Inferior Overall Survival Research Articles

Risk stratification in the clinical application of minimal residual disease assessment in acute myeloid leukemia.

In acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies. The authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected. In the favorable-risk and intermediate-risk groups, patients who underwent transplantation according to the protocol experienced significant 3-year overall survival (OS) benefits compared with those who did not (favorable-risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20-0.73l p=.004; intermediate-risk group: HR, 0.53; 95% CI, 0.33-0.85; p=.008). In the intermediate-risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p=.009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28-0.79; p=.004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable-risk and intermediate-risk groups, regardless of whether they underwent transplant or not. In the adverse-risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38-0.69; p<.001). Early clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable-risk and intermediate-risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation.

Beta-2-Microglobulin Maintains Overall Survival Prediction in Binet A Stage Chronic Lymphocytic Leukemia Patients with Compromised Kidney Function in Both Treatment Eras of Chemoimmunotherapy and Targeted Agents

Background: Elevated beta-2-microglobulin (B2M) plasma levels commonly imply a higher CLL-IPI risk category for short overall survival (OS), but the risk model was not adjusted for compromised kidney function and not validated in Binet A stage CLL patients. Methods: CLL patients were identified from 2000 to 2022 at Innsbruck University Hospital, Austria. B2M levels, CLL-IPI risk stratification, and kidney function were assessed. Treatment modalities in case of disease progression and OS data during follow-up were evaluated. Results: A total of 259 Binet A stage CLL patients were identified; 16.9% (n = 44/259) presented with concurrent chronic kidney disease (CKD, GFR &lt; 60 mL/min). Median OS was 170 months and was similar in CKD and non-CKD patients (p = 0.25). The CLL-IPI facilitated prognostic segregation in both CKD (p = 0.02) and non-CKD patients (p = 0.008). Although more frequently elevated in CKD patients (44.1% versus 10.6%, p &lt; 0.001), B2M &gt; 3.5 mg/L remained associated with inferior OS in this subgroup (p = 0.03). Contrary to the CLL-IPI, the prognostic value of B2M alone was also maintained in CLL patients diagnosed and potentially treated frontline in the era of targeted agents (2014–2022, p = 0.03). Conclusions: B2M retains its prognostic value for OS in early-stage CLL patients with concurrent CKD and still represents a promising covariate for up-coming prognostic models to identify patients at high risk for inferior OS in the era of targeted agents.

Inferior Overall Survival After Haploidentical Donor Lymphocyte Infusions in Relapsed Myeloid Neoplasms.

Allogeneic hematopoietic stem cell transplantation (HSCT) effectively treats high-risk myeloid neoplasms, but relapses post-HSCT, particularly in acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS), pose significant challenges. Donor lymphocyte infusion (DLI) has been utilized, but its effectiveness, especially in haploidentical settings, remains insufficiently clarified, and graft-versus-host disease (GvHD) poses a substantial risk. In this retrospective cohort study, 57 patients with AML or MDS who received DLI after allogeneic HSCT at our center from 2002 to 2023 were analyzed. Herein, only preemptively or therapeutically applied DLI were included, and endpoints included overall survival (OS), progression-free survival (PFS), and GvHD incidence post-DLI. Median OS after DLI was 517 days, with a 1-year OS of 62.5%. Factors associated with longer OS included patient age, HLA-identical donor, post-HSCT treatment naivety, and preemptive DLI indication. Haploidentical DLI was associated with inferior OS compared to HLA-identical DLI; however, PFS and GvHD incidence post-DLI did not differ significantly. Our study findings indicate that OS rate is inferior in patients with relapsed AML or MDS treated with haploidentical DLI in comparison to those who received HLA-identical DLI. Given the limitations of haploidentical DLI, alternative strategies, such as higher cell doses or combination treatment approaches, warrant further investigation.

Racial and ethnic disparities in outcomes of diffuse large B cell lymphoma in adolescent and young adults: a SEER database analysis.

Data regarding racial disparities in the incidence, treatment, and outcomes of diffuse large B-cell lymphoma (DLBCL) is limited in the adolescent and young adult (AYA) population. We utilized the surveillance, epidemiology, and end-result (SEER) registry research plus database to evaluate racial/ethnic disparities in 8605 AYA patients with DLBCL. Race/ethnicity was categorized into three main subsets: non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and 'other races' that included Hispanics (H), American Indian/Alaskan Native (AI/AN), Asian or Pacific Islander (A/PI). NHB were more likely to present with advanced stage disease (p < 0.001) and B symptoms (p < 0.001) and were less likely to receive chemotherapy(p < 0.001) compared to non-Hispanic white (NHW) patients and other races respectively. NHB patients had inferior 5-year disease specific survival (DSS) (70% vs 85% vs 80%, p < 0.001) and 5-year overall survival (OS) (66% vs 82% vs 77%, p < 0.001) compared to NHW and other races respectively. Black race was independently associated with both inferior DSS (HR 1.55, 95% CI 1.17-2.05, p = 0.002) and OS (HR 1.41, 95% CI 1.10-1.83, p = 0.007) after adjusting for age, gender, stage, presence of B symptoms, receipt of chemotherapy and radiation. NHB-DLBCL patients also had a lower 1-year relative survival rate (RSR) compared to NHW and other races. The low RSR in NHB patients persisted up to 5 years from diagnosis unlike NHW and other races. Our study shows that despite significant therapeutic advances in DLBCL over the last two decades, NHB AYA patients with DLBCL continue to have inferior survival outcomes compared to other ethnic and racial groups with disparities arising as early as the first year of diagnosis.

Lymphopenia Predicts Poor Outcomes in Newly Diagnosed Multiple Myeloma

Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while anti-tumor immune responses are inhibited. Although clinical and genomic markers of high-risk MM have been described, the immune status is just being recognized as a potential mediator of disease behavior. This is even more important with the development of a number of immune-based therapies. Based on these considerations, we evaluated peripheral blood absolute lymphocyte count (ALC) as an easily accessible marker representing immune microenvironment at diagnosis and following treatment of MM. We retrospectively evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at Veteran’s Administration hospitals using ALC obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 ALC categories: severely low, low, and normal (<1, 1-1.5, and >1.5 x 103/mm3, respectively). Lymphopenia (including severely low and low ALC) was present in 53% of patients at MM diagnosis and was associated with inferior overall survival (OS). Median OS of patients with severely low, low, and normal ALC at diagnosis was 2.7, 3.3, and 4.2 years (P < .001), respectively. Moreover, persistent or new development of lymphopenia during treatment and follow-up was also associated with inferior OS. Our findings support the use of ALC as a biomarker for risk stratification in MM.

A Decade of Experience Between Open and Minimally Invasive Hepatectomies for Hepatocellular Carcinoma

Background and Objectives: Hepatic resection offers promising outcomes for patients with hepatocellular carcinoma (HCC) but can be constrained by factors like patient suitability. Continuous advancements in laparoscopic and robotic technologies have made minimally invasive hepatectomies (MIHs) a viable alternative to open hepatectomies with benefits in terms of recovery and complications. Materials and Methods: We completed a retrospective review on 138 HCC patients who underwent OH or MIH between 2010 and 2020 at the Hume-Lee Transplant Center. Univariate and multivariate analyses were completed on demographic, clinical, and tumor-specific data to assess the impact of these variables on overall and disease-free survival at 1, 3, and 5 years. Preoperative metrics like length of hospital stay (LOS) and operation duration were also evaluated. Results: Of the 109 OH and 29 MIH patients, MIH patients demonstrated shorter LOS and operative times. However, overall survival (OS) and disease-free survival (DFS) were similar between groups, with no significant variations in 1-, 3-, and 5-year survival rates. Age &gt; 60 years and a lack of preoperative transcatheter arterial chemoembolization (TACE) were significant predictors of inferior OS and DFS in multivariate analyses. Conclusions: MIH is an efficient substitute for OH with comparable survival, even in older patients. The reduced LOS and operation time enhance its feasibility, and older patients previously denied for curative resection may qualify for MIH. Preoperative TACE also enhances survival outcomes, emphasizing its general role in managing resectable HCCs. Both robotic and laparoscopic hepatectomies offer acceptable short- and long-term clinical outcomes, highlighting MIH as the standard choice for HCC patients.

Long-term follow-up of methotrexate and cytarabine in adult patients with Langerhans cell histiocytosis.

The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m2) was administered by 24 h infusion on day 1 and AraC (0.1 g/m2) by 24 h infusion for 5 days. The primary end-point was event-free survival (EFS). The median patient age was 32 years (range 18-65 years). The overall response rate was 89.5%. Seven patients in this cohort died, and 38 experienced disease reactivation. No degenerative central nervous system diseases were observed. The estimated 6-year overall survival (OS) and EFS rates were 93.2% and 55.2% respectively. Multivariate analysis revealed that risk organ (RO) involvement at baseline (hazard ratio [HR] 6.135 [95% confidence interval (CI) 1.185-32.259]; p = 0.031) and age >40 years at diagnosis (HR 7.299 [95% CI 1.056-21.277]; p = 0.042) were associated with inferior OS. RO (HR 2.604 [95% CI 1.418-4.762]; p = 0.002) and skin (HR 2.232 [95% CI 1.171-4.255]; p = 0.015) involvement at baseline were poor prognostic factors for EFS. Regarding adverse events, four patients developed a second primary malignancy. In conclusion, the MA regimen was a valid and safe therapeutic approach for adult patients newly diagnosed with LCH.

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma.

Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer.

ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer (EC). A de-identified retrospective analysis of 1988 patients with advanced/recurrent EC was performed. In addition, an analysis of a real-world evidence (RWE) cohort was completed (n=1266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA. Among 1988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n=1821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%) and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%) and EGFR (19.3%). From the RWE cohort, those with TP53 mutations had a worse overall survival (OS) vs those without TP53 mutations (p=0.02) and those with TP53 co-mutations had an inferior OS in comparison to TP53-mutated only (p=0.016). Amongst these, patients with a PIK3CA co-mutation (p=0.012) and CCNE1 amplification (p=0.01) had inferior OS compared to those with only TP53 mutations. 57 patients with newly diagnosed EC had at least 2 serial ctDNA samples showing evolution in detected variants compared to baseline samples, with TP53 being the most frequent change. This study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.

Real-world study and prognostic analysis of angioimmunoblastic T-cell lymphoma.

To analyze the clinical prognostic factors and treatments for angioimmunoblastic T-cell lymphoma (AITL) and develop a novel prognostic model specifically for AITL. We retrospectively analyzed 231 patients with AITL from the First Affiliated Hospital of Zhengzhou University. Patients were enrolled between January 2014 and July 2023. The primary end points were overall survival (OS) and progression-free survival (PFS). The patients' median age was 63 years, with 88.3% at an advanced stage (III/IV). The majority of patients (47.6%) received anthracycline-containing regimens, and there was no significant difference in survival compared with those treated with epigenetic-targeting and gemcitabine- containing regimens. The median PFS and OS were 6 and 17 months, respectively. In multivariate analysis, age >60 years, Eastern Cooperative Oncology Group performance status ≥2, elevated LDH, and splenomegaly were associated with inferior OS. Based on these four factors, a novel prognostic model (AITL model) was constructed that stratified patients into low-, intermediate-, and high-risk groups, with 2-year OS estimates of 63.6%, 42.1%, and 18.6%, respectively. Currently, there is no consensus on the optimal initial therapy for AITL, and the efficacy of anthracycline-containing regimens remains suboptimal. The novel model developed herein demonstrates predictive significance for both OS and PFS, and exhibits better stratification and discrimination capabilities.

Population-based long-term prognosis analysis of subcutaneous gastrointestinal stromal tumors.

Subcutaneous gastrointestinal stromal tumors (scGISTs) are extremely rare tumors, and the analysis of their long-term prognosis remains unreported. Therefore, our objective is to analyze the long-term prognosis of patients with scGISTs using the Surveillance, Epidemiology, and End Results database. Patients diagnosed with GISTs between 2000 and 2019 were included in the study. To handle missing data, multiple imputation techniques were employed. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival (OS) and cancer-specific survival (CSS), and subgroup analyses were conducted for various variables. A total of 12,882 patients were enrolled, with 12,636 diagnosed with GISTs and 246 with scGISTs. In comparison to GISTs patients, scGISTs patients exhibited inferior OS [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.45-1.98, P < 0.001] and CSS (HR 2.16, 95% CI 1.78-2.61, P < 0.001). Across various subgroups, including age, sex, surgical intervention, marital status, and chemotherapy, scGISTs patients consistently demonstrated significantly poorer OS and CSS outcomes compared to GISTs patients (P < 0.05). The 1-, 3-, and 5-year OS rates for scGISTs patients were 78.4%, 60.3%, and 49.3%, respectively, with corresponding CSS rates of 83.3%, 67.8%, and 57.4%. Notably, scGISTs patients who received surgical treatment had significantly higher 5-year OS rates (62.1% vs 30.9%, P < 0.001) and CSS rates (67.8% vs 40.0%, P < 0.001) compared to those who did not undergo surgery. Multivariate Cox regression analysis identified age, surgical status, and mitotic rate as risk factors influencing OS in scGISTs patients, while surgical status and mitotic rate were identified as risk factors affecting CSS. Compared to GISTs patients, scGIST patients exhibit a less favorable prognosis; nonetheless, surgical intervention has been demonstrated to enhance their prognosis.

Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin

AbstractMeasurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos]) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)–based MRD assay with a limit of detection of 10−4 to 10−5, we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the AMLSG16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. Achievement of MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .001) and overall survival (OS) (4y-OS; 70% vs 44%; P = .012). This survival advantage was also seen among patients who underwent allogeneic hematopoietic-cell transplantation during first complete remission (4y-CIR, 14% vs 39%; P = .001; 4y-OS, 71% vs 49%; P = .029). Multivariate models for CIR and OS after Cy2 revealed FLT3-ITD MRDneg as the only consistent favorable variable for CIR (hazard ratio [HR], 0.29; P = .006) and OS (HR, 0.39; P = .018). An NPM1 co-mutation correlated with a deeper molecular response as reflected by stronger MRD reduction and a higher rate of FLT3-ITD MRDneg after Cy2. During follow-up, conversion from MRDneg to MRDpos was a strong, independent factor for inferior CIR (HR, 16.64; P < .001) and OS (HR, 4.05; P < .001). NGS-based FLT3-ITD MRD monitoring allows for the identification of patients at high risk for relapse and death following treatment with intensive chemotherapy and midostaurin. Using NGS-based technology, FLT3-ITD emerges as a novel, highly clinically relevant target for MRD monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT01477606.

Outcomes for high-risk defining events in follicular lymphoma following frontline immunochemotherapy

Progression of follicular lymphoma (FL) or transformation (tFL) within 24 months of immunochemotherapy (ICT) represent high-risk defining events (HRDE) with poor overall survival (OS). We examined baseline clinical characteristics, imaging and outcomes for patients experiencing HRDE in an international retrospective cohort of newly diagnosed FL patients requiring ICT. We defined HRDE groups as: relapse or progression of FL within 24 months (FL24); Early TFL (transformation <24 months of ICT); Late TFL (transformation >24 months of ICT). 433 patients were categorised: reference FL n=352 (no HRDE), FL24 n=43, Early TFL n=29, or Late TFL n=9. Chemotherapy regimens included bendamustine (63%), CHOP (27%) or CVP (10%); 85% received rituximab/15% obinutuzumab and 48% received maintenance therapy. Compared to the reference FL group, OS from HRDE was inferior for FL24 (HR 3.93, 95% CI 2.14-7.23), Early TFL (HR 8.16, 95% CI 4.38-15.2) and Late TFL (HR 8.23, 95% CI 3.18-21.25). OS from HRDE was inferior for Early TFL compared to FL24 (HR 2.08, 95% CI 1.02-4.21). In multivariable analysis, baseline performance status, elevated lactate dehydrogenase, elevated beta-2-microglobulin and grade 3A were associated with Early TFL. Clinical characteristics were not able to differentiate Early TFL from FL24. Standardised uptake value max was higher in Early TFL but not FL24 compared to reference FL. Early TFL and FL24 represent different HRDEs in FL after ICT and are associated with inferior OS. Distinguishing between early TFL and FL24 is important for biomarker development, management and to develop and interpret clinical trials in this area of unmet need.

TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice.

Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

Maximum disease diameter is associated with outcomes in stage II follicular lymphoma treated with radiation therapy alone

PurposeThe optimal management of stage II follicular lymphoma (FL) is unclear. Radiation therapy (RT) alone has been the gold standard treatment, but a proportion of patients relapse. We sought to characterize outcomes and prognostic factors for stage II FL treated with RT alone to identify a high-risk subgroup of patients who may benefit from treatment intensification. MethodsThis was a population-based, province-wide, retrospective study. Included patients had grade 1–3A, non-mesenteric, stage IIA or IIAE FL diagnosed between 1986 and 2016 and treated with curative-intent (≥20 Gy) RT alone. Results102 patients were included. Median follow-up was 10.4 years (range, 0.3–22.3). Median age was 59 years (range, 33–86). Median greatest disease diameter was 3.6 cm (range, 1.5–11.5). Freedom from progression (FFP) was 60.3% at 5 years and 40.7% at 10 years. Overall survival (OS) was 89.2% at 5 years and 81.8% at 10 years. Greatest disease diameter of >3.6 cm was associated with inferior FFP (10-year FFP 34% vs. 47%, p = 0.013) on univariable analysis and inferior FFP (hazard ratio [HR] 1.87, p = 0.019) and inferior OS (HR 2.12, p = 0.027) on multivariable analysis (MVA). Older age was associated with inferior OS (HR 1.08, unit = 1 year, p < 0.001) on MVA. Conclusions40.7% of stage II FL patients treated with RT alone remained disease-free at 10 years. Greatest disease diameter >3.6 cm was associated with inferior FFP and OS, representing a novel prognostic indicator in this population that may help in the decision-making process on whether to complement RT with systemic therapy.

Less frequent radiological exams to avoid futile response assessments from 177-LuDOTATE therapy for patients with advanced neuroendocrine tumors.

177-LuDOTATE is an effective but expensive treatment for neuroendocrine tumors (NETs). Reducing treatment-related costs, such as the number of images, could improve access to 177-LuDOTATE. We evaluated early radiological tumor progression and prognostic factors in patients with NETs treated with 177-LuDOTATE. We retrospectively included all patients with NETs who received at least one cycle of 177-LuDOTATE. The primary endpoint was the rate of early radiological progression between cycles 2 and 3 (in 10-16 weeks). Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to prognostic factors (tumor grade, primary site, functioning syndrome, 177-LuDOTATE treatment line) in Cox proportional hazards models. The median number of 177-LuDOTATE cycles was 3 (range 1-6) among 59 patients included. Ten (17%) patients had early progression. Among 14 patients who received ≤2 cycles of 177-LuDOTATE, ten (72%) stopped treatment due to disease progression, with five patients having a G2 (ki67: 5-25%) and 4, a G3 (ki67: 25-90%) NET. In the Cox multivariable analysis, higher grade (G2 or G3 vs G1) were significantly associated with inferior PFS and OS. The median PFS of G1, G2 and G3 NET patients were: 34.1, 11.7 and 6.1 months (P = 0.015), respectively. It is feasible to perform imaging tests after 177-LuDOTATE completion for patients with indolent NETs with the intent to avoid futile assessments. For patients with more aggressive diseases, such as G3 NETs and G2 tumors with high tumor burden, we advise to perform more frequent images during 177-LuDOTATE therapy.

Hypoalbuminemia and hypercalcemia are independently associated with poor treatment outcomes of anti-PD-1 immune checkpoint inhibitors in patients with recurrent or metastatic head and neck squamous cell carcinoma

BackgroundRecent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes .MethodsWe retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs.ResultsLow tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001).ConclusionsHypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.

Prognostic value of nucleotide excision repair and translesion DNA synthesis proteins in muscle-infiltrating bladder carcinoma

BackgroundCisplatin (CDDP) remains a key agent in the treatment of muscle-infiltrating bladder carcinoma (MIBC). However, a proportion of MIBC patients do not respond to chemotherapy, which may be caused by the increased repair of CDDP-induced DNA damage. The purpose of this study was to explore the prognostic value of proteins involved in nucleotide excision repair (NER) and translesion DNA synthesis (TLS) in MIBC patients.MethodsThis is a retrospective analysis of 86 MIBC patients. The XPA, XPF, XPG, ERCC1, POLI, POLH and REV3L proteins were stained in primary bladder tumors and their levels were analyzed both in the total cohort and in a subgroup with metastatic urothelial carcinoma (mUC) that received gemcitabine and CDDP as a first-line therapy. Both cohorts were divided by percentage of cancer cells stained positive for each protein into subgroups with high and low expression. In the same manner, the combined expression of NER (XPA + ERCC1 + XPF + XPG) and TLS (POLI + POLH + REV3L), as the whole pathways, was analyzed.ResultsMortality was 89.5% at the median follow-up of 120.2 months. In the total cohort, patients with tumors stained positive for XPA, XPG and POLI had significantly worse overall survival (OS) compared to those with negative staining [hazard ratio (HR) = 0.60, 0.62 and 0.53, respectively]. Both XPG and POLI were independent prognostic factors in multivariate analyses (MVA). In addition, an increase in NER and TLS pathway expression was significantly associated with worse OS in the total cohort (HR = 0.54 and 0.60, respectively). In the mUC subgroup, high POLI expression was associated with significant deterioration of OS (HR = 0.56) in univariate analyses, and its independent prognostic value was shown in MVA.ConclusionsOur study showed significant correlations between the tumor expression of XPG and POLI, as well as NER and TLS as the whole pathways, and inferior OS. Hence, they could constitute prognostic biomarkers and potentially promising therapeutic targets in MIBC. However, a prospective trial is required for further validation, thereby overcoming the limitations of this study.

Evaluation of prognostic factors in patients with high-risk classical Hodgkin lymphoma undergoing autologous transplantation

AbstractThere are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or stable disease (SD) by imaging after completion of frontline treatment (PR/SD); (3) progression of disease by imaging (and confirmed by biopsy) within 12 months of frontline therapy completion after prior documentation of complete response (CR; early relapse [ER]). A total of 478 patients were included in the analysis. Among these, 217 (45%) were PP, 86 (18%) were PR/SD, and 175 (37%) were ER. The 6-month and 1-year cumulative incidence of nonrelapse mortality after auto-HCT were 0.9% and 1.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) after auto-HCT were 4.33 and 10.09 years, respectively. Although those not in CR at the time of auto-HCT were associated with inferior PFS and OS, advanced age and diagnosis before 2011 were associated with inferior OS. This study showcases the safety and long-term efficacy of auto-HCT, even in patients with high-risk disease who are traditionally considered chemotherapy refractory, and will serve as a benchmark for the ongoing transplant vs no transplant trials.

Comprehensive Analysis of Metastatic Prostate Cancer: Real-World Data From the Middle East.

Metastatic prostate cancer (Pca) is a complex disease with diverse clinical characteristics and outcomes across the geographical distribution. Herein, we present a series of patients from the Middle East, aiming at identifying disease outcomes and prognostic factors specific to this regional context. This is a retrospective study of patients with metastatic Pca, diagnosed at King Hussein Cancer Center, Jordan, between 2006 and 2018. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Factors that significantly affected overall survival (OS) in the univariable analysis were examined in a multivariable Cox regression analysis. A total of 188 patients with metastatic Pca were included in this analysis, of whom 168 (89%) had de novo metastatic disease. The median age at diagnosis was 68 years, 144 (77%) had bone metastasis, 32 (17%) had visceral metastasis, and 126 (67%) had high-volume disease. At a median follow-up of 67 months, the median OS was 44.3 months. The following factors predicted inferior OS in univariable analysis: smoking, normal BMI, high-volume disease, high alkaline phosphatase (ALP), previous local therapy for prostate, and orchiectomy versus medical androgen deprivation therapy (ADT). On multivariable analysis, high-volume disease (hazard ratio [HR], 1.92 [95% CI, 1.17 to 3.13]; P = .0094), high ALP (HR, 2.136 [95% CI, 1.38 to 3.31]; P < .001), and orchiectomy (HR, 2.40 [95% CI, 1.51 to 3.82]; P < .001) emerged as independent factors for inferior OS. Metastatic Pca outcomes in our population closely align with the global benchmark. High volume status, elevated ALP, and performance of surgical as opposed to medical ADT emerge as prognostic indicators of poor survival.