Advanced Cutaneous Malignancies Research Articles

The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis.

Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated. For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS). Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021). The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC.

Abstract CT003: Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS)

Abstract Background: Skin cancers are common post-transplant malignancies in solid organ transplant (SOT) recipients. The use of immune checkpoint inhibitors has improved outcomes in the general patient (pt) population but is associated with a high risk of allograft rejection in transplant recipients. RP1 is an oncolytic immunotherapy that expresses a fusogenic glycoprotein (GALV-GP-R−) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study is to assess the safety and efficacy of single-agent RP1 in SOT recipients with skin cancer (NCT04349436). Methods: The trial will enroll up to 65 transplant recipients with histologically confirmed advanced cutaneous squamous cell carcinoma (CSCC) and up to 10 pts with advanced non-CSCC skin cancer in 2 parts. Part A (completed) enrolled kidney and liver transplant recipients until safety was established, and Part B is enrolling kidney, liver, heart, and lung transplant recipients. Pts must have stable allograft function and ECOG performance status ≤1. Pts with visceral metastases are excluded. Pts receive an initial RP1 dose at 1 × 106 plaque-forming units (PFU)/mL followed by 1 × 107 PFU/mL after 2 weeks and continuing every 2 weeks until prespecified study endpoints are met. Tumor biopsies are collected for biomarker analyses and HSV-1 serostatus is monitored. Results: At the data cutoff (Sept 18, 2023), 27 transplant recipients were enrolled (kidney, n = 22; liver, n = 4; lung, n = 1) with a median (range) age of 68 (48-86) years; 24 pts had CSCC and 3 had Merkel cell carcinoma. Nearly half of pts (44%) had metastatic disease at study baseline. The investigator-assessed objective response rate (ORR) for efficacy-evaluable pts was 35% (8/23); 22% of pts (5/23) had complete response (CR). Most responses were ongoing. The most common (>20%) treatment-emergent adverse events were fatigue (33%), chills (26%), and pyrexia (26%). There was no evidence of allograft rejection. Eight deaths were reported; none were related to RP1. Immunohistochemistry from tumor biopsies indicated influx of CD8+ T cells and upregulation of PD-L1 expression after RP1 treatment. Additional biomarker data from gene expression analysis will be presented. Conclusions: This is the first trial assessing single-agent RP1 activity in solid organ transplant recipients with advanced cutaneous malignancies. RP1 monotherapy showed compelling antitumor activity (ORR 35%; 22% CR) in evaluable pts. Additionally, RP1 monotherapy was well tolerated, and the safety profile was similar to non-immunocompromised pts with advanced skin cancers (IGNYTE study). Citation Format: Michael R. Migden, Wanxing Chai-Ho, Gregory A. Daniels, Theresa Medina, Trisha M. Wise-Draper, Meenal Kheterpal, Jennifer C. Tang, Sherrif F. Ibrahim, Diana Bolotin, Claire Verschraegen, Nathalie C. Zeitouni, Katy K. Tsai, Laxminarasimha Donthireddy, Praveen K. Bommareddy, Jeannie W. Hou, Walter Hong, Diwakar Davar. Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT003.

Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies.

Immune checkpoint inhibitors (ICI) are standard of care therapy for patients with cutaneous malignancies, the most frequently diagnosed cancers in solid organ transplant (SOT) recipients. The activity and rate of allograft rejection in SOT recipients with advanced skin cancers treated with ICI is understudied. We conducted a retrospective analysis of SOT recipients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), and merkel cell carcinoma (MCC) who were treated with ICI. Unpublished cases from our institution and published cases from the literature were aggregated. Demographics, type of immunosuppressive therapy, type of ICI(s) administered, prior systemic therapies, tumor response to ICI, and evidence of organ rejection and/or failure were recorded. Objective response rates (ORR) and rates of graft rejection and failure are reported. Ninety patients were identified; four patients from our institution and 86 unique patients from a literature review. ORR to first-line ICI for the entire cohort was 41.1% (37/90). ORR by tumor type was 31% (18/58), 64.3% (18/28), and 25.0% (1/4) for melanoma, cSCC, and MCC, respectively. The rate of graft rejection was 37.8% (34/90) with 61.8% (21/34) of these cases progressing to graft failure. Number of immunosuppressive agents (0, 1, 2, or 3) was inversely associated with rate of graft failure. In this retrospective analysis, ICIs demonstrate clinical activity in SOT recipients with cutaneous malignancies; however, the rate of graft rejection is high. Treatment plans should be individualized through thorough interdisciplinary discussion. Immunosuppressive modifications may be considered prior to starting treatment, but when feasible, enrollment on clinical trials is preferred.

An open-label, multicenter, phase 1b/2 study of RP1, a first-in-class, enhanced potency oncolytic virus in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS).

TPS9597 Background: RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity. Clinical data in combination with nivolumab has demonstrated a high rate of deep and durable response in patients with advanced skin cancer. Solid organ transplantation (SOT) is an important lifesaving procedure for patients with a wide range of end-organ diseases, but requires patients (pts) to undergo lifelong immunosuppression to prevent allograft rejection, and skin cancers (SCs) – including cutaneous squamous cell carcinoma (CSCC) – are common post-transplant malignancies. SC in SOT pts is generally managed with surgical resection, radiation therapy, and chemotherapy or targeted therapy. The use of immune checkpoint inhibitors in SOT recipients has improved outcomes but is associated with a high risk of allograft rejection. Thus, there is a high unmet need for a safe and effective treatment that also protects pts from allograft rejection. The objective of this study is to assess the safety and efficacy of single-agent RP1 in SOT patients with SCs, with a focus on CSCC. Methods: This study will enroll up to 65 evaluable SOT pts with locally advanced or metastatic SCs. The study has two parts. In Part A, pts will receive an initial dose of 1 x 106 plaque-forming units (PFU) of RP1. Two weeks later they will receive 1 x 107 PFU of RP1 and continue every two weeks until pre-specified study endpoints are met. In Part B, after determining the safety and tolerability in the initial cohort with kidney and liver transplants, the study may also enroll heart and lung transplant recipients. RP1 will be administered by intra-tumoral injection, utilizing image guidance as clinically appropriate. Key inclusion criteria are pts with confirmed recurrent, locally advanced or metastatic CSCC and up to 10 pts with non-CSCC SC, stable allograft function and ECOG performance status of ≤1. Pts with prior systemic anti-cancer treatment are allowed. Key exclusion criteria are prior treatment with an oncolytic therapy, active herpetic infections or prior complications of HSV-1 infection and a history of organ graft rejection within 12 months. The primary objective of the trial is to assess efficacy determined by objective response rate and safety of single agent RP1. Additional secondary endpoints include duration of response, complete response rate, disease control rate, progression-free survival and overall survival. Clinical trial information: NCT04349436.

550 ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies

BackgroundSolid organ transplantation (SOT) has emerged as an important lifesaving procedure for patients with a wide range of end-organ diseases characterized by dysfunction or specific organ function failure. SOT rejection is a major complication requiring patients (pts) to undergo lifelong immunosuppression to prevent allograft rejection.1Skin cancers (SCs) including cutaneous squamous cell carcinoma (CSCC) are common post transplant malignancies.2 SC in SOT pts is generally managed with surgical resection, radiation therapy and chemotherapy or targeted therapy. Use of immune checkpoint inhibitors in SOT recipients has improved outcomes but are associated with the high risk of allograft rejection.3–5 Thus, there is a high unmet need for a safe and effective treatment that also protects pts from allograft rejection. RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity6 and clinical data in combination with nivolumab has demonstrated a high rate of deep and durable response in patients with advanced SCs.7 The objective of this study is to assess the safety and efficacy of single agent RP1 in kidney and liver transplant recipients with SCs, with focus on CSCC. After determining the safety and tolerability in the initial cohort with kidney and liver transplants the study may also enroll heart and lung transplant recipients.MethodsThis study will enroll up to 65 evaluable allograft transplantation pts with locally advanced or metastatic SCs. Key inclusion criteria are pts with confirmed recurrent, locally advanced or metastatic CSCC and up to 10 pts with non-CSCC SC, stable allograft function and ECOG performance status of ≤1. Pts with prior systemic anti-cancer treatment are allowed. Key exclusion criteria are prior treatment with an oncolytic therapy, active herpetic infections or prior complications of HSV-1 infection and a history of organ graft rejection within 12 months. Pts will receive an initial dose of 1 x 10^6 plaque-forming units (PFU) of RP1. Two weeks later they will receive 1 x 10^7 PFU of RP1 and continue every two weeks until pre-specified study endpoints are met. RP1 will be administered by intra-tumoral injection including through imaging guidance as clinically appropriate. The primary objective of the trial is to assess efficacy determined by ORR and safety of single agent RP1. Additional secondary endpoints include DOR, CR, DCR, PFS and OS.Trial RegistrationNCT04349436ReferencesFrohn C, Fricke L, Puchta JC, Kirchner H. The effect of HLA-C matching on acute renal transplant rejection. Nephrol Dial Transplant 2001;16(2):355–60.Madeleine MM, Patel NS, Plasmeijer EI, Engels EA, Bouwes Bavinck JN, Toland AE, Green AC; the Keratinocyte Carcinoma Consortium (KeraCon) Immunosuppression Working Group. Epidemiology of keratinocyte carcinomas after organ transplantation. Br J Dermatol 2017;177(5):1208–1216.Spain L, Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol 2016;27(6):1135–1137.Herz S, Höfer T, Papapanagiotou M, Leyh JC, Meyenburg S, Schadendorf D, Ugurel S, Roesch A, Livingstone E, Schilling B, Franklin C. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer 2016;67:66-72.Kittai AS, Oldham H, Cetnar J, Taylor M. Immune checkpoint inhibitors in organ transplant ptss. J Immunother 2017;40(7):277–281.Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer 2019 10;7(1):214.Middleton M, Aroldi F, Sacco J, Milhem M, Curti B, Vanderwalde A, Baum S, Samson A, Pavlick A, Chesney J, Niu J, Rhodes T, Bowles T, Conry R, Olsson-Brown A, Earl-Laux D, Kaufman H, Bommareddy P, Deterding A, Samakoglu S, Coffin R, Harrington K. 422 An open-label, multicenter, phase 1/2 clinical trial of RP1, an enhanced potency oncolytic HSV, combined with nivolumab: updated results from the skin cancer cohorts. J Immunother Cancer 2020;8(3): doi: 10.1136/jitc-2020-SITC2020.0422Ethics ApprovalThe study was approved by institutional review board or the local ethics committee at each participating site. Informed consent was obtained from patients before participating in the trial.

A phase 1, open-label, dose escalation study of the safety and tolerability of T3011 in advanced cutaneous or subcutaneous malignancies.

2526 Background: T3011 is a genetically modified, next-generation oncolytic HSV-1 with 2 exogenous genes encoding the active heterodimer human interleukin 12 (IL-12) and the Fab fragment of an anti-human PD-1 antibody. Locally produced IL-12 induces the synthesis of interferon-gamma (IFN-γ) production, enhancing cytolytic activity of natural killer cells and cytotoxic T lymphocytes. The anti PD-1 antibody blocks checkpoint inhibition of T effector cells. Extensive preclinical studies demonstrate that T3011 (and murine equivalent T3855) has potent antitumor activities. Methods: This phase 1 multicenter, open-label, dose escalation study evaluates the safety of intratumoral (IT) T3011 given once every other week (Q2W) in patients (pts) with advanced cutaneous or subcutaneous malignancies. The primary objective is to determine the Recommended Phase 2 Dose of T3011 based on the overall safety, pharmacokinetic and pharmacodynamic profile. Eligible pts are ≥ 18 years, have cutaneous or subcutaneous advanced cancer that has progressed on standard treatment and at least 1 measurable tumor lesion (≥ 10 mm) suitable for T3011 IT injection. Part 1 of the study uses a 3+3 design to evaluate the safety and tolerability of T3011 monotherapy in 4 escalating doses (1 × 106, 1 × 107, 5 × 107, and 1 × 108 PFU/mL). Up to 4 mL of T3011 may be injected based on tumor size. Total enrollment will be determined by toxicities observed. Results: As of Feb. 14, 8 pts have received IT T3011 (Q2W): 3 in Cohort 1 (1 × 106), 3 in Cohort 2 (1 × 107), and 2 in Cohort 3 (5.0 × 107 PFU/ml). Maximum doses per pt was 11. Enrollment continues in Cohort 3. T3011 was well tolerated with no ≥ Grade 3 treatment-related adverse events (AEs), no DLTs or treatment-related SAEs reported to date. Common AEs were pain at injection site, leukopenia, anemia, hypocalcemia, nausea, fever, headache, dermatitis, and diaphoresis. Viral shedding was analyzed in blood, urine and saliva at various times during the study. No Viral DNA was detected in blood or urine samples (first 3 pts analyzed) to date. Biopsy samples taken from injected tumors from 2 melanoma pts (Cohort 1) revealed significant reduction of viable tumor cells after 4 injections (Week 9) compared with baseline. In particular, one post-treatment biopsy contained 45% tumor necrosis area with dramatic increases of CD8 + and NKT cells. CD3+ and CD4+ cells as well as PD-1 expression were increased in post-treatment biopsies of both pts. Conclusions: T3011 IT injection was well tolerated at the first 2 dose levels. Post treatment biopsies from 2 pts (Cohort 1) demonstrated significantly reduced tumor cell viability as well as increased lymphocyte infiltration indicating on-target anti-tumor activities of T3011. To date, 5 out of 6 evaluable pts had SD as best response and 6 enrolled pts remain on study. Dose escalation is continuing. Clinical trial information: NCT04370587.

Research Techniques Made Simple: Preclinical Development of Combination Antitumor Targeted Therapies in Dermatology

The identification and application of targeted therapies that inhibit critical pathways in malignant cells have shown tremendous promise for improving clinical outcomes for patients with advanced cutaneous malignancies. However, tumor cell heterogeneity, development of drug resistance, and risks of off-target effects remain barriers to prolonged remission and definitive cure. Herein, we describe the potential that combinations of antitumor targeted agents may offer in overcoming these challenges and detail techniques whereby promising combination regimens can be identified and further evaluated preclinically. Cancer cell lines and primary patient-derived malignant cells can be utilized to perform dose-response screenings invitro for individual targeted agents before moving toward the evaluation of potential synergistic combinations. Mathematical analyses, including the Chou-Talalay method, determine combination indices and Hill slopes that permit relative comparisons among various drug combinations by quantification of synergistic activities. Further preclinical invivo evaluation of promising single versus combination regimens may be studied in relevant mouse models of cutaneous malignancy. Ultimately, the formulation of combination targeted therapy regimens may be more broadly effective and less toxic, helping to better inform clinical trial design and prioritization.

Back to square one: Peripheral margin control of advanced cutaneous malignancies in a multidisciplinary setting

Back to square one: Peripheral margin control of advanced cutaneous malignancies in a multidisciplinary setting

Immunotherapy efficacy and safety in elderly cutaneous malignancy patients.

e21524Background: Immunotherapy (IT) has become the mainstay treatment for advanced cutaneous malignancies (ACM), with superior efficacy and tolerability than chemotherapy. Use in elderly patients ...

Approach to the advanced stage cutaneous, tumors of the head and neck: A retrospective analysis of 50 cases

Skin cancer is the most common form of malignancy in the world, the incidence of cutaneous malignancies has increased dramatically over the past several decades. More than 80% of cases involve the head and neck region, resection and latter reconstruction of advanced cutaneous malignancies constitute significant problems due to aesthetic and functional concerns. Aim of this study is to discuss the therapeutic options and challenges usually seen in the treatment course. From 2006 to 2016, 50 patients with advanced stage (TNM stage of 3 or greater) cutaneous head and neck cancers were included in the study. Patients were evaluated according to demographic data and treatment options. The mean age of patients was 61.4 (26-87), 32 were male and 18 were female. Most common tumor type was squamous cell carcinoma (36 patients), most common localizations were mandible (7 patients) and orbita (6 patients). After tumor ablation, most commonly performed reconstruction was free tissue transfer (31 patients). 38 patients received adjuvant therapy (chemotherapy, radiotherapy or interferon) at the postoperative period. Six patients were lost at following one year period. Head and neck region are more exposed to direct sunlight than any other body part. Especially advanced stage cutaneous malignancies can be seen in these region due to patient negligence and previous failed treatment attempts. Surgical therapy is long standing option, usually necessitates 3D reconstruction with free flaps and multidisciplinary approach is crucial in the treatment course. Postoperative rehabilitation is complex and demanding process which requires extra patient and family motivation, also must be individualized for each patient.

Bone resection for facial cutaneous malignancies.

The aim of this study is to analyze the clinical outcomes of patients who underwent bone resection for cutaneous malignancy of the face and scalp. We retrospectively collected patient data from 62 patients who underwent bone resection for craniofacial cutaneous malignancy of the face and scalp over the last 10 years. We investigated risk factors for disease progression and assessed the utility of pre-operative imaging to predict bone, dura, and brain infiltration. Out of all factors analyzed, brain invasion, surgical margin involvement, and dural margin involvement were found to significantly reduce survival. CT and MRI correctly predicted bone infiltration in 88% and 89% of cases. MRI correctly predicted dura invasion in 89% but grossly underestimated the amount of dural invasion in 23% of reports. Our data indicate that the resection of bone is a reasonable surgical option in the treatment of patients with advanced cutaneous malignancies of the face and scalp. Brain invasion and positive margins reduced the probability of survival.

Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial

Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies. In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m(2) bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm(2)). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed. Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred. TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials. PCI Biotech.

Management of Facial Paralysis due to Extracranial Tumors.

Treatment of advanced parotid or cutaneous malignancies often requires sacrifice of the facial nerve as well as resection of the parotid gland and surrounding structures. In addition to considerations regarding reinnervation and dynamic reanimation, reconstruction in this setting must take into account unique factors such as soft tissue volume deficits and the high likelihood of adjunctive radiation therapy. Furthermore, considerations of patient comorbidities including advanced age and poor long-term prognosis often influence reconstructive modality. The optimal reconstructive technique would provide potential for restoration of facial tone and voluntary movement as well as immediate restoration of facial support and function. Beyond considerations of facial movement and rest position, restoration of lost soft tissue volume is critical to obtain facial symmetry. To control long-term volume in the setting of adjunctive radiation therapy, vascularized tissue is required. In this chapter, we describe a comprehensive approach to the management of radical parotidectomy and similar facial defects that addresses these concerns and also describes management strategies over time. Specific techniques employed include anterolateral thigh free flaps, nerve grafting utilizing motor nerves to the vastus lateralis muscle, and orthodromic temporalis tendon transfer. Further considerations relative to the eye, forehead, and long-term facial refinement are also discussed.

The management of non-melanocytic skin malignancies of the scalp and calvarium.

Background:The management of advanced cutaneous malignancies has been controversial. Thirteen patients with nonmelanoma skin neoplasias that had invaded the bone of the calvarium and scalp were treated in our centre.Objective:The purpose of this study was to evaluate our experience in treating these malignancies with scalp resection and full or partial thickness cranium reconstruction.Patients and Methods:From June 2008 to March 2012, thirteen patients with locally advanced tumours of the scalp invading the calvarium were treated with wide local excision of the scalp combined with an underlying craniectomy and dural resection if needed.Results:Using histopathological diagnosis eleven patients were diagnosed with basal cell carcinoma and two patients with squamous cell carcinoma. A full thickness cranium resection was performed in seven patients and partial in six patients.Conclusion:These large cancers occasionally invade adjacent structures, as well as bone, presenting a challenging surgical problem. In general, giant rotational or island scalp flaps and free tissue transfers are needed to close the area. Finding clean margins are an important part of treating patients with bone involvement and can usually be attained using outer tabula curettage thus preventing unnecessary morbidity.

Systemic treatment in the management of head and neck cutaneous malignancies

For many advanced cutaneous malignancies, combined modality approaches with surgery, radiation, and systemic treatment with chemotherapy and/or biotherapy can maximize outcome for skin cancers of head and neck regions. Use of systemic therapies when given together or separately from radiation therapy, as the case may be, can often lead to better outcomes, with less overall morbidity and a higher likelihood of complete extirpative surgery. Good examples of this concept would be the use of concurrent chemoradiation for locally advanced squamous cell carcinoma of the skin, in which very large invasive tumors can be rendered dramatically smaller, if not completely gone. A novel oral biological drug that targets the Hedgehog signaling pathway, vismodegib, can shrink initially locally advanced unresectable basal cell carcinomas to a resectable, if not completely regressed, and hence curable state with the need for less aggressive and potentially disfiguring surgery. Adjuvant systemic therapies given after definitive surgery may also improve survival by reducing the likelihood of metastatic relapse in patients with aggressive melanoma or Merkel cell carcinoma. This review will provide further detail with regard to the use of some of the available systemic treatments for the common cutaneous malignancies of the head and neck, including squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and Merkel cell carcinoma, to provide a better understanding of the multimodality approaches in these malignancies.

Immunotherapy for Cutaneous Malignancy

Immunotherapy for cutaneous malignancy involves manipulating the immune system to treat and prevent skin cancer. Although initial efforts were fraught with low success rates and technical challenges, more-recent endeavors have yielded response rates approaching 50% for treating metastatic melanoma. Many of these advances are a result of increasing knowledge of the immune system's intricacies and continued progress in laboratory techniques. To review our current understanding of the skin immune system and discuss how these factors contribute to the host response to malignancy and to report the current state of immunotherapeutic techniques. An extensive PubMed literature search was conducted in topics involving immunotherapy with specific relevance to cutaneous malignancy using the MeSH terms "immunotherapy" and "skin cancer." Despite initially poor patient responses to these treatment modalities, recent gains in scientific knowledge and clinical intervention protocols have brought immunotherapy to the forefront of prospective skin cancer therapeutics, particularly for advanced melanoma. Current treatment options for advanced cutaneous malignancies such as melanoma are low in efficacy. Immunotherapies have the potential to provide novel approaches to address this, particularly when used in combination. The authors have indicated no significant interest with commercial supporters.

Microsurgical Reconstruction of Large, Locally Advanced Cutaneous Malignancy of the Head and Neck

Large, locally advanced cutaneous malignancy of the head and neck region is rare. However, when present, they impart a significant reconstructive challenge. These cancers have a tendency to invade peripheral tissues covering a large surface area as well as expose deeper structures such as skull, dura, orbit, and sinus after resection. Complicating the reconstructive dilemma is the high incidence of individuals who have undergone previous surgery in the region as well as adjuvant radiation therapy, which may preclude the use of local flaps or skin graft. Free tissue transfer provides a reconstructive surgeon the ability to provide well-vascularized tissue with adequate volume not limited by arc of rotation.

Applicability of the Pittsburgh Staging System for Advanced Cutaneous Malignancy of the Temporal Bone

The objectives are to evaluate the applicability of the Pittsburgh staging system (PSS) (designed for primary temporal bone malignancies) to advanced periauricular cutaneous malignancies with temporal bone involvement and to study treatment outcomes and prognostic factors predicting recurrence-free survival. Ten patients with advanced periauricular cutaneous malignancy with temporal bone involvement were identified. Patients with primary temporal bone or parotid gland malignancies were excluded. All patients were clinically T4 at presentation by the American Joint Committee on Cancer (AJCC) staging system. Using Pittsburgh staging, six were T1 (stage I) and four were T4 (stage III). The mean follow-up was 13.6 months (3 to 24 months). Patients with basal cell carcinoma were managed with wide local excision and lateral temporal bone resection (WLE/LTBR) without adjuvant therapy. Two of three (66%) are alive and free of disease; one patient died of other causes. Treatment for squamous cell carcinoma patients involved multimodality therapy. Kaplan-Meier survival curves show a worse prognosis in terms of disease-specific survival for patients with higher-staged PSS tumors. This did not reach statistical significance. The PSS may provide additional prognostic information on advanced cutaneous malignancies of the temporal bone over the more widely used AJCC staging system. However, further prospective multicenter studies with larger sample size are required to validate our findings. Basal cell carcinoma was well controlled with WLE/LTBR alone without adjuvant therapy, whereas squamous cell carcinoma required multimodality therapy: WLE/LTBR and postoperative radiation with or without chemotherapy.

Applicability of the Pittsburgh Staging System for Advanced Cutaneous Malignancy of the Temporal Bone

Applicability of the Pittsburgh Staging System for Advanced Cutaneous Malignancy of the Temporal Bone

Isolated limb infusion with melphalan for the treatment of advanced nonmelanoma cutaneous malignancies

Isolated limb infusion with melphalan for the treatment of advanced nonmelanoma cutaneous malignancies