Cutaneous adverse events associated with PD-1 inhibitor-based therapy in patients with non-small-cell lung cancer.

Aim: To analyze the incidence and characteristics of cutaneous adverse events (CAEs) in non-small-cell lung cancer patients treated with PD-1 inhibitor-based therapy. Methods: A total of 150 non-small-cell lung cancer patients under PD-1 inhibitor-based therapy from February 2018 to September 2021 were included and were followed up with regularly. Results: Over one-half of patients (88/150; 58.7%) had CAEs. Reactive cutaneous capillary endothelial proliferation, maculopapular rash and pruritus were the most common CAEs. The incidences of CAEs were 50.0 (18/36), 67.0 (50/75) and 51.3% (20/39) with PD-1 inhibitor monotherapy, PD-1 inhibitor in combination with chemotherapy and PD-1 inhibitor in combination with antivascular/targeted therapy, respectively. Conclusion: CAEs occur frequently in PD-1 inhibitor-based therapy but are generally tolerable.

Xanthoma Disseminatum in a Young Patient with Diabetes Insipidus.

Xanthoma disseminatum (XD) is a nonfamilial type of normolipidemic mucocutaneous xanthomatosis that belongs to the group of non-Langerhans cell histiocytoses. More than 100 cases of XD have been reported. In this study we report a case of XD in a 4-year-old boy with diabetes insipidus (DI). This boy is one of the youngest patients ever to present with XD combined with DI.

Blastic plasmacytoid dendritic cell neoplasm of the skin associated with myelodysplastic syndrome.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a recently described, rare hematologic malignancy with prominent skin involvement. The prognosis of this disease is poor in most cases, with rapid progression despite chemotherapy administration. The first reported case of this disease was in 1994, and less than 200 cases worldwide have been described in the literature to date. Moreover coexistence of BPDCN and MDS is extremely rare. In this study, we describe a typical patient with BPDCN in China who presented with cutaneous involvement as the first manifestation associated with MDS; a brief review of literature is also given.

Cutaneous adverse events in lung cancer patients on the therapy based on PD-1/PD-L1 inhibitors: A prospective observational cohort study.

AIM: This is a prospective study of cutaneous adverse events (CAEs) in lung cancer patients treated by programmed cell death-1(PD-1) inhibitors and programmed cell death-ligand 1(PD-L1) inhibitors-based single or combination therapy. PATIENTS & METHODS: It were included that lung cancer patients who developed CAEs from January 2019 to July 2021 after applying PD-1/PD-L1 inhibitors in our institution. RESULTS: A total of 107 patients with 112 CAEs were enrolled, of which 71 patients received PD-1/PD-L1 inhibitors plus chemotherapy, 31 patients received PD-1/PD-L1 inhibitors plus anti-angiogenic/targeted therapy, and 5 patients received PD-1/PD-L1 inhibitors monotherapy. The median time to CAEs onset was 8.7w (0.3w-70.7w) for PD-1/PD-L1 inhibitors plus chemotherapy, 10.1w (0.4w-103.0w) for PD-1/PD-L1 inhibitors plus anti-angiogenic/targeted therapy, and 13.6w (0.7w-50.6w) for PD-1/PD-L1 inhibitors monotherapy. The most common CAEs were reactive cutaneous capillary endothelial proliferation (RCCEP) (30.8%, 33/107), followed by eczematous (21.5%, 23/107) and pruritus only (15.9%, 17/107). 7 patients (6.5%, 7/107) had grade 3-4 CAE. CONCLUSION: Most CAEs are mild to moderate and easily controlled. Early diagnosis and intervention for CAEs are important.

Antifungal activity of the repurposed drug disulfiram against Cryptococcus neoformans.

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 µg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.

Long-term survival in gliosarcoma with radiation-induced meningeal sarcomas: Case report and molecular features.

Gliosarcoma is a rare primary malignant tumor of the central nervous system with poor prognosis. The median survival time of this disease ranges from 6 months to 14.8 months. However, a computer literature search indicated few long-term survivors. We investigated a case of a survivor of gliosarcoma with radiation-induced meningeal sarcomas, who showed no indication of recurrence for more than 9 years. A battery of molecular studies was performed to develop a molecular profile of this unique patient. We also reviewed the distinct clinical and molecular features of the tumor.

Clinical outcomes of cyberknife stereotactic radiosurgery for lung metastases.

BACKGROUND: Cyberknife stereotactic radiosurgery is an emerging noninvasive technique for treating oligometastatic cancer. The aim of this study is to evaluate the efficacy and tolerability of cyberknife for the treatment of patients with lung metastases. MATERIALS AND METHODS: A total of 134 lung metastases in 95 patients were treated with cyberknife in the radiotherapy center of our hospital from March 2009 to March 2013. The number of lung metastases per patient ranged from one to four (single lesions in 63 patients, 66.3%). The average tumor volume was 14.6 cm(3) and the prescribed radiation dosage ranged from 30  to 60 Gy, fractionated one to five times with a 60% to 88% isodose line. The primary end point was local control (LC); secondary end points were survival and toxicity. RESULTS: The median follow-up was 17 months (ranging from 4 to 46 months). The 1-year LC rate was 97.6%, the 2-year LC rate was 90.6%, and the 3-year LC rate was 87.0%. The median survival time was 38.0 months and the median progression-free survival (PFS) time was 14.0 months. The 2-year PFS rate was 29.0% and the overall survival (OS) rate was 61.3%. No grade 4 or higher toxicity was encountered. CONCLUSIONS: Cyberknife is safe and effective treatment for patients with lung metastases.

CyberKnife Treatment for Kaposiform Hemangioendothelioma of the Ilium in an adult: case report and review of the literature.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that mainly affects infants. KHE rarely develops in adolescents and adults. These tumors tend to be locally invasive, but are not known to produce distant metastases. Numerous treatment modalities are available for KHE, but the optimal therapy is unknown. CASE REPORT: A 51-year-old woman was diagnosed with KHE of the ilium in September 2005. The lesion recurred within 5 years of local excision, and was subsequently treated with CyberKnife. Within 1 month of CyberKnife therapy, pain intensity was significantly reduced and the patient's quality of life was significantly improved. Since January 2011, she has remained pain-free and has had no signs of recurrence or metastasis for more than 2 years following CyberKnife therapy. CONCLUSION: We report the first CyberKnife treatment of an adult with KHE of the bone without accompanying cutaneous changes and Kasabach-Merritt syndrome. CyberKnife treatment could be a useful temporizing measure for bone KHE.

CyberKnife radiotherapy for malignant fibrous histiocytoma of the chest wall: A case report and review of the literature.

Malignant fibrous histiocytoma (MFH) is the most common type of soft tissue sarcoma, but rarely originates in the chest wall. Surgical resection is considered to be the most reliable treatment, however, no consensus has been reached concerning the best treatment for unresectable MFH. The current study presents the case of a 77-year-old male with MFH of the chest wall. The patient developed a painless mass and intermittent fever over a four-month period. A computed tomography scan demonstrated a large inhomogeneous lesion in the right chest wall, which was subsequently diagnosed via biopsy as a MFH. Since the tumor was an unresectable mass, CyberKnife® radiotherapy was conducted. Following the treatment, a marked reduction in the tumor size was observed with a tolerable level of toxicity. The sequencing analysis also revealed an in-frame deletion (delE746-A750) in exon 19 of the epidermal growth factor receptor gene. Based on this result, gefitinib was administered to the patient at a dose of 250 mg/day.

Gefitinib combined with stereotactic radiosurgery in previously treated patients with advanced non-small cell lung cancer.

BACKGROUND: Disease progression remains the major challenge in the management of advanced (stage IIIb or IV) non-small cell lung cancer (NSCLC) after the failure of first-line or second-line chemotherapy, or even of targeted therapies such as gefitinib. The current study evaluated the tolerability and efficacy of stereotactic body radiation therapy (SBRT) in combined with gefitinib as a second-line or third-line treatment in patients with advanced NSCLC. METHODS: Fourteen advanced NSCLC patients showing disease progression after platinum-based chemotherapy regimens were recruited. Eligible patients started taking gefitinib (250 mg/d) 7 days before SBRT and continued for 1 year until disease progression, unacceptable toxicity or withdrawal of consent. SBRT was delivered in median 3 fractions within 3 to 5 days. Treatment-associated toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v.3.0). Local control was assessed according to the Response Evaluation Criteria in Solid Tumors criteria and symptom assessments were measured by the Functional Assessment of Cancer Therapy-Lung instrument (V4.0). RESULTS: With an overall median follow-up of 15.5 months (range, 4 to 27 mo), most patients were well tolerated with common side effects from grade 1 to 2. No grade 4 or higher toxicity was encountered. The clinical disease-related symptom improvement rate was reached 57.1% with the median duration of symptom improvement of 8.0 months. The 1-year local control and overall survival (OS) rates were 83.9% and 69.6%, respectively. The median progression-free survival and OS were 7.0 and 19.0 months, respectively. CONCLUSIONS: The SBRT combined with gefitinib is a promising treatment strategy for advanced (stage IIIb or IV) NSCLC after the failure of previously chemotherapy. This method improves local control and disease-related symptoms with tolerated toxicity, and even increases the progression-free survival and OS.