bluuebunny/crossref_metadata_2025 huggingface dataset:
TACE combined with tislelizumab and lenvatinib in the treatment of advanced liver cancer: A real world study.
Authors: Li Bo , Yang Xiaoli , Tang Hao , Qin Shu , Peng Fangyi , Su Song
Published: July 2024

e16270

Background: The combination of transcatheter arterial chemoembolization (TACE) plus Lenvatinib prolonged progression-free survival (PFS) and overall survival (OS) than Lenvatinib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of Lenvatinib plus monoclonal antibody against programmed cell death 1 (anti-PD1) and TACE for patients with advanced HCC. Methods: Pts with advanced HCC who treated with Lenvatinib plus anti-PD1 and TACE were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. Consecutive pts were identified from September 2021 to August 2023.The Patients were included based on the following chief eligibility criteria. After signing the informed consent form, patients received sequential treatment with TACE in combination with Lenvatinib and tislelizumab. The anti-PD1 were recommended to be used continually every 3 weeks until disease progression, or intolerable toxicity. Lenvatinib was recommended to be used continually every day until disease progression, or intolerable toxicity. Follow up TACE should be given according to the patient's condition, no more than 3 times. Results: Between Sep. 2021 to Aug. 2023, 45 were enrolled. All pts received at least one dose of study treatment. The median age was 56 years(range34,73), 4 of the pts are BCLC-B stage, 41 of the pts are BCLC-C stage.Progression occurred in 8 of 45 patients and 14 patients died. The median PFS was 13.4 months (95% CI: 10.9-15.8 months) and the median OS was 20 months (95% CI: 9.8-30.4months). Of the 45 patients, a total of 3 (6.7%) patients achieved complete response (CR), and these 3 patients were treated with surgical resection. Partial Response (PR) was achieved in 12 patients (20%), Stable Disease (SD) in 22 pts (33.3%), Progressive Disease (PD) in 8 pts (17.8%), and Objective Response Rate (ORR) in patients. The Objective Response Rate (ORR) was 33.3% and the Disease Control Rate (DCR) was 82.2%.Treatment-related adverse events included increased AST 44.4%(20/45), increased ALT 51.1%(23), increased total bilirubin 42.2%(19/45), rash 44.4%(20/45), pruritus 42.2%(19/45), gastrointestinal reaction 33.3%(15/45), abdominal pain 24.4%(11/45), sensory abnormality 20%(9/45), and arthralgias 4.4%(2/45), etc., and Grade 3 Adverse events were increased ALT 2.2%(1/45), increased AST 4.4%(2/45), increased total bilirubin 2.2%(1/45), rash 2.2%(1/45), and gastrointestinal reaction 2.2%(1/45).No grade 4 or above adverse events occurred. Conclusions: In this study, TACE plus anti-PD1 and targeted therapies showed favorable efficacy and manageability in patients with advanced HCC. Toxicity was manageable with a low incidence of grade 3-4 adverse events. There were no unexpected safety signals.
Laparoscopic versus open hepatectomy for hepatocellular carcinoma following conversion therapy: A systematic review and meta-analysis.
Authors: Lech Gabriele Eckerdt , Viana Patricia , Silva Raquel Oliveira de Sousa , Melão Bárbara , De Paiva Reis Camila Mariana de Paiva , Neto Edgar Paulo da Silva , Freitas João Luís Reis , Morriello Rafael
Published: July 2024

e16272

Background: Conversion therapy for hepatocellular carcinoma (HCC) has emerged as a novel strategy allowing patients with previously unresectable HCC to transition to a resectable disease through a combination of therapies. Laparoscopic hepatectomy is associated with reduced blood loss and early recovery without compromising oncological results in cirrhotic patients. However, the specific benefits of laparoscopic hepatectomy in patients who have undergone conversion therapy are not clear. Methods: We searched PubMed, Embase, and Cochrane Central for any studies that compared laparoscopic versus open hepatectomy after the use of conversion therapy (transarterial chemoembolization, portal vein embolization, hepatic arterial infusion chemotherapy, or liver ablation) in patients with hepatocellular carcinoma. The outcomes of interest were length of hospital stay, blood loss, operative time, pedicle clamping, postoperative complications, and transfusion. Statistical analysis was performed using R statistical software 4.2.1. Heterogeneity was assessed with I². Results: We included 535 patients from 4 retrospective nonrandomized studies. The mean age in the laparoscopic group was 60.33, ranging from 29 to 83. Length of hospital stay was significantly reduced in the laparoscopic group (MD -5.01; 95% CI -9.76–-0.27; p = 0.04; I² = 92%), as well as the blood loss (MD -97.26; 95% CI -200.54–6.01; p = 0.06; I² = 76%). Postoperative complications also favored the laparoscopic group (OR 0.40; 95% CI 0.17–0.94; p = 0.035; I² = 0%). The endpoints of pedicle clamping (OR 0.7; 95% CI 0.11–4.36; p = 0.70; I² = 91%), transfusion (OR 0.69; 95% CI 0.36–1.33; p = 0.273; I² = 0%), and operative time (MD 34.21; 95% CI -36.68–105.10; p = 0.34; I² = 97%) did not favor any of the groups. Conclusions: In this meta-analysis, laparoscopic hepatectomy after conversion therapy was proven to be safe and feasible, without significant differences compared to open hepatectomy regarding pedicle clamping, transfusion, and operative time. Furthermore, the laparoscopic group presented less blood loss and a significantly reduced length of hospital stay. These findings suggest that laparoscopic resection could be safely used after conversion therapy and may improve surgical outcomes in these patients.
Longitudinal survival and complete tumor resection rates in Native American patients with hepatocellular carcinoma treated at academic institutions.
Authors: Becken Aidan John , Murugan Vikram , Bine Christopher Reese , Silberstein Peter T.
Published: July 2024

e16281

Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions, notably cirrhosis induced by hepatitis B or hepatitis C infection. Past literature has demonstrated the impact certain socioeconomic factors (eg. race, occupation, place of residence) have on the prognosis of HCC, however the analysis of facility types where treatment was received in relation to HCC has yet to be further examined. Historically, Native American patients have exhibited a higher incidence of advanced-stage cancers at the time of diagnosis compared to white counterparts and experience the lowest cancer survival rates among all racial and ethnic groups. Using the NCDB, this study analyzed the relationship between the facility type where care was received and survival in Native American patients with HCC. Methods: The National Cancer Database (NCDB) was used to identify Native American patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: Of 1186 Native American patients included in the sample, 697 (45%) received treatment at an academic facility. Native American patients treated at academic facilities experienced greater survival as compared to those who were treated at nonacademic facilities (52 months vs 30 months, p < 0.05). When controlling for age, year of diagnosis, surgical status, income bracket and surgical margins, receiving care at an academic facility was associated with an independent decrease in hazard (HR = 0.403; p < 0.05). Native American patients who went to an academic facility were more likely present with Stage I and II tumors, receive surgery, have no residual tumor after surgery and have private insurance (p < 0.05). Nonacademic facility patients, on the other hand, were more likely to present with Stage III and IV tumors, poorly differentiated and undifferentiated tumors, and have bone, brain, liver and lung metastases (p < 0.05). No differences were seen in Charlson-Deyo score, adjuvant therapy type, or same hospital readmission within thirty days of hospital discharge. Conclusions: This study found that Native American patients with HCC who received treatment at academic facilities experienced improved overall survival. These results follow previous trends, wherein academic institutions may offer more specialized care or a greater spectrum of services that yield improved patient outcomes. Further research can explore other treatment differences that Native American HCC patients face and elucidate the cause of the disparity described here.
Predictors of malignancy and survival in patients with pheochromocytoma and paraganglioma.
Authors: Gonzalez-Sanchez Hector Raul , Aranda-Gutierrez Alejandro , Meraz-Brenez Andres , Verduzco-Aguirre Haydee Cristina , De la Peña-Lopez Roberto
Published: July 2024

e16289

Background: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors for which the definitive diagnosis of malignancy hinges on the detection of metastatic disease, rather than histological features, making prognostication particularly challenging. Consequently, identifying reliable clinical predictors for both malignancy and survival is of utmost importance. Methods: We retrospectively analyzed records of patients with biopsy-proven PCC or PGL treated at a single center in Mexico City from 2008 to 2022. Patients with follow-up > =12 months were eligible. Data was collected from electronic medical records. Independent-samples T-test and X2 and Fisher’s exact tests were used to evaluate associations between variables. We used the Kaplan-Meier method to calculate disease-free survival (DFS) and overall survival (OS) rates, and utilized the log-rank test to compare these outcomes across clinicopathological features. Cox regression analysis was used to determine survival hazard ratios (HR). Results: Among 60 patients, the mean age at diagnosis was 41 years, 37 (62%) had PCC, and 12 (20%) had malignant disease (6 distant recurrences and 6 de novo metastatic cases). Clinicopathological features according to disease type (i.e. benign or malignant) are shown in Table 1. Patients with malignant disease were more likely to have PGL (67% vs. 31%, p = 0.024) and have a body mass index of > =30 kg/m2 at diagnosis (67% vs. 8%, p < 0.01). With a median follow-up of 42 months (95% CI 35-49), 8 recurrences (2 local and 6 distant) and 6 deaths were recorded, yielding 3-year DFS and OS rates of 92% and 91%, respectively. In a multivariate analysis including factors associated with DFS and OS in univariate analyses (i.e. obesity status and hypertension at diagnosis), only obesity (HR 4.93, 95% CI 1.02 - 23.79; p = 0.047) remained associated with a worse DFS, with no influence on OS. Conclusions: This study highlights obesity as a significant predictor of malignancy and recurrence in patients with PCC and PGL, marking a novel finding in the literature on these tumors. Further research is warranted to explore the underlying mechanisms linking obesity with more aggressive disease in PCC and PGL. [Table: see text]
Impact of bowel ischemia on mortality in gastrointestinal malignancies: A nationwide analysis.
Authors: Polpichai Natchaya , Saowapa Sakditad , Wattanachayakul Phuuwadith , Jaroenlapnopparat Aunchalee , Abdalla Monzer , Lopimpisuth Chawin , Sirachainan Ekaphop
Published: July 2024

e16370

Background: Bowel ischemia, characterized by reduced blood supply to the gastrointestinal (GI) tract, critically influences the pathogenesis and outcomes of GI malignancies through complex interactions involving vascular compromise, tumor biology, and systemic consequences. Despite this, the link between bowel ischemia and increased mortality in GI cancers remains unknown. This study aims to evaluate the impact of bowel ischemia on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without bowel ischemia. Hospital mortality was analyzed using STATA 18, adjusting for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 3,240 were hospitalized with bowel ischemia. Patients with bowel ischemia were older (mean age 68.10 vs. 67.07 years, P = 0.033), predominantly from the Southern region (33.49%, P = 0.019), and urban and teaching hospitals (76.83%; P = 0.006). Bowel ischemia was most associated with Pancreatic cancer (37.35%), Colon cancer (35.49%), and Hepatocellular carcinoma (11.57%). Within the cohort of patients with bowel ischemia, gastric cancer patients had the highest mortality rates of 45.83%. After adjusting for potential confounders, patients with gastric, esophageal, colon, and pancreatic cancers had significantly higher odds of in-hospital mortality of 11.90, 6.45, 4.14, 4.08, and 2.71, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and bowel ischemia, leading to increased mortality despite adjusting for potential confounders. Bowel ischemia significantly heightens the mortality risk in GI cancers through impaired nutrient and oxygen delivery, enhanced tumor aggressiveness, systemic inflammation, immune suppression, and compromised treatment efficacy. Understanding the intricate interplay between vascular compromise and cancer biology is crucial to improving patient care and outcomes in the face of these challenging malignancies.
Epidemiological investigation of neuroendocrine differentiation in carcinomas: Focus on pancreatic and cholangiocarcinoma cohorts.
Authors: Wen Yaru , Shi Susheng
Published: July 2024

e16375

Background: Neuroendocrine differentiated (NED) occurs in various non-neuroendocrine organs and is associated with unique clinical profiles, disease progression, and poorer prognosis. However, global research on NED is scarce. To address this, our study utilized standardized detection methods to explore NED's prevalence in several solid tumors. This research aims to clarify NED pathological characteristics and prognostic significance, enhancing diagnostic and treatment approaches in clinical practice. Methods: Patients (18-75 years) with cancers including pancreatic, cholangiocarcinoma, gastric, colorectal, lung, breast, and prostate, were analyzed post-surgery at our hospital (January 2017- June 2018). Criteria for inclusion were normal organ function and no pre-surgery neoadjuvant therapy. Tumors were staged postoperatively using AJCC 8th criteria (stages I-III), followed by standard adjuvant chemotherapy. NED markers like Chromogranin A, Synaptophysin, and CD56 were detected in tumors via immunohistochemical staining. Results: Between January 2017 and June 2018, over 450 cases were enrolled. Initial analysis included 46 pancreatic cancer and 49 cholangiocarcinoma samples. NED markers were found in 11 (23.9%) of the pancreatic cancer patients, comprising 5 Syno (+), 10 ChrA (+), and 1 CD56 (+) cases. In cholangiocarcinoma patients, 12 (24.5%) expressed NED markers, including 4 Syno (+) and 11 ChrA (+) cases. Conclusions: This study reveals a significant occurrence of neuroendocrine differentiation in pancreatic cancer and cholangiocarcinoma. The notable prevalence of NED underscores its potential as a reference for tailoring clinical treatments. The association between NED and patient prognosis warrants further investigation.
Small bowel adenocarcinoma: A SEER database analysis.
Authors: Isaac Sangeetha , Pasha Mohammed Afraz , Hussain Ali , Zareef Sumaira , Arora Aakriti , Valasapalli Srijan , Mainkar Nayan , Tasleem Azka , Paracha Munizay , Muzaffar Mahvish
Published: July 2024

e16383

Background: Small bowel malignancies (SBM) account for about 3% of all gastrointestinal malignancies. Small bowel adenocarcinoma (SBA) accounts for the majority of the SBM. SBA is associated with poor prognosis and treatment options are limited in patients with advanced cancer. We analyzed SEER data to study the factors that impacted survival in patients with SBA. Methods: We reviewed data on the SEER database (version Stat 8.4). We extracted data to include patients with adenocarcinoma with labeled primary site as small bowel diagnosed between 2000-2019. We excluded other histology. Variables included were age at diagnosis, race, gender, stage at diagnosis, and grade of malignancy. Chi-square test was used to analyze the association between each variable and survival. Results: We identified 3415 cases of SBA that met our inclusion criteria. The number of annual cases increased from 2000-2019. The mean age was 65.3 years (range 57-75 years). The Male to Female ratio was 11:9. 76% were white, 13.7% were black, 13% were others. Duodenum was the most common primary site with 58%, jejunum at 15.5%, ileum at 13%, and 13.5% overlapped sites or unknown. SEER combined summary stage at diagnosis was 32% regional, 18% localized, 29% distant, and 23% unknown. 6% was grade I, 37% grade II, 27% grade III, 1% grade IV, and 28% unknown. Median survival in patients with SBA was 13 months. The median survival for patients less than or equal to 60 years was 24 months compared to 11 months in patients over 60 years of age (p < 0.0001). Median survival in males was 13 months vs 12 months in females, (p = 0.548). There was no significant difference in survival per race (p = 0.5849). In this cohort, jejunal adenocarcinoma had better outcomes with a survival of 27 months (p < 0.0001). Grade I and II were associated with better outcomes with survival of 21.5 months and 24 months (p < 0.0001). Multivariate analysis showed that age less than 60, early-stage disease, jejunal primary site, and low-grade disease were associated with a better outcome. Conclusions: The number of cases of SBA in the SEER database has increased over the last few decades. SBA is associated with poor outcomes and our analysis shows that patients with early-stage disease, and younger age have better outcomes. Management of SBA is based on retrospective data and data extrapolated from management of colon adenocarcinoma, due to sparsity of prospective data. Clinical trials are needed to identify appropriate therapeutic options for the management of SBA.
Unveiling inequalities: An analysis of treatment disparities of primary gallbladder neuroendocrine tumors by race, ethnicity, and socioeconomic status from the National Cancer Database.
Authors: Mohsin Aleenah , Ganiyani Mohammad Arfat , Ahmad Shahzaib , Podder Vivek , Garje Rohan
Published: July 2024

e16385

Background: Gallbladder neuroendocrine tumors (NETs) are exceedingly rare tumors and carry a poor prognosis. Racial/ethnic disparities and socioeconomic status have been known to influence cancer treatment and outcomes. This study explores racial/ethnic and socioeconomic disparities in treatment patterns of primary gallbladder NETs, focusing on factors affecting receipt of chemotherapy and multimodal therapy. Methods: We analyzed primary gallbladder NETs patients using the National Cancer Database (NCDB) from 2004 to 2020. Racial groups were divided into White and Black categories, and then those groups were further divided into Hispanic White, non-Hispanic White, Hispanic Black, and non-Hispanic Black categories according to ethnicity. We considered socioeconomic factors, tumor histology, and facility type. Logistic regression was used to determine the odds of receiving chemotherapy and multimodality therapy. The significance of disparities was determined using odds ratio (OR) and p-value. Results: Of 1,195 primary gallbladder NET patients, 59% (708 patients) underwent surgery. These patients had a median age of 65 years, with a female majority (64%) and predominantly White ethnicity (73.6%). Insurance coverage varied, with 48.9% having Medicare and 35.6% private insurance, while 3.9% were uninsured and 8.6% were covered by Medicaid. The study highlighted key factors affecting the receipt of surgery. Notably, racial disparities were apparent, with Black patients less likely to receive surgery compared to White patients (OR: 0.52; P < .001). Furthermore, patients with typical carcinoid tumors were markedly more likely to receive surgery than those with other histology (OR: 10.93; P < .001). The type of treatment facility was influential, with patients in Academic/Research Programs more likely to receive surgery (OR: 0.41; P < .001) than those in Community Cancer Programs. Conclusions: This study highlights racial and socioeconomic disparities in chemotherapy and multimodality therapy for gallbladder NETs, with Black, uninsured, and Medicaid-insured patients less likely to receive treatment. These findings call for targeted policy and healthcare reforms to ensure equitable access and outcomes for all patients with this condition. [Table: see text]
Prognostic nomogram, demographics and comparative analysis of prostate small cell and large cell neuroendocrine carcinoma.
Authors: Karki Nabin R , Khan Yasinzai Abdul Qahar , Ullah Asad , Lee Kue Taylor , Chaudhury Tristin , Chaudhury Hannah , Chandasir Abdullah , Waheed Abdul , Khan Marjan , Goyal Aman , Sohail Amir , Del Rivero Jaydira
Published: July 2024

e17010

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences from common types of prostate cancer. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was found to be 71.5 years and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasians (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients of stage 3 tumors, as well as patients who underwent surgery and radiation. The nomogram also indicated a slight increase in mortality with tumors of greater size. Conclusions: Small-cell and large-cell neuroendocrine carcinomas of the prostate are rare; their aggressive nature calls for a deeper understanding and improved prognostic tools. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging arena of oncology.
Decade of insights: Bleomycin-induced pneumonitis and use of G-CSF in chemotherapy-treated germ cell testicular tumors and Hodgkin lymphoma—Real-world outcomes from an academic cancer center.
Authors: Shah Manan , Mortazavi Amir , Folefac Edmund , Wang Peng , Collier Katharine A. , Meng Lingbin , Slavens Kelly , Hinkley Meghan , Monk Paul , Bond David Alan
Published: July 2024

e17013

Background: Bleomycin induced pulmonary toxicity (BIP) occurs in 4-10% of treated patients. Preclinical reports suggest G-CSF use may increase BIP risk, due to neutrophil migration to lung tissues. Limited real-world clinical data is available and G-CSF use may reduce risk of treatment related toxicity with curative bleomycin combination treatment. Methods: We conducted a retrospective study of patients with GCT (Germ cell tumor) and HL (Hodgkin’s lymphoma) receiving bleomycin containing chemotherapy and at-least on dose of G-CSF at The James Cancer Center from 2010-2022 using the institutional database. BIP was diagnosed mainly using clinical symptoms complemented by radiological evidence when possible. We reviewed 361 patients, 145 in GCT group and 216 in HL group and clinically relevant information was recorded.Descriptive statistics for the study variables were presented using frequencies and percentages overall. The bivariate associations between G-CSF use and clinical outcomes were assessed using chi-square tests or fisher’s exact tests for the overall sample, and by chemotherapy type. We used SPSS 26.0 for all the statistical analyses, and an alpha level of 0.05 (two-sided) was used for all the tests. Results: Data on 361 patients, including 145 GCT and 216 HL patients treated with at least one dose of bleomycin was available. The median age was 36.3 years in the GCT group and 44.2 years in the HL group.144 patients in the GCT and 50 patients in the HL group received at least 1 dose of G-CSF. BIP occurred in 4.8% in the GCT and 7.4% of patients in the HL group. Only 2 out of 16 patients developing BIP in the HL group received G-CSF. All patients with BIP developed symptomatic disease. On bivariate analysis, no association was noted between BIP and G-CSF in either group (p-value =1.00 in GCT and p-value = 0.32 in HL). Febrile neutropenia (FN) was reported in 4 patients in the GCT group and 29 in the HL group. In the HL subgroup, 28 (28/29) patients developing FN did not receive G-CSF (p-value=0.0008). All patients who developed FN required hospital admission. Conclusions: Use of G-CSF in patients receiving bleomycin was not associated with an increased incidence of BIP. Incidence of FN was higher in patients not receiving G-CSF leading to hospital admissions. [Table: see text]
Metastatic testicular cancer (TC) presentations and outcomes: A contemporary analysis based on the National Cancer Database (NCDB).
Authors: Yu Eun-mi , Wang Hongkun , Hwang Min Woo , Aragon-Ching Jeanny B.
Published: July 2024

e17016

Background: While most cases of testicular cancers are cured, patients with metastatic or refractory disease continue to have a poor prognosis in recent years (Shah et al; Urology 2023). We sought to determine sites of metastases and survival based on the National Cancer Database (NCDB). Methods: We extracted patient-level data from the NCDB during 2004 to 2020, and identified incidence, demographics, regional differences, treatment, metastatic sites and outcomes in men who had testicular cancer diagnoses (non-seminoma, NS; seminoma, S) with differences in metastatic presentation and outcomes. Results: There were 89550 pts in all, 51623 S pts and 37927 NS pts. Median age for S pts was 37 years and NS was 29 years. 81571 pts were White, 2860 pts were Black. 5396 S pts identified as Hispanic (H) and 5609 NS pts H with other races/unknown for the rest. More S patients were treated at comprehensive community cancer programs (17%) compared to NS pts (6.1%). The majority of patients had a Charlson-Deyo Score of 0 (92.7% of S pts and 93.7% of NS pts), had private insurance (74.1% S pts, 69.1% NS pts). Most were diagnosed with Stage I (29.6%) and Stage II and III (16.3%) though it was unknown/missing for 54%. Overall survival (OS) was better for S compared to NS in all pts (p<0.0001), and in stages II & III (p<0.001). OS was similar for S compared to NS for brain metastasis presentation (p=0.6776), lung (p=0.8967), liver (p=0.1688), but better for S compared to NS for bone metastases (p=0.0002) and distant lymph nodes (p=0.0.0392). Conclusions: Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma in bone and distant lymph node metastases though not for brain, lung and liver metastases, highlighting the need for better therapies for the poorest prognostic groups of TC patients.
Brain metastases in testicular cancer: A single-institution experience in Guatemala.
Authors: Molina Estrada Allan Keithel , Marroquin Flores Diana Beatriz
Published: July 2024

e17019

Background: Brain metastases secondary to germ cell tumors develop in 2 to 3% of patients, in addition to implying a poor prognosis, its incidence in advanced stages increases to 10-15%. The European Urology Association guidelines recommend performing imaging studies using MRI or brain contrasted tomography to rule out metastases in patients with multiple lung metastases, or high beta subunit of human Chorionic Gonadotropin (β-HCG) values, or those in the poor-prognosis International Germ Cell Cancer Collaborative Group (IGCCCG) risk group. Methods: Retrospective descriptive study in patients with brain metastasis for testicular cancer at the Liga Nacional Contra el Cáncer – INCAN Guatemala, from 2018 to 2022. From medical records, we obtained: demographic, clinico-pathological and treatment data. Median was calculated for age, while frequencies and percentages were computed for the categorical variables. Results: Of the 238 patients diagnosed with testicular cancer, 22% (52) presented a β-HCG above 5,000 IU/L, of which 27% (14) developed brain metastases with a mean age of 28 years. Corresponding to 6% of the total cases studied. Among histological subtypes the most common was choriocarcinoma (43%), follow by mixed germ cell cancer (36%), embrionary carcinoma (14%) and classic seminoma (7%). All of the patients belonged to prognostic group S2. Most patients reported first symptom was headache (42%), followed by seizures (21%), cognitive dysfunction (15%), motor dysfunction (10%) and others (12%). Management of these patients included: orchidectomy in all of them, 57% (8) of patients died, of them 50% (4) of patients died before any other therapy. The rest of them, received chemotherapy and none received radiotherapy or surgery for the brain metastases. Conclusions: The presence of brain metastases in testicular cancer increases the mortality produced by the disease as previously reported in other regions of the world, reason why the early suspicion of it, should prompt the evaluation with a brain MRI or computed tomography.
Comparing patient profiles and treatment outcomes with radium-223 (223Ra) in real-world settings: Academic vs. community practice in the US—Insights from the REASSURE study.
Authors: Higano Celestia S. , Brookland Robert K. , Conti Peter S. , George Saby , Given Robert , Mantz Constantine , Sylvester John , Taplin Mary-Ellen , Babajanyan Svetlana , Korn Matthew J. , Meltzer Jeffrey , Parkin Jacqueline , Tomaszewski Jeffrey , Sartor A. Oliver
Published: July 2024

e17040

Background: Our aim was to evaluate two distinct clinical settings catering to US patients with metastatic castration-resistant prostate cancer (mCRPC): academic (A) and community (C) practice. We used data from a real-world non-interventional study (REASSURE; NCT02141438) examining the use of 223Ra. Methods: Patients with mCRPC who received at least one dose of 223Ra in the US were included. Enrolment occurred between 2014 and 2017; median follow-up was nearly 12 months. Our analysis included patient disease characteristics, treatment history, short- and long-term safety of 223Ra, patient overall survival (OS), and patient-reported pain (Brief Pain Inventory – Short Form [BPI–SF] scores). A clinically meaningful pain response was a ≥2-point decrease from a baseline score of ≥2 in the BPI-SF worst pain item during treatment until last dose. Results: Analysis included 498 patients (A: 147; C: 351). Comparing A with C, the median ages were 70 and 76 years, respectively, and the majority of patients (74% and 84%) had bone-only metastases. A higher percentage of patients in A (69%) than in C (49%) had completed at least one life-prolonging therapy (LPT) prior to 223Ra; these included abiraterone (A: 38%; C: 19%), enzalutamide (A: 32%; C:17%), docetaxel (A: 38%; C: 19%), and sipuleucel-T (A: 18%; C: 25%). Most patients received 5–6 223Ra injections in both settings (A: 65%; C: 71%). 223Ra was used concomitantly with LPTs in 48% of patients in A and 57% in C, predominantly with abiraterone (A: 25%; C: 25%) or enzalutamide (A: 25%; C: 36%); fewer patients in A (35%) received concomitant bone health agents than in C (52%). For safety outcomes, refer to the table. During treatment, 47% and 62% of patients with a baseline BPI-SF ≥2 had a clinically meaningful pain response in A and C, respectively. The median OS was 17.2 months (95% CI 14.0–19.4) in A and 18.4 months (14.8–21.0) in C. More patients in A (42%) than in C (26%) received a LPT after 223Ra, most commonly docetaxel (A: 25%; C: 12%). Conclusions: Patients treated in A tended to be younger and more heavily treated, as evidenced by a higher number of patients receiving LPTs prior to and following 223Ra treatment. Bone health agents were more frequently used in C. Additionally, more patients in C had a clinically meaningful pain response and more drug-related AEs were reported in A. Despite the observed differences, overall survival was comparable for both practice settings. Clinical trial information: NCT02141438 . [Table: see text]
Cardiotoxicity in tumor-bearing mice receving thoracic radiation plus tumor radiation and PD-1 inhibitor therapy.
Authors: Liu Yao , Su Shengfa
Published: July 2024

e20509

Background: At present, most preclinical studies explore the cardiotoxicity caused by radiotherapy combined with Anti-PD1s in tumor-free mice. we assessed the overall cardiotoxicity of radiotherapy combined with Anti-PD1, the possibility that blocking HMGB1 does not affect the anti-tumor effect, and the possibility that radiotherapy combined with Anti-PD1 reduces heart damage in tumor-bearing mice. Methods: 25 tumor-bearing C57BL/6 mice on both hind limbs were treated with anti-PD1 or PBS or Anti-HMGB1 with or without thoracic irradiation 20gy and right hind limb tumor 8gy×3F irradiation. HE staining was used to observe the cardiac structure and morphological changes. Flow cytometry was used to observe the distribution of CD3+, CD4+, CD8+T cells in cardiac and peripheral blood. Cardiac function was examined by echocardiography. The expression of myocardial injury marker LDH in peripheral blood was detected by Elisa. Results: Five group was established:A = Control;B = anti-PD1,C = RT,D = RT+Anti-PD1,E = RT+Anti-PD1+Anti-HMGB1.HE showed the myocardial injury in A(without any treatment) was the most severe,and and B and D was slightly severe than C group, administration of Anti-HMGB1 partially attenuated myocardial injury in D. Elisa showed the LDH of A was highest, B were consistent with D in LDH expression, RT was lower. Cardiac function showed no difference in ejection fraction and fractional shortening in five groups. Peripheral blood flow cytometry showed the absolute counts of CD3+T-cell and cd8+T cells were greatest in B group, followed by A, C, D, and E groups. Absolute CD4+ T cell values were highest in the B. The results of myocardial tissue infiltrating lymphocytes showed that the absolute CD3+T-cell and cd8+T cells counts were biggest in the B group, followed by A, C, D, and Egroups. Absolute CD4+T cell counts were highest in B group. C, D had the best anti-tumor effect, and the use of Anti-HMGB1 partially attenuated the cardiac injury caused by D group. Conclusions: (1)Without any treatment, the cancer cachexia induced by tumor will cause serious damage to myocardial. (2) The overall cardiotoxicity of radiotherapy combined with Anti-PD1 group was only slightly increased compared to RT or anti-PD1 alone. Maybe radiotherapy killed part of the Anti-PD1-activated lymphocytes, only resulting in a slight increase in cardiac infiltrating lymphocytes. Anti-HMGB1 maintain the anti-tumor effect of RT+Anti-PD1 and partially attenuated the cardiac damage. [Table: see text]
Are the results of clinical trials in patients with NSCLC reflected in real life? The Registurk-Lung study.
Authors: Artac Mehmet , Yildirim Mahmut Emre , Sümbül Ahmet Taner , Ozturk Akin , Karadurmus Nuri , Koral Lokman , Demirci Umut , Arslan Cagatay , Gumus Mahmut , Kefeli Umut , Ercelep Ozlem , Celik Sinemis , Bozkurt Oktay , Oven Bala Basak , Cubukcu Erdem , Karaca Mustafa , Bilici Ahmet , Tural Deniz , Harputluoglu Hakan , Dane Faysal
Published: July 2024

e20512

Background: Evaluation of real-world data together with data in clinical studies is very important in the evaluation of treatment algorithms. In real life, treatments are applied to the elderly, patients with poor performance and unusual groups with comorbidities. Determining these treatment results is important in the creation of treatment algorithms. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 4250 patients without driver mutation, metastatic non-small cell lung cancer were recorded between December 2021 and December 2023 in 42 centers representing the whole country. The demographic, histopathological, molecular and clinical data of the patients were recorded. The relationship between progression-free survival (PFS) time and overall survival (OS) time with these characteristics was investigated. Results: 4250 patients were evaluated. The median age was 64 (26-90) years and 15.1% of the patients were female. The proportion of patients who never smoked was 10.4 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. PDL-1 level was higher than 50% in 24.0% of patients and < 1 in 40.4% of patients. Only 11.8 percent of patients received single agent immunotherapy or chemoimmunotherapy. Other patients had received only a combination of doublet chemotherapy. The PFS was 6.9 months (95% CI: 6.4-7.3) and OS 14.6 (95% CI: 12.3-16.8) months in the whole patient group. Compared to the group that received chemotherapy alone, PFS and overall survival were longer in the group that received chemoimmunotherapy. This difference between the two groups was found to be statistically significant (p:0,001 and 0,031 respectively). Conclusions: As shown in clinical studies, immunotherapy alone or chemoimmunotherapy according to PDL-1 expression status provides a significant survival contribution compared to chemotherapy alone.
Real-world effectiveness and safety of amivantamab for exon 20 EGFR-mutant non-small cell lung cancer (NSCLC) in French early access program: Amexon 20 GFPC.
Authors: Pierret Thomas , Guisier Florian , Daniel Catherine , Descourt Renaud , Galland Loick , Molinier Olivier , Decroisette Chantal , Cortot Alexis B. , Moreau Diane , Bigay-Game Laurence , Wislez Marie , Cloarec Nicolas , Curcio Hubert , Delberghe Nicolas , Cadranel Jacques , Duchemann Boris , Toffart Anne-Claire , Moreau Lionel , Greillier Laurent , Auliac Jean-Bernard
Published: July 2024

e20529

Background: Amivantamab is a bispecific EGFR/MET antibody approved for patients with NSCLC with EGFR exon 20 insertions. In France, early access has made it possible to use it as a second or further-line treatment after at least one line of chemotherapy. Methods: This is a retrospective multicentric cohort of consecutive patients with an adenocarcinoma and EGFR exon 20 insertions, who received at least one dose of amivantamab as part of the French early access program from September 3th, 2021 (date of approval in the French early access program) until April 30th, 2022. Patients gave consent for the data collection and were enrolled in 28 sites. Primary end point was Real world Progression free Survival (Rw PFS) and secondary endpoints were description of clinical characteristics, best response, duration of treatment, overall survival (OS), CNS activity, toxicities and subsequent treatment. Results: Thirty-nine patients received amivantamab in early French access. Median age was 60 years [39-83]; 64 % of patients were female and 54% never smoker; 33% had PS 2 or more and 66 % had brain metastasis at inclusion. Amivantamab was administered as a second or third line and more in 30% and 70% of patients respectively. Patients received a median number of 10 injections [1-47]. Overall, 37 patients were evaluable for response; response rate was 35 % and disease control rate (DCR) was 62%. After a median follow-up of 11.3 months [8-16.7], median Rw PFS and OS were 3.5 months [2.6-5.8] and 11.3 months [8-17.8] respectively. Rw PFS and OS at 6 months were 33.3% and 74.4% respectively. Duration of response was 5.8 months [2.3-11.9]. Overall, 23 patients were evaluable for CNS response; 26 % had CNS response and CNS DCR was 69%. Main sites of progression were lung (43%), bone (28%), liver (12.8%) and brain (10%). Grade III/IV adverse events were reported in 11 patients (28.2%), mainly skin toxicity (n = 5), infusion reaction (n = 2), digestive disorders (n = 1), interstitial pneumonia (n = 1), neurological disorders (n = 1), fever (n = 1). Amivantamab was permanently discontinued due to toxicities in 4 patients (10.3%). Subsequent treatment was administered to 21 patients (53.8%) after amivantamab, mostly consisting of mono chemotherapy (n = 13). Conclusions: Our real-world multicenter analysis showed that amivantamab was an effective monotherapy treatment in second line and after for patients with EGFR exon 20 insertions. No new toxicities were reported.
Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on lung cancer.
Authors: Bendale Yogesh Narayan , Shastry Padma , Pujari Radha , Nagre Surendra , Khot Nandinee , Kadam Avinash
Published: July 2024

e20573

Background: In contemporary allopathic medicine, intravenous administration of Arsenic trioxide is extensively investigated for its diverse applications in cancer treatment. However, the associated adverse effects demand exploration of alternative formulations. In present study, we propose the patented green technology-based compound “oral Arsenic Trioxide” (NTAX-44), in its unique form that can be administered orally, thereby reduces cost of treatment. This product presenting itself as a promising candidate for cancer therapy. Despite the ethnopharmacological uses of arsenicals in medicine, comprehensive understanding of their safety and efficacy remains limited. Thus, present study is proposed to investigate anticancer potential of NTAX-44 in lung adenocarcinoma cancer cell line A549. Methods: The effect of oral NTAX-44 was assessed on the viability of cell lines grown as 2D monolayers by MTS assay and 3D multicellular spheroid (MCS) model. Anti-metastatic potential of NTAX-44 was studied by using migration and colony formation assay while, expression of PD-L1 in A549 cell line treated with Arsenic Trioxide was checked by flow cytometry. The anti-metastatic capacity and cytocompatibility testing of Arsenic Trioxide was evaluated by in ovo chick embryo yolk sac membrane (YSM) angiogenesis assay and MTS assay using PBMCs respectively. Results: NTAX-44 is found to be effective to inhibit viability of A549 cell line (IC50 21.47±1.7 μg/ml for 48 hr and 14.65±0.92 for 72 hr of treatment); exhibiting its anti-proliferative activity. The A549 spheroids showed comparatively more resistance with loss of viability at higher concentration (50 and 100 µg/ml). Statistically significant decrease in scratch repair rate was observed at 24 hr and 72 hr of treatment and showing anti-migratory activity in A549 cells. In colony formation assay, complete inhibition of the colonization of A549 cells was observed after 48 hr of treatment; the survival fraction identified as 0%. NTAX-44 at 25µg/ml concentration inhibited PD-L1 expression in A549 cells, suggesting its potential to decrease expression of PD-L1 on tumor cells resulting in reversal of immune suppressive tumor microenvironment. Treatment of YSM with NTAX-44 resulted in approximately 40% inhibition in formation of quaternary blood vessels comparable to Bevacizumab (Avastin®). This significant anti-angiogenic potential is suggestive of its in vivo anti-metastatic effect. Notably, cytocompatibility testing of NTAX-44 at concentrations up to 200μg/ml was well-tolerated in PBMC cells emphasizing its favourable biocompatibility profile, providing crucial insights into its safety. Conclusions: Inhibitory effect of NTAX-44 on cell proliferation serves as a noteworthy attribute in context of its potential therapeutic utility against lung cancer. Its cytocompatibility further indicates application of arsenic trioxide as a candidate for clinical application.
Effects of lack of access to cancer medication on survival of patients with lung cancer.
Authors: El-Halabi Laura Nasser , Hodroj Mohammad Hassan Mahmoud , Rammal Firas , Ghais Ali , Tfayli Rami , Bou Orm Abdallah , Charafeddine Maya , Tfayli Arafat H.
Published: July 2024

e20585

Background: Lung cancer is the leading cause of cancer-related death. The treatment has evolved with the introduction of immunotherapy. During the economic crisis in Lebanon, cancer medications became unavailable forcing oncologists to adjust treatment protocols. This study aims to assess the effect of medication shortage on the progression-free survival (PFS) of lung cancer patients treated at a tertiary care center in Lebanon. Methods: A retrospective analysis of patients with metastatic NSCLC treated during the period of drug shortage (October 2021-December 2022) as compared to those treated in 2019-2020. The primary end point was progression-free survival (PFS) on first line of therapy and its association with dose density ratio (dose density given/standard dose density). Electronic medical records of 117 patients were reviewed and data of 83 eligible patients were collected and analyzed using IBM SPSS software. Results: The mean age at diagnosis was 68 years. Of the total, 63.5% were male. Additionally, 14.4% of the patients received chemotherapy, 39.7% received immunotherapy, and 42.1% received a combination of chemotherapy and immunotherapy. In total, 49 patients were eligible in the 2019/2020 category. 84% of the patients had the opportunity to receive immunotherapy. In contrast, 25 patients were eligible in the 2021/2022 category, and only 73% of them had the opportunity to receive immunotherapy. The median PFS of the 2019/2020 category was 11.2 months, compared to 5.4 months in 2021-2022 (p-value of 0.339). PFS was studied based on the dose density ratio for immunotherapy. Twenty-two patients received a full immunotherapy dose with a ratio of 1, and their PFS was 5.43 months. Twelve patients received a dose density ratio ranging from 0.01 to 0.50 and had a PFS of 10 months. Twenty-nine patients received a dose density ratio of 0.51-0.99 and had PFS of 12.8 months. Contrary to our initial expectations, we did not observe a statistically significant difference between the dose density of immunotherapy and PFS values with a p-value of 0.107. Conclusions: Despite significant shortages in immunotherapy medications, our study suggests that this has no significant detrimental effect on PFS. This unexpected discovery challenges the conventional notion that full immunotherapy doses are necessary and prompts further exploration of the complex relationship between dosage and treatment outcomes in patients.