The CNS Relapse in T-Cell Lymphoma Index Predicts CNS Relapse in Patients with T- and NK-Cell Lymphomas.

Little is known about risk factors for central nervous system (CNS) relapse in mature T- and NK-cell neoplasms (MTNKN). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKN, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (N=182), of whom 91 had CNS relapse, we applied a LASSO Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (N=566). CNS relapse was most frequently observed in patients with PTCL, NOS (25%). Median time to CNS relapse and median overall survival after CNS relapse was 8.0 months and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (N=158) and high-risk (N=188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (HR 5.24, 95%CI 1.50-18.26, P=0.018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at highest risk of developing CNS relapse.

Autologous hematopoietic cell transplantation consolidation for first response is associated with longer survival among patients with nodal peripheral T-cell lymphoma.

BACKGROUND: Nodal peripheral T-cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-SCT) as a consolidation strategy following initial chemotherapy response remains uncertain. OBJECTIVE: This study aims to evaluate the impact of upfront auto-SCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy. STUDY DESIGN: A retrospective cohort study was conducted at Moffitt Cancer Center, involving 123 patients with nodal PTCL treated between February 2005 and February 2021. Patients were stratified into two groups based on whether they received auto-SCT as part of their initial treatment strategy. Kaplan-Meier method and Cox proportional hazard models were used for statistical analysis to compare OS and EFS between groups. RESULTS: Patients undergoing auto-SCT after first response demonstrated significantly longer median OS (12.3 vs. 4.3 years; P = .035) and EFS (6.2 vs. 2.2 years; P = .003) compared to those who did not. Multivariate analyses indicated that auto-SCT at first response and younger age at diagnosis were favorable prognostic factors. CONCLUSION: The findings suggest that upfront auto-SCT consolidation can significantly improve long-term outcomes in patients with nodal PTCL, supporting the strategy of early auto-SCT consideration and referral following initial chemotherapy response. These results underscore the importance of integrating upfront auto-SCT into the treatment paradigm for nodal PTCL, emphasizing early referral to transplantation services to optimize patient outcomes.

Composite Lymphoma with Follicular Lymphoma Transformation to Clonally Related Epstein-Barr Virus (EBV) Positive Diffuse Large B-Cell Lymphoma and EBV-PositiveClassic Hodgkin Lymphoma.

While the Epstein-Barr virus (EBV) is known to drive de novo lymphomagenesis, it may rarely contribute to transformation of indolent lymphoma as well. Some EBV-related lymphomas represent a diagnostic challenge with important prognostic and therapeutic implications. We describe a case of follicular lymphoma (FL) transformation to both EBV + diffuse large B-cell lymphoma (DLBCL) and EBV + classic Hodgkin lymphoma (cHL), the latter of which was only identified retrospectively after selective outgrowth during DLBCL therapy. Finally, we describe successful salvage therapy with brentuximab vedotin plus nivolumab. This is the first known case of composite lymphoma with FL, EBV + DLBCL, and EBV + cHL within a single lymph node. The disease course highlights the importance of careful morphologic examination and comprehensive immunophenotypic characterization of EBV + lymphomas to ensure proper clinical care and underscores the potential for novel therapies currently under investigation. This trial is registered with NCT01671813.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023.

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Poor Outcome of Adult T-Cell Leukemia/Lymphoma with Current Available Therapy: An Experience of Two Centers.

INTRODUCTION: Adult T-cell leukemia lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. Despite its poor prognosis, there is no standard therapy for ATLL due to its low incidence and the disease affecting only endemic geographical clusters. METHODS: A retrospective evaluation of patients with the diagnosis of ATLL at Moffitt Cancer Center and Memorial Healthcare System was done to identify patients and disease characteristics along with the progression-free survival (PFS) and overall survival (OS) for the different therapies used. RESULTS: The 61 patients analyzed showed a median age of 58 with 82.5% of them being of African American descent. The acute variant contributed to the majority of cases (43.9%), followed by 36.8% presenting as a lymphoma variant. There was no statistical difference in the PFS (6.4 m, 3.1 m, 2.1 m; p = 0.23) or OS (14 m, 8.9 m, 18.5 m; p = 0.14) between cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), intensive chemotherapy regimens, and other modalities, respectively. However, the patients who had complete or partial remission with first-line therapy had better OS (15.9 m vs. 7.2 m; p = 0.004). CONCLUSIONS: The study highlighted the poor outcome of the current regimens and the lack of a unifying protocol for this vicious disease. The acute variants were treated with more intensive regimens, but there was no difference in the OS between the three major options of CHOP, intensified chemotherapy, and others. This underscores the need for more clinical trials to develop better outcomes.

Toxicity of a Modified PEG-Asparaginase-Based SMILE Regimen Is Comparable to L-Asparaginase-Based SMILE in a Non-Asian Population.

INTRODUCTION: L-asparaginase-based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer- (NK-) cell neoplasms. To treat these lymphoma subtypes in Asia, where NK/T-cell lymphomas are more prevalent, the NK-Cell Tumor Study Group developed the SMILE regimen, which includes a steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide. In the US however, the only commercially available form of asparaginase is the pegylated form (PEG-asparaginase) which has been incorporated into a modified SMILE (mSMILE). We sought to study the toxicity associated with replacing L-asparaginase with PEG-asparaginase in mSMILE. PATIENTS AND METHODS: We retrospectively identified all adult patients treated with the mSMILE chemotherapy regimen in our database at Moffitt Cancer Center (MCC) between December 1, 2009, and July 30, 2021. Patients were included if they were treated with mSMILE irrespective of their underlying diagnosis. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The rate of toxicity in our mSMILE treatment group was numerically compared to data published in a metanalysis of the SMILE regimen's toxicity (Pokrovsky et al., 2019). RESULTS: A total of 21 patients were treated with mSMILE at MCC during the 12-year analysis window. Compared to patients receiving the L-asparaginase-based SMILE, patients receiving mSMILE experienced grade 3 or 4 leukopenia less often, with a toxicity rate of 62% (median with SMILE, 85% [95% CI, 74%-95%]); thrombocytopenia, however, was more common, with a toxicity rate of 57% (median with SMILE, 48% [95% CI, 40%-55%]). Other hematological, hepatic and coagulation related toxicities were also reported. CONCLUSION: In a non-Asian population, the mSMILE regimen with PEG-asparaginase is a safe alternative to the L-asparaginase-based SMILE regimen. There is a comparable risk of hematological toxicity, and no treatment-related mortality was seen in our population.

Delineation of clinical course, outcomes, and prognostic factors in patients with T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare, post-thymic T-cell neoplasm with a diverse clinical course. T-PLL is typically associated with a poor prognosis; however, a subset of patients have inactive disease on initial presentation. There is a lack of accurate delineation of the disease based on initial clinical presentation and pathological assessment, hindering clinical decision-making. To characterize and delineate disease subtypes based on initial clinical presentation and pathologic assessment, we retrospectively reviewed 81 patients with T-PLL treated at our institution. We compared patients with T-PLL who initially presented with a relatively indolent or stable disease course to those with an aggressive disease course. Clinicopathologic characteristics, overall survival (OS), and prognostic factors were analyzed. Patients with inactive disease had a significantly longer OS than patients with active disease. At diagnosis, presence of B symptoms, low hemoglobin, low platelet count, lymphocyte doubling time of fewer than 3 months, and abnormal cytogenetics were associated with shorter OS. Cell morphology, immunophenotype, absolute lymphocyte count, lactate dehydrogenase levels, involvement of liver, spleen, skin or central nervous system, presence of TCL1 rearrangement or inv (14)/t(14;14), presence of chromosome 8 abnormalities, and presence of deletion of 11q were not associated with significant OS difference among the patients. Receiving alemtuzumab as first-line treatment and consolidation with allogeneic hematopoietic stem cell transplant were associated with better outcomes. T-PLL inactive and active disease subtypes can exhibit overlapping yet different clinical and pathological features. We describe several prognostic factors at diagnosis that can be used for risk stratification and aid in guiding treatment decisions.

Outcomes of patients with limited-stage plasmablastic lymphoma: A multi-institutional retrospective study.

Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021.

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody-drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1-mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies.

NKTR-255 is an investigational polyethylene glycol-modified recombinant human IL-15 (rhIL-15) receptor agonist, designed to improve the immunotherapeutic and anti-cancer benefit observed with rhIL-15 while circumventing the toxicities associated with this therapy. In preclinical studies, NKTR-255 has demonstrated enhanced proliferation and function of CD8+ T cells and natural killer cells, as well as enhanced anti-tumor activity and survival both as monotherapy and in combination with monoclonal antibodies in multiple cancer models. Here, we describe the rationale and design of the first-in-human Phase I, dose-escalation and dose-expansion study of NKTR-255 alone and in combination with daratumumab or rituximab in adults with relapsed/refractory multiple myeloma or non-Hodgkin's lymphoma that will determine the maximum tolerated dose and recommended Phase II dose for NKTR-255.

Lay abstract Interleukin-15 (IL-15) is a protein that helps the body's natural immune system to defend itself against infections and diseases like cancer. This article discusses a clinical trial in patients with multiple myeloma or non-Hodgkin's lymphoma that evaluates a new investigational medicine, NKTR-255, a polymer-modified form of IL-15 that has been engineered to improve its ability to provide a sustained anti-tumor immune response. The trial will explore different doses of NKTR-255 to determine patient side effects and to find the highest acceptable dose that patients can tolerate. Based on this, a dose will be chosen that offers an optimal balance between having a positive anti-cancer effect and minimizing side effects. This dose will be tested further in patients who have had different treatments in the past. If the side effects are acceptable, this dose will be tested in a new trial in a large number of patients. Clinical Trial Registration: NCT04136756 (ClinicalTrials.gov).

Classical Hodgkin Lymphoma: Clinicopathologic Features, Prognostic Factors, and Outcomes From a 28-Year Single Institutional Experience.

INTRODUCTION: Classical Hodgkin lymphoma (cHL) is a curable malignancy, with a complete remission rate of approximately 90%. However, relapse remains a significant cause of mortality. Prognostic factors are useful in guiding therapy. This is a large, single-institution study defining the clinicopathologic features, prognostic factors, and treatment outcomes of patients with cHL. PATIENTS AND METHODS: We reviewed 727 patients with cHL treated at H. Lee Moffitt Cancer Center and Research Institute from 1990 to 2017. Data on demographics, laboratory studies, and disease statuses were collected from the institutional database and electronic medical records. Statistical analyses, overall survival (OS), progression-free survival (PFS), and multivariate analyses were performed. RESULTS: The median age was 35 years. Fifty-four percent of patients were men; 45.6% had advanced stage disease; 82% were treated with ABVD (doxorubicin hydrochloride [adriamycin], bleomycin sulfate, vincristine, and dacarbazine) as frontline therapy; and 70% achieved complete response. The median PFS after first-line treatment was 16.8 years. The median OS of patients with early stage and advanced stage cHL was 19 and 12.9 years, respectively. Poor prognostic factors for OS included older age, advanced stage disease, presence of B symptoms, and a higher International Prognostic Score. CONCLUSION: Despite high cure rates, cHL accounted for the cause of death in 47% of patients who died during follow-up. Prognostic factors, such as age, stage at diagnosis, International Prognostic Score, and B symptoms, are helpful to guide treatment. Outcomes observed in this study are comparable with those reported in previously published studies.

Extranodal NK/T Cell Lymphoma: Evidence-based Review of Safety and Toxicity of the Available Regimens.

Extranodal natural killer/T cell lymphoma (ENKTL) is a rare type of mature T and NK neoplasm. It is more prevalent in Asia and Latin America where the Epstein-Barr virus is endemic and has been linked to the disease. Most studies have emerged from those 2 regions to evaluate best management options. There are no standards of care in the management owing to the lack of unified approach depending on the treatment region and availability of different therapy options. Several reviews have focused on the outcome of the different chemotherapy combinations. There are no systematic reviews of the toxicity of those regimens despite the fact that many of them incorporate the use of asparaginase and/or radiation in combination with chemotherapy. We have found that although integration of asparaginase and/or radiation have led to improved outcome, it was done at the expense of increased toxicity. The most recent studies are showing promising outcomes while decreasing toxicity.

Ten-year survival outcomes for patients with early stage classical Hodgkin lymphoma: An analysis from Kentucky Cancer Registry.

OBJECTIVE/BACKGROUND: Early stage classical Hodgkin lymphoma (cHL) has an excellent outcome. Recent studies focus on decreasing toxicity related to the addition of radiation along with chemotherapy. Real-life reporting of the addition of radiation to chemotherapy is lacking. This study investigates the outcomes obtained from a statewide cancer registry for early stage cHL patients treated with chemotherapy alone (CT) versus patients treated with the combined modality of chemotherapy and radiation (CMT). METHODS: A retrospective study of cHL patients diagnosed and treated was identified using a statewide cancer registry from 2005 to 2014. Patients with early stage disease (I, II) were then grouped on the basis of the presence of B symptoms into favorable and unfavorable groups. Baseline characteristics (age, gender, extranodal involvement, and histology) as well as overall survival were compared for both groups depending on whether they received CT or CMT as first line therapy for their cHL. RESULTS: A total of 961 patients were identified; of those, 127 were excluded as they received only radiation or another form of treatment. Of the remaining patients, 293 were categorized as early stage favorable cHL (Group 1) and 130 adults were in the unfavorable cHL (Group 2). There were 335 patients with advanced stage cHL (Group 3) and 76 patients in an unknown stage. The 10-year overall survival for Group 1 was 81.3% versus 76.3% for Group 2 and 52.7% for Group 3. For Group 1, 10-year overall survival was 86.7% with CMT versus 75.1% for those receiving CT only (p = .004). For Group 2, there was no difference in 10-year overall survival between the CMT group (80.0%) and CT (72.5%) (p = .73). CONCLUSION: While radiation therapy might increase long-term toxicity in cHL, in our large data cohort, radiotherapy consolidation as part of the initial therapy for early stage disease provides superior survival at 10 years, especially in favorable risk cHL.

Copper deficiency anemia: review article.

Copper is a crucial micronutrient needed by animals and humans for proper organ function and metabolic processes such as hemoglobin synthesis, as a neurotransmitter, for iron oxidation, cellular respiration, and antioxidant defense peptide amidation, and in the formation of pigments and connective tissue. Multiple factors, either hereditary or acquired, contribute to the increase in copper deficiency seen clinically over the past decades. The uptake of dietary copper into intestinal cells is via the Ctr1 transporter, located at the apical membrane aspect of intestinal cells and in most tissues. Copper is excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking the transporter towards the basolateral membrane. Zinc is another important micronutrient in animals and humans. Although zinc absorption may occur by direct interaction with the Ctr1 transporter, its absorption is slightly different. Copper deficiency affects physiologic systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system in general. Detailed pathophysiology and its related diseases are explained in this manuscript. Diagnosis is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper deficiency anemia is treated with oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride. Hematological manifestations are fully reversible with copper supplementation over a 4- to 12-week period. However, neurological manifestations are only partially reversible with copper supplementation.

Age adjusted hematopoietic stem cell transplant comorbidity index predicts survival in a T-cell depleted cohort.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria. METHODS: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was performed. Kaplan-Meier's curve, log-rank tests, Cox model and Pearson correlation was used in the analysis. RESULTS: Of the 114 patients that underwent allogeneic transplant in our institution, 75.4% were ≥40 years old. More than 58% had a DLCO ≤80%. Although scores were positively correlated (correlation coefficient 0.43, p < 0.001), HCT-CI/Age more accurately predicted 2-year overall survival (OS) and non-relapse mortality (NRM) in patients with lower (0-4) and higher (5-7) scores (52% and 36% versus 24% and 76%, p = 0.004, 0.003 respectively). PAM score did not reach statistical significance for difference in OS nor NRM between the low (<24) and high-risk (≥24) groups (p = 0.19 for both). CONCLUSIONS: Despite our small sample population, HCT-CI/Age was more discriminative to identify patients with poor outcome that might benefit from intensified management strategies or other therapeutic approaches rather than allogeneic HCT.

Multimodality therapy improves survival in intramedullary spinal cord metastasis of lung primary.

BACKGROUND: Most metastatic spinal cord lesions are located either in the intradural, extramedullary, or in the epidural compartments. Intramedullary spinal cord metastasis (ISCM) is a rare central nervous system spread of cancer. The aim of this report was to evaluate ISCM in the published literature. METHODS: A literature review of PubMed from 1960 to 2016 was undertaken for the publications having demographic, clinical, histological, and outcome data. RESULTS: A total of 59 relevant papers were identified, showing 128 cases of intramedullary metastasis from lung cancer. The incidence of lung cancer as the primary malignancy with intramedullary metastasis was 56%. The median time from diagnosis of primary to intramedullary metastasis was 6months. Survival improved with multimodality therapy compared to monotherapy (4monthsvs. 6.3months) (hazard ratio=0.501; 95% confidence interval, 0.293-0.857). CONCLUSION: Lung cancer is the predominant cause of intramedullary involvement of the spinal cord. Overall prognosis is poor, although a multimodality approach was associated with improved survival.

Effect of complications on oncologic outcomes after pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND: Although adjuvant therapy (AT) is a necessary component of multimodality therapy for pancreatic ductal adenocarcinoma (PDAC), its application can be hindered by post-pancreaticoduodenectomy (PD) complications. The primary aim of this study was to evaluate the impact of post-PD complications on AT utilization and overall survival (OS). METHODS: Patients undergoing PD without neoadjuvant therapy for stages I-III PDAC at a single institution (2007-2015) were evaluated. Ninety-day postoperative major complications (PMCs) were defined as grade ≥3. Records were linked to the Kentucky Cancer Registry for AT/OS data. Early AT was given <8 wk; late 8-16 wk. Initiation >16 wk was not considered to be AT. Complication effects on AT timing/utilization and OS were evaluated. RESULTS: Of 93 consecutive patients treated with surgery upfront with AT data, 64 (69%) received AT (41 [44%] early; 23 [25%] late). There were 32 patients (34%) with low-grade complications and 24 (26%) with PMC. With PMC, only six of 24 patients (25%) received early AT and 13 of 24 (54%) received any (early/late) AT versus 35 of 69 (51%) early AT and 51 of 69 (74%) any AT without PMC. PMCs were associated with worse median OS (7.1 versus 24.6 mo, without PMC, P < 0.001). Independent predictors of OS included AT (hazard ratio [HR]: 0.48), tumor >2 cm (HR: 3.39), node-positivity (HR: 2.16), and PMC (HR: 3.69, all P < 0.02). CONCLUSIONS: Independent of AT utilization and biologic factors, PMC negatively impacted OS in patients treated with surgery first. These data suggest that strategies to decrease PMC and treatment sequencing alternatives to increase multimodality therapy rates may improve oncologic outcomes for PDAC.