No abstract

4570 Background: Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a small subset of urothelial carcinoma (UC) and confer a sensitivity to immunotherapy in multiple solid tumors. Due to the rarity of this patient subset in UC, there is a lack of prospective data on their prevalence or of clinical outcomes with immunotherapy and other treatment modalities. Methods: We performed a systematic review with the objectives of estimating the prevalence of dMMR and MSI-H in urothelial bladder cancer (BC) and upper tract urothelial carcinoma (UTUC) apart from estimating survival and clinical outcomes of treatment. We searched for published prospective and retrospective studies, review articles, case reports, case series, conference proceedings, letters, commentaries, and editorials on dMMR and MSI-H in BC and UTUC published up to 10/26/2022 in PubMed, Cochrane CENTRAL, Embase and Web of Science: Core Collection databases. The study protocol is registered on the PROSPERO database (CRD42022365690). Prevalence data were analyzed using meta-analysis with random-effects models and are reported here. Results: A total of 1,750 studies were screened, of which 125 were included. Thirty-six studies (including 5,113 patients) reported frequencies of dMMR, and 42 studies (including 21,291 patients) reported on MSI-H. Of the total included patients, sex was reported in 11,225, with 72.6% being male and 27.4% female. Age ranged from 17-97 years. Reported primary site was BC in 64.4%, UTUC in 16.3% and not stated in 19.3%. Disease stage reported in 5,341 patients was M0 in 75.0% and M1 in 25.0%. Of the M0 patients, tumor stage data were available in 3,149 patients: Ta-T1 in 33.6% and T2-T4 in 66.4%. The pooled weighted prevalence of dMMR in UC patients was 6% (95% CI 5-8%). The breakdown for BC and UTUC were 2% (95% CI 1-3%) and 9% (95% CI 7-12%), respectively. The three most frequent MMR protein loss patterns in UC, BC and UTUC are shown in the table. Out of 42 studies reporting MSI status, 21 used polymerase chain reaction (PCR) and 21 used next-generation sequencing (NGS). Pooled weighted prevalence of MSI-H in UC was 3% (95% CI 2-3%). In BC, the prevalence was 1% (95% CI 1-1%) and in UTUC, it was 11% (95% CI 8-13%). Conclusions: dMMR and MSI-H were observed more frequently in UTUC than BC. Further analysis on survival and clinical outcomes of dMMR/MSI-H UC with different treatment modalities is ongoing. Additionally, clinical trials in dMMR and/or MSI-H UC are in development to study immunotherapeutic strategies to improve outcomes in both early and advanced stages for this small but important subset of patients. [Table: see text]

ÖzChordomas are rare primary bone tumors tought to originate from embryological remnants of the notochord. Upper cervical spine chordomas constitute about 5% of all chordomas. Extension from upper cervical spine to nasopharynx, oropharynx or parapharyngeal space extremely uncommon in head and neck surgical practice. These tumors present with features of compression of adjacent structures resulting in dysphagia, dyspnea or as a palpable neck mass, oropharyngeal mass. In this case report, chordoma originating from upper cervical spine involving the oropharyx is presented. The difficulty of diagnosis, its radiological features along with surgical findings is discussed. Kordomalar, notokordun embriyolojik artıklarından kaynaklanan nadir primer kemik tümörleridir. Servikal bölge yerleşimli kordomalar oldukça nadir görülmektedir. Tüm kordomaların %5 kadarını oluşturan servikal kordomalar, komşu oldukları parafarengeal bölge, orofarenks gibi anatomik boşluklara uzanım gösterip; boyunda şişlik, orofarenkste kitle, yutma güçlüğü, nefes darlığı benzeri klinik bulgular verebilirler. Bu olgu sunumunda yutma güçlüğü şikayeti ile başvuran ve orofarenkste kitle olarak bulgu veren servikal kordoma olgusunun klinik özellikleri sunulmuş, tanıda yaşanan güçlükler ve cerrahi bulgular tartışılmıştır.

Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase 1 study. We now report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase 1 patients and 7 expansion cohorts. CaboNivo cohorts included: 1) mUC, 2) mRCC, 3) adenocarcinoma of the bladder/urachal, and CaboNivoIpi cohorts included: 1) mUC, 2) mRCC, 3) penile cancer, 4) rare GU tumors, and an exploratory biomarker correlation with peripheral blood immune subsets (NCT02496208). Patients (n = 120) received CaboNivo (n = 64) or CaboNivoIpi (n = 56), with median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), 33 of whom had mUC, ORR was 38% (overall study) and 42% in mUC, complete response 11% and 21%, partial response 27% and 21%, duration of response 20 and 28 months, respectively. Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. In response to treatment, immunosuppressive monocytic MDSCs, classical monocytes, and all dendritic cell subsets decreased; Activated proliferative CD4+ T cells and CD8+ T cells and CTLA-4 on CD4+ T cells increased and were associated with improved PFS and OS. Both CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in many metastatic GU histologies, with distinctive patterns of response among innate and adaptive peripheral blood immune subsets and potential differential adaptive resistance in response between CaboNivo and CaboNivoIpi to prolonged effector T-cell activation.

No abstract