POCHER (preoperative chemotherapy for hepatic resection) with cetuximab (Cmab) plus CPT-11/5-fluorouracil (5-FU)/leucovorin(FA)/oxaliplatin (L-OHP) (CPT-11-FFL) in unresectable colorectal liver metastases (CLM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15020-e15020
Author(s):  
C. Garufi ◽  
A. Torsello ◽  
S. Tumolo ◽  
M. Mottolese ◽  
C. Campanella ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Gene Copy Number ◽  
Clinical Results ◽  
Median Number ◽  
Complete Resection ◽  
Gene Copy ◽  
Resection Rate ◽  
Toxicity Analysis ◽  
Unresectable Colorectal Liver Metastases

e15020 Background: We have previously shown preliminary data with Cmab+ all active drugs, CPT-FFL, with primary end- point CLM resectability (Garufi C. et al ASCO GI 2008). Here we report definitive clinical results. Methods: Unresectability criteria: size>5 cm (a), multinodular (b), ilar location (c), extrahepatic disease (d), >3 stable mets after chemotherapy before surgery (e). Aim of the study was to have at least 30% liver resection rate (power of 80% for p0=10% and p1=25%). Pts received weekly Cmab 400 then 250 mg/m2/wk plus CPT-11, 130 mg/m2/d1, 6 h infusion, (peak at 13:00) and a 12-h, days 2–5, infusion of L-OHP 20 mg/m2/day (peak at 16:00), FA 150 mg/m2/day plus 5-FU 600 mg/m2/d (peak at 4:00), q 2 wks; after the first 17 pts 5-FU and L-OHP were reduced to 550 and 15 mg/m2 respectively. Results: Since 07/20/2006 we enrolled 43 pts, irrespective of EGFR, K-ras and gene copy number (gcn): M/F 27/16, median age 60,7 y (33–76), median PS 0. Primary tumor: colon/rectum 34/9, primary tumor resected 39 pts (79%), synchronous metastases: 35 pts (81%), liver <25%/25%: 9/34 ((21/79%); median CEA/CA19–9: 55 ng/ml (1–6,600)/91.8 U/L (2.66440); unresectability: (a): 9 (21%), (b):14 (33%), (c) 1, (d): 4 (9%), (e): 15 (35%). We had 34 partial responses (79%, CI 79.1–87.0), 5 SD (11.6%) and 4 patients not evaluable becouse of toxicity. Complete Resection of CLM was obtained in 27 pts (63%) with 4 pts still to be resected. Median number (n.) of courses (c) was 10 (2–18), median n. of c before surgery (s) was 5 (3–10) and after s was 6 (1–6); median time from last c to s was 2 wks (2–4), from s to recovery chemo was 10 wks (2–16). Median follow-up was12 months, median PFS 13 months (7–19), median OS not reached with 2-y survival of 61%, 8 pts alive without recurrence (19%), 11 deaths (25%).Major limiting toxicity was diarrhea, with no difference after dose reduction: Grade 0–1: 6% of pts, G2 6%, G3 76%, G4 12%; neutropenia G3 6% with no febrile neutropenia. Conclusions: This is the first phase II study with CPT-FFL + Cmab in pts with unresectable CLM. Complete resection was obtained in 63% of pts with diarrhea being limiting toxicity. Analysis of EGFR status, K-ras and gcn will be further presented. No significant financial relationships to disclose.

scholarly journals Chemotherapy and target therapy as neo-adjuvant approach for initially unresectable colorectal liver metastases

2012 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Luigi Rossi ◽  
Angelo Zullo ◽  
Federica Zoratto ◽  
Anselmo Papa ◽  
Martina Strudel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Target Therapy ◽  
Resection Rate ◽  
Biological Drugs ◽  
Unresectable Colorectal Liver Metastases ◽  
Neo Adjuvant Chemotherapy ◽  
Colorectal Cancer Patients

Although surgery is the most effective treatment for liver metastases in colorectal cancer patients, only 15-20% of these patients are suitable for a radical surgical approach, and metastases recurrence may occur at follow up. In the last decade, the use of pre-operative chemotherapy in combination with new biological drugs has been introduced. We reviewed data of neo-adjuvant chemotherapy strategies aimed at increasing the resection rate of liver metastases in colorectal cancer patients who were initially considered unresectable.

Predictive and prognostic values of circulating tumor DNA (ctDNA) clearance in osimertinib treated advanced non-small cell lung cancer cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3036-3036 ◽  
Author(s):  
Yong Song ◽  
Shenglin Ma ◽  
Meiqi Shi ◽  
Xingxiang Xu ◽  
Xueqin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Disease Progression ◽  
Clonal Evolution ◽  
Gene Copy Number ◽  
Circulating Tumor Dna ◽  
Allelic Frequency ◽  
Gene Copy ◽  
Early Detection Of Disease ◽  
Molecular Changes

3036 Background: Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at the molecular level. CtDNA, validated as a tool for mutation detection in lung cancer, reflects dynamic molecular changes. Here, we evaluated the potential of ctDNA in monitoring molecular changes and predicting clinical outcomes of EGFR T790M-positive osimertinib treated NSCLC pts. Methods: This prospective multicenter study, enrolled 72 T790M positive osimertinib-treated advanced NSCLC pts who progressed on prior EGFR-TKI to evaluate the potential of ctDNA in monitoring, is part of the ongoing ASTRIS study (NCT02474355). Longitudinal plasma samples, collected from 52 pts, were subjected to sequencing using a panel consisting of 168 lung cancer-related genes. Results: Genomic profile prior to the initiation of osimertinib revealed that mutations participating in cell cycle (14 pts, p = 0.004) and P53 pathways (43 pts, p = 0.032) were associated with shorter OS ( p53 was excluded from analysis due to high mutation frequency). Interestingly, pts with undetectable ctDNA at first follow-up (within 50 d, n = 41) were correlated with longer PFS (p = 0.009) and OS (p = 0.022). With a median follow-up of 168 d (ranged from 40 - 550 d), 32 pts experienced radiological disease progression. Among them, 11 (34%) experienced molecular progression reflected by emergency of new mutation or increased allelic frequency of existing mutation prior to radiological progression, with an average leading time of 74 days. Pts with molecular PD prior to radiological PD were more likely to harbor any gene copy number amplification (CNA, p = 0.035) and p53 (p = 0.023) mutations at radiological PD. In addition, pts with CNA at radiological PD had shorter PFS (p = 0.002) and OS (p = 0.052). Conclusions: This clinical trial study demonstrates that ctDNA clearance at first follow-up can serve as a predictive and a prognostic marker for pts undergoing osimertinib treatment. Furthermore, it revealed the potential of ctDNA in early detection of disease progression, preceding imaging modalities with an average lead time of 74 days.

scholarly journals Outcome of surgical management of hemophilic pseudotumor: Review of 9 Cases from single-center

2020 ◽  
Author(s):  
Yunfeng Yao ◽  
Chenxi Xue ◽  
Wang Fang ◽  
Jingcai Niu ◽  
Pengde Kang ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Soft Tissues ◽  
Bone Destruction ◽  
Coagulation Factor ◽  
Perioperative Period ◽  
Clinical Results ◽  
Complete Resection ◽  
Long Term Effects ◽  
Iliac Vessel

Abstract Background: Pseudotumours are a rare and serious complication of haemophilia, A slowly growing pseudotumour frequently destroys structures of bone and soft tissues. Surgical resection is the primary method for treatment of proximal pseudotumours. The purpose of this retrospective study was to evaluate the operative methods and clinical results of surgical treatment for those rare cases.Methods: We reviewed nine patients with hemophilic pseudotumours, who received surgical resection treatment in our hospital. The age range was 20-51 years. All operations were performed by one group surgeons. The method of operation depends on the origin and the extent of pseudotumor involvement. With the supplementary of recombinant coagulation factor VIII, six cases received complete resection; one received cytoreduction surgery as the pseudotumor closing to iliac vessel and nerve; two cases received complete resection and construction as bone destruction. Factor substitution was maintained for 14 days. Results: In our series, the average intraoperative blood loss volume was 710±35 ml(range ,240-2100ml). Six patients received blood transfusion during perioperative period. All wounds healed smoothly, no infection or chronic sinus formation. There is no iatrogenic vascular nerve injury in our series. Complete follow-up was performed in all patients. Mean follow-up duration was 14.5months (range, 6–26months). One patient with pseudotumor in the thigh had a recurrence of one year after operation, then secondary operation was performed, Conclusions: Surgical resection for haemophilic pseudotumours is an effctive and safe method . The choice of surgical procedure must be individualized according to the localization and the progress of pseudotumor. However, as relatively few cases and shorter follow-up time in our series. The long-term effects of these patients need further follow-up.

scholarly journals Chemotherapy and target therapy as neo-adjuvant approach for initially unresectable colorectal liver metastases

2012 ◽  
pp. e6
Author(s):  
Luigi Rossi ◽  
Angelo Zullo ◽  
Federica Zoratto ◽  
Anselmo Papa ◽  
Martina Strudel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Target Therapy ◽  
Resection Rate ◽  
Biological Drugs ◽  
Unresectable Colorectal Liver Metastases ◽  
Neo Adjuvant Chemotherapy ◽  
Colorectal Cancer Patients

Although surgery is the most effective treatment for liver metastases in colorectal cancer patients, only 15-20% of these patients are suitable for a radical surgical approach, and metastases recurrence may occur at follow up. In the last decade, the use of pre-operative chemotherapy in combination with new biological drugs has been introduced. We reviewed data of neo-adjuvant chemotherapy strategies aimed at increasing the resection rate of liver metastases in colorectal cancer patients who were initially considered unresectable.

Comparison between epidermal growth factor receptor (EGFR) gene in primary non-small cell lung cancer (NSCLC) and in fine needle aspirates from metastatic sites

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21081-21081
Author(s):  
C. Bozzetti ◽  
M. Tiseo ◽  
C. Lagrasta ◽  
R. Nizzoli ◽  
F. Leonardi ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Copy Number ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Gene Copy ◽  
Metastatic Site ◽  
Fine Needle ◽  
Egfr Gene ◽  
Fine Needle Aspirates ◽  
Metastatic Sites

21081 Background: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently proposed to predict which non-small cell lung cancer patients (NSCLC) are expected to benefit from EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared to primary NSCLC. In all studies, FISH have been performed on histological material. The possibility to perform FISH analysis on cytological material obtained by fine-needle aspiration from superficial and deep metastases would allow to know the real EGFR status when the metastatic site is not accessible for biopsy. Methods: EGFR gene copy number was analyzed by FISH on fine-needle aspirates (FNAs) obtained from 18 patients with metastatic NSCLC (11 lymphnod, 2 liver, 1 abdomen, 2 skin, 2 pleural effusion) and results were compared with those obtained on corresponding paraffin histological sections from the primary tumor. Results: The feasibility of EGFR-FISH on cytology was 89%; 2/18 samples were not evaluable because of lack of hybridization. EGFR-FISH was positive (= 4 EGFR copy number; Cappuzzo F. et al, JNCI 2005) in 69% (11/16) of the metastases and in 38% (6/16) of the primary tumors. Five of the 16 cases were EGFR positive on both primary tumor and metastatic site and 4 were negative on both primary tumor and metastasis. Seven cases (44%) showed primary tumor vs. metastasis discordance: in 6 cases EGFR was positive in the metastatic site but not in the primary tumor, while in one sample EGFR was positive in the primary tumor but not in the metastasis. Conclusions: EGFR-FISH can be reliably assessed on FNAs obtained from NSCLC metastases. Possible changes in EGFR status during the metastatic progression as well as cancer heterogeneity may account for discrepancies observed between primary tumor and metastatic sites. These findings should be considered in future studies which will be design to better elucidate the predictive role of EGFR-FISH in NSCLC. No significant financial relationships to disclose.

The prognostic impact of high MET gene copy number on non-small cell lung cancer: A meta-analysis of eight studies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22049-e22049
Author(s):  
Anastasios Dimou ◽  
Lemuel Non ◽  
Kostas N Syrigos
Keyword(s):  
Lung Cancer ◽  
Primary Tumor ◽  
Copy Number ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Prognostic Impact ◽  
Fixed Effects Model ◽  
Cross Sectional

e22049 Background: The risk stratification of NSCLC on the basis of molecular information is a key approach in the clinical management of patients with the disease. MET is the receptor for HGF and is present in the membrane of NSCLC cells. The most common genetic alteration associated with MET is the gene amplification. Methods: Two independent investigators applied parallel search strategies with the terms "MET" AND "lung cancer", "MET" AND "NSCLC", "met gene copy number" AND "prognosis" in PubMed through November 2012. We selected the studies that investigated the association of MET gene copy number with prognosis. A quality score that assessed the lab methods, the generalizability and the analysis, was assigned to each study that was finally included in the analysis. Results: Among 791 studies that were identified in the initial search, we retrieved 8 cross sectional studies on retrospective cohorts with adequate data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Among the studies, 5 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. All 8 studies used tissue from surgically resected specimens. MET gene copy number predicted worse overall survival when all studies were combined in a fixed effects model (HR=1.35, 95% CI 1.17-1.57). We calculated the I2 statistic to assess heterogeneity (I2=44%, p=0.09). There were four studies where a higher gene copy number predicted a better outcome and four in which the opposite was true. The Egger’s regression intercept showed no significant publication bias (p=0.38). Conclusions: Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC.

scholarly journals Clinical Outcomes of Endoscopic Submucosal Dissection for Early Esophageal Squamous Cell Neoplasms: A Retrospective Single-Center Study in China

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yanfang Chen ◽  
Ye Zhao ◽  
Xiaojing Zhao ◽  
Ruihua Shi
Keyword(s):  
Clinical Outcomes ◽  
Squamous Cell ◽  
En Bloc Resection ◽  
Bloc Resection ◽  
Complete Resection ◽  
Resection Rate ◽  
En Bloc ◽  
End Points ◽  
Squamous Cell Neoplasms

Aims. To retrospectively analyze the clinical outcomes for a large number of endoscopic submucosal dissections (ESDs) in early esophageal squamous cell neoplasms (ESCNs) at the First Affiliated Hospital of Nanjing Medical University.Patients and Methods. From January 2010 to February 2014, 296 patients (mean age 61.4 years, range 31–85 years; 202 men) with 307 early ESCNs (79 intramucosal invasive esophageal squamous cell carcinomas (ESCCs) and 228 high-grade intraepithelial neoplasia (HGIN) cases) were included from a total of 519 consecutive patients who were treated by esophageal ESD at our hospital. The primary end points of the study were rates of en bloc resection and complete resection. Secondary end points were complications, residual and recurrence rates, and mortality during follow-up.Results. The en bloc resection rate and complete resection rate were 93.5% and 78.2%, respectively. Complications included strictures (8.4%), perforations (1.0%), and bleedings (0.7%). Twenty-seven (9.1%) patients experienced residual and 18 (6.1%) patients experienced recurrence during a mean follow-up period of 30 months. Thirteen patients died from causes unrelated to ESCC, and no cancer-related death was observed.Conclusions. Our study showed that ESD is a successful and relatively safe treatment for intramucosal invasive ESCC and HGIN, fulfilling the criteria of lymph node negative tumors. This should encourage clinicians to select ESD performed by experienced operators as a potential or even preferred treatment option for lesions amenable to endoscopic treatment.

repp86 Expression and Outcome in Patients With Neuroblastoma

2003 ◽  
Vol 21 (9) ◽  
pp. 1810-1818 ◽  
Author(s):  
Matthias Krams ◽  
Hans-Juergen Heidebrecht ◽  
Barbara Hero ◽  
Frank Berthold ◽  
Dieter Harms ◽  
...  
Keyword(s):  
Gene Copy Number ◽  
Staging System ◽  
Prognostic Models ◽  
Gene Copy ◽  
Disease Free Interval ◽  
Hazard Ratios ◽  
Pathology Classification ◽  
Theoretical Molecular Mass

Purpose: Given the well-known challenges of neuroblastoma prognosis, we investigated whether the expression of restrictedly expressed proliferation-associated protein of 86 kDa theoretical molecular mass (repp86), a proliferation-associated protein expressed in S, G2, and M phases of the cell cycle, correlates with the clinical outcome in patients with neuroblastoma. Patients and Methods: 161 children with different stages of neuroblastoma were studied; the median follow-up time was 72.8 months. The patients were staged according to the International Neuroblastoma Staging System, and histologic grading of the tumors was performed according to the criteria of Hughes and those of the International Neuroblastoma Pathology Classification. The MYCN gene copy number was determined by Southern blot analysis or fluorescence in situ-hybridization, and repp86 expression was assessed immunohistochemically by means of monoclonal antibody Ki-S2 on paraffin sections from archival tumor samples. Results: A repp86 labeling index (RI) of more than 10% positive tumor cells significantly predicted a shortened disease-free interval and an increased tumor mortality (both P < .0001). Moreover, the RI allowed the identification of patients with favorable and adverse prognosis in subsets defined by stage, grade, age, and MYCN status. In a multivariate analysis, the RI emerged as the most important predictor of event-free and disease-specific survival with hazard ratios of 11.7 and 10.5, respectively (both P < .0001). Conclusion: It seems that repp86 expression is closely associated with the biologic behavior of neuroblastoma. Assessment of the RI might, therefore, considerably refine prognostic models.

Underwater endoscopic mucosal resection for superficial nonampullary duodenal adenomas

Endoscopy ◽  
2017 ◽  
Author(s):  
Yasushi Yamasaki ◽  
Noriya Uedo ◽  
Yoji Takeuchi ◽  
Koji Higashino ◽  
Noboru Hanaoka ◽  
...  
Keyword(s):  
Endoscopic Mucosal Resection ◽  
Large Scale ◽  
Complete Resection ◽  
University Hospital ◽  
Resection Rate ◽  
Mucosal Resection ◽  
Duodenal Adenomas ◽  
Complete Resection Rate ◽  
Medical Network

Abstract Background and study aim Underwater endoscopic mucosal resection (UEMR) was recently developed in a Western country. A prospective cohort study to investigate the effectiveness of UEMR was conducted in patients with small superficial nonampullary duodenal adenomas. Patients and methods Patients with duodenal adenomas ≤ 20 mm were enrolled. After the duodenal lumen had been filled with physiological saline, UEMR was performed without submucosal injection. Endoclip closure was attempted for all mucosal defects after UEMR. Follow-up endoscopy with biopsy was performed 3 months later. The primary end point was the complete resection rate, defined as neither endoscopic nor histological residue of adenoma at the follow-up endoscopy. Results 30 patients with 31 lesions were enrolled. The mean (SD) tumor size was 12.0 mm (7.3). The complete resection rate was 97 % (90 % confidence interval, 87 % – 99 %). The en bloc resection rate was 87 %. All mucosal defects were successfully closed by endoclips. No adverse events occurred except for one case of mild aspiration pneumonia. Conclusions UEMR is efficacious for the treatment of small duodenal adenomas, but further large-scale trials are warranted to confirm these results. Trial registered at University Hospital Medical Network Clinical Trials Registry (UMIN 000018710).

scholarly journals Prognosis and Survivability in Surgically Treated Metastasis of the Long Bones

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 10
Author(s):  
A. Bădilă ◽  
R. Manolescu ◽  
I. Japie ◽  
E. Bădilă ◽  
A. Papuc ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Malignant Disease ◽  
Weight Bearing ◽  
Clinical Results ◽  
Full Weight Bearing ◽  
First Year ◽  
Long Bones ◽  
The Mean ◽  
A Prospective Study

Abstract Aim: To assess the clinical results after osteosynthesis with locked intramedullary nail in metastasis of the long bones. Material and methods. We designed a prospective study in which we included all the patients with metastasis of the long bones admitted and surgically treated in our department between 2013 and 2015. Data for 64 were available at the final check-up. Our cohort totalized a number of 69 fractures (2 long bones required surgical treatment in 5 patients). The mean follow-up for survivors was 37 months (limits: 18-49 months). The primary tumor was known in 51 patients (79,69%). For the remaining 13 cases (20,31%), the primary tumor was not known and the pathological fracture was the first sign of the malignant disease. In the last group, the tumor could be identified by imagistic methods in 6 cases, while in other 3 cases, a biopsy and histological examination (which were performed in all the remaining 7 cases) determined the source organ. Clinical and radiological check-ups were performed at every 3 months in the first year and at every 6 months after that. Results. Pain amelioration and mobilization of the involved limb were achieved in all the cases. In 3 patients, the osteosynthesis could not compensate the progressive bone loss and the permanent use of an external orthosis was mandatory. The survival rate was 82,81% at 6 months and 67,19% at 12 months. Conclusions. All patients could be mobilized. Two thirds of the patients will survive more than a year. The goals of osteosynthesis are the same, regardless the location of the fracture and implant used: pain amelioration, stability for immediate full weight bearing, durability for patient’s life expectancy.

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