Enhancing radiotherapy for melanoma: the promise of high-Z metal nanoparticles in radiosensitization.

Melanoma is a type of skin cancer that can be challenging to treat, especially in advanced stages. Radiotherapy is one of the main treatment modalities for melanoma, but its efficacy can be limited due to the radioresistance of melanoma cells. Recently, there has been growing interest in using high-Z metal nanoparticles (NPs) to enhance the effectiveness of radiotherapy for melanoma. This review provides an overview of the current state of radiotherapy for melanoma and discusses the physical and biological mechanisms of radiosensitization through high-Z metal NPs. Additionally, it summarizes the latest research on using high-Z metal NPs to sensitize melanoma cells to radiation, both in vitro and in vivo. By examining the available evidence, this review aims to shed light on the potential of high-Z metal NPs in improving radiotherapy outcomes for patients with melanoma.

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Hypofractionated versus standard fractionation radiotherapy for merkel cell carcinoma.

PURPOSE/OBJECTIVE(S): Merkel cell carcinoma (MCC) radiation treatment has historically consisted of standard 1.8-2 Gy fractions treated daily over 4-6 weeks. Hypofractionated treatment regimens have demonstrated tumor control and toxicity equivalence to standard fractionation regimens for common cutaneous malignancies such as basal cell and squamous cell carcinomas. Herein we report the outcomes of hypofractionated versus standard fractionation radiotherapy for MCC at our institution. MATERIALS/METHODS: The study involved a retrospective review of MCC patients treated with radiotherapy. Treatment characteristics and patient outcomes, including acute toxicities, disease recurrence and survival data were collected. The cumulative incidence of local and distant failures was estimated, with death as a competing risk. RESULTS: A total of 29 treatment courses for 24 patients were included, of which 13 involved standard fractionation with curative intent, 10 involved hypofractionated radiotherapy with curative intent, and 6 involved single fraction (8 Gy) palliative radiation. Half the patients were treated to a head/neck site. A subset of patients treated adjuvantly with curative intent included 8 standard fractionation and 8 hypofractionated radiotherapy patients. No statistically significant differences in local and/or distant failure or overall survival was observed between the patient groups. CONCLUSION: Hypofractionated radiotherapy for MCC was associated with similar treatment outcomes relative to standard fractionation. In our limited patient sample, hypofractionated radiation treatment achieved similar results with similar toxicity and fewer treatments. Further analysis of a larger patient population with longer follow up is needed to confirm treatment tolerability and efficacy.

Cold plasma irradiation inhibits skin cancer via ferroptosis.

Cold atmospheric plasma (CAP) has been extensively utilized in medical treatment, particularly in cancer therapy. However, the underlying mechanism of CAP in skin cancer treatment remains elusive. In this study, we established a skin cancer model using CAP treatmentin vitro. Also, we established the Xenograft experiment modelin vivo. The results demonstrated that treatment with CAP induced ferroptosis, resulting in a significant reduction in the viability, migration, and invasive capacities of A431 squamous cell carcinoma, a type of skin cancer. Mechanistically, the significant production of reactive oxygen species (ROS) by CAP induces DNA damage, which then activates Ataxia-telangiectasia mutated (ATM) and p53 through acetylation, while simultaneously suppressing the expression of Solute Carrier Family 7 Member 11 (SLC7A11). Consequently, this cascade led to the down-regulation of intracellular Glutathione peroxidase 4 (GPX4), ultimately resulting in ferroptosis. CAP exhibits a favorable impact on skin cancer treatment, suggesting its potential medical application in skin cancer therapy.

Modern radiation therapy for keratinocyte cancer: What the general practitioner needs to know.

BACKGROUND: Keratinocyte cancer (KC) in Australia poses a unique healthcare challenge due to its high prevalence and the requirement for multidisciplinary management of many cases. Advances in radiation therapy (RT) have increased its use in treating different keratinocyte cancer presentations. Understanding the indications for RT and the role that general practitioners (GPs) play in the treatment pathway are imperative to ensure best patient outcomes. OBJECTIVE: This review examined the efficacy, advances and treatment considerations of RT for the management of keratinocyte cancer, and role of the GP in the treatment pathway. DISCUSSION: Radiation therapy offers effective alternatives to, or adjuvants for, surgery in existing keratinocyte cancer treatments in appropriate cases. The evolving RT landscape necessitates GPs to be well informed for effective case identification, referral and management. This includes understanding RT advances, protocols, treatment reactions and managing patient expectations. Continuing education in this space is important for GPs to understand the suitability of RT for their patients.

Mogamulizumab and Concomitant Hypofractionated Low-Dose Total Skin Electron Beam Therapy (2 × 4 Gy) in Cutaneous T-Cell Lymphoma: Proof of Principle, Report of Two Cases.

Patients with advanced-stage mycosis fungoides (MF IIB-IVB) and Sézary syndrome (SS) have poor prognoses, with survival ranging from 4.7 to 1.4 years depending on the disease stage. There is a need for therapeutic approaches that lead to long-lasting responses and improved quality of life and survival. Mogamulizumab, a humanized antibody against the CCR4 molecule, and low-dose total skin electron beam therapy (TSEBT) are two known established treatments for MF and SS as a monotherapy. However, little is known about the potential additive effect on the combination of both treatments. We report here for the first time the concurrent use of low-dose hypofractionated TSEBT (2 × 4 Gy) with mogamulizumab. Based on two relapsed/refractory and advanced-stage CTCL patients, we show that this combination may be well tolerated in advanced-stage MF or SS and may potentially lead to an additive treatment effect on response times, particularly in the skin and blood within two weeks. We propose that this combination may be a treatment option for patients with SS. Further research is needed to understand the efficacy and tolerability profile of this therapeutic combination and to determine if there is an additive effect of the combination on the response rates when compared with the monotherapy.

Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study.

Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. Rhenium skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm2 in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. Results: A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 (n = 19), grade 2 (n = 9), or grade 3 (n = 1). Conclusion: This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy.

Palliating hematologic oncologic emergencies with radiation in the age of targeted systemic therapies: three illustrative cases.

Hematologic oncologic emergencies with an urgent indication for radiation are a relatively routine occurrence for the radiation oncologist. As patients are living longer and have multiple treatment options for their relapsed or refractory diseases, it is important that palliative treatments avoid precluding patients from or delaying next-line potentially curative treatments wherever possible. We highlight the following experiences from our clinical practice: newly diagnosed plasma cell disease causing cord compression; life threatening cutaneous lymphoma with tumors covering the majority of the body surface area; and relapsed/refractory diffuse large B-cell lymphoma (DLBCL) requiring bridging radiation to a mass impinging on the brachial plexus combined with chimeric antigen receptor (CAR)-T cell therapy. In each case, urgent palliative radiation was utilized, but the approaches were nuanced, with careful consideration of subsequent potential therapies and how the current course of radiation should be tailored for the best interplay with the overall treatment course and trajectory of the disease. With the rapid development of new therapies, it can be difficult to stay up to date on the most recent practice guidelines. Drawing on hematologic-specific guidelines, such as those provided by the International Lymphoma Radiation Oncology Group, and disease site experts can aid in ensuring patients are appropriately palliated and eligible for future therapies.

Clinical and toxicity outcomes with 3D based-HDR surface mold brachytherapy in skin cancer.

INTRODUCTION: Surface mold brachytherapy (SMBT) is an established treatment modality in skin cancer, especially in accessible areas, and has shown comparable outcomes to surgery. We have presented our results for the skin tumor treatment with SMBT treated with high-dose-rate (HDR) brachytherapy in terms of clinical outcomes and toxicity at our institute. MATERIALS AND METHODS: In this retrospective analysis, 15 patients with skin cancer were treated with customized tube-based SMBT at our institute between January 2019 and July 2021. The patients were treated using HDR-brachytherapy using Iridium-192. The median dose was 40 Gy in 10 fractions. The dosimetric parameters were assessed, and patients were followed up as per the institutional protocol. All patients underwent individualized CT-based planning. Skin toxicity was assessed using the Dermatology Life Quality Index (DLQI). RESULTS: With the majority of the patients being male, the median age was 59 years and the most common site affected was the face (8/15; 53.3%). Among the 15 cases, five were squamous cell carcinoma, nine were basal cell carcinoma, and a single case of sebaceous cell carcinoma. The median depth of invasion was 4 mm, and the median catheter-to-surface distance was 1 mm. The complete response rate among the 10 definitive cases was 90% and partial response in one case. The treatment was well-tolerated with no grade 3-5 toxicities. The median V95% and V90% were 94.8% and 97.1%, respectively. The mean coverage index (C.I.), dose non-uniformity ratio (DNR), and overdose volume index (ODI) were 0.97, 0.13, and 0.05, respectively. After a median follow-up of 12 months, none of the patients had recurrence. On assessment of DLQI, the scores were found to be significant in association with the tumor size and tumor site with scores favoring <2 cm and non-exposed area lesions. CONCLUSION: SMBT is a safe and effective treatment modality for skin tumors providing excellent response and cosmetic outcomes. It is well-tolerated and a non-invasive option for elderly patients with comorbidities and lesions in inoperable areas.

Recurrence Rates of Mohs Micrographic Surgery vs Radiation Therapy for Basal Cell Carcinoma of the Ear.

Basal cell carcinoma (BCC) of the ear may have aggressive histologic subtypes and a greater propensity for subclinical spread than BCC in other anatomic locations. In this retrospective analysis, we evaluated recurrence rates of BCC of the ear in 102 patients who underwent treatment with Mohs micrographic surgery (MMS) or radiation therapy (RT) at a single institution between January 2017 and December 2019. Data on patient demographics, tumor characteristics, treatment modality, and recurrence rates were collected from medical records. Recurrence rates were assessed over a mean follow-up time of 2.8 years. Although MMS is the gold standard for treatment of BCC of the ear, RT may be a suitable alternative for nonsurgical candidates.

Wavelength-dependent photobiomodulation (PBM) for proliferation and angiogenesis of melanoma tumor in vitro and in vivo.

Photobiomodulation (PBM) has widely been used to effectively treat complications associated with cancer treatment, including oral mucositis, radiation dermatitis, and surgical wounds. However, the safety of PBM against cancer still needs to be validated as the effects of PBM on cancer cells and their mechanisms are unclear. The current study investigated the wavelength-dependent PBM effects by examining four different laser wavelengths (405, 532, 635, and 808 nm) on B16F10 melanoma tumor cells. In vitro tests showed that PBM with 808 nm promoted both proliferation and migration of B16F10 cells. In vivo results demonstrated that PBM with 808 nm significantly increased the relative tumor volume and promoted angiogenesis with overexpression of VEGF and HIF-1α. In addition, PBM induced the phosphorylation of factors closely related to cancer cell proliferation and tumor growth and upregulated the related gene expression. The current result showed that compared to the other wavelengths, 808 nm yielded a significant tumor-stimulating effect the malignant melanoma cancer. Further studies will investigate the in-depth molecular mechanism of PBM on tumor stimulation in order to warrant the safety of PBM for clinical cancer treatment.

A case of reed syndrome with an unusually extensive cutaneous burden treated with fully ablative Erbium:YAG laser resurfacing therapy.

Reed Syndrome, or hereditary leiomyomatosis and renal cell carcinoma syndrome, is a rare, autosomal dominant genetic condition that predisposes individuals to a triad of cutaneous leiomyomas, uterine leiomyomas and renal cell carcinoma. Cutaneous leiomyomas are often the first manifestation of the syndrome, occurring in 76% of patients and average 26 in number. We present a case of a 47 year old female with Reed Syndrome with an unusually extensive cutaneous burden, with a total of 361 cutaneous lesions, far above the average reported number of 26. Due to the extent of her cutaneous burden, painful nature of the lesions and failure to respond to standard therapies, she was referred for fully ablative Erbium:Yag laser resurfacing therapy. The use of fully ablative Erbium:YAG laser resurfacing therapy for treatment of cutaneous leiomyomas has not been reported in the literature to date. One year following laser therapy, the treatment area not only began to repigment, but there was also no evidence of cutaneous leiomyomas recurrence or associated pain. Given the effectiveness of this unique therapy, fully ablative Erbium:YAG laser resurfacing should be kept in mind as a treatment option for both cosmetic and symptomatic cutaneous leiomyomas.

Effectiveness of narrowband ultraviolet B monotherapy versus combination therapy with systemic agents in patients with early-stage mycosis fungoides and the association with plaque lesions.

OBJECTIVE: Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. METHODS: This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. RESULTS: In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. CONCLUSIONS: Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.

Reproducibility and air gap pockets of 3D-printed brachytherapy applicator placement in high-dose-rate skin cancer.

BACKGROUND AND PURPOSE: This study aimed to investigate the reproducibility of a novel approach using 3D printed brachytherapy applicators for the treatment of skin cancer. Specifically, we aimed to assess the accuracy of applicator placement and to minimize the existence of air gap pockets between the applicator and the patient's skin. MATERIALS AND METHODS: A total of 20 patients plans diagnosed with skin cancer were enrolled in this study. All patients underwent high dose rate (HDR) brachytherapy. To ensure precise applicator placement, patient-specific 3D printed applicators were designed based on individual body and tumor topography, utilizing data obtained from computer tomography (CT) scans. All applicators were fabricated using fused deposition modeling technology. RESULTS: The error in applicator placement was measured and found to be less than 1.0 mm on average, with a standard deviation of 0.9 mm. Additionally, the average error in air gap pockets between the applicator and the patient's skin was 0.4 mm (standard deviation was 0.5 mm). The study demonstrated that the personalized approach of 3D printed brachytherapy applicator placement in skin cancer treatment yielded highly accurate results. The average error of less than 1.0 mm in applicator positioning and the minimal air gap pockets demonstrated the reproducibility and precision of this technique. CONCLUSION: Our study establishes the reproducibility and accuracy of 3D-printed brachytherapy applicator placement in the treatment of skin cancer. This personalized treatment approach offers a highly precise method for delivering radiation therapy, minimizing the risk to adjacent healthy tissues, and enhancing overall patient outcomes.

Efficacy of 785-nm Picosecond Titanium Sapphire Laser for Treatment of Brown Nevus of Ota Lesions in FST II-V: A Retrospective Analysis.

BACKGROUND: Nevus of Ota (NOTA) is a dermal melanocytosis acquired in early childhood or pregnancy. Given their color variability, NOTA often require a combination of wavelengths for successful treatment. Quality-switched lasers have consistently shown efficacy in targeting dermal pigment, while picosecond lasers (PSLs) are an emerging technology for pigmentary disorders. OBJECTIVE: To further elucidate its efficacy, the authors conducted a retrospective review of 17 patients with NOTA treated with a 785-nm PSL for brown NOTA lesions between 2021 and 2023. MATERIALS AND METHODS: The primary end point analyzed clinical improvement based on before and after photography reviewed by 3 board-certified dermatologists using a five-point visual analog scale. RESULTS: Seventeen patients of Fitzpatrick skin types (FSTs) II to V, ranging from ages 14 to 38 years, were included in this study. Patients were treated for an average of 3.2 sessions in 2 to 3-month intervals. Visual analog scale scores demonstrated a mean clearance of 51% to 75%. No pigmentary alterations were noted. CONCLUSION: Because NOTA is common in higher FSTs, the authors believe that the 785-nm PSL is an excellent treatment option for brown NOTA in these skin types. This study highlights the need for further investigation to determine optimal treatment parameters for the color-based laser treatment approach for NOTA.

A scattering-foil free electron beam to increase dose rate for total skin electron therapy (TSET).

BACKGROUND: Electron beams are used at extended distances ranging between 300 to 700 cm to uniformly cover the entirety of the patient's skin for total skin electron therapy (TSET). Even with electron beams utilizing the high dose rate total skin electron (HDTSe) mode from the Varian 23iX or TrueBeam accelerators, the dose rate is only 2500 cGy/min at source-to-surface distance (SSD) = 100 cm. At extended distances, the decrease in dose rate leads to long beam delivery times that can limit or even prevent the use of the treatment for patients who, in their weakened condition, may be unable to stand on their own for extended periods of time. Previously, to increase dose rate, a customized 6 MeV electron beam was created by removing the x-ray target, flattening filter, beam monitor chamber, and so forth. from the beam path (Chen, et at IJROBP 59, 2004) for TSET. Using this scattering-foil free (SFF) electron beam requires the treatment distance be extended to 700 cm to achieve dose uniformity from the single beam. This room size requirement has limited the widespread use of the 6 MeV-SFF beam. PURPOSE: This study explores an application of a dual-field technique with a 6 MeV-SFF beam to provide broad and uniform electron fields to reduce the treatment distances in order to overcome treatment room size limitations. METHODS: The EGSnrc system was used to generate incident beams. Gantry angles between 6 MeV-SFF dual-fields were optimized to achieve the similar patient skin dose distribution resulting from a standard 6 MeV-HDTSe dual-field configuration. The patient skin dose comparisons were performed based on the patient treatment setup geometries using dose-volume-histograms. RESULTS: Similar dose coverage can be achieved between 6 MeV-SFF and 6 MeV-HDTSe beams by reducing gantry angles between dual-field geometries by 8° and 7° at treatment distances of 400 and 500 cm, respectively. To achieve 95% mean dose to the first 5 mm of skin depth in the torso area, the mean dose to depths of 5-10 mm and 10-15 mm below the skin surface was 74% (74%) and 49% (50%) of the prescribed dose when using 6 MeV-SFF (6 MeV-HDTSe) beam, respectively. CONCLUSIONS: The 6 MeV-SFF electron beam is feasible to provide similar TSET skin dose coverage at SSD ≥ 400 cm using a dual-field technique. The dose rate of the 6 MeV-SFF beam is about 4 times that of current available 6 MeV-HDTSe beams at treatment distances of 400-500 cm, which significantly shortens the treatment beam-on time and makes TSET available to patients in weakened conditions.

Radiation and Melanoma: Where Are We Now?

PURPOSE OF REVIEW: This review summarizes the current role of radiotherapy for the treatment of cutaneous melanoma in the definitive, adjuvant, and palliative settings, and combinations with immunotherapy and targeted therapies. RECENT FINDINGS: Definitive radiotherapy may be considered for lentigo maligna if surgery would be disfiguring. High risk, resected melanoma may be treated with adjuvant radiotherapy, but the role is poorly defined since the advent of effective systemic therapies. For patients with metastatic disease, immunotherapy and targeted therapies can be delivered safely in tandem with radiotherapy to improve outcomes. Radiotherapy and modern systemic therapies act in concert to improve outcomes, especially in the metastatic setting. Further prospective data is needed to guide the use of definitive radiotherapy for lentigo maligna and adjuvant radiotherapy for high-risk melanoma in the immunotherapy era. Current evidence does not support an abscopal response or at least identify the conditions necessary to reliably produce one with combinations of radiation and immunotherapy.

Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma.

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.