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. 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. ____________________ 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.

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NROC Installs Revolutionary Cancer Treatment System, TomoTherapy

The TomoTherapy HI×ART System® 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 System® 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).

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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.  

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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).

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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.