The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22â1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83â1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC

Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line

Lack of Correlation between Liver Tests Abnormalities and Trabectedin Efficacy in the Treatment of Soft Tissue Sarcoma: A Retrospective Study

Elevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m2 once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free survival (PFS) and overall survival (OS) were analyzed. Liver tests abnormalities during the first two cycles of chemotherapy or at any time during trabectedin treatment did not significantly affect PFS or OS. Nor were survival outcomes significantly different in the subgroups of patients with or without ALT/AST increases or with ALT/AST elevations ≥15 × the upper limit of normal (ULN) versus those with ALT/AST elevation <15 × ULN. Although liver tests abnormalities are common in patients treated with trabectedin, elevations in ALT and AST are usually transient, occur during the first two cycles of treatment, and do not appear to affect survival

Maxillary distalization by a rearrangement of the Leaf Expander® screw combined with palatal miniscrews: A case report on the MaXimo Appliance

ABSTRACT Introduction: This case report describes the treatment of a crowded dental Class II malocclusion in 13 years, 2 months female patient. Maxillary distalization was achieved by a novel compliance-free appliance referred to as MaXimo, which was built by a rearrangement of the Leaf Expander® screw having palatal miniscrews as the anchorage core. Case Presentation: Pre-treatment, post-treatment and 1-year follow-up records are shown. No side effects, breakage of the appliance or loss of miniscrews was encountered. The active distalization phase lasted 14 months, while the whole treatment, including the use of multibrackets appliance, lasted 25 months. A significant spontaneous distal drifting of the premolars and canines was seen. The treatment outcomes proved to be stable at the follow-up with acceptable aesthetic and functional results. Conclusion: The MaXimo appliance proved to be efficient and of easy management, and its use may be recommended when distalization of the maxillary dentition is required. Being mostly assembled by the manufactured, the MaXimo appliance is also cheap and of easy construction

Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.

The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level

Multiple endocrine neoplasias type 2B and RET proto-oncogene

Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities

Endoscopic ultrasound-guided entero-colostomy with lumen-apposing metal stent as a rescue treatment for malignant intestinal occlusion: a multicenter study

Background: Surgery is the first-choice treatment for malignant intestinal obstruction (MIO); however, many patients are deemed unfit for surgery. Endoscopic ultrasound-guided entero-colostomy (EUS-EC) with a lumen-apposing metal stent (LAMS) could represent a new treatment option. Methods: Consecutive patients undergoing EUS-EC for MIO from November 2021 to September 2023 at four European tertiary referral centers were retrospectively enrolled. Multidisciplinary meetings determined whether patients were unsuitable for surgery or colonic stent placement, or refused surgery. The primary outcome was technical success of EUS-EC and secondary outcomes were clinical outcome, safety, and hospital stay. Results: 12 patients were enrolled (median age 72.5 [range 42-85] years; 58.3% female). Colonic adenocarcinoma was the primary tumor in 75.0% of patients and 91.7% had stage IV disease. Technical success was 100%. No LAMS misdeployment or other procedural adverse events occurred; three patients (25.0%) had severe post-procedural complications. Clinical success was achieved in 10 patients (83.3%), with 5 (50.0%) resuming chemotherapy after the procedure. Median post-procedural hospital stay was 9 (1-20) days and median overall survival was 47.5 (2-270) days. Conclusions: EUS-EC was a feasible technique and could be considered a possible alternative to standard approaches for MIO in highly selected patients