Advanced Stages Of Disease Research Articles

Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate.

Cancer outcomes are largely measured in terms of disease-free survival or overall survival, which is highly dependent on timely diagnosis and access to treatment methods available within the country's existing health care system. Although cancer survival rates have markedly led in the past few decades, any improvement in the 5-year survival of gynecologic cancers has been modest, as in the case of ovarian and cervical cancers, or has declined, as in the case of endometrial cancer. The lack of effective screening options contributes to many women presenting with advanced-stage disease and the need for radical approaches to treatment. Although treatment for early-stage disease can lead to a cure, advanced-stage disease is fraught with a high potential for morbidity and mortality, and recent clinical trials have aimed to assess the noninferiority of minimally invasive options versus aggressive surgical approaches. Of particular interest is fertility-sparing treatments for endometrial and cervical cancers, which have recently been on the rise among younger women. Balancing morbidity with the risk of mortality, and loss of fertility and quality of life requires a targeted patient-centered approach to treatment. This is an ongoing area of intense research and sometimes may challenge current treatment paradigms. In this two-part review, we present an overview of current approaches to gynecologic cancer treatment and the need to de-escalate radical surgical approaches and preserve fertility. We also review the intricacies of ovarian and advanced endometrial cancer treatment, exploring the nuances in surgical debulking timing and its impact on outcomes.

The treatment outcomes of patients who failed to be randomly assigned after atezo/bev induction therapy in the Chinese TALENTop study.

e16183 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) are considered to be at an advanced stage of disease with limited treatment options. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has become a global standard of care for those patients and made conversion resection possible. The Chinese TALENTop study (NCT04649489) is aiming to clarify whether hepatic resection may provide additional benefit in HCC patients with MVI responding to atezo/bev. For patients without opportunity to receive hepatic resection, subsequent treatment outcomes will be reported. Methods: Potentially resectable HCC patients with MVI and without extrahepatic metastasis are eligible for this study. Eligible patients receive 3 cycles of atezo/bev and 1 cycle of atezo as primary systemic therapy (induction phase). Patients assessed as partial response (PR) or stable disease (SD) per RECIST v1.1 and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection followed by atezo/bev for 1 year, or Arm B, continuing atezo/bev therapy. The primary endpoint is the time to treatment failure. Patients failed to be randomized will enter the survival follow-up phase. After 296 patients entered induction phase, the patient profile, subsequent treatments per local standard of care and survival of patients who failed to be randomized were analyzed. Results: From Apr 2021 to Jun 2023, 296 patients were enrolled and entered induction phase and 175 patients failed to be randomized and were followed up until Sept 2023. The main reasons for failure to be randomized were disease progression (64.6%), investigator assessment of unsuitability for R0 hepatic resection (14.3%), and others. The 175 patients were characterized with a median age of 52 (26-76), and 166 (95%) had HBV infection. Among them, 165 (94%) had combined PVTT, 24 (14%) had combined HVTT and 5 (3%) had combined IVCTT. At a median follow-up time of 10.9 months (9.7-13.1), the median overall survival (mOS) is 13.8 months (8.9-15.8), 6- and 12-month survival rate were 71% and 53%, respectively. As the result of best response during induction phase, 3 patients (1.7%) achieved PR, 92 patients (52.6%) achieved SD and 65 patients (37.1%) were PD. 123 patients (70%) received subsequent therapy. The mOS of patients received different subsequent therapies was showed below. Conclusions: This study provides data on HCC patients with MVI after receiving atezo/bev. The result shows favorable survival even in patients failed to randomization to receive conversion resection, and subsequent treatment strategy may differ survival outcomes. Clinical trial information: NCT04649489 . [Table: see text]

Study on Correlation and Mechanism of Procollagen Lysine 2 Oxoglutarate 5 Dioxygenase on Stem Cell Characteristics and Vasculogenic Mimicry Formation in Esophageal Squamous Cell Carcinoma

In this study, we investigated the significance of the stem cell transcription factor PLOD2 in esophageal cancer to enhance our understanding of its occurrence, development, recurrence, metastasis, and potential treatment. We conducted the following experiments: (1) Immunohistochemistry revealed elevated PLOD2 protein levels in esophageal carcinoma compared to adjacent tissues, with higher levels associated with advanced disease stages and lower differentiation. (2) Immunofluorescence demonstrated increased PLOD2 expression in esophageal cancer cell lines TE-1 and Eca- 109, suggesting a connection to cell differentiation. (3) We successfully transfected fluorescently labeled PLOD2 siRNA into cells, achieving a transfection rate of 67.57% and silencing efficiency exceeding 80%. (4) Following transfection, we observed a decreased proliferation rate in PLOD2 siRNA-treated cells, indicating that PLOD2 reduction can slow esophageal cancer growth. These findings emphasize that PLOD2 plays a crucial role in esophageal cancer pathogenesis, particularly in low cell differentiation maintenance. It could serve as a promising target for inducing differentiation in esophageal cancer and evaluating its malignancy. The high PLOD2 expression in esophageal cancer cell lines suggests the presence of tumor stem cells. Moreover, reducing PLOD2 through RNAi technology slows cell proliferation, suggesting that inhibiting PLOD2 may offer a potential therapeutic approach for esophageal cancer treatment.

Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation

BackgroundA novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. ObjectivesThis study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. MethodsThis multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). ResultsA total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). ConclusionsDirect TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

Survival outcomes after autologous stem cell transplantation in T follicular helper type lymphoma.

7073 Background: T follicular helper (TfH)-type lymphoma is the most common subtype of peripheral T-cell lymphoma (PTCL). TfH lymphoma consists of angioimmunoblastic T-cell lymphoma (AITL), PTCL-TfH and Follicular T cell lymphoma. Most patients receive first-line treatment with anthracycline-based chemotherapy regimens with a potential role for consolidation with autologous stem cell transplantation (ASCT). In this study we analyzed survival outcomes in TfH lymphoma. Methods: This is an IRB approved retrospective analysis of patients with TfH lymphoma followed between 1997–2023 at the MD Anderson Cancer Center. Demographics, treatment history, response and survival outcomes were collected and analyzed. Next-generation sequencing (NGS) data was collected from a panel of 162 cancer-related genes. Survival analysis was performed with Kaplan Meier curves and comparisons were made with log-rank tests. Results: Of the 218 patients with TfH lymphoma for whom information was known about prior history of ASCT, 84 (39%) underwent ASCT (Table). At the time of diagnosis, the majority of patients had advanced stage disease (92% with stage III or IV) and elevated LDH (89%). NGS testing was available from 31 patients and the genes with recurrent somatic mutations identified were TET2 (65% patients), DNMT3A (29%), RHOA (13%), IDH2 (10%), PLCG1 (10%), TP53 (10%), ATM (6%), CCR7 (6%), JAK3 (6%) and STAT3 (6%). The three most common first-line treatments were CHOP (37%) followed by CHOEP (14%) and combination of brentuximab with either CHP or CHEP (13%). Patients who received ASCT were significantly younger (Table). The median overall survival (OS) for the cohort was 40.3 months with median progression-free survival (PFS) after first treatment of 12.5 months. Patients who received ASCT had a significantly higher overall survival (log-rank test p-value &lt; 0.01) compared to those who did not receive ASCT. Conclusions: This retrospective analysis of a large single institution cohort of patients with TfH lymphoma found significantly improved OS in those who underwent ASCT compared to those who did not. Given the sizeable proportion of patients who are transplant-ineligible due to age or comorbidities, there is a need for newer consolidation approaches for TfH lymphoma. [Table: see text]

Real world outcomes in patients with follicular lymphoma treated with RCHOP vs BR.

e19038 Background: In patients (pts) with (w) follicular lymphoma (FL), BR is associated w improved progression free survival (PFS) compared to RCHOP. In clinical practice, RCHOP is frequently utilized in pts w grade (G) 1-2 FL w high SUVs or Ki-67% proliferation index, and G 3A FL due to concern for transformation. Using real world data, we compared treatment trends and outcomes in pts w FL treated w first line (1L) BR versus (vs) RCHOP. Methods: This study used the nationwide Flatiron Health electronic health record-derived de-identified database. Pts diagnosed w FL G 1-2 or 3A and treated between (bt) 2011-2022 w 1L BR or RCHOP were included. The primary objective was to compare time to next treatment or death (TTNT) bt the two cohorts. Overall survival (OS), and transformation and POD24 rate were also analyzed. Univariable and multivariable Cox regression models were used to evaluate the impact of various clinical factors (sex, ethnicity, ECOG PS, treatment center type, FL G, FLIPI, rituximab maintenance [mtn]) on TTNT and OS. Results: The study included 2,089 pts; 1,475 pts received BR (BR n=1387, BO [obinutuzumab] n=88,), and 614 pts received RCHOP (RCHOP n=459, OCHOP n=8, RCEOP [etoposide] n=4, RCHP n=1, RCEP n=1, RCVP n=137, OCVP n=4). Median age at diagnosis was 64. Most patients were male (53%), non-Hispanic (90%), had advanced stage disease (82%), ECOG PS 0 (57%), G 1-2 FL (85%), intermediate FLIPI (62%), were treated at a community practice (83%), and did not receive rituximab mtn (54%). At median follow up of 90 mos, median TTNT bt BR and RCHOP was 96 vs 78 mos (HR 1.146, 95% CI 0.986-1.332, p = 0.076). In a multivariable model, there was no significant association bt RCHOP and TTNT. Male sex, ECOG PS ≥ 2, and high FLIPI were associated w worse TTNT, and Rituximab mtn w improved TTNT. Among G 3A pts (n=304), more pts received RCHOP (57% vs 43%), and median TTNT bt BR and RCHOP was 73 vs 78 mos (HR 0.787, 95% CI 0.542-1.142, p=0.207). Median OS bt BR vs RCHOP was 126 vs 138 months (HR 0.878, 95% CI 0.718-1.075, p=0.207). Male sex, ECOG PS ≥ 2, high FLIPI, and treatment in community setting were associated w worse OS. Rituximab mtn was associated w improved OS. 115 (5.5%) pts had transformation to aggressive lymphoma. Transformation rates bt BR vs RCHOP were 4.83% vs 6.50% (p=0.2) among all G 1-2 pts (n=1785), and 3.85% vs 9.2% (p=0.069) among all G 3A pts (n=304). 310 (14.8%) pts had POD 24, including 13.3% of all pts treated with BR and 18.6% with RHCOP (p=0.002). Autologous stem cell transplant (ASCT) was used in 26 (8.4%) POD 24 pts, among whom there was no difference in ASCT rate bt BR vs RCHOP (8.2% vs 8.8%, p=0.9). Conclusions: This retrospective analysis of real-world data showed clinical improvement in TTNT w BR compared to RCHOP in all FL patients. Among patients w G 3A FL, there was no significant improvement in TTNT with RCHOP. Rituximab mtn was associated w improved OS. Rate of transformation was higher in G 3A patients treated with RCHOP. There was low rate of ASCT in POD24 pts.

Characteristics, treatment, and outcomes of cutaneous mantle cell lymphoma: A decade-long study at MD Anderson Cancer Center.

e19037 Background: Mantle cell lymphoma (MCL) is a rare B cell neoplasm that accounts for 6% of all non-Hodgkin lymphomas and affects predominantly older Caucasian males. Cutaneous involvement is rare in MCL, but more commonly occurs in the advanced or terminal stages of the disease and lacks a standardized approach. Here we report our center’s experience with cutaneous MCL. Methods: We conducted a retrospective chart review of all MCL patients treated at the University of Texas MD Anderson Cancer Center from January 2013 to December 2023 and identified 20 MCL patients with cutaneous involvement. Demographic data, disease characteristics, imaging findings, therapies, and survival outcomes were collected. The study was performed in accordance with the guidelines of the institutional review board. Results: Among the 20 MCL patients with cutaneous involvement (Table), nearly all were Caucasian (n=19/20, 95%), and most were male (n=14/20, 70%). The median age at cutaneous MCL diagnosis was 63.5 years (range: 50-83). All patients had advanced stage disease. The median interval from MCL diagnosis to the emergence of cutaneous symptoms was 2.2 years (range 0-9.3). Most had relapsed/refractory disease (n=17/20, 85%). Most patients had blastoid (n=13/19) or pleomorphic (n=4/19) cytology with a Ki-67 proliferative index ≥50% (n=19/20, median 90%). Several patients had p53 expression (n=11/14) and/or TP53 aberrations (n=4/16). Immediate subsequent systemic therapy, most commonly immunochemotherapy (n=9/20), led to frequent responses (overall response rate: 61%). Most patients received low-dose radiotherapy (RT) for their cutaneous disease (n=19/20) achieving high rates of local control (n=16/18). Of those who are alive and in complete response (n=3) at data cutoff, 2 received chimeric antigen receptor (CAR) T cell therapy as their last MCL-directed treatment. The median survival time from MCL diagnosis to death was 6.83 years (95% confidence interval (CI):4.20-not estimable (NE)). The median survival time from the diagnosis of cutaneous involvement to death was 3.16 years (95%CI: 1.93-NE). The median follow-up duration from MCL diagnosis was 8.22 years. Conclusions: Cutaneous involvement in MCL is associated with aggressive disease biology and poor survival outcomes. Low-dose RT with concurrent immunochemotherapy should be considered the current standard therapeutic approach. CAR T cell therapy and/or bispecific T cell engagers may further improve outcomes in these high-risk patients. [Table: see text]

Prognostic value of circulating tumor DNA testing in surgically resected pancreatic cancer.

4134 Background: The majority of patients with pancreatic cancer who undergo curative intent resection have recurrence, but optimal surveillance is unknown. Circulating tumor DNA (ctDNA) tests, custom-designed multiplex-PCR tumor assays unique to each patient’s tumor, may assist in monitoring for recurrence. Methods: We performed a single center retrospective review of patients with surgically resected pancreatic cancer who had at least 1 ctDNA test performed post-operatively between 8/1/21 and 11/13/23 with Natera Inc.’s Signatera assay. Primary outcomes were documented radiographic progression and death. Results: 74 patients were identified, of whom 36 were positive for ctDNA at any point during the study (median follow up from surgery 19.1 months) while 38 remained negative for ctDNA (15.3 months). There was no difference in age (≥ or &lt; 70), sex, or race. Positive ctDNA at any time point was associated with advanced stage disease (p=0.013), positive resection margins (p=0.008), and having received neoadjuvant therapy (p=0.005). Those with any positive ctDNA were more likely to have radiographic progression (p&lt;0.0001) or death (p=0.0005) by the end of the study. These differences remained when the population was examined in subgroups of first post-operative ctDNA positive, first ctDNA negative but at least one subsequent ctDNA positive, and all ctDNA negative. In Cox proportional hazard models, both any positive ctDNA test and positive first ctDNA test (first ctDNA limited to ≤120 days post-op) were associated with higher risk of radiographic progression and/or death compared to never testing positive for ctDNA and negative first ctDNA test, respectively (HR 12.6 (3.0-51.9), p=0.0005; HR 5.6 (1.4-22.8), p=0.02). Conclusions: Positive ctDNA tests, both in the immediate post-operative and subsequent settings, are associated with higher risk of radiographic progression or death in patients with resected pancreatic cancer. These data suggest that ctDNA testing provides independent, meaningful prognostic information superior to traditional pathologic risk factors and CA19-9 testing alone. These findings have implications for future clinical study design and decisions about surveillance and treatment. [Table: see text]

The cachexia index is a prognostic factor for patients with recurrent pancreatic cancer.

Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer. This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival. The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011). The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI.

Rapid label expansion based on public-private collaboration in IMPRESS-Norway.

e13529 Background: Access to new cancer drugs requires knowledge of biomarkers. As a consequence, there is an increasing access gap to new treatments between different cancer subgroups. Several precision medicine trials aim to address this gap through drug repurposing (1-3). IMPRESS-Norway is a national precision cancer medicine trial providing treatment to patients with advanced-stage disease after standard therapy. Patients with biomarkers are identified through the national infrastructure for precision diagnostics, InPreD, a part of the national healthcare services for stratification into biomarker-driven clinical trials. IMPRESS-Norway opened for inclusion on April 1st, 2021. Currently InPreD identifies biomarker in 31% of patients, and 50 % of patients included in treatment cohorts in IMPRESS-Norway are diagnosed with a rare cancer (4). The IMPRESS-Norway has, together with the public-private partnership CONNECT (Norwegian Cancer Precision Medicine Implementation Consortium), developed a roadmap for expanding access through ordinary reimbursement decisions. Methods: New drugs can efficiently be incorporated into the IMPRESS-Norway drug portfolio and tested across all relevant indications through a three-stage process. In stage 1 and 2, a total of 24 patients are recruited into a drug/diagnosis/biomarker-specific cohort, with drug provided by the company and a per-patient fee. If ≥ 5 patients exhibit clinical benefit (stable disease or better at week 16), the drug may undergo further testing in stage 3 (expansion cohorts). The company provides drugs during the first 16 weeks of treatment and with public reimbursement after week 16 for all patients experiencing clinical benefit. Results: Positive reimbursement decisions in Norway can be made based on knowledge of effect from single armed studies (5). Norwegian payers can therefore make reimbursement decisions based on results from the expansion cohort. Similar systems are set-up in the Netherlands (6). Several drugs are currently concluding stage 2 in IMPRESS-Norway. The first expansion cohort in IMPRESS-Norway (jointly with other DRUP-like trials in the EU Cancer Mission project PRIME-ROSE), exploring the effect of olaparib in patients with biallelic BRCA1/2 inactivation in non-approved diagnosis, is based on the DRUP-trial, exemplifying the European collaboration in these trials. Conclusions: Public-private collaboration facilitates rapid identification of eligible patients, irrespective of cancer subgroup, providing potential for new indications. IMPRESS-Norway presents a feasible strategy for rapid label expansion. 1. DLvan der Velden et al, Nature 2019; 574:127-31. 2. PM Mangat et al, JCO Prec Oncol 2018; 10. 3. Å Helland et al, J Trans Oncol 2022; 20. 4. Puco K et al., 2024 in press. 5. GL Fagereng et al, Front Pharmacol 2014; doi:10.3389. 6. SBW Doorn-Khosrovani et al. Ann Oncol 2019; 30: 663-5. Clinical trial information: NCT04817956 .

Disparities by sex in Hispanic patients with cutaneous melanoma: A national database analysis.

e23045 Background: Melanoma is the fifth most common form of malignancy in the United States.1 Studies have established that Hispanic patients have worse melanoma-specific survival compared to non-Hispanic White individuals.2 However, there is a paucity of literature investigating sex differences in patient characteristics and outcomes within Hispanic melanoma patients. Thus, the aim of this study is to further examine sex differences in melanoma characteristics and disease-specific survival within Hispanic patients. Methods: Individuals of Hispanic descent diagnosed with microscopically confirmed cases of cutaneous melanoma (ICD-O-3 codes 8720/3-8780/3; Primary Site codes C44.0-C44.9) between 2000 and 2020 were identified through the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses involved Chi-squared tests, Kaplan-Meier and log-rank methods, and multivariate Cox regression, with significance set at a p-value &lt; 0.05. Results: In a cohort of 12,328 Hispanic melanoma patients (43.3% male, 56.7% female), a significant association between sex and age was found (p &lt; 0.001). The greatest proportion of males were in the 60-79 age group (39.7%), while females were predominantly in the 40-59 age group (39.0%). Greater number of males had truncal melanomas (31.4%) compared to females having lower extremity melanomas (35.2%) (p &lt; 0.001). Females exhibited higher rates of localized disease (80.3% vs 70.2%) while males were more frequently diagnosed with regional (18.5% vs 13.8%) and distant disease (11.3% vs 5.9%) (p &lt; 0.001). Males demonstrated greater mean Breslow thickness (1.80 vs 1.44; p &lt; 0.001), elevated rates of lymph node positivity (37.2% vs 27.2%; p &lt; 0.001), and metastatic disease (2.8% vs 1.6%; p &lt; 0.001). On univariate Kaplan-Meier analysis, males demonstrated significantly reduced disease-specific survival (182.9 months) compared to females (214.2 months) (p &lt; 0.001). After adjusting for age, disease stage, annual income, rural vs urban residence, and primary tumor site, male sex independently increased disease-specific mortality compared to females (HR = 1.31; 95% CI 1.16-1.48; p &lt; 0.001). Conclusions: Our investigation reveals that Hispanic males tend to receive melanoma diagnoses at older ages, advanced-stage disease, and primarily on the trunk.3 Furthermore, our study is the first to highlight a significantly reduced disease-specific survival in males compared to females. The observed sex differences may arise from a complex interplay of behavioral factors and immunological, hormonal, or genetic influences.4 Men exhibit a lower likelihood of engaging in skin self-examinations and seeking medical assistance. Limitations to this study include use of data reported through a national database. Nonetheless, this study underscores the significance of sex-specific variations in presentation and disease-specific survival among Hispanic patients.

Revisiting beta-2 microglobulin as a prognostic marker in diffuse large B-cell lymphoma.

Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M-NCCN-IPI) by adding β2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL.

Clinical and outcome patterns in epithelial ovarian cancer (EOC) within a Latin American cohort.

e23308 Background: Epithelial Ovarian Cancer (EOC) is an heterogenous disease which is usually diagnosed inadvanced stages. Despite the advent of new therapies, the outcomes for this disease remain poor in certain scenarios. We describe the clinical features and survival outcomes in a developing country. Methods: Retrospective study based on case review of women with newly diagnosed EOC between 2015 and 2017 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru. Descriptive analysis was conducted for clinical characteristics, epidemiological factors and treatment. PFS was calculated from the date of diagnosis until the first documented progression and OS from the date of diagnosis to death. Both were calculated using the Kaplan Meier curve. Results: 234 patients were included, the most common histology subtype was high grade serous carcinoma (47,5%), followed by mucinous (15.9%) and clear cell carcinoma (15.4%). Median age was 55.7 yo (range 19-88). Breast and ovarian cancer family history were reported in 3.8% and 3.0%, respectively. 35.8% of patients were overweight, and 12.5% were obese. Most patients (61.5%) were diagnosed at advanced disease (III-IV) and the most common site of metastasis was liver (43.6%) and lung/pleural (28.2%). BCRA testing was performed only in 6% of patients, and 4/14 patients had a pathologic mutation. Ca125 was elevated in 86.2% of patients. Regarding treatment, all patients with early stage disease (I-II) underwent surgical staging. For advanced stage disease, 47.6% (69/145) of patients underwent upfront surgery and 41.4% (60/145) received platinum-based chemotherapy in neoadjuvant setting; 57.3% (35/61) of these patients achieved optimal secondary cytoreduction. With a median follow up of 74,4 months, median PFS was 32.61 months (0.6-474) and global median OS was 58.13 months. Median OS for early disease (I-II) was not reached and for advanced disease (III-IV) was 33.73 months. Survival rate at 5y for all stages was 45.2%; 60.8% and 28.4% for early and advanced disease, respectively. Conclusions: These findings highlight the prevalence of high-grade serous carcinoma and the significance of advanced-stage diagnosis in the survival outcomes. In the era of targeted therapies, the lack of access to BRCA detection tests restricts therapeutic options and, consequently, hinders responses in this group of patients.

Measuring COVID-19's impact on diagnosis of cervical cancer by race/ethnicity, age, and region of the United States.

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race, stage at presentation, and regions of the US. Methods: Data on cervical cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 to calculate estimated and actual incidence rates per 100,000 women. We compared actual cervical cancer incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 245,618 cases of cervical cancer were identified. In 2019, prior to the pandemic, the incidence was 7.64 per 100,000 women. From 2001-2019, cervical cancer incidence decreased by 0.96% per year (p=0.023). Based on this trend, we expected the incidence to be 7.57 per 100,000 women in 2020, but the reported incidence was only 6.83 per 100,000, therefore, there were 9.8% less cervical cancer cases (1,189 cases) in 2020 than expected. This was most noticeable at the lower and upper ends of the age distribution, with 17.6% less cases than expected in the year 2020among 25-29 year-olds and 18.4% less cases than expected among 85+ year-olds. This is in comparison to the median age group for cervical cancer (50-54 year-olds) in whom there were 14.5% (193) less cases than expected in 2020. Based on stage of disease, for local, regional, and distant disease there were 16.3%, 2.8%, and 1.9%, less cases than expected in 2020, respectively. Within racial and ethnic groups, we found that Non-Hispanic Black (NHB) and Hispanic patients had 15.0% and 13.9% less cases than expected, versus 8.7% among Non-Hispanic White (NHW) and 5.8% among Non-Hispanic Asian and Pacific Islander (NHAPI) patients. Comparing U.S. regions, the Midwest, Northeast, West, and South had 14.6%, 10.2%, 10.2%, and 9.0% less cases than expected for 2020, respectively. Conclusions: Our data suggest that the reported cervical cancer cases were significantly less than predicted based on past trends during the COVID-19 pandemic.. Older age, NHB and Hispanic patients, and those residing in Midwest states had the greatest number of possible missed diagnoses of cervical cancer during this time. Mitigating strategies are needed to reinstate screening programs, particularly in these at-risk groups to prevent increased rates of advanced stage disease and mortality.

Results of IMPACT 2, a randomized study evaluating molecular profiling and targeted agents in metastatic cancer at MD Anderson Cancer Center.

3153 Background: To address the limitations of exploratory studies, we conducted IMPACT2. The primary endpoint was to compare the progression-free survival (PFS) between patients treated with matched targeted therapies (MTT) selected on the basis of tumor molecular alterations and those whose treatment was not selected on the basis of alteration analysis (non-targeted therapy, NTT). Methods: Patients with metastatic cancer and targetable alterations were randomized between the 2 arms when eligibility criteria were met (Part A, 5/2014-4/2017; sponsor, Foundation Medicine). In Part B (3/2019-9/2023; sponsor, Tempus), patients who declined randomization selected the treatment arm ( NCT02152254 ). PFS/OS analysis (Kaplan Meier, Cox model; reference group, comparison, NTT). All cases were presented at weekly Molecular Tumor Board meetings; initial plan, to randomize 300 of 1,362 enrolled patients. Results: Overall, 829 patients (Parts A, 391; B, 438); were enrolled (med. age 59.5 yrs, range 18-84; men 50%; med. No. of prior therapies 3, range 0-17; most common cancers: gastrointestinal 34%, head/neck 13.5%, gynecologic 10%, sarcoma 9.53%; most common genomic alterations RAS 38%, PI3K 31%, FGFR 28%). In Part A, 69 were randomized (MTT, n=35; NTT, n=34); Part B (MTT, n=11, NTT=13; Selected arm: n=16: MTT, n=13; NTT, n=3). Results are shown (Table). MTT group: median PFS by therapy type: FDA approved/off-label, 4.7 months (95% CI, 2.93, 7.1); investigational, 2.6 months (95% CI, 2.27,4.87), combined FDA approved/investigational, 1.7 months (1.7, NR) (p=0.22). Conclusions: Considering the challenges to randomize patients (doi: 10.1038/s41698-022-00317-0), and that the study was underpowered for its original goal, no differences in response, PFS (primary endpoint), or OS was noted between the 2 arms, possibly because of the advanced stage disease and the complexity of tumor biology that cannot be addressed by randomization. Clinical trial information: NCT02152254 . [Table: see text]

Safety and efficacy of biosimilar TDM-1: A real world retrospective study.

3022 Background: Ado-Trastuzumab emtansine (TDM1), an antibody-drug conjugate demonstrated significant efficacy in both metastatic and adjuvant treatment of HER 2 Positive Breast cancer. Cost of the drug was prohibitive for use in Low and Middle income countries (LMIC). A biosimilar version of TDM1 was introduced in India at a lower price in May 2021. Since then, the use of TDM1 in deserving patients has increased. We aimed to study the safety and efficacy of biosimilar TDM1 in our center. Methods: We retrospectively analysed the case records of all patients who were prescribed biosimilar TDM1 at our institute from 01.06.2021 to 20.10.2023. Indication for TDM1, line of therapy in which used, number of cycles used, response rates, adverse events, progression free survival and overall survival were calculated using simple statistical methods. The usage of any TDM1 after May 2021 was compared to the previous years’ usage. Results: A total of 116 patients were prescribed biosimilar TDM1 in the study period. Out of them, 51 patients received the drug in the adjuvant setting and 65 for advanced stage disease. Early stage (n=51): Out of the 51 patients, 32 (62.7%) completed planned cycles, 14 (27.5%) ongoing; 3 (5.9%) discontinued due to social reasons, 2 (3.9%) changed treatment due to adverse events. All of them tolerated the therapy well. Common adverse effects were fatigue. Only 5 patients (21.7%) required romiplostim for therapy related thrombocytopenia. None of them had grade ≥3 adverse affects. Advanced stage (n=65): At a median follow up of 9 months, 30 patients (46.2%) progressed; 15 (23%) ongoing; 15 (23%) defaulted due to various social reasons; 5 (7.7%) discontinued due to intolerance. The median number of cycles received was 8 cycles (IQR 5-13). Majority of them received TDM1 in the second line (84.6%). Response evaluation was available for 52 patients who completed at least three cycles of TDM1. Objective response rate was noted in 33 patients (50.8%). Clinical benefit rate (CR+PR+SD) was seen in 39 patients (75%). 5 patients (9.6%) had a Complete response, 28 (53.8%) had Partial response and 6 (11.5%) had a stable disease. The median duration of response was 5 months. The median Progression Free survival was 8 months (5.7– 10.2m) and the projected overall survival was 18 months (16.1-19.9 m). No serious adverse event or cardiac compromise was encountered. 3 patients had thrombocytopenia. One patient succumbed to non-neutropenic Septic shock. In a retrospective data analysis, TDM1 was used in 17 patients in one calendar year prior to the availability of generic TDM1. In the subsequent year, 60 patients received TDM1 at least once in either indication. Conclusions: The availability of biosimilar TDM1 increased the reach to deserving patients. No new adverse events were identified. The safety and efficacy of the biosimilar TDM1 were comparable.

Outcome analysis of the traditional therapeutic approach in patients with bronchopulmonary cancer and advanced anesthetic-surgical risk

Background. Lung cancer exhibits high global incidence and mortality rates. Surgical resection remains crucial to diagnosis, staging, and treatment of non-small cell lung cancer (NSCLC). However, advanced stages often require multimodal approaches. Prehabilitation, innovative perioperative techniques, and the exploration of immunotherapy hold promise for improving outcomes. Materials and methods. This two-phase observational cohort study included a retrospective arm (100 patients, traditional treatment) and a prospective arm (100 patients, innovative perioperative management, and risk stratification). Descriptive and inferential statistics were used to evaluate data, identify risk factors, and compare the 2-year survival between treatment groups. Results. Despite advances, lung cancer prognosis remains poor, with limited cure rates. Mean survival in the traditional approach was 1.3 years with a 5-year survival of only 1%. While prehabilitation and innovative techniques showed potential, no statistically significant differences in survival times were observed between the treatment groups. Patients with stage III (Charlson score 0-4) and stage I-II (Charlson score 5-12) demonstrated comparable outcomes, highlighting the importance of comorbidity burden. Conclusions. Targeted screening protocols are of paramount importance for early detection and intervention. Populationwide smoking cessation programs, environmental protection measures, and the promotion of healthy lifestyles are vital for prevention and reducing incidence. Standard chemotherapy and radiotherapy offer limited therapeutic benefits in advanced lung cancer. This highlights a pressing need for breakthroughs in basic research to develop novel treatment paradigms that significantly improve outcomes. While this study did not reveal statistically significant survival differences between traditional and innovative perioperative approaches, prehabilitation and optimization techniques hold promise and deserve further research. The development of anti-tumor immunotherapy offers a significant potential in non-surgical lung cancer treatment, especially given the limitations in advanced-stage disease management. Harnessing the immune system to fight cancer represents a promising new frontier.

Current Treatment Options: Uterine Sarcoma.

The cornerstone of treatment for uterine sarcoma, regardless of histologic type, remains en bloc surgical resection with total hysterectomy. In the case of incidental diagnosis during another procedure, such as myomectomy, where a hysterectomy was not performed initially, completion hysterectomy or cervical remnant removal is recommended. The completion of additional surgical procedures, including bilateral salpingo-oophorectomy and lymphadenectomy, remains nuanced. Bilateral salpingo-oophorectomy remains controversial in the setting of most subtypes of uterine sarcoma, except in the case of hormone-receptor positivity, such as in low grade endometrial stromal sarcoma, where it is indicated as part of definitive surgical treatment. In the absence of apparent nodal involvement, we do not recommend performing universal lymphadenectomy for patients with sarcoma. We recommend systemic therapy for patients with extra-uterine or advanced stage disease, high-grade histology, and recurrence. The most active chemotherapy regimens for advanced, high-grade disease remain doxorubicin or gemcitabine and docetaxol combination therapy. A notable exception is low grade endometrial stromal sarcoma, where we recommend anti-hormonal therapy in the front-line setting. Radiation therapy is reserved for selected cases where it can aid in palliating symptoms.

Inflammatory Burden Index as a promising new marker for predicting surgical and oncological outcomes in colorectal cancer.

The prognosis of colorectal cancer (CRC) has been historically reliant on the Tumor Node Metastasis (TNM) staging system, but there is variability in outcomes among patients at similar stages. Therefore, there is an urgent need for more robust biomarkers. The aim of this study was to assess the clinical feasibility of the recently reported Inflammatory Burden Index (IBI) for predicting short- and long-term outcomes in patients with CRC. This was a retrospective observational study of 555 CRC patients undergoing surgery for primary tumor resection. We determined the prognostic value of preoperative IBI for disease-free and overall survival, and its predictive value for perioperative risk of infectious complications, including surgical site infection. Increased preoperative IBI was significantly associated with advanced disease stage and poor oncological outcome in CRC patients. Higher IBI was independently linked to poorer disease-free and overall survival. Similar outcomes were observed in a subanalysis focused on high-risk stage II and stage III CRC patients. Elevated preoperative IBI was significantly correlated with an increased risk of surgical site infection and other postoperative infectious complications. Propensity score-matching analysis validated the impact of IBI on the prognosis in CRC patients. We established preoperative IBI as a valuable predictive biomarker for perioperative risks and oncological outcomes in CRC patients. Preoperative IBI is useful for designing effective perioperative management and postoperative oncological follow-up.

Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.