Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis

2016 ◽  
Vol 43 (11) ◽  
pp. 2068-2073 ◽  
Author(s):  
Carolina Birolo ◽  
Maria Elisabetta Zannin ◽  
Svetlana Arsenyeva ◽  
Rolando Cimaz ◽  
Elisabetta Miserocchi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Biological Agent ◽  
Treatment Modalities ◽  
Comparable Efficacy ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Ocular Complications ◽  
Significant Difference

Objective.Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)–associated uveitis refractory to anti–tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis.Methods.In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded.Results.Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile.Conclusion.ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

Second-line treatment of modified FOLFIRINOX or nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 458-458 ◽  
Author(s):  
Masato Ozaka ◽  
Takashi Sasaki ◽  
Ikuhiro Yamada ◽  
Ryo Kanata ◽  
Dai Akiyama ◽  
...  
Keyword(s):  
Disease Control ◽  
Pancreatic Adenocarcinoma ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Significant Difference ◽  
Similar Disease ◽  
First Line Treatment

458 Background: Both FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine(GnP) standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for second-line treatments for MPA. The aim of this study was to compare second-line modified FFX (mFFX) after GnP failure with second-line GnP after mFFX failure. Methods: From January 2015 to Jul 2017, medical records were retrospectively reviewed for consecutive patients receiving mFFX or GnP for a histologically proven MPA after failure of GnP or mFFX respectively. Patients were treated with mFFX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU) or GnP (Gemcitabine 1000 mg/m2/, nab-paclitaxel 125mg/m2 d1,8 15) until disease progression, patient refusal or unacceptable toxicity. Results: Second-line mFFX was administered to 50 patients and GnP was 25 patients. At baseline of second-line treatment, there was no difference in patient’s characteristics between mFFX group and GnP group. No significant difference in the response rate (mFFX, 16.6% vs. GnP, 10.5%, P = 0.63) or the disease control rate (mFFX, 50% vs. GnP, 64%, P = 0.82) was seen between the two groups. Median Progression free survival of GnP/mFFx were 4.3 months/4.6 months (p=0.89) and median survival (OS) from the 2nd line treatment of GnP/mFFx were 10.4 months/10.8 months (p=0.65) and OS from the first-line treatment of GnP/mFFx were 20.6 months/16.5 months (p=0.34). No toxic death occurred in both groups. There was no difference in the incident of adverse event between mFFX group and GnP group. Conclusions: Second-line mFFX and GnP achieved similar disease control and survival in unresectable pancreatic cancer. The use of the FFX and GnP in sequence is an attractive option to maximize disease control and survival. We need the clinical trial to compare with mFFX and GnP in sequence to guide the selection of initial chemotherapy.

Second-line systemic treatment for advanced cholangiocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 371-371 ◽  
Author(s):  
Jane Elizabeth Rogers ◽  
Lindsey Law ◽  
D. Van Nguyen ◽  
Wei Qiao ◽  
Milind M. Javle ◽  
...  
Keyword(s):  
Disease Control ◽  
Systemic Treatment ◽  
Disease Control Rate ◽  
Cancer Center ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Significant Difference ◽  
First Line Treatment

371 Background: Five-year survival for advanced cholangiocarcinoma (aCC) is reported at 5-10%. For advanced, unresectable patients, gemcitabine plus platinum (GEM-P) combination chemotherapy is common practice as first-line treatment with progression free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Data regarding chemotherapy treatment after first-line progression is limited. Methods: We performed a retrospective chart review of patients with aCC from 1/1/2009 to 12/31/2012 who received second-line chemotherapy at M.D. Anderson Cancer Center (MDACC). Median PFS was the primary endpoint. Secondary objectives included disease control rate (complete response + partial response + stable disease) and OS. Inclusion criteria: aCC diagnosis, progression on first-line therapy, and reimaging studies at MDACC. Exclusion criteria: patients who received localized treatment for aCC prior to second-line therapy or consolidative chemoradiation, mixed histology tumors, and those with a history of another malignancy. Results: 56 patients were identified, with the majority having intrahepatic aCC (95%). 80% of patients received gemcitabine based first-line treatment (GEM-P +/- erlotinib, GEM monotherapy). Second-line systemic treatment included GEM-P (19.6%), GEM + fluoropyrmidine (GEM-FU) (28.6%), fluoropyrmidine combination (FU-combo) (37.5%), and other consisting of chemotherapy or biotherapy monotherapy or combination (14.3%). Total median PFS was 2.7 months (95% CI = 2.3 to 3.8). Disease control rate was 50% with a median OS of 13.8 months (95% CI = 12 to19.3). No significant difference in PFS or OS was identified between the four second line treatment groups. A higher CA 19-9 at the start of second line treatment correlated with a worse survival (p= <0.01). Conclusions: This retrospective study revealed a 50% disease control rate, median PFS of 2.7 months, and a potential for improvement in OS in patients who received second line systemic treatment. Agents that may be considered include GEM + FU, FU-combination therapy, or GEM-P if not given first line.

First-line biological agents plus chemotherapy in elderly patients with metastatic colorectal cancer: A retrospective pooled analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4017-4017
Author(s):  
Pilar Garcia-Alfonso ◽  
Eduardo Diaz-Rubio ◽  
Albert Abad ◽  
Alfredo Carrato ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Biological Agents ◽  
Comparable Efficacy ◽  
Line Treatment ◽  
First Line ◽  
Younger Patients ◽  
Significant Difference ◽  
First Line Treatment

4017 Background: Biological agents, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding appropriate management of elderly patients with mCRC is lacking. This study compared the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy. Methods: This retrospective analysis used pooled data from five Spanish TTD collaborative group studies of adults with advanced CRC who received first-line treatment with bevacizumab, cetuximab or panitumumab, stratified by age (≥65 vs < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety. Results: In total, 999 patients from five studies were included in the analysis; 480 (48%) were aged ≥65 years and 519 (52%) were aged < 65 years; 733 (73.37%) were treated with bevacizumab, 189 (18.92%) received cetuximab and 77 (7.71%) received panitumumab. Median PFS did not significantly differ between patients aged ≥65 versus < 65 years (9.9 vs 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88–1.17). Median OS was significantly shorter in older versus younger patients (21.3 vs 25.0 months; HR 1.21; 95% CI 1.04–1.41; P = 0.0132). There was no significant difference between older versus younger patients in ORR (59% vs 62%). Older patients experienced more treatment-related grade ≥3 adverse events. Conclusions: Biological agents are an effective first-line treatment option for elderly patients with mCRC, with comparable efficacy in PFS and ORR to that observed in younger patients and a manageable safety profile.

Efficacy of second-line chemotherapy after standard combination chemotherapy in patients with metastatic pancreatic cancer: The results from the NAPOLEON study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 661-661
Author(s):  
Masaru Fukahori ◽  
Yoshinobu Okabe ◽  
Mototsugu Shimokawa ◽  
Taiga Otsuka ◽  
Futa Koga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Chemotherapy ◽  
Best Supportive Care ◽  
Metastatic Pancreatic Cancer ◽  
Survival Duration ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Number Of Patients ◽  
Significant Difference

661 Background: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) have been established as standard first-line combination chemotherapy (CTx) for patients with metastatic pancreatic cancer (MPC). However, the efficacy of second-line CTx and the significance of combination CTx in clinical practice are unclear. We therefore investigated the efficacy of second-line CTx in patients with MPC. Methods: Data were collected from CTx-naive MPC patients treated with first-line combination CTx at 14 hospitals in the Kyushu area of Japan from December 2013 to June 2018. The median overall survival (mOS) from second-line treatment was compared between patients who received second-line CTx (CT group) and those who received best supportive care (BSC group). Furthermore, in the CT group, the mOS was compared between the patients who received combination CTx and those who received mono-CTx. To control potential bias in the selection of second-line treatment, we also conducted a propensity score-adjusted analysis. Results: A total of 255 patients received GnP or FFX as first-line CTx. Of these, there were 156 (61%) in the CT group and 77 (30%) in the BSC group. The number of patients who received FFX/GnP as first-line CTx was 79 (51%)/77 (49%) in the CT group and 15 (20%)/62 (80%) in the BSC group, respectively (P < 0.01). The mOS in the CT group was significantly longer than that in the BSC group (5.2 vs. 2.7 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01 and 5.2 vs. 2.6 months; adjusted HR 0.39; 95% CI 0.28-0.55; p < 0.01). In the CT group, 89 (57%) patients received combination CTx, and 67 (43%) received mono-CTx. There was no significant difference in the mOS between the combination CTx and mono-CTx patients (5.5 vs. 4.4 months; HR 0.88; 95% CI 0.62-1.26; p = 0.88 and 5.6 vs. 4.4 months; adjusted HR 0.85; 95% CI 0.56-1.30; p = 0.47). Conclusions: Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination CTx conferred no improvement in the survival duration compared with mono-CTx.

The Lack of Survival Differences in Randomised Trials in CLL May Be Related to the Effect of Second Line Therapies. A Report from the LRF CLL4 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 304-304 ◽  
Author(s):  
Daniel Catovsky ◽  
Monica Else ◽  
Sue Richards ◽  
Peter Hillmen
Keyword(s):  
Partial Response ◽  
Single Agent ◽  
Survival Rates ◽  
Treatment Modalities ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Survival Differences

Abstract On behalf of the UK NCRI Haematological Oncology Clinical Studies Group and NCRI CLL Working Group The LRF CLL4 trial randomised 777 patients with previously untreated CLL who required therapy from January 1999 to October 2004 between fludarabine as single agent (n=194), fludarabine plus cyclophosphamide (FC; 196) and chlorambucil (387). Results presented at ASH 2005 and now with an extended follow-up show statistically significant better complete (CR) and overall (ORR) responses with FC (39% CR and 94% ORR) compared to fludarabine (15% and 80%) and chlorambucil (7% and 72%). Progression-free survival (PFS) at 5 years was also significantly better with FC (33%) than fludarabine (14%) or chlorambucil (9%). Better response rates and PFS for FC occurred in all age groups including those over 70, and all prognostic groups defined by VH mutations and cytogenetics. Despite these results with FC, also seen by others (Eichhorst et al, Blood 107, 885, 2006), no survival differences have emerged. The projected 5-year survival with FC and fludarabine is currently 54% and with chlorambucil 61% (p=ns). This is puzzling as survival in CLL has previously been demonstrated to correlate with the quality of response. In CLL4 this was confirmed and we have also shown that good responders to second line treatment survive better. We therefore analysed data from 180 patients who received second-line treatments: 125 originally in the chlorambucil arm, 44 in the fludarabine arm and 11 in the FC arm. Patients in the chlorambucil arm received, as second-line therapy, mostly fludarabine alone or in combinations including FC+/−Rituximab (R) (70% of cases), CHOP, alemtuzumab, high dose methylprednisolone and others. Patients from the fludarabine arm had CHOP (31%), FC+/−R (24%), or others. Results are summarised in the Table. In the chlorambucil arm the proportion of patients responding to second-line treatment was higher than the proportion responding to first-line chlorambucil. Median survival after progression in 496 patients was also better in the chlorambucil (42 months) and fludarabine arms (35 months) than FC (8 months). These figures were respectively 33, 49 and 7 months for 147 non-responders to first-line treatment, and 52, 37 and 27 months for 259 responders who had relapsed. We conclude from this analysis that the likely reason for the lack of survival differences in CLL4 (and in other CLL trials) relates directly to the better responses and improved survival rates after second line treatment in those receiving the less effective therapy first, i.e. chlorambucil in CLL4. This observation is also relevant for the analysis of results of salvage protocols, which need to take into account the quality of the initial treatments and the mechanisms underlying resistance. Our findings support the view that PFS and quality of life should be used when assessing new treatment modalities in CLL, while continuing to evaluate survival differences to ensure that there is no adverse effect. Responses to second-line treatment (%) First-line randomisation Number of pts. CR NodPR PR ORR NR/PD CR = complete response; NodPR = nodular partial response; PR = partial response; ORR = overall response rate; NR/PD = no response or progression of disease Chorambucil 125 13 17 44 74 26 Fludarabine 44 11 25 41 77 23 FC 11 0 0 45 45 55

scholarly journals Evaluation of Second-Line Anti-VEGF after First-Line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter “SLAVE” Study

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1259
Author(s):  
Alessandro Parisi ◽  
Alessio Cortellini ◽  
Katia Cannita ◽  
Olga Venditti ◽  
Floriana Camarda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Treated Group ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Significant Difference

Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7–34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95–1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3–18.1) and 12.7 (95%CI: 8.8–17.5) months, respectively (HR= 1.31 (95%CI: 0.89–1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02–2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99–2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Conclusion: Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.

Efficacy of nab-paclitaxel plus gemcitabine (AG) vs. FOLFIRINOX as first line chemotherapy for metastatic pancreatic cancer (mPC): Real world experiences.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 354-354
Author(s):  
Inhwang Hwang ◽  
Jihoon Kang ◽  
Changhoon Yoo ◽  
Kyu-Pyo Kim ◽  
Jae Ho Jeong ◽  
...  
Keyword(s):  
Performance Status ◽  
Pancreatic Head ◽  
Daily Practice ◽  
Comparable Efficacy ◽  
Practice Setting ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
Line Chemotherapy ◽  
First Line Treatment

354 Background: AG and FOLFIRINOX have been established as standard first-line treatment in mPC patients based on the improved efficacy compared to gemcitabine monotherapy. Because there was no head-to-head comparison between these regimens, however, there is lack of data which regimen is preferable in patients with mPC. Therefore, we performed retrospective analysis comparing the efficacy of AG and FOLFIRINOX in daily practice setting. Methods: We analyzed a total of 308 patients with confirmed mPC who received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016 at Asan Medical Center, Seoul, Korea. Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). Results: Median age was slightly older in AG group than FOLFIRINOX group (62 vs. 60 years, p = 0.02). Except this, there was no significant difference between the two groups in terms of baseline characteristics including sex (male, AG/FOLFIRNOX): 56%/67%, ECOG performance status (0-1): 97%/99%, pancreatic head location: 32%/40%, and baseline CA19-9 level ( > UNL): 77%/82%. ORR (28% vs. 31%) and disease control rate (74% vs. 74%) did not differ between two groups (p = 0.45, and p = 0.96, respectively). Although there was no significant difference in PFS between the two groups (AG: median 6.8 months [95% CI: 5.8-7.8] vs. FOLFIRINOX: 5.1 months [95% CI: 4.2-5.9]; p = 0.15), OS was significantly better in AG group compared to FOLFIRINOX group (median 12.3 months [95% CI: 11.0-13.7] vs. 9.7 months [95% CI, 8.1-11.4]; p = 0.001). Among the patients who showed progression, 81% (180/223) received second-line chemotherapy and there was no difference between the two groups (AG vs. FOLFIRINOX: 76% vs. 85%, p = 0.09). 5-FU monotherapy or combination with oxaliplatin were given in 97% (73/75) of patients in AG group and gemcitabine-based regimens (including 2 cases of AG) were given in 97% (102/105) of patients in FOLFIRINOX group. Conclusions: Both AG and FOLFIRINOX are feasible and active as first-line treatment for patients with mPC. In daily practice setting, AG showed comparable efficacy outcomes with FOLFIRINOX.

scholarly journals Clinicopathologic Features and Prognosis of BRAF Mutated Colorectal Cancer Patients

2020 ◽  
Vol 10 ◽  
Author(s):  
Wen-Long Guan ◽  
Miao-Zhen Qiu ◽  
Cai-Yun He ◽  
Li-Qiong Yang ◽  
Ying Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Pathological Features ◽  
First Line ◽  
Cdx2 Expression ◽  
Pathologic Features ◽  
Significant Difference ◽  
Worse Prognosis ◽  
Clinical And Pathological Features

Background:BRAFV600E mutation is associated with poor prognosis of colorectal cancer (CRC) patients, but the comparison of clinic-pathologic features between V600E and non-V600E mutation was not well-known in CRC patients. The aim of this study is to evaluate the clinical and pathological features, prognostic value of BRAF mutations in CRC.Methods: We conducted a retrospective study to characterize the clinical and pathological features and survival of patients with BRAF mutated CRC. Patients were classified according to BRAF status as BRAFV600E mutation and non-V600E mutations. Difference of characteristics and survival between the two groups was analyzed.Results: There was no significant difference in gender, family history, location of primary tumor, metastatic sites between patients with BRAF-V600E mutation and non-V600E mutations. Patients with V600E mutation were younger than those with non-V600E mutations (p = 0.002). Patients with BRAFV600E mutation showed a poorer outcome than those with non-V600E mutations (23.1 vs. 49.9 months, respectively, p = 0.0024). Lack of CDX2 expression was associated with worse prognosis (mOS: 9.4 m vs. not reached, respectively, p = 0.016). Status of V600E mutation did not affect the mPFS and ORR of first-line or second-line treatment.Conclusion:BRAFV600E mutation defines a distinct subgroup of CRC with worse prognosis. Lack of CDX2 expression is associated with poor OS. Status of V600E mutation did not affect the mPFS of first-line or second-line treatment.

Gain(1)(q21) Defines Group of Newly Diagnosed Multiple Myeloma Patients with Poor Prognosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2820-2820
Author(s):  
Pavel Nemec ◽  
Henrieta Greslikova ◽  
Romana Zaoralova ◽  
Jan Smetana ◽  
Hana Filkova ◽  
...  
Keyword(s):  
Czech Republic ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Line Treatment ◽  
Second Line ◽  
Newly Diagnosed ◽  
First Line ◽  
Significant Difference ◽  
First Line Treatment

Abstract Abstract 2820 Poster Board II-796 The presence of chromosomal abnormalities detected by FISH in plasma cells is considered to be an important prognostic factor for patients with multiple myeloma. In this study we analysed the impact of gain(1)(q21), del(13)(q14), del(17)(p13), t(4;14) and (non)hyperdiploidy on prognosis in MM patients. Taking together 194 MM patients (median age 66 years) were successfully examined by FISH for presence of above named chromosomal abnormalities in plasma cells. A total of 47 patients (median follow-up 43.2 months; 91% first line treatment, 9% second line treatment) were treated by peripheral blood stem cells transplantation (PBSCT). A total of 86 patients (median follow-up 38.4 months; 38% first line treatment, 43% second line treatment, 19% >2 previous treatment lines) were treated by thalidomide based regimen (86% together with glucocorticoids and alkylating agens). A total of 61 patients (median follow-up 46.5 months; 16% first line treatment, 36% second line treatment, 33% third line treatment, 15% >3 previous treatment lines) were treated by bortezomib based regimen (53% with glucocorticoids and alkylating agens, 20% with glucocorticoids + anthracycline). Gain(1)(q21) was found in 52% (101/194), del(13)(q14) in 55% (69/125), del(17)(p13) in 12% (13/112), t(4;14) in 20% (18/90) and 44% (56/126) of cases were hyperdiploid. In any of the three treatment based groups of patients we haven't found any significant difference in TTP, OS and treatment response (ORR) between any studied positive/negative chromosomal abnormality except gain(1)(q21). See Table 1 for results overview (TTP only). In patients treated by PBSCT (regardless of their pre-treatment) significant difference in TTP and OS for positive/negative patients was observed (15.6 vs. 27.3 months, p=0.002 for TTP; 47.2 vs. NR months, p=0.001 for OS). Furthermore, we entirely focused on newly diagnosed patients divided them into three subgroups: (1) patients treated by PBSCT in first line (n=42), (2) patients treated by thalidomide based regimen in first line (n=33) and (3) patients treated by bortezomib based regimen in first line (n=10). We confirmed unfavourable impact of gain(1)(q21) in patients treated with PBSCT whereas TTP and OS in gain(1)(q21) positive/negative patients was 15.6 vs. 27.3 months, p=0.003 (TTP); 47.2 vs. 66.9 months, p=0.002 (OS). This difference in TTP/OS among gain(1)(q21) positive/negative patients was observed neither in thalidomide based subgroup [NR vs. 11.7 months, p=0.956 (TTP); NR vs. 34.4 months, p=0.683 (OS)] nor in bortezomib based subgroup [(8.5 vs. 6.5 months, p=0.549 (TTP); NR vs. 6.8, p=0.254 (OS)]. See Table 2 for results overview (TTP only). In this study we revealed gain(1)(q21) almost in one half of MM cases, and we defined the newly diagnosed MM patients carrying gain(1)(q21) as a unique group of patients with poor prognosis. Nevertheless, treatment based on bortezomib / thalidomide combination probably suppresses unfavourable prognostic impact of all studied chromosomal abnormalities including gain(1)(q21). This study was supported by grant LC06027 of Masaryk University, Brno, Czech Republic, and by grants MSM0021622415 and MSM0021622434 of Ministry of Education, Czech Republic, and by IGA grants NR/9317-3 and NS/10207-3/2009 of Ministry of Medicine, Czech Republic. Disclosures: No relevant conflicts of interest to declare.

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