Total Skin Electron Beam Radiation Research Articles

O-152 - Role of total skin electron beam radiotherapy at relapse after allogeneic transplant in mycosis fungoides and Sézary syndrome

O-152 - Role of total skin electron beam radiotherapy at relapse after allogeneic transplant in mycosis fungoides and Sézary syndrome

A CASE SERIES OF PATIENTS WITH CUTANEOUS T‐CELL LYMPHOMA TREATED WITH COMBINATION MOGAMULIZUMAB AND OTHER THERAPIES AFTER SINGLE AGENT MOGAMULIZUMAB

Introduction: Mogamulizumab (moga) is an anti-CCR4, monoclonal antibody approved as monotherapy for the treatment of relapsed/refractory mycosis fungoides (MF) and Sezary syndrome (SS). Combination therapies are frequently utilized in cutaneous T-cell lymphoma (CTCL), in part due to the variation in response across blood, nodal, and skin compartments. Little is known about moga in combination with other therapies. Methods: We conducted a single institution retrospective analysis of MF/SS patients who were treated with moga in combination with other systemic therapies, including peginterferon alpha-2a (IFNα), bexarotene, extracorporeal photopheresis (ECP), and oral methotrexate between March 2019 and March 2023. Baseline characteristics and clinical outcomes were recorded and summarized. Responses were assessed by Olsen staging criteria (Olsen et al., 2022). Results: We identified 9 patients treated with moga combination therapy at our institution (Table 1). Six of 7 patients transitioned from mono to combination therapy due to progressive disease or stable disease with uncontrolled symptom burden. Median time to next treatment was 157.5 days (range 42-330) for moga monotherapy. The best response observed in the 8 patients to single agent moga was classified as: 4 (50%) partial responses (PR), 3 (37.5%) stable disease (SD), and 1 (12.5%) progressive disease (PD). We identified a total of 7 different treatment combinations in our 9 patients (6 systemic therapies and 2 skin-directed), which included IFNα (n = 4), bexarotene (2), ECP (2), total skin electron beam radiation (TSEB) (2), narrow band ultraviolet-B therapy (NBUVB) (1), IFNα + ECP (2), and oral methotrexate (1). Multiple patients received more than one combination treatment. Among the combination therapies, the median time to next treatment was 137 days (range 24-224 days) with 2 out of 6 patients having ongoing responses to moga + IFNα +/- ECP. The patient with PR on moga + IFNα received 7 prior therapies. His skin involvement improved from T4 to T1 but significant disease in the blood persisted (B2). He continues moga + IFNα now 846 days later. Conclusions: Mogamulizumab has improved outcomes for MF/SS patients, but global complete responses are rare with the best responses seen in blood. In our series, the addition of IFNα provided clinical benefits to patients with SD or PD on single agent moga. One patient achieved a lengthy partial response despite persistent disease seen in peripheral blood samples. We speculate the combination of moga + IFNα may augment antibody-dependent cellular cytotoxicity thereby improving efficacy of moga. Additionally, combinatorial approaches may improve responses in skin, nodes, and viscera where lower responses are observed to single agent moga. Further investigations of moga combinations are needed. Keywords: Combination Therapies, Cutaneous non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Near complete responses to concurrent brentuximab vedotin and ultra-hypofractionated low-dose total skin electron beam radiation in advanced cutaneous T-cell lymphoma.

Patients with advanced stage mycosis fungoides (MF) or Sézary syndrome (SS) have a poor prognosis. Despite many available active single agents for CTCL treatment, high remission rates and long-lasting responses are rarely achieved in advanced CTCL [1]. Therefore, it is important to find more effective strategies, e.g. combination therapy, which could enhance efficacy by targeting key pathways in a synergistic or additive manner. We report on three patients with tumor stage MF (IIB) with fast response and very good partial remission due to induction with BV with 1.8 mg/kg dose concurrently in combination with ultra-hypofractionated low dose TSEBT.

Ther-O-06 - Near complete responses to concurrent brentuximab vedotin and ultra-hypofractionated low-dose total skin electron beam radiation in advanced CTCL

Ther-O-06 - Near complete responses to concurrent brentuximab vedotin and ultra-hypofractionated low-dose total skin electron beam radiation in advanced CTCL

Development of transparent eye shields for total skin electron beam radiotherapy.

PurposeFor total skin electron (TSE) beam radiation therapy, the anterior eye and conjunctiva can be protected with eye shields to prevent keratitis, xerophthalmia, and cataractogenesis. Conventional metal eye shields can reduce patient balance by obscuring vision and thus increasing the risk for falls. We report on the design, fabrication, and clinical use of transparent acrylic eye shields for TSE.MethodsThe primary design goals were a seven‐fold reduction in the dose to the anterior eye and conjunctiva to meet published dose‐recommendations, preservation of vision for the wearer, and biocompatibility for external use. Resembling thick swim goggles, the design features 23 mm thick acrylic lenses that are mounted in a 3‐D printed support structure that conforms to the eye socket and can be worn with a strap. Dose measurements were performed in a simulated Stanford‐technique treatment with an anthropomorphic phantom using Gafchromic EBT filmResultsThe transparent eye shields were manufactured using a 3D‐printer and CNC‐machine. Based on measurements from the simulated treatments for each of the eye shields, the eye shields provided a 12‐fold reduction in dose to the lens. After use in more than 200 fractions, the shields were well tolerated by patients, and there were no reports of any incidents or adverse events.ConclusionTransparent TSE eye shields are able to reduce the dose to the eyes while maintaining vision during treatment at a reasonable cost.

Phase 1 Study of CD37-Directed CAR T Cells in Patients with Relapsed or Refractory CD37+ Hematologic Malignancies

Phase 1 Study of CD37-Directed CAR T Cells in Patients with Relapsed or Refractory CD37+ Hematologic Malignancies

Treatment Patterns and Clinical Outcomes of Patients with Sézary Syndrome at Emory University

Introduction Sézary syndrome (SS) is an aggressive, leukemic subtype of cutaneous T-cell lymphoma (CTCL) with a median survival of 3-5 years. Approved therapies include skin-directed therapy, radiation, and systemic therapies such as chemotherapy, histone deacetylase (HDAC) inhibitors, interferon, extracorporeal photopheresis (ECP), and oral retinoids. There is no consensus first-line therapy for SS and there is limited data regarding prognostic biomarkers. We assessed treatment patterns, outcomes, and racial differences at our institution. Methods We performed a retrospective review of 62 patients at Winship Cancer Institute of Emory University from 1990-2020 with a confirmed diagnosis of SS. Clinical data collected from the electronic medical record included demographics, baseline laboratory values, disease characteristics, and therapy. Clinical outcomes were measured by overall survival (OS) and time to next treatment (TTNT). OS was measured from time of diagnosis to date of death or last follow-up. TTNT was defined as the number of months from the start of the first line of therapy until the initiation of the subsequent therapeutic regimen. Descriptive analysis was performed for each variable and a comparison between African American (AA) and white patients was performed using ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS and TTNT were generated for the whole cohort. A Kaplan-Meier curve was also generated to compare time from diagnosis to initiation of first systemic therapy stratified by race along with the log-rank p-value. The univariate association of baseline variables with OS and TTNT was assessed by Cox proportional hazards models and the multivariable analyses (MVA) were performed on variables that had p-value less than 0.05 on univariate analyses. Results Males made up (58.1%) of our patients and the median age at diagnosis was 65.9 years. Nearly one-half (45.2%) of patients were AA. The median Sézary count at diagnosis was 1320 cells/uL. The median time from diagnosis to first systemic therapy was 2.4 months and the median number of systemic therapies was 3.0. Information regarding systemic treatments received after diagnosis is presented inTable 1. The most common first-line systemic therapies were oral retinoids (43.5%), ECP (32.3%), and interferon (30.6%). HDAC inhibitors and total skin electron beam (TSEB) radiation were common treatments beyond first line (46.8% received HDAC inhibitors, 38.7% received TSEB), but were rarely used in the first-line setting. The median OS and TTNT were 3.1 years and 6.3 months, respectively(Figure 1). In MVA, elevated WBC and LDH were significantly associated with shorter OS (WBC HR: 1.05, 95% CI: 1.01-1.08, p=0.01; LDH HR: 1.003, 95% CI: 1.001-1.005, p=0.011) and shorter TTNT (WBC HR: 1.04, 95% CI: 1.002-1.08, p=0.041; LDH HR: 1.002, 95% CI: 1.001-1.004, p=0.048). In analysis by race, AA patients had a higher proportion of females compared to non-hispanic white patients (53.6% vs 28.1%, p=0.045). AA patients also had lower median hemoglobin at diagnosis (12.6 vs 14.3, p=0.036), higher median LDH at diagnosis (360 vs 232, p=0.002), and longer median time from diagnosis to first systemic therapy compared to non-hispanic white patients (3.17 months vs 2.14 months, p=0.039,Figure 2). Conclusions SS is an aggressive subtype of CTCL with no consensus first-line therapy and limited data on prognostic biomarkers. In our cohort, oral retinoids, ECP, and interferon were the most commonly utilized treatments in the first-line setting. Elevated WBC and LDH were significantly associated with both OS and TTNT which suggests that these may have value as prognostic biomarkers in SS. AA patients may have delayed time from diagnosis to starting systemic therapy and higher LDH at diagnosis. This data is hypothesis-generating and should be validated in larger, prospective studies. Disclosures Allen: Bayer:Consultancy, Other;Imbrium:Consultancy, Other;Research to Practice:Speakers Bureau;Clinical Care Options:Speakers Bureau;Curio Sciences:Honoraria.

Low-dose total skin electron beam therapy for refractory cutaneous CD30 positive lymphoproliferative disorders

We describe a case of a 48-year-old woman with a refractory cutaneous CD30 positive lymphoproliferative disorder treated successfully with total skin electron beam radiotherapy (TSEBT).

Dosimetric evaluation and comparation of TL responses of LiF:Mg,Ti and μLiF:Mg,Ti in the clinical electron beams dosimetry applied to total skin irradiation (TSEB) treatments

The Total Skin Electron Beam (TSEB) irradiation is a radiotherapeutic technique that aims to provide the patient's skin surface with a more homogeneous dose, in order to treat cutaneous T-cell lymphomas, both for curative and palliative purposes. Electron irradiation penetrates a few millimeters into the skin, reaching the affected parts completely, without penetrating the internal organs. In vivo dosimetry has become an important role for the treatment of total skin irradiation within a rigorous quality assurance program that should be an integral part of the radiotherapy departments. The use of TLDs in vivo can identify variations in the prescribed dose because its measurement accuracy and great precision. The LiF:Mg,Ti is the most used TL material and widely studied in radiotherapy dosimetry due to near tissue-equivalence of the material, along with its overall reliability. The dosimeters of μLiF:Mg,Ti have been gaining considerable importance in the radiotherapy departments. These detectors allow measurements in vivo with great advantages due to their minimum dimensions of 1 × 1 × 1 mm3. This paper reports a comparative study of the TL responses of both materials to dose evaluation in TSEB treatments. The TL response of both materials in several TSEB parameter tests and in clinical application were evaluated, analyzing the dose distribution in a treatment simulation using AldersonRando anthropomorphic phantom. The results showed that the μLiF:Mg,Ti presented greater variation of the response in relation to LiF dosemeters in some parameters analyzed, due to the small dimensions and to evaluate doses absorbed in the surface over a large area in the treatment plan.

Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides

Background and purposeA lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT). Methods and materialsWe identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort. Results71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395–0.290, p < 0.001). ConclusionPeripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation.

Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202)

Introduction: Natural Killer cells (NK cells) play an important role in tumor immune-surveillance. NK-mediated cell killing can occur through distinct mechanisms: (1) by activating the receptor NKG2D and natural cytotoxicity receptors (NCR), and (2) through the potent activating receptor CD16 (FcγRIII) which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). Therapeutic strategies to harness the ability of NK cells to induce an ADCC response are emerging. AFM13 is a CD30/CD16A targeting high affinity bispecific tetravalent antibody that engages and activates NK cells. This study evaluates the ability of AFM13 to engage innate immunity through specific activation and recruitment of NK cells to tumors expressing CD30 and the impact of these effects on clinical outcome. In addition, it examines the immunologic changes in the tumor and peripheral blood as a function of the dose and method of administration of AFM13 over time.Methods: Subjects with relapsed or refractory CD30 expressing lymphoma with cutaneous involvement were recruited into 3 treatment cohorts: (1) 1.5 mg/kg IV weekly, (2) 7 mg/kg IV weekly and (3) 7 mg/kg continuous intravenous infusion (CIVI) over 5 days weekly. Each cohort consisted of 3 patients. Subjects received 8 weeks of therapy each cycle. Response assessment was performed on week 11 of each cycle by mSWAT, photography, PET imaging and peripheral blood flowcytometry. A second cycle was administered if there was no progression of disease. Subjects underwent mandatory tumor biopsies and peripheral blood immunologic studies during the first cycle of therapy as follows: pretreatment, day 5 post first dose, week 4 and week 8 of therapy. An optional biopsy was also collected at end of study. Tumor biopsies were analyzed and evaluated by a pathologist and IHC image analyzer to characterize immune cell subpopulations. Peripheral blood samples were analyzed by flowcytometry.Results: Nine subjects were accrued. Their age ranged from 37-79 years, 3 of 9 where white and 6 of 9 were men. The median number of prior therapies was 4 (1-11), 2 patients had progressed on Brentuximab vedotin, and 5 patients received total skin electron beam radiotherapy. The disease etiologies were as follows: 4 patients with transformed mycosis fungoides, 2 patients with systemic anaplastic large cell lymphoma-ALK negative, 2 patients with non- transformed mycosis fungoides and 1 patient with cutaneous anaplastic large cell lymphoma.Among the 8 subjects who were evaluable for response 4 of 8 (50%) achieved an objective response rate (ORR). In cohort 1 we observed 1 complete response (CR), 1 partial response (PR) and 1 stable disease (SD). In cohort 2, we observed 3 SD. In cohort 3, we observed 2 PRs and one subject awaiting disease assessment. Infusion related reaction (IRR) were observed in 4 of 9 subjects and managed conservatively. Cellulitis was noted in 3 subjects of which 2 developed bacteremia requiring intravenous antibiotics, and was not considered related to AFM13 treatment. There were no other treatment-emergent adverse events.In the peripheral blood, we observed a decrease in circulating NK cells during therapy (Weeks 1- 8) with post therapy recovery (by week 11) by following cells that were CD56+ CD3- , CD56+ CD16+ and NKp46+ by Flow Cytometry. We observed an increase over time in the expression of the activation marker CD69 on NK cells from responders compared to non-responders. Similarly, tumor biopsies in responders showed increased infiltration of CD56+ NK cells as opposed to non-responders. Flow quantitation of circulating CD4+ CD25+ T cells (Tregs) shows a decrease in responders vs. non-responders.Conclusions: AFM13 demonstrated a high ORR of 50 % among a population of heavily pretreated patients with a CD30 positive lymphoproliferative T-cell malignancy. AFM 13 exhibited activity post Brentuximab vedotin failure. In addition, biological changes in NK cells may predict response. This data are the first to demonstrate the therapeutic advantages of this bispecific, and the first to correlate changes in NK cells as a function of dose and schedule. AFM13 is able to engage the innate immune system through a specific activation and recruitment of circulating NK cells to tumors expressing CD30. This immunological tumor response may correlate with clinical response. We have begun to expand the patient cohorts, and pursue additional comprehensive correlative studies in this population. DisclosuresRodig:KITE: Research Funding; Bristol Myers Squibb: Research Funding; Affimed: Research Funding; Merck: Research Funding. O'Connor:Seattle Genetics: Research Funding; ADC Therapeutics: Research Funding; Celgene: Research Funding.

Evaluation of Maintenance Therapy in Cutaneous T-Cell Lymphoma Patients Receiving Total Skin Electron Beam Radiation Therapy

Introduction: Total skin electron beam (TSEB) therapy is a well-established treatment modality for patients suffering from cutaneous T-cell lymphoma (CTCL). It is often augmented with maintenance therapy, including skin directed and systemic therapies. However, the utility of maintenance therapy remains controversial. We performed a retrospective analysis in patients with CTCL to assess whether maintenance therapy following TSEB improved outcomes.Methods: We conducted a single center retrospective analysis at the Winship Cancer Center of Emory University analyzing CTCL patients who received TSEB from 1998 - 2018. Patients who received TSEB were selected from an existing cutaneous lymphoma database, and cross referenced with a list of patients obtained from the Emory Cancer registry through the Lymphoid Malignancies Enterprise Architecture Database (LEAD) under an IRB-approved protocol. Consent was waived due to the retrospective nature of the project. The primary objective was to assess progression free survival in patients who received maintenance therapy following TSEB (PFS-TSEB) compared to those who did not. Maintenance therapy was defined as therapy started either concurrently or within 1 month of the initiation of TSEB. Secondary objectives were to assess overall survival following TSEB (OS-TSEB), and OS following diagnosis (OS). Additionally, we evaluated patient demographics, number of treatments, and time to TSEB from diagnosis. Equality of variances between groups was assessed with F-test. Numerical variables were analyzed with unpaired two-tailed t-tests or Welch's t-test and categorical variables were analyzed with chi-squared tests.Results: 101 patients with a median age of diagnosis of 55 years (range 10 - 89, 95% CI 52 - 58) underwent TSEB. 52% of patients were male, 48% female; 50% were black, 46% white/Hispanic, 65 % had MF, 16% SS, 16% CTCL NOS, 1% CD30+ CTCL, and 2% other. At diagnosis, 33% were stage 1, 39% stage 2, 10% stage 3, and 18% stage 4.48% of patients received maintenance treatment and 52% did not; 36% of maintenance was given concurrently with TSEB, 34% after, and 30% unknown. The most common maintenance therapies were bexarotene (29%), interferon (23%), and PUVA (15%). From diagnosis, median time to first treatment was 48 days (IQR 11 - 152), time to TSEB was 429 days (IQR 136 - 1225), and median time to first treatment after TSEB was 51 days (IQR 18 - 115). A median of 2 therapies were received prior to TSEB (IQR 1 - 4; 1 skin-directed, 1 systemic, 0 RT). A median of 2 therapies occurred following TSEB (IQR 0 - 4.5; 0 skin-directed, 1 systemic, 0 RT). The most common skin directed and systemic treatments overall were topical steroids (pre, post-TSEB), PUVA (pre-TSEB), and retinoids (post-TSEB).Overall, 80% of patients progressed after TSEB with a median time to progression of 118 days (IQR 36.5 - 231.5). OS-TSEB and OS were 642.5 d (IQR 248 - 1587.5) and 1523 (IQR 785 - 2698), respectively, with 46% of patients alive and 54% dead. In comparing outcomes of maintenance to no maintenance, PFS-TSEB was 171 days (IQR 30.25 - 333.75) versus 66.5 days (IQR 30 - 178.75) (Welch's t-test, P = .067), OS-TSEB was 1135 days (IQR 476.5 - 1845.5) versus 433.5 (IQR 219 - 1309.75) (t-test, P = .046), and OS was 1871 (IQR 961 - 2698) versus 1329.5 days (IQR 676.5 - 2830.75) (t-test, P = 0.74), respectively. We found no difference in gender, race, diagnosis, stage, or age at diagnosis between maintenance and no maintenance groups. However, in comparing maintenance to no maintenance, time to initiate TSEB from diagnosis was shorter in the maintenance group (322 days [109.5 - 772] versus 456 days [IQR 152 - 1784]) (t-test, P = 0.041). Median total number of treatments was 8 (IQR 4 - 10) versus 5 (IQR 3-9) (t-test, P = 0.052), respectively.Conclusion:We defined demographics, diagnoses, stage, treatment number, treatment type, and outcomes in a cohort of CTCL patients undergoing TSEB. Patients receiving maintenance therapy had an increase in overall survival and a trend towards an increase in progression-free survival measured after TSEB. A possible limitation to these findings is that patients receiving maintenance therapy in our cohort received TSEB earlier than those without maintenance, with a trend towards more overall treatments. Our retrospective findings suggest a benefit of maintenance therapy in CTCL following TSEB and provide a basis for initiating prospective studies to further evaluate this approach. DisclosuresFlowers:Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Research Funding; Gilead: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech/Roche: Consultancy; BeiGene: Research Funding; Janssen Pharmaceutical: Research Funding; Pharmacyclics/ Janssen: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Abbvie: Research Funding; Genentech/Roche: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Celgene: Research Funding; Denovo Biopharma: Consultancy; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy.

Identifying intratumor heterogeneity in mycosis fungoides using high throughput DNA sequencing

The current model of the pathogenesis of mycosis fungoides (MF) relies on the assumption that the entire population of malignant cells develops from a single, mature lymphocyte residing in the skin. It was proposed that in most, if not all, cases this cell of origin is the skin resident memory T-cell. The ‘mature T-cell precursor’ model implies that MF is monoclonal rather than heterogeneous, and evolves in a linear fashion by stepwise progression from early (patch, plaque) to late (tumor) stages. In spite of its wide acceptance, the mature T-cell precursor model cannot easily explain why MF emerges simultaneously in many different areas of the skin rather than as a single skin lesion. Moreover, complete cures cannot be achieved even when total eradication of skin lymphocytes is accomplished, e.g. by total skin electron beam radiation and relapses occur in multiple skin regions, not necessarily within the areas previously affected. In this project we would like to test an alternative hypothesis, which assumes heterogeneity rather than homogeneity of this neoplasm. We wished to experimentally verify this hypothesis by examining clonal and subclonal heterogeneity of malignant cells in MF obtained by microdissection from 10 biopsies from MF plaques and tumors. Whole exome sequencing was performed using probe capture and Illumina sequencing and clonal hierarchy trees were constructed using bioinformatics pipelines for lineage tracing based on frequency distribution of point mutations and copy number aberrations. Surprisingly, both early and more advanced lesions (plaques and tumors, respectively) exhibited significant subclonal heterogeneity with only a small number of clonal mutations. These preliminary results suggest an early bifurcation step in the evolution tumors and plaques, contradicting the currently prevalent linear progression hypothesis.

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution.

PurposeWe aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes.Materials and MethodsTotal 19 patients confirmed with MF between 1999–2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed.ResultsEleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT.ConclusionBoth IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Comparative study of the TL response of LiF:Mg,Ti and CaSO4:Dy in the clinical electron beams dosimetry applied to total skin irradiation (TSEB) treatments

The commissioning and quality assurance The Total Skin Electron Beam (TSEB) irradiation treatment is based on the AAPM's report 23, which describes the six-dual-field (Standford) technique, and the Hospital Israelita Albert Einstein (HIAE) follows this recommended guidance. The Dosimetric Materials Laboratory of the Instituto de Pesquisas Energéticas e Nucleares (IPEN-LMD) has tradition in research related to thermoluminescent materials and its clinical applications. Thus, aiming to apply the LiF:Mg,Ti, the most common TLD material, and CaSO4:Dy + Teflon produced at IPEN as easy-to-use alternatives to electron beams dosimetry and its parameters applied to TSEB, this paper reports a comparative study of the TL responses of both materials to dose evaluation in TSEB treatments. The TL response of both materials was evaluated in several TSEB parameter tests such as clinical field homogeneity, Monitor Units (MU) calculation, absorbed doses over the reference line and throughout the surface of the skin in a treatment simulation using AldersonRando anthropomorphic phantom. Results show that the field homogeneity measurements remained within ± 8% acceptance limit from AAPM Report 23, little to no energy dependency over the range of 4 o 9 MeV electron beams and, for clinical measurements and MU calculations, both TLDs present compatible results and can be used as alternative tools in TSEB dosimetry.

Dosimetric evaluation employing TL and OSL techniques with different luminescent materials for clinical evaluation of extremity doses using electron beams applied to Total-Irradiation-of-Skin treatments

Total-skin electron beam (TSEB) irradiation is used to deliver a homogeneous dose distribution over the entire skin surface of a patient. TSEB dosimetry is quite complex as to the evaluation and measurement of absorbed dosage in the cutaneous region. This paper evaluates the performance of different dosimetric materials, using TL and OSL dosimetry, in the extremity-dose assessment of TSEB treatments using the six-dual-field technique and an anthropomorphic phantom. Dosimeters were selected with repeatability better than [Formula: see text] and calibrated to 6-MeV electron-beam dosimetry. Measurements were conducted in the abdominal region as a reference point and on the extremities. Results show expected deviations ranging up to [Formula: see text] in the dose received in the extremities and good results in dose assessment using all dosimetric materials tested.

Ringed telangiectasias: an unusual presentation of telangiectasia macularis eruptiva perstans

Telangiectasia macularis eruptiva perstans (TMEP) is a rare form of cutaneous mastocytosis. While most cutaneous mastocytoses occur in children and are asymptomatic, TMEP occurs predominantly in adults and is associated...

Circulating CD4:CD8 Ratio is Prognosticator of Response to Total Skin Electron Beam Radiation in Mycoses Fungoides

A lower proportion of CD8+ tumor infiltrating lymphocytes in mycoses fungoides (MF) patients is associated with poorer survival. However, whether circulating lymphocyte subsets, as reflected by circulating CD4:CD8 ratio, is a prognostic factor for radiotherapy response is not known. We hypothesized CD4:CD8 ratio is prognostic of outcomes in MF patients treated with total skin electron beam therapy (TSEBT) and performed multi-institutional retrospective analysis. We retrospectively examined 124 MF patients from MD Anderson Cancer Center (MDACC) and Yale Cancer Center (YCC) treated with TSEBT from 2001-2014. Circulating CD4:CD8 ratio (103/μL) was based on serum analysis obtained before TSEBT. TSEBT was delivered with 9mEV electrons from low (12 Gy) to conventional (≥12 Gy) doses. Cutaneous clinical treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) and mSWAT decrease of <75% was considered as having a partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in discovery cohort. Multivariate logistic regression examined the association between CD4:CD8 and TSEBT response. 71.8% and 28.2% of all patients achieved CR and PR to TSEBT, respectively. Higher CD4:CD8 ratio predicted poorer response: Median CD4:CD8 in patients with PR was 4.59 (interquartile range: 2.50-4.59) vs. 1.95 (1.10-3.09) in patients with CR (p=0.002). A threshold CD4:CD8 value of 4.4 optimally discriminated patients with CR vs. PR (sensitivity 90% specificity 59% AUC =0.71; P=0.002). 34.5% of patients with CD4:CD8 ≥4.4 (n=29), achieved CR compared to 83.2% of patients with CD4:CD8 < 4.4 (n=95). Among patients with low CD4:CD8 <4.4 (n=73), 74% achieved CR with low dose TSEB vs. 93% with conventional dose TSEB (Chi-square P=0.02); (Breslow Day P=0.26 for the modifying effect of CD4:CD8 on TSEB dose). After adjusting for baseline mSWAT, stage, and TSEB dose, CD4:CD8 remained a significant predictor of TSEB response (OR=0.113, 95% CI 0.04-0.31, p<0.001 for low vs. high CD4:CD8). For MF patients treated with TSEBT, CD4:CD8 ratio was an important prognostic factor of TSEBT treatment response at two high-volume academic centers. The potential for CD4:CD8 ratio’s modifying effect on the efficacy of low- vs. conventional-dose TSEBT warrants further investigation as a possible biomarker to inform radiation treatment decisions.

The Results of Low-Dose Total Skin Electron Beam Radiation Therapy (TSEB) in Patients With Mycosis Fungoides From the UK Cutaneous Lymphoma Group

Total skin electron beam radiation therapy (TSEB) is a very effective treatment of mycosis fungoides. Following reports of similar durations of response to lower doses of TSEB, a low-dose schedule of TSEB was introduced in the United Kingdom. A protocol of 12Gy in 8 fractions over a period of 2weeks was agreed on by use of the Stanford University technique.Data were collected prospectively, and the results were analyzed according to the European Organisation for Research and Treatment of Cancer-International Society for Cutaneous Lymphomas endpoints (EORTC-ISCL). Toxicity was scored according to CTCAE v4.0 (Common Terminology Criteria for Adverse Events version 4.0). One hundred three patients received treatment, with a median follow-up period of 20.6months (range, 3.3-53months). Of these patients, 54 had stage IB disease, 33 had stage IIB, 12 had stage III, and 4 had stage IV. The median age was 68years (range, 26-91years). The complete response rate was 18%, the partial response rate was 69%, stable disease was present in 8%, and progression on treatment was found in 5%. In the patients who had a complete response, the median time to relapse was 7.3months. The median response duration was 11.8months. Median progression-free survival for all patients was 13.2months. It was significantly longer, at 26.5months, in patients with stage IB disease compared with 11.3months in patients with stage IIB (P=.003; hazard ratio, 2.66) and 10.2months in patients with stage III (P=.002; hazard ratio, 4.62).The treatment was well tolerated with lower toxicity than higher-dose schedules. The low-dose TSEB schedule of 12Gy in 8 fractions over a period of 2weeks is well tolerated and is an effective option for patients with mycosis fungoides.

Recommendations for treatment in folliculotropic mycosis fungoides: report of the Dutch Cutaneous Lymphoma Group.

Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished indolent (early-stage FMF) and more aggressive (advanced-stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined. To evaluate initial treatment results in patients with early- and advanced-stage FMF. A study was undertaken of 203 patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF) included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR); sustained complete remission; partial remission (PR), > 50% improvement; and overall response (OR; CR + PR). Patients with early-stage FMF were treated with nonaggressive SDTs in 67 of 84 cases resulting, respectively, in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for ultraviolet B (UVB), and 30% and 88% for psoralen plus ultraviolet A (PUVA). In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR 100%), total skin electron beam irradiation (CR 59%; OR 100%) and PUVA combined with local radiotherapy (CR 5%, OR 75%) were most effective. The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis.