Magnetic resonance imaging in locally advanced rectal cancer : quantitative evaluation of the complete response to neoadjuvant therapy

Purpose: To assess the diagnostic performance of diffusion-weighted imaging (DWI) for the discrimination of complete responder (CR) from the non-complete responder (n-CR) in patients with locally advanced rectal cancer (LARC) undergoing chemotherapy and radiation (CRT). Material and methods: Between December 2009 and January 2014, 32 patients (33 lesions: one patient had two synchronous lesions) were enrolled in this retrospective study. All patients underwent a pre- and post-CRT conventional MRI study completed with DWI. For both data sets (T2-weighted and DWI), the pre- and post-CRT tumour volume (VT2; VDWI) and the tumour volume reduction ratio (ΔV%) were determined as well as pre- and post-CRT apparent diffusion coefficient (ADC) and ADC change (ΔADC%). Histopathological findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DWI volumetry, as well as ADC. Results: The area under the ROC curve (AUC) revealed a good accuracy of pre- and post-CRT values of VT2 (0.86; 0.91) and VDWI (0.82; 1.00) as well as those of ΔVT2% (0.84) and ΔVDWI% (1.00) for the CR assessment, with no statistical difference. The AUC of pre- and post-CRT ADC (0.53; 0.54) and that of ΔADC% (0.58) were significantly lower. Conclusions: Both post-CRT VDWI and ΔVDWI% (AUC = 1) are very accurate for the assessment of the CR, in spite of no significant differences in comparison to the conventional post-CRT VT2 (AUC = 0.91) and ΔVT2% (AUC = 0.84). On the contrary, both ADC and ΔADC% values are not reliable

Fulvestrant and trastuzumab in patients with luminal HER2-positive advanced breast cancer (ABC): an Italian real-world experience (HERMIONE 9)

Purpose The most appropriate therapy for HR+/HER2-positive (HER2+) advanced breast cancer (ABC) is a matter of debate. Co-targeting of both receptors represents an attractive strategy to overcome the cross-talk between them. Methods The HERMIONE 9 is an observational retrospective multicentric study which aimed to describe the clinical outcome of patients with HR+/HER2+ABC who received the combination of Fulvestrant (F) and Trastuzumab (T) as part of their routine treatment at 10 Italian Institutions. Results Eighty-seven patients were included. Median age was 63 (range, 35–87) years. The median number of previous treatments was 3 (range, 0–10) and F and T were administered as≥3rd line in 67 patients. Among the 86 evaluable patients, 6 (6.9%) achieved CR, 18 (20.7%) PR, and 44 (50.6%) had SD ≥24 weeks with an overall CBR of 78.2%. At a median follow-up of 33.6 months, mPFS of the entire cohort was 12.9 months (range, 2.47–128.67). No diference was observed in mPFS between patients treated after progression or as maintenance therapy (mPFS 12.9 and 13.9 months in 64 and 23 patients, respectively), neither considering the number of previous treatment lines (≤3 or<3). Conclusion The combination of F and T was active in this cohort at poor prognosis and deserves further investigations possibly in combination with pertuzumab in patients with high ER expression

Pathogenic hantaviruses, northeastern Argentina and eastern Paraguay

Fil: Padula, Paula. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Laboratorio de Hantavirus; Argentina.Fil: Martínez, Valeria Paula. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Bellomo, Carla. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Maidana, Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: San Juan, Jorge. Hospital de Enfermedades Infecciosas “Francisco J. Muñiz,”; Argentina.Fil: Tagliaferri, Paulina. Hospital de Pediatría de Posadas; Argentina.Fil: Bargardi, Severino. Universidad Nacional de Misiones; Argentina.Fil: Vazquez, Cynthia. Laboratorio Central de Salud Pública; Paraguay.Fil: Colucci, N. Colucci, N. Ministerio de Salud Pública y Bienestar Social. Laboratorio Central de Salud Pública; Paraguay.Fil: Estévez, Julio. Ministerio de Salud Pública Provincial, Misiones; Argentina.Fil: Almirón, María. Instituto de Investigaciones en Ciencias de la Salud; Paraguay.We describe the first, to our knowledge, cases of hantavirus pulmonary syndrome in northeastern Argentina and eastern Paraguay. Andes and Juquitiba (JUQ) viruses were characterized. JUQV was also confi rmed in 5 Oligoryzomys nigripes reservoir species from Misiones. A novel Akodonborne genetic hantavirus lineage was detected in 1 rodent from the Biologic Reserve of Limoy

Pathogenic hantaviruses, northeastern Argentina and eastern Paraguay

Fil: Padula, Paula. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Laboratorio de Hantavirus; Argentina.Fil: Martínez, Valeria Paula. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Bellomo, Carla. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Maidana, Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: San Juan, Jorge. Hospital de Enfermedades Infecciosas “Francisco J. Muñiz,”; Argentina.Fil: Tagliaferri, Paulina. Hospital de Pediatría de Posadas; Argentina.Fil: Bargardi, Severino. Universidad Nacional de Misiones; Argentina.Fil: Vazquez, Cynthia. Laboratorio Central de Salud Pública; Paraguay.Fil: Colucci, N. Colucci, N. Ministerio de Salud Pública y Bienestar Social. Laboratorio Central de Salud Pública; Paraguay.Fil: Estévez, Julio. Ministerio de Salud Pública Provincial, Misiones; Argentina.Fil: Almirón, María. Instituto de Investigaciones en Ciencias de la Salud; Paraguay.We describe the first, to our knowledge, cases of hantavirus pulmonary syndrome in northeastern Argentina and eastern Paraguay. Andes and Juquitiba (JUQ) viruses were characterized. JUQV was also confi rmed in 5 Oligoryzomys nigripes reservoir species from Misiones. A novel Akodonborne genetic hantavirus lineage was detected in 1 rodent from the Biologic Reserve of Limoy

GRAWITA: VLT Survey Telescope observations of the gravitational wave sources GW150914 and GW151226

We report the results of deep optical follow-up surveys of the first two gravitational-wave sources, GW150914 and GW151226, done by the GRAvitationalWave Inaf TeAm Collaboration (GRAWITA). The VLT Survey Telescope (VST) responded promptly to the gravitational wave alerts sent by the LIGO and Virgo Collaborations, monitoring a region of 90 and 72 deg2 for GW150914 and GW151226, respectively, and repeated the observations over nearly two months. Both surveys reached an average limiting magnitude of about 21 in the r band. The paper describes the VST observational strategy and two independent procedures developed to search for transient counterpart candidates in multi-epoch VST images. Several transients have been discovered but no candidates are recognized to be related to the gravitational wave events. Interestingly, among many contaminant supernovae, we find a possible correlation between the supernova VSTJ57.77559-59.13990 and GRB150827A detected by Fermi-GBM. The detection efficiency of VST observations for different types of electromagnetic counterparts of gravitational wave events is evaluated for the present and future follow-up surveys

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Laparoscopic sacrocolpopexy versus pelvic organ prolapse suspension for surgical management of pelvic organ prolapse: a retrospective study

This retrospective surgical clinical study compares clinical and functional effects of laparoscopic sacrocolpopexy (LSC) and laparoscopic pelvic organ prolapse suspension (L-POPS) for anterior and central prolapse correction. Thirty patients enrolled were affected by a symptomatic vaginal central compartment stage 2–3 prolapse and vaginal anterior compartment stage 1–3 prolapse without vaginal posterior compartment prolapse. A successful correction of anterior and central compartments prolapse without relapses were observed in both groups (LSC group versus L-POPS group). In patients who underwent L-POPS, a de novo posterior compartment prolapse was recorded. In this group, 7/15 patients complained more bowel symptoms and underwent vaginal colpoperineoplasty. In 20% (group LSC) and in 13.3% (group L-POPS) of cases, a condition of de novo urinary stress incontinence was described. LSC seems to remain the gold standard for pelvic organ prolapse correction, while further preventive strategies should be carried out in L-POPS to avoid a de novo posterior compartment prolapse.Impact Statement What is already known on this subject? Laparoscopic sacrocolpopexy is the gold standard technique for the correction of pelvic organ prolapse; however, laparoscopic pelvic organ prolapse suspension, based on the surgical technique of lateral suspension, is an innovative surgical method for the treatment of POP. What do the results of this study add? L-POPS could be considered a valid alternative to LSC for women with multiple comorbidities because of less operative time and reduced surgical risks. However, in the long follow-up period, some patients underwent L-POPS complained rectal discomfort and dysfunction on quality of life questionnaire and on clinical evaluation from six to twelve months after surgery probably due to the post-operative appearance of posterior compartment prolapse. What are the implications of these findings for clinical practice and/or further research? Considering the retrospective design and the small sample size the major limits of this study, larger, prospective, randomized studies could be encouraged to better compare a modified technique of L-POPS with posterior mesh apposition (preventing the post-operative appearance of posterior compartment prolapse) with the gold standard LSC for the correction of multi-compartment POP

Identification of Cdk8 and Cdkn2d as New Prame-Target Genes in 2C-like Embryonic Stem Cells

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame&rsquo;s downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, Cdk8 and Cdkn2d, bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the Cdk8 and Cdkn2d genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of na&iuml;ve pluripotency

Could a Personalized Strategy Using Accelerated Partial Breast Irradiation be an Advantage for Elderly Patients? A Systematic Review of the Literature and Multidisciplinary Opinion

Introduction. Elderly patients are underrepresented from a majority of clinical trials and the choice of the best treatment becomes a challenge. The optimal treatment should be personalized and based on a multidisciplinary approach that includes radiation oncologists, surgeons, geriatricians, medical oncologists, social workers, and support services. The global evaluation of the patients and the creation of nomograms may facilitate the definition of long-term treatment benefits minimizing the use of unnecessary therapy. Material and Method. A systematic research using PubMed, Scopus, and Cochrane library was performed to identify full articles analyzing the efficacy of APBI in elderly patients with breast cancer. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results. Seven papers fulfilled the eligibility criteria. The number of evaluated patients was 405 and the median age was 77.7 years. The disease-free survival (DFS) range was 96.1%–100%, the grade 3-4 toxicity range was 0%–6.6%, the cancer-specific survival (CSS) range was 97.9%–100%, and the overall survival (OS) range was 87%–100%. All studies reported excellent/good cosmetic results in a range of 74% to 99%. Conclusion. Accelerated partial breast irradiation (APBI) results in a safe and effective substitute for the adjuvant external beam radiotherapy in selected elderly early-stage breast cancer patients. Based on the relatively low toxicity, APBI should be advised in selected patients with life expectancies larger than 5–10 years