Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer.

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)-complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.

Epigenetic targets to enhance antitumor immune response through the induction of tertiary lymphoid structures.

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates found in sites of chronic inflammation such as tumors and autoimmune diseases. The discovery that TLS formation at tumor sites correlated with good patient prognosis has triggered extensive research into various techniques to induce their formation at the tumor microenvironment (TME). One strategy is the exogenous induction of specific cytokines and chemokine expression in murine models. However, applying such systemic chemokine expression can result in significant toxicity and damage to healthy tissues. Also, the TLS formed from exogenous chemokine induction is heterogeneous and different from the ones associated with favorable prognosis. Therefore, there is a need to optimize additional approaches like immune cell engineering with lentiviral transduction to improve the TLS formation in vivo. Similarly, the genetic and epigenetic regulation of the different phases of TLS neogenesis are still unknown. Understanding these molecular regulations could help identify novel targets to induce tissue-specific TLS in the TME. This review offers a unique insight into the molecular checkpoints of the different stages and mechanisms involved in TLS formation. This review also highlights potential epigenetic targets to induce TLS neogenesis. The review further explores epigenetic therapies (epi-therapy) and ongoing clinical trials using epi-therapy in cancers. In addition, it builds upon the current knowledge of tools to generate TLS and TLS phenotyping biomarkers with predictive and prognostic clinical potential.

Implantación de una política de episiotomía selectiva en el Hospital de Baza. Resultados materno-fetales / Implantation of a selective episiotomy policy in the Hospital of Baza. Maternal and fetal outcomes

Objetivo. Valorar los resultados materno-fetales relacionados con el uso selectivo de episiotomía. Metodología. Estudio analítico retrospectivo de los partos asistidos en el Hospital de Baza (Granada). Resultados. Las tasas de episiotomía han descendido del 69% (89% de nulíparas y 51.75% de multíparas) al 20% (35.7% de nulíparas y 8.43% de multíparas). Los test de asociación muestran que la realización de episiotomía se relaciona con nuliparidad, edad materna avanzada en nulíparas, analgesia epidural, partos instrumentales y posición de litotomía. La episiotomía selectiva no afecta al test de Apgar del recién nacido. Posiciones distintas a litotomía reducen la realización de episiotomía y protegen de desgarros severos. La política de episiotomía selectiva incrementa los perinés íntegros, aunque incrementa los desgarros perineales de I y II grado. Conclusiones. La implantación de una política selectiva de episiotomía favorece el parto humanizado, conservando más perinés íntegros, sin empeorar los resultados materno-fetales (AU)

Objective. To evaluate maternal and fetal outcomes associated with the selective use of episiotomy. Methods. A retrospective analytical study of births attended in the Hospital of Baza (Granada, Spain). Results. Episiotomy rates fell from 69% (89% of nulliparas and 51.75% of multiparas) to 20% (35.7% of nulliparas and 8.43% of multiparas). Association tests showed that episiotomy was associated with nulliparity, maternal age in nulliparas, epidural analgesia, instrumental delivery and lithotomy position. Selective episiotomy did not affect neonatal Apgar scores. Different lithotomy positions reduced the performance of episiotomy and protected against severe lacerations. A selective episiotomy policy helped to preserve the perineum intact but also increased grade I and II perineal tears. Conclusions. The implementation of a selective episiotomy policy favors humanized birth and helps to preserve the perineum intact, without worsening maternal and fetal outcomes (AU)