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Abstract Context. —Sarcomatous transformation is a rare complication of Paget disease of bone. Prognosis in patients with other types of sarcomas arising in bone has improved in the last several decades because of therapeutic advances. However, because of the rarity of Paget sarcoma, outcome studies in these patients are limited. Objective. —To determine whether prognosis for Paget sarcoma has improved. Design. —Seventy cases of sarcomas arising in the setting of Paget disease were collected, and the histologic and clinical findings were reviewed. Clinical follow-up was obtained in 67 cases. Results. —Sarcoma arising in Paget disease tended to arise in older men (46 men, 24 women; age range, 31–88 years; mean age, 66 years) and predominated in the axial skeleton (n = 37), especially in the pelvis. Thirty-three patients had a clinical history of Paget disease ranging in duration from 16 months to 30 years (mean, 15 years). No significant difference in incidence between monostotic (n = 33) and polyostotic (n = 36) disease was noted. Most tumors were osteosarcomas (88%). All tumors were high grade. Follow-up information was obtained in 67 of 70 cases (range of follow-up, 1–252 months). Survival ranged from 1 month to 20 years, with a 5-year survival rate of 10%. Conclusions. —Prognosis remains poor in patients with Paget sarcoma. There is no significant correlation between the number of bones involved with Paget disease or the duration of disease and development of Paget sarcoma. Poor prognosis in Paget sarcoma is unrelated to site or stage at presentation.

Background After critical illness, patients are often left with impairments in physical, social, emotional, and cognitive functioning. Peer support interventions have been implemented internationally to ameliorate these issues. Objective To explore what patients believed to be the key mechanisms of effectiveness of peer support programs implemented during critical care recovery. Methods In a secondary analysis of an international qualitative data set, 66 telephone interviews with patients were undertaken across 14 sites in Australia, the United Kingdom, and the United States to understand the effect of peer support during recovery from critical illness. Prevalent themes were documented with framework analysis. Results Most patients who had been involved in peer support programs reported benefit. Patients described 3 primary mechanisms: (1) sharing experiences, (2) care debriefing, and (3) altruism. Conclusion Peer support is a relatively simple intervention that could be implemented to support patients during recovery from critical illness. However, more research is required into how these programs can be implemented in a safe and sustainable way in clinical practice.

Abstract In December 2019, the Antibacterial Resistance Leadership Group (ARLG) was awarded funding for another 7-year cycle to support a clinical research network on antibacterial resistance. ARLG 2.0 has 3 overarching research priorities: infections caused by antibiotic-resistant (AR) gram-negative bacteria, infections caused by AR gram-positive bacteria, and diagnostic tests to optimize use of antibiotics. To support the next generation of AR researchers, the ARLG offers 3 mentoring opportunities: the ARLG Fellowship, Early Stage Investigator seed grants, and the Trialists in Training Program. The purpose of this article is to update the scientific community on the progress made in the original funding period and to encourage submission of clinical research that addresses 1 or more of the research priority areas of ARLG 2.0.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel’s discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.

Background: Here we describe an online network of patients with cancer, clinicians and researchers, layered on top of a comprehensive real world database of treatments and outcomes, continuously updated in near real time, and initially focused on multiple myeloma. Methods: Patients with multiple myeloma register at www.all4cure.com and sign HIPAA release forms to provide access to all of their medical records from all of the institutions from which they have received care. From the medical records, a structured dataset of treatments and lab results is extracted by a myeloma-dedicated team for display on each patient's de-identified, personalized dashboard. A discussion panel allows more than 1200 participating patients, clinicians and researchers to post comments or questions regarding each patient's specific circumstances. For each patient, lines of therapy and responses are determined according to IMWG and published criteria (Blood [2015] 126: 921-922). Here we report initial results from the treatments and responses among patients with multiple myeloma and plasma cell leukemia. Results: A total of 493 patients includes 26 with monoclonal gammopathy of undetermined significance (MGUS), 51 with smoldering myeloma, 408 with multiple myeloma, and 8 with primary plasma cell leukemia. Among patients with multiple myeloma, 42 (10.3%) had antecedent MGUS and/or smoldering myeloma. The average age is 65.6 (+/- 9.7). 50.9% are male and 49.1% are female. 42 states in the U.S. and 8 other countries are represented. Two patients with multiple myeloma had not started treatment by the time of this report. The remaining 414 patients with multiple myeloma or plasma cell leukemia received 1 to 16 lines of therapy. Among the 414 patients that received at least one line of therapy, a remarkable 89 distinct first line therapies were administered. The most common first line therapies were lenalidomide, bortezomib, dexamethasone (n=92), cyclophosphamide, bortezomib, dexamethasone (n=50), lenalidomide, bortezomib, dexamethasone + autologous stem cell transplant + lenalidomide maintenance (n=41), lenalidomide and dexamethasone (n=29), and bortezomib and dexamethasone (n=22). 62 patients received a first line therapy that was not received by any other patient in our database. This variation was attributable to participation in clinical trials, variation in the availability of drugs over time and different geographic locations, and the very large number of distinct combinations associated with multi-agent regimens. Seventy six percent of patients with multiple myeloma or plasma cell leukemia received a second line of therapy, 52% received a third line of therapy, 34% received a fourth line of therapy, 23% received a fifth line of therapy, and 18% received a sixth line of therapy. We observed a trend toward a decline in favorable responses with successive lines of therapy (Table 1) consistent with previous reports, with a correlation coefficient between the line of therapy and overall response rate of -0.74. Among the 76 patients who received 6 or more lines of therapy (247 lines of therapy in total), only 7 achieved stringent complete responses (sCRs), of which 5 were associated with a CAR-T therapy. Table 1 also shows a trend toward more rapid changes in treatment associated with later lines of therapy. 57 of 493 patients (12%) are deceased. Conclusions: Our findings reveal remarkable variation in the treatment of myeloma and provide a potentially valuable resource of up to date and current clinical features, prognosis, treatments, side effects, and outcomes of patients with myeloma in the real world. Table 1. Summary of lines of therapy and outcomes across 414 patients with multiple myeloma and plasma cell leukemia. The percentages of patients achieving sCR, ≥ PR (overall response rate - ORR), and ≥MR (clinical benefit rate - CBR) are shown for each line of therapy. Also depicted is the interval mortality and the mean and median number of days between the beginning of a line therapy and the beginning of the next line of therapy. Table Disclosures Richter: Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Sanofi: Consultancy; X4 pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Adaptive biotechnologies: Consultancy; Secura bio: Consultancy; Astra Zeneca: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; Antengene: Consultancy. Chhun:All4Cure: Current Employment. Zheng:All4Cure: Current Employment. Piboonvaranggoon:All4Cure: Current Employment. Mallick:All4Cure: Current Employment. Wren:All4Cure: Current Employment. Nam:All4Cure: Current Employment. Lopez Barquilla:All4Cure: Current equity holder in private company. Blau:All4Cure: Current equity holder in private company. Cowan:Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy; Bristol Myers Squibb: Research Funding. Bensinger:BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kumar:Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Genecentrix: Consultancy; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Adaptive Biotechnologies: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; MedImmune: Research Funding; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Cellectar: Other; Sanofi: Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Kite Pharma: Consultancy, Research Funding. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Anderson:Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees. Blau:All4Cure: Current Employment, Current equity holder in private company.

Introduction: Patients with acute myeloid leukemia (AML) are often treated with intensive induction chemotherapy to achieve complete remission (CR). Early response to standard anthracycline plus cytarabine induction (7+3) is assessed by a day 14 nadir bone marrow biopsy. The nadir marrow has limitations, though, including sampling issues and ambiguity as to whether blasts are leukemia cells vs. regenerating marrow. In prior studies, the predictive value for remission of the nadir marrow is only 67-84%. A more accurate predictor of residual disease (RD) would give clinicians an opportunity to modify therapy earlier. Positron emission tomography (PET/CT) with 3'-deoxy-3'-[18F]fluorothymidine (FLT) is a molecular imaging modality that can assess cellular proliferation in the bone marrow compartment. A prior single-institution pilot study showed a significant difference in the marrow FLT uptake between patients with AML who achieved CR and those who had RD after count recovery. Methods: EAI141 was an ECOG-ACRIN-led, prospective, multi-center study designed to assess FLT PET/CT as a predictor of CR after AML induction. The primary objective was to evaluate the predictive value of post-treatment FLT PET/CT imaging for detecting RD, with the secondary objectives of evaluating the predictive value for detecting CR and estimating the sensitivity and specificity. Maximum standardized uptake value (SUVmax) of > 7 g/mL in total bone marrow compartment was chosen prospectively based on data from a pilot study as a marker for presence of leukemia cells at nadir. The predictive values, sensitivity, and specificity of the FLT PET/CT and the nadir bone marrow biopsy were calculated. Eligible subjects were 18 years or older with previously untreated AML who were to receive induction with 7+3. Subjects underwent a nadir marrow biopsy and an FLT PET/CT scan 10-17 days after starting induction, and prior to any re-induction if disease was noted on the nadir marrow. A recovery marrow was performed 28-35 days after initial treatment or re-induction to assess CR or RD. Subjects could undergo an optional pre-treatment scan. Relapse-free survival (RFS) and overall survival (OS) were additional clinical outcomes. Results: 87 subjects from 9 centers were enrolled between 2016-2018, and 61 were considered evaluable. Reasons for being not evaluable included study ineligibility (n=3), no post-treatment scan (n=13), and no remission marrow (n=10). Median age was 58 years (range 21-73); 56% were men and 44% were women. CR was achieved in 56% (34/61). Treatment was a single induction course in 79% (48/61) and re-induction in 21% (13/61). Predictive value based on FLT PET/CT was 60% (9/15, 95% CI 32%-84%) for RD and 61% (28/46, 95% CI 45%-75%) for CR. Of patients who achieved CR, 28/34 had SUVmax ≤ 7 g/mL (sensitivity of 82%) and 9/27 of those who did not had high SUVmax > 7 g/mL (specificity 33%). Predictive value of an aplastic marrow was 59% (26/44) for CR and 56% (9/16) for RD. Of patients who achieved CR, 26/33 had marrow hypoplasia (sensitivity 79%) and 9/27 with RD had disease in the nadir marrow (specificity 33%). Significant heterogeneity of bone marrow compartment post treatment (SUVhetero ranging from 0.24 to 1.07) was observed in FLT-PET/CT scans. Heterogeneity of bone marrow compartment decreased about 50% from pre-treatment to post-treatment FLT PET/CT. OS for all participants, stratified by post-treatment FLT PET/CT response and nadir marrow results, are summarized in the Figure. Conclusions: Although this study did not show significant advantage of FLT PET/CT compared to nadir marrow to predict RD or CR on the average, it did show signal heterogeneity in the study population that may be relevant to disease biology not appreciated by a single sampling site for the nadir or remission marrow. For example, in patients with false negative nadir biopsy, in approximately 20% of patients assessment with FLT PET/CT was correct, likely reflecting bone marrow heterogeneity and limitation of a single point sampling. Similarly, in almost 60% of patients with false positive nadir biopsy, FLT PET/CT assessment was correct. Figure 1 Disclosures Jeraj: AIQ Solutions: Current equity holder in private company. Kostakoglu:F. Hoffmann-La Roche: Consultancy. Strickland:KiTE: Consultancy; Kura: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Sunesis: Research Funding; ArcherDx: Consultancy; AbbVie: Consultancy. Uy:Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Perlman:GE Healthcare: Research Funding; AIQ: Research Funding.

AimsHip reconstruction after resection of a periacetabular chondrosarcoma is complex and associated with a high rate of complications. Previous reports have compared no reconstruction with historical techniques that are no longer used. The aim of this study was to compare the results of tantalum acetabular reconstruction to both historical techniques and no reconstruction.MethodsWe reviewed 66 patients (45 males and 21 females) with a mean age of 53 years (24 to 81) who had undergone acetabular resection for chondrosarcoma. A total of 36 patients (54%) underwent acetabular reconstruction, most commonly with a saddle prosthesis (n = 13; 36%) or a tantalum total hip arthroplasty (THA) (n = 10; 28%). Mean follow-up was nine years (SD 4).ResultsThere was no difference in the mean age (p = 0.63), sex (p = 0.110), tumour volume (p = 0.646), or type of resection carried out (p > 0.05) between patients with and without reconstruction. Of the original 66 patients, 61 (92%) were ambulant at final follow-up. There was no difference in the proportion of patients who could walk in the reconstruction and 'no reconstruction' groups (p = 0.649). There was no difference in the mean Musculoskeletal Tumor Society (MSTS) score between patients who were reconstructed and those who were not (61% vs 56%; p = 0.378). Patients with a tantalum THA had a significantly (p = 0.015) higher mean MSTS score (78%) than those who were reconstructed with a saddle prosthesis (47%) or who had not been reconstructed (56%). Patients who had undergone reconstruction were more likely to have complications (81% vs 53%; p = 0.033).ConclusionReconstruction after resection of the acetabulum is technically demanding. In selected cases, reconstruction is of benefit, especially when reconstruction is by tantalum THA; however, the follow-up for these patients remains mid-term. When not feasible, patients with no reconstruction have an acceptable functional outcome. Level of Evidence: Level III Therapeutic. Cite this article: Bone Joint J 2021;103-B(2):391–397.