Role of Chemotherapy, VEGFR Inhibitors, and mTOR Inhibitors in Advanced Perivascular Epithelioid Cell Tumors (PEComas).

PURPOSE: Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. EXPERIMENTAL DESIGN: This was an observational, retrospective, international study that included patients with advanced/metastatic PEComa treated with systemic therapy at 5 European sarcoma reference centers and within the Italian Rare Cancer Network. Survival analyses were performed using the Kaplan-Meier method and the Cox hazards regression models. RESULTS: A total of 53 patients were included. Cytotoxic chemotherapy regimens were active only in a small proportion of PEComas. Gemcitabine-based regimens [objective response rate (ORR): 20%, median progression-free survival (PFS): 3.4 months] seemed to have the same activity of anthracycline-based regimens (ORR: 13%, median PFS: 3.2 months). Antiangiogenic agents resulted in disease stabilization in some patients, with a number having density changes/tissue response on imaging, with an ORR of 8.3% and a median PFS of 5.4 months. mTOR inhibitors were the most active agents, with an ORR of 41% and a median PFS of 9 months. CONCLUSIONS: Our study provides data for the selection of systemic therapy in patients with advanced/metastatic PEComa: mTOR inhibitors are the most active agents. Antiangiogenics and chemotherapy with gemcitabine-based regimens or anthracycline-based regimens are options in further line, but with a lower response rate and PFS.

Pediatric lung adenocarcinoma presenting with brain metastasis: a case report.

BACKGROUND: Diagnosis and treatment of primary lung adenocarcinoma in children remains challenging given its rarity. Here we highlight the clinical history, pathological evaluation, genomic findings, and management of a very young patient with metastatic lung adenocarcinoma. CASE PRESENTATION: A 10-year-old white girl presented with brain metastases due to primary pulmonary adenocarcinoma. Next generation sequencing analysis with "Comprehensive Cancer Panel" highlighted the presence of multiple non-targetable mutations in the FLT4, UBR5, ATM, TAF1, and GUCY1A2 genes. She was treated aggressively with chemotherapy, surgery, and radiation therapy for local and distant recurrence. Eventually, therapy with nivolumab was started compassionately, and she died 23 months after diagnosis. CONCLUSIONS: Extremely rare cancers in children such as lung adenocarcinoma need accurate and specific diagnosis in order to develop an optimal plan of treatment. It is also necessary to underline that "children are not little adults," thus implying that an adult-type cancer in the pediatric population might have a different etiopathogenesis. Diagnostic confirmation and primary treatment of such rare conditions should be centralized in reference centers, collaborative networks, or both, with multidisciplinary approaches and very specific expertise.

Sarcomas with spindle cell morphology.

In the days before the term "high-grade undifferentiated pleomorphic sarcoma" came into use, one of the most common sarcoma diagnoses was "malignant fibrous histiocytoma," and before that, in an era before immunohistochemistry, "fibrosarcoma" was used to describe most sarcomas. "Spindle cell" is a descriptive phrase that denotes the cellular shape of many of the sarcomas encountered in the adult population. As a result, they are usually treated differently from small round cell sarcomas, and have different biological characteristics than those tumors and sarcomas with epithelioid morphology. As a very broad generalization, sarcomas with a spindle cell microscopic morphology occur in adults and are treated primarily with surgery and often adjuvant or neoadjuvant radiation as primary therapy. In comparison to small round cell sarcomas such as Ewing sarcoma, the use of adjuvant chemotherapy remains controversial, and the sensitivity of these tumors to chemotherapy in the metastatic setting is highly variable. In this article, we describe some of the clinical and biological characteristics of this group of sarcomas.

Radiation-induced thyroid changes: a retrospective and a prospective view.

AIM OF THE STUDY: Incidental/therapeutic thyroid irradiation causes hypothyroidism and nodular disease. Increasing numbers of children are being cured of cancers by treatments that include radiation also involving the thyroid bed: these children warrant an early diagnosis and treatment of any radiation-related thyroid changes. METHODS: In 1998 we retrospectively evaluated thyroid parenchyma/function in all patients irradiated between 1975 and 1997; thereafter, we prospectively evaluated all patients given thyroid irradiation by means of thyroid ultrasound and serum fT3, fT4, TSH and thyroglobulin. RESULTS: Of 596 eligible patients, 468 agreed to the retrospective evaluation: 128/468 had one or more thyroid nodules, and 73 of these 128 had concomitant or previously untreated hypothyroidism, while 22/128 had a differentiated carcinoma. Another 144/157 patients treated between 1998 and 2004 were evaluated and any iatrogenic hypothyroidism was promptly treated: 19/144 had nodules, all smaller than 1cm in diameter. The first patient group was studied retrospectively, so we have no precise record of the time of nodule occurrence or of their initial sizes. We found, however, that both the number of patients with nodules and the sizes of the nodules were significantly lower (p<0.01) in the prospectively studied group (after a median follow-up of 81 months) than in the retrospectively studied group. Among all the patients with nodules, significantly more females developed cancer than males (p<0.04). CONCLUSIONS: Early treatment for hypothyroidism and ultrasound evaluation of the parenchyma are needed to limit nodule onset and growth.