BACKGROUND. Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed. METHODS. An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.

At present, storage capacities of single tank and tank farm have been greatly increasing. This change poses a real challenge for the applicability of current design standards. This article focuses on the applicability of safety spacing between tanks, which is one of the most important parameters of tank farm safety design. Taking PHAST and FDS as main research tools, the consequences of representative accidental scenarios were evaluated for different sizes of oil tanks to study the safety performance change caused by the increase of capability. The research results show that, when current standards are used to design the safety spacing between tanks, the safety performance increases as the capability increases. Considering the high property density, it is suggested that a higher safety performance objective has to be chosen when designing the safety spacing for ultra‐large oil tanks. © 2012 American Institute of Chemical Engineers Process Saf Prog, 2012.

BACKGROUNDExtracapsular spread (ECS) of metastatic squamous cell carcinoma of the head and neck to regional lymph nodes is the most reliable predictor of poor treatment outcomes. Recently, the authors have shown that ECS is significantly associated with higher rates of locoregional recurrence, distant metastasis, and decreased survival in patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this review was to determine if the degree of ECS impacts distant metastasis rates and survival.METHODSTwo hundred sixty‐six patients treated for SCCOT with surgery +/− adjuvant radiotherapy from 1980–1995 were reviewed. The setting was a tertiary referral center. The extent of ECS on histopathologic review of involved lymph nodes was measured from the capsular margin to the farthest perinodal extension in mm. Extent of ECS and the number of pathologic lymph nodes with or without ECS were analyzed for disease‐free interval, survival rates, and distant metastases.RESULTSNo differences in the survival of patients with ECS of ≤ 2 mm or > 2 mm was found (P = 0.92). Patients with both ECS and multiple positive lymph nodes had decreased overall survival (P = 0.0003), disease‐specific survival (P = 0.0005), and a shorter disease‐free interval (P = 0.019) when compared with those with a single positive lymph node with ECS. Those with multiple ECS+ lymph nodes had the worst prognosis (P = 0.001).CONCLUSIONSBased on these findings, the authors recommended that all patients with SCCOT with ECS or multiple positive lymph nodes with or without ECS on pathologic review be considered for clinical trials that intensify regional and systemic adjuvant therapy. Cancer 2003;97:1464–70. © 2003 American Cancer Society.DOI 10.1002/cncr.11202

Purpose: We evaluated the safety, maximum tolerated dose, pharmacokinetics, and biological effects of the combination of the Raf-1, RET, KIT, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor 2 kinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib. Experimental Design: A standard 3 + 3 phase I dose-escalation design was used with a 28-day cycle (sorafenib daily and tipifarnib for 21 days, by mouth). Results: Fifty patients were treated; 43 reached restaging evaluation after cycle 2. The most common side effects were grade 1 to 2 rash, hyperglycemia, and diarrhea. Doselimiting toxicity was rash, and the recommended phase II dose is sorafenib 400 mg p.o. qam/200 mg p.o. qpm and tipifarnib p.o. 100 mg bd. Despite the low doses of tipifarnib, one quarter of patients had ≥50% reduction in farnesyltransferase levels. Interestingly, six of eight patients with medullary thyroid cancer had durable stable disease (n = 3) or partial remissions (n = 3), lasting 12 to 26+ months. Five of the six responders had available tissue, and RET gene mutations were identified in them. Prolonged (≥6 months) stable disease was also seen in nine patients as follows: papillary thyroid cancer (n = 4; 18+ to 27+ months), adrenocortical cancer (n = 2; 7 and 11 months), and one each of melanoma (platelet-derived growth factor receptor mutation positive; 14 months), renal (6 months), and pancreatic cancer (6 months). Conclusions: Our study shows that the combination of tipifarnib and sorafenib is well tolerated. Activity was seen, especially in patients with medullary thyroid cancer, a tumor characterized by RET mutations. (Clin Cancer Res 2009;15(22):7061-8)

Medullary thyroid carcinoma (MTC) is an uncommon malignancy of hereditary and sporadic presentation. Mutations in the RET proto-oncogene are involved in the pathogenesis of familial MTC and >50% of the sporadic cases. Currently, there is no effective treatment for recurrent or metastatic MTC. We report here a rapid response to a sorafenib (RET and RAF kinase and vascular endothelial growth factor receptor inhibitor) -based regimen in a patient with sporadic MTC who had advanced, progressive disease and a novel RET kinase aberration at exon 11 shown in tumor tissue.

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