Chemotherapy Following PD-1 Inhibitor Blockade in Patients with Unresectable Stage III/Stage IV Metastatic Melanoma: A Single Academic Institution Experience.
不可切除的III期/IV期转移性黑色素瘤患者PD-1 抑制剂阻断后的化疗: 单个学术机构的经验。
- 作者列表："Karachaliou GS","Ayvali F","Collichio FA","Lee CB","Ivanova A","Ollila DW","Moschos SJ
:Retrospective case studies in various cancers have shown clinical benefit from chemotherapy following PD-1 inhibitor progression. We asked whether we see a similar clinical benefit with chemotherapy following PD-1 inhibitor progression in metastatic melanoma. We performed a retrospective study in patients with metastatic melanoma, who had received PD-1 inhibitor-based treatments, subsequently progressed, and eventually received chemotherapy. We identified 25 patients (median age 58 years; range 31-77 years; 13 females). Most patients had cutaneous melanoma (72%), were BRAFV600E-negative (75%), and received single-agent temozolomide (84%). At a median follow-up of 21.0 months (range: 4.1-154.2 months), 2 patients had durable response to chemotherapy (progression-free survival is 31.9+ and 21.6+ months, respectively), and 1 patient had a partial, short-term response. We conclude that in this poor prognosis group administration of chemotherapy has a 12% response rate that can be durable. Overall, the clinical benefit is not inferior to that of PD-1 inhibitor-based treatments.
: 各种癌症的回顾性病例研究表明，PD-1 抑制剂进展后化疗可获得临床益处。我们询问，在转移性黑色素瘤中，PD-1 抑制剂进展后，化疗是否有类似的临床获益。我们对转移性黑色素瘤患者进行了一项回顾性研究，这些患者接受了基于PD-1 抑制剂的治疗，随后进展，最终接受了化疗。我们确定了 25 例患者 (中位年龄 58 岁; 范围 31-77 岁; 13 例女性)。大多数患者有皮肤黑色素瘤 (72%)，BRAFV600E-negative (75%)，并接受单药替莫唑胺 (84%)。中位随访 21.0 个月 (范围: 4.1-154.2 个月)，2 例患者对化疗有持久反应 (无进展生存期为 31.9 + 和 21.6 + 个月，分别) 和 1 例患者有部分短期反应。我们的结论是，在这个预后不良的组中，化疗的给药有 12% 的反应率，可以持久。总体而言，临床效益不逊于PD-1 抑制剂为基础的治疗。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.