Technical note: A comparison of in-house 3D-printed and commercially available patient-specific skin collimators for use with electron beam therapy.

PURPOSE: Skin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient-specific skin collimation (in-house 3D printed and vendor-provided machined brass) using clinically relevant metrics. METHODS: Attenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials. RESULTS: Clinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation. CONCLUSION: Both skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in-house or outsource the fabrication to a vendor.

Sweeping-beam technique with electrons for large treatment areas as total skin irradiation : Dosimetric and technical aspects of a modified Stanford technique.

PURPOSE: Total skin electron beam therapy (TSEBT) is still a technical and therapeutic challenge today. Thus, we developed TSEBT using a sweeping-beam technique. METHODS: For treatment delivery, a linear accelerator Versa HD (ELEKTA, Stockholm, Sweden) with high-dose-rate electrons (HDRE) was used with a dose rate of 9000 MU/min. Dosimetry quality assurance was performed by multiple measurements with film dosimetry, 2D array, and Roos chamber. RESULTS: Clinical experience shows that treatment durations of 75 to 90 min are usual for the Stanford technique without using HDRE. With this new sweeping-beam irradiation technique, the total treatment time of a daily fraction could be reduced to 20 min while keeping over- and underdosing low. The treatment area is about 60 cmâ€¯× 200 cm and the dose distribution is uniform within 2% and 5% in vertical and horizontal directions, respectively. Initially, the electron energy of 6 MeV is reduced to 3.2 MeV by 1­cm polymethylmethacrylat (PMMA) scatter and the irradiation conditions of a source-surface distance (SSD) of 350 cm. The photon contamination drops to under 1%. CONCLUSION: These results show that the mean dose to total skin varies between 1.3 and 1.8 Gy. The sweeping-beam technique with electrons has a homogeneous dose distribution in connection with a short treatment time.

Short-term efficacy and safety of total skin electron beam therapy in mycosis fungoides: Systematic review and meta-analysis.

Total skin electron beam therapy (TSEBT) is one of the mainstays of treatment for mycosis fungoides. The most common modalities are standard dose (30-36 Gy) and low dose (10-12 Gy). To review the literature on the efficacy and safety profiles of standard dose and low dose TSEBT. We searched electronic databases for studies that enrolled patients with Mycosis Fungoides and treated with TSEBT. We estimated the event rates associated with low dose and standard dose TSEBT. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Main outcomes were complete response rate, partial response rate, mild and severe adverse events rate low dose TSEBT had a Complete Response Rate of 28% [0.19, 0.37], an Overall Response Rate of 85% [0.76, 0.93], a mild adverse events rate of 93% [0.82, 1.04] and a severe adverse events rate of 5% [-0.04; 0.14] Standard dose TSEBT had a Complete Response Rate of 57% [0.41; 0.73], the Overall Response Rate was 99% [0.97; 1.02], the mild adverse events rate was 100%, the severe adverse events rate was 7% [-0.01; 0.16]. Comparing standard dose TSEBT in the early versus advanced stages, advanced stages patients had a Risk Ratio = 0.77 in obtaining a Complete Response [0.64, 0.92](p = 0.0158). TSEBT is an associated with an excellent short term safety profile. Both schedules show high ORR, with standard dose TSEBT demonstrating highest CRR. Advanced stage of disease negatively influence the CRR.

Total skin electron beam therapy (TSEBT) in management of mycosis fungoides: A case series.

A retrospective review was conducted In Aga Khan University from January 2013-December 2020 for patients who received Total Skin Electron Beam Therapy (TSEBT) on the management of Mycosis Fungoides (MF). The clinical response rate and disease-free interval (DFI) was evaluated for three patients. All of the patients received a 3600 cGy dose of radiation. Clinical complete remission (cCR) was observed in two out of three patients, while one patient showed clinical partial response. Following the cCR to TSEBT, the DFI of the first patient with stage 1B lasted 30 months, while the second patient with stage IIB remained disease free for five months. TSEBT is an effective treatment for MF disease. It can thus be expected that patients with limited disease in the early stage can acquire a cCR with a longer DFI. The clinical outcomes of our study show concordance with the literature. The patients who had extensive (T3) skin involvement and had refractory diseases showed lower DFI with radiation.

Changes in total skin electron beam therapy modalities for mycosis fungoides: A single-centre study.

BACKGROUND: Mycosis fungoides (MF) is a highly radiosensitive disease. Total skin electron beam therapy (TSEBT) is an effective option that may allow prolonged response for several months. Recently, a low-dose regimen (12 Gy) has been reported more frequently, with less complete response than for standard doses (36 Gy) but better safety. Our aim was to compare patients treated with 12-Gy and 36-40-Gy TSEBT regimens at our centre for efficacy and safety. METHODS: This retrospective, monocentric study in Bordeaux University Hospital included all MF patients treated with 12-Gy or 36-40-Gy TSEBT between 2011 and 2020. RESULTS: Patients presented with MF at the following stages: 15 T2, including 9 folliculotropic MF; 2 T3, including 1 folliculotropic; 8 T4, including 2 Sézary syndromes. The mean follow-up time after TSEBT was 43.5 months [range: 2-128] for the 36-40-Gy group and 25.2 months [range: 4-45] for the 12-Gy group. The 3-month overall response rate (ORR) was similar for both groups (84.6% for 36-40 Gy and 91.7% for 12 Gy), but there was a tendency to more complete response in the 36-40-Gy group (30.8% vs 8.3%, P=0.35). Progression-free survival (PFS) tended to be better in the 36-40-Gy group than in the low-dose group (15.7 months vs 5.3 months; P=0.28). Patients treated with low-dose TSEBT had a lower incidence of radiation dermatitis (16.7% vs 38.4%, P=0.42). CONCLUSION: We confirm that TSEBT is an effective option, including at lower doses. Differences between low- and standard-dose regimens were not significant in our series. Although a low-dose regimen seemed to result in lower complete response and long-term efficacy rates in comparison with a standard dose, treatment at lower doses presents the advantage of repeatability, with fewer and weaker side effects, in the event of disease recurrence. Second-line treatments were mostly skin-directed in this group.

A prospective cohort study of condensed low-dose total skin electron beam therapy for mycosis fungoides: Reduction of disease burden and improvement in quality of life.

BACKGROUND: Low-dose total skin electron beam therapy (TSEBT) for mycosis fungoides is popular because of reduced toxicity with effective palliation. We condensed TSEBT, reducing visits by half and overall treatment length by one third. OBJECTIVE: To determine the efficacy and safety of a novel condensed low-dose TSEBT for mycosis fungoides. METHODS: We conducted a cohort study (2014-2018) with a median follow-up of 22.8 months. We delivered 12 Gy per 6 fractions with the modified Stanford technique, 3 fractions per week, with boosts to shadowed sites at risk between treatments, completing in 2 weeks. Primary outcomes included clinical response, duration of and time to response, and toxicity. Secondary outcomes included patient-reported quality of life (pain, pruritus, and Dermatology Life Quality Index) and physician-scored disease burden (body surface area involvement and Modified Skin Weighted Assessment Tool). RESULTS: Of 25 patients, stage IB was most common at the time of TSEBT (36%). The overall response rate was 88%. Most common was a near complete response (36%), and complete response was achieved in 6 (24%) patients. The median duration of response was 17.5 months (3.5-44.2), and the median time to response was 2 months (range, 0.9-4.1). No patients had toxicity of grade 3 or greater. QOL and disease burden showed significant benefit after TSEBT (P < .001). LIMITATIONS: Cohort study with limited sample size. CONCLUSIONS: Condensed, low-dose TSEBT has favorable outcomes and toxicity with logistical convenience.

Low dose total skin electron beam therapy for the management of T cell cutaneous lymphomas.

Mycosis fungoides (MF) represent the most common type of primary cutaneous lymphomas. Total skin electron beam (TSEB) therapy to a total skin administered dose of 36 Gy represents a very effective treatment regimen and its role in the management of MF is well established. Unfortunately, the issue in MF is that despite the proved effectiveness of radiation therapy, disease regress, and the main goal of TSEB treatment seems to be the prolongation of the overall response duration time. Taking into consideration the high radio-sensitivity of the disease, lower radiation doses have been tested with acceptable and comparable results. We prospectively analyzed low dose TSEB in 14 patients treated at ATTIKON University Hospital from 2011 to 2017. After a median duration of follow up time of 39 months we found that low dose TSEB is an effective treatment option, since therapeutic results are more than acceptable, with minimal toxicity. The fact that it can be repeated safely in the natural course of a "regressive" disease makes it more attractive than the standard full dose scheme of 36 Gy.

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center.

AIM: The aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT). BACKGROUND: Primary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative. MATERIALS AND METHODS: This is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality. RESULTS: Eight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (n = 5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12 Gy), 1 patient, the intermediate-dose RT scheme (24 Gy), and 2 patients, the conventional-dose RT scheme (36 Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6-8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months. CONCLUSION: This study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.

Low- vs. Middle-dose Total Skin Electron Beam Therapy for Mycosis Fungoides: An Efficiency-based Retrospective Survey of Skin Response.

Optimal doses of total skin electron beam therapy for mycosis fungoides remain to be established. Clinical efficiency and adverse effects of middle-dose (25 Gy) vs. low-dose (10-12 Gy) total skin electron beam therapy were retrospectively compared in a series of 14 and 12 mycosis fungoides, respectively. Overall skin response rate was 96.2% (92.9% middle-dose and 100% low-dose; not significant (NS)). Overall complete and partial skin response rates were 57.7% (42.9% middle-dose and 75% low-dose; NS) and 38.5% (50% middle-dose and 25% low-dose; NS), respectively. All responding patients relapsed after an overall median time of 5 months (7 months middle-dose vs. 4 months low-dose; p = 0.164, NS). Tolerance was equally fair in both groups, with only grade 1 and 2 adverse events observed in 100% vs. 66.7% of patients in middle-dose and low-dose groups (NS). Although no significant difference was observed, middle-dose protocol may be recommended owing to a longer relapse-free survival for a similar tolerance.

Heart-sparing radiotherapy with three-dimensional printing technology after mastectomy for patients with left breast cancer.

The purpose of this study was to analyze the effectiveness of electron beam therapy (EBT) with patient-tailored bolus (PTB) using three-dimensional printing technology to reduce heart and lung doses during post-mastectomy radiotherapy (PMRT). For 28 patients with left breast cancer, we designed customized virtual bolus for PMRT to compensate for surface irregularities on computed tomography images and developed optimized plans for EBT. As comparison between the PTB and tangential plans, the PTB plan reduced unnecessary exposure to heart and ipsilateral lung with better target coverage compared with the tangential technique.

T2 signal intensity as an imaging biomarker for patients with superficial Fibromatoses of the hands (Dupuytren's disease) and feet (Ledderhose disease) undergoing definitive electron beam irradiation.

OBJECTIVE: Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI. MATERIALS AND METHODS: The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7 years. Standard 6 MeV electron beam treatment included 3 Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1-5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain. RESULTS: Mean volume decreased from 1.5 to 1.2 cm3 (p = 0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p < 0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p < 0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p = 0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p = 0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ = -0.37 and 0.16, respectively). CONCLUSIONS: MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials.

BACKGROUND: Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with significant toxicity. OBJECTIVE: We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT. METHODS: Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit. RESULTS: In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible. LIMITATIONS: Conclusions are limited because of the small number of patients. CONCLUSIONS: Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.

Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome): part II. Prognosis, management, and future directions.

Both mycosis fungoides (MF) and Sézary syndrome (SS) have a chronic, relapsing course, with patients frequently undergoing multiple, consecutive therapies. Treatment is aimed at the clearance of skin disease, the minimization of recurrence, the prevention of disease progression, and the preservation of quality of life. Other important considerations are symptom severity, including pruritus and patient age/comorbidities. In general, for limited patch and plaque disease, patients have excellent prognosis on ≥1 topical formulations, including topical corticosteroids and nitrogen mustard, with widespread patch/plaque disease often requiring phototherapy. In refractory early stage MF, transformed MF, and folliculotropic MF, a combination of skin-directed therapy plus low-dose immunomodulators (eg, interferon or bexarotene) may be effective. Patients with advanced and erythrodermic MF/SS can have profound immunosuppression, with treatments targeting tumor cells aimed for immune reconstitution. Biologic agents or targeted therapies either alone or in combination--including immunomodulators and histone-deacetylase inhibitors--are tried first, with more immunosuppressive therapies, such as alemtuzumab or chemotherapy, being generally reserved for refractory or rapidly progressive disease or extensive lymph node and metastatic involvement. Recently, an increased understanding of the pathogenesis of MF and SS with identification of important molecular markers has led to the development of new targeted therapies that are currently being explored in clinical trials in advanced MF and SS.

Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults.

BACKGROUND: Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear. AIM: The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012. RESULTS: MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30-36 Gy delivered in 6-10 weeks. CONCLUSION: TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies.

Total skin electron beam (TSEB) therapy in pediatric patients: A review of the literature.

AIM: A literature review was undertaken to identify current TSEB therapy in pediatric patients. BACKGROUND: Total skin electron beam (TSEB) therapy is a method of irradiation with low energy electron beam dedicated to patients who have superficial skin lesions all over their body. Such skin malignancies are sparse among adults and even more uncommon with pediatric population. MATERIALS AND METHODS: In this study, all reported case reports were summed up with a special emphasis on techniques used, doses prescribed and special shielding of critical organs. Moreover, potential problems that were encountered during TSEB irradiation of very young patients were depicted. RESULTS: The literature has described only seven case reports of children undergoing TSEB therapy. Most of them were infants; however, two adolescents were also treated. For all infants, general anesthesia was provided to allow safe and accurate TSEB irradiation. The prescribed dose varied from 16 Gy to 28 Gy depending on the irradiation schedule and patient condition. Usually, boost fields were applied to the scalp and perineum. Typical shields for fingernails, toenails and lenses were usually used. CONCLUSION: This paper revealed that TSEB therapy may be considered as a palliative treatment for pediatric patients with leukemia cutis. However, its role is still unclear and should be further investigated.

Review of the results of the in vivo dosimetry during total skin electron beam therapy.

This work reviews results of in vivo dosimetry (IVD) for total skin electron beam (TSEB) therapy, focusing on new methods, data emerged within 2012. All quoted data are based on a careful review of the literature reporting IVD results for patients treated by means of TSEB therapy. Many of the reviewed papers refer mainly to now old studies and/or old guidelines and recommendations (by IAEA, AAPM and EORTC), because (due to intrinsic rareness of TSEB-treated pathologies) only a limited number of works and reports with a large set of numerical data and proper statistical analysis is up-to-day available in scientific literature. Nonetheless, a general summary of the results obtained by the now numerous IVD techniques available is reported; innovative devices and methods, together with areas of possible further and possibly multicenter investigations for TSEB therapies are highlighted.

Clinical results of the total skin electron irradiation of the mycosis fungoides in adults. Conventional fractionation and low dose schemes.

BACKGROUND: Mycosis fungoides (MF) is a rare skin condition, effectively treated by irradiation. Since 1951, different methods of total skin irradiation have been developed. Although dose-response effect has been demonstrated in many publications, controversies about low dose treatment still exist. AIM: The analysis of results of the total skin electron irradiation (TSEI), especially low dose TSEI in comparison with standard dose treatment is the subject of this review. Also, acute and late side effects of radiotherapy in MF are discussed. MATERIALS AND METHODS: Medline search and analysis of studies published between 1995 and 2012, containing key words: mycosis fungoides, standard dose TSEI, low dose TSEI, total skin electron beam therapy (TSEBT). RESULTS: Detailed analysis of relevant studies demonstrated that standard dose radiotherapy 30-36 Gy is the most effective treatment used in clinical practice. Objective response rate (ORR) is high, especially for less advanced stages of disease. Complete response rate (CR), although slightly lower, is still relatively high. For more advanced MF, TSEI serves as a very good method of palliative treatment and relief of symptoms, like pruritus, pain or desquamation. There is no consensus regarding low dose TSEI; the method is widely accepted as a palliative treatment or in case of reirradiation. CONCLUSIONS: Standard dose TSEI is an effective method of MF treatment for radical and palliative treatment, producing high rate of ORR and reasonably long time to progression (TTP). Acute and late side effect of treatment are mostly mild and easy to manage. Low dose TSEI is still in the phase of clinical studies.

Mycosis Fungoides Presenting With Multiple Tumors on the Face.

An 84-year-old female experienced progressive erythema on her limbs and chest over the past year. Initially managed with topical steroids, the erythema eventually spread throughout her body, forming erosions. A biopsy confirmed the diagnosis of mycosis fungoides (MF) (Stage IIB, T2bN0M0B0). Treatment with oral bexarotene (300 mg/day) and narrow-band UVB therapy showed limited improvement. Electron beam therapy (30 Gy in 10 fractions) applied to facial and plantar tumors resulted in a reduction of the tumors. This case highlights the treatment of tumors of MF on the face showing the effectiveness of combining electron beam therapy with bexarotene.

[Investigation of the Usefulness of Monte Carlo Simulation in Electron Beam Therapy Using Body Surface Lead Cutout].

PURPOSE: The purpose of this study was to understand the PDD and OAR during electron beam therapy using lead cutout on the body surface. METHODS: The Monte Carlo code PHITS version 3.24 was used to simulate PDD and OAR. The simulation results were compared with actual measurements using a silicon diode detector to evaluate the validity of the simulation results. RESULTS: The simulated PDD and OAR parameters of the linac agreed with the measured values within 2 mm. When the lead cutout on the body surface was used, all parameters except for R100 agreed with the measured values within 2 mm. The cutout sizes of the broad-beam square irradiation fields were 3 cm for 6 MeV, 5 cm for 12 MeV, and 8 cm for 18 MeV when the lead cutout on the body surface was used. CONCLUSION: The Monte Carlo simulation was useful for understanding the PDD and OAR of the lead cutout irradiation fields, which are difficult to measure.