Optimal adjuvant radiotherapy dose for stage I, II or III Merkel cell carcinoma: an analysis of the National Cancer Database.
- 作者列表："Yusuf M","Gaskins J","Wall W","Tennant P","Bumpous J","Dunlap N
BACKGROUND:We performed an analysis of the National Cancer Database to determine optimal doses of conventionally-fractionated adjuvant radiotherapy for patients with stage I/II or III Merkel cell carcinoma. METHODS:The cohort included 2735 patients with resected Merkel cell carcinoma of the head and neck, trunk or extremities receiving radiotherapy. Exclusion criteria included doses of radiotherapy <30 or >80 Gy, or dose per fraction >200 or <180 cGy. Recursive partitioning analysis and spline models were used to select dose thresholds. Multivariable Cox regression was performed to validate thresholds with respect to overall survival. RESULTS:Recursive partitioning analysis models defined a threshold of 57 Gy for stage I/II Merkel cell carcinoma, above which 3-year overall survival rate was decreased (P < 0.0001). The 3-year overall survival rate for patients receiving 50.0-57.0 Gy (81.2%) was greater compared to doses of 30.0-49.9 Gy (75.3%) or >57.0 Gy (70%, P < 0.0001). Doses > 57.0 Gy were associated with an increased hazard of death (1.31, confidence interval 1.07-1.60) with respect to doses of 50.0-57.0 Gy. Doses < 50.0 Gy for stage III Merkel cell carcinoma were associated with worsened 3-year overall survival (P < 0.0001) and increased hazard of death (2.01, confidence interval 1.43-2.82) with respect to doses between 50.0 and 57.0 Gy. CONCLUSIONS:Our results support doses of 50-57 Gy for most patients with stage I/II Merkel cell carcinoma receiving conventionally-fractionated adjuvant radiotherapy. In contrast to a prior National Cancer Database analysis, our results suggest doses ≥ 50 Gy should be strongly considered for patients with stage III Merkel cell carcinoma regardless of anatomic subsite.
背景: 我们对国家癌症数据库进行了分析，以确定I/II期或III期Merkel细胞癌患者常规分割辅助放疗的最佳剂量。 方法: 队列包括 2735 例切除的头颈部、躯干或四肢Merkel细胞癌接受放疗的患者。排除标准包括放疗剂量 <30 或> 80 Gy，或每部分剂量> 200 或 <180 cGy。采用递归分区分析和样条模型选择剂量阈值。进行多变量Cox回归以验证总生存期的阈值。 结果: 递归分区分析模型定义了I/II期Merkel细胞癌的阈值为 57 Gy，超过此阈值，3 年总生存率降低 (P <0.0001)。接受 50.0-57.0 Gy (81.2%) 的患者的 3 年总生存率高于 30.0-49.9 Gy (75.3%) 或> 57.0 Gy (70%，P <0.0001)。剂量> 57.0 Gy与 1.31-1.07 Gy剂量相比，死亡风险增加 (1.60，置信区间 50.0-57.0)。剂量 <50.0 Gy的III期Merkel细胞癌与恶化的 3 年总生存率 (P < 0.0001) 和死亡风险增加相关 (2.01，置信区间 1.43-2.82) 关于 50.0 和 57.0 Gy之间的剂量。 结论: 我们的结果支持大多数接受常规分割辅助放疗的I/II期Merkel细胞癌患者 50-57 Gy的剂量。与之前的国家癌症数据库分析相反，我们的结果表明，对于III期Merkel细胞癌患者，无论解剖部位如何，都应强烈考虑剂量 ≥ 50 Gy。
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.