Status of hyperthermia in the treatment of advanced liver cancer

Dear Sir,We read with interest the review of the status of hyperthermia in the treatment of liver cancer by Moroz and colleagues in a recent issue of the Journal of Surgical Oncology [1]. The authors concluded, ''the results of trials involving IHP (isolated hepatic perfusion) hitherto have been disappointing'' and that ''it is difficult to envisage a role for IHP in the treatment of liver cancer.'' We have been actively evaluating the use of IHP over the past 8 years and were disappointed not to see any reference to our published work by the authors. We would agree, based on the cited references in the article, that some results with IHP have been disappointing. We have tried to place those trials in perspective with several reviews on this topic that address the current results of IHP from various centers [2][3][4][5][6]. We disagree that there are other treatments such as local ablative therapies or systemic chemotherapy that are ''more effective and safer.'' All patients treated with IHP at our institution are not candidates for local ablative treatment based on size, number, and location of lesions in the liver and, except for those with ocular melanoma, most have failed previous systemic or regional chemotherapy.We have also published results of several prospectively conducted phase I and II trials to define the utility of tumor necrosis factor (TNF) and melphalan administered as a one hour hyperthermic IHP. Our initial results with TNF and melphalan showed a 74% radiograpic response rate (RR) in 33 assessable patients with unresectable metastases confined to liver [7]. We subsequently reported that using a standard operative technique that complete vascular isolation is routinely achieved with IHP and that, with or without TNF, this therapy can be administered with minimal morbidity and a mortality of less than 4% [6,8]. IHP appears to have significant anti-tumor activity against a variety of histologies. Our initial results in 22 patients with ocular melanoma metastatic to liver who underwent hyperthermic IHP demonstrated an overall RR of 62% [9] and more recent unpublished results show an overall RR of 71%. Our experience in 51 patients with unresectable hepatic metastases from colorectal cancer who underwent IHP has also been reported [10]. Half of the patients in this study had failed prior systemic therapy and seven had failed prior hepatic arterial infusional therapy (HAI). The overall objective RR was 76%. Of note, in those receiving IHP followed by post-IHP HAI of a floxuridine-based regimen the median duration of response was over 14 months and median survival was 27 months. There was only one peri-operative death. Based on these data, we believe that continued clinical evaluation to better define the role of IHP in the treatment of patients with unresectable cancers confined to liver is justified.

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confidence: 92%

Hyperthermic isolated hepatic perfusion for the treatment of unresectable cancers confined to the liver

Carroll

Alexander

2002

Journal of Surgical Oncology

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“…Typically, hyperthermia is applied mildly in clinics, using temperatures ranging from 41 to 46°C for a period of 30 min to a few hours on tissue. The goal of the hyperthermia is to affect certain regulatory proteins, kinases or cyclins, resulting in alternations to the cell cycle and even apoptosis (Despa et al 2005;Moroz et al 2001). Large volumes of tissue are heated by microwave, ultrasound, radio frequency, or conductive energy sources (Diller and Ryan 1998).…”

Section: Introductionmentioning

confidence: 99%

Single-cell-based measurement of supraphysiological thermal injury in human carcinoma cells utilizing a micropatterned hydrogel chip

2010

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Hyperthermia affects certain regulatory proteins, kinases or cyclins, resulting in alternations to the cell cycle and even to apoptosis. Damage to the cell plasma membrane is a key factor in the killing of a cell by hyperthermia. Analysis at the single-cell level is necessary for understanding the fundamental mechanisms of hyperthermia-induced cell death and the generation of thermotolerance in surviving cells. Engineering approaches achieving precise control of cellular micropatterning provide the potential for investigating the mechanisms of thermal injury to cells at the single-cell level. The main purpose of this study is to fabricate a hydrogel chip with microwells for cellular patterning and to demonstrate the feasibility of measurement of supraphysiological thermal injury in human carcinoma cells (HeLa cells) at the singlecell level. To accomplish this, measurement of membrane injury by dye leakage post-thermal insult was performed and reported in this work. A hydrogel chip with microwells with different diameters was fabricated. For cell concentrations at 0.5 9 10 6 cells/mL, the occupancy of cells on the microchip with 40 lm microwells was up to 86.6%, a value far higher than that found on the 30 lm microwells (approximately 78.5%). Most microwells of 30 lm in diameter (about 70%) were occupied by a single cell; hence, the hydrogel chip with 30 lm microwells was suitable for the applications of single-cell-based analysis. The fluorescent images showed that calcein leakage occurred when cell membranes were damaged under supraphysiological temperatures between 43 and 50°C. The normalized intensity of calcein decreased to 32% under a supraphysiological temperature of 43°C for 20 min. The intensity of calcein in cells was less than 20% under a supraphysiological temperature of 50°C. The feasibility of the single-cell-based experiment of thermal injury in the microchip with hydrogel microwells was therefore successfully demonstrated.

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“…6,7 It is thought that thermal tissue sensitization (using hyperthermia for site heating up to 45 C) leads to changes on the function of many structural and enzymatic proteins within cells, which, in turn, alters cell growth and differentiation and can induce apoptosis. 8 Thermal ablation (site heating above 45 C) usually induces necrosis instead. 9 Furthermore, the principle of magnetic site localization of magnetic drug delivery systems is based on submicron host particles encapsulating simultaneously magnetic nanoparticles and drug molecules.…”

Section: Introductionmentioning

confidence: 99%

Selol-loaded magnetic nanocapsules: A new approach for hyperthermia cancer therapy

Falqueiro

Primo

Morais

et al. 2011

Journal of Applied Physics

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Polylactic-co-glycolic nanocapsules, loaded with nanosized magnetic particles and Selol (a selenium-based anticancer drug), were successfully prepared by the precipitation method. Maghemite (γ-Fe2O3) nanoparticles were incorporated into the nanocapsules using a highly stable ionic magnetic fluid sample. The obtained nanocapsules presented no agglomeration, negative surface charge while revealing a narrow monomodal size distribution. All the nanocapsule formulations exhibited a good physical stability at 4 °C during 3 month storage period. The in vitro antitumoral activity of Selol-magnetic nanocapsules was assessed using a murine melanoma cell line. The influence of nanocapsules on cell viability was investigated by spectrophotometric assay. The results demonstrated that Selol-loaded magnetic nanocapsules (at 100 μg/ml/5 × 109 particle/ml) showed antitumoral activity of 50% on melanoma cells (absence of magnetic field). These results clearly indicate that the loaded nanocapsules represent a novel and promising magnetic drug delivery system suitable for cancer treatment via the active drug and magnetohyperthermia.

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Status of hyperthermia in the treatment of advanced liver cancer

Cited by 103 publications

References 76 publications

Hyperthermic isolated hepatic perfusion for the treatment of unresectable cancers confined to the liver

Hyperthermic isolated hepatic perfusion for the treatment of unresectable cancers confined to the liver

Single-cell-based measurement of supraphysiological thermal injury in human carcinoma cells utilizing a micropatterned hydrogel chip

Selol-loaded magnetic nanocapsules: A new approach for hyperthermia cancer therapy

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