The importance of maintenance chemotherapy in the first and second lines of treatment of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15583-e15583
Author(s):  
Danila Gridnev ◽  
Anatoly Popov ◽  
Dina Islamova ◽  
Vladislav Makarov ◽  
Edouard Vozny ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Locally Advanced ◽  
Long Term Results ◽  
Maintenance Chemotherapy ◽  
Group A ◽  
Group B ◽  
The Right

e15583 Background: The first and second lines of CT is decisive in the treatment of colorectal cancer. Choosing the right one allows you to increase PFS and improve long-term results. Surgical treatment and maintenance chemotherapy (MT) increase PFS and OS, as they can be prescribed at any stage of treatment. Methods: The analysis included 192 patients diagnosed with metastatic colorectal cancer (mCRC) who received treatment between 2014 and 2019. The average age of the patients was 62 years. At the beginning of treatment, the overall condition of all patients was ECOG1. Primary mCRC had 129 (67%) patients. In 63 (33%) patients, locally advanced disease was first diagnosed, which were included in the study after progression. PFS and OS for all patients were calculated from the start of the 1st line. Localization of the primary tumor in 42 (22%) patients was on the right side of the colon and on the left side in 149 (78%) and 1 patient did not show primary tumor. Among the patients with primary metastatic disease, 100 (52%) had isolated metastases, while the remaining 92 (48%) had 2 or more localizations. Different types of surgical treatment of metastases in the liver occurred in 41 (21%) patients. 119 patients never received MT (with any number of lines) and made a comparison group(A). 73 patients received MT in at least one of the CT lines (B). 12 patients received MT in the 1st and 2nd CT (C). These groups were homogeneous in terms of gender, age, ECOG, accessibility of surgical treatment of distant metastasis, mutational status of the tumor, and accessibility of biotherapy. Evaluation of the effect was performed using RECIST criteria, at intervals of 3 months or the appearance of clinical symptoms of progression. The treatment was carried out before the progression. At the time of analysis, 94 patients are alive and continue to receive treatment. Results: We compared in all three groups: In group A: OS - 12.9 months, PFS 1-line CT - 9.5 months, PFS 2-line CT - 4.5 months In group B: OS - 27.6 months, PFS 1-line CT - 13.6 months, PFS 2-line CT - 9.1 months In group C: OS - 38.3 months, PFS 1-line CT - 14.2 months, PFS 2-line CT - 9.1 months. “Five-year” survival (In those patients who were observed from the start of the study for all 5 years) in group A was 5,8 %, in group B 15 %, and in group C 16 %. Conclusions: Increase of PFS and OS in patients who received MT at least at one of the stages of treatment, and continues to increase in patients receiving MT in the first two lines CT. Thus, MT is a necessary component of the treatment of mCRC.

The role of combined treatment of metastatic colorectal cancer inpatients with liver metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16026-e16026
Author(s):  
Mikhail Trandofilov ◽  
Danila Gridnev ◽  
Anatoly Popov ◽  
Anna Sizova ◽  
Dina Islamova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Metastatic Colorectal Cancer ◽  
Molecular Genetic ◽  
Combined Treatment ◽  
Surgical Techniques ◽  
Genetic Characteristics ◽  
Complex Therapy ◽  
Group A ◽  
Group B

e16026 Background: Combined treatment for patients with metastatic colorectal cancer (mCRC) offers better long-term outcomes and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. Methods: The analysis included 132 patients diagnosed with mCRC having metastases in the liver treated from 2015 to 2020. Of these, 62 (47%) were men and 70 (53%) women. The average age of the patients was 63 years. At the beginning of the treatment, the overall condition of all patients met ECOG 0-1 points. Primary metastatic CRC had 93 (71%) patients. A total of 39 (29%) patients were diagnosed with advanced disease. Localization of the primary tumor in 25 patients (18.9%) was in the right part of the large intestine and 107 (81.1%) in the left part of the colon. At the time of the sample, metastases were detected only in the liver in 73 patients (55.3%). In the remaining 59 (44.7%) other organs were affected besides the liver. Various types of surgical treatment of metastases in the liver received 42 (31.8%) patients. The decision on the choice of chemotherapy was made by the attending physician on the basis of the recommendations of NCCN and RUSSCO, taking into account the molecular genetic characteristics of the tumor. The decision to apply and choose the method of surgical treatment was taken in conjunction with the surgeon. Results: From the general population of patients receiving complex therapy, 2 groups were identified, between which a comparison was made. The first group (group A) was 42 (31.8%) patients who received some surgical treatment of the liver. The second group (group B) included 90 (68.2%) patients, who for some reason or another, did not receive any surgical treatment. The groups are fairly homogeneous in their characteristics. The median overall survival (OS) in group A was 40.1 months, and in group B, 22.3 months. A similar trend continued in subgroup analysis. The calculation of the PFS was complicated by the fact that surgical operations were given at different stages of complex treatment. Three-year survival in group A was approximately 50%, and in group B, 28%. "Five-year" survival (In those patients who were observed from the start of the study for all 5 years) in group A was 15 %, and in group B, 5,5%. Conclusions: The inclusion of modern surgical techniques in the complex therapy of metastatic colorectal cancer, if possible, at any stage, can significantly increase the life expectancy of patients.

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

1996 ◽  
Vol 14 (5) ◽  
pp. 1599-1603 ◽  
Author(s):  
P Percivale ◽  
S Bertoglio ◽  
P Meszaros ◽  
G Canavese ◽  
F Cafiero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Primary Tumor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Primary Chemotherapy ◽  
Radioimmunoguided Surgery ◽  
Group A ◽  
Group B

PURPOSE To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

scholarly journals Surgical treatment of pulmonary sequestration in adults and children: long-term results

2020 ◽  
Vol 31 (1) ◽  
pp. 71-77
Author(s):  
Beatrice Trabalza Marinucci ◽  
Giulio Maurizi ◽  
Camilla Vanni ◽  
Giuseppe Cardillo ◽  
Camilla Poggi ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Respiratory Symptoms ◽  
Pulmonary Sequestration ◽  
Adult Patients ◽  
Long Term Results ◽  
Study Results ◽  
Group A ◽  
Group B ◽  
Histological Results

Abstract OBJECTIVES Few experiences comparing paediatric and adult patients treated for pulmonary sequestration (PS) have been reported. Surgical treatment is considered the best choice, but the time of surgery is still controversial. We present our experience in this setting, comparing characteristics, histological results and outcome of paediatric and adult patients undergoing PS resection. METHODS Between 1998 and 2017, a total of 74 patients underwent lobectomy or sublobar resection for PS. Sixty patients were children (group A: ≤16 years old) and 14 were adults (group B: >16 years old). Preoperative diagnosis was radiological. PS was intralobar (42 cases) and extralobar (32 cases). The operation was a muscle-sparing lateral thoracotomy or video-assisted thoracoscopic surgery. Preoperative characteristics, histological results and short-/long-term results of the 2 groups were retrospectively analysed and compared. RESULTS Thirty-seven percent of the patients in group A presented with respiratory symptoms and 79% in group B (P = 0.44). Most symptomatic patients were treated with a lobectomy. In group A, 2 patients (3%) had a malignant transformation of the lesion. Patients with a prenatal diagnosis treated after the age of 1 year became more symptomatic than those operated on before the age of 1 year (57% vs 23%; P = 0.08). No differences were found in postoperative complications. Long-term stable remission of respiratory symptoms was obtained in 91% of patients in group A and 100% in group B. Adulthood (P = 0.03) and the association with congenital cystic adenomatoid malformation (P = 0.03) were negative prognostic factors for the development of respiratory symptoms. CONCLUSIONS Surgical treatment of PS is safe and feasible. Despite the small number of patients included, study results indicated that an early operation during childhood may prevent the subsequent development of respiratory symptoms. Surgical treatment is also recommended to prevent the rare transformation into malignancy.

Surgical management of synchronous colorectal liver metastases: Simultaneous versus staged resections.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 616-616
Author(s):  
Igor Shchepotin ◽  
Andrii Lukashenko ◽  
Olena Kolesnik ◽  
Anton Burlaka
Keyword(s):  
Colorectal Cancer ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Liver Metastases ◽  
Metastatic Cancer ◽  
Economic Effect ◽  
Hepatic Metastases ◽  
Group A ◽  
Bed Days ◽  
Group B

616 Background: Surgical treatment of metastatic colorectal cancer remains the only method that improves overall 5-year survival. This study aimed to compare the surgical outcome and survival benefit between synchronous and staged resection of liver metastases from colorectal cancer. Methods: Clinicopathologic data, treatments, and postoperative outcomes from 110 patients who underwent simultaneous (48 patients, group A) or staged (62 patients, group B) colorectal and hepatic resections at clinic of National cancer institute in period of 2008-2013 were reviewed. Results: Postoperative complications in patients with simultaneous resections (group A) were observed in 13 cases (27.1%), including 5, 1, 4, 2, 0, and 1 of grades I, II, IIIa, IIIb, IV, and V, respectively. Similar results have been reported in group B after staged resections, where overall postoperative complications registered in 16 patients (25.8 %), including 4, 3, 6, 3, 0 of grades I, II, IIIa, IIIb, and IV respectively. Overall level of post-operative complications in the groups A and B after surgical stages finishing did not differ statistically (p=0.96). Shorter operative intervention duration was registered in the group A – (311±10.1) min, whereas in the group B it was (496.6±16.2) min (р<0.001). Patients after staged resection stayed in clinic for a longer time – 23.9±0.8 bed-days, when simultaneous resections provided with shorter recovery terms in post-operative period – 9.8±0.5 bed-days (p<0.001). Overall 3-year survival in the group of patients with simultaneous resections (group А) was 42 % and in the group B 55 % (р=0.22). Conclusions: Analysis of our research indicated necessity of the development of differentiated approach in management of synchronous colorectal liver metastatic cancer. Simultaneous resections of colorectal cancer primary lesions and hepatic metastases were safe and could serve as a primary option for selected patients. Subsequent research should be directed towards study of prognosis factors and criteria for patients’ selection for surgical treatment groups, assessment of economic effect, and patients life quality.

Survival outcome in HER2-amplified metastatic colorectal cancer (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 642-642
Author(s):  
Kentaro Sawada ◽  
Wataru Okamoto ◽  
Yoshiaki Nakamura ◽  
Takeharu Yamanaka ◽  
Satoshi Yuki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Survival Outcome ◽  
Braf V600e ◽  
Her2 Status ◽  
Her2 Amplification ◽  
Braf Mutations ◽  
Signal Ratio ◽  
Group B

642 Background: HER2 amplifications have been observed in approximately 3% of patients (pts) with metastatic colorectal cancer (mCRC). Early clinical trials with combined HER2-targeted therapies showed promising activities. However, it remains unclear whether HER2 amplification in mCRC is as prognostic as RAS or BRAF V600E mutant (mt). We aimed to evaluate survival outcome for mCRC pts with HER2 amplification compared to those with RAS or BRAF mt. Methods: mCRC pts who received a palliative resection of the primary tumor with metastatic diseases at presentation, or recurred after curative resection of the primary tumor between 2005 and 2015, were analyzed. HER2 immunohistochemistry (IHC) was performed using formalin-fixed and paraffin-embedded (FFPE) sections obtained from the primary tumor, and HER2 amplification was confirmed by fluorescence in situ hybridization (FISH) in case of IHC 2+ or 3+. Criteria for HER2 amplification were a HER2- to CEP17- signal ratio of 2.0 or higher. RAS / BRAF status was centrally assessed by a PCR-based method. The pts were classified into four subgroups based on RAS, BRAF and HER2 status: Group R , RAS mt; Group B, BRAF V600E mt; Group H, HER2 amplification with RAS / BRAF wild-type (wt); and Group W, RAS / BRAF wt. Results: Among 370 pts, 359 pts (97%) were successfully analyzed. A total of 15 pts (4%) had HER2 amplifications, out of which four pts had overlapped RAS mt (subclassified as Group R). RAS or BRAF mutations are mutually exclusive. The number in Group R, B, H and W was 204 (57%), 13 (4%), 11 (3%) and 131 (36%), respectively. There was no remarkable difference in baseline characteristics among groups. With a median follow-up time of 63 months (mos), the median overall survival of the 359 pts was 27 mos (95%CI 24 - 29 mos); Group R, 24 mos; Group B, 14 mos; Group H, 20 mos; and Group W, 39 mos. The HR of R vs. H is 0.83 (95%CI 0.41-1.70, p= 0.618), B vs. H is 1.16 (95%CI 0.47-2.84, p= 0.748), and W vs. H is 0.52 (95%CI 0.25-1.08, p= 0.080), respectively. Conclusions: This study suggests that the prognosis of mCRC pts with HER2 amplification tends to be worse as compared to those with RAS / BRAF wt, similar to those with RAS mt, and better than those with BRAF mt, although these comparisons were not statistical significant.

Surgical Versus Non-Surgical Treatment of Calcaneal Fractures in Children: A Long-term Results Comparative Study

2000 ◽  
Vol 21 (10) ◽  
pp. 825-832 ◽  
Author(s):  
Francesco Ceccarelli ◽  
Cesare Faldini ◽  
Franco Piras ◽  
Sandro Giannini
Keyword(s):  
Surgical Treatment ◽  
Skeletal Maturity ◽  
Long Term Results ◽  
Calcaneal Fractures ◽  
Articular Fractures ◽  
Fractures In Children ◽  
Group A ◽  
Group B ◽  
Non Surgical Treatment

This study compared surgical and non-surgical treatment of 46 calcaneal fractures in children aged 3-17 years. Patients were divided into: Group A ranging 3-14 years and Group B 15-17 years, and classified according to surgical or non-surgical treatment. Mean follow-up was 22.8 years. Extra-articular fractures were treated non-surgically and all results were satisfactory. Results of articular fractures in Group A were satisfactory regardless of the type of treatment. Articular fractures surgically treated in group B were satisfactory, and those non-surgically treated were mainly poor. Extra-articular fractures can be treated non-surgically. Articular fractures in skeletally immature children can be treated non-surgically; conversely, those in children with skeletal maturity must be treated surgically.

Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1.

1996 ◽  
Vol 14 (8) ◽  
pp. 2274-2279 ◽  
Author(s):  
E Jäger ◽  
M Heike ◽  
H Bernhard ◽  
O Klein ◽  
G Bernhard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Side Effects ◽  
Metastatic Colorectal Cancer ◽  
Low Dose ◽  
Multicenter Trial ◽  
World Health ◽  
High Dose ◽  
Who Grade ◽  
Group A ◽  
Group B

PURPOSE To determine the most effective dose of leucovorin (folinic acid [FA]) within a weekly bolus fluorouracil (FU) schedule, we conducted a randomized multicenter trial to compare therapeutic effects and toxicity of high-dose FA versus low-dose FA combined with FU at equal doses in both treatment groups. PATIENTS AND METHODS Patients with measurable inoperable or metastatic colorectal cancer were randomized to receive weekly FU 500 mg/m2 by intravenous (IV) bolus combined with high-dose FA 500 mg/m2 (group A) or low-dose FA 20 mg/m2 (group B) by 2-hour infusion. RESULTS Of 291 assessable patients (group A, n = 148; group B, n = 143), we observed, in group A, complete response (CR)/partial response (PR) in 32 (21.6%), no change (NC) in 64 (43.2%), and progressive disease (PD) in 52 (35.1%); and in group B, CR/PR in 25 (17.5%), NC in 63 (44.1%), and PD in 55 (38.5%). The median response duration was 24.8 weeks in group A and 23.1 weeks in group B. Median progression-free intervals were 29.3 weeks (group A) and 30 weeks (group B). The median survival time was 55.1 weeks in group A and 54.1 weeks in group B. Overall toxicity was moderate. Mild nausea and vomiting, and stomatitis were common side effects in both groups. The incidence of World Health Organization (WHO) grade III/IV diarrhea was significantly higher in group A (40 v 23 patients). Severe side effects were observed only in a minority of patients in both arms. WHO grade IV diarrhea was observed in seven patients: four in group A and three in group B. The rate of toxicity-related adjustments of dose and schedule was comparable in both groups. CONCLUSION High-dose FA/FU is not superior to low-dose FA/FU within a weekly treatment schedule. Response rates and survival were comparable in both treatment arms. Treatment-related toxicity was higher in group A (high-dose FA). Therefore, low-dose FA combined with weekly FU may be considered the preferred treatment for metastatic colorectal cancer.

Association of bevacizumab-free interval with efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 610-610
Author(s):  
Azusa Komori ◽  
Hiroya Taniguchi ◽  
Yukiya Narita ◽  
Shiori Uegaki ◽  
Sohhei Nitta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Short Interval ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Free Interval ◽  
Significant Difference ◽  
Group A ◽  
Group B

610 Background: Both bevacizumab (Bev) and anti-EGFR agents are sequentially used for metastatic colorectal cancer (mCRC). Some basic studies reported the interaction between Bev and anti-EGFR agents in vivo. Therefore we hypothesized the shorter Bev-free interval may lead to poor outcome of anti-EGFR therapy. The aim of this study is to examine the association of the interval between last Bev administration and initial anti-EGFR agents with efficacy of anti-EGFR therapy. Methods: We retrospectively reviewed consecutive mCRC patients who underwent combination therapy of anti-EGFR agents and irinotecan after failure of fluoropyrimidines, oxaliplatin, irinotecan, and Bev at a single institution. We divided patients in two groups (group A: the interval between Bev and anti-EGFR agents <6M, group B: ≥6M). Results: A total of 114 patients constituted the cohort of analysis. The median age was 63; 78 (68%) patients were male. Most patients (N=100, 88%) were treated with cetuximab, and 14 patients were panitumumab. Seventy-four patients were group A and 40 patients group B, respectively. There was no significant difference in patient characteristics. Response rate was 24.7% in group A, and 50.0% in group B (p=0.0072). The patients in group B have significantly longer progression free survival (4.2 vs. 6.6 M, HR 0.65, 95% CI 0.43- 0.98, p=0.042) and longer overall survival (11.6 vs. 14.3 M, HR 0.62, 95% CI 0.39- 0.97, p=0.038). Conclusions: The short interval (<6M) between last Bev and anti-EGFR agents may interfere with the efficacy of anti-EGFR therapy.

Continuous versus intermittent chemotherapy in metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3582-3582 ◽  
Author(s):  
C. G. Alexopoulos ◽  
A. A. Kotsori
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Stable Disease ◽  
Randomized Study ◽  
Intermittent Chemotherapy ◽  
Group A ◽  
Group B ◽  
Line Chemotherapy

3582 Background: The current policy concerning the duration of chemotherapy in metastatic colorectal cancer (MCC) varies considerably (Clin Oncol 1997;9:248) while no benefit of continuous versus intermittent 5-FU was found in a published randomized study (Lancet 2003;361:457). Serious cumulative toxicity is not usually a problem with long-term 5-FU/FA, but this is not the case with contemporary triple regimens (FOLFIRI, FOLFOX). We, therefore, performed a randomized study of continuous versus intermittent FOLFIRI as first line chemotherapy in MCC. Methods: Patients with MCC and ECOG 0–2 were given 6 biweekly courses of FOLFIRI (Irinotecan 180mg/m2 + De Gramont). Patients with response or stable disease were randomized to continue with another 6 FOLFIRI (group A) or discontinue until relapse when 6 FOLFIRI were readministered (group B). Time to progression (TTP) was calculated from study entrance until 1st progression for group A, and 2nd progression for group B, and overall survival (OS) from study entrance until death. Results: Fifty eight (M=38, F=20) patients entered into the study. Two (3.4%) withdrew before evaluation, 1 (1.7%) died of stroke, 1 (1.7%) was lost to FU and 15 (26%) progressed before or at the completion of 6 FOLFIRI. Thirty nine (67%) patients (M=25, F=14), median age 69 (38–79) responded (21=54%) or had stable disease (18=46%) and were randomized: 19 (49%) to group A and 20 (51%) to group B. Median TTP was 8 months 95% CI: 5.3–10.7) for group A and 9 (95% CI: 7.8–10) for group B (p=NS). 10/19 (52%) in group A received 2nd line chemotherapy vs 7/20 (35%) in group B (p=NS). With a median follow-up of 13 months, 21 patients are alive (12 in group A and 9 in group B). Median OS was 21 months (95% CI: 15 - 26.7) in group A vs 15 (95% CI: 12.6 - 17.3) in group B (p=NS), and 18 months (95% CI: 15.5 - 21) for all 39 patients. Conclusions: In MCC, when response or stability has been achieved after 6 courses ofFOLFIRI there seemstobe little more benefit from continuing chemotherapy than from retreating patients at relapse No significant financial relationships to disclose.

Relative impact of chemotherapy with or without bevacizumab on cytokines and angiogenic factors (CAFs) in metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 401-401 ◽  
Author(s):  
C. H. Lieu ◽  
H. T. Tran ◽  
S. Fiorentino ◽  
Z. Jiang ◽  
M. Mao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Relative Impact ◽  
Sample Collection ◽  
Prior Chemotherapy ◽  
Group A ◽  
Wilcoxon Paired Test ◽  
Chemotherapy Dose ◽  
Group B ◽  
Induced Changes

401 Background: CAFs were previously shown to be modulated in patients (pts) with metastatic colorectal cancer (mCRC) after bevacizumab-containing chemotherapy. Validation of these prior findings is warranted. In addition, the relative impact of bevacizumab and the cytotoxic chemotherapy components on CAFs has not been previously described. Methods: Plasma samples from 403 mCRC pts were obtained prior to any chemotherapy (Group A) or after progression on a regimen without or with bevacizumab (Group B and C, respectively) between 2002 and 2008. Samples were matched for number of metastatic disease sites (Groups A, B, C) and for prior chemotherapy duration, and time from last chemotherapy dose to sample collection (Groups B, C). Levels of 48 CAFs were measured by suspension bead multiplex assays (BioRad and EMD). Comparisons of Groups A v C (n=169 pairs) and Groups B v C (n=65 pairs) were by the two-sided, nonparametric Wilcoxon paired test, with p<0.05 significance for confirmation of previous CAF results. Results: Prior chemotherapy duration (6.5mo, 6.7mo), and time from last chemotherapy dose to sample collection (1.3mo, 1.2 mo) were similar for Groups B and C, respectively. Results were available for 80% of the samples. Compared to Group A, Group B had reductions in multiple CAFs, including IL-8 (-38%, p<0.0001) and PDGF (-62%, p<0.0001). Commensurate with prior results, PlGF, Eotaxin and TRAIL were increased in Group C by 30% (p<0.0001), 23% (p=0.024) and 19% (p=0.008) respectively. Most CAF changes were attributable to chemotherapy alone. However, PlGF (-31%, p<0.0001) and TRAIL (+26%, p=0.037) significantly differed in Groups B v C. In group C compared to A, multiple changes were seen in the EGFR-axis including decreases in EGF (-52%, p=0.032), epiregulin (-25%, p=0.0023), and HB-EGF (-40%, p<0.0001) as well as an increase in sEGFR (+10%, p=0.004). Conclusions: Most changes in CAFs after treatment with bevacizumab-containing chemotherapy appear to be due to chemotherapy alone and not attributable to anti-VEGF therapy, with several notable exceptions. Chemotherapy-induced changes in the EGFR-axis have not previously been described in mCRC and warrant further investigation. [Table: see text]

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