Citations

Context.— Controversies and uncertainty persist in prostate cancer grading. Objective.— To update grading recommendations. Data Sources.— Critical review of the literature along with pathology and clinician surveys. Conclusions.— Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 + 4 = 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace “tertiary grade pattern” in radical prostatectomy (RP) with “minor tertiary pattern 5 (TP5),” and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)-targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 + 5 = 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (>50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) “atypical intraductal proliferation (AIP)” is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice.

Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.

AbstractObjectives: To determine the usefulness of social media for rapid communication with experts to discuss strategies for prioritization and safety of deferred treatment for urologic malignancies during COVID‐19 pandemic, and to determine whether the discourse and recommendations made through discussions on social media (Twitter) were consistent with the current peer‐reviewed literature regarding the safety of delayed treatment. Methods: We reviewed and compiled the responses to our questions on Twitter regarding the management and safety of deferred treatment in the setting of COVID‐19 related constraints on non‐urgent care. We chronicled the guidance published on this subject by various health authorities and professional organizations. Further, we analyzed peerreviewed literature on the safety of deferred treatment (surgery or systemic therapy) to make made evidence‐based recommendations. Results: Due to the rapidly changing information about epidemiology and infectious characteristics of COVID‐19, the health authorities and professional societies guidance required frequent revisions which by design take days or weeks to produce. Several active discussions on Twitter provided real‐time updates on the changing landscape of the restrictions being placed on non‐urgent care. For separate discussion threads on prostate cancer and bladder cancer, dozens of specialists with expertise in treating urologic cancers could be engaged in providing their expert opinions as well as share evidence to support their recommendations. Our analysis of published studies addressing the safety and extent to which delayed cancer care does not compromise oncological outcome revealed that most prostate cancer care and certain aspects of the bladder and kidney cancer care can be safely deferred for 2‐6 months. Urothelial bladder cancer and advanced kidney cancer require a higher priority for timely surgical care. We did not find evidence to support the idea of using nonsurgical therapies, such as hormone therapy for prostate cancer or chemotherapy for bladder cancer for safer deferment of previously planned surgery. We noted that the comments and recommendations made by the participants in the Twitter discussions were generally consistent with our evidence‐based recommendations for safely postponing cancer care for certain types of urologic cancers. Conclusion: The use of social media platforms, such as Twitter, where the comments and recommendations are subject to review and critique by other specialists is not only feasible but quite useful in addressing the situations requiring urgent resolution, often supported by published evidence. In circumstances such as natural disasters, this may be a preferable approach than the traditional expert panels due to its ability to harness the collective intellect to available experts to provide responses and solutions in real‐time. These real‐time communications via Twitter provided sound guidance which was readily available to the public and participants, and was generally in concordance with the peerreviewed data on safety of deferred treatment.

8546 Background: The PI bortezomib is commonly used in first-line therapy of AL, but new therapies are needed that are tolerable in the context of multi-organ dysfunction and that, in RRAL, offer improved outcomes following prior bortezomib. Ixazomib is an oral PI, and in TOURMALINE-AL1, the first phase 3 trial conducted in RRAL, while the first primary endpoint of hematologic overall response rate (ORR) was not met, all clinically relevant time-to-event endpoint data favored Ixa-Dex vs PC (Dispenzieri et al, ASH 2019). Methods: RRAL pts with 1–2 prior therapies were randomized (1:1) to Ixa-Dex (n = 85) or PC (n = 83; Dex plus lenalidomide [n = 47], melphalan [n = 24], cyclophosphamide [n = 10], or thalidomide [n = 2]), stratified by cardiac stage, relapsed vs refractory disease, and prior PI exposure. The primary endpoints were hematologic ORR and 2-yr rate of vital organ deterioration or death. We report subgroup analyses of ORR and outcomes by prior PI exposure. Results: Of the 168 pts enrolled, 90 were PI-naïve and 78 PI-exposed (46 and 39 in the Ixa-Dex arm; 44 and 39 in the PC arm) per stratification; 28 and 27 pts in the Ixa-Dex and PC arms had received bortezomib in their last prior line. Hematologic ORR was 63% vs 50% for Ixa-Dex vs PC (odds ratio [OR] 1.71; 95% confidence interval [CI] 0.74–3.96) in PI-naïve pts, and 41% vs 51% (OR 0.66; 95% CI 0.27–1.62) in PI-exposed pts. For time-to-event outcomes (Table), hazard ratios (HRs) were 0.46–0.85 in favor of Ixa-Dex vs PC in both PI-naïve and PI-exposed pts. Conclusions: Hematologic ORR was higher with Ixa-Dex vs PC in PI-naïve pts but lower in PI-exposed pts (although not statistically significant), and long-term clinically relevant outcomes favored Ixa-Dex in both groups. Based on HRs, the magnitude of benefit appeared similar or greater in PI-naïve vs PI-exposed pts. Clinical trial information: NCT01659658 . [Table: see text]

TPS4661 Background: Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50 mg/m2 free base + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin (OX) 60 mg/m2 on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). Herein, we present the design of the phase 3 NAPOLI-3 study investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC. Methods: NAPOLI-3 (NCT04083235) is a phase 3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma not previously treated in the metastatic setting. Patients are required to have one or more metastatic tumors measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec 2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (regimen as per phase 1/2 study) or nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival (OS). Secondary endpoints (progression-free survival [PFS] and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1 criteria) will be compared only if the primary endpoint shows superiority for liposomal irinotecan + 5-FU/ LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2 months until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT04083235 .

Worldwide, millions of women live with breast implants. Therefore, it is important that physicians be aware of an uncommon but possibly serious complication arising from breast implants: breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Breast implant–associated anaplastic large-cell lymphoma most commonly presents as a delayed fluid collection around a textured breast implant or as a mass in the capsule surrounding the implant. The exact pathogenesis of the disease remains unclear. The neoplastic cells of BIA-ALCL show strong uniform staining for CD30 and are consistently negative for activin receptor-like kinase 1. Patients with confirmed cases should be referred to a lymphoma specialist or breast medical oncologist for a complete oncologic evaluation before any surgical intervention. For disease confined to the fluid accumulation or capsule, or both, surgical removal of the implant and complete capsulectomy is the preferred treatment. Postoperative chemotherapy or radiation, or both, are not considered necessary for patients with limited-stage disease and are reserved for advanced disease stages. Generally, BIA-ALCL is a local disease that follows an indolent course and has an excellent prognosis. Although complete remission of disease has occurred in patients with BIA-ALCL, median overall survival is reduced. As of March 2018, approximately 529 unique, confirmed BIA-ALCL cases had been reported in 23 countries. To date, 16 patients have died from BIA-ALCL, and all had extracapsular involvement. The aim of this article is to summarize the diagnosis, evaluation, and management of BIA-ALCL, based on established guidelines, for all practitioners who may care for patients with breast implants.

AbstractA peripheral blood flow cytometric assay for Sézary syndrome (SS) or circulating mycosis fungoides (MF) cells must be able to reliably identify, characterize, and enumerate T‐cells with an immunophenotype that differs from non‐neoplastic T‐cells. Although it is also important to distinguish SS and MF from other subtypes of T‐cell neoplasm, this usually requires information in addition to the immunophenotype, such as clinical and morphologic features. This article outlines the approach recommended by an international group with experience and expertise in this area. The following key points are discussed: (a) At a minimum, a flow cytometric assay for SS and MF should include the following six antibodies: CD3, CD4, CD7, CD8, CD26, and CD45. (b) An analysis template must reliably detect abnormal T‐cells, even when they lack staining for CD3 or CD45, or demonstrate a phenotype that is not characteristic of normal T‐cells. (c) Gating strategies to identify abnormal T‐cells should be based on the identification of subsets with distinctly homogenous immunophenotypic properties that are different from those expected for normal T‐cells. (d) The blood concentration of abnormal cells, based on any immunophenotypic abnormalities indicative of MF or SS, should be calculated by either direct enumeration or a dual‐platform method, and reported.

5565 Background: The goal of this study was to determine the recurrence rates (R) of patients with grade 1 and 2 stage 1A and IB ovarian tumors treated with and without chemotherapy. Methods: We conducted a five-center retrospective study of patients with Stage 1A/B grade 1 and 2 ovarian carcinoma. All women underwent comprehensive staging including a minimum of unilateral salpingo-ophorectomy, unilateral pelvic and para-aortic lymphadenectomy, and omentectomy. Clear cell histologies were classified as grade 3 and excluded. The minimum cancer-free survivor follow-up was 3 years. Results: We identified 82 patients with Stage 1A/B grade 1 and 2 who met criteria for the study. The median age was 58 yrs (range 29 to 83) and the median follow-up was 5.3 yrs (range 3 to 11 yrs). The majority were of endometrioid histology (51), followed by mucinous (19), papillary serous (11), and mixed (1). Recurrences were of endometrioid (4), mucinous (1), or papillary serous (1) histology. For Stage 1A, overall recurrence rate was 9% (6/67). The overall recurrence rates for Stage 1A, grade1 tumors was 6% and among grade 2 tumors 12% (p=0.40). Among Stage 1A patients not treated with chemotherapy, there was a 7% (2/29) and 9.5% (2/21) recurrence rate for grade 1 and grade 2 tumors, respectively. For the grade 1 tumors, both patients are alive with disease at 3 and 5 yrs. For the grade 2 tumors, one is alive without evidence of disease at 7 yrs and the other died from disease at 4 yrs. Time to recurrence (TTR) was 2.3 yrs for grade 1 tumors and 2.6 yrs for grade 2 tumors. For Stage 1A patients treated with a platinum chemotherapy regimen, there were no recurrences (0/5) for grade 1 tumors and a 16% (2/12) recurrence rate for grade 2 tumors. Of the recurrences, one patient died from disease at 1.4 yrs and the other is alive with stable disease at 6 yrs. Time to recurrence was 2.85 yrs for grade 2 tumors. For grade 1 or 2, Stage 1A tumors, recurrence rates and time to recurrence were not effected by chemotherapy administration (R, p=0.55 and p=0.54, respectively; TTR, grade 2, p=0.85). No recurrences were observed in the 15 patients with Stage IB, grade 1 and 2 tumors. Conclusions: In comprehensively staged patients with Stage 1A/B, grade 1 and 2, low recurrence rates suggest adjuvant chemotherapy may not be indicated. No significant financial relationships to disclose.