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Fast Neutron Therapy
written and compiled by doctordee
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Fast Neutron Therapy

Neutron Radiation is produced from a large and expensive particle accelerator called a cyclotron. This high-LET (high linear-energy-transfer) radiation is also called "fast neutron therapy". Neutrons, pions and heavy ions (such as carbon, neon and argon) deposit more energy along their path than x-rays or gamma rays, thus causing more damage to the cells they hit. The cyclotron accelerator produces protons and then a series of powerful magnets bend and aim the beam to strike a beryllium target, where the interaction produces neutrons.

High-LET radiation has increased energy deposition in tissue per-unit-tract-length. Neutrons interact with the atomic nuclei of cells and produce densely ionizing protons. These proton particles transfer high amounts of energy to the tumor and inflict a significant percentage of single-hit double-stranded DNA damage. This type of damage is generally considered lethal to a cell. By contrast, low-LET radiation is more sparsely ionizing and causes a higher percentage of single-stranded DNA events, which have a greater capacity for repair.

Photon radiation [Xrays or Gamma rays] causes most of its cellular damage through the generation of free radicals. Neutrons have a greater tendency to cause death to the cell through direct interaction.

Because the biological effectiveness of neutrons is so high, the required tumor dose is about one-third the dose required with photons, electrons or protons. A full course of neutron therapy is delivered in only 10 to 12 treatments. Side effect severity depends on the total dose delivered and the general health of the patient. The treatment field is shaped by computer so that the radiation beam conforms to specific volume with reduced exposure to adjacent normal tissue.

High Energy Neutrons can be very effective in killing tumor, but they can be equally lethal to normal tissue. Evaluate the site and the probable side effects from the radiation on the structures which might be in the beam, ask what they could be and discuss these carefully with the radiation oncologist. For large inoperable tumors that photon radiation would not be able to treat, high energy neutrons could be a lifesaver.

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When To Use It

Patients who may benefit from neutron therapy include:

Newly diagnosed patients with unresectable (inoperable) disease, or residual disease following surgery (positive margins).

Patients whose disease has recurred after surgery.

Patients who want to avoid the surgical option of amputation.

Patients with localized brain metastasis from primary sarcoma

Patients whose tumors are too large to be effectively treated with photon therapy.

Patients with metastasis from a radioresistant primary tumor


Neutron therapy is appropriate for:

Very large tumors

Slow-growing tumors

Radioresistant Tumors [including leiomyosarcoma]

Large hypoxic tumors - tumors with poor oxygenation

Metastatic radioresistant tumors

Advanced Brain Tumors

Tumors which resist treatment by low LET radiation such as photons (x-rays), electrons, or protons



Brain
Radioresistance
Soft Tissue
Metastasis
More Information

Search Pubmed for Sarcoma and Neutron Therapy

Annotated Medical Journal Citations


1: Int J Radiat Oncol Biol Phys. 2001 Jun 1;50(2):449-56.
Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence.
Schwartz DL, Einck J, Bellon J, Laramore GE.
Department of Radiation Oncology, Seattle VA Medical Center/Puget Sound Health Care System, WA 98108, USA. david.schwartz2@med.va.gov

...the University of Washington employ[s] fast neutron radiotherapy for soft tissue sarcoma lesions with prognostic features predictive for poor local control. These include gross residual disease/inoperable disease, recurrent disease, and contaminated surgical margins.
...Eighty-nine soft tissue sarcoma lesions in 72 patients were treated with neutron radiotherapy in our department between 1984 and 1996. ... Seventy-three percent were treated with fast neutron radiation alone, the rest with a combination of neutrons and photons. ... Forty-two patients with solitary lesions were treated with curative intent. Thirty-one patients (including 7 previously treated with neutrons) with 41 lesions were treated with the goal of local palliation. Tumors were predominantly located in the extremity and torso. Thirty of 35 (85%) of curative group patients treated postoperatively had close or positive surgical margins. Thirty-four (82%) lesions treated for palliation were unresectable. Thirty-five patients (53%) were treated at the time of recurrence. Median tumor size at initial presentation was 8.0 cm (range 0.6-29), median treated gross disease size was 5.0 cm (range 1-22), and 46/69 evaluable lesions (67%) were judged to be of intermediate to high histologic grade. Fourteen patients (21%) had chondrosarcomas.

Median follow-up was 6 months (range 2-47) and 38 months (range 2-175) for the palliative and curative groups, respectively. Kaplan-Meier estimates were obtained for probability of local relapse-free survival (68%), distant disease-free survival (59%), cause-specific survival (68%), and overall survival (66%) at 4 years for the curatively treated group. For the palliatively treated group, estimated local relapse-free survival at 1 year was 62%. Log-rank analysis of the curative group revealed recurrent disease to be the only risk factor predictive for significantly worse local and distant disease-free survival. Intermediate-/high-grade histology was predictive for inferior overall survival. Effective clinical response was documented for 21/27 (78%) lesions treated palliatively. Ten patients (15%) experienced serious chronic radiation-related complications. All of these patients had clinical situations requiring delivery of high neutron doses and/or large radiotherapy fields.

Fast neutron radiotherapy is locally effective for soft tissue and cartilaginous sarcomas having well-recognized high-risk features. Results in the palliative setting appear to be particularly encouraging, with neutrons frequently providing significant symptomatic response for gross disease, with minimal serious chronic sequelae. Fast neutron radiotherapy should be considered in patients at high risk for local recurrence in both the curative and palliative settings.
Fetch PMID: 11380233


2: Strahlenther Onkol. 1999 Jun;175 Suppl 2:76-8.
Treatment results of fast neutron irradiation in soft tissue sarcomas.
Prott FJ, Micke O, Haverkamp U, Potter R, Willich N.
Klinik und Poliklinik fur Strahlentherapie-Radioonkologie-Westfalische Wilhelms-Universitat, Munster.

...Surgery is the standard treatment of soft-tissue sarcomas. Adjuvant radiotherapy with photons after less radical resection can improve local control. The rate of tumor control achieved in patients with G1 and G2 soft tissue sarcomas incompletely resected and treated postoperatively with neutron irradiation is similar to that seen in patients undergoing complete tumor resection and adjuvant photon irradiation.

...At the Department of Radiotherapy and Radiation Oncology of the University of Munster, 61 patients with soft tissue sarcomas were irradiated postoperatively with fast neutrons. Mainly tumors of low or intermediate malignancy (R0; 27%; R1, 21%; R2, 52%) were treated. Malignant fibrous histiocytoma, liposarcoma, and neurogenic sarcomas dominated. 46 patients were irradiated with fast neutrons alone, and 15 patients were treated with mixed beam therapy (photons and neutrons).

...The median follow-up period was 44 months. Overall five-year survival probability analysed by Kaplan-Meyer method was 42.5%. The local control rate was 57.7%. 15 patients showed complete remission, 18 patients had a partial remission. Only 11% of the patients showed grade III and IV side effects during neutron irradiation.
...Neutron irradiation is efficocious in treating highly and intermediately differentiated soft tissue sarcomas. The result of surgical resection seems to be a very important prognostic factor for patients with soft tissue sarcomas. Clinical Trial
Fetch PMID: 10394404


3: Anticancer Res. 1999 May-Jun;19(3B):2355-9.
Radiotherapy on adult patients with soft tissue sarcoma with fast neutrons or photons.
Schonekaes KG, Prott FJ, Micke O, Willich N, Wagner W.
Paracelsus Strahlenklinik Osnabruck, Germany.

... We compared the results of a group of patients with soft tissue sarcoma treated with those having received photon therapy (100 patients) or neutron therapy (61 patients). The median dose in the photon treated group was 60 Gy (range 45 to 65 Gy). The neutron therapy group received a median dose of 14.1 Gy (range 5.0 to 18.57 Gy). Patients treated with mixed-beam irradiation received an average dose of 36.5 Gy photon and 8.5 Gy neutrons.

The 5-year survival rate of the photon group rated 43.1%. In the neutron group we found 42.5%, respectively. In both groups the results of surgical resection and grading were of high significance according to survival. 4% of the patients belonging to the photon group developed grade III/IV WHO side effects. In the neutron group side effects grade III/IV WHO were observed in 11% of the cases. Comparing treatment results of neutron and photon therapy we demonstrated that incompletely resected G1 and G2 tumor patients show greater benefit in the case of neutron radiotherapy. Clinical Trial
Fetch PMID: 10472355


4: Skeletal Radiol. 1996 Aug;25(6):537-43.
MR characterization of post-irradiation soft tissue edema.
Richardson ML, Zink-Brody GC, Patten RM, Koh WJ, Conrad EU.
Department of Radiology SB-05, University of Washington, Seattle 98195, USA.

...Our study was carried out to better define these features of the edema seen following neutron and photon radiation therapy.
... There is a relatively wide variation in the duration and degree of post-irradiation edema in soft tissues. This edema seems to persist longer in the intramuscular septa than in fat or muscle. Although the duration of follow-up was limited, our study suggests that this edema resolves in roughly half the photon-treated patients within 2-3 years post-treatment and in less than 20% of neutron-treated patients by 3-4 years post-treatment. Muscle atrophy was seen in both photon- and neutron-treated patients, but was more severe in the neutron-treated group.
Fetch PMID: 8865487


5: Bull Cancer Radiother. 1996;83 Suppl:122s-4s.
Fast neutron therapy in treatment of soft tissuesarcoma--the Berlin-Buch study.
Steingraber M, Lessel A, Jahn U.
Virchow-Klinikum, Humboldt-Universitat Berlin, Berlin-Buch, Germany.

From 1975-1994, 221 adult patients with a total of 232 radiation sites for soft tissue sarcomas were irradiated with fast neutrons with a mean energy of 6.2 MeV in Berlin-Buch/Dresden-Rossendorf. The tumour dose ranged between 6 and 12 Gy and was limited by the low dose penetration of the neutron beam. A local control rate of 66% was obtained. The local control was affected by the tumour differentiation, residual status and histological subtype. Severe fibrosis of the subcutaneous tissues occurred in 40% usually after 2 years. No serious general side effects occurred. To optimize neutron therapy, a high energy clinically-based cyclotron with a fully rotational gantry and a multileaf collimator should be utilized. It seems that patients with locally advanced and well differentiated sarcomas can benefit from this therapy.
Fetch PMID: 8949763



6: Bull Cancer Radiother. 1996;83 Suppl:115s-21s. Related Articles, Links
Ten years of fast neutron therapy in Munster.
Prott FJ, Haverkamp U, Willich N, Wagner W, Micke O, Potter R.
Klinik und Poliklinik fur Strahlentherapie und Radioonkologie, Westfalische Wilhelms-Unversitat, Munster, Germany.

...We therefore would like to present our experience of neutron therapy for different tumors in different localizations and discuss the indications for radiotherapy with neutrons.
In Munster, 269 patients were treated with neutrons between 1985 and 1995, [including 42 soft tissue sarcomas]

...Forty-two patients with soft tissue sarcomas after resection (R1, R2) and different gradings had an overall survival rate after 5 years of 53%.

...In agreement with the results in the literature, there seems to be an indication for neutron therapy in cases of unresectable primaries, unresectable recurrences or residual tumor after surgery in adenoid cystic carcinomas. Results regarding soft tissue sarcoma treatment with neutrons seem to show superiority in comparison with photon therapy. The treatment with neutrons of rectal recurrences has a very good palliative effect. The radiotherapy treatment with neutrons in all the other tumors did not demonstrate any proven superiority in comparison with photon radiation. Publication Types: Multicenter Study
Fetch PMID: 8949762


7: HNO. 1995 Apr;43(4):250-2.
[Rare tumor of the nose and paranasal sinuses. Leiomyosarcoma] [Article in German]
Schmal F, Laubert A.
Universitats-HNO-Klinik Munster.

Leiomyosarcoma is a rare malignant tumor of the nose and paranasal sinuses. Including our patient, 32 cases have been reported in the literature. Radical surgery is currently the best therapy. In comparison with results of conventional irradiation, postoperative neutron treatment appears to be more effective.
Fetch PMID: 7790237


8: Strahlenther Onkol. 1990 Jan;166(1):52-60.
Fast neutron therapy at the end of 1988--a survey of the clinical data.
Wambersie A.
Universite Catholique de Louvain, Cliniques Universitaires St-Luc, Brussels, Belgium.

The clinical results reported from the different neutron therapy centres, in USA, Europe and Asia, are reviewed. ...Neutrons were shown to bring a benefit in the treatment of well differentiated slowly growing soft tissue sarcomas. The reported overall local control rates are 53% and 38% after neutron and photon irradiation respectively. Better results were also reported for bone- and chondrosarcomas. The reported local control rates are 54% for osteosarcomas and 49% for chondrosarcomas after neutron irradiation; the corresponding values are 21% and 33% respectively after photon irradiation. ...It can be concluded that fast neutrons are superior to photons for at least 10% of the radiotherapy patients. It is likely that the new high- energy hospital-based cyclotrons will further extend the indications of neutron therapy. However, patient selection remains one of the main problems and there is a need for development of individual predictive tests. Randomized Controlled Trial Review
Fetch PMID: 2405533
Fermilab

Midwest Institute for Neutron Therapy at Fermilab operated by Provena Saint Joseph Hospital, Elgin, Il

For information about referral or for further information

phone:
the Fermilab Neutron Therapy Facility staff
(630)840-3865, Monday through Friday, 8:30 A.M. to 5:00 P.M. CDT.

Fax : (630) 840-8766

or E-Mail: neutrons@fnal.gov

or write:
Midwest Institute for Neutron Therapy at Fermilab
P.O. Box 5004,
MS 301
Batavia, Il 60510-0500

Correspondence

Treatment with Fast Neutrons at the Midwest Institute for Neutron Therapy at Fermilab
Written by Bruce, July 2001

My mother was diagnosed with an LMS of the Inferior Vena Cava in January, 2001, and termed inoperable by MD Anderson within 6 months [after 3 different visits for tests and 1 other surgery in Florida.] She was accepted for treatment at the Fermilab in Elgin, Ill for her inoperable LMS of the IVC. Medicare approved the treatment for payment, also the staff were very helpful to get us through this process.

As of November 06, 2002 My mother is 14 months after Fermi. Scans are clear except for the expected "dead" mass per Fermi. Blood work is fine and the liver is clear. She is doing great, she is back in FL for the winter... it is along way from her surgeon & oncologist giving her 2-3months in January of 2001 after what became an exploratory surgery, and MDAnderson telling her she was inoperable in April of 2001.

[It is now late 2003, and Bruce's mom is still going strong. Ed.]

Prayers to you in your search.
Bruce


compiled by doctordee
updated November 2003


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