- Email: [email protected]
2057 Assessment oftumor-infiltrating lymphocytes in metastatic colorectal cancer patients treated by Bevacizumab-based chemotherapy
Abstracts left, 18.2% right, 37.1% unknown. Mutation analysis of AYAp showed: no mutations of KRAS 58/78 (74.4%), NRAS 9/11 (81.8%), and BRAF 9/12 (75%) patients. Total 104 AYAp received 1st-line chemotherapy for metastatic CRC: CAPOX/FOLFOX n = 80, CAPIRI/FOLFIRI n = 10, FLOX n = 5, FOLFIRINOX n = 3 with concurrent bevacizumab n = 63, cetuximab n = 7, panitumumab n = 3. Total of 81 (61.3%) underwent surgical intervention throughout their course of treatment. Hazard ratios showed no association between age group and OS, PFS 2 as it demonstrated adjusted HR of 1.26 (95% CI: 0.70–2.26) and 1.19 (95% CI:0.66–2.15) respectively. However, association was seen in PFS 1 with adjusted of HR 2.00 (95% CI: 1.22–3.28). (Table 1) Conclusion: Both AYAp and MATp had similar OS, in line with published literature. However, association between age groups in PFS 1 may illustrate more aggressive nature of CRC in AYAp subgroup. Further collaboration analyzing AYAp with CRC is required to better elucidate treatment patterns and outcomes. No conflict of interest. 2055 POSTER Tumor size as a prognostic factor in patients with IIa stage colon cancer F. Santullo1 , R. Persiani1 , A. Biondi1 , C. Coco1 , G. Rizzo2 , D. D’Ugo1 . 1 Catholic University of The Sacred Heart, Surgery, Roma, Italy; 2 Complesso Integrato Columbus, surgery, Rome, Italy Background: Resection is the gold standard treatment in most of T1−3N0 (stage I-IIa) colon cancer (CC) patients, conversely, it is currently matter for debate the administration of adjuvant treatment among this group of patients. The aim of the study was to identify patients with higher risk of recurrence who could benefit from post-operative chemotherapy. Material and Methods: All patients, with stage I and IIa CC, who underwent surgical resection from 2003 to 2011, were retrospectively enrolled in the study. High risk IIa stage patients with poor prognostic features (G3, lymphovascular invasion, obstruction, perforation, R1 or R2 resection and less than 12 harvested lymph nodes) who underwent postoperative chemotherapy were excluded from the study. The primary outcomes measured were 5-years overall (OS) and diseasefree survival (DFS). Factors considered for analysis were: sex, age at diagnosis, tumor location, median value of the maximum tumor diameter (DMAX), serum preoperative CEA level, total number of lymph nodes resected, charlson comorbidity, BMI, hemoglobin level, smoke. Moreover, the DFS of IIa stage CC was compared with the outcome of high risk IIa, IIb/c stage CC treated at the same institution. Results: During the study period 225 patients with a diagnosis of stage I and IIa CC underwent surgical resection. One hundred and eleven stage I and 114 IIa CC patients were reviewed. Follow-up data were available for all patients. Median follow-up was 39 months. Five-years OS and DFS were 97.2% and 96.5% respectively. At survival analysis in stage I patients we could not identify any significant prognostic factor. On univariable analysis in IIa stage only DMAX <4cm (5 yrs DFS 71.7% vs. 87.6% − p:0.028) was associated with statically worse DFS. On univariable Cox regression analysis DMAX <4cm was associated with an increased risk of recurrence (HR: 3.436; 95% Confidence Interval: 1,058–11.161; p: 0.04). All IIa stage patients were divided into 2 groups, according to DMAX (small CC and large CC). In the same period 100 high risk IIa, IIb/c were treated. Median follow-up was 47.5 months, and five-years DFS was 78.3%. Seventy-nine patients received adjuvant chemotherapy. Moreover, the outcome of small and large IIa stage CC were compared with the outcome of high risk IIa, IIb/c stage CC. DFS in large IIa CC was significantly better than high risk IIa, IIb/c (5 years DFS 92.7% vs 79.3% − p: 0.023). Instead, at survival analysis recurrence rate in small IIa CC was similar to high risk IIa, IIb CC (5 years DFS 71.7% vs 79.3% − p: 0.839). Conclusions: For patients with stage IIa CC treated with resection alone, evaluation of tumor size as a prognostic factor may help identify those patients who could benefit from additional postoperative therapy. No conflict of interest. 2056 POSTER Locally advanced rectal cancer with neoadyuvant treatment strategies: Our experiences M.L. Blanco Villar1 , A. Rodriguez Gutierrez1 , A. Nieto Palacio1 , A. Matias Perez1 , P. Soria Carreras1 , V.M. Macias Hernandez1 , O. Alonso Rodriguez1 , M. Sanchez Barba1 , L.A. Perez Romasanta1 , J. Garc´ıa2 . 1 Hospital Universitario, Radiation Oncology, Salamanca, Spain; 2 Hospital Universitario, Surgery, Salamanca, Spain Background: Preoperative chemo-radiotherapy (CRT) followed by radical surgery, has emerged as the preferred treatment for locally advanced rectal cancer.
S347 This study reports outcomes of patients with locally advanced rectal cancer with (CRT) followed by surgery. The Primary end-point was evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response and the rate of sphincter preservation for distal cancers. Secondary end-point was report local control and distant relapse. Methods: Present a single-centre retrospective study of consecutive patients with clinical stage II − III rectal adenocarcinoma that received preoperative treatment with short-course radiotherapy (25 Gy in 5 daily fractions) or long-course radiotherapy (45−46 Gy in 25 fractions) with concomitant chemotherapy based in fluoropirimidines. The study group consisted of 275 (171 males, 104 females) retrospectively accrued patients with locally advanced rectal cancer treated from 2004 to 2015 at our institution. Median age at diagnosis was 71 years. All patients had biopsy-proven rectal adenocarcinoma. Results: All of them completed radiotherapy. The median time of radiotherapy was 5 weeks. The elder patients who couldn’t receive chemotherapy were only 6,9% (19 of 275 patients) and they had received short-course radiotherapy. The rest of them received long-course radiotherapy. Most of patients received preoperative chemotherapy (230 of 275) using capecitabine in the most of cases. The toxicity was evaluated using RTOG/EORTC toxicity criteria. Acute toxicity was observed in 160 patients (60,2%). We reported gastrointestinal acute toxicity in 49% of patients (grade 1 in 29,2% of them and grade 2 in 21%). The most common toxicity was gastrointestinal. There were only 2 patients with acute gastrointestinal toxicity grade 3. The genitourinary acute toxicity and skin reactions were less observed. Surgery was performed in 264 patients with 88,2% R0 resection (Table 1). The median time to surgery was 8 weeks. 68,7% (189 of 264) of patients achieved pathological downstaging and 14’8% (28 of 189) had a pathologic complete response. In 110 patients the localization of tumor was in lower part of rectum. 25 of these patients had anterior resection (22’7%) allowing the preservation of the anal sphincter. Table 1. Surgical status Surgical status
Frequency
Percentage
R1 R2 R0 Irresectable Total
16 7 232 8 264
6.1 2.7 88.2 3.0 100
At median follow-up was a 2.5 year. 40 patients (14.5%) had a local relapse. 56 (20.6%) had distant relapse. Conclusions: We believe that locally advance rectal cancer can be managed satisfactory with chemo-radiotherapy followed surgery. Our study provides right evidence that neoadyuvant treatment for rectal cancer was safe and well tolerated with right local control and distant relapse. We report right rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. No conflict of interest. 2057 POSTER Assessment of tumor-infiltrating lymphocytes in metastatic colorectal cancer patients treated by Bevacizumab-based chemotherapy J.P. Spano1 , A. Gobert2 , C. Mateescu2 , R. Mouawad3 , A. Bardier4 , J.B. Bachet5 , O. Dubreuilh5 , J. Varinot6 , R. Mitri5 , D. Khayat3 , G. Malouf3 , ´ ˆ ere ` University Hospital − INSERM UMR_S F. Capron7 . 1 Pitie-Salp etri 1136, GHPS-CFX, APHP, IUC/UPMC, Medical Oncology, Paris, France; 2 ´ ˆ ere, ` Groupe Hospitalier Pitie-Salp etri Medical Oncology, Paris, France; 3 ´ ˆ ere ` Hospital, GRC5 IUC/UPMC, Medical Oncology, Paris, Pitie-Salp etri 4 ´ ˆ ere, ` France; Groupe Hospitalier Pitie-Salp etri Anatomy Pathology, Paris, ´ ˆ ere, ` France; 5 Groupe Hospitalier Pitie-Salp etri Internal Medecine, Paris, 6 ´ ˆ ere, ` France; Groupe Hospitalier Pitie-Salp etri anatomy patologic, Paris, 7 ´ ˆ ere-UPMC, ` France; Groupe Hospitalier Pitie-Salp etri Anatomy Pathology, Paris, France Background: Previous studies recently demonstrated that the immune system dictates prognosis and response to chemotherapy in several tumor subtypes. Furthermore, programmed death-1 (PD-1) has become a potential target in oncology. However, it remains unknown if the expression of tumor-infiltrating cells (TIL) and PD-1 can predict outcome of patients with metastatic colorectal cancers treated by Bevacuzimab-based chemotherapy. Methods: We analyzed the correlation between the quantity and location of lymphocytic infiltrate (primary and metastasis) in a large cohort of colorectal
S348
Abstracts
cancers treated in our institution between January 2009 and January 2015 by Bevacuzimab-based chemotherapy (Bbc). For this purpose, a tissuemicroarray composed of 130 samples related to 93 patients has been constructed. The results of TIL were scored as negative/low or high. The percentage of PD-1 expressed has also been assessed. Results: The TIL assessment was available for 75 primary tumors and 55 metastastic sites including liver (n = 35), peritoneum (n = 15) and others (n = 5). There was no difference of TIL expression between primary tumors and metastatic sites (p = 0.79). Surprisingly, higher TIL and CD4/CD8 ratio were observed in liver metastases as compared to other sites (p = 0.0097). PD-1 expression was identified in 11 (14.6%) primary tumors and 6 (10.9%) metastatic sites (p = 0.79). Of note, three out of 8 cases with available matched primary-liver metastasis gained PD-1 expression in metastastic sites. This was associated with increase of lymphocytic infiltration. Clinical data were available for 76 patients (48 M; 28F) for correlation with time to progression. Time to progression (TTP) under Bbc was 6.4 months and 7.5 months in TIL negative/low and high primary tumors, respectively (p = 0.9). Likewise, no difference in TTP was observed between PD-1 expressing primary tumors versus others (p = 0.1). Conclusion: No differences in response rate to Bbc were observed according to TIL and PD-1 expressions. High variability of TIL expression was identified between liver and other metastatic sites in colorectal cancers, suggesting that immune response might differ according to tumor location. No conflict of interest.
similar in both early- and non-early response groups, except for a smaller largest lesion diameter in the early-responders (median, 37 vs 60 mm, p = 0.02). Main Grade 3−4 toxicities per patient did not differ with statistical significance between both groups (neutropenia, 50.0% vs 43.9; abdominal pain, 25% vs 29.3%,;diarrhea, 6.3% vs 22.0%,), except for asthenia (0% vs 26.8%, p = 0.024). The rate of pts with R0-R1 liver metastases resection was nearly twice as large in early responders as compared to those without an early response (7 pts, 43.8% vs 10 pts 24.4%, p = 0.20). Median OS was larger in the early-responders as compared to the non-early responders: 34.5 months [32.1–36.9] vs 20.2 [13.6–26.8] (p = 0.010). Both extent of liver involvement and chronomodulated delivery were independent predictors of an early response according to logistic regression (0,025 and 0.043, respectively). Conclusions: This retrospective analysis suggests for the first time, that an early tumor response on hepatic artery infusion and systemic cetuximab may predict increased conversion rate to metastases resection, and prolonged OS. These findings need confirmation on a larger sample size. Supported by ARTBC International, Villejuif; Merck-Serono, Lyon; and Pfizer, Paris (France) No conflict of interest.
2058 POSTER Early tumor shrinkage as a predictor for long-term outcome in patients (pts) with unresectable liver metastases from wt-KRAS colorectal cancer (LM-CRC) treated with hepatic artery infusion (HAI) of Irinotecan, 5-Fluorouracil and Oxaliplatin plus intravenous Cetuximab (IV-Cet) after failure of one to three systemic protocols (European phase II clinical trial NCT00852228)
R. Font1,2 , J.A. Espinas ` 1,2 , J. Sola` 1,2 , L. Layos3 , M. Tobena ˜ 4, J. Capdevila5 , M. Martinez6 , J. Alfaro7 , T. Bonfill8 , J. Albanell9 , D. Paez4 , E. Dotor7 , P. Manchon-Walsh1,2 , J. Borras ` Andres ` 1,2 . 1 Department of Health, Government of Catalonia, Catalonian Cancer Strategy, L’Hospitalet Llobregat Barcel, Spain; 2 Biomedical Research Institute of Bellvitge IDIBELL, University of Barcelona-, Department of Clinical Sciences, Barcelona, Spain; 3 Germans Trias i Pujol Hospital, ICO-Badalona, Department of Medical Oncology, Badalona, Spain; 4 Santa Creu i Sant Pau Hospital, Department of Medical Oncology, Barcelona, Spain; 5 Department of Medical Oncology, Valle Hebron Hospital, Barcelona, Spain; 6 Bellvitge Biomedical Research Institute, Catalonian Institute of Oncology, Department of Medical Oncology, Barcelona, Spain; 7 Terrassa Health Consortium, Department of Medical Oncology, Terrassa, Spain; 8 Parc Taulı Health Corporation, Department of Medical Oncology, Sabadell, Spain; 9 Del Mar Hospital, Department of Medical Oncology, Barcelona, Spain
M. Bouchahda1 , D. Michel2 , S. Denis3 , K. Abdoulaye4 , H. Mohamed5 , 6 L. Celine ´ , F. Christian7 , G. Rosine8 , I. Pasquale9 , A. Sameh10 , C. Carlos11 , T. Salvatore12 , T. Stephanie5 , D.B. Thierry13 , C. Denis14 , R. Philippe6 , B. Valerie ´ 13 , M. Jean Fran¸cois4 , A. Rene´ 15 , L. Francis16 . 1 Paul Brousse Hospital, Medical Oncology, villejuif, France; 2 Institut Gustave Roussy, Service d’Oncologie Digestive, Villejuif, France; 3 ˆ ´ Medical Oncology Centre Hospitalo-Universitaire, Hopital Saint-Andre, Department, Bordeaux, France; 4 Paul Brousse hospital, Medical Oncology ˆ Department, Villejuif, France; 5 Hopital Huriez, Medical Oncology ˆ ´ Department, Lille, France; 6 Hopital Europeen Gorges Pompidou, Service ´ ´ ´ Hepato-Gastro-Ent erologie, Paris, France; 7 Centre Hospitalier Chretien, ` Clinique Saint-Joseph, Department of Oncology, Liege, Belgium; 8 University Hospital of Purpan, Oncology Department, Toulouse, France; 9 Paul Brousse hospital, Medical Oncology Department, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Villejuif, France; 10 Paul Brousse hospital, Radiology Department, Villejuif, France; 11 Hospital Fernando Fonesca, Medical Oncology Unit, Amadora, Portugal; 12 Santa Maria DegliAngeli General Hospital, Oncology Department, Pordenone, Italy; 13 Institut Gustave Roussy, Service d’Oncologie Digestive, Villejuif, France; 14 Paul Brousse hospital, Hepatobiliary Center, Villejuif, France; 15 Paul Brousse hospital, Hepatobiliary Center, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Villejuif, France; 16 Paul Brousse hospital, Medical Oncology Department, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Warwick Medical School, Villejuif, France Background: Early tumor shrinkage (ETS) has been associated with improved long-term outcome in pts with chemotherapy (chemo)-refractory LM-CRC receiving Cetuximab (Piessevaux et al. JCO2013). Purpose: to assess overall survival in early responding pts with unresectable LM-CRC on hepatic artery infusion of triplet chemo plus IV-Cet. Methods: Pts received IV-Cet (500 mg/m2 ) and chronomodulated or conventional HAI of Irinotecan (180mg/m2 ), 5-Fluorouracil (2800 mg/m2 ), and Oxaliplatin (85mg/m2 ) q2 wks. Radiologic assessments were performed after 3, 6 or 9 courses to calculate the sum of the largest diameters of the target lesions and identify tumor response according to RECIST criteria. Pt population was categorized in early-responders (CR or PR after 3 courses) and non-early-responders. Overall survival (OS), progression free survival (PFS), macroscopic liver resection (R0-R1) and overall response rate were compared between the two groups. P-value <0.05 was considered as statistically significant. Results: Fifty-seven of 64 registered pts received 3 or more chemo courses and were assessed for response. There were 16 early-responders and 41 non-early-responders. The early-response group involved 9M and 7F, aged 33−76 years, with good PS (0/1−2: 12/4). LM were bilateral in 13 pts (81.3%), with a median of 12 metastasis (2−50), 5 segments involved (1−8), and largest diameter of 37 (15−93). The pt characteristics were
2059 POSTER Adherence to oral therapy in rectal cancer patients in Catalonia, Spain
Background: Oral treatments for cancer could have a differential impact on adherence to chemotherapy compared to iv treatments and suggest the need to assess it in the most frequent tumours. The aim of this study was to assess the adherence to oral neoadjuvant therapy in rectal cancer as well as the related explanatory factors. Materials and Methods: This study included all newly diagnosed stage II and III rectal cancer patients treated with four-five weeks capecitabine in preoperative combined radio-chemotherapy from September 2012 to January 2014 in the 7 hospitals in Catalonia with a high volume of patients. Adherence was assessed on the basis of physician report and patient selfreport (SMAQ). Persistence was measured by refill prescriptions. We used the alternative Kappa index to compare adherence measures and logistic regression to evaluate adherence-related factors. Results: 120 patients were included in the study. 63.3% were males. Mean age at diagnosis was 64.8 years (DS±10.0); 19.2% were with IIA or IIIA stage, 43.3% with IIIB stage and 35.0% with IIIC. Almost all patients (98..3%) underwent a surgical procedure with radical intent. GI bleeding (80.0%) and asthenia (25.8%) were the most frequent symptoms previous to the neoadjuvant therapy. The adherence using the refill data from the Administrative drug-reimbursement database was of 80.0% while using SMAQ was of 90.7%. Instead, the highest adherence was observed for physician report (100%). Good concordance between measures was observed (alternative Kappa range: 0.72–0.90). Patients aged 55−64 year and over showed higher adherence than those aged younger than 55 years measured by the prescription refill of the drug (OR: 3.72, 95% CI 0.78–17.87; OR 1.88, 95% CI 0.54–6.54 respectively). Patients with stage IIIB-IIIC were more likely to be adherents (OR 1.50 95% CI 0.41–5.55). Furthermore, tumoral grade higher than one decreases the probability of adherence to treatment. Higher levels of anxiety and depression were also associated with lower adherence (OR: 0.90 95% CI 0.82–0.98). Further analyses are ongoing. Conclusions: Even for a short duration treatment in the adjuvancy context, adherence to oral chemotherapy using refill prescription data indicated that his is an issue in the management of rectal cancer patients, and should be assessed in clinical practice. In this framework, it is relevant that physicians did not record any adherence problem in the clinical records. Funded by PI11/02011 No conflict of interest.
S347 This study reports outcomes of patients with locally advanced rectal cancer with (CRT) followed by surgery. The Primary end-point was evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response and the rate of sphincter preservation for distal cancers. Secondary end-point was report local control and distant relapse. Methods: Present a single-centre retrospective study of consecutive patients with clinical stage II − III rectal adenocarcinoma that received preoperative treatment with short-course radiotherapy (25 Gy in 5 daily fractions) or long-course radiotherapy (45−46 Gy in 25 fractions) with concomitant chemotherapy based in fluoropirimidines. The study group consisted of 275 (171 males, 104 females) retrospectively accrued patients with locally advanced rectal cancer treated from 2004 to 2015 at our institution. Median age at diagnosis was 71 years. All patients had biopsy-proven rectal adenocarcinoma. Results: All of them completed radiotherapy. The median time of radiotherapy was 5 weeks. The elder patients who couldn’t receive chemotherapy were only 6,9% (19 of 275 patients) and they had received short-course radiotherapy. The rest of them received long-course radiotherapy. Most of patients received preoperative chemotherapy (230 of 275) using capecitabine in the most of cases. The toxicity was evaluated using RTOG/EORTC toxicity criteria. Acute toxicity was observed in 160 patients (60,2%). We reported gastrointestinal acute toxicity in 49% of patients (grade 1 in 29,2% of them and grade 2 in 21%). The most common toxicity was gastrointestinal. There were only 2 patients with acute gastrointestinal toxicity grade 3. The genitourinary acute toxicity and skin reactions were less observed. Surgery was performed in 264 patients with 88,2% R0 resection (Table 1). The median time to surgery was 8 weeks. 68,7% (189 of 264) of patients achieved pathological downstaging and 14’8% (28 of 189) had a pathologic complete response. In 110 patients the localization of tumor was in lower part of rectum. 25 of these patients had anterior resection (22’7%) allowing the preservation of the anal sphincter. Table 1. Surgical status Surgical status
Frequency
Percentage
R1 R2 R0 Irresectable Total
16 7 232 8 264
6.1 2.7 88.2 3.0 100
At median follow-up was a 2.5 year. 40 patients (14.5%) had a local relapse. 56 (20.6%) had distant relapse. Conclusions: We believe that locally advance rectal cancer can be managed satisfactory with chemo-radiotherapy followed surgery. Our study provides right evidence that neoadyuvant treatment for rectal cancer was safe and well tolerated with right local control and distant relapse. We report right rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. No conflict of interest. 2057 POSTER Assessment of tumor-infiltrating lymphocytes in metastatic colorectal cancer patients treated by Bevacizumab-based chemotherapy J.P. Spano1 , A. Gobert2 , C. Mateescu2 , R. Mouawad3 , A. Bardier4 , J.B. Bachet5 , O. Dubreuilh5 , J. Varinot6 , R. Mitri5 , D. Khayat3 , G. Malouf3 , ´ ˆ ere ` University Hospital − INSERM UMR_S F. Capron7 . 1 Pitie-Salp etri 1136, GHPS-CFX, APHP, IUC/UPMC, Medical Oncology, Paris, France; 2 ´ ˆ ere, ` Groupe Hospitalier Pitie-Salp etri Medical Oncology, Paris, France; 3 ´ ˆ ere ` Hospital, GRC5 IUC/UPMC, Medical Oncology, Paris, Pitie-Salp etri 4 ´ ˆ ere, ` France; Groupe Hospitalier Pitie-Salp etri Anatomy Pathology, Paris, ´ ˆ ere, ` France; 5 Groupe Hospitalier Pitie-Salp etri Internal Medecine, Paris, 6 ´ ˆ ere, ` France; Groupe Hospitalier Pitie-Salp etri anatomy patologic, Paris, 7 ´ ˆ ere-UPMC, ` France; Groupe Hospitalier Pitie-Salp etri Anatomy Pathology, Paris, France Background: Previous studies recently demonstrated that the immune system dictates prognosis and response to chemotherapy in several tumor subtypes. Furthermore, programmed death-1 (PD-1) has become a potential target in oncology. However, it remains unknown if the expression of tumor-infiltrating cells (TIL) and PD-1 can predict outcome of patients with metastatic colorectal cancers treated by Bevacuzimab-based chemotherapy. Methods: We analyzed the correlation between the quantity and location of lymphocytic infiltrate (primary and metastasis) in a large cohort of colorectal
S348
Abstracts
cancers treated in our institution between January 2009 and January 2015 by Bevacuzimab-based chemotherapy (Bbc). For this purpose, a tissuemicroarray composed of 130 samples related to 93 patients has been constructed. The results of TIL were scored as negative/low or high. The percentage of PD-1 expressed has also been assessed. Results: The TIL assessment was available for 75 primary tumors and 55 metastastic sites including liver (n = 35), peritoneum (n = 15) and others (n = 5). There was no difference of TIL expression between primary tumors and metastatic sites (p = 0.79). Surprisingly, higher TIL and CD4/CD8 ratio were observed in liver metastases as compared to other sites (p = 0.0097). PD-1 expression was identified in 11 (14.6%) primary tumors and 6 (10.9%) metastatic sites (p = 0.79). Of note, three out of 8 cases with available matched primary-liver metastasis gained PD-1 expression in metastastic sites. This was associated with increase of lymphocytic infiltration. Clinical data were available for 76 patients (48 M; 28F) for correlation with time to progression. Time to progression (TTP) under Bbc was 6.4 months and 7.5 months in TIL negative/low and high primary tumors, respectively (p = 0.9). Likewise, no difference in TTP was observed between PD-1 expressing primary tumors versus others (p = 0.1). Conclusion: No differences in response rate to Bbc were observed according to TIL and PD-1 expressions. High variability of TIL expression was identified between liver and other metastatic sites in colorectal cancers, suggesting that immune response might differ according to tumor location. No conflict of interest.
similar in both early- and non-early response groups, except for a smaller largest lesion diameter in the early-responders (median, 37 vs 60 mm, p = 0.02). Main Grade 3−4 toxicities per patient did not differ with statistical significance between both groups (neutropenia, 50.0% vs 43.9; abdominal pain, 25% vs 29.3%,;diarrhea, 6.3% vs 22.0%,), except for asthenia (0% vs 26.8%, p = 0.024). The rate of pts with R0-R1 liver metastases resection was nearly twice as large in early responders as compared to those without an early response (7 pts, 43.8% vs 10 pts 24.4%, p = 0.20). Median OS was larger in the early-responders as compared to the non-early responders: 34.5 months [32.1–36.9] vs 20.2 [13.6–26.8] (p = 0.010). Both extent of liver involvement and chronomodulated delivery were independent predictors of an early response according to logistic regression (0,025 and 0.043, respectively). Conclusions: This retrospective analysis suggests for the first time, that an early tumor response on hepatic artery infusion and systemic cetuximab may predict increased conversion rate to metastases resection, and prolonged OS. These findings need confirmation on a larger sample size. Supported by ARTBC International, Villejuif; Merck-Serono, Lyon; and Pfizer, Paris (France) No conflict of interest.
2058 POSTER Early tumor shrinkage as a predictor for long-term outcome in patients (pts) with unresectable liver metastases from wt-KRAS colorectal cancer (LM-CRC) treated with hepatic artery infusion (HAI) of Irinotecan, 5-Fluorouracil and Oxaliplatin plus intravenous Cetuximab (IV-Cet) after failure of one to three systemic protocols (European phase II clinical trial NCT00852228)
R. Font1,2 , J.A. Espinas ` 1,2 , J. Sola` 1,2 , L. Layos3 , M. Tobena ˜ 4, J. Capdevila5 , M. Martinez6 , J. Alfaro7 , T. Bonfill8 , J. Albanell9 , D. Paez4 , E. Dotor7 , P. Manchon-Walsh1,2 , J. Borras ` Andres ` 1,2 . 1 Department of Health, Government of Catalonia, Catalonian Cancer Strategy, L’Hospitalet Llobregat Barcel, Spain; 2 Biomedical Research Institute of Bellvitge IDIBELL, University of Barcelona-, Department of Clinical Sciences, Barcelona, Spain; 3 Germans Trias i Pujol Hospital, ICO-Badalona, Department of Medical Oncology, Badalona, Spain; 4 Santa Creu i Sant Pau Hospital, Department of Medical Oncology, Barcelona, Spain; 5 Department of Medical Oncology, Valle Hebron Hospital, Barcelona, Spain; 6 Bellvitge Biomedical Research Institute, Catalonian Institute of Oncology, Department of Medical Oncology, Barcelona, Spain; 7 Terrassa Health Consortium, Department of Medical Oncology, Terrassa, Spain; 8 Parc Taulı Health Corporation, Department of Medical Oncology, Sabadell, Spain; 9 Del Mar Hospital, Department of Medical Oncology, Barcelona, Spain
M. Bouchahda1 , D. Michel2 , S. Denis3 , K. Abdoulaye4 , H. Mohamed5 , 6 L. Celine ´ , F. Christian7 , G. Rosine8 , I. Pasquale9 , A. Sameh10 , C. Carlos11 , T. Salvatore12 , T. Stephanie5 , D.B. Thierry13 , C. Denis14 , R. Philippe6 , B. Valerie ´ 13 , M. Jean Fran¸cois4 , A. Rene´ 15 , L. Francis16 . 1 Paul Brousse Hospital, Medical Oncology, villejuif, France; 2 Institut Gustave Roussy, Service d’Oncologie Digestive, Villejuif, France; 3 ˆ ´ Medical Oncology Centre Hospitalo-Universitaire, Hopital Saint-Andre, Department, Bordeaux, France; 4 Paul Brousse hospital, Medical Oncology ˆ Department, Villejuif, France; 5 Hopital Huriez, Medical Oncology ˆ ´ Department, Lille, France; 6 Hopital Europeen Gorges Pompidou, Service ´ ´ ´ Hepato-Gastro-Ent erologie, Paris, France; 7 Centre Hospitalier Chretien, ` Clinique Saint-Joseph, Department of Oncology, Liege, Belgium; 8 University Hospital of Purpan, Oncology Department, Toulouse, France; 9 Paul Brousse hospital, Medical Oncology Department, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Villejuif, France; 10 Paul Brousse hospital, Radiology Department, Villejuif, France; 11 Hospital Fernando Fonesca, Medical Oncology Unit, Amadora, Portugal; 12 Santa Maria DegliAngeli General Hospital, Oncology Department, Pordenone, Italy; 13 Institut Gustave Roussy, Service d’Oncologie Digestive, Villejuif, France; 14 Paul Brousse hospital, Hepatobiliary Center, Villejuif, France; 15 Paul Brousse hospital, Hepatobiliary Center, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Villejuif, France; 16 Paul Brousse hospital, Medical Oncology Department, INSERM, UMRS 776 “Biological Rhythms and Cancers”, Warwick Medical School, Villejuif, France Background: Early tumor shrinkage (ETS) has been associated with improved long-term outcome in pts with chemotherapy (chemo)-refractory LM-CRC receiving Cetuximab (Piessevaux et al. JCO2013). Purpose: to assess overall survival in early responding pts with unresectable LM-CRC on hepatic artery infusion of triplet chemo plus IV-Cet. Methods: Pts received IV-Cet (500 mg/m2 ) and chronomodulated or conventional HAI of Irinotecan (180mg/m2 ), 5-Fluorouracil (2800 mg/m2 ), and Oxaliplatin (85mg/m2 ) q2 wks. Radiologic assessments were performed after 3, 6 or 9 courses to calculate the sum of the largest diameters of the target lesions and identify tumor response according to RECIST criteria. Pt population was categorized in early-responders (CR or PR after 3 courses) and non-early-responders. Overall survival (OS), progression free survival (PFS), macroscopic liver resection (R0-R1) and overall response rate were compared between the two groups. P-value <0.05 was considered as statistically significant. Results: Fifty-seven of 64 registered pts received 3 or more chemo courses and were assessed for response. There were 16 early-responders and 41 non-early-responders. The early-response group involved 9M and 7F, aged 33−76 years, with good PS (0/1−2: 12/4). LM were bilateral in 13 pts (81.3%), with a median of 12 metastasis (2−50), 5 segments involved (1−8), and largest diameter of 37 (15−93). The pt characteristics were
2059 POSTER Adherence to oral therapy in rectal cancer patients in Catalonia, Spain
Background: Oral treatments for cancer could have a differential impact on adherence to chemotherapy compared to iv treatments and suggest the need to assess it in the most frequent tumours. The aim of this study was to assess the adherence to oral neoadjuvant therapy in rectal cancer as well as the related explanatory factors. Materials and Methods: This study included all newly diagnosed stage II and III rectal cancer patients treated with four-five weeks capecitabine in preoperative combined radio-chemotherapy from September 2012 to January 2014 in the 7 hospitals in Catalonia with a high volume of patients. Adherence was assessed on the basis of physician report and patient selfreport (SMAQ). Persistence was measured by refill prescriptions. We used the alternative Kappa index to compare adherence measures and logistic regression to evaluate adherence-related factors. Results: 120 patients were included in the study. 63.3% were males. Mean age at diagnosis was 64.8 years (DS±10.0); 19.2% were with IIA or IIIA stage, 43.3% with IIIB stage and 35.0% with IIIC. Almost all patients (98..3%) underwent a surgical procedure with radical intent. GI bleeding (80.0%) and asthenia (25.8%) were the most frequent symptoms previous to the neoadjuvant therapy. The adherence using the refill data from the Administrative drug-reimbursement database was of 80.0% while using SMAQ was of 90.7%. Instead, the highest adherence was observed for physician report (100%). Good concordance between measures was observed (alternative Kappa range: 0.72–0.90). Patients aged 55−64 year and over showed higher adherence than those aged younger than 55 years measured by the prescription refill of the drug (OR: 3.72, 95% CI 0.78–17.87; OR 1.88, 95% CI 0.54–6.54 respectively). Patients with stage IIIB-IIIC were more likely to be adherents (OR 1.50 95% CI 0.41–5.55). Furthermore, tumoral grade higher than one decreases the probability of adherence to treatment. Higher levels of anxiety and depression were also associated with lower adherence (OR: 0.90 95% CI 0.82–0.98). Further analyses are ongoing. Conclusions: Even for a short duration treatment in the adjuvancy context, adherence to oral chemotherapy using refill prescription data indicated that his is an issue in the management of rectal cancer patients, and should be assessed in clinical practice. In this framework, it is relevant that physicians did not record any adherence problem in the clinical records. Funded by PI11/02011 No conflict of interest.