Oncologic outcomes following transanal total mesorectal excision: the United States experience.

AIM: The benefits and short-term outcomes of transanal total mesorectal excision (taTME) for rectal cancer have been demonstrated previously, but questions remain regarding the oncologic outcomes following this challenging procedure. The purpose of this study was to analyze the oncologic outcomes following taTME at high-volume centers in the USA. METHODS: This was a multicenter, retrospective observational study of 8 tertiary care centers. All consecutive taTME cases for primary rectal cancer performed between 2011 and 2020 were included. Clinical, histopathologic, and oncologic data were analyzed. Primary endpoints were rate of local recurrence, distal recurrence, 3-year disease recurrence, and 3-year overall survival. Secondary endpoints included perioperative complications and TME specimen quality. RESULTS: A total of 391 patients were included in the study. The median age was 57 years (IQR: 49, 66), 68% of patients were male, and the median BMI was 27.4 (IQR: 24.1, 31.0). TME specimen was complete or near complete in 94.5% of cases and the rates of positive circumferential radial margin and distal resection margin were 2.0% and 0.3%, respectively. Median follow-up time was 30.7 months as calculated using reverse-KM estimator (CI 28.1-33.8) and there were 9 cases (2.5%) of local recurrence not accounting for competing risk. The 3-year estimated rate of disease recurrence was 19% (CI 15-25%) and the 3-year estimated overall survival was 90% (CI 87-94%). CONCLUSION: This large multicenter study confirms the oncologic safety and perioperative benefits of taTME for rectal cancer when performed by experienced surgeons at experienced referral centers.

Discordance in Total Mesorectal Excision Specimen Grading in a Prospective Phase 2 Multicenter Rectal Cancer Trial: Are We Overestimating the Quality of Our Resections?

OBJECTIVES: To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase 2 trial of transanal TME. BACKGROUND: Grading of TME specimens is based on the macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described. METHODS: A phase 2 prospective transanal TME trial was conducted from 2017 to 2022 across 11 North American centers with TME quality as the primary study endpoint. QC measures included (1) training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance before trial reporting. Cohen Kappa statistic was used to assess agreement in grading. RESULTS: Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ = 0.35; 95% CI: 0.10-0.61; P < 0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases, respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre versus postreconciliation rates of complete or NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC-NC; N = 1) or major downgrade (NC/C-IC, N = 4) in 5 cases overall (5%). CONCLUSIONS: A 14% rate of major discordance was observed in TME grading between the site and central reviewers. The resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through a central review of TME photographs and reconciliation of major discordances is strongly recommended.

Trial designs and endpoints for immune therapies in multiple myeloma.

Immune therapies, including CAR-T cells, bispecific antibodies, and antibody-drug conjugates, are revolutionizing the treatment of multiple myeloma. In this review, we discuss clinical trial design considerations relevant to immune therapies. We first examine issues pertinent to specific populations, including elderly, patients with renal impairment, high-risk/extramedullary disease, and prior immune therapies. We then highlight trial designs to optimize the selection of dose and schedule, explore rational combination therapies based on preclinical data, and evaluate the nuances of commonly used endpoints. By exploiting their pharmacokinetic/pharmacodynamic profiles and utilizing novel translational insights, we can optimize the use of immune therapies in multiple myeloma.

A Prospective, Dual-Center Trial of Circumferential Radiofrequency Ablation of Anal High-Grade Squamous Intraepithelial Lesions Demonstrate Improved Long-term Efficacy Over Historical Controls of Targeted Ablation.

BACKGROUND: Targeted ablation of anal canal high-grade dysplasia results in high recurrence over time. Circumferential radiofrequency ablation might decrease recurrence. OBJECTIVE: This study aimed to determine the safety and efficacy of circumferential radiofrequency ablation for anal high-grade dysplasia. DESIGN: This was a dual-center, prospective trial of circumferential radiofrequency ablation with a 1-year follow-up with longer follow-up data abstracted from medical records of study patients returning after trial for surveillance. Ten participants from the identically conducted pilot circumferential radiofrequency ablation trial were included to improve sample size for longer-term analysis. SETTINGS: This study included 3 surgeons at 2 sites. PATIENTS: The study included 51 patients undergoing circumferential radiofrequency ablation for anal canal high-grade dysplasia. INTERVENTION: Circumferential radiofrequency ablation of anal canal high-grade dysplasia and targeted radiofrequency ablation of recurrence. MAIN OUTCOME MEASURES: The primary outcome measures were circumferential radiofrequency ablation efficacy and associated morbidity. RESULTS: Fifty-one participants underwent circumferential radiofrequency ablation but 48 participants returned for 1 or more postprocedure high-resolution anoscopy and were evaluable. The mean age of participants was 43 years, most were male (94%), 33% were living with HIV, and 58% had 3 or more high-grade dysplasias treated. Sixty percent had no recurrence, whereas 19% had 1 recurrence, 15% had 2 recurrences, and 6% had 3 recurrences. Most recurrences (66%) developed within the first 6 months. Kaplan-Meier probability of recurrence combining both series was 19% at 3 months, 30% at 6 months, and approximately 40% after 6 months out to 30 months. Most common morbidities were pain (85.4%) lasting for a median of 21 (range, 4-91) days and bleeding (91%) lasting for a median of 21 (range, 5-87) days. Of those with pain and bleeding, 65% and 85%, respectively, described it as mild. No patients developed fistulas, stricture, or incontinence. No serious adverse events related to circumferential radiofrequency ablation occurred. Having a previous recurrence was the only significant predictor of a subsequent recurrence (HR, 28.53) for recurrence at 9 months or before. LIMITATIONS: Enrollment ended prematurely, 10 participants from the pilot study were combined to increase the sample size, and longer-term follow-up was collected retrospectively were the limitations of this study. CONCLUSIONS: Circumferential radiofrequency ablation has improved efficacy over targeted ablation but with increased pain and bleeding. See Video Abstract at http://links.lww.com/DCR/B973 . ESTUDIO PROSPECTIVO BICNTRICO SOBRE LA ABLACIN POR RADIOFRECUENCIA CIRCUNFERENCIAL DE LESIONES ANALES INTRAEPITELIALES ESCAMOSAS DE ALTO GRADO DEMOSTRANDO MAYOR EFICACIA A LARGO PLAZO CON RELACIN A CONTROLES HISTRICOS DE ABLACIN DIRIGIDA: ANTECEDENTES:La ablación dirigida de la displasia de alto grado en el canal anal proporciona como resultados una alta recidiva a largo plazo. La ablación por radiofrecuencia circunferencial podría disminuir la reincidencia.OBJETIVO:Determinar la seguridad y eficacia de la ablación por radiofrecuencia circunferencial para la displasia anal de alto grado.DISEÑO:Estudio prospectivo bicéntrico de ablación por radiofrecuencia circunferencial con un seguimiento de 1 año, en base al monitoreo prolongado de datos, obtenidos de los registros medicos, de todos los pacientes incluidos en el estudio y que fueron controlados clinicamente. Diez participantes del estudio piloto de ablación por radiofrecuencia circunferencial realizada de manera idéntica, se combinaron para mejorar el análisis del tamaño de la muestra a largo plazo.PACIENTES:Se incluyeron 51 pacientes sometidos a la ablación por radiofrecuencia circunferencial de una lesion displásica de alto grado en el canal anal.AJUSTES:Tres cirujanos en 2 centros.INTERVENCIÓN:Ablación por radiofrecuencia circunferencial de la displasia de alto grado en el canal anal y ablación por radiofrecuencia dirigida de la recidiva.PRINCIPALES MEDIDAS DE RESULTADOS:Las medidas primarias fueron la eficacia de la ablación por radiofrecuencia circunferencial y la morbilidad asociada.RESULTADOS:Cincuenta y un participantes se sometieron a la ablación por radiofrecuencia circunferencial, de los cuales, 48 regresaron para ser evaluados con ≥1 anuscopias de alta resolución, después del procedimiento. La edad media de los participantes fue de 43 años, en su mayoría hombres (94%), el 33% eran portadores de VIH y el 58% tenía ≥3 lesiones displásicas de alto grado tratadas. El sesenta por ciento no tuvo recidiva, mientras que el 19%, 15% y 6% tuvieron 1, 2 o 3 recidivas. La mayoría de las recaídas (66%) se desarrollaron dentro de los primeros 6 meses. La probabilidad de recurrencia de Kaplan-Meier combinando ambas series fue del 19 % a los 3 meses, del 30 % a los 6 meses y aproximadamente del 40 % entre los 6 y 30 meses. Los indicadores de morbilidad más frecuentes fueron, el dolor (85,4%) con una mediana de duración de 21 días (rango, 4-91) y sangrado (91%) con una mediana de duración de 21días (rango, 5-87). Aquellos pacientes con dolor (65%) y sangrado (85%) respectivamente, los describieron como leves. Ningún paciente desarrolló fístula, estenosis o incontinencia. No se produjeron eventos adversos graves relacionados con la ablación por radiofrecuencia circunferencial. Tener una recurrencia previa fue el único factor predictivo importante de una recidiva ulterior (RH 28,53) en casos de recaída a los 9 meses o antes.LIMITACIONES:Como el registro finalizó prematuramente, se agregaron 10 participantes del estudio piloto para aumentar el tamaño de la muestra. El seguimiento a largo plazo fué recopilado retrospectivamente.CONCLUSIONES:La ablación por radiofrecuencia circunferencial ha mejorado la eficacia sobre la ablación dirigida pero con dolor y sangrado mas importantes. Consulte Video Resumen en http://links.lww.com/DCR/B973 . ( Traducción-Dr. Xavier Delgadillo ).

Neuroticism is associated with increase in depression symptoms over time in older adults with type 2 diabetes.

OBJECTIVES: The likelihood of depression symptoms in those with type 2 diabetes (T2D) is high. Psychological risk factors enhancing comorbidity of depression symptoms in T2D are yet to be determined. The present study examines the cross-sectional and longitudinal relationship between personality traits and distinct depression dimensions in older adults with T2D. METHODS: Participants were older adults (age ≥65yeas) with T2D from the Israel Diabetes and Cognitive Decline (IDCD) study (N = 356), with complete data on depression [Geriatric Depression Scale (GDS) - 15 item version] and its dimensions- namely, dysphoric mood, apathy, hopelessness, memory complains and anxiety, and on personality [Big Five Inventory (BFI)]. Logistic and mixed linear regression models examined cross-sectional and longitudinal associations while adjusting for socio-demographics, cognition, cardiovascular and diabetes-related factors. RESULTS: Cross-sectionally, high neuroticism was associated with high scores in total GDS and in all depression-dimensions, except memory complaints. Higher extroversion was associated with lower total GDS and with lower scores on all depression dimensions, except anxiety. High levels of neuroticism were associated with increase in total number of depression symptoms over time. CONCLUSIONS: In older adults with T2D, neuroticism and extroversion are associated with most depression dimensions suggesting that these traits relate to a global depression symptomatology rather than to any specific dimension or phenomenology. High neuroticism was associated with increase in depression symptoms over time, highlighting its role in the development of depression symptoms in older adults with T2D.

Multicenter phase II trial of transanal total mesorectal excision for rectal cancer: preliminary results.

BACKGROUND: Transanal TME (taTME) combines abdominal and transanal dissection to facilitate sphincter preservation in patients with low rectal tumors. Few phase II/III trials report long-term oncologic and functional results. We report early results from a North American prospective multicenter phase II trial of taTME (NCT03144765). METHODS: 100 patients with stage I-III rectal adenocarcinoma located ≤ 10 cm from the anal verge (AV) were enrolled across 11 centers. Primary and secondary endpoints were TME quality, pathologic outcomes, 30-day and 90-day outcomes, and stoma closure rate. Univariable regression analysis was performed to assess risk factors for incomplete TME and anastomotic complications. RESULTS: Between September 2017 and April 2022, 70 males and 30 females with median age of 58 (IQR 49-62) years and BMI 27.8 (IQR 23.9-31.8) kg/m2 underwent 2-team taTME for tumors located a median 5.8 (IQR 4.5-7.0) cm from the AV. Neoadjuvant radiotherapy was completed in 69%. Intersphincteric resection was performed in 36% and all patients were diverted. Intraoperative complications occurred in 8% including 3 organ injuries, 2 abdominal and 1 transanal conversion. The 30-day and 90-day morbidity rates were 49% (Clavien-Dindo (CD) ≥ 3 in 28.6%) and 56% (CD ≥ 3 in 30.4% including 1 mortality), respectively. Anastomotic complications were reported in 18% including 10% diagnosed within 30 days. Higher anastomotic risk was noted among males (p = 0.05). At a median follow-up of 5 (IQR 3.1-7.4) months, 98% of stomas were closed. TME grade was complete or near complete in 90%, with positive margins in 2 cases (3%). Risk factors for incomplete TME were ASA ≥ 3 (p = 0.01), increased time between NRT and surgery (p = 0.03), and higher operative blood loss (p = 0.003). CONCLUSION: When performed at expert centers, 2-team taTME in patients with low rectal tumors is safe with low conversion rates and high stoma closure rate. Mid-term results will further evaluate oncologic and functional outcomes.

Correlation of the Ki67 Working Group prognostic risk categories with the Oncotype DX Recurrence Score in early breast cancer.

BACKGROUND: The relationship between Ki67 assessed by immunohistochemistry (IHC) and the Oncotype DX Recurrence Score (RS) is unclear. The objective of this study was to determine the correlation between the 21-gene RS and IHC-measured Ki67 with the prognostic classification groups recommended by the International Ki67 Working Group (IKWG). METHODS: The authors performed a retrospective chart review of women who had hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative early breast cancer with zero to three positive lymph nodes and both Ki67 and the 21-gene RS performed at their institution from 2013 to 2021. Patients were categorized into low (≤5%), intermediate (6%-29%), and high Ki67 groups (≥30%) according to IKWG recommendations. Overall agreement and risk-stratified agreement between Ki67 and RS were assessed with the proportion of agreement and the κ statistic. RESULTS: The study included 525 patients with HR-positive breast cancer. Among the 49% of patients with intermediate Ki67 values of 6%-29%, the distribution of low (0-10), intermediate (11-25), and high RS (26-100) was 19%, 66%, and 15%, respectively. There was slight agreement (κ = 0.01-0.20) between Ki67 and RS (κ = 0.027) in the overall population, although this was not significant (p = .1985). There was fair agreement (κ = 0.21-0.40) between high Ki67 and RS values (κ = 0.280; p < .0001). A higher progesterone receptor percentage was associated with lower RS values (p > .0001) but not lower Ki67 values. A positive nodal status and a larger tumor size were associated with higher Ki67 values (p = .0059 and p < .0001) but not with RS. CONCLUSIONS: In this group of patients selected to have a 21-gene RS, there was no significant correlation between Ki67 and RS in the overall population, and there was fair agreement between high Ki67 and high RS values. LAY SUMMARY: In patients with early-stage, hormone receptor-positive breast cancer, decisions on adjuvant chemotherapy are based on certain biological features of the cancer and genomic assays such as the Oncotype DX Recurrence Score (RS). The goal of this study was to determine the correlation between Ki67, a marker of proliferation, and the Oncotype DX RS, a 21-gene assay demonstrated to be predictive of an adjuvant chemotherapy benefit in patients with early-stage breast cancer. In 525 patients, the authors did not find a significant correlation between Ki67 and RS.

Racial Disparities in Time to Treatment Persist in the Setting of a Comprehensive Breast Center.

BACKGROUND: Racial disparities in breast cancer care have been linked to treatment delays. We explored whether receiving care at a comprehensive breast center could mitigate disparities in time to treatment. METHODS: Retrospective chart review identified breast cancer patients who underwent surgery from 2012 to 2018 at a comprehensive breast center. Time-to-treatment intervals were compared among self-identified racial and ethnic groups by negative binomial regression models. RESULTS: Overall, 2094 women met the inclusion criteria: 1242 (59%) White, 262 (13%) Black, 302 (14%) Hispanic, 105 (5%) Asian, and 183 (9%) other race or ethnicity. Black and Hispanic patients more often had Medicaid insurance, higher American Society of Anesthesiologists (ASA) scores, advanced-stage breast cancer, mastectomy, and additional imaging after breast center presentation (p < 0.05). After controlling for other variables, racial or ethnic minority groups had consistently longer intervals to treatment, with Black women experiencing the greatest disparity (incidence rate ratio 1.42). Time from initial comprehensive breast center visit to treatment was also significantly shorter in White patients versus non-White patients (p < 0.0001). Black race, Medicaid insurance/being uninsured, older age, earlier stage, higher ASA score, undergoing mastectomy, having reconstruction, and requiring additional pretreatment work-up were associated with a longer time from initial visit at the comprehensive breast center to treatment on multivariable analysis (p < 0.05). CONCLUSION: Racial or ethnic minority groups have significant delays in treatment even when receiving care at a comprehensive breast center. Influential factors include insurance delays and necessity of additional pretreatment work-up. Specific policies are needed to address system barriers in treatment access.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

BACKGROUND: Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data. Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. PATIENTS AND METHODS: From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set. A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors. Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. RESULTS: Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery. When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. CONCLUSION: Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Impact of Screening Mammography on Treatment in Young Women Diagnosed with Breast Cancer.

BACKGROUND: There is little data exploring the impact of screening mammography on subsequent treatment in the 40-49-year age group with breast cancer. We sought to assess the association between frequency of mammography in young women and extent of surgery and chemotherapy required. METHODS: An IRB-approved retrospective review was performed of patients diagnosed with breast cancer between ages 40 and 49 years from 1 January 2010 to 19 November 2018 within a single health system. Patients were grouped based on last screening 1-24 months prior to diagnosis (1-24 group), > 25 months prior to diagnosis (> 25 group), never screened, and > 25+ never screened (combination group). Multivariate logistic regression models were used to assess for associations between screening intervals and tumor and nodal stage, chemotherapy use, and extent of surgery. RESULTS: Of 869 patients included for analysis, 20% were never screened, 60% screened 1-24 months, and 19% screened > 25 months prior to diagnosis. Compared with the 1-24 months group, the never-screened group, > 25 months group, and combined group were more likely to receive chemotherapy. The never-screened and combined groups were more likely to undergo mastectomy and/or axillary lymph node dissection. Of patients undergoing upfront surgery, the > 25 months and combined groups were more likely to receive adjuvant chemotherapy, while the never-screened and combined groups were more likely to have nodal disease. CONCLUSION: Our findings support the initiation of screening mammography at age 40 years to reduce the risk of aggressive treatments for newly diagnosed breast cancers in this group.

Persistent leukocytosis in polycythemia vera is associated with disease evolution but not thrombosis.

There are unresolved questions regarding the association between persistent leukocytosis and risk of thrombosis and disease evolution in polycythemia vera (PV), as much of the published literature on the topic does not appropriately use repeated-measures data or time-dependent modeling to answer these questions. To address this knowledge gap, we analyzed a retrospective database of 520 PV patients seen at 10 academic institutions across the United States. Taking hematologic laboratory data at ∼3-month intervals (or as available) for all patients for duration of follow-up, we used group-based trajectory modeling to identify latent clusters of patients who follow distinct trajectories with regard to their leukocyte, hematocrit, and platelet counts over time. We then tested the association between trajectory membership and hazard of 2 major outcomes: thrombosis and disease evolution to myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia. Controlling for relevant covariates, we found that persistently elevated leukocyte trajectories were not associated with the hazard of a thrombotic event (P = .4163), but were significantly associated with increased hazard of disease evolution in an ascending stepwise manner (overall P = .0002). In addition, we found that neither hematocrit nor platelet count was significantly associated with the hazard of thrombosis or disease evolution.

Robot-assisted vs ultrasonography-guided transversus abdominis plane (TAP) block vs local anaesthesia in urology: results of the UROTAP randomized trial.

OBJECTIVES: To prospectively analyse robotically administered transperitoneal transversus abdominis plane (robot-assisted transversus abdominis plane [RTAP]) compared with both ultrasonography-guided transversus abdominis plane (UTAP) and local anaesthesia (LA) with regard to pain control and narcotic use in patients undergoing robot-assisted prostatectomy (RARP) or robot-assisted partial nephrectomy (RAPN). SUBJECTS/PATIENTS AND METHODS: Patients undergoing RARP or RAPN were randomized in a single-blind 2:2:1 fashion to RTAP:UTAP:LA, with the study powered to evaluate superiority of UTAP to LA and non-inferiority of RTAP to UTAP. We compared time to deliver the block, operating room time, postoperative pain scores using the visual analogue scale, and intra-operative and postoperative analgesia consumption. RESULTS: A total of 143 patients were randomized and received treatment. There was no significant difference in patient baseline characteristics. UTAP did not demonstrate superiority to LA in terms of pain control. RTAP and LA were faster to administer than UTAP (time to perform block 2.5 vs 2.5 vs 6.25 min; P < 0.001). There was no difference in postoperative narcotic, acetaminophen, ketorolac or ondansetron requirements among the three groups (P > 0.05). The study was terminated early due to the unexpected efficacy of LA. CONCLUSION: This study showed that UTAP and RTAP do not provide superior pain control to LA. The efficiency, effectiveness, and ease of administration of LA make it an excellent option for first-line therapy for postoperative analgesia.

Neoadjuvant therapy for gastrointestinal stromal tumors: A propensity score-weighted analysis.

Retrospective and single-arm prospective studies have reported clinical benefit with neoadjuvant imatinib for GISTs. In the absence of randomized Phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival compared to upfront resection (UR) remains unknown. We identified N = 16 308 patients within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting adjusted for covariable imbalance among treatment groups. We estimated the effect of NAT on overall survival with a weighted time-dependent Cox proportional hazards model, and on 90-day postoperative mortality and R0 resection with weighted logistic regressions. Eight hundred sixty-five (5.3%) patients received NAT compared to 15 443 (94.7%) who underwent UR. Median NAT duration was 6.3 months. 53.7% of NAT patients were male vs 48.6% of UR patients, 67.3% vs 65.1% had primary gastric GIST and 72.8% vs 49.7% were at high risk. NAT patients had larger tumors and higher mitotic index. >3 months of NAT was associated with a significant survival benefit (weighted HR 0.85 [0.80-0.91]). 90-day postoperative mortality rate was 4/865 (0.5%) among NAT patients vs 346/15443 (2.2%). NAT was associated with lower odds of 90-day postoperative mortality. R0 resection rate was not significantly different between groups. In conclusion, despite higher risk features among NAT patients, this analysis suggests that NAT for localized GIST is associated with a modest survival benefit and lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection.

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB).

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2 + breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2 + BC, where information from surgical pathology could impact adjuvant treatment decisions. Utilizing the NCDB, we evaluated the trend of NAC use compared to upfront surgery in patients with small HER2 + BC. METHODS: We identified NCDB female patients diagnosed with T1 N0 HER2 + BC from 2010 through 2015. Prevalence ratios (PR) using multivariable robust Poisson regression models were calculated to measure the association between baseline characteristics and the receipt of NAC. Analysis of trends over time was denoted by annual percent change (APC) of NAC versus surgery upfront. RESULTS: Of the 14,949 that received chemotherapy and anti-HER2 therapy during the study period, overall 1281 (8.6%) received NAC and 13,668 (91.4%) received adjuvant treatment. Patients receiving NAC increased annually from 4.2% in 2010 to 17.3% in 2015, with the most rapid increase occurring between years 2013 (8.5%) and 2014 (14.2%). The greatest increase was seen in patients with cT1c tumors with an APC of 37.8% over the study period (95% CI 29.0, 47.3%, p < 0.01), although a significant trend was likewise seen in patients with cT1a (APC = 26.1%,95% CI 1.59, 56.6%), and cT1b (APC = 27.4%, 95% CI 18.0, 37.7%) tumors. Predictors of neoadjuvant therapy receipt were age younger than 50 (PR = 1.69, 95% CI 1.52, 1.89), Mountain/Pacific area (PR = 1.24, 95% CI 1.05, 1.46), and estrogen receptor negativity (ER- PR + : PR = 2.01, 95% CI 1.51, 2.68; ER- PR- : PR = 1.49, 95% CI 1.32, 1.69). CONCLUSIONS: Neoadjuvant therapy for T1 N0 HER2 + BC increased over the study period and was mostly due increased use in clinical T1c tumors. This may be consistent with secular change in Pertuzumab treatment following FDA approval in 2013.

Prognostic Factors and Survival Outcomes among Patients with Breast Cancer and Brain Metastases at Diagnosis: A National Cancer Database Analysis.

INTRODUCTION: The aim of this study was to assess for clinicopathologic and socioeconomic features that predict improved survival for patients with advanced breast cancer with synchronous brain metastases at diagnosis. METHODS: We utilized the National Cancer Database (NCDB) to identify all patients with brain metastases present at diagnosis, with adequate information on receptor status (ER, PR, Her2), clinical T stage of cT1-4, clinical M1, with 3,943 patients available for analysis. The association between brain metastases patterns and patient/disease variables was examined by robust Poisson regression model. Cox proportional hazards model was used to quantify the associations between overall survival (OS) and these variables. RESULTS: In univariable analysis, OS was significantly associated with the number of sites of metastases (p < 0.0001). Patients with 2 or more additional extracranial sites of metastases had significantly worse OS (median 8.8 months, 95% confidence interval [CI] 7.8, 9.9) than patients with brain metastases only (median OS 10.6 months, 95% CI 9.4, 12.9) or brain metastases plus one other extracranial site of metastases (median OS 13.1 months, 95% CI 11.8, 14.4). Risk factors which predicted poor prognosis included triple-negative disease, high comorbidity score, poorly differentiated tumors, invasive lobular histology, multi-organ involvement of metastases, and government or lack of insurance. Factors which improve survival include younger age and Hispanic race. DISCUSSION/CONCLUSION: Using a large NCDB, we identified various factors associated with prognosis for patients with brain metastases at the time of breast cancer diagnosis. Insurance status and related socioeconomic challenges provide potential areas for improvement in care for these patients. This information may help stratify patients into prognostic categories at the time of diagnosis to improve treatment plans.

Secondary Invasive Breast Events among Patients with Hormone-Positive Breast Cancer and High-Risk Oncotype DX Recurrence Scores 26-30 and ≥31.

BACKGROUND: The Oncotype DX Recurrence Score (ODx RS) is the most widely adopted genomic assay used to guide treatment for patients with early-stage, hormone-positive (HR+) breast cancer (BC), with higher scores predicting greater risk of recurrence and benefit from chemotherapy. Patients with ODx RS >25 typically recieve adjuvant chemotherapy; however, data regarding efficacy of chemotherapy for reducing recurrence in this population have been mixed. OBJECTIVES: This study aimed to evaluate outcomes of patients with early-stage HR+ BC with high-risk ODx RS (26-30 and ≥31) in order to assess treatment patterns and outcomes. We hypothesized that the benefit of chemotherapy in these groups may be minimal and that select patients may forgo chemotherapy in favor of more aggressive endocrine therapy and ovarian suppression. METHODS: We performed a retrospective analysis of 515 patients with early-stage, HR+ BC with high-risk ODx RS 26-30 and ≥31 treated between 2006 and 2018. Patients were stratified by RS: low-risk (≤10), intermediate-risk (11-25), and high-risk (≥26). The Kaplan-Meier method was used to estimate the time to secondary invasive breast events (SIBE) or distributions overall and among different RS groups with the log rank test used to compare distributions between groups. RESULTS: Rates of chemotherapy administration were 7% among the low-risk group, 18% among the intermediate-risk group, and 83% among high-risk patients with 41 SIBE (8%) reported. When stratified by ODx RS, 5-year rates of SIBE were 4%, 6%, and 16% for low-risk, intermediate-risk, and high-risk RS, respectively. Among the 27 lymph node (LN)-negative patients with ODx RS 26-30, 74% received chemotherapy. The 5-year rate of SIBE was 25% among patients who received chemotherapy and 33% among those who did not (p = 0.5489). Among the 23 LN-negative patients with ODx RS ≥31, 91% of patients received chemotherapy. The 5-year rate of SIBE was 0% both with and without chemotherapy. CONCLUSIONS: There was no statistically significant difference in SIBE for patients with high-risk ODx RS based on chemotherapy treatment. More aggressive endocrine therapy with ovarian suppression has become an alternative to chemotherapy among patients with intermediate-risk ODx RS (16-25). This approach may be useful among patients with high-risk ODx RS, with additional studies needed in this patient population.

Clinical Benefit Derived from Decitabine Therapy for Advanced Phases of Myeloproliferative Neoplasms.

Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8-29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP.

Safety, Efficacy, and Long-Term Outcomes of Anticoagulation in Cirrhotic Portal Vein Thrombosis.

BACKGROUND: The role of anticoagulation (AC) in the management of cirrhotic patients with portal vein thrombosis (PVT) remains unclear. AIMS: We conducted a retrospective study of cirrhotic patients diagnosed with PVT from 1/1/2000 through 2/1/2019, comparing those who received AC to those who did not. METHODS: Outcomes included rate of complete radiographic resolution (CRR) of PVT, recanalization of occlusive PVT (RCO), PVT extension, major bleeding, and overall survival (OS). The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox-proportional-hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: A total of 214 patients were followed for a median 27 months (IQR 12-48). Eighty-six patients (39%) received AC. AC was associated with significantly greater CRR (48% vs. 27%, p = 0.0007), (multivariable HR for CRR with AC; 2.49 (1.54-4.04, p = 0.0002)). AC was also associated with significantly greater RCO (69% vs. 28%, p = 0.0013), (multivariable HR for RCO with AC; 4.86 (1.91-12.37, p = 0.0009)). Rates of major bleeding were similar with and without AC (20% vs. 17%, p = 0.5207), multivariable HR for major bleeding with AC; 1.29 (0.68-2.46, p = 0.4423)). OS rates in the AC and no-AC groups were 83% and 70%, respectively (p = 0.1362), (HR for death with AC; 0.69 (0.38-1.28, p = 0.2441)). Among 75 patients who had CRR, 10 (13%) experienced recurrent PVT during follow-up (none were receiving AC at the time of recurrence). CONCLUSIONS: AC appears safe and effective for the treatment of cirrhotic PVT; however, prospective studies to confirm these findings and evaluate additional outcomes are needed.

Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. METHODS: Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. RESULTS: Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50 years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. CONCLUSIONS: NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.

Portal vein thrombosis patients harboring JAK2V617F have poor long-term outcomes despite anticoagulation.

Non-cirrhotic portal vein thrombosis (ncPVT) most often occurs in the setting of intraabdominal proinflammatory processes. Less often, ncPVT may result from primary hematologic thrombophilia (most commonly JAK2V617F). Although these etiologic categories are pathophysiologically distinct, they are treated similarly using anticoagulation. We conducted a retrospective assessment of outcomes among ncPVT patients harboring JAK2V617F, and compared them to outcomes among patients with other etiologies for ncPVT, to determine whether anticoagulation alone is adequate therapy for JAK2V617F associated PVT. Outcomes were complete radiographic resolution (CRR) of PVT, recanalization (RC) of occlusive PVT, and development of significant portal hypertension (SPH). Three-hundred-thirty ncPVT patients seen between 1/2000 and 1/2019, including 37 harboring JAK2V617F (JAK2), 203 with other evident etiology (OE) for PVT, and 90 with no evident etiology (NE) for PVT followed for a median 29 months (53, 21, and 32 months respectively). Outcomes among the JAK2 cohort were dismal relative to the other groups. CRR rates were 8%, 31%, and 55% for the JAK2, NE, and OE cohorts respectively (multivariable HR JAK2:OE = 0.15 (0.05, 0.49), p = 0.0016). RC rates were 16%, 33%, and 49% for the JAK2, NE, and OE cohorts respectively (multivariable HR for RC JAK2:OE = 0.24 (0.09, 0.63), p = 0.0036). SPH rates were 49%, 32%, and 17% for the JAK2, NE, and OE cohorts respectively (multivariable HR for SPH JAK2:OE = 1.23 (0.62, 2.42), p = 0.5492). Given the strikingly poor outcomes among patients harboring JAK2V617F, anticoagulation alone does not appear to be adequate therapy for this cohort. Further investigation into thrombolysis and/or thrombectomy as an adjunct to anticoagulation is merited in this high-risk group.