Biomedical Engineering Reference
In-Depth Information
enrolled if they were deemed either unsuitable for surgery (
n
= 6)
or had refused surgical resection (
n
= 16). Using the tumor node
metastasis (TNM) staging, four patients were at stage I, nine at
stage IIA, eight at stage IIB, and one at stage IV. The tumor and
surrounding margins of 1.5-2.0 cm were treated. Axillary lymph
node dissection was performed on patients with stage IIB dis-
ease 4-8 weeks following ablation (except in three patients who
refused the surgery). All patients received six cycles of adjuvant
chemotherapy and radiotherapy after HIFU ablation. On the
completion of the chemotherapy, two years of hormone therapy
(tamoxifen) followed. Outcome measures included radiological
and pathologic assessment of the treated tumor, cosmesis, local
recurrence, and cumulative survival rates.
After HIFU therapy, all patients experienced a palpable breast
lump as anticipated, which extended to the whole treatment area
(tumor and margin), and was therefore greater than the origi-
nal tumor. Although patients were advised of this in advance, it
did give rise to anxiety, and two of the 21 patients were elected
to have mastectomy as a result. Radiological imaging showed
absence of tumor blood flow in 19 of 22 patients, the regres-
sion of treated lesions in all patients, and disappearance in eight
patients after HIFU treatment. Follow-up biopsy revealed coag-
ulation necrosis of the targeted tumor and subsequent replace-
ment by fibroblastic tissue.
After a median follow-up of 54.8 months, one patient died,
one was lost to follow-up, and 20 were still alive. Two patients
with stage IIB disease developed local recurrence at the 18th
and 22nd months. They received modified radical mastectomy,
followed by chemotherapy. Five-year disease-free survival and
recurrence-free survival were reported as 95% and 85%, respec-
tively. Cosmetic result was judged as good to excellent in 94%
of patients. It is noted that in the Chinese patient population,
breast cancer is often diagnosed at the advanced stage and that
the average tumor size was larger than that which would typi-
cally be treated conservatively in the West (the typical size for
conservative resection in China versus in the West is 4 cm versus
2 cm in diameter).
Currently, another clinical trial is underway at the European
Institute of Oncology in Milan, Italy, wherein 12 patients with
small breast cancers (<1.5 cm) have been treated with USgHIFU
(personal communication). All tumors were removed for patho-
logic evaluation after HIFU. The pathologic results showed that
all the tumors were completely ablated. Even though local edema
was observed in 30% of the patients, the edema usually subsided
in one day. No other side effects were observed.
transcranial Doppler, have allowed noninvasive imaging of brain
parenchyma and color flow imaging of intracranial vessels, and
have become reliable methods for examination of patients with
stroke [122-127].
These studies imply that despite the anatomical
obstacle, US beams have been transmitted through bones.
In the field of HIFU, it has been discovered that focused US
can cause thermal lesions in animal brains through the skull
[128, 129]. As an aggressive malignant neoplasm, most osteosar-
comas may be lytic regardless of the limited production of min-
eralized osteoid or bone tissue [130]. Slight to complete cortical
destruction within tumor lesions makes possible ultrasound
beam propagation through the damaged osteogenic structure
into the medullary space in which osteosarcoma originates.
Therefore, HIFU can be used as a noninvasive therapy to treat
patients with osteosarcoma through the bone containing soft
tissue of tumor and the weakened bone.
HIFU has been performed as a noninvasive approach in the
treatment of patients with osteosarcoma. In a perspective clini-
cal trial, we used USgHIFU combined with neoadjuvant chemo-
therapy to treat 34 patients with biopsy-proven malignant bone
tumors (Enneking's Stage II
b
) for conserving the diseased-limb,
and HIFU was used alone for 10 patients with stage III
b
for pal-
liative intent [131]. After a mean follow-up time of 17.6 months,
the overall survival rate of 44 cases was 84.1%. For the 34 cases
of stage IIb, 30 cases continued to survive disease-free, two
died of lung and brain metastases, and the other two had local
recurrence. Among 10 of the stage IIIb cases, five survived with
tumor, one had local recurrence, and five died of lung metasta-
ses. The complication occurrence rate was 18.2%, including two
cases with secondary infection, three with pathologic fracture,
one with epiphysis separation, and two with common peroneal
nerve injury. Enneking comprehensive function scoring of the
36 cases was not less than 15 points.
Li et al. [132] reported the preliminary experience of using
USgHIFU for the treatment of 25 patients with primary and
metastatic bone malignancy. Follow-up MRI/PET-CT showed
that therapeutic response rate was 84.6% in 13 patients with pri-
mary bone tumors, including six patients (46.2%) with complete
response and five (38.4%) with partial response. The therapeu-
tic response rate was 75.0% in 12 patients with metastatic bone
tumors, including five cases (41.7%) with complete response and
four (33.3%) with partial response. The one-, two-, three-, and
five-year survival rates were 100%, 85%, 69%, and 39%, respec-
tively, in patients with primary bone tumors, and 83%, 17%, 0%,
and 0%, respectively, in patients with metastatic bone tumors.
Recently, Chen et al. [133] evaluated long-term follow-up
results of USgHIFU ablation for 80 patients with primary
bone malignancies. From December 1997 to November 2004,
80 patients with primary bone malignancy were treated with
USgHIFU, including 60 in stage IIb and 20 in stage III (Enneking
staging). HIFU combined with chemotherapy was performed on
62 patients with osteosarcoma, one with periosteal osteosarcoma,
and three with Ewing's sarcoma; the remaining 14 patients (with
chondrosarcoma, malignant giant cell tumor of bone, sarcoma
of the periosteum, or unknown histology) received HIFU alone.
15.7.5 HIFU therapy for Bone Malignancy
An ultrasound beam is easily transmitted through soft tissues
and parenchymatous organs
in vivo
, except air-containing
organs such as lungs. Because of its high attenuation in osse-
ous tissues, it is generally believed that US propagation through
the bone is almost impossible in the diagnosis and treatment
of bone disease. However, recent transcranial ultrasound tech-
niques, like transcranial color-coded real-time sonography and
