Neutron Radiation Therapy for Treatment of Refractory Merkel Cell Carcinoma

Macomber, Meghan W.; Tarabadkar, Erica S.; Mayr, Nina A.; Laramore, George E.; Bhatia, Shailender; Tseng, Yolanda D.; Liao, Jay J.; Arbuckle, Tom; Nghiem, Paul; Parvathaneni, Upendra

doi:10.14338/ijpt-17-00003.1

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…At the University of Washington (UW), we continue to find fast neutron therapy clinically more useful and effective in the treatment of patients at high risk for local recurrences in both curative and palliative settings (Laramore et al 1989a, 1989b, Douglas et al 1999, Schwartz et al 2001, Liao et al 2014, Davis et al 2016. Macomber et al (2017) recently reported an especially striking example of the use of fast neutron therapy in the treatment of recurrent Merkel cell carcinoma (MCC). After the disease progressed through three courses of photon and electron treatments (total dose of up to 91.2 Gy in equivalent 2 Gy fractions to the scalp), the patient had a complete clinical and radiologic response two months after a neutron treatment of 18 Gy in 12 daily fractions.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric characteristics of the University of Washington Clinical Neutron Therapy System

et al. 2018

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The University of Washington (UW) Clinical Neutron Therapy System (CNTS), which generates high linear energy transfer fast neutrons through interactions of 50.5 MeV protons incident on a Be target, has depth-dose characteristics similar to 6 MV x-rays. In contrast to the fixed beam angles and primitive blocking used in early clinical trials of neutron therapy, the CNTS has a gantry with a full 360° of rotation, internal wedges, and a multi-leaf collimator (MLC). Since October of 1984, over 3178 patients have received conformal neutron therapy treatments using the UW CNTS. In this work, the physical and dosimetric characteristics of the CNTS are documented through comparisons of measurements and Monte Carlo simulations. A high resolution computed tomography scan of the model 17 ionization chamber (IC-17) has also been used to improve the accuracy of simulations of the absolute calibration geometry. The response of the IC-17 approximates well the kinetic energy released per unit mass (KERMA) in water for neutrons and photons for energies from a few tens of keV up to about 20 MeV. Above 20 MeV, the simulated model 17 ion chamber response is 20%-30% higher than the neutron KERMA in water. For CNTS neutrons, simulated on- and off-axis output factors in water match measured values within ~2% ± 2% for rectangular and irregularly shaped field with equivalent square areas ranging in a side dimension from 2.8 cm to 30.7 cm. Wedge factors vary by less than 1.9% of the measured dose in water for clinically relevant field sizes. Simulated tissue maximum ratios in water match measured values within 3.3% at depths up to 20 cm. Although the absorbed dose for water and adipose tissue are within 2% at a depth of 1.7 cm, the absorbed dose in muscle and bone can be as much as 12 to 40% lower than the absorbed dose in water. The reported studies are significant from a historical perspective and as additional validation of a new tool for patient quality assurance and as an aid in ongoing efforts to clinically implement advanced treatment techniques, such as intensity modulated neutron therapy, at the UW.

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Section: Introductionmentioning

confidence: 99%

Dosimetric characteristics of the University of Washington Clinical Neutron Therapy System

et al. 2018

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“…As reported in Macomber et al [18], a 78-year-old white male with no history of immunosuppression had recurrent MCC disease following intralesional and systemic anti-PD1 immunotherapy (pembrolizumab) with disease progression inside and outside prior low LET radiation therapy fields. The patient was treated with definitive doses of fractionated NRT for the fungating gross disease on the central scalp to a total dose of 18 Gy neutron in 12 fractions (1.5 Gy per day, 4 days per week), the bilateral parotid/cervical lymph nodal disease (18 Gy neutron in 10 fractions), and frontal scalp lesions (16 Gy neutrons in 8 fractions).…”

Section: Patient B: Update On Patient With Progression On Anti-pd1 Immentioning

confidence: 61%

“…The exact underlying mechanism(s) and triggers to reproducibly generate this effect remain to be elucidated. To gain insight into the clinical significance of short-course NRT as it relates to in-field and out-of-field organ at risk (OAR) toxicity, updated dosimetry and clinical observations for a previously reported patient case by Macomber et al [18] is also presented (patient B). This case series illustrates the use of NRT in combination with immunotherapy to achieve potentially durable clinical responses in patients who had exhausted other treatment options.…”

Section: Introductionmentioning

confidence: 99%

Does Neutron Radiation Therapy Potentiate an Immune Response to Merkel Cell Carcinoma?

Schaub

Stewart

Sandison

et al. 2018

International Journal of Particle Therapy

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Background: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. In the advanced setting, MCC is often treated with immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies. X-ray radiation therapy (XRT) is commonly used for palliation. There is an unmet need for new treatment options in patients progressing on immunotherapy and XRT. We present 2 patients with progressive MCC who were successfully treated with high linear energy transfer neutron radiation therapy (NRT). Clinical Observations: Patient A, an 85-year-old white male with chronic lymphocytic leukemia had progressive MCC with multiple tumors on the face despite prior XRT and ongoing treatment with pembrolizumab. The 5 most symptomatic lesions were treated with a short course of NRT (2 3 3 Gy) while continuing pembrolizumab. All irradiated facial lesions demonstrated a complete response 2 weeks after NRT. Remarkably, an additional 4 lesions located outside the NRT fields also completely resolved. Patient B, a 78-year-old white male with no immunosuppressive condition had recurrent MCC in the scalp and bilateral cervical nodes. The painful, ulcerative tumors on his scalp were progressing despite multiple courses of XRT and multiple immunotherapy regimens, including pembrolizumab. He was treated with NRT (16-18 Gy) to the scalp and had a complete response with successful palliation. While his disease subsequently progressed outside the NRT fields, the response to NRT bridged him to receive further investigational immunotherapies, and he remains disease free 3 years later. Conclusion: Short courses of high linear energy transfer particle therapy deserve consideration as a promising modality for local tumor control in XRT refractory tumors. The out-of-field response suggests that NRT has potential for synergizing with immunotherapy. While more data are required to identify optimal NRT parameters, the NRT dose that potentiates an antitumor immune response appears to be well below organ-at-risk tolerance.

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“…Macomber et al [82] applied FNT for refractory cutaneous Merkel cell carcinoma in a patient with a previous treatment failure; LC was achieved with 18 Gy in 12 fractions and lasted for 2 years. Schaub et al [83] presented 2 promising observations of Merkel cell carcinoma treated with FNT, noting a potential relationship between high-LET neutron beam irradiation and elevated immune response.…”

Section: Clinical Experiencementioning

confidence: 99%

Fast and Furious: Fast Neutron Therapy in Cancer Treatment

Гордон

Гулидов

Fatkhudinov

et al. 2022

International Journal of Particle Therapy

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Fast neutron therapy has been used for decades. In conjunction with recent advances in photonic techniques, fast neutrons are no longer of much oncologic interest, which is not unequivocally positive, given their undoubted therapeutic value. This mini-review recalls the history of medical research on fast neutrons, considers their physical and radiobiological properties alongside their benefits for cancer treatment, and discusses their place in modern radiation oncology.

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Neutron Radiation Therapy for Treatment of Refractory Merkel Cell Carcinoma

Cited by 9 publications

References 21 publications

Dosimetric characteristics of the University of Washington Clinical Neutron Therapy System

Dosimetric characteristics of the University of Washington Clinical Neutron Therapy System

Does Neutron Radiation Therapy Potentiate an Immune Response to Merkel Cell Carcinoma?

Fast and Furious: Fast Neutron Therapy in Cancer Treatment

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