10541 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The evidence of AKT activation in a small group of chordoma patients (pts) prompted us to combine an mTOR inhibitor—sirolimus—to IM in IM-resistant advanced chordoma. Methods: Since July 2007, 7 progressive advanced chordoma patients (F=4, M=3; mean age 53 yrs; PS 0–2) with a secondary resistance to IM and biochemical evidence of AKT expression and activation, have started IM 400 mg/day + sirolimus (2–3 mg/day) on an individual use basis. Sirolimus blood levels were evaluated every 2 weeks. 2 pts were biopsed after 3 months of treatment. Results: Six pts are still on treatment, while one stopped therapy after 3 months for progression. 4 pts are evaluable for response (3 pts too early for response assessment). Treatment was in general well tolerated. The most common side effect requiring treatment discontinuation was G3 leucopenia, with one case of concomitant pneumonia and one case of G3 mucositis. In all cases, pts recovered after stopping treatment. After 4–6 weeks, 3 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease confirmed on CT/MRI after 3 months of treatment. In one pt, an ulcerated lesion shrunk in a few weeks. Post- treatment AKT assessment in pts undergoing biopsy is under evaluation. Conclusions: In 3 out of 4 evaluable advanced chordoma pts progressing on IM, tumor response was re-established by adding sirolimus to IM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, MedImmune, Novartis, Pfizer Oncology, sanofi-aventis Novartis, PharmaMar, SigmaTau Jansen Cilag, Novartis, Pfizer Oncology, Sigma Tau Novartis, PharmaMar
To evaluate the predictive capability of the pre- and post-pembrolizumab Vesical Imaging-Reporting and Data System (VI-RADS) to identify ypT0N0 or ypT≤1N0 response in muscle-invasive bladder cancer (MIBC) within the PURE-01 trial (ClinicalTrials.gov identifier: NCT02736266).
Purpose To determine the activity of pembrolizumab as neoadjuvant immunotherapy before radical cystectomy (RC) for muscle-invasive bladder carcinoma (MIBC) for which standard cisplatin-based chemotherapy is poorly used. Patients and Methods In the PURE-01 study, patients had a predominant urothelial carcinoma histology and clinical (c)T≤3bN0 stage tumor. They received three cycles of pembrolizumab 200 mg every 3 weeks before RC. The primary end point in the intention-to-treat population was pathologic complete response (pT0). Biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay), genomic sequencing (FoundationONE assay), and an immune gene expression assay. Results Fifty patients were enrolled from February 2017 to March 2018. Twenty-seven patients (54%) had cT3 tumor, 21 (42%) cT2 tumor, and two (4%) cT2-3N1 tumor. One patient (2%) experienced a grade 3 transaminase increase and discontinued pembrolizumab. All patients underwent RC; there were 21 patients with pT0 (42%; 95% CI, 28.2% to 56.8%). As a secondary end point, downstaging to pT<2 was achieved in 27 patients (54%; 95% CI, 39.3% to 68.2%). In 54.3% of patients with PD-L1 CPS ≥ 10% (n = 35), RC indicated pT0, whereas RC indicated pT0 in only 13.3% of those with CPS < 10% (n = 15). A significant nonlinear association between tumor mutation burden (TMB) and pT0 was observed, with a cutoff at 15 mutations/Mb. Expression of several genes in pretherapy lesions was significantly different between pT0 and non-pT0 cohorts. Significant post-therapy changes in the TMB and evidence of adaptive mechanisms of immune resistance were observed in residual tumors. Conclusion Neoadjuvant pembrolizumab resulted in 42% of patients with pT0 and was safely administered in patients with MIBC. This study indicates that pembrolizumab could be a worthwhile neoadjuvant therapy for the treatment of MIBC when limited to patients with PD-L1–positive or high-TMB tumors.
Authors analyze three cases of growing fractures they observed in infants under the age of one year. It is noticeable that in two cases, even if the lesion was already present when babies underwent the first procedure, no specific treatment was adopted, thus resulting in a progressive enlargement of the extracranial mass. Surgical treatment must be performed quickly after the diagnosis of growing fracture is done due to the necessity of an early repair of the bone defect to avoid the eventual onset of neurological deficits since they are not reversible.
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