Hypofractionated Low-Dose Total Skin Electron Beam Therapy for Primary Cutaneous T-Cell Lymphoma: Analysis of Efficacy and Toxicity

Introduction Cutaneous T-cell lymphoma (CTCL) is a rare form of lymphoma that is characterized by the localization of malignant cells to the skin. While considerable advances have been made in both the diagnosis and treatment of this disease, management and long-term disease control continue to be significant challenges. In particular, total skin electron beam therapy (TSEBT)-a technique that allows for homogenous irradiation of the entire skin-has proved to be efficacious for palliatively treating CTCL (Heumann TR et al IJROBP 2015), but a large proportion of patients continue to relapse over time with a limited possibility of retreatment due to skin toxicity (Wilson LD et al J Am Acad Dermatol 1996; Becker M et al IJROBP 1995). Recently, low-dose TSEBT to ~12 Gy has largely replaced traditional TSEBT to ~36 Gy for the palliative treatment of CTCL due to similar high response rate with less toxicity and more room to re-treat as necessary (Hoppe et al J Am Acad Dermatol 2015). However, there is little consensus on the optimal fractionation and dose per fraction (i.e. number of total treatments needed to deliver 12 Gy). At our institution, we have implemented a novel condensed hypofractionated scheme for low-dose TSEBT, where instead of giving ½ cycle (3 positions) per fraction, we give a full cycle (all 6 positions) per fraction, leading to half as many treatments (6 instead of 12) for the same total dose (12 Gy). We hypothesize that condensed low-dose TSEBT given in 6 fractions, compared to 12, will have similar toxicity and efficacy with the additional convenience of half as many treatments. Methods We conducted a single-institution retrospective review of patients with primary CTCL who received TSEBT at UT Southwestern between 2012 and 2021. We stratified patients based on whether they received high-dose TSEBT (18 Gy or above) or low-dose TSEBT (12 Gy), and among those with low-dose TSEBT substratified them between standard fractionation (12 fractions) or hypofractionation (6 fractions). We recorded each patient's primary outcomes, which included response to radiation (complete response, near complete response, partial response, stable disease, or progressive disease), time to response, duration of response, and any acute toxicities. Physician-assessed secondary outcomes, demographic information, and any systemic treatments given concurrently or adjuvantly with TSEBT were also included. Results Overall, 46 patients received 59 courses of TSEBT, with 39 patients receiving 52 courses of low-dose TSEBT. Of the 52 low-dose courses evaluated, median age at treatment was 62.5 years old (range, 21-91). Most patients had stage IB, IIB, or IVA disease before initiation of TSEBT. The overall response rate was 87%. Nine courses (17%) resulted in a complete response, 5 courses (9.6%) resulted in a near complete response, and 25 courses (48%) resulted in a partial response. The incidence of progression of skin disease was 17% at 6 months and 21% at 1 year. Of the 59 total courses, 40 patients had hypofractionation (full cycle) and 8 patients had standard fractionation (half cycle). There was no significant difference in the response rate between these two groups. The median time to response for the hypofractionation compared to the standard fractionation was 7 weeks versus 8.5 weeks, respectively, while the duration of response was 46 weeks versus 54 weeks, respectively. Concurrent treatments included bexarotene for 2 patients, brentuximab for 2 patients, interferon for 1 patient, and romidepsin for 1 patient. Importantly, no patients experienced significant toxicities including those in the hypofractionation group, with the exception of 1 patient (2.5%) who experienced grade 3 desquamation. Conclusion In the largest series to date of low-dose TSEBT using a hypofractionation scheme, our results suggest that it is equally safe and effective as traditional fractionation. This novel condensed low-dose TSEBT comes with the added benefits of convenience and cost-effectiveness, as well as decreased patient exposure to the healthcare system during the current pandemic, and should be considered for all CTCL patients needing TSEBT. Moving forward, we look to evaluate the impact of radiation therapy with concurrent or adjuvant treatments for patients with CTCL as alternative options for possibly supplementing the efficacy of radiotherapy and/or reducing the need for recurrent radiation altogether. Disclosures Desai: Boston Scientific: Consultancy, Research Funding.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience

Background Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it’s use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. Methods Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan–Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Results Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58–106 months, range, 8–106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41–72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0–4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0–4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0–1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2–8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37–6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6–12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03–1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26–9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96–25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03–7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00–1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08–16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. Conclusions In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Bio-Polyurethane Resins Derived from Liquid Fractions of Lignin for the Modification of Ramie Fibers

In this study, technical lignin from black liquor was used as a pre-polymer for the preparation of bio-polyurethane (Bio-PU) resins. Briefly, the isolated lignin was fractionated using ethyl acetate (EtAc) and methanol (MeOH). The liquid fractions of lignin, such as lignin-EtAc (L-EtAc) and lignin-methanol (L-MeOH), were mixed with 10% of polymeric isocyanate (based on the weight of liquid fractions) to obtain Bio-PU resins. The isolated lignin, fractionated lignin, and lignin-derived Bio-PU resins were characterized using several techniques. The obtained Bio-PU resins were then used to modify ramie fibers using vacuum impregnation method. Fourier Transform Infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA) revealed that the isolated lignin had quite similar characteristics to the lignin standard. Fractionation of lignin with EtAc and MeOH altered its characteristics. FTIR, DSC, and TGA showed that solid fractions of lignin had similar characteristics to lignin standard and isolated lignin, while the liquid fractions had characteristics from lignin and the solvents. The absorption band of isocyanate (−N=C=O) groups was shifted to 2285 cm−1 from 2240 cm−1 owing to the reaction with the −OH groups in lignin, forming urethane (R−NH−C=O−R) groups at 1605 cm−1 in Bio-PU resins. Thermal properties of Bio-PU resins derived from L-EtAc exhibited greater endothermic reaction compared to Bio-PU-L-MeOH. As a result, the free −N=C=O groups in Bio-PU resins have reacted with –OH groups on the surface of ramie fibers and improved its thermal properties. Modification of ramie fibers with Bio-PU resins improved the fibers’ thermal stability by 15% using Bio-PU-LEtAc for 60 min of impregnation.Keywords: Bio-polyurethane resins, Impregnation, Lignin fractions, Ramie fibers, Thermal stability

Less is more when treating the nasal ala with superficial radiotherapy

Skin cancer is the most common malignancy, is increasing in incidence, and occurs most commonly on the head and neck. Cancers of the nasal ala pose therapeutic challenges given the cosmetic and functional importance. Both surgery and radiotherapy (RT) have similar oncological outcomes. RT is tissue-conserving and may have an advantage in cosmetic and functional outcomes, but more comparative trials are needed. RT needs to be delivered well to avoid late effects such as skin atrophy, fibrosis and telangiectasia, which may increase with higher dose per fraction. We describe three cases of self-reported thinning of the nasal ala following definitive mildly hypofractionated superficial radiotherapy (SXRT) of 2.5 Gy per fraction. SXRT to skin cancers of the nasal alar with standard fractionation of at most 2 Gy per fraction may be important in ensuring excellent cosmetic outcomes and patient satisfaction.