Intralesional Therapy Research Articles

Efficacy and Safety of Intralesional Platelet Rich Plasma (PRP) Therapy in the Management of Chronic Non-healing Leg Ulcers in our Population

Background: Autologous Platelets Rich Plasma (PRP) therapy not only hastens chronic wounds and ulcers healing but also diminishes the rate of amputations of lower leg caused by non-healing recalcitrant ulcers. In this study we have demonstrated the magical results of intralesional autologous PRP in the healing of resistant to heal chronic leg ulcers. Methods: In this metacentric study 26 patients having 30 chronic leg ulcers of more than 6 weeks duration and various etiologies, were treated with intralesional autologous PRP application on weekly basis for a duration of 8 weeks and the final results were calculated by percentage improvement in the volume and area of the ulcer/wound. Results: In our study 26 patient with 30 chronic recalcitrant leg ulcers/wounds were treated with intralesional autologous PRP therapy on weekly basis. Mean age of the included patients was 34.5 years. 19 were male patients and 7 were female. The mean time period of the healing of chronic ulcers was 5.3 weeks. The final mean percentage improvement outcome in the volume and area of the ulcers was calculated as 86% and 88% respectively. Conclusions: PRP therapy is safe, cost effective office based simple procedure in treating recalcitrant chronic leg ulcer/wounds. Keywords: Non-healing, intralesional, autologous platelet rich plasma, chronic ulcers

Preclinical Evaluation of LVR01 Attenuated Salmonella as Neoadjuvant Intralesional Therapy in Combination with Chemotherapy for Melanoma Treatment

Treatment of malignant melanoma has improved in the last few years owing to early detection and new therapeutic options. Still, management of advanced disease remains a challenge because it requires systemic treatment. In such cases, dacarbazine-based chemotherapy has been widely used, despite low efficacy. Neoadjuvant therapies emerge as alternative options that could help chemotherapy to achieve increased benefit. In this work, we evaluate LVR01, an attenuated Salmonella enterica serovar typhimurium, as neoadjuvant intralesional therapy in combination with dacarbazine in a preclinical melanoma model. B16F1 melanoma‒bearing mice received intraperitoneal administration of dacarbazine for 3 consecutive days. LVR01 treatment, consisting of one single intratumoral injection, was applied 1 day before chemotherapy began. This therapeutic approach retarded tumor growth and prolonged overall survival, revealing a strong synergistic antitumor effect. Dacarbazine induced a drastic reduction of secondary lymphoid organ cellularity, which was partially restored by Salmonella, particularly potentiating activated cytotoxic cell compartments. Systemic immune reactivation could be a consequence of the intense inflammatory tumor microenvironment induced by LVR01. We propose that the use of LVR01 as neoadjuvant intralesional therapy could be considered as an interesting strategy with close clinical application to boost chemotherapy effect in patients with melanoma.

Fractional carbon dioxide laser, platelet –rich plasma and narrow band ultraviolet B in the treatment of Vitiligo (A prospective randomized comparative trial)

Abstract Vitiligo is a disease that causes the loss of skin color in patches due to loss of melanin pigmentation of specific areas of the skin. Although several hypotheses have been proposed, the leading theory is still the auto-immune etiology linked to specific genetic mutations. Vitiligo can also be associated with several autoimmune diseases. There is no curative treatment for vitiligo but, several treatment modalities are considered. Topical therapies like steroids and Calcineurin inhibitors are of popular use in clinical settings also, steroids can be administered systemically in vitiligo patients. Physical therapies as fractionated CO2 (Fr: CO2) laser and Narrowband-UV (NBUV) phototherapy represent a gold standard in treatment in clinical practice. Moreover, intralesional therapies are emerging, one of which is autologous platelet-rich plasma injection. Aim of the study This study aimed to evaluate and compare the efficacy and safety of Fr: CO2 laser, PRP, combined Fr: CO2 laser and PRP, combined Fr: CO2 laser and NB-UVB, combined Fr: CO2 laser, PRP and NB-UVB in the treatment of vitiligo as well as reporting the side effects. Patients and methods This study included 20 vitiligo patients with at least 6 patches of stable vitiligo (120 patches), the patches were divided into six groups according to the treatment modality. Assessment of treatment response was done through patient satisfaction score and Vitiligo analysis by computer-assisted grid (VACAG). Results Regarding surface area reduction in included patients, fractional CO2 laser achieved the best results followed by triple combination therapy (CO2 with PRP and NB-UVB), the least response was with CO2 with PRP treatment. Patient satisfaction in the current study had a different outcome, PRP treated patients exhibited the highest satisfaction scores while triple combination treated group showed the least satisfaction scores.

Unusual presentation of angiolymphoid hyperplasia with eosinophilia treated with intralesional and topic corticosteroid combination therapy.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon angioproliferative benign disorder. A 24- year-old Caucasian female patient presented with multiple itchy reddish pearly nodule.

Multimodal Intralesional Therapy for Reshaping the Myeloid Compartment of Tumors Resistant to Anti-PD-L1 Therapy via IRF8 Expression.

Intralesional therapy is a promising approach for remodeling the immunosuppressive tumor microenvironment while minimizing systemic toxicities. A combinatorial in situ immunomodulation (ISIM) regimen with intratumoral administration of Fms-like tyrosine kinase 3 ligand (Flt3L), local irradiation, and TLR3/CD40 stimulation induces and activates conventional type 1 dendritic cells in the tumor microenvironment and elicits de novo adaptive T cell immunity in poorly T cell-inflamed tumors. However, the impact of ISIM on myeloid-derived suppressor cells (MDSCs), which may promote treatment resistance, remains unknown. In this study, we examined changes in the frequencies and heterogeneity of CD11b+Ly-6CloLy-6G+ polymorphonuclear (PMN)-MDSCs and CD11b+Ly-6ChiLy-6G- monocytic (M)-MDSCs in ISIM-treated tumors using mouse models of triple-negative breast cancer. We found that ISIM treatment decreased intratumoral PMN-MDSCs, but not M-MDSCs. Although the frequency of M-MDSCs remained unchanged, ISIM caused a substantial reduction of CX3CR1+ M-MDSCs that express F4/80. Importantly, these ISIM-induced changes in tumor-residing MDSCs were not observed in Batf3-/- mice. ISIM upregulated PD-L1 expression in both M-MDSCs and PMN-MDSCs and synergized with anti-PD-L1 therapy. Furthermore, ISIM increased the expression of IFN regulatory factor 8 (IRF8) in myeloid cells, a known negative regulator of MDSCs, indicating a potential mechanism by which ISIM decreases PMN-MDSC levels. Accordingly, ISIM-mediated reduction of PMN-MDSCs was not observed in mice with conditional deletion of IRF8 in myeloid cells. Altogether, these findings suggest that ISIM holds promise as a multimodal intralesional therapy to alter both lymphoid and myeloid compartments of highly aggressive poorly T cell-inflamed, myeloid-enriched tumors resistant to anti-PD-L1 therapy.

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma.

Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma.

Surgical approach in the management of ear keloids: our experience with 30 patients.

Ear keloids are benign, fibrous proliferations due to excessive collagen synthesis and deposition. It is a popular practice to pierce earlobes for decorative earrings and adornment; this might trigger the keloid process. Although there are varied treatment modalities, it is unsatisfactory and has always been a challenge. The aim is to evaluate the efficacy of surgical treatment with intralesional therapy in auricular keloids. We included 30 patients with 45 keloids over the ear. Patients were evaluated (including detailed history, complete physical and local examination), and photographs and written informed consent were taken. They were treated with: excision and closure, intralesional and/or surface cryotherapy, ablative laser, intralesional steroids, and 5-fluorouracil. Excision and closure, and intralesional cryotherapy were done under local anesthesia. Closure was done after intramarginal excision with or without raising auto flaps, followed by intraoperative intralesional steroids to margins. Recurrence was assessed at 3 weeks, 3 months, 6 months, and 1 year. The age group of patients ranged from 14 to 57 years. A total of 32 out of 45 (71.1%) keloids were excised and were combined with intraoperative and postoperative intralesional steroid injection, with sessions depending on the patient's response. Eight (17.7%) and five (11.1%) keloids were treated using intralesional cryotherapy and only intralesional steroids, respectively. A total of 16.6% of patients had recurrence with one patient having recurrence of bilateral earlobes keloid. Keloidectomy with intraoperative and postoperative intralesional steroid injections has been very effective in the treatment of ear keloids. Different treatment modalities act synergistically, but excision surgery gives good results as it aims at maintaining ear architecture.

Canadian provider perspectives on Collagenase Clostridium histolyticum for the treatment of Peyronie's disease and the impact of its discontinuation.

Intralesional Collagenase Clostridium histolyticum (CCh) was the first non-surgical therapy approved for Peyronie's disease (PD). However, CCh's cost and poor market uptake has led to its discontinuation in Europe and Canada. In Canada, Xiaflex® is the trade name for CCh and it is produced by Paladin Labs Inc, an operating company of Endo International. The paper aims to better understand CanadianCCh providers' perspectives regarding its treatment efficacy and the potential impact of its discontinuation. All Xiaflex®-approved Canadian providers were asked to complete an anonymous 21-question survey using an online platform. Analysis consisted of descriptive statistics. Outcomes of interest included previous experience with CCh, protocols utilized, experience with insurance coverage, clinical and patient-reported outcomes, and provider perspectives on the discontinuation of CCh. Overall response rate was 48.3% (29/60). A total of 89% of respondents were male, 61% were in practice more than 10 years, 32% were in an academic practice, and 46% had completed an Andrology/Sexual Medicine fellowship. A total of 93% of respondents felt that CCh was superior to other intralesional therapies for PD. In all, 86% reported a patient satisfaction rate of at least 50%, and the majority (75%) saw a clinically meaningful response. Only 7% expressed difficulty obtaining insurance coverage, with many providers (71%) achieving an insurance approval rate between 75 and 100%. Only 54% of respondents reported that they would continue treating PD in light of CCh's discontinuation, and 96% felt that CCh's discontinuation represents a loss to Canadian patients. In light of CCh's discontinuation, most (79%) are now more likely to offer surgical treatment. In conclusion, mostCCh providers found CCh to be effective and were dismayed by its discontinuation. The survey demonstrated that due to the withdrawal of CCh from Canada, physicians' abilities to offer effective medical therapy may become limited, with more providers offering surgical options for PD.

Giant Subcutaneous Granuloma Annulare

Subcutaneous granuloma annulare is an uncommon, benign self-limiting cutaneous disease, almost exclusively seen in young children. We report a case of 31-year-old male patient, presented with asymptomatic firm plaques over the left lateral malleoli and dorsum of the feet. Histopathological examination was done to confirm the diagnosis and the lesions responded well to monthly doses of the combination of rifampicin, ofloxacin, minocycline (ROM) therapy and intralesional steroid therapy. This case is reported for its unusual presentation of very large plaque in an adult male and its resolution after combined ROM and intralesional steroid therapy.

Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors

BackgroundChemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients.MethodsIn this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA).ResultsIn this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b+Gr-1+ cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α.ConclusionsThese results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer.

Inflammatory Myofibroblastic Tumor of the Larynx: Report of a Case

PurposeInflammatory myofibroblastic tumor (IMT) is a rare tumor composed of mesenchymal myofibroblastic spindle cells enveloped by an inflammatory infiltrate. Historically, this tumor sparked debate regarding whether it was a true malignancy with metastatic potential or merely a locally destructive physiologic inflammatory response. Few reports of IMT exist in the recent literature, with the majority of cases occurring in the pediatric population and favoring the lungs. Here we present an exceedingly rare case of IMT involving the larynx of a 22-year-old female. ResultsA hemorrhagic and solid mass of the right true membranous vocal fold was excised and sent for histopathological assessment. Features of the surgical specimens were diagnostic for IMT. Intralesional steroid therapy was selected for additional treatment. Panendoscopy facilitated surveillance for any additional or recurrent lesions, of which there were none. At 11 months post-excision, follow-up MRI revealed symmetric vocal cords without evidence of any masses. ConclusionsAlthough rare, laryngeal IMT should be considered in any patient presenting with hoarseness due to a vocal fold mass. Based on the successful treatment of our patient, we suggest that our approach of surgical excision followed by intralesional corticosteroid injection may be an efficacious treatment approach for this rare tumor. However, more research is warranted to elucidate the most effective, safe, and cost-effective treatment approach.

Surgical Resection After Talimogene Laherparepvec for Melanoma: Persistent Fuorodeoxyglucose Avidity on Positron Emission Tomography Despite No Viable Disease

Talimogene laherparepvec (TVEC) is an injectable attenuated oncolytic herpes simplex virus (HSV-1) used in the treatment of loco regionally metastatic melanoma. Lesions managed by TVEC are generally considered unresectable at time of initiation of intralesional therapy; however, a subset of patients go on to have surgical resection of loco regionally controlled disease. We sought to review our experience with surgical excision of treated lesions to offer an insight into the radiologic correlate, treatment effect, and pathological findings of intralesional TVEC therapy. This is a retrospective descriptive case series of patients who underwent TVEC injection at Mayo Clinic, Rochester, MN, between October 2016 and July 2020. Institutional Institutional Review Board approval was obtained. Twenty-one patients underwent intralesional TVEC, met inclusion criteria, and were included in this series. Seven went on to surgical excision of the injected lesions after an initial course of TVEC. Of those 7 patients, 4 had residual melanoma in the specimen on final pathology, while 3 had a complete pathologic response. All 3 patients who had no residual disease on pathology continued to have fluorodeoxyglucose (FDG) avidity on preoperative positron emission tomography scan of the excised lesions. Despite ongoing FDG avidity on PET scan, patients who have well-controlled disease and stability over time of the injected lesions may benefit from surgical excision following a course of TVEC. This may render the patient clinically disease free and/or allow them a reprieve from TVEC treatment.

Talimogene laherparepvec with systemic immunotherapy in melanoma: A real-world experience.

e21549 Background: Talimogene laherparepvec (TVEC) is an FDA approved oncolytic herpes virus for intralesional therapy in unresectable metastatic melanoma. Real world data is sparse regarding the efficacy of TVEC in combination with other systemic therapies used in melanoma. We present outcomes of the largest single institution observational study of the off-label use of TVEC in combination with systemic immunotherapy. Methods: Patients with metastatic melanoma receiving TVEC simultaneously with ipilimumab-nivolumab (Ipi/Nivo) or single agent immunotherapy (either nivolumab or pembrolizumab) were evaluated. The demographics, clinicopathological characteristics, responses to injected lesions and remote metastatic lesions were evaluated. Clinical documentation was used to assess improvement in injected lesion size; time points for initial response and best response were identified. Review of imaging by a radiologist was evaluated to assess responses in remote metastatic lesions. Results: A total of 67 patients receiving TVEC from 2016 to 2020 were evaluated, of which 50 remained evaluable after excluding Merkel cell carcinoma, patients on clinical trial, TVEC monotherapy or those on BRAF-MEK inhibitors, and patients lost to follow up. In total, 29 received systemic immunotherapy simultaneously with TVEC and had been followed for at least a year, with a median follow-up time of 34 months (range, 12-56). At the time of analysis, 14 of 29 patients were alive. 6 of the 29 patients had received prior lines of therapy. Four patients received Ipi/Nivo, while 25 patients received monotherapy including 9 on nivolumab and 16 on pembrolizumab. The median number of TVEC doses received was 6 (range, 2-55) with median average TVEC dose being 3.47 ml (0.5-4 ml). Median time to initial local response was 6 weeks, whereas time to best local response was 14 weeks. Overall response rate in the injected target lesions was in 19 (66%), with complete local response (CR) in 12 (41%), partial response (PR) in 7 (24%), and progressive disease (PD) in 8 (28%). The response rate in distant non-injected lesions was 4 out of 16 (25%), 2 of which had previously progressed on prior systemic therapy. Stable disease was observed in 8 (50%) patients, and progression of disease in 4 (25%). The 1-year overall survival rate in patients receiving TVEC with systemic monotherapy was 80%, 95% CI 0.651-0.9730. Progression free survival at 1-year in the monotherapy group was 71.6%, 95% CI 0.557-0.918. Conclusions: This is the largest single institution, real world experience to our knowledge, which assesses the efficacy of TVEC in combination with systemic immunotherapy. Our cohort suggests that TVEC is an effective treatment in combination with systemic immunotherapy, with a better overall survival observed with combination TVEC and anti-PD1 than seen with historical data from clinical trials of anti-PD-1 monotherapy.

Intralesional photodynamic therapy in hidradenitis suppurativa: Getting closer to the target

BackgroundThe successful treatment of hidradenitis suppurativa (HS) with intralesional photodynamic therapy (IL-PDT) has been previously reported in some case series published a few years ago. We present additional data and patient outcome for this form of PDT. MethodsThis is an observational retrospective study including all patients diagnosed with HS and treated with IL-PDT in the Hospital Universitari Son Espases from February 2019 to February 2020. Under local or general anesthesia, 5-aminolevulinic acid (5ALA) in gel 2 % or solution 1 % was introduced in the lesion. After two hours, the lesion was intralesionally irradiated (1.4 W, fluence 168 J/cm2) with the tip of a 0.4-mm thick optical fiber connected to a continuous 630-nm diode laser. The main outcome variable was the result (remission, improvement or no change) for each lesion 3 months after the therapy. The result at 6 months and the side effects were secondary outcomes. A multivariate analysis was carried out in order to obtain adjusted odds ratios for no change vs improvement or remission at 3 months for significant variables. ResultsA total of 117 lesions (28 nodules and 89 fistulae) were treated in 42 patients. At 3 months, 26 lesions (22.2 %) had resolved, 73 (62.4 %) had improved in size or symptoms, and 18 (15.4 %) experienced no change. The most frequent side effects were skin burns (53 lesions, 45.3 %), and abscess formation (8 lesions, 6.8 %). In the multivariate analysis, significant variables for no benefit were: a higher International Hidradenitis Suppurativa (IHS4) score, active smoking and gluteal and inguinal location. ConclusionsAlthough our results did not present the level of remission of the previous studies, IL-PDT was useful in most of our patients. Early interventions in patients with lower inflammatory burden were the most valuable.

Single-cell Transcriptomics Uncover a Novel Role of Myeloid Cells and T-lymphocytes in the Fibrotic Microenvironment in Peyronie’s Disease

BackgroundPeyronie’s disease (PD) is an acquired fibrotic disease affecting the penile tunica albuginea that can lead to curvature and deformities, shortening, and erectile dysfunction. Although immunological mechanisms have been suggested for the pathophysiology of PD, these have not been investigated using single-cell transcriptomics. ObjectiveTo investigate the immunological signature of plaques from PD patients using immunohistochemistry (IHC) and single-cell RNA sequencing (scRNA-Seq). Design, setting, and participantsTunica albuginea biopsy was performed in patients undergoing penile surgery for either PD (n = 12) or plication or penile cancer (control, n = 6). The inclusion criteria for PD patients were stable chronic disease (≥12 mo in duration) and no previous penile surgery or intralesional injection therapy. Outcome measurements and statistical analysisIHC was performed on surgical samples from ten patients with PD and five control subjects. An additional two PD and one control sample were used for scRNA-Seq (droplet-based; 10X Genomics). Cell clusters were visualised using heatmaps and t-distributed stochastic neighbour embedding plots (BioTuring v2.7.5). Results and limitationsIHC revealed the presence of myeloid dendritic cells (DCs; CD68+, TLR4+, CD206+), cytotoxic T lymphocytes (CTLs; CD3+, CD8+), and B lymphocytes (CD20+) in PD plaques, which were absent in controls. scRNA-Seq yielded results for 3312 PD and 5658 control cells. Cell clusters contained fibroblasts (COL1A2+), myofibroblasts (COL1A2+, ACTA2+), smooth muscle cells (ACTA2+, DES+), endothelial cells (VWF+), myeloid cells (CD14+), T lymphocytes (CD3D+), and neutrophils (ALPL+). Myeloid cell subclustering showed infiltration of monocyte-derived cells; control tissue contained classical DCs and resident macrophages. Lymphocyte subclustering revealed mucosal-associated invariant T (MAIT) cells and CTLs in PD. Differential gene expression suggests an increase in inflammatory and immune responses in chronic PD. The study is limited by the small scRNA-seq sample size (n = 3) for IHC, mitigated by a larger cohort of historic paraffin-embedded samples (n = 15), which showed largely parallel findings. Owing to tissue stiffness and extracellular matrix adhesion, our single-cell yield was lower for PD than for the control sample. ConclusionsOur data suggest that even in the chronic PD stage (painless and stable curvature) there is a sustained inflammatory reaction. While vascularisation and collagen production are elevated, the inflammation is driven by specialised monocyte-derived CTL and MAIT cells. These findings could uncover new avenues for medical treatment of PD. Patient summaryWe looked at the role of the immune system in patients suffering from Peyronie’s disease, a condition causing shortening and curvature of the penis. We found that even in a stable, chronic stage of the disease, there is activation of the immune system. Our results suggest that there is potential for novel treatments for this condition.

Contemporary Neoadjuvant Therapies for High-Risk Melanoma: A Systematic Review.

Simple SummaryThe risk of relapse for stage III melanoma remains high. Subsequently, there has been a surge of interest in the role of contemporary therapies in the neoadjuvant setting. Results of 8 phase II trials show safety, remarkable pathologic response and relapse-free survival.Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS—outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial.

Abstract PS14-05: Phase 1/2 clinical trial of a topical submicron particle paclitaxel (SOR007) for the treatment of cutaneous metastases

Abstract Background: Cutaneous Metastases (CM) are an infrequent presentation of advanced solid tumors and are usually associated with symptoms of pain, pruritus, and secondary infections, all of which negatively affect quality of life and result in additional morbidity. Systemic chemotherapy, advanced wound care, topical agents, cryo-, electro-, photodynamic-, laser and intralesional therapies have been limited by inconsistent efficacy, inconvenience, or toxicity. In this open-label phase 1/2 clinical trial, submicron particle paclitaxel in an anhydrous base (SOR007) was evaluated for topical treatment of CM from breast cancer (n=21), leiomyosarcoma (n=1) and Paget’s disease (n=1). Previously, in vitro, in vivo, and clinical studies demonstrated penetration of paclitaxel into the dermis with the silicone-based anhydrous producing subtoxic plasma levels in GLP toxicology studies and early clinical trials. Trial Design: The phase 1/2 open label trial evaluated 3 doses of SOR007 (0.15%, 1.0%, 2.0%). Approximately 0.5 grams (1 FTU) of SOR007 per 50 cm2 treatment area was applied BID during a 3+3 dose-rising phase for 28 days (n=10) or a dose-expansion phase at 2% strength BID for 28 days (n=2) or 56 days (n=11) unless discontinuation became necessary due to clinical course of the underlying disease. Results: At least one eligible lesion was treated per subject and classified per RECIST 1.1. In the 28-day application group, 10 subjects were treated and in the 56-day application group, 11 subjects were treated. Lesion response is summarized in the table below for data to date. Lesion response was evaluated within 2 weeks of last treatment day in most subjects. Conclusions: SOR007 was safe when applied to CM lesions. SOR007 resulted in decreased lesion progression or reduced lesion area in the majority of CM subjects. These clinical benefits became more consistent and pronounced at 2% strength with longer treatment suggesting a dose/duration response. Lesion pain reduction is also suggested from the study. Additional clinical research with more subjects and longer treatment periods is in the early planning stage. Lesion ResponseLesion response by SUBJECTLesion response by SUBJECTLesion response by INDIVIDUAL LESIONLesion response by INDIVIDUAL LESIONDose-rising 0.15%, 1%, 2% & Dose expansion 2%Dose-expansion 2%Dose-rising 0.15%, 1%, 2% & Dose expansion 2%Dose-expansion 2%BID x 28 daysBID x 56 daysBID x 28 daysBID x 56 daysN (subjects or lesions)8111823Complete Response0% (0/8)9.1% (1/11)5.5% (1/18)26% (6/23)Objective Response Rate13% (1/8)45% (5/11)17% (3/18)43% (10/23)No lesion progression in evaluable subjects 63% (5/8)82% (9/11)61% (11/18)83% (19/23) Citation Format: Mario E Lacouture, Julie E Lang, Sant Chawla, Shari Goldfarb, Alina Markova, Alexander Pan, Rose Marie Cavanna-Mast, Peter Mast, Christopher Savoie, Gere diZerega. Phase 1/2 clinical trial of a topical submicron particle paclitaxel (SOR007) for the treatment of cutaneous metastases [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-05.

Nicolau Syndrome Following Intralesional Sclerotherapy: A Dreaded Complication of a Simple Office Procedure

Introduction: Nicolau syndrome is an iatrogenic dreaded adverse skin reaction leading to ischemic necrosis of skin and underlying tissue after parenteral drug injection. The etiopathogenesis is poorly understood. However, inflammation, reflex vasospasm, and thrombo-embolic occlusion of blood vessels, including arterioles and arteries, are suggested as the cause of ischemia. Case Presentation: We report a 12-year-old girl who developed Nicolau syndrome after a simple office procedure of intralesional sclera therapy with sodium tetradecyl sulfate for a apyogenic granuloma on her right index finger. Three days later, she reported complaints of excruciatingly painful swelling with bluish discoloration of the right hand involving the palm, entire index, middle, and ring fingers, and distal part of the little finger. Nicolau syndrome was documented after intramuscular injections of drugs. Nevertheless, there are very few reports of Nicolau syndrome following post intralesional sclerotherapy. Conclusions: Sclerotherapy is a simple office procedure routinely performed by health care professionals (e.g., dermatologists and surgeons), and awareness about its dreaded entity is key. Stringent precautions and prompt management can prevent unfavorable complications. Additionally, prudent patient selection and detailed counseling with explicit informed consent regarding Nicolau syndrome are imperative while planning any parenteral drug injection or intralesional sclerotherapy to avoid litigation.

Durability of Complete Response to Intralesional Interleukin-2 for In-Transit Melanoma.

BackgroundIntralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes.ObjectivesTo provide long-term data on patients with a complete response to IL-2 therapy for ITM.MethodsConsecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease.ResultsSixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3).ConclusionWith long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.

Digital Myxoid Cysts: Correlation of Initial and Long-Term Response to Steroid Injections

Digital mucous cysts (DMCs) are benign myxoid pseudocysts that develop on the distal interphalangeal joint's lateral or dorsal aspects. Management consists either of a surgical approach, conservative therapy, or simple follow-up. To correlate the initial and long-term response with clinical and ultrasound parameters in DMCs treated with intralesional steroids as first-line therapy. A single-center prospective open-label study recruited 15 patients affected by DMCs, who had been treated with a cycle of up to 3 steroid injections at a 6 to 9 week time interval. At the first follow-up visit, 53.3% of patients were cleared of DMCs, achieving a complete response, whereas 46.7% experienced a >30% decrease in their DMC volume, and were considered partial responders. After 1 year of follow-up, the cure rate decreased to 40%, and the recrudescence rate was 27.3%. Clinical and sonographic characteristics that positively correlated with a maintained complete response at follow-up were as follows: young age, absence of osteophytes, low volume, complete clearance at T1, and short disease duration (p < .05). Intralesional steroid therapy is an easy approach for DMC, with minimal side effects; identifying predictive hallmarks is useful to offer a straightforward surgical treatment to patients who have nonresponder characteristics.