Pembrolizumab versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase III KEYNOTE-177 study.

Background: Results from the phase III KEYNOTE-177 study established pembrolizumab as a new first-line standard of care for microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC. Results after >5 years of follow-up are reported.

Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D.

Background: The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.

Patients And Methods: Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.

Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study.

Background: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis.

Methods: Eligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX).

Molecular determinants of clinical outcomes with pembrolizumab versus paclitaxel in a randomized, open-label, phase III trial in patients with gastroesophageal adenocarcinoma.

Background: In the phase III KEYNOTE-061 trial (NCT02370498), pembrolizumab did not significantly improve overall survival versus paclitaxel as second-line therapy for gastric/gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors. The association of tissue tumor mutational burden (tTMB) status and clinical outcomes was determined, including the relationship with CPS and microsatellite instability-high (MSI-H) status.

Patients And Methods: In patients with whole exome sequencing (WES) data [420/592 (71%); pembrolizumab, 218; paclitaxel, 202], the association of tTMB with objective response rate (ORR; logistic regression), progression-free survival (PFS; Cox proportional hazards regression), and overall survival (OS; Cox proportional hazards regression) were measured using one-sided (pembrolizumab) and two-sided [paclitaxel] P values.

KEYNOTE-859: a Phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma.

Current guidelines recommend two-drug cytotoxic chemotherapy with a fluoropyrimidine (fluorouracil or capecitabine) and a platinum-based agent (oxaliplatin or cisplatin) as first-line treatment for advanced gastric cancer. Pembrolizumab monotherapy has demonstrated durable antitumor activity in patients with advanced programmed death ligand 1-positive (combined positive score ≥1) gastric/gastroesophageal junction adenocarcinoma. Accumulating evidence indicates that combining pembrolizumab with standard-of-care chemotherapy for the treatment of advanced or metastatic cancer improves clinical outcomes.

Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials.

Importance: Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability-high (MSI-H) tumors.

Objective: To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received.

Design, Setting, And Participants: This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062.

KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer.

Background: Surgical resection is the only curative treatment option for gastric cancer. Despite widespread adoption of multimodality perioperative treatment strategies, 5-year overall survival rates remain low. In patients with advanced gastric or gastroesophageal junction adenocarcinoma, pembrolizumab has demonstrated promising efficacy and manageable safety as monotherapy in previously treated patients and as first-line therapy in combination with cisplatin and 5-fluorouracil.

Transscleral fixation of a foldable posterior chamber intraocular lens.

Unlabelled: We describe an approach to transscleral fixation of a foldable posterior chamber intraocular lens (PC IOL) using a 25-gauge pars plana vitrectomy. The technique was used in 80 consecutive eyes, and the results were analyzed for corrected distance visual acuity and safety indicators. Postoperative complications included retinal detachment in 2 eyes (2.

A phase I study of TRC105 anti-endoglin (CD105) antibody in metastatic castration-resistant prostate cancer.

Objective: TRC105 is a chimeric immunoglobulin G1 monoclonal antibody that binds endoglin (CD105). This phase I open-label study evaluated the safety, pharmacokinetics and pharmacodynamics of TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: Patients with mCRPC received escalating doses of i.

Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer.

Objective: To assess the efficacy and toxicity of cediranib, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, in patients with metastatic castration-resistant prostate cancer (CRPC) previously treated with docetaxel-based therapy.

Patients And Methods: The study used a Simon two-stage trial design, which required at least two of 12 patients in the first cohort to be progression-free at 6 months. We enrolled a total of 35 evaluable patients who all received cediranib 20 mg orally daily.

A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer.

A single nucleotide polymorphism (SNP) in CYP2C8 (rs1934951), was previously identified in a genome-wide association study as a risk factor for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for multiple myeloma. To determine if the same SNP is also associated with the development of ONJ in men receiving BPs for bone metastases from prostate cancer, we genotyped 100 men with castrate-resistant prostate cancer treated with bisphosphonates for bone metastases, 17 of whom developed ONJ. Important clinical characteristics, including type and duration of bisphosphonate therapy, were consistent among those who developed ONJ and those who did not.

Emergencies related to cancer chemotherapy and hematopoietic stem cell transplantation.

As a vast majority of oncologic treatments are being administered in the outpatient setting, emergency department (ED) physicians are increasingly encountering patients who present with a wide array of toxicities that are a direct effect of chemotherapy. This review aims to highlight the most often encountered and clinically relevant toxicities of the more commonly administered chemotherapeutic drugs. In addition, because stem cell transplantation is being used increasingly for various malignancies, a brief introduction to post-transplant complications is included.

Nanophthalmic uveal effusion managed with scleral windows and topical mitomycin-C.

The authors treated a 38-year-old man with nanophthalmic uveal effusion with scleral windows and local application of mitomycin-C. The patient underwent two separate surgical procedures, involving placement of scleral windows in all four quadrants and topical application of mitomycin-C in one quadrant. Episcleral scarring led to closure of scleral windows in all quadrants except one quadrant where mitomycin-C was applied during the first surgery.

Ophthalmomyiasis interna posterior. Report of a case with optic atrophy.

Purpose: The prognosis for patients with ophthalmomyiasis Interna posterior is variable. In many patients the larva remains in the eye for years without inducing inflammation or loss of vision. Sometimes, however, the migrating larva involves the macula and optic nerve and results in permanent visual loss or even blindness.

Diagnostic indocyanine green angiography in preeclampsia.

Purpose: To determine the role of the choroidal vasculature in the pathogenesis of exudative retinal detachments in preeclampsia using indocyanine green angiography.

Methods: We reviewed both fluorescein and indocyanine green angiographic findings for four patients with preeclampsia.

Results: Indocyanine green angiographic findings in patients with preeclampsia include nonperfusion in the early phases of the angiogram and staining of the choroidal vasculature with subretinal leakage in the late phases of the angiogram and multiple punctate areas of blocked fluorescence.

Branch retinal artery occlusion caused by a mitral valve papillary fibroelastoma.

Purpose: We studied clinicopathologically a branch retinal artery occlusion caused by an embolus from a mitral valve papillary fibroelastoma.

Methods: At initial examination the patient, a 37-year-old woman, had visual acuity of 20/400 in her left eye, and eight months later her visual acuity improved to 20/20. The diagnosis required echocardiographic and radiologic studies to localize the lesion.

Transretinal membrane formation in diffuse unilateral subacute neuroretinitis.

Background: Diffuse unilateral subacute neuroretinitis (DUSN) is characterized by unilateral visual loss with vitreous inflammation, optic disc swelling, and the presence of gray-white lesions in the deep retina, and can be associated with intraocular nematode infection. To date, no cases of transretinal membrane formation in DUSN have been reported.

Methods: A 22-year-old woman was examined for a 2-week history of unilateral decreased vision and neuroretinitis.

Surgery for subfoveal membranes in myopia, angioid streaks, and other disorders.

Objective: A retrospective analysis of patients who underwent surgical removal of subfoveal neovascular membranes caused by factors other than age-related macular degeneration (AMD) and presumed ocular histoplasmosis syndrome (POHS) was performed.

Methods: 17 eyes (16 patients) were identified in which subfoveal neovascularization was caused by myopic degeneration (5 eyes), angioid streaks (5 eyes of 4 patients), idiopathic neovascularization (4 eyes), punctate inner choroidopathy (1 eye), multifocal choroiditis (1 eye), or candida chorioretinitis (1 eye).

Results: Visual acuity remained stable after surgery in 10 of 17 eyes (59%), improved by 2 or more Snellen lines in 6 eyes (35%) and decreased in 1 eye (6%).

Abnormalities in color vision and contrast sensitivity in Parkinson's disease.

Dopamine is a neurotransmitter found in the retina. Delays in the visual evoked responses and abnormalities in contrast sensitivity occur in patients with Parkinson's disease. Improvement in the P100 has followed L-dopa therapy.

Mononuclear phagocytes have the potential for sustained hydroxyl radical production. Use of spin-trapping techniques to investigate mononuclear phagocyte free radical production.

Monocytes lack lactoferrin and have much less myeloperoxidase than neutrophils. They also acquire a potential catalyst for .OH production (tartrate-resistant acid phosphatase) as they differentiate into macrophages.

The intravenous fluorescein test: use in timing of groin flap division.

Successful division or delay of the arterial groin flap requires an accurate prediction of viability. The fluorescein dye test is an objective test to determine the earliest possible time a pedicle can be divided. It is an easy, quick, and comfortable test that can be repeated many times without injuring or altering the flap.