Hospital Recoletas Campo Grande

Introduction: The prognosis of PMBCL has improved in the modern era; however, there is no a standard frontline treatment and when to associate radiotherapy remains controversial. Refractory/relapsed (R/R) disease traditionally had a dismal prognosis, but nowadays new therapeutic alternatives are available that could be effective. Methods: We conducted a retrospective multicenter study within GELTAMO group. Each participating center included patients with histological diagnosis of PMBCL from 2007 to 2023. In the present analysis, we evaluated the influence on prognosis of several clinical characteristics by uni and multivariate analysis and the efficacy of frontline and subsequent treatments by Kapplan Meier method. Results: 329 patients from 41 Spanish centers were included. Patient characteristics are summarized in table 1. All patients received chemoimmunotherapy as first-line, mainly DA-EPOCH-R or R-CHOP-21, often combined with consolidative radiotherapy (RT). A significantly higher rate of patients treated with R-CHOP-21 versus DA-EPOCH-R received RT (51% vs. 17%, p < 0.01). The overall and complete response (OR, CR) rates after first-line were 86% and 79%, respectively. Among patients treated with DA-EPOCH-R +/− RT, 83% achieved CR versus 73% of patients treated with R-CHOP-21 +/− RT (p = 0.04). With a median follow-up (mFU) in alive patients of 54 months (4–214), 4-year progression free survival (PFS) and overall survival (OS) were 72% and 90%, respectively. Patients treated with DA-EPOCH-R had better PFS (78% vs. 61%, p < 0.01) and a trend to better OS (91% vs. 84%, p = 0.08) than patients treated with R-CHOP-21. In addition, first-line chemoimmunotherapy regimen had independent influence on PFS (HR 2.3, 95% CI: 1.4–3.7, p < 0.01) in a Cox regression model adjusted by other prognostic factors highligted in table 1. 85 patients (26%) had R/R disease after a median of 6 months (0–30) with a higher relapse rate in patients treated with R-CHOP-21 versus DA-EPOCH-R (36% vs. 21%, p < 0.01). With a mFU of 52 months (5–178) from relapse, 4-year PFS and OS were 37% and 66%, respectively. At first relapse, 30 patients (35%) received autologous stem cell transplantation (ASCT) as consolidation therapy, with a 4-year PFS from ASCT of 76%. 36 patients (42%) received CAR-T cell therapy in second or subsequent treatment lines. Of them, 20 patients (56%) achieved prolonged CR, after a mFU from CAR-T infusion of 25 months (5–72) in CR patients. In 24 patients (28%) a checkpoint inhibitor (50% monotherapy) was used as salvage treatment in second or subsequent treatment lines. Five (29%) patients reached sustained CR (mFU of 11 months) without CAR-T or transplant consolidation. Conclusions: Our results indicate that DA-EPOCH-R has significantly higher efficacy than R-CHOP-21 with lower use of RT. The prognosis is good for most patients, even R/R patients seem to have better prognosis than reported in historical series, probably related to new treatment approaches. Research funding declaration: No disclosure Keywords: aggressive B-cell non-Hodgkin lymphoma No potential sources of conflict of interest.

Human papillomavirus (HPV) infection and menopause entail a considerable impairment in health-related quality of life (HRQoL). The objective of the present study was to analyze the impact of the menopause status on HRQoL in women with HPV infection. A cross-sectional, nationwide, multicenter sample of women with HPV infection was conducted throughout clinics of gynecology representative of the Spanish population with regard to age, geographic density, and autonomous regions. Demographic and clinical characteristics and the specific HPV-QoL questionnaire score with its domains were compared according to reproductive status: premenopausal and peri-/postmenopausal. Correlation with other validated patient-reported outcomes measurements was also tested, including General Health Questionnaire-12 (GHQ-12), Female Sexual Function Index (FSFI), and Hospital Anxiety and Depression Scale (HADS). A sample of 1,016 noninstitutionalized women, aged 18-80 y, was recorded, 191 (18.8%) peri-/postmenopausal and 825 (81.2%) premenopausal. Total HPV-QoL scoring was significantly lower in peri-/postmenopausal (38.8, 95% CI [35.2-42.4]) compared to premenopausal (46.4, 95% CI [45.0-47.8]) women, and also in every domain of the scale (P < 0.05), except in social well-being and health domains, with a small effect size of 0.39. In women with sexual dysfunction according to FSFI, adjusted total scoring and domains sexuality, general well-being, and psychological well-being scored significantly higher in premenopause women (P < 0.01), although the magnitude of differences were of small to moderate size. HRQoL was impaired during menopause in women with HPV infection according to HPV-QoL questionnaire. The sexuality domain was the most differentiating dimension between these populations.

Abstract Objectives To demonstrate the benefit of robotic extraperitoneal endoscopic approach for the treatment of ventral incisional hernia in obese patients. Materials and Methods Descriptive video of the eTEP endoscopic technique using a lower approach for the treatment of multiple incisional hernias in obese patients. Utilizing a PLP mesh with silver ions. Results The postoperative period without complications, discharge 24 hours after surgery, first follow-up at 10 days post-intervention; the patient only required continuous analgesia for the first 72 hours. Three months after surgery, the patient reported no pain, physical examination showed no recurrence and excellent aesthetic results. Conclusions The repair of Ventral incisional hernia using the robotic Rives-Stoppa eTEP preperitoneal endoscopic eTEP Rives-Stoppa technique is a feasible and reproducible technique approach. It meets the same criteria as open surgery (broad sublay mesh and tension-free closure) and is safe for obese patients. Additionally, it offers advantages such as less postoperative pain, reduced need for analgesia, promotes rapid recovery, early resumption of work and daily activities and daily in safe manner, and excellent aesthetic result.

The identification of subpopulations harboring druggable targets has become a major step forward in the subclassification of solid tumors into small groups suitable for specific therapies. BRAF fusions represent a paradigm of uncommon and targetable oncogenic events and have been widely correlated to the development of specific malignancies. However, they are only present in a limited frequency across most common tumor types. At this regard, we performed a genomic screening aimed to identifying rare variants associated to advanced prostate cancer development. Tumoral tissue genomic screening of 41 patients developing advanced prostate cancer was performed at our center as part of the GETHI XX study. The project, sponsored by the Spanish Collaborative Group in Rare Cancers (GETHI), aims to analyze the molecular background of rare tumors and to discover unfrequent molecular variants in common tumors. Here we present the clinical outcome and an in-deep molecular analysis performed in a case harboring a SND1-BRAF fusion gene. The identification of such rearrangement in a patient refractory to standard therapies led to the administration of trametinib (MEK inhibitor). Despite unsensitive to standard therapies, the patient achieved a dramatic response to trametinib. A comprehensive study of the tumor demonstrated this event to be a trunk alteration with higher expression of MEK in areas of tumor invasion. Our study describes the patient-driven discovery of the first BRAF fusion-driven prostate cancer effectively treated with trametinib. Consequently, MAPK pathway activation could define a new subtype of prostate cancer susceptible to a tailored management.

Abstract Identification of “agnostic” genetic drivers in cancer is foreseen as a major step forward in precision medicine. Thus, treatment selection could be based on the molecular background of the disease rather than on tumor histology in the near future. However clinical validation of most alterations is lacking and only preclinical models are available. We describe a prostate cancer patient refractory to standard therapies that was found to harbor both a c-Met activating mutation and a BRAF fusion that greatly responded to the MEK inhibitor (MEKi) trametinib. EXPERIMENTAL PROCEDURES The Next Generation Sequencing (NGS) platforms (Oncomine Assay and Archer Variant Plex) were used to characterize molecularly FFPE tissue from the primary tumor of a 73 years old man with metastatic castration-resistant prostate cancer (mCRPC) refractory to Docetaxel, Enzalutamide and Radium 223. Immunostaining was performed to evaluate the status of protumoral pathways activated by the identified genomic alterations. RESULTS Oncomine assay detected a pathogenic c-MET mutation that affected the splicing of exon 14 and the patient was included in a clinical trial with a c-MET inhibidor. He developed Grade 3 anemia, G3 bone pain which required major opioids, a rise of PSA over 900 ng/ml and progressive disease as best response. An extended screening using Archer platform detected a SND1/BRAF fusion. Immunohistochemistry revealed homogeneous tumor positive staining for c-MET, and a punctured staining on pERK in FFPE regions with perineural tumor invasion suggesting a critical role of the BRAF fusion in the spread of the disease. After a comprehensive review of the literature a similar model was identified, where the SND1/BAF function raised in a cell culture of gastric cancer as mechanism of resistance to MET inihibitors (Lee NV et al PLoS One 2012). In preclinical experiments the MEKi trametinib induced significant cell mortality. After given written consent, the patient was put on trametinib (2mg/day) under compassionate use. We observed a large decrease of PSA levels to 90 ng/ml after two weeks of treatment, an increase of hemoglobin levels and significant clinical benefit, with no need of analgesics. After two months on treatment the patient continues on tumor response by the time of communication of this abstract. CONCLUSIONS According to our knowledge, this is the first published study able to demonstrate that cancer patients harboring c-MET exon 14 splicing mutation and SND1-BRAF fusion genes could benefit from therapies with MEK inhibitors. Further experimental procedures are needed to validate this hypothesis. 1. Lee NV, Lira ME, Pavlicek A, Ye J, Buckman D, et al. (2012) A Novel SND1-BRAF Fusion Confers Resistance to c-Met Inhibitor PF-04217903 in GTL16 Cells though MAPK Activation. PLoS ONE 7(6): e39653. doi:10.1371/journal.pone.0039653. Citation Format: Sergio Ruiz, María Dolores Fenor de la Maza, Juan Francisco Rodríguez Moreno, Elena Sevillano, Paloma Navarro, Sandra Amarilla, Teresa García Donas, Eduardo Caleiras, Juan Carlos Torrego, Jesus García Donas. Targeting c-MET and MAPK pathway in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4475.

Identification of “agnostic” genetic drivers in cancer is foreseen as a major step forward in precision medicine. Thus, treatment selection could be based on the molecular background of the disease rather than on tumor histology in the near future. However clinical validation of most alterations is lacking and only preclinical models are available. We describe a prostate cancer patient refractory to standard therapies that was found to harbor both a c-Met activating mutation and a BRAF fusion that greatly responded to the MEK inhibitor (MEKi) trametinib. EXPERIMENTAL PROCEDURES The Next Generation Sequencing (NGS) platforms (Oncomine Assay and Archer Variant Plex) were used to characterize molecularly FFPE tissue from the primary tumor of a 73 years old man with metastatic castration-resistant prostate cancer (mCRPC) refractory to Docetaxel, Enzalutamide and Radium 223. Immunostaining was performed to evaluate the status of protumoral pathways activated by the identified genomic alterations. RESULTS Oncomine assay detected a pathogenic c-MET mutation that affected the splicing of exon 14 and the patient was included in a clinical trial with a c-MET inhibidor. He developed Grade 3 anemia, G3 bone pain which required major opioids, a rise of PSA over 900 ng/ml and progressive disease as best response. An extended screening using Archer platform detected a SND1/BRAF fusion. Immunohistochemistry revealed homogeneous tumor positive staining for c-MET, and a punctured staining on pERK in FFPE regions with perineural tumor invasion suggesting a critical role of the BRAF fusion in the spread of the disease. After a comprehensive review of the literature a similar model was identified, where the SND1/BAF function raised in a cell culture of gastric cancer as mechanism of resistance to MET inihibitors (Lee NV et al PLoS One 2012). In preclinical experiments the MEKi trametinib induced significant cell mortality. After given written consent, the patient was put on trametinib (2mg/day) under compassionate use. We observed a large decrease of PSA levels to 90 ng/ml after two weeks of treatment, an increase of hemoglobin levels and significant clinical benefit, with no need of analgesics. After two months on treatment the patient continues on tumor response by the time of communication of this abstract. CONCLUSIONS According to our knowledge, this is the first published study able to demonstrate that cancer patients harboring c-MET exon 14 splicing mutation and SND1-BRAF fusion genes could benefit from therapies with MEK inhibitors. Further experimental procedures are needed to validate this hypothesis. 1. Lee NV, Lira ME, Pavlicek A, Ye J, Buckman D, et al. (2012) A Novel SND1-BRAF Fusion Confers Resistance to c-Met Inhibitor PF-04217903 in GTL16 Cells though MAPK Activation. PLoS ONE 7(6): e39653. doi:10.1371/journal.pone.0039653. Citation Format: Sergio Ruiz, Maria Dolores Fenor de la Maza, Juan Francisco Rodriguez Moreno, Elena Sevillano, Paloma Navarro, Sandra Amarilla, Teresa Garcia Donas, Eduardo Caleiras, Juan Carlos Torrego, Jesus Garcia Donas. Targeting c-MET and MAPK pathway in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4475.