Hyperthermia
By Cheng B. Saw, PhD
Hyperthermia therapy is the medical
application of heat to elevate body temperature
in the treatment of cancers. The effect of high
body temperature causing tumor regression had been
observed in patients having fever since ancient
times. The idea of using heat to treat cancer has
been around for a while but early attempts in the
1970s had mixed results. For instance, it was difficult
to maintain the right temperature in the right area
while limiting the effects on other parts of the
body. But today, newer tools allow for better control
and more precise delivery of heat.
Hyperthermia is being studied
for use against many types of cancer. Research has
shown that higher temperatures can damage and kill
cancer cells usually with minimal injury to normal
tissues. By killing cancer cells and damaging proteins
and structures within the cells, hyperthermia has
been shown to shrink tumors. Very high temperatures
can kill cancer cells outright but they also can
injure or kill normal cells and tissues. This is
why hyperthermia must be carefully controlled and
should be done by doctors with experience using
it. Although hyperthermia can kill cancer cells,
the treatment is almost always used in combination
with other forms of cancer therapies such as radiation
therapy and chemotherapy.
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| In local hyperthermia, heat is applied to a small area by to heat the tumor. Photo courtesy Northeast Radiation Oncology Centers (NROC). |
The elevation of temperatures
a few degrees above the normal to 41 to 42 degrees
C. by prolonged heating causes changes in the cellular
environment of the tumors. In combination with other
stresses, hyperthermia can cause cell death by apoptosis.
There are many biochemical consequences to the heat
shock response mechanism which induces the heat
shock proteins 70 (HSP 70) synthesis. Heat shock
inhibits DNA synthesis and transcription as well
as blocks the progression of cell cycle. The overheating
of the tumor cells creates a lack of oxygen so that
the pH level of the heated cells become overly acidic,
which leads to a lack of nutrients in the tumor.
Overall, hyperthermia weakens
the integrity of the tumor cells, allowing for increased
blood flow. The increase in blood flow also increases
the oxygen level in the tumors, making the tumor
environment more potent to both chemotherapy and
radiation therapy. In fact, hypoxia tumors that
are known to be radio-resistant can be treated effectively
with a combination of hyperthermia and radiation
therapy. These two modalities typically are given
within one hour. Hyperthermia, if performed at the
recommended temperature and used conscientiously,
will not have lasting serious side effects.
There are three ways of delivering
hyperthermia: (a) local hyperthermia, (b) regional
hyperthermia, and (c) whole body hyperthermia. The
effectiveness of hyperthermia treatment is related
to the temperature achieved during the treatment
as well as the length of treatment and cell and
tissue characteristics. To ensure that the desired
temperature is achieved but not exceeded, the temperature
of the tumor and surrounding tissue is monitored
throughout the treatment.
In local hyperthermia, heat is
applied to a small area by various techniques that
deliver energy to heat the tumor. Energy types may
include microwave, radiofrequency and ultrasound.
External applicators, probes and needles are used
to introduce heat to the tumors for local and regional
hyperthermia. At much higher temperatures, radiofrequency
ablation (RFA) is a type of interstitial hyperthermia
that uses radio waves to heat and kill cancer cells
directly. Fluid circulation through a heat warming
device in combination with anticancer drugs is another
form of regional hyperthermia to treat limbs and
the abdominal cavity. Heat warming or thermal chambers
are used in whole-body hyperthermia.
The state of hyperthermia can
be assessed through the experience of clinical practice
and also global and national clinical trials. Available
literature shows that the scientific basis of hyperthermia
is well established. Many research efforts have
involved treatment of deep seated tumors with the
aim of heating the tumor and delivering chemotherapy.
For instance, the use of nanoparticles and induction
heating of magnetic material implanted into a tumor
are some types of hyperthermia to improve heat application.
Studies are also looking at ways
to reach deeper organs and other sites that cannot
be treated with hyperthermia at this time.[1]
Ongoing clinical trials include deep regional methods
to treat pancreatic cancers (phase III), recurrent
rectal (phase II) and anal carcinoma (phase II).
Plans also are underway for the treatment of non-muscle
invasive bladder, prostate and recurrent tumors,
and muscle invasive bladder tumors. There also is
an ongoing phase II trial in the U.S. using hyperthermia
and a heat-sensitive liposomal targeted chemotherapy
for breast cancers. The ongoing national trials
can be accessed through the ClinicalTrials.gov website,
a service of the National Institutes of Health.[2]
While hyperthermia technology
has improved significantly with better heat delivery
systems offering thermal dose planning and heat
control and better thermometry, the interest in
this modality has waned over the last 20 years in
the United States. This lack of interest is due
in part to (a) the need for expert personnel, (b)
the need of time and attention and (c) limited reimbursements.[3]
Hence, information about hyperthermia outcomes often
is restricted to reports from clinical practices.
Northeast Radiation Oncology Centers
(NROC) has three local hyperthermia systems distributed
among its six radiation therapy facilities in Pennsylvania,
New Jersey and New York. Harmar D. Brereton,
MD, CEO of NROC, stated, "We have always had impressive
outcomes with hyperthermia as an excellent radiosensitizer,"
adding, "Without hyperthermia, the higher radiation
doses used would increase the radiation toxicity
significantly." NROC has conducted more than 5,000
procedures including chestwall recurrence, melanoma,
superficial tumors, neck nodes, sarcoma, and metastatic
tumors. While the treatment of chestwall using hyperthermia
is well established, the impact of local hyperthermia
on the neck nodes and sarcoma is very impressive.
While the use of hyperthermia
has been limited to less than 100 centers in the
United States, this modality is well supported in
Europe and Asia, particularly in many university-based
hospitals. This commitment may be due to the strong
scientific basis of hyperthermia and its outcomes
in combination with radiation therapy and/or chemotherapy.
Three associations--the European Society for Hyperthermic
Oncology, International Clinical Hyperthermia Society
and Society for Thermal Medicine--have facilitated
a number of global clinical trials,[4-6] with significant
interest in regional and whole-body hyperthermia.
In addition to heating and drug delivery mechanism
research, technology advancements are ongoing with
particular focus on non-invasive thermometry such
as an MRI system for temperature mapping and monitoring.
It is hoped that continued clinical trials will
show promising results of this modality in the very
near future.
References
1.http://www.cancer.org/treatment/treatmentsandsideeffects
/treatmenttypes/hyperthermia
2.http://www.clinicaltrials.gov/
3.http://jnci.oxfordjournals.org/content/102/2/79.full.pdf
4.http://www.hyperthermia-ichs.org/hyperthermia_treatment_facilities.htm
5.http://www.esho.info/professionals/studies/
6.http://psfebus.allenpress.com/eBusSFTM/
Cheng B. Saw, PhD, is director
of medical physics at Northeast Radiation Oncology
Centers (NROC), based in Scranton, Pa.
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Results of NROC’s Vitamin D Study Presented
at National Conference
Vitamin D Deficiency Common in Cancer
Patients
A clinical research study conducted at Northeast
Radiation Oncology Center (NROC) has revealed widespread
Vitamin D deficiency in cancer patients, and an
association with more advanced stages of cancer.
The results were shared at the national meeting
of ASTRO (the American Society for Radiation Oncology),
in Miami, Florida, conducted October 2nd through
6th.
Christopher A. Peters, M.D., radiation oncologist
and coordinator of clinical research at NROC, directed
the study, and Thomas Churilla, a third-year medical
student of The Commonwealth Medical College, Northeast
Pennsylvania, served as lead author. Other members
of the study team included radiation oncologist
Harmar D. Brereton, M.D., and Mary Klem, M.S., R.D.,
CSO LDN, NROC’s nutritionist.
“We had noticed low levels of Vitamin D in our
patients, and decided to study it in a scientific
fashion,” states Dr. Peters, “but the median level
of Vitamin D for cancer patients in our region was
much lower than we had originally anticipated—the
study revealed that 75% of patients had sub-optimal
levels of Vitamin D.” Tom Churilla, who presented
the abstract, “Vitamin D Deficiency is Widespread
in Cancer Patients and Correlates with Advanced
Stage Disease: a Community Oncology Experience,”
at the conference, shares, “Until recently, studies
have not investigated whether vitamin D has an impact
on the prognosis or course of cancer. Researchers
are just starting to examine how vitamin D may impact
specific features of cancer, such as the stage or
extent of tumor spread, prognosis, recurrence or
relapse of disease, and even sub-types of cancer.”
The study involved 150 patients with a median
age of 64 years and a 1:1 ratio of men to women.
The five most common primary diagnoses were breast,
prostate, lung, thyroid and colorectal cancer. A
total of 77 percent of patients had vitamin D concentrations
either deficient (less than 20 ng/mL) or sub-optimal
(20-30 ng/mL). The median serum vitamin D level
was 23.5 ng/mL. Regardless of the age or sex of
the patient, these low levels predicted advanced
stage disease in the patient group.
Patients who were found to be vitamin D deficient
were administered replacement therapy, increasing
serum D levels by an average of 14.9 ng/mL. Investigators
will be analyzing if vitamin D supplementation had
an impact on tumor progression or survival in the
long-term.
Both Dr. Peters and Mr. Churilla added that further
studies need to be conducted to understand the relationship
between Vitamin D and cancer. Additional studies
are planned at NROC, focusing on a cancer subset
population.
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NROC’s Cancer Clinical Research
Yields National Award
Center is one of only six in U.S. to
receive honor
Northeast Radiation Oncology Center (NROC)
is one of only six community oncology practices in America
to receive the Clinical Trials Participation Award from
the Conquer Cancer Foundation this year. The Foundation
is part of ASCO, the American Society of Clinical Oncology,
and selected NROC for excellence in “improving cancer care
through its high-quality clinical trials program.”
The award was officially presented at ASCO’s 47th Annual
Meeting, June 5th in Chicago. Christopher A. Peters, M.D.,
one of NROC’s radiation oncologists and medical coordinator
of its Clinical Research program, accepted the award. “We
put an emphasis on enrolling patients in NCI (National Cancer
Institute) sponsored trials like you’d find in major cities,
at no additional cost to the patient,” states Peters. “It’s
humbling and gratifying to know that we were nominated for
the award, and I’m honored that we are one of only six centers
nationally to receive this distinction.”
ASCO judges three criteria in particular when issuing this
award to cancer centers: the number of patients enrolled
in clinical trials, numbers of underrepresented populations,
and innovative techniques in overcoming barriers to participation
in clinical trials. NROC has several unique factors that
make its clinical research efforts innovative.
The physicians of NROC, including Peters, Harmar D. Brereton,
M.D., Madhava Baikadi, M.D., and Chi K. Tsang, M.D., have
implemented a combined modality working conference with
their colleagues in medical oncology, radiation oncology,
radiology, surgery and pathology. This weekly working conference
allows them to prospectively manage new cases as well as
patients already treated, and get the opinion of the various
members. When new patients are seen, members of clinical
research both on the physician level as well as research
associate level are able to screen what trials are available
for each patient and the group can list the pros and cons
of any particular trials for that patient.
Dr. Peters adds, “This has not only increased the quality
of the care being given, but also has facilitated speedier
access to key health care providers, and in and of itself,
provides intrinsic quality assurance when different members
of a given specialty can weigh in on their opinions for
each case.”
Other innovations include two clinical trials initiated
by Northeast Radiation Oncology Center specifically for
NEPA residents. The Center teamed with The Commonwealth
Medical College in a trial that studied the molecular mechanisms
of cancer development in both colorectal and prostate cancer.
Additionally, an ongoing clinical research study in conjunction
with NRCI, the Northeast Regional Cancer Institute, is addressing
why there is a 40% higher than national incidence of thyroid
cancer here in Northeast Pennsylvania.
Of the 1.3 million people who will be diagnosed
with cancer this year, only 3 to 5 percent will participate
in cancer clinical trials. In 2010, NROC enrolled 25 patients
in clinical trials at its Dunmore and Scranton campuses,
giving them the chance to receive state-of-the-science cancer
therapies without traveling outside the area. Northeast
Radiation Oncology Center currently has 25 ongoing clinical
trials, focused on breast, prostate, lung, colorectal, brain,
pancreas and thyroid cancers. These are primarily “Phase
III” NCI trials: randomized, controlled studies on large
patient groups, aimed at assessing the effectiveness of
a drug or treatment that has already gone through two initial
stages.
“The Conquer Cancer Foundation and ASCO are pleased to award
the Clinical Trials Participation Award to Northeast Radiation
Oncology Center for providing patients with access to high-quality
clinical research that ultimately contributes towards progress
against cancer,” says Martin J. Murphy, Jr., Ph.D., DMedSc,
chair of the Conquer Cancer Foundation Board of Directors.
The Foundation is working to create a world free from the
fear of cancer by funding breakthrough research, sharing
knowledge with physicians and patients worldwide, and supporting
initiatives to ensure that all people have access to high-quality
cancer care. The American Society of Clinical Oncology is
the world’s leading professional organization representing
physicians who care for people with cancer. With nearly
30,000 members, ASCO is committed to improving cancer care
through scientific meetings, educational programs and peer-reviewed
journals. For more information and resources, you may visit
www.asco.org., or
www.conquercancerfoundation.org.
Patient-oriented cancer information is also available at
www.cancer.net.

Radiation Oncologists of NROC are from left:
Chi K. Tsang, M.D., Christopher A. Peters, M.D.,
Harmar D. Brereton, M.D., and Madhava Baikadi, M.D.
____________________
NROC Installs Revolutionary
Cancer Treatment System, TomoTherapy
The TomoTherapy HI×ART SystemŽ is a first of its kind,
providing 3-D imaging of a tumor immediately prior to treatment
and delivering radiation from 360 degrees. This allows more
accurate identification and treatment of cancerous tumors,
and reduces exposure of healthy tissue to radiation.
Residents of Northeast Pennsylvania can now access the world’s
most advanced cancer treatment system in two convenient
locations: Northeast Radiation Oncology Center in Dunmore,
and Upper Delaware Valley Cancer Center in Milford. Our
Milford campus has offered TomoTherapy since July 2006.
TomoTherapy is the most precise radiation cancer treatment
for people with the most complex and challenging cases.
“This cutting-edge technology allows the delivery of 360
degree precision radiation therapy, and has tremendous positive
impact on patients,” states Dr. Pino-y-Torres, medical director
of Upper Delaware Valley Cancer Center, and one of the most
experienced radiation oncologists in the world in the use
of TomoTherapy. “It is the first system that provides 3-D
imaging immediately prior to each treatment.”
Dr. Harmar Brereton adds, “We are excited to add TomoTherapy
to our Dunmore campus services--The ability to do 3-D imaging
immediately before each treatment to verify the location
of a tumor increases precision. Often between treatments
a patient’s tumor can move, so by verifying before each
treatment, the tumor can be precisely targeted. This reduces
exposure of healthy tissue to radiation, and also means
it can reduce the side effects for our patients.”
“Our goal is to win the war against cancer,” says Dr. Fred
Robertson, CEO of Madison, Wisconsin-based TomoTherapy Incorporated,
manufacturer of the HI×ART System. “We set out to integrate
and simplify the radiation therapy process while improving
accuracy.” Traditional radiation therapies often require
a patient to transfer between several different stations
to receive treatment, which takes time. “Our system enables
the clinician to plan, verify and deliver treatment in one
system. It can also reduce the chance of errors since all
patient information is contained in one unit, and it reduces
patient treatment time,” says Robertson.
How The TomoTherapy HI×ART SystemŽ Works
1. Before each treatment, the patient, lying on the couch,
moves through the HI×ART machine for a 3-D TomoImage™. Images
taken verify the shape, size and location of the tumor.
2. Dosage and location of delivery via the radiation beam
are determined.
3. The patient then moves through the HI×ART machine again
where radiation is delivered in a helical pattern (360 degrees)
to the tumor.
4. Each procedure takes approximately 15 minutes.
The concept of helical tomotherapy was first developed by
researchers at the University of Wisconsin-Madison. Two
of these researchers later founded TomoTherapy Incorporated
in 1997. The company is privately held and based in Madison,
Wisconsin. For information visit
www.tomotherapy.com
For more information on TomoTherapy at Northeast Radiation
Oncology Center, please call 866-923-TOMO (8666), and at
Upper Delaware Valley Cancer Center, please call 866-549-TOMO
(8666).
____________________
A New Source of Hope in Cancer Treatment
Comes to NROC at Mercy Hospital, Scranton
Northeast Radiation Oncology Center at Mercy
Hospital (now Regional Hospital of Scranton) has become
one of only two locations in Pennsylvania where patients
can benefit from Hyperthermia Therapy. This technology presents
a brighter future for cancer patients, as it can improve
their quality of life, and diminish cancer recurrences.
Hyperthermia therapy is a treatment used in battling cancer
by heating tumors. Research has shown that heat can damage
or kill cancer cells in some tumors while also making radiation
therapy more effective in treating some tumors, despite
conventional therapy. Coupled with radiation therapy, studies
show that hyperthermia may double the tumor response rate
for some recurrent and progressive tumors, when compared
to using radiation therapy alone.
How The BSD-500 Hyperthermia System Works
1. Heat (108 F) kills or weakens the cells of the tumor.
2. Heat increases blood flow through the weakened tumor,
which can allow therapies to permeate the tumor, not just
attack it from the outside.
3. Increased blood flow raises oxygen levels in tumors so
that the cancer can be more effectively treated by radiation
therapy.
4. When the body senses fever, it stimulates the natural
immune system, attacking the cancerous cells.
For more information on Hyperthermia at Northeast Radiation
Oncology Center, or to find out if Hyperthermia is right
for you, please call 570-348-7200, or 888-808-NROC (6762).
More information can also be obtained at
www.TreatWithHeat.com.
____________________
New Liquid Radiation Cancer Treatment
is First in NEPA
(Eliminates Travel for non-Hodgkin’s Lymphoma Patients)
NNortheast Radiation Oncology Center in
Dunmore has become the site of the area’s first Zevalin
‘liquid radiation’ procedure—a new cancer treatment designed
specifically for non-Hodgkin’s lymphoma (NHL) patients.
The Zevalin therapeutic regimen is indicated for patients
with NHL that does not respond to conventional therapy,
or lymphoma that returns after initially responding to therapy.
The procedure involves separate infusions and is administered
in a few stages--partly by an oncologist, and subsequently
by a radiation oncologist. Chi Tsang, M.D., of Radiation
Medicine Associates of Scranton, is the physician at Northeast
Radiation Oncology Center (NROC) performing the latter infusion.
Previously, candidates for this procedure had to travel
out of Northeast Pennsylvania for the treatment. The effectiveness
of this new treatment was determined by how well patients
responded to treatment in clinical trials. According to
Biogen Idec, Inc., in separate clinical studies the overall
response rate of patients who received the Zevalin therapeutic
regimen was between 74 and 80%.
That encouraging response rate helped to inspire the NROC
physicians to achieve the necessary collaboration between
radiation oncology, medical oncology and nuclear medicine
services, and meet the stringent requirements to offer the
procedure in Northeast PA. Anyone desiring more information
on this new procedure is asked to call Northeast Radiation
Oncology Center at 570-504-7200, or 888-808-NROC (6762).
____________________
World’s Most Advanced Cancer Treatment
Comes to Milford
Continuing the pioneering efforts of bringing
to Northeast Pennsylvania and the Tri-state area the most
advanced technologies, the physicians of Northeast Radiation
Oncology Centers have introduced their newest service, the
TomoTherapy Hi-Art System. Until now available only in the
largest metropolitan centers around the country, the very
latest innovation in radiotherapy is conveniently available
at home at Upper Delaware Valley Cancer Center in Milford,
Pennsylvania.
Dr. Mike Gallagher states, “We are also pleased that our
new partner in NROC’s medical group, Jose Luis Pino-y-Torres,
M.D., is one of the most experienced radiation oncologists
in the world in the use of TomoTherapy. Dr. Pino-y-Torres
trained at Johns Hopkins, brought Intensity Modulated Radiation
Therapy to MD Anderson/Orlando, and was instrumental in
bringing the first TomoTherapy Hi-Art System in the United
States to that facility.”
TomoTherapy is the most precise radiation cancer treatment
for people with the most complex and challenging cases.
“This cutting-edge technology allows the delivery of 360
degree precision radiation therapy, and will have tremendous
positive impact on patients,” states Dr. Pino. “It
is the first system that provides 3-D imaging immediately
prior to each treatment, confirming with pinpoint accuracy
the exact location for the delivery of radiation.”
The TomoTherapy Hi-Art System advances the 15-year commitment
of the NROC group with Wayne Memorial Hospital, Honesdale,
Bon Secours Hospital, Port Jervis, and Mercy Hospital (now
Regional Hospital of Scranton), Scranton, in providing the
very best cancer treatment and research for patients.
On October 12, the Center took a break for a few hours to
host an open house. More than 130 patients, physicians and
community leaders joined Dr. Pino and his partners and staff
in the celebration. Those attending enjoyed tours
of the newly refurbished Center, learning about treatment
planning and the Hi-Art System.
Serving tri-state area patients and families with compassion
and premier radiation therapy services, Upper Delaware Valley
Cancer Center is located in beautiful Pike County, Pennsylvania.
As medical director of the Center, Dr. Jose Pino oversees
a dynamic team of fully certified therapists, dosimetrists,
physicists, nurses, a social worker and dietitian.
Patients of the center are assured they are getting the
most up-to-date care, via both TomoTherapy and ongoing clinical
trials.
For more information on TomoTherapy at Upper Delaware Valley
Cancer Center, please call 570-296-4411, or 866-549-TOMO.
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NROC First in Northeast PA to Offer
New Treatment for Prostate
Cancer
Northeast
Radiation Oncology Center (NROC) has become the first facility
in Northeast PA to offer High-Dose Rate (HDR) Brachytherapy,
a new treatment option for prostate cancer patients. NROC
has been a national center of excellence for the treatment
of prostate cancer, offering patients the choice of nine
weeks of external beam radiation treatments, five weeks
of the treatments followed by seed implantation, or often
seed implant alone.
HDR Brachytherapy
gives patients yet another option in the fight against cancer,
and is performed in the Operating Room at Mercy Hospital
(now Regional Hospital of Scranton) by a team headed by
a radiation oncologist and a urologist. Catheters are placed
securely near the treatment area, allowing an exact pathway
for radiation to travel to the tumor later that day.
“This new
method helps us to protect three critical organs:
the urethra, rectum and bladder,” says Madhava Baikadi,
M.D. “It enables the physics team to conduct treatment
planning more precisely, and has a low level of side effects
for our patients. Additionally, it furthers the opportunity
to continue the nationally recognized clinical research
performed by our group for the past 15 years.”
As a member
of the Jefferson Cancer Network, (Jefferson University,
Philadelphia), NROC at Mercy Hospital (now Regional Hospital
of Scranton) is following RTOG (Radiation Therapy Oncology
Group) clinical trial protocols for HDR Brachytherapy.
This service is not available elsewhere in Northeast or
Central Pennsylvania, and before it was offered by NROC
at Mercy Hospital (now Regional Hospital of Scranton), those
from Northeast PA had to travel at least as far as Philadelphia
for this option.
The procedure
requires one overnight admission to Mercy Hospital (now
Regional Hospital of Scranton), is available to prostate
cancer patients after five weeks of external beam radiation
visits, and is covered by most insurances. For more
information on HDR Brachytherapy at NROC, please call 570-348-7200.
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