Biomedical Engineering Reference
In-Depth Information
of 82°C. Direct comparative analysis of endpoints is difficult, but
results were promising with a median OS-2 of 13.4 months (as
compared to 5.8 months for chemotherapy) and median OS-1
of 23.2 months (as compared to 14.6 months for the reference
group). In addition, levels of key metabolites of iron were tested
before and after injection, with no indication of iron release
from the nanoparticle deposits.
17.5.2.3 Esophageal Carcinoma
Phase I investigation of MFH treatment in 11 patients with
incurable esophageal carcinoma is in progress (Steinbach et al.
[draft]). Two patients received thermal monotherapy and nine
patients received combination thermal, chemoradiotherapy.
Nanoparticle injection was performed endoscopically, under
camera guidance. Preplanning of nanoparticle deposits was
not possible, due to the flexible geometry of the esophagus.
Significant mechanical resistance was encountered in pre-irra-
diated tissue, and some leakage occurred after injection, but was
remedied by sealing with fibrin glue. Imaging of the nanoparti-
cle deposits indicated that most of the injected load was focused
in the center mass of the tumor. Insufficient loading occurred in
two patients, and injection had to be repeated. Upon treatment,
all patients complained of pain arising from hot spots (generally
at bone interfaces) and tolerated an average field of 3.6 kA/m.
Combination therapy involved simultaneous infusion of cis-
platin, with adjunct radiotherapy at an average dose of 45 Gy.
Treatment had to be stopped in four patients due to pneumo-
nia and decreases in general health conditions. Perforation of
the esophageal wall occurred during injection in one patient.
Results of the study are still under analysis and not yet available.
17.5.2.2 prostate Carcinoma
Two separate phase I trials have been completed investigat-
ing MFH treatment of locally recurrent prostate cancer as a
monotherapy and with adjunctive permanent seed brachy-
therapy (Johannsen, Gneveckow, Taymoorian, Cho et al. 2007;
Johannsen et al. 2010; Wust et al. 2006; Johannsen, Gneveckow,
Taymoorian, Thiesen et al. 2007). Ten patients received six
weekly thermotherapy sessions and for another eight patients,
125-Iodine seeds were also implanted at the time of nanoparti-
cle injection. Injections were made transperineally with the aid
of a template and under TRUS with X-fluoroscopy guidance.
Deposit trajectories were preplanned, but significant mechani-
cal resistance was encountered in the pre-irradiated tumors,
and it was difficult to achieve a homogenous distribution.
Treatments began at a field strength of 2.5 kA/m, which was
gradually increased to the threshold before the patient experi-
enced significant discomfort, and temperatures were held for 60
minutes. Hot spots generally occurred at skin folds of the scro-
tum or rectum and could be somewhat alleviated with cooling
and by keeping the skin dry, but tolerated fields only reached
3 to 5 kA/m. Skin temperatures up to 44°C were measured.
Minimally invasive temperature mapping was conducted dur-
ing the first and last sessions with four catheter-based probes,
and intraluminal temperatures were monitored in the urethra
and rectum throughout all treatments. Temperature map-
ping indicated fairly heterogeneous temperature distributions
throughout the tumor. Treatment of the prostate is often com-
plicated due to high perfusion rates of the surrounding struc-
tures, but this was also likely exacerbated by heterogeneous
nanoparticle distributions. Intratumoral temperatures agreed
reasonably well with the predicted temperatures, but the mea-
sured urethral temperature was on average 1.1°C lower than
the calculated values.
For the monotherapy group, a maximum temperature of 55°C
was achieved, with a median
T
90
of 40.1°C, equating to a median
CEM43 of 7.8 minutes (mean 20.9 minutes). The large variabil-
ity in these values again demonstrates the heterogeneity of the
temperatures achieved, which could be a significant obstacle for
application as a viable treatment. Although it was not a specific
end point, prostate-specific antigen (PSA) levels were also mea-
sured; 8 of the 10 patients demonstrated PSA decreases, rang-
ing from <25% to 70%, with some apparent correlation to the
homogeneity of the nanoparticle deposits and temperatures
reached. In the combined therapy group, median
T
90
of 39.3°C
and CEM43 of 5.8 minutes were achieved. These were adequate
thermal doses for combination treatment, but fell short as a
monotherapy (Johannsen et al. 2006).
17.5.2.4 Local recurrences of Different Origins
Phase I study was conducted on 22 patients with various forms
of locally recurrent cancer, aimed mainly at investigating feasi-
bility for several modes of implantation and validity of calcu-
lated temperatures at various sites (Wust et al. 2006). Groups
included: implantation under CT guidance (sarcoma, cervi-
cal and ovarian carcinoma, rectal cancer), implantation under
TRUS with X-fluoroscopy guidance (prostate), and intraopera-
tive implantation under visual guidance (treatment of residual
tumors after cervical resection). Implantation was preplanned
for the image-guided injection methods, but intraoperative
injection relied on the surgeon's discretion and the magnetic
fluid was administered liberally. However, no nanoparticle
deposits were detected in two of the intraoperative implantation
patients. It is suspected that the nanoparticle solution drained
through tissue gaps and was suctioned during surgery. One to
15 thermal treatments were administered once to twice a week
for 60 minutes. Tolerable field strengths varied between differ-
ent regions of the body. Generally, field strengths of 3 kA/m to 6
kA/m were used in the pelvic regions and up to 7.5 kA/m in the
thoracic and neck regions. All patients also received combina-
tion radio- and/or chemotherapy. Results of the study are still
under analysis and are not yet available.
17.5.2.5 Liver Carcinoma
Phase I study was completed on 13 patients, intended to inves-
tigate the feasibility of transarterial injection of magnetic fluid
for potential treatment of hepatocellular carcinoma (HCC)
(Dudeck et al. 2006). The patients underwent transarterial
chemostabilization (TACE) in combination with the infu-
sion of iron oxide nanoparticles. HCC draws its blood supply
