorded the following parameters: treatment schedule (3 wks vs weekly), estramustine use (yes vs no), PSA response (↓ > 50%) at the previous DOC course, baseline parameters (hemoglobin, alkaline phosphatase, pain presence, ECOG), number of previous DOC courses, PSA parameters (slope LOG, doubling time, velocity) during both previous DOC course and treatment holiday, duration of treatment holiday before ReC. A binary logistic regression analysis was applied. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. RESULTS In 67% of 91 ReCs we observed a PSA reduction > 50%. After a median follow-up of 25 mos, the median survival is 32 mos and the projected 2-years overall survival is 77.5%. ReC was well tolerated with no more than grade 1-2 hematological and non-hematological toxicities. Having an interval log-PSA equal to or more than 0.62 [(exp(beta) 8.965; p= 0.020], an interval from the previous cycle equal to or more than 23 weeks [(exp(beta) 8.212; p= 0.002], a response to the previous cycle [(exp(beta) 7.658; p= 0.014], resulted to be independently predictive of a response to ReC. CONCLUSIONS In our experience, for CRPC pts sensitive to DOC, ReC appears to be a good option to obtain further response. Response to the previous cycle, interval log-PSA and interval from the previous cycle are factors able to identify the pts having more probabilities to respond to ReC.

539 Background: Ki67LI is a relevant marker EBC. The 2009 St Gallen Consensus considered Ki67LI as an important parameter for the addition of chemotherapy to endocrine therapy in hormonereceptor-positive EBC, suggesting three cutoffs: low <15%, intermediate 15-30% and high >30%. Our study aimed to evaluate if these cutoffs can be used in different subgroups of EBC, or if to apply different cutoffs in distinct biological setting. Methods: Ki67LI 1 was identified by immunohistochemical staining in 3802 EBC pts treated from 1995 to 2008. Median age was 61. The relationship with clinic-pathological parameters and the prognostic significance of KI67LI was investigated in all EBCs and in subgroups of ER+ cases based on homogeneous grading (656 G1, 1535 G2, 1113 G3). Results: Median Ki67LI values were 22% in all cases and 10, 20 and 36% in ER+ G1, G2 and G3 respectively. High Ki67LI was significantly (p<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER /PR, positive HER-2, triple negative subtypes, larger use of chemo±hormonotherapy. At median f-up of 51 months DFS and OS were 84 and 85% respectively in high, 89 and 90% in intermediate, 92 and 94% respectively in low Ki67LI group (p <0.001). There were 456 relapses (12%): 207 (5.4%) in high, 136 (3.6%) in intermediate and 113 (3%) in low Ki67LI group. Using median ki67LI value for different homogenous ER+ grading groups (ER+GG) we stratified these populations in low and high risk. The results are shown in the table. Conclusions: Ki67 LI confirms to be a significant prognostic biomarker for DFS and OS in EBC, associated with other clinical-pathological characteristics. Cutoffs are different into ER+GG. They can cathegorize at least two biological entities in every grading group providing additional prognostic information in planning therapies and outcome prediction. Subgroups At median follow-up DFS (%) P value At median follow-up OS (%) P value G1 High Low 90 95 0.058 93 97 0.005 G2 High Low 93 87 <0.001 94 90 0.001 G3 High Low 87 88 NS 85 87 0.008

Abstract PURPOSE: To examine interactions between mib-1 and clinical-pathological markers and their impact on outcomes. PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 3402 EIBC pts treated from 1995 to 2008. Mib-1 was defined as low (15%), intermediate (16%-30%) and high (>30%) value. Correlation between mib-1 and age, tumor size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by X2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and its correlation with other known prognostic factors. RESULTS: Median mib-1 was 25%. Mib-1 was low in 1135, intermediate in 1094 and high in 1173 pts. Median age was 62 years. High mib-1 was significantly (P<0.001) associated with younger age, ductal type, greater size, positive N, poor G, absent or low ER and/or PR expression level, positive HER-2, triple negative subtypes, larger use of chemo±hormonotherapy. High mib-1 was a significant predictor of worse DFS and OS (P<0.001). At median follow up of 42 months DFS and OS were 83.1 and 84.8% respectively in high, 88.9 and 89.3% in intermediate, 92.7 and 93.6% respectively in low Mib-1 group. There were 401 relapses (12%): 197 (6%) in high, 121 (3.5%) in intermediate and 83 (2,5%) in low mib-1 group. BC deaths were 368 (10.8 %): 178 (5.2%) in high, 117 (3.4%) intermediate and 73 (2.2%) in low mib-1 group. High mib1 was predictive of poorer prognosis in > 40 years pts (P<0.001), small tumors (T1) (P<0.001), N+ (P<0.001) and N0 (p=0.007), G1 (p=0.02), ER+ and/or PR+ (P<0.001), negative HER-2 (p=0.007), ductal type (P<0.001) respect to intermediate and low Mib1. At Cox regression analysis Mib1 showed independent prognostic value. According to the median value, high mib-1 (>25%) resulted a prognostic factor of worse outcome (P<0.001, HR=1.81, 95% CI=1.42-2.29), along with positive lymph nodes (P<0.001, HR=2.14, 95% CI=1.67-2.74), age<40 yrs (p=0.002, HR=1.93, 95% CI=1.30-2.86), greater tumors (P<0.001, HR=3.11, 95% CI=2.21-4.39), and ER/PR positive tumors (P<0.001, HR=1.742, 95% CI=1.305-2.327). CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in EIBC, providing additional information besides other clinico-pathological parameters to help decision-making of treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-14.

e14678 Background: PFC is effective in G-GEJA, both preoperatively with 20% pCR rates after chemoradiotherapy (Ajani JCO 2005) and in advanced disease, with 34% OR rates (Jin JCO 2007). We report our experience with PFC in patients with locally advanced or metastatic G-GEJA. Methods: Between January 2006 and December 2009 twenty-seven consecutive pts, 16 with operable (Group A) and 11 with metastatic G-GEJA (Group B), were treated with: paclitaxel at 200 mg/sm i.v. on day 1, 5-fluorouracil at 750 mg/sm/d by continuous infusion on day 1 to 5 and cisplatin at 15 mg/sm/d i.v. on days 1 to 5, every 3 weeks for 2 cycles, followed, for patients with operable cancer, by radiotherapy (45 Gy on 25 fractions of 1.8 Gy over 5 weeks) with concomitant 5-FU (250 mg/sm/d continuosus infusion). Prophylactic G-CSFs were administered on days 6 to 16 in all patients. Results: In group A, 14 pts were males and 2 females, with a median age of 60 years (43-74). Ten pts received two cycles of chemotherapy followed by chemo-radiotherapy, while 6 pts received chemotherapy alone: 2 CR (12.5%), 10 PR (62.5%), 2 SD (12.5%) and 1 PD (6.25%) were obtained (1 not evaluable for early death). Nine pts underwent surgery, and 6 (66%) had a R0 resection, however no pathological CR was observed. In group B, 8 pts were males and 3 females, with a median age of 61 years (32-68). Pts received a median of 4 cycles of chemotherapy (range 2-8), obtaining 7 PR (63.6%), 1 SD (9%) and 3 PD (27.2%). In both groups, 92 cycles of chemotherapy were administered, with no WHO grade 4 toxicity or treatment related death. Grade 3 hematologic and non hematologic toxicities included neutropenia (2.1%), mucositis (2.1%), nausea or vomiting (2.1%) or diarrhoea (2.1%). Conclusions: In our experience, a substantial antitumor activity was observed with PFC in localized or advanced G-GEJA, with acceptable/low toxicity, if prophylactic G-CSF are provided. No significant financial relationships to disclose.

Abstract INTRODUCTION: Mib-1 is a proliferation biomarker and a prognostic factor for breast cancer as reported in several studies.PURPOSE: The aim of the present study was to examine interactions between mib-1 and other clinical-pathological markers and their impact on outcomes in early invasive breast cancer.PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 2660 EIBC patients treated in our institution from 2000 to 2008. Mib-1 was dichotomized at the value of 20%. Correlation between mib-1 (> or ≤10620%) and age, tumour size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by χ2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and evaluate its correlation with other known prognostic factors.RESULTS: Mib-1 was > 20% in 1276 and ≤106 20% in 1384. Mib-1> 20% was significantly (p=.000) associated with younger age, greater size, positive lymph nodes, poor grading, absent or low ER and/or PR expression level, HER-2 over-expression or amplification with or without co-expression of ER and/or PR, triple negative subtypes. Mib-1 was a significant predictor of worse DFS and OS (p=.000). At a median follow up of 32 months the DFS and OS were 97.4 and 99.2% respectively in Mib-1 ≤20% group and 92.4 and 97.2% respectively in Mib-1 > 20%. There were 195 relapses (7,3%): 139 (5.2%) in Mib-1 > 20% and 56 (2.1%) in Mib-1 ≤ 20%. Breast cancer related deaths were 74 (2.8%) with 58 (2.2%) in mib-1 > 20% group and 16 (0.6%) in mib-1 ≤ 20%.Mib1 >20% was predictive of poorer prognosis in > 40 years patients, small tumors (T1), lower grading (G1 and G2), positive ER and/or PR group with high or intermediate expression, negative HER-2 tumors. However, in Cox multivariate analysis mib-1 didn't maintain independent prognostic value.CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in early breast cancer. It could provide additional information beside other clinico-pathological parameters to perform the risk stratification of early breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6054.