scholarly journals Conversion Chemotherapy With a Modified FLOX Regimen for Borderline or Unresectable Liver Metastases From Colorectal Cancer: An Alternative for Limited-Resources Settings

2019 ◽  
pp. 1-6
Author(s):  
Renata Colombo Bonadio ◽  
Paulo Henrique Amor Divino ◽  
Jorge Santiago Madero Obando ◽  
Karolina Cayres Alvino Lima ◽  
Débora Zachello Recchimuzzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Median Overall Survival ◽  
Low Cost ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
R0 Resection ◽  
Free Survival ◽  
Unresectable Liver Metastases

PURPOSE Conversion chemotherapy is often used for borderline or unresectable (B/U) liver metastases from colorectal cancer (CRC) with the aim of achieving resectability. Although intensive and costly regimens are often used, the best regimen in this scenario remains unclear. We aimed to evaluate the outcomes of patients with B/U liver metastases from CRC treated with conversion chemotherapy with the modified fluorouracil, leucovorin, and oxaliplatin (mFLOX) regimen followed by metastasectomy. METHODS We performed a single-center retrospective analysis of patients with B/U liver metastases from CRC treated with chemotherapy with the mFLOX regimen followed by surgery. B/U disease was defined as at least one of the following: more than four lesions, involvement of hepatic artery or portal vein, or involvement of biliary structure. RESULTS Fifty-four consecutive patients who met our criteria for B/U liver metastases were evaluated. Thirty-five patients (64%) had more than four liver lesions, 16 (29%) had key vascular structure involvement, and 16 (29%) had biliary involvement. After chemotherapy, all patients had surgery and 42 (77%) had R0 resection. After a median follow-up of 37.2 months, median progression-free survival (PFS) was 16.9 months and median overall survival (OS) was 68.3 months. R1-R2 resections were associated with worse PFS and OS compared with R0 resection (PFS: hazard ratio, 2.65; P = .007; OS: hazard ratio, 2.90; P = .014). CONCLUSION Treatment of B/U liver metastases from CRC with conversion chemotherapy using mFLOX regimen followed by surgical resection was associated with a high R0 resection rate and favorable survival outcomes. On the basis of our results, we consider mFLOX a low-cost option for conversion chemotherapy among other options that have been proposed.

Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Hans-Rudolf Raab ◽  
Juergen Weitz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinical Trial Information

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]

scholarly journals Multielectrode Radiofrequency Ablation for Resectable Metachronous Liver Metastasis from Colorectal Cancer

2021 ◽  
Vol 10 (16) ◽  
pp. 3712
Author(s):  
Hou-Ying Cheng ◽  
Kai-Wen Huang ◽  
Jin-Tung Liang ◽  
Been-Ren Lin ◽  
John Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
Liver Metastases ◽  
Median Overall Survival ◽  
Systemic Treatment ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Metachronous Liver Metastasis ◽  
Similar Survival

The outcome of radiofrequency ablation (RFA) for liver metastases from colorectal cancer (CRLM) has been thought to be inferior to metastasectomy. However, the recent development of multielectrode RFA (multi-RFA) systems has made the ablation zone larger and more complete. Thus, we assessed the survival benefits of this modality in cases of metachronous CRLM. This retrospective study assessed patients diagnosed with resectable metachronous CRLM between 2013 and 2016; 132 patients were categorized by treatment for liver metastases: multi-RFA (n = 68), hepatectomy (n = 34), or systemic treatment only (n = 30). Therapeutic effectiveness, outcomes, and intervention-related complications were compared between groups. Median overall survival (OS), recurrence-free survival (RFS), and intrahepatic recurrence-free survival (IHRFS) were 69.8, 85.2, and 59.7 months for the hepatectomy group; 53.4, 41.3, and 32.3 months for the multi-RFA group; and 19.1, 7.1, and 7.1 months for the systemic treatment group. No significant differences were observed between the multi-RFA and hepatectomy groups after a median follow-up of 59.8 months. This study demonstrated that multi-RFA and hepatectomy provide similar survival benefits for patients with resectable CRLM. Multi-RFA may represent a reliable treatment option for the management of resectable liver metastases.

scholarly journals Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1223
Author(s):  
Daniel Pink ◽  
Dimosthenis Andreou ◽  
Sebastian Bauer ◽  
Thomas Brodowicz ◽  
Bernd Kasper ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Future Studies ◽  
Entire Cohort

We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

scholarly journals Bevacizumab plus capecitabine as later-line treatment for patients with metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeong Hak Bang ◽  
Jeong Eun Kim ◽  
Ji Sung Lee ◽  
Sun Young Kim ◽  
Kyu-Pyo Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Free Survival ◽  
Medical Need ◽  
Significant Disease

AbstractThere is an unmet medical need for later-line treatment options for patients with metastatic colorectal cancer (mCRC). Considering that, beyond progression, co-treatment with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate, we aimed to evaluate the efficacy of capecitabine and bevacizumab. This single-center retrospective study included 157 patients between May 2011 and February 2018, who received bevacizumab plus capecitabine as later-line chemotherapy after progressing with irinotecan, oxaliplatin, and fluoropyrimidines. The study treatment consisted of bevacizumab 7.5 mg/kg on day 1 and capecitabine 1,250 mg/m2 orally (PO) twice daily on day 1 to 14, repeated every 3 weeks. The primary endpoint was progression-free survival (PFS). The median PFS was 4.6 months (95% confidence interval [CI] 3.9–5.3). The median overall survival (OS) was 9.7 months (95% CI 8.3–11.1). The overall response rate was 14% (22/157). Patients who had not received prior targeted agents showed better survival outcomes in the multivariable analysis of OS (hazard ratio [HR] = 0.59, 95% CI 0.43–0.82, P = 0.002) and PFS (HR = 0.61, 95% CI 0.43–0.85, P = 0.004). Bevacizumab plus capecitabine could be a considerably efficacious option for patients with mCRC refractory to prior standard treatments.

scholarly journals Clinical Presentation, Natural History, and Therapeutic Approach in Patients with Solitary Fibrous Tumor: A Retrospective Analysis

Sarcoma ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
P. Schöffski ◽  
I. Timmermans ◽  
D. Hompes ◽  
M. Stas ◽  
F. Sinnaeve ◽  
...  
Keyword(s):  
Solitary Fibrous Tumor ◽  
Systemic Therapy ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Response Rates ◽  
Free Survival ◽  
Metachronous Metastasis ◽  
Third Line ◽  
Fibrous Tumor

Background. Solitary fibrous tumor (SFT) is a rare variant of soft tissue sarcoma (STS). Materials and Methods. We reviewed SFT patients (pts) treated at our institution between 12/1990 and 09/2017. Results. We identified 94 pts with a median follow-up (mFU) of 4.7 years (range: 0.1–21.53). Primary sites were the chest (33%), abdomen (21.3%), brain (12.8%), and extremities (9.6%); 6.4% of pts presented with synchronous metastasis. Median overall survival (mOS) from the first diagnosis was 56.0 months (m) (0.3–258.3). Doege–Potter syndrome was seen in 2.1% of pts. Primary resection was performed in 86 pts (91.5%). Median progression-free survival was 34.1 m (1.0–157.1), and 43% of pts stayed SFT-free during FU. Local recurrence occurred in 26.7% after a mFU of 35.5 m (1.0–153.8), associated with an OS of 45.1 m (4.7–118.2). Metachronous metastasis occurred in 30.2% after a mFU of 36.0 m (0.1–157.1). OS in metastatic pts was 19.0 m (0.3–149.0). Systemic therapy was given to 26 pts (27.7%) with inoperable/metastatic disease. The most common (57.7%) upfront therapy was doxorubicin, achieving responses in 13.3% of pts with a PFS of 4.8 m (0.4–23.8). In second line, pts were treated with ifosfamide or pazopanib, the latter achieving the highest response rates. Third-line treatment was heterogeneous. Conclusion. SFT is an orphan malignancy with a highly variable clinical course and a considerable risk of local failure and metachronous metastasis. Surgery is the only curative option; palliative systemic therapy is used in inoperable/metastatic cases but achieves low response rates. The highest response rates are seen with pazopanib in second/third line.

scholarly journals Prognostic factors for patients treated with abiraterone

2020 ◽  
Vol 6 (2) ◽  
pp. FSO436 ◽  
Author(s):  
Cecília M Alvim ◽  
André Mansinho ◽  
Rita S Paiva ◽  
Raquel Brás ◽  
Patrícia M Semedo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Hazard Ratio ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Prognostic And Predictive Factors

Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10−0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14−0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.

scholarly journals Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1638
Author(s):  
Lea Hitpass ◽  
Daniel Heise ◽  
Maximilian Schulze-Hagen ◽  
Federico Pedersoli ◽  
Florian Ulmer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Confidence Interval ◽  
Portal Vein ◽  
Liver Metastases ◽  
Portal Vein Embolization ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Free Survival ◽  
Right Hemihepatectomy

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan–Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2–10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3–40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

2008 ◽  
Vol 26 (30) ◽  
pp. 4906-4911 ◽  
Author(s):  
Emmanuel Mitry ◽  
Anthony L.A. Fields ◽  
Harry Bleiberg ◽  
Roberto Labianca ◽  
Guillaume Portier ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Complete Resection ◽  
Hazard Ratio ◽  
Free Survival ◽  
Cancer Metastases ◽  
Colorectal Cancer Metastases

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m2 administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m2 [FFCD] × 5 days or FU 370 mg/m2 plus l-leucovorin 100 mg/m2 IV × 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9013-9013 ◽  
Author(s):  
Axel Hauschild ◽  
Jean Jacques Grob ◽  
Lev V. Demidov ◽  
Thomas Jouary ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Primary Analysis ◽  
Free Survival ◽  
Independent Review ◽  
Clinical Trial Information

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]

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