To the Editor: The drawbacks to photodynamic therapy (PDT) for actinic keratoses (AK) include pain during illumination and patient access to a light source that is approved by the US Food and Drug Administration. To address this, dermatologists are exploring daylight PDT.1 Clinical studies in Europe and South America provide initial evidence that daylight exposure is efficacious.2,3 This randomized, single-blind trial investigated the tolerability and safety of daylight PDT for AK on the face and scalp in Northern California.

Background: Undifferentiated pleomorphic sarcoma (UPS) encompasses rare neoplasms that can arise either in the dermis or in the subfascial soft tissue. The behavior of UPS ranges from indolent to aggressive, but data predicting outcomes are limited. Objective: Identify predictors of poor outcomes by analyzing a large collection of UPS cases. Methods: We evaluated all available cases of UPS (including those termed atypical fibroxanthoma, malignant fibrous histiocytoma, pleomorphic dermal sarcoma, and subfascial UPS) across 3 tertiary care centers. Results: Among the 319 patients, 45 experienced recurrence, 33 experienced metastasis, and 96 died of any cause. Risk factors for recurrence were clinical tumor size larger than 5 cm and invasion beyond subcutaneous fat. Risk factors for distant metastases were tumor site, tumor size larger than 2 cm, invasion beyond subcutaneous fat, and lymphovascular invasion. Risk factors for overall mortality were age, immunosuppression, tumor size larger than 2 cm, and lymphovascular invasion. History of skin cancer was associated with a lower risk of recurrence and metastasis. Limitations: This was a retrospective study. Conclusions: Using the unbiased approach of pooling all UPS cases regardless of terminology, we identified clinical and histologic factors predicting poor outcomes. We propose subcategorization of UPS (into superficial versus deep UPS), which is consistent with the American Joint Committee on Cancer staging of soft-tissue sarcoma.

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at 5 years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal. With this comprehensive review, we provide an update of MCC epidemiology, pathogenesis, clinical presentation, diagnostic evaluation and prognostic markers. The second article in this continuing medical education series explores the evolving landscape in MCC management.

Merkel cell carcinoma (MCC) is an uncommon primary cutaneous neuroendocrine cancer. It most commonly presents as an indurated plaque or nodule on sun-damaged skin in elderly patients and is characterized by high rates of local recurrence and nodal metastasis. Survival at 5 years is 51% for local disease and as low as 14% for distant disease, which underscores the aggressive nature of this tumor and challenges in management. Advances in immunology and molecular genetics have broadened our understanding of the pathophysiology of MCC and expanded our therapeutic arsenal. With this comprehensive review, we provide an update of MCC epidemiology, pathogenesis, clinical presentation, diagnostic evaluation and prognostic markers. The second article in this continuing medical education series explores the evolving landscape in MCC management.

Basal cell carcinoma (BCC) arises from loss-of-function mutations in tumor suppressor patched homologue 1, which normally inhibits smoothened homologue in the sonic hedgehog signaling pathway.1,2 Vismodegib, a smoothened homologue inhibitor,2 is US Food and Drug Administration (FDA) approved for metastatic or locally advanced BCC that has recurred after surgery or for patients who are not candidates for surgery and radiation.1,2 Common adverse effects of vismodegib are muscle spasms, alopecia, dysgeusia, nausea, and weight loss.

Total body irradiation (TBI) is an important component of hematopoietic stem cell transplant (SCT) for pediatric malignancies. With increasing survival rates, late effects of SCT become more important. Younger children may be at particular risk of late effects of radiation and SCT.

PURPOSE:We have clinically observed that larger rotational setup errors are more prominent in pediatric patients who received radiation therapy for brain tumors. In this work, we quantitatively evaluated the daily setup corrections in pitch, roll, and yaw axes for children who received intracranial radiation therapy under x-ray image guidance. METHODS:Daily localization data of 43 patients between the ages of 10 months and 21.9 years were analyzed in this study. Patients were immobilized with thermoplastic mask during treatments, and 2D orthogonal x-ray images wereacquired for setup corrections before each treatment. Rotational setup corrections in pitch, roll, and yaw axes were extracted from 873 treatment fractions, and were analyzed for the whole group of patients and for two age groups: < 5 and = 5 years old. RESULTS:The mean values for the pitch corrections were 1.91° and 1.65° (p:0.02), roll corrections were 1.37° and 1° (p<0.001), and yaw corrections were 1.93° and 1.47° (p<0.001), respectively. For patients < 5 years, 21.7% of treatments had pitch corrections more than 3°, versus 15.6% of treatments required pitch corrections more than 3° for patients >= 5 years. Similarly, 10.6% of roll corrections and 20.9% of yaw corrections were more than 3° for patients < 5 years. On the other hand, 2.1% of roll and 13.8% of yaw corrections were more than 3° for patients = 5 years old. CONCLUSIONS:Data indicate that children less than 5 years old are more prone to rotational setup errors during intracranial radiation therapy. This can be attributed to reduced efficacy of immobilization devices due to smaller and rounder anatomicalfeatures of pediatric patients, and challenges in setup while the patient is under anesthesia. The role of daily image guidance and rotational setup corrections becomes important to ensure target coverage, especially for children < 5 years old.

Atypical teratoid/rhabdoid tumors (ATRT) are rare, highly malignant, embryonal CNS tumors with a poor prognosis. Therapy relies on highly toxic chemotherapy and radiotherapy. To improve outcomes and decrease morbidity, more targeted therapy is required. Gene expression analysis revealed elevated expression of multiple kinases in ATRT tissues. Aurora Kinase A was one of the candidate kinases. The objective of this study was to evaluate the impact of Aurora Kinase A inhibition in ATRT cell lines. Our analysis revealed that inhibition of Aurora Kinase A induces cell death in ATRT cells and the small molecule inhibitor MLN 8237 sensitizes these cells to radiation. Furthermore, inhibition of Aurora Kinase A resulted in decreased activity of pro-proliferative signaling pathways. These data indicate that inhibition of Aurora Kinase A is a promising small molecule target for ATRT therapy.