Systemic Treatment for Brain Metastasis and Leptomeningeal Disease in Breast Cancer Patients.

PURPOSE OF REVIEW: Breast cancer with brain metastasis (BCBM) and leptomeningeal disease (LMD) are important clinical problems. Traditionally, patients with metastases to the brain and meninges were excluded from clinical trials; hence, robust, evidence-based treatment recommendations are lacking. In this review, we outline the systemic treatment options and ongoing clinical trials. RECENT FINDINGS: Several recent studies have added to the systemic treatment options available. Antibody-drug conjugates have changed the therapeutic landscape. Combination treatment modalities that target multiple mechanisms including disruption of the blood brain barrier are increasingly being studied. Breast cancer with brain metastases and LMD is a heterogenous disease. While the prognosis remains grim, with more systemic treatment options, patients with BCBM are now living longer. Many ongoing clinical trials hold promise to further improve outcomes.

High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study.

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

Highlights on Ocular Toxicity of Immune Checkpoint Inhibitors at a US Tertiary Cancer Center.

Introduction: Immune checkpoint inhibitors (ICIs) have improved prognosis in advanced malignancies; however, they may be associated with extensive ocular immune-related adverse events (irAEs) that are sight threatening. Our study aimed to identify the presentation, characteristics, management, and clinical outcomes of ocular irAEs. Methods: In this retrospective, observational case series, we reviewed the medical records of 1280 patients at a large US tertiary cancer center between 2010 and 2020. Results: We identified 130 patients who presented with ocular irAEs (10%) with 69 males (53%) and 61 females (47%). The mean time to toxicity was 6.1 months. Adverse events include corneal toxicity (31%), neuro-ophthalmic (14%), uveitis and scleritis (13%), retinopathy (13%), periocular disorders (11%), and others. IrAEs occurred most frequently with nivolumab (26%). Most ocular irAEs were treated with topical therapy. Advanced cases required systemic corticosteroids and even cessation of ICIs. Conclusion: Our cohort is a large case series highlighting the increased potential of ocular toxicity associated with ICIs. Prompt recognition and management of ocular irAEs can minimize their effect.

The Extent of Retinal Involvement of Canthaxanthin Crystalline Retinopathy Demonstrated by Multimodal Imaging.

Limited information is known about the extent of canthaxanthin crystalline retinopathy on the retinal layers. The authors describe a 51-year-old woman who was taking canthaxanthin for tanning purposes for 7 years. Three years after cessation of this agent, she presented with asymmetric crystalline retinopathy affecting both eyes. She was lost to follow-up, and upon returning 4 years later, the crystalline retinopathy persisted but the number of crystals had decreased. Using swept-source optical coherence tomography, the authors showed that the crystalline retinopathy affected all retinal layers. In addition, retinal pigmented epithelial detachments were present suggesting persistent damage caused by the canthaxanthin. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:727-731.].

Usefulness of patient-reported outcomes to assess the effectiveness of topical hormonal therapy for gynecologic symptoms after antihormonal treatment for breast cancer.

The aim of this retrospective study was to assess the efficacy of topical hormonal therapy (THT) to relieve vaginal symptoms resulting from antihormonal therapy in women with hormone receptor-positive breast cancer. A total of 74 breast cancer patients who received THT for vaginal complaints were retrospectively identified and statistically matched with 74 control breast cancer patients with vaginal complaints with no documented use of THT. Symptom scores were recorded from the center's proprietary patient-reported outcomes database, Patient Care Monitor (ConcertoHealthAI, Boston). A baseline score was noted at the initiation of antihormonal therapy and was followed at 6 and 12 months. The median differences between baseline, 6-month, and 12-month scores were analyzed. Repeated measures analysis of variance assessed the impact of topical hormonal replacement. There was no statistically significant difference in score change between the two groups at 6 and 12 months. In the active THT group, there were no statistically significant differences in vaginal complaints or sexual problems over time: {F (2, 146) = 0.99, P = 0.369; and F (2, 146) = 1.56, P = 0.217}, respectively. In this study, the use of topical hormonal replacement was not effective in alleviating vaginal symptoms.

Unusual recurrent metastasizing benign breast papilloma: a case report.

BACKGROUND: Papillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor. CASE PRESENTATION: Our patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7-9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery. CONCLUSIONS: We present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

BACKGROUND: Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. HYPOTHESIS: Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. METHODS: Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. RESULTS: Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. CONCLUSIONS: In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings.

HIV and Hepatitis C Virus Screening Practices in a Geographically Diverse Sample of American Community Health Centers.

Because of the advent of highly effective treatments, routine screening for HIV and hepatitis C virus (HCV) has been recommended for many Americans. This study explored the perceived barriers surrounding routine HIV and HCV screening in a diverse sample of community health centers (CHCs). The Community Health Applied Research Network (CHARN) is a collaboration of CHCs, with a shared clinical database. In July, 2013, 195 CHARN providers working in 12 CHCs completed a survey of their attitudes and beliefs about HIV and HCV testing. Summary statistics were generated to describe the prevalence of HIV and HCV and associated demographics by CHCs. HIV and HCV prevalence ranged from 0.1% to 5.7% for HIV and from 0.1% to 3.7% for HCV in the different CHCs. About 15% of the providers cared for at least 50 individuals with HIV and the same was true for HCV. Two-thirds saw less than 10 patients with HIV and less than half saw less than 10 patients with HCV. Less than two-thirds followed USPHS guidelines to screen all patients for HIV between the ages of 13 and 64, and only 44.4% followed the guidance to screen all baby boomers for HCV. Providers with less HIV experience tended to be more concerned about routine screening practices. More experienced providers were more likely to perceive lack of time being an impediment to routine screening. Many US CHC providers do not routinely screen their patients for HIV and HCV. Although additional education about the rationale for routine screening may be indicated, incentives to compensate providers for the additional time they anticipate spending in counseling may also facilitate increased screening rates.

Comparison of Surgical Outcomes Between Phacocanaloplasty and Phacotrabeculectomy at 12 Months' Follow-up: A Longitudinal Cohort Study.

PURPOSE: To compare operative outcomes of patients after phacocanaloplasty and phacotrabeculectomy through 12 months' follow-up. DESIGN: Retrospective, nonrandomized, comparative case series. MATERIALS AND METHODS: We included 36 eyes of 36 patients with open-angle glaucoma who underwent combined phacoemulsification and canaloplasty (phacocanaloplasty) and 41 eyes of 41 patients with open-angle glaucoma who underwent combined phacoemulsification and trabeculectomy with mitomycin C (phacotrabeculectomy) with 12 months' of postoperative follow-up. All surgeries were performed by a single surgeon (R.S.A.) between January 2007 and May 2011. MAIN OUTCOME MEASURES: Failure was based on intraocular pressure (IOP; >18 or <4 mm Hg at 1 y), second operative procedure (any eye requiring reoperation), or decrease in visual acuity by 0.20 logMAR. Change in IOP, visual acuity (VA), glaucoma medications, and complication rates at 12 months were analyzed. RESULTS: There were no differences in demographics other than the sex between the groups. There were also no significant differences in previous surgery or in preoperative VA, IOP, or use of glaucoma medications between the groups, though the phacotrabeculectomy group had a higher preoperative IOP at baseline and a larger SD. Both groups showed significant reduction in IOP from baseline at every time point (P<0.001). No significant difference in mean IOP at 12 months was found, with a mean of 14.1±4.4 mm Hg in the phacocanaloplasty group and 11.8±5.4 mm Hg in the phacotrabeculectomy group (P=0.07). The phacotrabeculectomy group showed a significantly greater median absolute (8 vs. 5 mm Hg) and percent (40% vs. 28%) reduction in IOP at 12 months (P=0.02). Postoperative glaucoma medication use was similar between the 2 groups.Overall failure rates at 1 year were comparable between the 2 groups: 22% for phacocanaloplasty versus 20% for phacotrabeculectomy (P=0.79). Phacotrabeculectomy eyes experienced more visual failures (5% vs. 0%, P=0.50), whereas phacocanaloplasty experienced more IOP failures (17% vs. 12%, P=0.75). No difference in operative failure rate was found between the phacocanaloplasty and phacotrabeculectomy groups (6% vs. 5%, P=1.00) and this held after controlling for covariates. Final VA was not statistically different between the 2 groups. CONCLUSIONS: Phacocanaloplasty and phacotrabeculectomy both achieved significant reduction in IOP and improvement in VA at 12 months with comparable success rates. Phacotrabeculectomy achieved a statistically greater median percentage decrease in IOP, but the 2 procedures resulted in comparable mean IOP at 12 months.

Comparison of surgical outcomes between canaloplasty and trabeculectomy at 12 months' follow-up.

PURPOSE: To compare operative outcomes of patients after canaloplasty and trabeculectomy through 12 months' follow-up. DESIGN: Retrospective, nonrandomized, comparative case series. PARTICIPANTS: We included 33 eyes of 33 patients who underwent canaloplasty and 46 eyes of 46 patients who underwent trabeculectomy with 12 months' of postoperative follow-up. METHODS: Patients with open-angle glaucoma who underwent either canaloplasty or trabeculectomy with mitomycin C to control the intraocular pressure (IOP) between January 2007 and December 2008 were included. All surgeries were performed by a single surgeon (R.S.A.). MAIN OUTCOME MEASURES: Change in IOP, visual acuity (VA), postoperative medications, failure based on IOP (>18 or <4 mmHg at 1 year) or second operative procedure (any eye requiring reoperation) and complication rates at 12 months. RESULTS: There were no differences in demographics, previous surgery, or preoperative and postoperative VA between the groups. The mean percentage reduction in IOP from preoperative values at 12 months after surgery was 32% (± 22%) for the canaloplasty group compared with 43% (± 28%) for the trabeculectomy group (P = 0.072, Student t test). The median reduction in the number of medications at 12 months' follow-up was 3 in the trabeculectomy group and 2 in the canaloplasty group (P = 0.064). A higher percentage of patients treated with canaloplasty than trabeculectomy (36% vs. 20%) required postoperative medications, although this did not attain significance (P = 0.12). Failure based on IOP (IOP >18 or <4 mmHg at 12 months) was 12.1% (4/33 patients) for the canaloplasty group and 4.3% (2/46 patients) for the trabeculectomy group (P = 0.23, Fisher exact test). There was no difference in surgical failure rates between the canaloplasty (n = 5; 15%) and trabeculectomy (n = 5; 11%) groups (P = 0.74). CONCLUSIONS: Canaloplasty and trabeculectomy both achieved significant reduction in IOP at 12 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Acceptance of repeat esophagogastroduodenoscopy to detect gastric cancer in a Chinese immigrant cohort.

GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer "nearly always" in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes.

Follow-up care after a diagnosis of Helicobacter pylori infection in an Asian immigrant cohort.

GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a "regular doctor" was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a "regular doctor" appeared to increase the likelihood of receiving appropriate follow-up care.