Definitive irradiation as a first treatment strategy for primary and metastatic sites of newly diagnosed IVB cervical cancer that presented with synchronous oligometastases

Abstract Background The present study identified survival and progression-free rates and evaluated prognostic factors for IVB stage cervical cancer in patients that presented with synchronous oligometastases (sync-oligometastases) who received definitive irradiation for primary and metastatic sites. Methods The study retrospectively included 60 patients with newly diagnosed stage IVB cervical cancer. Patients received definitive radiation for both primary and metastatic sites through Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) followed by three dimensional-intracavitary/interstitial brachytherapy at our institution between July 2014 to December 2020. All patients were staged based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 guidelines. Overall survival (OS), progression-free survival (PFS), and patient prognostic factors were analyzed. Results The 60 patients who received curative-intent irradiation for primary and metastatic sites showed a 5-year OS rate of 51.4% and a 5-year PFS rate of 25.9%. The median PFS was 52.3 months, and the median OS had not been reached. Lymphatic metastases had a better OS compared with hematogenous metastases (3-year OS rates: 57.2% vs. 20%, p = 0.017). Patients with one metastasis site showed a more favorable prognosis than patients with ≥ 2 metastases sites (3-year OS rates: 60.4% vs. 20.6%, p = 0.003). Patients that presented with tumors larger than 4 cm in diameter before treatment demonstrated a poorer prognosis (5-year OS rates: 41.2% vs. 65.2%, p = 0.029; 5-year PFS rates: 10.4% vs. 53.7%, p = 0.021). Conclusion Definitive irradiation for both primary and oligo-metastatic sites for selected IVB patients is a feasible treatment strategy. Metastatic type, number of metastatic sites, and pre-treatment tumor diameter were significant prognostic factors. Neoadjuvant chemotherapy, the lymph nodal metastatic type (supraclavicular or inguinal), and number of lymphatic metastatic sites failed to reach statistical significance as prognostic factors

RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release

Abstract Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR‐containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase‐activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine‐nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR‐containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A

A pilot trial of consolidation bevacizumab after hypo‐fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non‐squamous non‐small‐cell lung cancer

Abstract Purpose To determine the feasibility of incorporating bevacizumab consolidation into hypo‐fractionated concurrent chemoradiotherapy (hypo‐CCRT) for patients with unresectable locally advanced non‐squamous non‐small‐cell lung cancer (LA‐NS‐NSCLC). Patients and Methods Eligible patients were treated with hypo‐RT (40Gy in 10 fractions) followed by hypo‐boost (24‐28Gy in 6–7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo‐CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment‐related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression‐free survival (PFS), overall survival (OS), locoregional failure‐free survival (LRFS), distant metastasis‐free survival (DMFS), and objective response rate (ORR). All time‐to‐event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy. Results Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow‐up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9–65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0–18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months. Conclusions This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo‐CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA‐NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration