Abstract
National Comprehensive Cancer Network (NCCN) guidelines represent the consensus standard of care for diagnosis and management of the majority of known cancers. NCCN guidelines on breast ...implant-associated anaplastic large cell lymphoma (BIA-ALCL) have been recognized by the US Food and Drug Administration and widely advocated by national specialty societies. Consensus guidelines have helped create a treatment standardization for BIA-ALCL at all stages of disease. NCCN guidelines are evidence-based where possible and utilize expert consensus opinion to fill in gaps that may exist. NCCN undergoes annual panel review by multidisciplinary faculty members, and this article represents the most up-to-date 2019 guidelines. Recommendations focus on parameters for achieving reliable diagnosis and disease management and emphasize the critical role for complete surgical ablation. Suggestions for adjunct treatments and chemotherapy regimens are included for advanced BIA-ALCL with lymph node involvement. BIA-ALCL recurrence and management of unresectable disease, and organ metastasis are addressed. Adherence to recognized BIA-ALCL guidelines ensures patients receive the most current efficacious treatment available.
Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a recently described form of T-cell non-Hodgkin lymphoma now formally recognized by the World Health Organization classification ...of lymphoid neoplasms. The disease most often presents with a delayed seroma around the breast implant, almost exclusively with a textured surface, and manifests with breast pain, swelling or asymmetry, capsular contracture, but can also present with a breast mass, and lymph node involvement. The prognosis of BIA-ALCL is favorable compared with many other subtypes of systemic T-cell lymphoma; however, unlike other non-Hodgkin lymphomas, complete surgical excision for localized disease is an important part of the management of these patients. In this paper, we share our recommendations for a multidisciplinary team approach to the diagnosis, workup, and treatment of BIA-ALCL in line with consensus guidelines by the National Comprehensive Cancer Network.
To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).
CITN-10 is a single-arm, multicenter phase II trial of 24 ...patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria.
Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature.
Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.
Published case series demonstrate a lack of treatment standardization for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) with a wide variety of therapeutic strategies being ...employed at all stages of disease. The National Comprehensive Cancer Network (NCCN) annually publishes Clinical Practice Guidelines for Non-Hodgkin Lymphomas. For the first time, BIA-ALCL management will be included which signifies an important and needed guideline addition. The new BIA-ALCL guideline was achieved by a consensus of lymphoma oncologists, plastic surgeons, radiation oncologists, and surgical oncologists. NCCN guidelines focus on the diagnosis and management throughout the stages of many lymphoma subtypes based upon the most current data available. This article summarizes the essential recommendations and optimal therapeutic strategies of the NCCN guidelines critical to the plastic surgery community. We encourage international adoption of these BIA-ALCL treatment standards by our specialty societies across the oncology and surgery disciplines.
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In this short contribution, I summarize the four papers that comprise the symposium on Microfoundations and Macroeconomics: An Austrian Perspective and then address several themes that they ...raise. Specifically, I discuss the roles of capital and capital goods, human capital, adjustment costs after monetary shocks, W. H. Hutt’s understanding of idleness in the labor market, and the ways in which Austrian macroeconomic concepts can be deployed in doing economic history. I argue that intertemporal discoordination remains the key concept in Austrian macroeconomics and encourage present and future scholars to explore the coordinating role of capital and to challenge the institutional and historical contingencies that have defined the canonical Austrian business cycle theory story.
Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We ...aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Interpretation Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Funding Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.
The risk of BIA-ALCL for patients with textured breast implants has been estimated between 1/2832 and 1/30,000 women. Existing studies estimating the numbers exposed and at risk, may have under ...reported cases, and/or lacked comprehensive follow-up. Our objective is to determine the risk of BIA-ALCL in a defined cohort of patients reconstructed with macro-textured breast implants and consistently followed long-term.
A prospective cohort study was conducted in patients who underwent breast reconstruction by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC) from December 1992 to December 2017. Major events related to implants were prospectively recorded. We identified cases of BIA-ALCL by cross-checking clinical, pathology and external records data. Patients were followed until lymphoma occurrence or last follow-up. The primary outcomes were incidence rate per person-years and cumulative incidence.
From 1992 to 2017, 3546 patients underwent 6023 breast reconstructions, mainly after breast cancer removal, or contralateral prophylactic mastectomy, using macro-textured surface expanders and implants. All reconstructions were performed by a single surgeon (PGC). Median follow-up was 8.1 years (range, 3 months – 30.9 years). Ten women, 1/354, developed ALCL after a median exposure of 11.5 years (range, 7.4–15.8 years). Overall risk of BIA-ALCL in our cohort is 1/355 women or 0.311 cases per 1000 person-years (95% CI 0.118 to 0.503).
This study, the first to evaluate the risk of macro-textured breast implants from a prospective database with long term follow-up, demonstrates that the incidence rate of BIA-ALCL may be higher than previously reported. These results can help inform implant choice for women undergoing breast reconstruction.
Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given ...the clinical and public health implications of the syndrome.
We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms.
We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 92%) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).
Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).
Histone deacetylase inhibitors (HDACi) are epigenetic modifiers with single-agent activity in patients with cutaneous and peripheral T-cell lymphoma (CTCL, PTCL). The mechanisms for this preferential ...activity remain unclear, and although some would term this as 'class effect,' there are differences in efficacy and safety, likely a result of the varying chemical structures/classes, histone and non-histone targets, potencies, and clinical dosing for each. Three HDACi have single-agent approval in relapsed/refractory TCL in the United States: romidepsin in CTCL and PTCL, vorinostat in CTCL, and belinostat in PTCL. Although comparison of these agents is difficult due to differences in patient populations, through this review we aimed to provide a detailed overview of the clinical data for HDACi in TCL and their use in clinical practice. Despite early concerns, data demonstrate the cardiac safety of HDACi, while highlighting the need to maintain electrolytes in the normal range and monitor QT interval when initially co-administering antiemetics or other drugs that prolong QT. To further improve response rates and durability of responses, HDACi are under clinical investigation in combination with chemotherapy regimens and various novel agents.
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