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Background: There continues to be controversy regarding the treatment of early-stage arthritis of the wrist, particularly in young patients, because of the large number of techniques, the poor long-term results for many of these techniques, and the overall paucity of high-level scientific data. Proximal row carpectomy (PRC) and 4-corner arthrodesis (4CA) have been established as the mainstay motion-sparing surgical treatment options in cases of early scapholunate advanced collapse and scaphoid nonunion advanced collapse arthritis. However, there is marked controversy surrounding the best treatment option for younger patients with greater physical demands because of the questionable outcomes associated with these motion-sparing options in such patients 1–9 . Traditionally, many surgeons prefer 4CA over PRC for young, high-demand patients, in part because studies have suggested that young age and work status as a laborer are important risk factors for worse outcomes following PRC 1,8 . However, the concern for symptomatic nonunion and potential for radiolunate arthritis in 4CA, as well as the lack of medium to long-term comparative studies in this subset, make this recommendation controversial 10 . Description: The wrist is accessed via the dorsal approach, creating a retinacular flap and a radially based ligament-sparing capsulotomy. The scaphoid, lunate, and triquetrum are then excised en bloc. The radioscapholunate ligament is protected. The capsule and retinaculum and then repaired. Alternatives: Alternatives to PRC include nonoperative treatment, 4CA, capitolunate arthrodesis, posterior and anterior interosseous neurectomies, total wrist arthroplasty, and total wrist arthrodesis. Rationale: A recent study by Wagner et al. compared patients <45 years old who underwent either PRC or 4CA 11 . Overall, PRC and 4CA had similar complication rates, postoperative pain levels, wrist function, and long-term outcomes free of conversion to arthrodesis. Patients who underwent PRC had improved motion and fewer complications, whereas patients who underwent 4CA had slightly lower rates of radiocarpal arthritis. Therefore, in this technique article, we describe PRC for wrist arthritis in patients <45 years old.

Abstract Background: The COVID-19 pandemic rapidly altered health care worldwide. To save protective equipment and minimize exposures, many hospitals stopped some or all cancer surgery, leading oncologic providers to quickly adjust patient management. The goal of this study is to describe the breast cancer patient level changes which occurred during the initial months of COVID-19 in the United States. Methods: The American Society of Breast Surgeons developed a COVID-19 specific registry, within the established HIPPA compliant Mastery of Breast Surgery Program. Surgeons entered patient demographic data as well as their surgical and medical care (Neoadjuvant endocrine (NET) vs Neoadjuvant chemotherapy (NCT)). Data fields tracked whether decisions were usual for that practice, or modified due to COVID-19. Results: Between 3/1 and 6/17/2020, data from 1781 patients was entered by 154 surgeons. Mean age was 63, 78% Caucasian, 10% African American, 6% Hispanic; with geographic distribution ranging from 10.8% Northwest to 29.5% Northeast. Initial consultation took place in-person for 94.8% and only 5.2% (89) occurred via video/telephone. To date, just over 1% (14) of patients tested positive for COVID-19. Mean invasive tumor size was 21.2mm and 15.7% were node positive. Of 1445 invasive breast cancers 75% (1081) were ER +/HER2-, 13.5% (195) HER2+, 11.1% (160) triple negative (TNBC) (9/missing data). DCIS comprised 18.2% (325) of the cohort. Of 267 cases of ER+ DCIS, 49% (131) had primary surgery and 49% (130) received NET. The majority of NET use was due to COVID-19, 95% (124). Almost all (50/52) ER- DCIS underwent primary surgery (6/missing ER). Table 1 describes the management for the 1436 patients with invasive cancer with known biomarkers. NET due to COVID-19 was utilized in 45% (482), with only 5% (54) as part of usual practice. Increasing age was not a statistically significant factor in the use of NET (OR 0.99, 95% CI 0.97-1.01). In comparison to patients from the Northwest, patients from the Southwest and Northeast had the greatest use of NET(COVID-19) vs NET(usual) (ORs 14.4 and 4.6) Genomic assay testing was performed on the core biopsy in 216 patients, with 65% (141) due to COVID-19. Among the patients who had genomic testing due to COVID-19, 116 (82%) had NET, 18 (13%) had NCT, with the remaining having primary surgery. Of 472 patients treated with primary surgery for which the impact of COVID-19 was provided, surgery was delayed in 20% (96). Patients from the Northeast had a 2.1 x greater odds of having surgery delayed in comparison to those from the Midwest. Patients also experienced changes to their surgical plan with the most common changes being 6% (27) converting from mastectomy to breast conservation and 7% (34) from mastectomy with reconstruction to mastectomy without reconstruction. Conclusion: COVID-19 led to significant modifications in breast cancer treatment, including high rates of NET, genomic assay testing on core biopsies as well as delays in surgery; each of which were consistent with the prioritization and treatment recommendations from the COVID-19 Pandemic Breast Cancer Consortium. The majority of patients with TNBC and HER2+ disease received guideline concordant NCT. The ASBrS Mastery COVID-19 registry provides a snapshot into the rapid care changes caused by the pandemic, has ongoing data entry and analysis and will enable understanding of the impact on long term breast cancer outcomes. Table 1: Biomarker specific treatmentsER+/HER2- (1081)TNBC (160)HER2+/any ER (195)Mean Age656159African American (%)97(9%)21(13%)27(14%)Primary Surgery (usual)386 (36%)50 (31%)37 (19%)Primary Surgery (COVID-19)28 (2.6%)6 (3.7%)6 (3.1%)NET (usual)54 (5%)NA1(0.5%)NET (COVID-19)482 (45%)NA6 (3.6%)NCT (usual)90 (8.3%)98 (61%)137 (70%)NCT (COVID-19)39 (3.6%)6 (3.7%)8 (4.1%) Citation Format: Lee Gravatt Wilke, Toan T Nguyen, Qiuyu Yang, Bret M Hanlon, Kathryn A Wagner, Pamela Strickland, Eric A Brown, Jill Dietz, Judy C Boughey. Impact of the COVID-19 pandemic on the multidisciplinary management of breast cancer: Initial analysis of the american society of breast surgeons mastery COVID-19 registry [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-01.

PURPOSE Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.

Hematological malignancies comprise a genetically heterogeneous spectrum of diseases caused by abnormal proliferation or maturation of a variety of hematological cell lineages. Genomic abnormalities including chromosomal translocations, copy number variations and sequence level gene mutations underlie the pathogenesis of these disorders and frequently serve as important diagnostic, prognostic and/or therapeutic markers. However, the substantial discrepancy in interpretation and reporting of these genomic abnormalities among testing labs creates challenges for patient management. Therefore, standardizing the curation, clinical interpretation and reporting of somatic alterations within the context of their diagnostic, prognostic and therapeutic significance in hematological cancers is critical. In January 2020, the ClinGen Somatic Cancer Clinical Domain working group formed the Hematological Cancer Taskforce (HCT) with a goal to undertake systematic curation and evidence-based clinical interpretation of genes/somatic variants associated with hematological malignancies. The HCT has recruited 32 multi-disciplinary experts including oncologists, molecular pathologists, clinical lab directors, genomic scientists and biocurators with expertise in hematological malignancies. In collaboration with the Clinical Interpretation of Variants in Cancer (CIViC) (civicdb.org) knowledgebase, variants from peer-reviewed publications are curated with editor review for clinical utility as evidence items. Monthly discussions based on these evidence items lead to the creation of summary variant assertions using the AMP/ASCO/CAP guidelines (Li M, et al., Journal of Molecular Diagnostics, 2017). The HCT is currently focused on expert curation and clinical interpretation of somatic variants in FLT3 (internal tandem duplication, tyrosine kinase domain and non tyrosine kinase domain variants) in acute myeloid leukemia (AML). Expert curation of gene fusions in Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) in collaboration with the ClinGen somatic pediatric cancer taskforce is currently underway. To date, the HCT has curated 45 evidence items from clinical and pre-clinical studies on the aforementioned genes/variants. In addition, three AMP Tier I, level A variant assertions of FLT3-ITD, D835 and I836, which predict response to Gilteritinib, an FDA-approved drug for relapsed or refractory AML, have been curated. In the future, the HCT plans to extend its focus on curation of BCR-ABL1 kinase domain mutations in chronic myeloid leukemia (CML). Based on the initial pilot curation phase, the HCT will develop gene-specific recommendations to standardize the reporting and interpretation of somatic variants to better assist clinical decisions and apply to become official ClinGen Somatic Expert Panels in each of these gene-disease domains. Disclosures Blombery: Novartis: Consultancy; Invivoscribe: Honoraria; Amgen: Consultancy; Janssen: Honoraria.

Background: Multiple myeloma (MM) is typically diagnosed in patients (pts) aged 65-74 y (SEER: Myeloma. 2019); therefore, many pts present with concomitant metabolic disorders such as diabetes (18%-22% prevalence of type 2 diabetes [T2D; BMC Cancer. 2020;20:489]). Obesity (body mass index [BMI], ≥ 30 kg/m2) is associated with increased prevalence of T2D (Int J Clin Pract. 2007;61:737), and both are suggested risk factors for MM (Blood. 2012;119:4845; Bone Marrow Transpl. 2014;49:1009). Results from single-center, retrospective studies have shown poorer clinical features and survival outcomes in diabetic pts with MM vs their nondiabetic counterparts (Eur J Haematol. 2012;89:320, Br J Cancer. 2014;111:628). The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of largely community-based pts with NDMM. Reported here is a descriptive analysis assessing differences in baseline (BL) characteristics, treatment patterns, and survival outcomes in diabetic vs nondiabetic pts enrolled in the Connect MM Registry. Methods: Pts with NDMM (N = 3011) were enrolled at 250 community, academic, and government sites. Eligible pts were aged ≥ 18 y with symptomatic MM diagnosed ≤ 2 months (mo) pre-enrollment per International Myeloma Working Group criteria (Leukemia. 2009;23:3). Diabetic pts were defined as those with a history of diabetes and also receiving antidiabetic treatment at BL; those without a history of diabetes and not receiving antidiabetic treatment at BL were defined as nondiabetic pts. Descriptive statistics were used for BL characteristics and treatment regimens. Survival outcomes (progression-free survival [PFS] and overall survival [OS]) were analyzed using Cox regression and adjusted for covariates. Results: Of the 2845 pts included in this analysis, 467 (16%) were diabetic, and 2378 (84%) were nondiabetic. The median age was 69 y for diabetic pts and 66 y for nondiabetic pts, with fewer Black pts (12.2% vs 19.5%) in the nondiabetic group. The proportion of men was higher in the diabetic vs the nondiabetic group (61.9% vs 56.6%). Similar percentages of pts had ECOG PS of 0-1 in both groups (53.3% vs 55.3%). Obesity was more prevalent in diabetic vs nondiabetic pts (55.9% vs 30.4%). More diabetic pts had a history of hypertension requiring treatment vs nondiabetic pts (84.2% vs 52.5%). The prevalence of chromosomal abnormalities was comparable between the groups (within the limitation that data were missing in a substantial number of pts). Among MM-defining criteria, diabetic pts had a higher incidence of hypercalcemia (11.8% vs 8.5%), anemia (50.3% vs 46.5%), and increased creatinine (23.8% vs 19%), whereas measured kidney function was similar. A lower proportion of diabetic than nondiabetic pts received stem cell transplantation (SCT; 28.9% vs 41.5%) and triplet regimens during first induction (48.2% vs 52.8%%). The use of ≥ 2 novel agents during first line (1L) was lower in diabetic than nondiabetic pts (27.8% vs 34.6%), but use of a single novel agent (63.4% vs 60%) and alkylator in 1L (20.6% vs 22.4%) was comparable. The top five 1L regimens were similar for both groups, with lenalidomide + bortezomib + dexamethasone being the most common 1L regimen, and lenalidomide the most common maintenance therapy. Diabetic pts had significantly shorter adjusted median PFS (24.4 vs 31.5 mo; hazard ratio [HR], 1.24; P = 0.001; Fig. 1A) and median OS (60 vs 72.6 mo; HR, 1.29; P = 0.001; Fig. 1B) than nondiabetic pts. In a subgroup analysis by BMI, diabetic pts had significantly shorter OS than nondiabetic pts (for BMI &lt; 30 [50.8 vs 73.1 mo; HR, 1.51; P = 0.0001] and BMI ≥ 30 [56.4 vs 78.6 mo; HR, 1.51; P &lt; 0.0001]). Conclusions: Diabetic pts with NDMM had poorer BL features and were less likely to receive SCT and triplet regimens and/or aggressive upfront treatment. Regardless of BMI, diabetic pts had shorter median OS than nondiabetic pts, suggesting that diabetes might be a stronger factor for survival than obesity. These results support a previous analysis of the Connect MM Registry that identified history of diabetes as a predictive prognostic factor for poor OS (Br J Haematol. 2019;187:602). Limitations of this analysis include limited detail on the care/management of diabetes and steroid use/dosage (which can be challenging for glycemic control). These findings highlight the need to provide better supportive care for diabetes management in MM pts to improve survival. Disclosures La: Celgene BMS: Consultancy. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Ailawadhi:Amgen: Research Funding; Celgene: Honoraria; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Gasparetto:Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria. Hardin:Celgene Pharmaceutical Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Lee:Sanofi: Consultancy; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding. Narang:Maryland Oncology Hematology: Current Employment; Beigene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; J&J: Consultancy, Honoraria. Omel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rifkin:McKesson: Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other: Stock ownership; Takeda, Amgen, Celgene, BMS, Mylan, Coherus BioSciences, Fresenius: Consultancy; AbbVie: Other: Investigator in AbbVie sponsored clinical trials; Takeda, Amgen, BMS (Celgene): Membership on an entity's Board of Directors or advisory committees. Terebelo:Newland Medical Associates: Current Employment; BMS: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene Inc.: Membership on an entity's Board of Directors or advisory committees; Connect Multiple Myeloma Registry: Membership on an entity's Board of Directors or advisory committees. Dhalla:BMS: Current Employment, Current equity holder in publicly-traded company. Liu:TechData Inc: Consultancy. Yang:BMS: Current Employment, Current equity holder in publicly-traded company. Joshi:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Eisai Inc.: Ended employment in the past 24 months. Abonour:Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding.

Study Design: Retrospective cohort study. Objective: Studies investigating the impact of interbody subsidence in ACDF suggest a correlation between subsidence and worse radiographic and patient-reported outcomes. The purpose of this study was to assess whether allograft subsidence assessed on CT is associated with worse cervical alignment. Methods: We performed a retrospective review of a prospective cohort of patients undergoing 1 to 3 level ACDF. Cervical alignment was assessed on standing radiographs performed preoperatively, less than 2 months postoperatively, and greater than 6 months postoperatively. Allograft subsidence was assessed on CT scan performed at least 6 months postoperatively. Patients with at least 1 level demonstrating greater than 4mm of cage subsidence were classified as severe subsidence. Student’s t-test was used to compare all means between groups. Results: We identified 66 patients for inclusion, including 56 patients with non-severe subsidence and 10 patients with severe subsidence. For the entire cohort, there was a significant increase in C2-7 Lordosis (p = 0.005) and Segmental Lordosis (p < 0.00 001) from preoperative to early postoperative. On comparison of severely and non-severely subsided levels, severely subsided levels demonstrated a significantly greater loss of segmental lordosis from early to mid-term follow-up than non-severely subsided levels (-4.89 versus -2.59 degrees, p < 0.0001), manifesting as a significantly lower segmental lordosis at >6 months postoperative (0.54 versus 3.82 degrees, p < 0.00 001). There were no significant differences in global cervical alignment parameters between patients with severe and non-severe subsidence. Conclusions: Severe subsidence is associated with a significant increase in loss of segmental lordosis, but has minimal effect on global cervical alignment parameters.

Germ line mutations in H3F3A and H3F3B cause a previously unidentified neurodevelopmental syndrome.

AbstractIntroductionThe proximal humerus is a common location for primary and non‐primary tumors. Reconstruction of the proximal humerus is commonly performed with an endoprosthesis with low rates of structural failure. The incidence and risk factors for stress shielding are under reported.MethodsThirty‐nine (19 male, 20 female) patients underwent resection of the proximal humerus and reconstruction with a cemented modular endoprosthesis between 2000 and 2018. The mean resection length was 12 ± 4 cm and was most commonly performed for metastatic disease (n = 26, 67%).ResultsStress shielding was observed in 9 (23%) patients at a mean of 29 (6–132) months postoperatively. Patients with stress shielding were noted to have shorter intramedullary stem length (87 vs. 107 mm, p < .001), longer extramedullary implant length (16 vs. 14 cm, p = .01) and a higher extramedullary implant to stem length ratio (2.1 vs. 1.1, p < .001). The incidence of stress shielding was higher (p = .003) in patients reconstructed with 75 mm stem (n = 6, 67%) lengths.ConclusionStress shielding of the humerus was associated with the use of shorter stems and long extramedullary implants. The long‐term ramifications of stress shielding on implant stability, complications at the time of revision surgery, and overall patient outcomes remain unknown.