scholarly journals Prospective evaluation of percutaneous hepatic perfusion with melphalan as a treatment for unresectable liver metastases from colorectal cancer

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261939
Author(s):  
T. Susanna Meijer ◽  
Jan H. N. Dieters ◽  
Eleonora M. de Leede ◽  
Lioe-Fee de Geus-Oei ◽  
Jaap Vuijk ◽  
...  
Keyword(s):  
Adverse Events ◽  
Liver Metastases ◽  
Progression Free Survival ◽  
Safe Procedure ◽  
Serious Adverse Events ◽  
Primary Tumors ◽  
Hepatic Perfusion ◽  
Overall Response ◽  
Treatment Regimens ◽  
Percutaneous Hepatic Perfusion

Purpose Percutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM. Materials and methods Prospective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. Results A total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable. Conclusion M-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.

scholarly journals Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma

2021 ◽  
Author(s):  
Cornelia Lieselotte Angelika Dewald ◽  
Jan B. Hinrichs ◽  
Lena Sophie Becker ◽  
Sabine Maschke ◽  
Timo C. Meine ◽  
...  
Keyword(s):  
Adverse Events ◽  
Uveal Melanoma ◽  
Cardiovascular Events ◽  
Liver Tumors ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
High Dose ◽  
Free Survival ◽  
Hepatic Perfusion ◽  
Percutaneous Hepatic Perfusion

Purpose Chemosaturation percutaneous hepatic perfusion (CS-PHP) allows selective intrahepatic delivery of high dose cytotoxic melphalan in patients with curatively untreatable liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. Aim of this study was to investigate the response to therapy, survival and safety of the CS-PHP procedure in patients with liver-dominant metastatic uveal melanoma (UM). Materials and Methods Overall response rate (ORR) and disease control rate (DCR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic progression-free survival (mhPFS) were analyzed using Kaplan-Meier estimation. Adverse events were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5. Results Overall, 30 patients were treated with 70 CS-PHP in a salvage setting from October 2014 to January 2019. In total, ORR and DCR were 42.3 % and 80.8 %, respectively. Overall, mOS was 12 (95 % confidence interval (CI) 7–15) months, and both, mPFS and mhPFS were 6 months, respectively (95 % CI 4–10; 95 % CI 4–13). Adverse events (AE) most frequently included significant but transient hematologic toxicities (87 % of grade 3/4 thrombocytopenia), less frequent AEs were hepatic injury extending to liver failure (3 %), cardiovascular events including one case of ischemic stroke (3 %). Conclusion Salvage treatment with CS-PHP is effective in selected patients with UM. The interventional procedure is safe. Serious hepatic and cardiovascular events, although rare, require careful patient selection and should be closely monitored. Key Points:  Citation Format

scholarly journals Thermal Ablation versus Stereotactic Ablative Body Radiotherapy to Treat Unresectable Colorectal Liver Metastases: A Comparative Analysis from the Prospective Amsterdam CORE Registry

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4303 ◽  
Author(s):  
Sanne Nieuwenhuizen ◽  
Madelon Dijkstra ◽  
Robbert S. Puijk ◽  
Florentine E. F. Timmer ◽  
Irene M. Nota ◽  
...  
Keyword(s):  
Adverse Events ◽  
Liver Metastases ◽  
Local Control ◽  
Thermal Ablation ◽  
Colorectal Liver Metastases ◽  
Progression Free Survival ◽  
Risk Scores ◽  
Stereotactic Ablative Radiotherapy ◽  
Serious Adverse Events ◽  
Stereotactic Ablative Body Radiotherapy

Thermal ablation and stereotactic ablative radiotherapy (SABR) are techniques to eradicate colorectal liver metastases (CRLM). This study compares the safety, efficacy and long-term oncological outcomes of these treatment methods. All prospectively registered patients (AmCORE registry) treated with thermal ablation or SABR alone for unresectable CRLM between 2007 and 2020 were analyzed using multivariate Cox-proportional hazard regression. In total 199 patients were included for analysis: 144 (400 CRLM) thermal ablation; 55 (69 CRLM) SABR. SABR patients were characterized by older age (p = 0.006), extrahepatic disease at diagnosis (p = 0.004) and larger tumors (p < 0.001). Thermal ablation patients were more likely to have synchronous disease, higher clinical risk scores (p = 0.030) and higher numbers of CRLMs treated (p < 0.001). Mortality was zero and morbidity low in both groups: no serious adverse events were recorded following SABR (n = 0/55) and nine (n = 9/144 [6.3%]; all CTCAE grade 3) after thermal ablation. SABR was associated with an inferior overall survival (OS) (median OS 53.0 months vs. 27.4 months; HR = 1.29, 95% CI 1.12–1.49; p = 0.003), local tumor progression-free survival (LTPFS) per-tumor (HR = 1.24, 95% CI 1.01–1.52; p = 0.044) and local control per-patient (HR = 1.57, 95% CI 1.20–2.04; p = 0.001) and per-tumor (HR = 1.89, 95% CI 1.44–2.49; p < 0.001). In this study thermal ablation was superior to SABR with regard to OS, LTPFS and local control, albeit at the cost of a limited risk of serious adverse events. Further studies are required to assess whether the worse outcomes following SABR were the effect of true differences in ablative treatment or a result of residual confounding.

scholarly journals Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4726
Author(s):  
Martijn S. Bethlehem ◽  
Dimitrios Katsarelias ◽  
Roger Olofsson Bagge
Keyword(s):  
Liver Metastases ◽  
Uveal Melanoma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Invasive Technique ◽  
Free Survival ◽  
Hepatic Perfusion ◽  
Study Results ◽  
Isolated Hepatic Perfusion ◽  
Percutaneous Hepatic Perfusion

Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. Conclusion: There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP.

scholarly journals The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098054
Author(s):  
Huilin Xu ◽  
Ximing Xu ◽  
Wei Ge ◽  
Jinju Lei ◽  
Dedong Cao
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Good Survival ◽  
Solid Cancer ◽  
Cancer Type ◽  
Early Effect ◽  
Overall Response

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

scholarly journals HIFU for the treatment of gastric cancer with liver metastases with unsuitable indications for hepatectomy and radiofrequency ablation: a prospective and propensity score-matched study

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Zhou ◽  
Ning He ◽  
Jiaze Hong ◽  
Tong Yang ◽  
Derry Minyao Ng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Radiofrequency Ablation ◽  
Propensity Score ◽  
Adverse Events ◽  
Liver Metastases ◽  
Hepatic Metastasis ◽  
Focused Ultrasound ◽  
Progression Free Survival ◽  
High Intensity Focused Ultrasound ◽  
Entire Cohort

Abstract Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 17 ◽  
Author(s):  
Vinod Solipuram ◽  
Harish Gopalakrishna ◽  
Gayatri Naira ◽  
Akhila Mohan
Keyword(s):  
Pancreatic Cancer ◽  
Placebo Group ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Thromboembolic Events ◽  
Serious Adverse Events ◽  
Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

scholarly journals Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma

2019 ◽  
Vol 37 (18) ◽  
pp. 1529-1537 ◽  
Author(s):  
Vatche Tchekmedyian ◽  
Eric J. Sherman ◽  
Lara Dunn ◽  
Crystal Tran ◽  
Shrujal Baxi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Adenoid Cystic Carcinoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
End Point ◽  
Adenoid Cystic

PURPOSE Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of predominantly salivary gland origin for which effective therapies are lacking. We conducted a phase II trial evaluating the multitargeted tyrosine kinase inhibitor lenvatinib in patients with R/M ACC. PATIENTS AND METHODS This study was conducted with a two-stage minimax design. Patients with histologically confirmed R/M ACC of any primary site with radiographic and/or symptomatic progression were eligible. Any prior therapy was allowed except previous lenvatinib. Patients received lenvatinib 24 mg orally per day. The primary end point was overall response rate. Secondary end points were progression-free survival and safety. An exploratory analysis of how MYB expression and genomic alterations relate to outcomes was conducted. RESULTS Thirty-three patients were enrolled; 32 were evaluable for the primary end point. Five patients (15.6%) had a confirmed partial response, 24 patients (75%) had stable disease, two patients (6.3%) discontinued treatment as a result of toxicity before the first scan, and one patient (3.1%) had progression of disease as best response. Median progression-free survival time was 17.5 months (95% CI, 7.2 months to not reached), although only eight progression events were observed. Patients otherwise were removed for toxicity (n = 5), as a result of withdrawal of consent (n = 9), or at the treating physician’s discretion (n = 6). Twenty-three patients required at least one dose modification, and 18 of 32 patients discontinued lenvatinib for drug-related issues. The most common grade 3 or 4 adverse events were hypertension (n = 9; 28.1%) and oral pain (n = 3; 9.4%). Three grade 4 adverse events were observed (myocardial infarction, n = 1; posterior reversible encephalopathy syndrome, n = 1; and intracranial hemorrhage, n = 1). CONCLUSION This trial met the prespecified overall response rate primary end point, demonstrating antitumor activity with lenvatinib in R/M ACC patients. Toxicity was comparable to previous studies, requiring monitoring and management.

Efficacy, Safety, and Regulatory Approval of Food and Drug Administration–Designated Breakthrough and Nonbreakthrough Cancer Medicines

2018 ◽  
Vol 36 (18) ◽  
pp. 1805-1812 ◽  
Author(s):  
Thomas J. Hwang ◽  
Jessica M. Franklin ◽  
Christopher T. Chen ◽  
Julie C. Lauffenburger ◽  
Bishal Gyawali ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Drug Administration ◽  
Mechanism Of Action ◽  
Food And Drug Administration ◽  
Progression Free Survival ◽  
Cancer Drugs ◽  
Serious Adverse Events ◽  
Hazard Ratios ◽  
Fda Approval

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non–breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non–breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non–breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non–breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy–designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non–breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non–breakthrough-designated drugs.

Ocular melanoma liver metastases treated by percutaneous hepatic perfusion with melphalan followed by ipilimumab: A case report.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20008-e20008
Author(s):  
Ahmad Fitri Idris ◽  
Michael John Martin ◽  
Ian R Davidson ◽  
Gerard J O'Sullivan ◽  
Ahmad A Jamaludin ◽  
...  
Keyword(s):  
Side Effects ◽  
Gall Bladder ◽  
Liver Metastases ◽  
Epigastric Pain ◽  
Ocular Melanoma ◽  
High Dose ◽  
Hepatic Perfusion ◽  
Pulmonary Angiogram ◽  
Unresectable Liver Metastases ◽  
Percutaneous Hepatic Perfusion

e20008 Background: Patients with unresectable liver metastases from ocular melanoma have a poor prognosis with just 10% surviving 1 year with standard treatments. High-dose melphalan via percutaneous hepatic perfusion (PHP) and filtration system (ChemoSat, Delcath Inc.) is licensed in Europe for treatment of liver-only metastases from ocular melanoma and neuroendocrine tumours. Ipilimumab (Ipi), anti-CTLA4 immunotherapy is licensed in US and Europe for treatment of metastatic malignant melanoma. A 32-year-old man was referred to our unit with unresectable liver metastases from primary ocular melanoma treated 8 years earlier. Here we describe the first report of sequential ChemoSat and Ipi in this setting. Methods: With assistance of an international proctoring team, and following on-site training, we treated this patient with ChemoSat according to manufacturer’s instructions (details at meeting). There were no immediate complications or subsequent hematological or other systemic chemotherapy side-effects. On day 4, the patient developed acute epigastric pain, pyrexia, ST elevation, and elevated troponin. Cardiac ECHO, coronary angiogram, CT pulmonary angiogram, abdominal USS and gastroscopy were normal. Blood cultures were repeatedly negative. He developed acute kidney injury secondary to intravenous contrast and NSAIDs. Repeat abdominal USS showed a thickened wall of gall bladder. A diagnosis of acute chemical cholecystitis was made. His symptoms settled, kidney function improved and he was discharged on day 23 of procedure. 10 weeks post ChemoSat the patient underwent treatment with Ipi 3mg/kg i.v. day 1, q 3/52 x 4 cycles which he received without significant side-effects. Results: MRI scan of liver 8 weeks post-ChemoSat (pre-Ipi) showed the liver lesions to be unchanged. CT scan 6 weeks post-Ipi treatment showed significant improvement. Conclusions: ChemoSat treatment is feasible and safe but can cause unexpected gall-bladder toxicity. Subsequent treatment with ipilimumab seems to be effective in this single case with short-term follow up.

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