Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy.

Background Predicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC). Methods Gene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used. Results Basal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7 %, 30.6 %, 18.2 %, and 10.3 % of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2-positive disease, and in TNBC. The pCR rate of Basal-like disease was >35 % across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5 % (92.8-100.0 %) was observed in these neoadjuvant-treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4 % of Luminal A tumors with clinically node-negative disease). Conclusions Intrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any)

Frequency and characteristics of familial melanoma in Spain: The FAM-GEM-1 Study

Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

Safe anti-programmed cell death-1 rechallenge with antibody switching after immune-related adverse events: brief communication

Aim: To evaluate the safety of rechallenge with a different anti-PD-1 antibody after an immune-related adverse event (irAE) that has prompted the discontinuation of anti-PD-1 therapy. Patients & methods: We describe two patients with metastatic melanoma who developed potentially disabling and early irAEs following anti-PD-1 treatment. Therapy was discontinued and toxicities resolved with corticosteroids. Results: Rechallenge switching to an alternative anti-PD-1 antibody did not lead to a new or recurrent irAE. Conclusion: Switching to a different anti-PD-1 antibody when resuming therapy after an irAE might be a safe strategy and warrants further investigation. Structural and biological differences between antibodies might explain the different safety outcomes

Prospective study comparing laparoscopic and open radical cystectomy: Surgical and oncological results

Introducción: La cistectomía radical laparoscópica con linfadenectomía y derivación urinaria es una cirugía de empleo creciente. Se necesitan estudios que avalen la efectividad oncológica y la seguridad de este abordaje mínimamente invasivo. Pacientes y métodos: Estudio prospectivo comparativo no aleatorizado entre cistectomía radical abierta (CRA) y laparoscópica (CRL) llevado a cabo en un hospital universitario. El objetivo principal fue comparar la supervivencia cáncer-específica, y el objetivo secundario comparar resultados operatorios y complicaciones según la escala Clavien-Dindo. Resultados: Ciento cincuenta y seis pacientes con cáncer vesical invasivo de alto grado fueron tratados mediante CRA (n = 70) o CRL (n = 86). El seguimiento medio fue 33,5 ± 23,8 (rango 12-96) meses. La edad media fue 66,9 + 9,4 años y la proporción hombre/mujer 19:1. Ambos grupos fueron equivalentes en edad, estadio, ganglios positivos, carcinoma in situ, uropatía obstructiva preoperatoria, quimioterapia adyuvante y tipo de derivación urinaria. No hubo diferencias entre grupos en supervivencia cáncer-específica (log-rank; p = 0,71). El estadio histopatológico fue la única variable independiente predictiva de pronóstico. La estancia hospitalaria (p = 0,01) y la tasa de transfusión operatoria (p = 0,002) fueron menores para CRL. La duración de la cirugía fue mayor para CRL (p < 0,001). No hubo diferencias en la tasa de complicaciones totales (p = 0,62) ni complicaciones mayores (p = 0,69). El riesgo de evisceración (p = 0,02), infección de herida quirúrgica (p = 0,005) y neumonía (p = 0,017) fue mayor en CRA. El riesgo de lesión rectal (p = 0,017) y fístula uretrorrectal (p = 0,065) fue mayor en CRL. Conclusión: La CRL es un tratamiento equivalente a la CRA en términos de eficacia oncológica, y ventajoso respecto a tasa de transfusión y estancia hospitalaria, pero no respecto a la ocupación de quirófano o a la seguridad global. Se necesitan estudios que definan mejor el perfil de seguridad específico de cada abordaje.Introduction: Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. Patients and methods: A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale. Results: We treated 156 patients with high-grade invasive bladder cancer with either ORC (n = 70) or LRC (n = 86). The mean follow-up was 33.5 ± 23.8 (range 12-96) months. The mean age was 66.9 + 9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P = .71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P = .01) and operative transfusion rates (P = .002) were less for LRC. The duration of the surgery was greater for LRC (P <. 001). There were no differences in the total complications rate (p = .62) or major complications (P = .69). The risk of evisceration (P =. 02), surgical wound infection (P = .005) and pneumonia (P = .017) was greater for ORC. The risk of rectal lesion (P = .017) and urethrorectal fistulae (P = .065) was greater for LRC. Conclusion: LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach.Sin financiación1.136 JCR (2018) Q4, 68/80 Urology & Nephrology0.332 SJR (2018) Q3, 66/107 UrologyNo data IDR 2018UE

Adjuvant nivolumab versus ipilimumab (CheckMate 238 trial): Reassessment of 4-year efficacy outcomes in patients with stage III melanoma per AJCC-8 staging criteria

Abstract Purpose: Nivolumab was approved as adjuvant therapy for melanoma based on data from CheckMate 238, which enrolled patients per American Joint Committee on Cancer version 7 (AJCC-7) criteria. Here, we analyse long-term outcomes per AJCC-8 staging criteria compared with AJCC-7 results to inform clinical decisions for patients diagnosed per AJCC-8. Patients and methods: In a double-blind, phase 3 trial (NCT02388906), patients aged 15 years with resected, histologically confirmed AJCC-7 stage IIIB, IIIC, or IV melanoma were randomised to receive nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for 4 doses and then every 12 weeks, both intravenously 1 year. Recurrence-free sur vival (RFS) and distant metastasis-free survival (DMFS) were assessed in patients with stage III disease, per AJCC-7 and AJCC-8. Results: Per AJCC-7 staging, 42.4% and 57.3% of patients were in substage IIIB and IIIC, respectively; per AJCC-8, 1.1%, 30.4%, 62.8%, and 5.0% were in IIIA, IIIB, IIIC, and IIID. After 4 years’ minimum follow-up, the AJCC-7 superior efficacy of nivolumab over ipilimumab in patients with resected stage III melanoma was preserved per AJCC-8 analysis. No statistically significant difference in RFS between stage III substage hazard ratios was observed per AJCC-7 or -8 staging criteria (interaction test: AJCC-7, P Z 0.8115; AJCC-8, P Z 0.1051; P Z 0.8392 ((AJCC-7) and P Z 0.8678 (AJCC-8) for DMFS). Conclusions: CheckMate 238 4-year RFS and DMFS outcomes are consistent per AJCC-7 and AJCC-8 staging criteria. Outcome benefits can therefore be translated for patients diag nosed per AJCC-8

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238

lumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB–C or stage IVmelanoma,with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings. Patients and Methods: Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. Results: At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR ¼ 0.72; 95% confidence interval, 0.60–0.86; 5-year rates of 50% vs. 39%). Five year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8þ T cells and IFNg-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value. Conclusions: Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome. See related commentary by Augusti