OBJECTIVE

To identify the current practices of ophthalmology subspecialists involved in the treatment of retinopathy of prematurity (ROP) in the Philippines.

A survey was conducted among members of the Vitreo-Retina Society of the Philippines (VRSP) and the Philippine Society of Pediatric Ophthalmology and Strabismus (PSPOS) who treat ROP. The electronic questionnaire covered treatment preferences and factors influencing these preferences regarding the use of anti-vascular endothelial growth factor (anti-VEGF), laser indirect ophthalmoscopy (LIO), cryotherapy, and surgical interventions. Questions about referral system and ROP recurrences encountered by the respondents were included.

A total of 73 out of 86 (85.00% response rate) possible respondents were included in the study, majority (80.82%) of whom were retina subspecialists. The initial treatment preference for type 1 ROP was laser indirect ophthalmoscopy (43.84%), while anti-VEGF injection (67.12%) was preferred for aggressive posterior ROP (APROP). Among the available anti-VEGF agents, bevacizumab was the most favored (68.11%). Most ROP consultations (59.79%) occurred through referrals, primarily from pediatricians or neonatologists (91.78%). Subspecialists reported encountering more recurrences with anti-VEGF injections compared to LIO. LIO was the most preferred treatment after failed initial anti-VEGF therapy, with most recurrences occurring in patients older than 50 weeks post-conceptual age.

This study underscored the diverse treatment practices for ROP in the Philippines, influenced by factors such as variable access to equipment or drugs, clinician experience with specific treatments, and ocular factors such as faster regression of neovascularization. LIO was preferred as the initial therapy for Type 1 ROP and for managing recurrences, while anti-VEGF injections were favored for APROP and as an alternative treatment for Type 1 ROP. Given the absence of an established standard for treating recurrent ROP cases, long-term monitoring is necessary to facilitate timely interventions and prevent blindness.

BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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Humans ; Bevacizumab ; Carcinoma, Non-Small-Cell Lung ; ErbB Receptors ; Lung Neoplasms ; Mutation ; Protein Kinase Inhibitors

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Angiogenesis Inhibitors/pharmacology* ; Bevacizumab/therapeutic use* ; Brain/metabolism* ; Consensus ; Humans ; Lung Neoplasms/drug therapy* ; Necrosis/etiology* ; Radiation Injuries/etiology* ; Vascular Endothelial Growth Factor A/metabolism*

Background: Neurofibromatosis-2 (NF2) is a rare neurocutaneous syndrome that typically presents with hearing loss, tinnitus, or weakness associated with few subcutaneous nodules. In contrast to neurofibromatosis-1 (NF1), NF2 presents clinically with more central lesions rather than peripheral lesions. The presence of bilateral vestibular schwannomas through imaging studies distinguishes NF2 from other neurocutaneous syndromes. Case: This is a case of an 18-year-old male who presented with lower paraparesis with associated hearing loss, cataract, and a few subcutaneous nodules. Centrally located lesions were suspected, thus brain and spine magnetic resonance imaging (MRI) were done revealing bilateral vestibular schwannomas and spine neurofibromas. The patient and family were advised for tumor surveillance, and apprised of surgical intervention once with brainstem compression symptoms. Conclusion NF2 is a rare debilitating disease that may lead to multiple neurologic deficits. The absence of recommended medical treatment and the multifocality of the tumors leave surgical resection a high-risk treatment option. Early recognition by tumor surveillance may give patients with NF2 a better prognosis and survivability.
Neurofibromatoses ; Neurilemmoma ; Neurofibroma ; Paraparesis ; Bevacizumab

Targeted and immunotherapy drugs for hepatocellular carcinoma (HCC) have been rapidly developed. Atezolizumab in combination with bevacizumab has been recommended as the first-line standard of care for unresectable or advanced HCC in several national and international guidelines. The combination therapies with sindilizumab and bevacizumab biosimilar, apatinib and carrilizumab, dulvalizumab and tremelimumab are also recommended as first-line standard regimens for advanced HCC in the guideline of Chinese Society of Clinical Oncology. Local therapy combined with targeted drugs (such as sorafenib and lenvatinib) or immune checkpoint inhibitors can significantly improve outcomes. Therefore, some progress has also been made in the study of single-agent or combination regimens as perioperative neoadjuvant therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Sorafenib/therapeutic use* ; Liver Neoplasms/pathology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Bevacizumab/therapeutic use* ; Biosimilar Pharmaceuticals/therapeutic use*

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Bevacizumab/adverse effects* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Pemetrexed/adverse effects* ; Platinum/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01; anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.
Activin Receptors, Type II ; Adult ; Aged ; Bevacizumab/therapeutic use* ; Epistaxis/etiology* ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Telangiectasia, Hereditary Hemorrhagic/drug therapy*

Objective: To report the clinical profile and treatment outcomes of neovascular glaucoma (NVG). Methods: A retrospective cohort study was done in a single tertiary hospital. Medical records of patients diagnosed with NVG from January 2000 to August 2018 were reviewed and pertinent data were collected. Study outcomes included visual acuity (VA) and intraocular pressure (IOP) and were analyzed for eyes that received any of the following: intravitreal bevacizumab (IVBe), pan-retinal photocoagulation (PRP), trabeculectomy with mitomycin (trab-MMC), or diode laser cyclophotocoagulation (DLCP) with at least 1 month of follow-up. Results: There were 162 patients (181 eyes) diagnosed with NVG. Mean age at the time of diagnosis was 55.6 ± 14 years. Diabetic retinopathy (DR) was observed in 81 (45%) eyes and central retinal vein occlusion (CRVO) in 48 (27%) eyes. Baseline VA was hand movement in 67 (37%) eyes and no light perception (NLP) in 49 (27%) eyes. Only 60 (33%) eyes had ≥1 month of follow up (mean of 73 ± 119.1 weeks) after procedures were done. IVBe was done in 22 (37%) eyes, trab-MMC in 20 (33%), PRP in 22 (37%), and DLCP in 24 (40%) eyes. IOP decreased from 45 to 20 mmHg (p<0.001) but VA decreased from LogMAR 1.7 to 2.1 (p<0.01). There was significant VA decrease in eyes that underwent a single procedure (p<0.02) but none in eyes that underwent 2 or 3 procedures. Nonetheless, there was significant IOP decrease (p<0.05) when one procedure was done. Of the 49 eyes that had baseline sight, 19 (41%) converted to NLP (p<0.01). Conclusion Most patients presenting with advanced NVG had DR and CRVO. Procedures led to better IOP but not VA and some lost vision. Aggressive screening for NVG among high-risk groups is warranted to institute treatment early.
Bevacizumab ; Retinal Vein Occlusion ; Diabetic Retinopathy ; Glaucoma, Neovascular ; Trabeculectomy

PURPOSE: To compare the efficacy of intravitreal dexamethasone implants according to previous response to bevacizumab treatment in patients with diabetic macular edema (DME).METHODS: Forty-nine eyes of 49 patients who received intravitreal dexamethasone implants for DME were reviewed retrospectively. Of these patients, 13 were treatment-naïve and 36 had previously received intravitreal injections of bevacizumab. Of the 36 previously treated patients, 24 comprised a refractory group showing no response to previous injections, and 12 comprised a responder group showing a response to previous treatments. The best-corrected visual acuity, central macular thickness (CMT), and retreatment percentages were assessed monthly for 6 months.RESULTS: After the intravitreal dexamethasone implants, visual acuity improved significantly over 6 months in the treatment-naïve group, while in the responder group, a significant improvement in visual acuity was seen at the 2-month follow-up. In the refractory group, there was no significant improvement in visual acuity during the follow-up period. The CMT showed a significant decrease in all three groups, and there was no significant difference in the CMT among the three groups at any time point. Five patients in the treatment-naive group (38.5%), 19 patients in the refractory group (79.2%), and nine patients in the responder group (75.0%) needed retreatment for recurrent macular edema, and there was a significant difference among the three groups in the rate of recurrence (p = 0.034).CONCLUSIONS: In DME patients, intravitreal dexamethasone implants were associated with a significant anatomical improvement irrespective of previous bevacizumab treatment response. However, the treatment-naïve and responder groups showed improvements in visual acuity, whereas the refractory group showed limited improvement.
Bevacizumab ; Dexamethasone ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Macular Edema ; Recurrence ; Retreatment ; Retrospective Studies ; Visual Acuity