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Hyperthermia
written and compiled by doctordee
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Introduction

"According to an article published in Nature magazine ("Coley's Toxin's in Perspective", Vol 357, May 1992) there was a Dr. William B. Coley in NY in the 1890s who intentionally induced an erysipelas infection (streptococcal skin infection) in his sarcoma patients. Eventually he mixed two different heat-killed bacteria to make what was termed "Coley's toxin" to give to the sarcoma patients DAILY over a period of weeks or months. The fevers evidently were the forces at work, not the infections. It seems he had some pretty good results. Coley died in 1936. The article goes on to mention some trials done by Dr. Demetri, along these lines, too...I think in an even broader array of cancer patients. It seems that some kinds of sarcomas in particular responded the best to this treatment." Kel in Orlando

"Hyperthermia dramatically increases the uptake of chemotherapy drugs by cancer cells. ... When the temperature of tumors is raised to high-fever level (hyperthermia), tumors become much more absorbent to chemotherapy drugs. Increased blood flow is the body's natural response to heat, raising the uptake of drugs in tumor membranes. As a result, hyperthermia "increases drug delivery and antitumor efficacy in patients," ... Once drugs are delivered, hyperthermia can also be used as an activator to accelerate drug chemical reactions. Hyperthermia is further demonstrating a role as a valuable companion therapy when chemotherapy drugs are injected into the blood in encapsulated form (liposomes)... when a liposome-encapsulated drug is used in combination with hyperthermia, tumor drug penetration greatly increases. According to a research team from Munich, this boost in the effectiveness of chemotherapy is good news for victims of high-risk soft-tissue sarcomas, ..."[2*]

" ... Some researchers advocate heating just one region of the body, but Dr. Bull at The University of Texas-Houston Health Science Center is testing whole-body hyperthermia. The study is being conducted in patients with cancer of the colon, stomach, and pancreas. Although the number of study participants whose tumors completely disappeared remains small, ...up to 50 percent of patients in the study who undergo both hyperthermia and chemotherapy have seen their tumors either shrink or stop growing. In pancreatic cancer, the partial response rate is as high as 70 percent."[1*]


Hyperthermia is a technique useful in loco-regional control. It seems to be most effective, when combined with other treatments like surgery, chemotherapy and/or radiation, in preventing local recurrence, if the surgical resection margins are clear. Local use does not prevent distant metastasis. In certain circumstances, used along with other types of treatment, hyperthermia might contribute to an increase in survival time.

Generally, local recurrence rates are influenced by tumor site, type of trial, maximum tumor temperature, and local toxicity, whereas overall survival is influenced by the presence of metastasis, tumor grade, and response to treatment. [26]

NOTE: Many of these studies are referring to SARCOMAS, not leiomyosarcoma. However, leiomyosarcoma has shown response to hyperthermic treatment.

Hyperthermia [heating tissue to higher than normal body temperatures] greater than or equal to 42 degrees C is tumoricidal in vitro and in many animal models. [167] Hyperthermia is an older technique, used since the 1970's in combination with radiation to control tumor growth in hypoxic malignant tumors of low radiation sensitivity, especially in superficial and shallow tissue regions. [178] It was well tolerated without serious side effects. [178] Later, hyperthermia was also included with chemotherapy. Hyperthermia can be local [superficial or deep], regional, or with whole body involvement. So it can be used to treat superficial tumors, or deep ones. It can be used to treat pelvic or abdominal sarcomatosis by regional treatment. It can be accomplished with isolated limb perfusion of extremities. Even whole body treatment can be done. The technical choices of how to achieve the hyperthermia vary with the location. It is usually combined with other modalities of therapy, usually chemotherapy or radiation.

In 1981, with development of a radiofrequency device that provided safe hyperthermia, to any depth without surface tissue injury, a study was done evaluating the effects of hyperthermia on advanced human sarcomas. "Intratumor temperatures greater than or equal to 42 degrees C [about 108 deg F] were observed in all tumors, with virtually no normal tissue injury. ... [The treatment] resulted in significant tumor necrosis and pain relief in some patients. Hyperthermia of advanced sarcomas is possible with little host toxicity and may be of potential therapeutic benefit." [167]

Another early study: "Soft tissue sarcomas continue to present problems with both local control of disease and death from distant metastases after accepted surgical therapy. Multimodality management has been established in the literature to be superior to traditional therapy of wide excision or amputation .... One-third of the patients presented with local recurrent disease after unsuccessful primary treatment. Over-all local recurrence for all patients treated by a combination of the aforementioned modalities was 3.4 per cent at two years and 11.1 per cent at five years. ... Not only are the treatment results with regional hyperthermic perfusions excellent for both primary and locally recurrent sarcomas of the extremities, but limbs previously considered unsalvageable can be spared." [150]

From another early study, "Bone and soft tissue sarcomas are good targets for hyperthermia combined with radiotherapy and chemotherapy. Some tumors indicated for this study were too large to heat with the present heating apparatus." But they got a 65% response rate with heating to 42 deg C [92]

Leiomyosarcoma shows high levels of chemoresistance to many chemotherapy agents. [101] A 1994 study concluded "These findings suggest that ...when ... leiomyosarcoma tumors show resistance to antitumor drugs, then resection at the time of initial exploration and combined modalities, including radiation and hyperthermia, should be considered." [101]
Limb

"The treatment options available for extremity sarcomas are amputation or limb-sparing surgery. Hypothermic isolated limb perfusion (HILP) in association with other treatments like radiation and chemotherapy may be an attractive option in extremity sarcomas for unresectable lesions to preserve limb function and maintain quality of life. [12, 67, 74, 150] Complete remission has occurred in at least one extremity LMS following preoperative regional hyperthermia and chemotherapy [intra-arterial doxorubicin]. [107] "Complications [of hyperthermic isolated limb perfusion] included chronic lymphedema, neuropathic pain, and prolonged wound healing." [12]

In another study radio-hyperthermo-chemotherapy (RHC) was given to 44 patients with high-grade soft-tissue sarcomas of the limbs. ... "Tumor shrinkage was observed in 98% (43/44) of the patients. Of the 36 patients with M0 tumors, 30 were disease-free at final follow-up, 2 had no evidence of disease, 1 was alive with disease, and 3 had died of the disease. Amputation was required only in the first patient, and the affected limb was preserved in the other 43 patients. The surgical margin was wide in 9 patients and marginal in 29 patients and intralesional excision was performed in 5 patients. There was recurrence in only 1 of the 44 patients. CONCLUSION: RHC is currently the most potent and relatively safe treatment method for high-grade soft-tissue sarcomas that is available clinically." [3]
In a study using hyperthermia with doxorubicin to treat STS limb lesions, "the local recurrence rate was influenced by tumor site, type of trial, maximum tumor temperature, and local toxicity, whereas the overall survival was influenced by the presence of metastasis, tumor grade, and response to treatment." [26]

HOWEVER, in yet another study long-term results of hyperthermic isolated limb perfusion [ILP] showed a considerable local recurrence rate and a low disease-free survival. Perfusion in patients without tumor-free resection margins does not prevent local recurrence. We conclude that ILP with cisplatin, melphalan and Adriamycin should be considered carefully and is not an additional treatment strategy of first choice. [65]
Bone

The Chinese have been using local microwave induced intracorporeal [heat source is placed within the body] hyperthermia followed by immunotherapy to spare limbs while treating bone tumors. [57, 71, 72] The Chinese have also treated patients with malignant bone tumor by intraoperative microwave heating of tumor bearing bone in place [to 50 deg C for 15 minutes], wide excision of tumor in soft tissue, and neoadjvant chemotherapy. [60] Healing [revascularization] of the tumor site could be demonstrated in a year or more. Pathological fracture however, can occur at devitalized bone. [57, 71] The advantage of intraoperative microwave hyperthermia for bone tumors is that it keeps the shape and continuity of the bone, without osteotomy or internal fixation, and may benefit bone remodeling. [60] The treatment is an alternative to replacement by prosthesis or allograft [graft to patient using patient's tissue] bridging techniques. [72]
Lung

"A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients [none were sarcomas]. Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function." [70]
Liver

[Too dangerous, the toxicity in this study is not acceptable. Ed.]
"A phase I trial [was done] to determine the toxicity and efficacy of isolated hepatic perfusion with tumor necrosis factor alpha (TNF-alpha) and melphalan (Alkeran) under mild hyperthermic conditions." Subjects were eleven patients with unresectable metastatic liver malignancies. [37] The combination of these chemotherapy agents with isolated liver perfusion and hyperthermia had considerable toxicity. However there was a partial response in one or two leiomyosarcoma patients, mean survival time was 20 months, which is within the same range as seen in previous isolated hepatic perfusion (IHP) studies." [37]
Brain

This will be discussed under the Brain section of Treatment by Site.
Abdomen: Peritoneal Sarcomatosis

Preoperative Hyperthermia and Radiation

Neoadjuvant Preoperative Thermochemotherapy and Postoperative Chemoradiation

Preoperative Hyperthermia and Systemic Chemotherapy

Hyperthermic Intraoperative Intraperitoneal Chemotherapy / Hyperthermic Total Abdominal Perfusion


Preoperative Hyperthermia and Radiation

Surgical resection was planned 4-6 weeks after the completion of radiation and hyperthermia in 97 patients with surgically resectable high grade STS, without metastases. "Ten-year actuarial overall survival, cause-specific survival, and relapse-free survival are 50, 47, and 47% respectively. The predominant pattern of failure has been distant metastases with only 2 patients developing local failure alone. Ten-year actuarial local control for extremity tumors is 94%, 63% for the 19 patients with tumors at sites other than the extremity. ... For these aggressive high-grade soft tissue sarcomas, this treatment program of preoperative thermoradiotherapy provided excellent local regional control for extremity lesions (95%) and satisfactory local regional control (63%) of nonextremity sarcomas, but did not appear to influence the rate of distant metastases or survival. Complications were frequent but apart from the direct thermal burns, not too different from those reported for preoperative radiotherapy alone. More effective adjuvant systemic therapy is necessary to impact favorably on survival. [27]


Neoadjuvant Preoperative Thermochemotherapy and Postoperative Chemoradiation
"Patients with retroperitoneal or visceral (RP/V) soft-tissue sarcomas (STS) have a poor prognosis with a median survival of 20 months" 58 [21 primary, 18 recurrence, 19 inadequately resected] patients with RP/V STS were treated with 4 cycles of EIA [etoposide, ifosfamide, adriamycin] concurrently with regional hyperthermia, then surgery, then another 4 cycles of EIA and external beam radiation. "Median overall survival for the group was 31 months," for those with NED median survival was 76 months, for NON-NED 20 months. "Patients responding to neoadjuvant thermochemotherapy associated significantly with NED... In conclusion, response to neoadjuvant thermochemotherapy is predictive for a better survival in patients with high-risk STS at unfavorable RP/V sites. Since local recurrence without distant metastasis often results in death for patients with RP/V tumors, local tumor control accomplished in part by neoadjuvant thermochemotherapy seems to improve survival. In order to prove the impact of RHT on the efficacy of neoadjuvant treatment, a randomized multicentric phase III trial (EORTC 62961/ ESHO RHT-95) has been initiated. [4*, also ASCO abstract 1388 in 2001]


Preoperative Hyperthermia and Systemic Chemotherapy
There is improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas. [122] Not only are the treatment results with regional hyperthermic perfusions excellent for both primary and locally recurrent sarcomas of the extremities, but limbs previously considered unsalvageable can be spared. [150]

"In this phase II study, activity and safety of neoadjuvant regional hyperthermia (RHT) combined with chemotherapy was investigated in 59 patients with primary advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT followed by surgical resection and adjuvant treatment. The overall objective response (OR) rate was 17%, with one complete (2%) and eight partial (15%) responses. In addition, 13 minor responses (25%) were seen. At time of surgery, complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable histological response (FHR)) in 12 patients. At the completion of protocol treatment, 36 patients were rendered disease-free which was significantly associated with the initial radiographic and/or pathological tumour response (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow-up of 82 months, local treatment failure occurred in 33 patients, median overall survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence interval (CI): 36-61%). OS which did not differ for extremity versus non-extremity STS (P=0.21) was better for patients responding to EIA combined with RHT (P<0.01)." [4] [Note: these were ADVANCED or recurrent sarcomas, not stage one, and the survival statistics reflect that. ]

"The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% ... 59% ... 26% ... and 40% ...respectively. OS was in favour of patients responding to neoadjuvant treatment .... In comparison to a preceding ... study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival." [5]


Hyperthermic Intraoperative Intraperitoneal Chemotherapy / Hyperthermic Total Abdominal Perfusion
Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal sarcomatosis involves treating the patient regionally with hyperthermia, while also bathing the abdominal cavity and its contents in a solution of chemotherapy agents, during an operation. [17]

Hyperthermic intraperitoneal intraoperative chemotherapy using doxorubicin and cisplatin, combined with cytoreductive surgery was investigated as a new multimodal treatment for peritoneal [abdominal] ... sarcomatosis. Thirty-one patients were enrolled in a phase I trial. During an operation, tumor bulk was removed leaving only nodules of 3mm or less. They concluded: "Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging," they will consider further investigation. [1]

"Surgery remains the principal modality of therapy in the management of primary and recurrent retroperitoneal STS." 33 patients [with retroperitoneal STS] underwent complete resections. Eleven of them received locoregional chemotherapy by HTAP. "The overall cumulative 5-year survival rates in patients with stage IIA and advanced disease were 82% and 22%, respectively ... tumor stage, use of HTAP and type of operation were found to have significant influence on overall survival (P<0.05)." Results showed "complete resection along with HTAP chemotherapy may improve survival in patients with retroperitoneal STS. These phase II data could be used to support the initiation of a phase III trial to test HTAP in patients submitted to complete resection of retroperitoneal STS." [36]

Leila of the LMS List, in Brasil, underwent this procedure because of continuous recurrence of her Uterine LMS. Leila's Website

She states: Hi Doreen,

I am so glad you wrote me! I have high grade LMS that has caused me eight surgeries in the last two years. The recurrences were happening in interval of four months each. I almost had lost hopes for treatment and was expecting for the worst. In 31st October of 2001, I had a major surgery performed with hyperthermic and intraoperative chemotherapy. Since then I am clear. That is, for me, a paradise. Now, on the 14th of June, I will do new CT scans and I hope to still be clear.

What really makes me happy is the fact that you are paying attention to hyperthermia as an instrument for controlling sarcomatosis. You have asked about the temperature. Well, they heated my abdominal cavity at 43 deg centigrade. The surgery lasted 16 hours and the entire tumor between bladder and sigmoid was removed. For one hour and half the hyperthermic chemo was done with the drug Mitomicin at 43 deg C. They put four catheters intra-abdominally for the postoperative chemo at room temperature. Afterwards, the abdomen was closed and I went to a Intensive Care Unity, where I stayed for five days, two of them receiving chemo intra-abdominal with the drug Cisplatin in room temperature. Doctor Sugarbaker from Washington developed this technique. Dr. Sugarbaker's website

I have side effects after the surgery with hyperthermic and intraoperative chemo. I stayed for two months with problems in my hands (peripheral neuropathy) and in February I stayed for eight days in the hospital with intestinal blockage. But now I am very well, and especially: I am clear! I pray every day to continue clear. In my case, the hyperthermia was a miracle.
Whole Body Hyperthermia

Whole-body hyperthermia combined with chemotherapy can be shown to increase tumor cell death without increasing bone marrow suppression. [23]

In one study, seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with BCNU [a chemotherapy agent]. All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases. [113]

In another study, 10 of 12 adult patients with refractory sarcoma had a response or stable disease after entering a phase II trial of 41.8 degrees C (x 60 min) extracorporeal whole body hyperthermia (WBH) with ICE, [ifosfamide, carboplatin, etoposide. 8 patients had a history of prior chemotherapy associated with disease progression. Following WBH/ICE, 7 partial remissions were observed (58%); 3 patients experienced disease stabilisation; the aforementioned 10 patients each received four cycles of therapy. 2 patients exhibited progressive disease. Major toxicities were targeted to bone marrow and kidneys. Minor toxicities included anasarca, diarrhea, irregular heartbeats, pressure sores, and oral herpes simplex sores. [76]

In a third study, 11 patients with advanced soft tissue sarcoma were treated with whole body hyperthermia (41.8 degrees C-43.0 degrees C) for 2 hours, doxorubicin (45 mg/m2) at the beginning of peak temperature and cyclophosphamide (1000 mg/m2) 6 hours after doxorubicin. Warming was accomplished with a nylon and vinyl mesh water perfused suit and heating blankets under barbiturate anesthesia. Thirty-five thermochemotherapy treatments were administered after an initial baseline euthermic course. There were two complete and two partial responses including three of three liposarcomas and one of two leiomyosarcomas, and there were two disease stabilizations. Morbidity included anasarca, nausea and vomiting, diarrhea, myalgias, mild surface burns, perioral herpes simplex, reversible neuropathy, hypotension, and cardiac arrhythmias. Hyperglycemia and hypophosphatemia were found during heating, and normalized at 24 hours. Liver enzyme elevations occurred 24 hours after heating and normalized within 1 week. A uniform platelet decrease (mean, 107,000/microliter) was found at 24 hours. Thermochemotherapy was found to be a feasible approach for selected patients with advanced soft tissue sarcoma for the subset of liposarcomas and leiomyosarcomas. [157]

"Hyperthermia is known to enhance the therapeutic index of numerous cytotoxic drugs, including alkylating agents and platinum derivatives. Due to technical improvement WBH has become a feasible treatment option as an adjunct to standard chemotherapy. Earlier clinical trials have produced promising results in relapsed/refractory sarcoma (Wiedemann et al., 1996) by combining ... WBH with ICE chemotherapy. ... We therefore started a phase II clinical trial to investigate efficacy and feasibility in untreated and relapsed/refractory soft tissue sarcoma using an identical protocol. ..."[3*]

12 untreated and 11 relapsed/refractory patients were entered into the study: 6 were LMS and 5 were GIST....
Previously untreated responses: 10 previously untreated patients were evaluable, with 3 PR [one a leiomyosarcoma and one a GIST], 4 SD and 2 PD. Apparent response rate is 70%. [3*]

"All pts in the relapsed/refractory group are evaluable with 2 minor responses, 4 SD and 4 PD, representing a clinical benefit of 56%. We had 1 early death in each group, one due to tumor lysis and one due to sepsis. The median time to progression and median survival by Kaplan-Meier estimates is not reached in de novo pts. and is 18 weeks (range 0-81) and 66 weeks (range 1-112), respectively for relapsed/refractory pts." [3*]

"Conclusion: concerning PR rates in relapsed/refractory sarcoma, we could not reproduce the promising results, reported elsewhere (PR rate of 25%, Wiedemann et al., ASCO 2000) in our small series of pts. This may be due to a more intense pretreatment. Nevertheless, results concerning clinical benefit especially in untreated pts. are encouraging and warrant further investigation. Updated results will be presented at the meeting. "[3*]
Complications and Side Effects

Hyperthermia with/without Radiation

Complications directly attributable to hyperthermia when used in conjunction with radiation are usually second- or third-degree burns, blistering, areas of superficial soft tissue necrosis, and possible fistula formation. The hyperthermia complications were generally not severe and either healed readily or were excised at the time of surgical resection of the primary tumor. The persistent complications noted included induration and fibrosis, ulceration at the site of prior tumour and ulceration in normal tissue. [27, 74, 110,165] Height of tissue temperature attained had a slight association with increased complications. "Macroscopic tumours had greater incidence of complications than for microscopic residual disease. The rate and type of persistent and/or late complications seen following combined radiation and hyperthermia did not appear to dramatically differ from those that would be anticipated from irradiation alone in this patient population, with the exception of an increased incidence of areas of induration and tumour necrosis." [110]

Intraoperative Microwave Hyperthermia
With intraoperative microwave hyperthermia the complications can include infection, subsequent pathological fracture of the devitalized bone. [72]

Isolated Limb Perfusion
During hyperthermic isolated limb perfusion, common side effects are redness and edema, skin reactions, and transient nerve dysfunction. [126] When chemotherapy agents are perfused, there can be leakage of the chemotherapy agent into the systemic circulation can occur. [6] There can also be neuromuscular toxic effects, worse with pre-existing neuropathy. [24] Isolated limb perfusion patients might have atrophy, and/or chronic edema [swelling due to fluid accumulation]. [29] Vascular complications after isolated limb perfusion are rare, consisting mainly of clots at the arterial site where the artery was entered, and can be successfully treated by prompt operation to remove the clot. It happens in women, possibly because of the smaller size of their arteries. Therefore, close observation of the peripheral circulation after ILP is necessary. [42]

Whole Body Hyperthermia
Whole-body Hyperthermia [WBH] combined with chemotherapy can be shown to increase tumor cell death without increasing bone marrow toxicity. [23, 170] However, there can be a treatment-limiting problem with nephrotoxicity [kidney damage]. ICE treatment [ifosfamide, carboplatin, etoposide] can cause temporary kidney damage, but if given with Whole Body Hyperthermia, this damage PERSISTS. Extracorporeal WBH [where blood was warmed outside the body] was more toxic to the kidneys than radiant-heat-induced WBH. [23]

WBH in combination with chemotherapy also can cause an acute systemic inflammatory response resulting in Multiple Organ Dysfunction Syndrome [in this case, brain dysfunction, low blood pressure, respiratory failure, renal dysfunction] [30] WBH alone can also cause transient thrombocytopenia in all patients, non-cardiogenic pulmonary edema, and mild hypotension. [113]
Evaluation of Response

"In one study, among 12 tumors showing no decrease in size after treatment by hyperthermia + either radiation or chemotherapy showed necrosis of the tumour when evaluated histologically, or development of a prominent hypodense area on CT scan. ... Six cases were studied to correlate the X-ray CT findings, angiography and histological findings before and after hyperthermic treatment. The data were also used to interpret the thermal curve. The increased hypodensity area was roughly proportional to the development of necrosis, but there was one case in which hypodensity was not correlated with the necrosis. On the contrary, even in the contrast-enhanced area around the tumour in which the presence of residual tumour was strongly suspected clinically, no tumour cells were visualized. Clinical evaluation of the effect by size of the tumour can be supplemented by CT findings and histology, but should be cautiously adopted." [136]

"The average time for heating to 42 degrees C and the average maximum temperature did not correlate with the local effect. The percentage of the low density area on CT images and the average maximum temperature were well correlated. ... Percent low density and percent necrosis were correlated to some degree, but adoption of this phenomenon as a criterion for evaluation should be considered carefully." [92]
More Information

Search Pubmed for LMS and hyperthermia

Search Pubmed for sarcoma and hyperthermia
Where Is It Done?

From a PubMed Search:
Hyperthermia has been done in many countries; articles on hyperthermic treatment of cancer have been published from the following USA institutions. Presumably, hyperthermia in one or another of its treatment modes would be available at these sites or the investigators would have further knowledge of where it is currently being used. This is not an exhaustive list. You might find further sites by searching Pubmed for hyperthermia and cancer treatment
and doing a "Find" [see toolbar on internet browser] for USA or whichever country you are interested in.

Dr. Joan Bull, director of the oncology division at UT-Houston's Medical School, is currently conducting two studies in whole-body hyperthermia. The study is being conducted in patients with cancer of the colon, stomach, and pancreas. The University of Texas-Houston Health Science Center [1*]
Joan M C Bull, Professor, Oncology
Medical School
University of Texas-Houston Health Science Center
P.O. Box 20708, Houston, TX 77225-0708

Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Radiat Oncol Biol Phys 1998 Mar 1;40(4):815-22
Magnetic resonance thermometry during hyperthermia for human high-grade sarcoma.
Carter DL, MacFall JR, Clegg ST, Wan X, Prescott DM, Charles HC, Samulski TV.

Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ann Thorac Surg 1996 Jun;61(6):1609-17
Isolated lung perfusion with tumor necrosis factor for pulmonary metastases.
Pass HI, Mew DJ, Kranda KC, Temeck BK, Donington JS, Rosenberg SA.

Cultaneous Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla. 33612-9497, USA
Cancer Control 2001 May-Jun;8(3):269-73
Hyperthermic isolated limb perfusion for extremity sarcomas.
Kim CJ, Puleo C, Letson GD, Reintgen D.

Department of Surgery, School of Medicine, University of Washington, Seattle 98195, USA. vocelka@u.washington.edu
Perfusion 2000 Nov;15(6):549-52
Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal carcinomatosis and sarcomatosis using a cardioplegia heat exchanger and a two-pump system: a case report.
Vocelka CR, Anderson DL, Crockett GI.

University of Wisconsin, School of Medicine, Madison, Wisconsin USA.
J Immunother 1999 Jan;22(1):67-70
Heat shock protein antibodies in sarcoma patients undergoing 41.8 degrees C whole body hyperthermia.
Katschinski DM, Benndorf R, Wiedemann GJ, Mulkerin DL, Touhidi R, Robins HI.

References
1*. UT-Houston Oncologist Studying Heat Treatment for Cancer
News Release

2*. ASCO Presentations Show Hyperthermia Enhances Cancer Drug Delivery
SAN FRANCISCO, May 17, 2001-BSD Medical Corp. (OTCBB:BSDM).

3*. WHOLE BODY HYPERTHERMIA (41.8C) COMBINED WITH IFOSFAMIDE (IFO), CARBOPLATIN (CBDCA) AND ETOPOSIDE (VP-16) IN PATIENTS WITH UNTREATED AND RELAPSED/REFRACTORY SOFT TISSUE SARCOMA
CTOS poster

4*. Response to Neoadjuvant Thermochemotherapy as Significant Prognosticator for Long-Term Survival of Patients with Retroperitoneal or Visceral High-Risk Soft-Tissue Sarcomas.
ASCO 1388 - 2001

1: Cancer 2002 Jan 15;94(2):492-9
Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study.
Fetch PMID: 11900234

3: Int J Clin Oncol 2001 Oct;6(5):253-8
Results of surgery and radio-hyperthermo-chemotherapy for patients with soft-tissue sarcoma.
Otsuka T, Yonezawa M, Kamiyama F, Matsushita Y, Matsui N.
Department of Orthopaedic Surgery, Nagoya City University Medical School, 1 Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan. t.otsuka@med.nagoya-cu.ac.jp
Fetch PMID: 11723748

4: Eur J Cancer 2001 Sep;37(13):1599-608
Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults: long-term results of a phase II study.
Issels RD, Abdel-Rahman S, Wendtner C, Falk MH, Kurze V, Sauer H, Aydemir U, Hiddemann W.
Department of Internal Medicine III, Klinikum Grosshadern Medical Center (KGMC), Ludwig-Maximilians-University, Munich, Germany. issels@med3.med.uni-uenchen.de
Fetch PMID: 11527684

5: Eur J Cancer 2001 Sep;37(13):1609-16
Comment in: Eur J Cancer. 2001 Sep;37(13):1587-9.
Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia.
Wendtner C, Abdel-Rahman S, Baumert J, Falk MH, Krych M, Santl M, Hiddemann W, Issels RD.
Department of Internal Medicine III, Klinikum Grosshadern Medical Center (KGMC), Ludwig-Maximilians-University, D-81377, Munich, Germany. clemens.wendtner@med3.med.uni-muenchen.de
Fetch PMID: 11527685

6: Ann Surg Oncol 2001 Aug;8(7):566-72
Comment in: Ann Surg Oncol. 2001 Aug;8(7):564-5.
Continuous leakage measurement during hyperthermic isolated limb perfusion.
Daryanani D, Komdeur R, Ter Veen J, Nijhuis PH, Piers DA, Hoekstra HJ.
Division of Surgical Oncology, University Hospital Groningen, The Netherlands.
Fetch PMID: 11508617

12: Cancer Control 2001 May-Jun;8(3):269-73
Hyperthermic isolated limb perfusion for extremity sarcomas.
Kim CJ, Puleo C, Letson GD, Reintgen D.
Cultaneous Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla. 33612-9497, USA
Fetch PMID: 11378653

17: Perfusion 2000 Nov;15(6):549-52
Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal carcinomatosis and sarcomatosis using a cardioplegia heat exchanger and a two-pump system: a case report.
Vocelka CR, Anderson DL, Crockett GI.
Department of Surgery, School of Medicine, University of Washington, Seattle 98195, USA. vocelka@u.washington.edu
Fetch PMID: 11131220

23: J Cancer Res Clin Oncol 2000 Mar;126(3):173-7
Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia.
Gerke P, Filejski W, Robins HI, Wiedemann GJ, Steinhoff J.
Department of Internal Medicine I, Medical University of Lubeck, Germany.
Fetch PMID: 10741912

24: Cancer Chemother Pharmacol 2000;46(6):517-22
Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents.
Bonifati DM, Ori C, Rossi CR, Caira S, Fanin M, Angelini C.
Department of Neurological and Psychiatric Sciences, University of Padova, via Giustiniani 5, Padova, Italy.
Fetch PMID: 11138466

29: Eur J Surg Oncol 1999 Oct;25(5):503-8
Long-term functional morbidity after mild hyperthermic isolated limb perfusion with melphalan.
Vrouenraets BC, in't Veld GJ, Nieweg OE, van Slooten GW, van Dongen JA, Kroon BB.
Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek ziekenhuis), Amsterdam, The Netherlands.
Fetch PMID: 10529261

26: Cancer 1999 Nov 1;86(9):1742-9
Soft tissue limb sarcomas: Italian clinical trials with hyperthermic antiblastic perfusion.
Rossi CR, Foletto M, Di Filippo F, Vaglini M, Anza' M, Azzarelli A, Pilati P, Mocellin S, Lise M.
Clinica Chirurgica II, Universita' di Padova, Padua, Italy.
Fetch PMID: 10547547

27: Int J Radiat Oncol Biol Phys 1999 Nov 1;45(4):941-9
The treatment of high-grade soft tissue sarcomas with preoperative thermoradiotherapy.
Prosnitz LR, Maguire P, Anderson JM, Scully SP, Harrelson JM, Jones EL, Dewhirst M, Samulski TV, Powers BE, Rosner GL, Dodge RK, Layfield L, Clough R, Brizel DM.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Fetch PMID: 10571201

30: Intensive Care Med 1999 Sep;25(9):1013-6
Multiple organ dysfunction syndrome induced by whole-body hyperthermia and polychemotherapy in a patient with disseminated leiomyosarcoma of the uterus.
Pereira Arias AM, Wester JP, Blankendaal M, Schilthuis MS, Kuijper EJ, Rademaker BM, Stoutenbeek CP, Rietbroek RC.
Department of Internal Medicine, Academic Medical Center, P. O. Box 22700, NL-1100 DE Amsterdam, The Netherlands.
Fetch PMID: 10501762

36: Tumori 1999 Jul-Aug;85(4):259-64
Retroperitoneal soft tissue sarcoma: effect of hyperthermic total abdominal perfusion.
Eroglu A, Kocaoglu H, Demirci S, Akgul H.
Department of Surgical Oncology, Ankara University Medical School, Turkey.
Fetch PMID: 10587028

37: Eur J Surg Oncol 1999 Apr;25(2):179-85
Isolated hepatic perfusion with extracorporeal oxygenation using hyperthermia, tumour necrosis factor alpha and melphalan.
Lindner P, Fjalling M, Hafstrom L, Kierulff-Nielsen H, Mattsson J, Schersten T, Rizell M, Naredi P.
Department of Surgery, Sahlgrenska University Hospital, Goteborg, Sweden.
Fetch PMID: 10218462

42: Eur J Surg Oncol 1998 Aug;24(4):288-91
Vascular complications of isolated limb perfusion.
Klicks RJ, Vrouenraets BC, Nieweg OE, Kroon BB.
Department of Surgery, The Netherlands Cancer Institute (Antoni van Leeuwenhoek ziekenhuis.
Fetch PMID: 9724995

57: Zhonghua Wai Ke Za Zhi 1997 Aug;35(8):484-7
[Treatment of malignant or aggressive bone tumors with microwave induced hyperthermia]
[Article in Chinese]
Fan Q, Ma B, Guo A.
Department of Orthopedic Surgery, Second Hospital, Fourth Military Medical University, Xian.

Fetch PMID: 10678071

60: Zhonghua Wai Ke Za Zhi 1997 Apr;35(4):196-9
[Microwave heating and neoadjuvant chemotherapy for malignant bone tumor]
[Article in Chinese]
Lu S, Wang J, Hu Y.
General Hospital of Chinese People's Liberation Army, Beijing.
Fetch PMID: 10374534

65: Chirurg 1996 Dec;67(12):1237-43
Comment in: Chirurg. 1997 Jun;68(6):649.
[Results of isolated hyperthermic extremity perfusion in soft tissue sarcomas within the scope of a multimodality treatment concept]
[Article in German]
Schwarzbach M, Lehnert T, Willeke F, Hinz U, Herfarth C.
Chirurgische Klinik und Poliklinik, Universitat Heidelberg.
Fetch PMID: 9081786

67: Eur J Surg Oncol 1996 Oct;22(5):528-31
Hyperthermic isolated limb perfusion with cisplatin in four patients with sarcomas of soft tissue and bone.
van Ginkel RJ, Schraffordt Koops H, de Vries EG, Molenaar WM, Uges DR, Hoekstra HJ.
Department of Surgical Oncology, University Hospital Groningen, the Netherlands.
Fetch PMID: 8903498

70: Ann Thorac Surg 1996 Jun;61(6):1609-17
Isolated lung perfusion with tumor necrosis factor for pulmonary metastases.
Pass HI, Mew DJ, Kranda KC, Temeck BK, Donington JS, Rosenberg SA.
Fetch PMID: 8651757

71: Chin Med J (Engl) 1996 Jun;109(6):425-31
Surgical treatment of bone tumors in conjunction with microwave-induced hyperthermia and adjuvant immunotherapy. A preliminary report.
Fan Q, Ma B, Guo A, Li Y, Ye J, Zhou Y, Qiu X.
Department of Orthopedic Surgery, Second Affiliated Hospital, Fourth Military Medical University, Xi'an.
Fetch PMID: 9206073

72: Chin Med J (Engl) 1996 Jun;109(6):432-6
Limb salvage in primary malignant bone tumors by intraoperative microwave heat treatment.
Lu S, Wang J, Hu Y.
Orthopedic Department, General Hospital of PLA, Beijing.
Fetch PMID: 9206074

74: Radiol Med (Torino) 1996 Jun;91(6):796-8
[Hyperthermia and palliative radiotherapy for sarcoma] [Article in Italian]
Amichetti M, Graiff C, Romano M, Bolner A, Busana L, Fellin G, Pani G, Valdagni R.
Divisione di Radioterapia Oncologica, Ospedale S. Chiara, Trento.
Fetch PMID: 8830368

76: Eur J Cancer 1996 May;32A(5):888-92
Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8 degrees C whole body hyperthermia in patients with refractory sarcoma.
Wiedemann GJ, Robins HI, Gutsche S, Mentzel M, Deeken M, Katschinski DM, Eleftheriadis S, Crahe R, Weiss C, Storer B, Wagner T.
Department of Internal Medicine, Medical University of Lubeck, Germany.
Fetch PMID: 9081372

92: Radiat Med 1994 Sep-Oct;12(5):231-6
Hyperthermia for bone and soft tissue sarcoma: relationship between computerized tomographic and histological findings.
Tsukiyama I, Ogino T, Egawa S.
Department of Radiation Therapy, Tochigi Cancer Center Hospital, Japan.

101: Anticancer Res 1994 Jan-Feb;14(1A):169-71
Antitumor chemosensitivity differs between clinical sarcoma and adenocarcinoma tissues.
Takeuchi H, Baba H, Inutsuka S, Takahashi I, Kusumoto H, Maehara Y, Sugimachi K.
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Fetch PMID: 8166444

107: J Surg Oncol 1993 Apr;52(4):272-5
Complete disappearance of a leiomyosarcoma of the lower extremity following preoperative hyperthermia and intra-arterial doxorubicin.
Khalek Y, Vilor M, Sorrentino J, Brown M, Wills J, Herrera L.
Department of Surgery, Medical Center of Delaware, Wilmington 19806.
Fetch PMID: 8468991

110: Int J Hyperthermia 1992 Nov-Dec;8(6):733-45
Persistent and/or late complications of combined radiation therapy and hyperthermia.
Ben-Yosef R, Kapp DS.
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Fetch PMID: 1479199

113: Int J Hyperthermia 1992 May-Jun;8(3):297-304
Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU).
Bull JM, Cronau LH, Newman BM, Jabboury K, Allen SJ, Ohno S, Smith T, Tonnesen AS.
Houston Department of Internal Medicine, University of Texas Medical School 77030.
Fetch PMID: 1607734

122: J Cancer Res Clin Oncol 1991;117 Suppl 4:S141-7
Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.
Issels RD, Mittermuller J, Gerl A, Simon W, Ortmaier A, Denzlinger C, Sauer H, Wilmanns W.
Institut fur Klinische Hamatologie, University of Munich, Federal Republic of Germany.
Fetch PMID: 1795003

126: Eur J Surg Oncol 1990 Aug;16(4):370-5
Hyperthermic limb perfusion for malignant melanoma and soft tissue sarcoma.
Kettelhack C, Kraus T, Hupp T, Manner M, Schlag P.
Department of Surgery, University of Heidelberg, FRG.
Fetch PMID: 2379595

136: Int J Hyperthermia 1989 Jan-Feb;5(1):23-35
Characteristics of the response of soft tissue sarcoma to hyperthermia: the correlation between temperature distribution, radiological examination and histology.
Egawa S, Tsukiyama I, Kajiura Y, Akine Y, Ogino T, Takayasu K, Fukuma H, Beppu Y, Mukai K.
Department of Radiation Therapy, National Cancer Center Hospital, Tokyo, Japan.
Fetch PMID: 2921532

150: Surg Gynecol Obstet 1986 Feb;162(2):149-52
Improved survival for soft tissue sarcoma of the extremities by regional hyperthermic perfusion, local excision and radiation therapy.
Lehti PM, Moseley HS, Janoff K, Stevens K, Fletcher WS.
Fetch PMID: 3945892

157: Cancer 1984 Jun 15;53(12):2585-91
Doxorubicin, cyclophosphamide, and whole body hyperthermia for treatment of advanced soft tissue sarcoma.
Gerad H, van Echo DA, Whitacre M, Ashman M, Helrich M, Foy J, Ostrow S, Wiernik PH, Aisner J.
Fetch PMID: 6722720

165: Cancer 1982 Jan 15;49(2):205-16
Clinical hyperthermia: results of a phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy.
Manning MR, Cetas TC, Miller RC, Oleson JR, Connor WG, Gerner EW.
Fetch PMID: 6274503

167: J Surg Oncol 1981;17(2):91-8
Radio frequency hyperthermia of advanced human sarcomas.
Storm FK, Elliott RS, Harrison WH, Kaiser LR, Morton DL.
Fetch PMID: 7242101

170: Klin Wochenschr 1979 Dec 17;57(24):1311-5
[Influence of hyperthermia on toxic side effects of cytostatic agents (author's transl)]
[Article in German]
Neumann H, Engelhardt R, Fabricius HA, Stahn R, Lohr GW.
Fetch PMID: 232202

178: Med Klin 1976 Jul 9;71:1183-7
[Effects and mechanism of a locally combined treatment with radiation and heat therapy (author's transl)]
[Article in German]
Hymmen U, Wieland C.
Fetch PMID: 986537


Compiled/written by doctordee
June 2002


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