radiation-induced subcutaneous fibrosis was found in 8 patients (5%) with a slight difference in disfavor of arm B (7%) vs 4% in arm A. Three patients (2%) presented a grade 2 pneumonitis (all in arm A). Overall, quality of life and cosmesis were good to excellent. Conclusions: Concurrent or sequential adjuvant radiohormonotherapy with letrozole is feasible in daily practice. Identifying hypersensitive patients with CD8 RIA or ATM screening will help tailoring treatments and details will be presented at the congress.
The metzincin metalloproteinase, tumor necrosis factor--converting enzyme (TACE), also known as ADAM (a disintegrin and metalloproteinase) 17, has recently been identified as an important enzyme for cleavage of the GH receptor (GHR) and shedding of GH-binding protein (GHBP). Proteolysis can be induced by phorbol esters, platelet-derived growth factor and serum; it is dependent on protein kinase C and partially on MAP kinase pathways. Proteolysis occurs at the cell surface, leading to extracellular release of GHBP and intracellular GHR remnant accumulation. The GHR remnant is further processed by -secretase activity, possibly leading to biologically active products. TACE-dependent GHR proteolysis can be inhibited by GH as the dimerized GHR is resistant to cleavage. The cleavage site lies within a short juxtamembranous stem region that extends between the transmembrane helix and the globular dimerization domain of the GHR. GHR proteolysis leads to downregulation of functional GHRs at the cell surface, and has complex secondary effects on GH action via GHBP and GHR remnant generation.
Background Linear and parallel are the two leading models of metastatic progression. In this study we propose a simple way to differentiate between them. While the linear model predicts accumulation of genetic and epigenetic alterations within the primary tumor by founder cells before spreading as waves of metastases, the parallel model suggests preclinical distribution of less advanced disseminated tumor cells with independent selection and expansion at the ectopic sites. Due to identical clonal origin and time of dispatching, linear metastases are expected to have comparable diameters in any specific organ while parallel metastases are expected to appear in variable sizes. Methods and findings Retrospective revision of chest CT of oncological patients with lung metastases was performed. Metastasis number and largest diameters were recorded. The sum number of metastases with a similar diameter (c) and those without (i) was counted and the linear/parallel ratio (LPR) was calculated for each patient using the formula (∑c-∑i)/(∑c+∑i). A LPR ratio of 1 implies pure linear progression pattern and -1 pure parallel. 12,887 metastases were measured in 503 patients with nine malignancy types. The median LPR of the entire group was 0.71 (IQR 0.14–0.93). In carcinomas of the pancreas, prostate, and thyroid the median LPR was 1. Median LPRs were 0.91, 0.65, 0.60, 0.58, 0.50 and 0.43 in renal cell carcinomas, melanomas, colorectal, breast, bladder, and sarcomas, respectively. Conclusions Metastatic spread of thyroid, pancreas, and prostate tumors is almost exclusively by a linear route. The spread of kidney, melanoma, colorectal, breast, bladder and sarcoma is both linear and parallel with increasing dominance of the parallel route in this order. These findings can explain and predict the clinical and genomic features of these tumors and can potentially be used for evaluation of metastatic origin in the individual patient.
Cancers of the nasal cavity and septum are associated with poor prognosis and are usually treated with surgery followed by post-operative radiotherapy with or without concurrent chemotherapy. Definitive radiotherapy is used in cases where the tumor is unresectable, patient is unfit for surgery, and/or the patient declines surgical intervention. Here, we present a case of a patient, who for non-medical reasons, opted to have non-surgical management of his rapidly progressing nasal cavity tumor. He was successfully treated with concurrent chemoradiotherapy utilizing a combination of intensity modulated proton therapy (IMPT) with passive scatter boost to reduce dose to the adjacent critical neural structures. Post-treatment clinical examination and imaging demonstrated complete clinical and metabolic response at the primary site and neck. This case highlights the use of IMPT and passive scatter boost in combination to achieve delivery of therapeutic dose to nasal cavity tumor and neck whilst limiting dose to numerous adjacent organs-at-risk.
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