Using the HER2/CEP17 FISH Ratio to Predict Pathologic Complete Response Following Neoadjuvant Anti-HER2 Doublet Therapy in HER2+ Breast Cancer.

BACKGROUND: Clinical trials of HER2-directed therapy that omit neoadjuvant conventional chemotherapy for HER+ breast cancer demonstrate that a subset of patients still obtains a pCR. Identifying tumor characteristics which predict pCR may help select patients for de-escalated neoadjuvant dual HER2-targeted treatment without chemotherapy. This is the first study evaluating the HER2/CEP17 ratio by FISH as a biomarker to predict pCR among patients who received neoadjuvant anti-HER2 regimens without chemotherapy. PATIENTS AND METHODS: Data from patients with locally advanced HER2+ breast cancer who received neoadjuvant dual HER2-targeted therapy without conventional chemotherapy from a single center was retrospectively reviewed. All patients were enrolled in one of 3 clinical trials evaluating chemotherapy de-escalation. Logistic regression modeling assessed for a relationship between the HER2/CEP17 FISH ratio obtained from baseline tissue biopsy and pCR based on pathology at the time of definitive breast surgery following neoadjuvant treatment. RESULTS: Following neoadjuvant treatment with dual HER2-targeted therapies in 56 patients, the probability of pCR was 73% among patients with a HER2 ratio of 13.1 compared to a probability of 38% among patients with HER2 ratio of 5.5 (OR 4.14, 95% CI 1.44-11.89; P = .012). This positive association persisted after controlling for different treatment regimens administered (OR 2.87, 95% CI 0.9-9.18, P = .020). CONCLUSIONS: These data found a positive association between the HER2/CEP17 FISH ratio and pCR following neoadjuvant dual HER2-targeted therapy without chemotherapy. Larger prospective studies are needed to validate the HER2 ratio as a biomarker to select patients for neoadjuvant dual anti-HER2 therapy without chemotherapy.

Nonmyeloablative, HLA-Mismatched Unrelated Peripheral Blood Transplantation with High-Dose Post-Transplantation Cyclophosphamide.

High-dose post-transplantation cyclophosphamide (PTCy) is an effective platform for prevention of severe graft-versus-host disease (GVHD) after allogeneic bone marrow (BM) transplantation with mismatched unrelated donors (mMUDs). Previous studies evaluating PTCy with mMUDs favored BM allografts over peripheral blood stem cell transplantation (PBSCT) due to concerns that PBSCT may be associated with an increased risk of acute and chronic GVHD. In addition, haploidentical PBSCT is associated with high rates of cytokine release syndrome (CRS), which is another concern with mMUD PBSCT. This study was conducted to determine the feasibility and safety of using mMUD PBSCT with PTCy as GVHD prophylaxis. Patients who received mMUD PBSCT using a PTCy-based GVHD prophylaxis at Johns Hopkins Hospital as part of a prospective clinical trial of mMUD and non-first-degree relative haploidentical transplantation with PTCy (ClinicalTrials.gov identifier NCT01203722) were included. All patients underwent T cell-replete PBSCT between November 2012 and August 2020. Statistical analyses were performed using the Kaplan-Meier method and proportional subdistribution hazard regression model for competing risks. The 29 patients in the study had a median age of 54 years, with 10 patients (34%) age ≥60 years. Nineteen grafts (66%) were matched for 9/10 HLA loci, 6 (21%) were match for 8/10, and 4 (14%) were matched for 7/10. No primary or secondary graft failure occurred. The median time to neutrophil recovery (≥500/µL) was 17 days, and that to platelet recovery (≥20,000/µL) was 28 days. Full donor chimerism was achieved in all patients by day +60. The cumulative incidence (CuI) of grade II-IV acute GVHD at 180 days was 15% (90% confidence interval [CI], 3% to 26%). There were no cases of severe chronic GVHD, 3 cases of mild chronic GVHD, and 1 case of moderate chronic GVHD. The CuI of nonrelapse mortality (NRM) was 7% (90% CI, NA to 18%) at 1 year. Eighteen patients (62%) experienced mild CRS (grade 1-2), and 1 patient (3%) experienced severe CRS (grade 3-5). At 1 year, the CuI of relapse was 29% (90% CI, 8% to 50%), overall survival was 93% (90% CI, 85% to 100%), progression-free survival was 64% (90% CI, 46% to 88%), GVHD-free relapse-free survival was 41% (90% CI, 23% to 73%), and chronic GVHD-free relapse-free survival was 64% (90% CI, 46% to 88%). Our data indicate that mMUD PBSCT using PTCy-based GVHD prophylaxis is safe and feasible. All patients engrafted, and rates of NRM (7%) and acute GVHD (15%) at 1 year were low. There was only 1 case (3%) of severe CRS. Compared with previously published outcomes, mMUD PBSCT using PTCy-based GVHD prophylaxis has a safety and efficacy profile that may not be different from that of PBSCT from matched donors. These results further solidify that all patients who require blood or BM transplantation should be able to find an acceptable donor.

Patient expectations of benefit from systemic treatments for metastatic prostate cancer.

BACKGROUND: Metastatic prostate cancer is incurable, but systemic therapies can improve quality of life and prolong survival. Accurate perceptions of treatment risks and benefits are vital as patients with metastatic disease make treatment decisions. We assessed treatment-related expectations for benefit among patients with metastatic prostate cancer and explored associated sociodemographic characteristics. METHODS: Men with metastatic prostate cancer (N = 100) completed surveys assessing their treatment-related expectations for cancer cure, symptom relief, and prolonged life expectancy. Frequencies were used to describe the proportions of reported expectations. Fisher's exact tests were used to assess the associations of sociodemographic characteristics with treatment expectations. RESULTS: One third (33%) of participants believed treatment was at least a little likely to cure their metastatic cancer. Most participants believed treatment could provide symptom relief (76%) and extend life expectancy (95%). Among participants reporting that cancer cure was at least a little likely vs not at all, more men identified as non-white (24% vs 5%; P = .01), self-reported good health (90% vs 58%; P < .01), and had greater optimism (78% vs 47%; P < .01). Among participants reporting that symptom relief was at least a little likely vs not at all, more men were less than 70 years old (62% vs 0%; P = .01). CONCLUSION: A large proportion of patients with metastatic prostate cancer reported beliefs inconsistent with understanding that treatment was not curative. Race, better self-reported health, and greater optimism were related to unrealistic expectations. Efforts to ensure alignment of patient and clinician expectations may facilitate more effective shared decision-making for treating metastatic disease.

Knee Fat Pad Volumes in Patients with Hemophilia and Their Relationship with Osteoarthritis.

Hemophilic arthropathy is a progressive, disabling condition with poorly understood pathobiology. Since there is an emerging interest to study the role of intra-articular fat pad size and biology in arthritic conditions, we explored fat pad volume changes in hemophilic arthropathy and to what extent they differed from osteoarthritis. We matched a cohort of 13 adult patients with hemophilic arthropathy of the knee with age- and gender-matched cohorts without osteoarthritis ("control cohort") and with the same degree of radiographic osteoarthritis ("OA cohort") in 1 : 2 fashion. Infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) volumes were calculated based on magnetic resonance imaging and differences in fat pad volumes, demographics, height, weight, and osteoarthritis scores were evaluated. Fat pad volumes were positively associated with body size parameters in all three cohorts but were unaffected by the degree of osteoarthritis. While IPFP volumes did not differ between cohorts, SPFP volumes expanded disproportionally with weight in hemophilia patients. Our observations indicate that IPFPs and SPFPs behave biologically differently in response to different arthritic stimuli. The exaggerated expansion of the SPFP in hemophilia patients highlights the importance of further studying the implications of fat pad biology for progression of hemophilic arthropathy.

Pigmented hidrocystoma of nasal epithelium (PHONE): report of a man with a pigmented hidrocystoma of his nose and literature review.

BACKGROUND: Hidrocystomas are benign tumors of apocrine or eccrine epithelium. They most commonly occur on the head and neck, especially periorbitally. Albeit rare, these adnexal tumors may present as pigmented lesions. PURPOSE: To describe a patient with a pigmented eccrine hidrocystoma of his nose and to review the features of other individuals with pigmented hidrocystoma of the nasal epithelium. MATERIAL AND METHODS: PubMed was used to search the follow terms: hidrocystoma and pigmented. All papers were reviewed and relevant manuscripts, along with their reference citations were evaluated. RESULTS: A 52-year-old man who presented with a pigmented eccrine hidrocystoma on his nasal bridge was described. The features of three previously described patients with pigmented hidrocystoma of the nose were evaluated. The tumors presented as single or multiple, less than 2mm, blue papules. Our patient's tumor would intermittently bleed, which prompted consideration of a possible basal cell carcinoma. Biopsy established the diagnosis showing a cystic lesion lined by eccrine epithelium with pigmented secretion within the cyst's lumen. The cyst content stained positive with Fontana-Masson stain. Our patient's excisional biopsy resulted in excellent cosmetic appearance and complete removal of the benign adnexal tumor. CONCLUSION: Pigmented hidrocystomas may be mistaken for other skin lesions, such as a pigmented basal cell carcinoma and melanoma. A biopsy readily establishes the diagnosis. We respectfully suggest that a hidrocystoma located on the nose that is pigmented be referred to as a PHONE: pigmented hidrocystoma of the nasal epithelium.