Characterization and Prognostic Significance of Cutaneous Adverse Events to Anti-Programmed Cell Death-1 Therapy

BACKGROUND: Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. METHODS: We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. RESULTS: Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1–378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. CONCLUSION: Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response.

Case of Secondary Cutaneous Peripheral T Cell Lymphoma, NOS / 대한피부과학회지

No abstract available.

Pancreatic Extraskeletal Osteosarcoma Metastasizing to the Scalp

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

Immediate Breast and Chest Wall Reconstruction for Advanced Breast Cancer

PURPOSE: Advanced breast cancer traditionally has been perceived as a contraindication to immediate breast reconstruction, because of concerns regarding adjuvant treatment delays and the cosmetic effects of radiotherapy to breast reconstruction, so delayed reconstruction is usually preferred in advanced breast cancer patients undergoing mastectomy. However, with the improved outcome using multimodality therapy, consisting of perioperative chemotherapy and radiotherapy, immediate breast reconstruction is now being performed as surgical option for selected advanced breast cancer patients. Additionally, advanced breast cancer patients may be needed soft tissue coverage of an extensive skin and soft tussue defect after mastectomy. Current authors have experienced several types of immediate breast and chest wall reconstruction for advanced breast cancer. METHODS: From December of 2007 to June of 2009, 14 women performed for immediate breast and chest wall reconstruction for advanced breast cancer. They had been treated with neoadjuvant chemotherapy or chemoradiotherapy followed by modified radical mastectomy or radical mastectomy. Four different techniques were used immediate breast and chest wall reconstruction, which are pedicled TRAM flap(4 cases), extended LD flap with STSG(3 cases), thoracoabdominal flap(4 cases) and thoracoepigastric flap(3 cases). RESULTS: The mean age was 53 years and mean follow up period was 9 months. Patients' oncologic status ranged stage IIIa to stage IV. Two patients had major complications: partial flap necrosis of TRAM flap and one distal necrosis of thoracoabdominal flap. Three patients with stage IV disease died from metastases. CONCLUSION: The result of this study suggests that immediate breast and chest wall reconstruction can be considered as surgical option for advanced breast cancer. But we need long term follow up and large prospective studies for recurrence and survival.

Chest Wall Reconstruction with Thoracoabdominal Flap for Large Skin Defects after Mastectomy of Advanced Breast Cancer

PURPOSE: Radical surgical extirpation in advanced breast cancer patients produces extensive loss of skin with large defects requiring plastic surgical procedures for the closure. Many reconstructive methods exist, the choice of which depends upon the characteristic of the wound, extent of resection and patient comorbidities. For adequate coverage of the large skin defects following resection of advanced breast cancer, current authors have performed a thoracoabdominal flap. METHODS: From August 2008 to June 2009, 4 cases of thoraco-abdominal flap were performed for chest wall reconstruction after mastectomy of advanced breast cancer. Flap dissection was entirely performed in a subfascial plane and the flap involving the external oblique abdominal muscle. The flap was rotated clockwise in left chest wall defects and counterclockwise in right chest defects and the donor site was closed directly. RESULTS: Their mean age, 55.7 years and the average follow-up interval was 9 months. Patients' oncologic status ranged from stage IIIc to stage IV, it was classified according to the TNM staging system. Flap dimensions ranged between 15 x 15 and 25 x 25 cm. One flap sustained a partial loss at the distal margin and revision with pectoralis major musculocutaneous island flap. CONCLUSION: Large chest wall reconstructions are usually required after radical excision of advanced cancer stages patients with poor general conditions. Thoracoabdominal flap is a simple, quick single-stage procedure, and offer to patient fast recovery, low complication rate, enabling further concomitant adjuvant therapy.

Osteogenic Differentiation of Bone Marrow Stem Cell using Bi-phase Alginate Scaffold Including BMP-2

PURPOSE: The object of this study is to develop a novel BMP-2 delivery system for continuous osteogenic differentiation and to induce osteogenesis of stem cells using a bi-phase alginate carrier in vitro. METHODS: Alginate nanoparticle loaded BMP-2 was prepared by the reverse emulsification-diffusion technique. Physical properties and release profiles of alginate carriers were measured by Instron and ELISA kit, respectively. Cell viability and alkaline phosphate activity of hBMSCs differentiation was also evaluated by MTS and Metra(R)BAP assays, respectively. RESULTS: Optimal concentration for bi-phase alginate carrier was determined as 2wt% by evaluating mechanical and biological properties, and differentiation of BMSCs for bone regeneration. The 2% bi-phase alginate carrier had the lowest initial and final release ratio. In addition, the 2% bi-phase alginate carrier had a little higher ALP activity than the homogeneous carrier. An improved controlled release profile was obtained by combining alginate hydrogel with lyophilized particles. CONCLUSION: Bi-phase alginate carrier has many advantages such as biocompatibility and controlled release capability. It is expected to be effective as a scaffold and carrier in bone tissue engineering.