bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of early response in association with pathological response in patients with breast cancer receiving neoadjuvant chemotherapy.
Authors: Wang Yongjiu , Feng Zequn , Liu Xinyu , Yu Lixiang , Li Liang , Zhang Qiang , Fu Qinye , Zheng Chao , Xiang Yujuan , Zhou Fei , Zhou Wenzhong , Guo Mingming , Wang Fei , Yu Zhigang
Published: July 2024

e12628

Background: Neoadjuvant therapy (NAT) has now been widely used for patients with operable breast cancer (BC) to test drug sensitivity. Studies have indicated that early assessment of clinical response to NAT can help identify patients who are resistant to initial regimens, providing an additional opportunity to change treatment plan. However, there is a lack of evidence regarding the optimal timing for conducting early evaluations of clinical response. This prospective study was conducted to evaluate the association between early evaluation of clinical response at different timing (post 2 cycles versus post 4 cycles) and pCR post NAT, in order to determine the most appropriate timing for NAT response evaluation. Clinical evaluations using ultrasound and MRI (magnetic resonance imaging) were also compared. Methods: A prospective cohort study including BC patients who received NAT was conducted between January 2018 and December 2023. Multivariable logistic regression analysis was used to estimate the Odds Ratios (OR) and 95% confidence intervals (CI) for the clinical response evaluated at different timings in association with pCR. The heterogeneity of the associations for the post-cycle 2 and post-cycle 4 assessments was assessed. Linear regression analyses were used to assess the associations between extent of tumor reduction post 2 cycles and that post 4 cycles of NAT. Agreement of tumor measurements using ultrasound and MRI was also assessed. Results: A total of 186 BC patients were consecutively enrolled and included in this analysis. 55 (29.6%) of them achieved pCR. Partial response (PR) post 2 cycles and 4 cycles of NAT were both significantly associated with pCR post NAT, though the point estimate of association for PR post 2 cycles of NAT (OR=5.06, 95%CI:2.29-12.09) was more evident than that post 4 cycles (OR=2.79, 95%CI:1.20-7.21). Extent of tumor reduction post two cycles of NAT was highly correlated with that post four cycles (r=0.89, 95%CI=0.79-0.98, P< 0.01). Poor concordance was observed between ultrasound and MRI measurements of tumor size, whether at initial diagnosis (r=0.66, adjusted r2=0.43) or after two cycles of NAT (r=0.59, adjusted r2=0.35). Among those patients who had PR post 2 cycles of NAT, tumor reduction by greater than 50% was not associated with higher probability of reaching pCR in comparison to those lower than 50% (OR=1.86, 95%CI=0.82-4.37, P=0.143). Conclusions: Tumor response assessed using MRI after two cycles of NAT was highly correlated with pCR, and may be adopted as an optimal strategy for early evaluation of the efficacy of NAT regimen. Further studies are warranted to evaluate changes in treatment plan at early phase of NAT for those resistant to initial regimens.
Demographic disparities influencing survival of patients with glioblastoma.
Authors: Ayoobkhan Fathima Shehnaz , Ganiyani Mohammad Arfat , Pustake Manas , Ahmad Shahzaib , Podder Vivek , Bellur Shreyas S , Howal Prashant , Shah Aditya , Goodman Judie R.
Published: July 2024

e13795

Background: Glioblastoma Multiforme (GBM) is an aggressive brain tumor with a life expectancy of less than a year post-diagnosis despite multimodal therapy. Recent Advancements have significantly prolonged the survival period. However, barriers still exist in survivorship care for minority populations. We aim to delve deeper into understanding these disparities in survival outcomes based on demographic characteristics. Methods: We included patients diagnosed with Glioblastoma Multiforme in the National Cancer Database from 2004-2021. Demographic characteristics were taken into account. Kaplan Meir curve and Log-rank test were utilized to compare survival rates in different groups. Results: A total of 169793 patients were identified from 2004-2021 with an increased incidence in the age groups 64-74. Overall survival has increased steadily since 2011 (2004-2011 OS 8.84 months Vs 10.55 months from 2011-2021 p-value=0.058). Age is an independent predictor of survival. The younger the patient, the better the survival period. Young adults (<50 years) have a better OS of 19.22 months with a decline in age 50-64 (13.22 months), and age 64-74(8.18 months, p value <0.001). Worsen OS is seen in the geriatric population (3.75 months). African Americans (AA) have a better survival period as opposed to Whites (10.91 months Vs. 9.63 months, p value <0.001). Multivariate analysis revealed that age, race and the time frame of diagnosis (before 2011 vs after 2011) have a major role in predicting survival. Conclusions: Demographic disparities seen in the survival patterns, with worse outcomes seen in elderly, White people. Future research directions should be emphasized in the marginalized group White, elderly population. [Table: see text]
Addressing cancer survivorship needs in geriatric survivors: Feasibility of a primary care–based survivorship clinic.
Authors: Ramachandran Maya Kavita , Steele Natasha , Kim Jennifer , Schapira Lidia , Yurkiewicz Ilana
Published: July 2024

e13797

Background: The largest segment of the growing population of cancer survivors is at least 65 years of age, a population that is likely to have comorbidities and requires co-management between primary care and specialist physicians. The goal of this study was to characterize care for this patient population in a specialized primary care for cancer survivorship clinic that manages survivorship issues and ongoing primary care in one place. Methods: This study collected demographic and clinical data via electronic chart review of patients aged 65 and over who established care in the Primary Care for Cancer Survivorship clinic at an academic center from November 1, 2021 through November 30, 2023. Results: Out of 228 total patients who established primary care in the clinic, 63 patients were over the age of 65. The mean age of the group was 73, with the range 65 to 90. Seventy-three percent of patients were female, and 27% were male. The most common cancers were breast (38%), lung (10%), leukemia (13%), lymphoma (8%), prostate (8%), and multiple myeloma (6%). Twenty-five patients (40%) had active disease, 37 patients (58%) were post-treatment, and 1 patient was a “previvor” with Li-Fraumeni syndrome. Cancer surveillance was discussed with 81% of patients, and 2 patients (5% of post-treatment patients) were diagnosed with recurrent cancer. Secondary cancer screening was performed in 86% of patients, with no secondary cancers diagnosed. The most common referral sources were medical oncology from the same institution (40%), self-referrals (25%), and hematology (13%). The average number of visits per year was 2.8 with 61% in person and 29% via video. Cardiovascular risk was addressed in 98% of patients; 32% had at least one cardiovascular medication started and 17% were referred to a cardiologist for management. Long term and late effects were addressed in 84% of patients, including mental health (70%), bone health (65%), cognitive function (21%), cancer-related fatigue (13%), and sexual health (11%). Ten percent had end-of-life issues or goals of care addressed. Conclusions: This study demonstrates the feasibility of a primary care-based cancer survivorship clinic to address the ongoing needs of geriatric cancer survivors. Quality review of these patient encounters can identify gaps in care delivery and inform new models of comprehensive care for the growing geriatric cancer survivor population. [Table: see text]
Travel-associated carbon emissions of patients receiving cancer treatment from an urban safety net hospital.
Authors: Yusuf Hasiya , Gor Rajvi , Memon Roha Saeed , Kumar Abhishek
Published: July 2024

e13812

Background: Climate change is one of the grand challenges of the 21st century. The U.S. currently emits 11% of the annual global greenhouse gases, and 8-10% of its emissions result from the healthcare industry. Studies on the contribution of patients' commute for cancer treatment to healthcare-associated CO2 emissions remain limited. This study aims to determine the CO2 emissions of patients’ commute for cancer treatment among patients with malignancies at an urban safety net hospital. Methods: We conducted a retrospective study of patients seen at an oncology clinic from July 1, 2022 - June 30, 2023. Demographic data, data on visit diagnosis and indication (e.g., laboratory, infusion, or follow-up visits), and patients' home addresses were collected from the EMR. Distance between patients’ homes and the hospital was calculated using a Google Map API and a macro for distance. Total CO2 emissions from patients’ travel in miles were estimated at 400 grams of CO2 per mile based on the Environmental Protection Agency’s estimate of the average CO2 emissions for a passenger vehicle. The primary outcome was CO2 emissions from patients’ round-trip travel. The total estimated CO2 emissions were converted to equivalents of coal burned, smartphones charged, and gallons of gasoline used based on the EPA equivalencies calculator. Results: Of the 8,235 visits, 5,095 (61.8%) were follow-up/laboratory visits, and 3,137 (38.1%) were chemotherapy infusion visits. Of the 1,080 patients who attended the clinic, the mean age was 63.8 years, 700 (64.8%) were males, 379 (35.1%) were females, 525 (48.6%) were black or African American, 139 (12.9%) were whites. Breast cancer was the most common diagnosis, with 423 (39.2%) of patients. Each patient traveled an average of 9.6 miles round trip (Range = 0.7-298.6 miles) to receive cancer care. An estimated 1,520 grams of CO2 was emitted for each patient’s visit. A total of 79,582 round trip miles was made in 8,235 visits, which corresponds to 31,832 kg of CO2 emissions, equivalent to 35,658 pounds of coal burned, 1,462 propane cylinders used for a home, or 3,872,250 smartphones charged. Conclusions: Cancer care is associated with significant CO2 emissions. Efforts to decrease the overall carbon footprint of cancer treatment through adoption of telemedicine and alternative treatment schedules, are needed to reduce the effect of cancer treatment on the climate. [Table: see text]
Stereotactic radiosurgery (SRS) for non-small cell lung cancer (NSCLC) in the oncogene-addicted era: A real-world UK tertiary center experience.
Authors: Mcmahon David , De Boisanger James , John Alexius , Brewer Martin , Cartwright Elizabeth , Manickavasagar Thubeena , Milner-Watts Charlotte , Welsh Liam , Creak Antonia , Yousaf Nadia , Davidson Michael , Bhosle Jaishree , Minchom Anna Rachel , O'Brien Mary E.R. , Popat Sanjay , Solda Francesca , Taylor Helen , Konadu Jessica , Tokaca Nadza , Rosenfelder Nicola
Published: July 2024

e14011

Background: 30-50% of NSCLC patients develop brain metastases (BM). Re-evaluation of the role of SRS is required with evolving understanding of molecular subtypes of NSCLC and increasing intracranial efficacy of systemic agents. Methods: We conducted a retrospective analysis of NSCLC patients receiving SRS at our centre from 05/16-11/23. Primary objective was median overall survival (mOS months). Analysis was performed on Prism 10.1.1. Multivariate analysis was conducted using Cox Proportional Hazards Regression, with age, gender, KPS, BM size, total BM volume and oncogene status as predictor variables. Extraction from medical records was undertaken by authors, with local R&D committee approval. Results: 237 patients were evaluable. 59% (N=139) were oncogene-addicted (oNSCLC) and 41% (N=98) non-oncogene-addicted (non-oNSCLC). Median duration of follow up was 43.3m. m OS was 11.9m overall. For oNSCLC mOS was 13.1m vs 8.8m for non-oNSCLC (HR 1.49, P=0.02). mOS was 20.7m for EGFR sensitizing NSCLC (N=48) vs 10.5m without (HR 1.40 P=0.12). mOS for ALK+ (N=22) was 29.3m vs 11.6m for non-ALK+ (HR 1.90, P=0.05). mOS for KRAS+ (N=32) was 11.6m vs 12.0m without (HR 0.91, P=0.68). Significantly inferior mOS was seen for single (N=186 [78%]) vs multiple (N=51[22%]) SRS courses (8.4m vs 38.8m, [HR 0.34 P=<0.0001]). SRS at diagnosis of BM (N=118) had a mOS of 12.3m vs at nadir (N=9, not reached [HR0.44, P=0.18]), progression on 1st line TKI (N=31, 22.1m [HR 1.1, P=0.79]) and at any other time (N=157, 7.8m [HR 1.33, P=0.11 ]). There was no significant difference in survival for patients diagnosed with brain metastases at the diagnosis of metastatic disease compared to those who developed brain metastases during their disease course (12.3m vs 10.6m [HR 1.18, P=0.33]). Survival of those with 1 site of metastatic disease (18.3m) was numerically improved compared to those with 2 (10.7m, HR 1.26, P=0.25) sites, and statistically significant compared to those with 3 (10.1m, HR 1.69, P<0.02) and ≥4 (4.4m, HR 4.41, P<0.0001) sites. Conclusions: Median OS in oNSCLC was superior to non-oNSCLC, driven by numerically superior survival in EGFR+ and ALK+ cohorts. Significantly improved OS was observed in patients with multiple vs single SRS treatments, however this may be confounded by biases. Patients treated with SRS at nadir had numerically superior OS to those treated at other timepoints, however this must be interpreted with caution due to small sample size. Further prospective research is needed to interrogate these findings and guide local therapies in NSCLC with BM. [Table: see text]
Alterations of the tumor microenvironment (TME) in recurrent glioblastoma following apatinib in combination with temozolomide.
Authors: Zhang Junping , Ge Jingjing , Li Cheng , Xue Fengjun , Zhao Chi , Kong Chenchen , Qi Shaopei , Duan Qianqian , Zhang Qin , You Xia
Published: July 2024

e14018

Background: Glioblastoma (GBM) is the highly malignant primary central nervous system tumor. The standard treatment for glioblastoma is maximal surgical resection followed by concomitant radiotherapy and temozolomide chemotherapy, but patient’s survival still remains poor. At present, apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Methods: This retrospective study was enrolled 22 rGBMs treated with apatinib in combination with TMZ and 6 patients who received standard radiotherapy combined with TMZ and experienced recurrence. At the same time, we collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. In prognosis analysis, long survival benefit is defined as a PFS≥4.2 months, and short survival benefit is defined as a PFS<4.2 months. This PFS threshold was primarily referenced from a Phase III study of bevacizumab combined with chemotherapy for rGBM. The study was approved by the institutional ethics committee of Sanbo Brain Hospital, Capital Medical University (SBNK-YJ-2021-010-02) and informed consent was also obtained from the patients. Results: The differential gene of pre and post standard chemoradiotherapy results suggest that standard treatment has reduced the expression of genes associated with tumor proliferation and up-regulated the expression of the genes associated with the immune response in rGBM. In apatinib combined TMZ patients, compared to the non-response group, the response group had significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, compared with the short-survival benefit group (< 4.2 months), four tumor progression-associated genes were down-regulated in response group (≥4.2 months). Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Conclusions: Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment. Clinical trial information: NCT04814329 .
Analysis of transition metals in glioblastoma tumor and plasma samples.
Authors: Shenoy Ganesh , Kuhn Madison , Sahu Aurosman , Khristov Vladimir , Heebner Madison , Wilding Hannah E. , Clegg Taylor , Bhanja Debarati , Wade Quinn , Liermann Laura J. , Wang Dongxiang , Smith Nataliya , Khunsriraksakul Chachrit , Palsa Kondaiah , Slagle-Webb Becky , Mansouri Alireza , Zacharia Brad , Proctor Elizabeth , Connor James
Published: July 2024

e14029

Background: Transition metals such as copper, iron, zinc, and manganese are known to play essential roles in human physiology as evidenced in conditions where these metals are dysregulated. The role of transition metals in glioblastoma biology has been largely understudied. Here we investigated whether plasma and tumor transition metal content is associated with glioblastoma patient outcomes. Methods: Transition metal content was measured in 31 glioblastoma tumor samples, 21 of which had matched plasma samples, using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES). Concentrations of transition metals in plasma and tumor were then then correlated with clinical parameters including median overall survival (mOS) as well as plasma cytokines. Results: Spearman correlation analysis of transition metals in glioblastoma tumor samples found that tumor manganese and tumor zinc (R = 0.52, p = 0.0048) as well as tumor copper and tumor zinc (R = 0.36, p = 0.038) were positively correlated. Plasma transition metal content did not correlate with tumor transition metal content. Kaplan-Meier and Cox regression survival analysis between high and low expressors of each respective transition metal, separated at the median, revealed that high plasma iron content was associated with prolonged survival (median overall survival: 30.1 vs 12.4 months, P = 0.0036). Plasma from glioblastoma patients in the high plasma iron group had increased levels of IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004). Plasma or tumor concentrations of copper, zinc, or manganese did not associate with survival. Conclusions: Increased plasma iron content is associated with prolonged survival as well as increased plasma IFN-β levels, suggesting a possible link between iron and immune responses in glioblastoma patients.
Impact of next generation sequencing in high grade glioma management.
Authors: Barry Simon , Mustafa Yazan Hani , McGibney Carol , Royo Laura , Higgins Martin , Mohammed Wail , Iqbal Mahzar , Lim Chris , Janssen Michael , Bermingham Niamh , Faisal Jamaluddin Muhammad , O'Sullivan Michael , Kamel Mahmoud , O'Reilly Seamus , Bambury Richard Martin , Gleeson Jack
Published: July 2024

e14031

Background: Recent advances in genomic profiling have improved our understanding of the molecular pathogenesis of high grade gliomas. Increased availability of high-throughput Next Generation Sequencing (NGS) allows the identification of genetic alterations which could direct personalized cancer treatments for HGG patients. Methods: All patients with high grade glioma (WHO Grade ≥3 glioma by 2016 or 2022 classification) in our institution, who underwent NGS testing between 2019-2023, were identified from a prospectively maintained electronic database. NGS results, from the Oncomine Precision Assay, a multi-gene panel which tests for 50 different mutations, were collated. Medical records were systematically reviewed to collect demographic, treatment and survival data. Alterations detected on NGS were characterized using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Results: 53 patient samples underwent NGS testing (34 males [64%]; 19 females [36%]). Median age at diagnosis was 52 years (range: 20-72 years). Thirty patients (57%) had an ECOG PS 1 at first clinical review. 18 tumors (34%) were found to have MGMT promoter hypermethylation. 28 patients (53%) were found to have potentially actionable alterations according to the ESCAT scale; 19 (35%) EGFR mutations (ESCAT IIIA level evidence) were detected, 5 PIK3CA (9%) mutations (ESCAT IIIA), 3 FGFR3 (6%) alterations (ESCAT IIB), 2 patients with CDK 4 (4%) copy number gain (ESCAT IIIA), 2 PTPRZ1-MET (4%) fusions (ESCAT IIIA) and 1 BRAF V600E (2%) mutation (ESCAT IB). 4 patients were found to have multiple mutations on NGS. 1 sample had insufficient tissue for analysis. 2 patients (4%) were considered for targeted therapy based on NGS results (1 BRAF V600E mutation and 1 FGFR3 alteration) but both deteriorated in advance of commencing treatment. One patient received nivolumab for MSI-H recurrent GBM (ESCAT IIIB) but progressed within 3 months of commencing treatment. Conclusions: Despite advances in our understanding of the pathogenesis of these high grade gliomas and improved awareness of molecular targets, the delivery of targeted therapy to patients with HGG remains challenging. Rapid access to targeted therapy via compassionate access programmes and improved availability and access to clinical trials for patients with rare cancers and molecular alterations, is paramount.
Beyond scalpels: A meta-analysis of robotic and laparoscopic gastrectomy in long-term oncological outcomes in gastric cancer.
Authors: Silva Caroliny , Hespanhol Larissa , Oliveira João Pedro , Silva Isadora Mamede Mendes da , Vilbert Maysa , Araújo-Filho Irami
Published: July 2024

e16125

Background: Gastric cancer persists as a substantial worldwide health concern, serving as a prominent contributor to both the incidence and fatalities associated with cancer. In this context, robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in patients with gastric cancer is a subject of extensive scientific investigation, reflecting the ongoing evolution of minimally invasive surgical techniques. RG has been posited as a potentially advantageous alternative to LG, as it is associated with improved precision and maneuverability, particularly in complex anatomical scenarios. Conversely, LG, with its established history and widespread adoption, is characterized by a shorter learning curve and potential cost advantages. Scientific literature suggests comparable outcomes between the two techniques, while others report divergent results in terms of operative time, blood loss, and complication rates. However, the impact of both techniques in long-term oncological outcomes remains unclear. Therefore, we aimed to perform a systematic review and meta-analysis for RG and LG for oncological outcomes in patients with gastric cancer. Methods: A systematic search was performed in PubMed, Cochrane and Embase in January 2024 for randomized controlled trials or observational studies comparing RG with LG in patients with gastric cancer. Risk ratios (RR) for binary outcomes with a 95% confidence interval (CI) were pooled and a p-value < 0.05 was considered statistically significant. Rayyan and Review Manager 5.3 software were selected, respectively, to manage the reported references and perform the statistical analysis of this study. Results: A total of 3727 results were screened, of which 13 were included in the meta-analysis, totalizing 25428 patients. There were no differences between RG and LG for 3-year overall survival (RR 1.03, 95% CI 1.00 - 1.06, I2 = 50%, p = 0.06), 3-year disease free survival (RR 1.01, 95% CI 0.95 - 1.06, I2 = 45%, p = 0.82), recurrence free survival (RR 0.51, 95% CI 0.22 - 1.20, I2 = 100%, p = 0.12), 5-year disease free survival (RR 1.02, 95% CI 0.99 - 1.05, I2 = 0%, p = 0.23), and ≥ 3-year overall survival (RR 1.02, 95% CI 1.00 - 1.05, I2 = 38%, p = 0.03). Conclusions: These findings from this comprehensive meta-analysis reveal a lack of discernible disparity between RG and LG in terms of oncological outcomes. The collective evidence suggests comparable results, emphasizing the need for continued research to refine our understanding and guide clinical decision-making in the pursuit of optimized patient care. These results contribute to the ongoing dialogue surrounding optimal treatment strategies for the assessed condition.
Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.
Authors: Li Hongli , Ge Shaohua , Zang Fenglin , Ren Peng , Cao Fuliang , Liu Rui , Yang Yuchong , Ning Tao , Bai Ming , Wang Xia , Ji Zhi , Duan Jingjing , Liang Han , Ba Yi , Deng Ting , Deng Jingyu
Published: July 2024

e16128

Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-Fu 2600 mg/m2, q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .
Preliminary data of a phase Ib/II trial evaluating the efficacy and safety of adebrelimab, camrelizumab plus apatinib as first-line therapy in patients with advanced hepatocellular carcinoma.
Authors: Long Yin , Yang Qiong , Huang Ziqi , He Xiaodong , Huang Jue , Liao Jianguo , Chen Yajin , Hu Hai , Zhang Lei
Published: July 2024

e16221

Background: The CARES-310 study has demonstrated that the combination of the anti-PD-1 antibody camrelizumab and the VEGFR2 tyrosine kinase inhibitor apatinib exhibits improved progression-free survival (PFS) and overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). We conducted this study to investigate whether the addition of the anti-PD-L1 antibody adebrelimab to camrelizumab and apatinib would further improve clinical outcomes. Methods: This is a prospective, phase 1b/2 clinical trial employing the i3 + 3 dose escalation design. Eligibility includes adults with unresectable or metastatic HCC, a ECOG PS of 0 or 1, a Child-Pugh score ≤ 7, and at least one measurable lesion per RECIST v 1.1. In phase 1b, patients (pts) received adebrelimab (10 mg/kg or 20 mg/kg, I.V., D1, Q3W), camrelizumab (200mg, I.V., D1, Q3W), and apatinib (250 mg orally daily). Phase 2 is a single arm, open-label trial in the first-line setting. The primary objective were dose-limiting toxicity (DLT), maximal tolerated dose (MTD), and recommended phase II dose (RP2D). With α = 0.05 and 80% power, the pts needed for stage I and total of the Simon 2-stage design was 17 and 41 pts, respectively. Results: As of 4 February 2024, 6 HCC pts progressed after or were intolerant to first-line treatment (systemic therapy ± surgical resection) were treated in 1 dose cohorts. 1 DLT occurred (Grade 3 elevated blood bilirubin increased). The RP2D was adebrelimab (10 mg/kg), camrelizumab (200mg), and apatinib (250 mg). The most common drug-related AEs were Hypertension (83.3%) and Rash (50%); and Serum amylase increased, Itching, ALT/AST increased, and Hypothyroidism (each 33.3%). Immune-related AEs were similar to those seen with other checkpoint blockade agents. No drug-related AEs led to death. 1 pts (16.7%) discontinued due to drug-related AEs. Conclusions: The combination of Adebelimumab, Camrelizumab, and Apatinib demonstrated manageable safety for unresectable HCC. Enrollment in the phase II trial is ongoing and updated clinical data will be presented. Clinical trial information: NCT05924997 .
Risk factors associated with liver cancer in all US participants.
Authors: Xiong Chenxi , Su Jing , Dong X Charlie
Published: July 2024

e16276

Background: Liver cancer incidence rates have risen in recent years, more than tripled since 1980, and the liver cancer-caused death rates have more than doubled during the same time. The objective of this research was to identify significant risk factors (both genetic and environmental) that may contribute to the liver cancer development. Methods: The study cohort was obtained from the All of Us (AoU) population with the latest data (data cutoff date 07/01/22) of 413,457 participants. The baseline survey data, genomics data, and electronic medical data have been queried for studying the risk factors to the liver cancer. Baseline demographics, comorbidities, AUDIT-C score (positive score, defined as > = 5 for men and > = 4 for women, was considered as with high risk of alcoholic hepatitis), social determinants of health (SDoH), and genetic variants were evaluated using the logistic regression models respecting the prevalence of liver cancer. Results: The study cohort included total 254,356 participants with their EMR data, genomics data, and AUDIT-C answers (median age 55 years, 61% women, 45% from minority groups, 19% Hispanics). Among them, 1,048 patients were diagnosed liver cancer. Using the logistic regression models, SDoHs showed association with the development of liver cancer. Retired groups demonstrated higher risk (adjusted odds ratio or aOR: 1.34, 95%CI:1.09-1.67) as well as the unemployed groups (aOR: 1.19, 95%CI: 0.98-1.46). C > G variants at 22:43928847 (aOR: 1.18, 95%CI: 1-1.39), G > G variants at 22:43937814 (aOR: 1.35, 95%CI: 0.97-1.82), and G > A variants at 22:43932850 (aOR: 1.18, 95%CI: 0.99-1.39) of gene PNPLA3 were associated with higher risks. C > T variants at 19:19268740 of gene TM6SF2 demonstrated higher risks (aOR: 1.23, 95%CI: 0.97-1.54) as well. The following demographic and comorbidities factors significantly contributed to the development of liver cancer: 45 to 65 age group (aOR: 6.89, 95%CI: 4.05-13), greater than 65 (aOR: 9.99, 95%CI: 5.84-18.91), hepatitis c virus infection (aOR: 12.46, 95%CI: 10.51-14.75), diabetes with chronic complications (aOR: 1.49, 95%CI: 1.25-1.78 ), diabetes without chronic complications (aOR: 1.81, 95%CI: 1.53-1.2.14). Conclusions: This study reveals that multiple risk factors are significantly associated with the liver cancer ranging from common genetic variants, socioeconomic conditions, age, viral infection, and diabetes. Thus, it is very important to take a comprehensive approach for the liver cancer prevention.
Factors associated with surgical intervention in Native American patients with hepatocellular carcinoma.
Authors: Murugan Vikram , Becken Aidan , Bine Christopher Reese , Silberstein Peter T.
Published: July 2024

e16279

Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions. Past literature has demonstrated the impact certain socioeconomic factors have on the prognosis of HCC. Native American patients often face late-stage cancer diagnoses and have the lowest survival rates among racial and ethnic groups. While surgery offers potential for cure, factors related to surgical interventions in liver cancer for Native American patients remain largely unexplored. Through the NCDB, this study analyzed factors associated with surgical intervention and survival trends 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 1193 Native American patients included in this sample, 172 (14.4%) patients received surgical treatment for HCC, while 1021 (85.6%) patients did not receive surgical treatment for HCC. Native American patients who received surgery for HCC experienced a greater mean overall survival (90 months) when compared to the mean overall survival (24 months) in HCC Native American patients who did not receive surgical treatments (p < 0.001). When controlling for age, year of diagnosis, stage, grade, facility type and income status, receiving surgery showed an independent decrease in hazard (HR = 0.245; p < 0.05). HCC Native American patients who received surgery were more likely to be treated an at academic facility, have stage I disease, and have less aggressive tumors (grade) (p < 0.05). Native American patients who did not receive surgery were more likely to be older (62 vs 60 years old), have larger tumors, and have brain, bone, lung, and liver metastases (p < 0.05). No associations of surgical versus non-surgical treatment were seen in Charlson-Deyo score, urban or rural residence, and primary payor at diagnosis. Conclusions: Native American patients with HCC who received surgical intervention experienced improved overall survival compared to non-surgical treatment groups. Native American patients undergoing surgical intervention more often received care at academic or private institutions and had lower stages of HCC. These results follow previous trends, where cancer patients receiving adequate surgical intervention generally survive longer. Further research is needed to examine other treatment differences among Native American patients and how these findings compare across other disadvantaged groups.
Claims-based analysis of treatment practices of patients with metastatic gastroenteropancreatic neuroendocrine tumors (mGEP-NET) in the USA.
Authors: Pavel Marianne , Abraham Ivo , Halfdanarson Thorvardur Ragnar , Princic Nicole , Bernhardt Dirk
Published: July 2024

e16286

Background: GEP-NET is a rare disease with variable tumor biology. An indolent disease course with subtle symptoms renders timely diagnosis difficult; 2/3 of patients (pts) are diagnosed at locally advanced or metastasized stage. In clinical decision-making, disease-specific factors, patient (pt) age and long-term disease control must be balanced against the aggressiveness of therapies. NCCN, NANETS and ENETS guidelines recognize the diversity of mGEP-NET by recommending individualized treatment approaches. We aimed to describe treatment (Tx) utilization patterns in mGEP-NET. Methods: Retrospective cohort study using MarketScan® Commercial and Medicare Databases spanning 07/01/2017-01/31/2023. Eligible were GEP-NET pts with ≥1 inpatient or ≥2 outpatient claims, a subsequent new diagnosis of metastatic disease (index), no secondary malignancy, and follow-up time of ≥12 months (m) after index. Results: Of 16218 GEP-NET pts, 2002 (mean age 60y; 50% female) met inclusion criteria. Mean follow-up time after index was 17m, with 49%, 27% and 15% followed up for ≥12, 24 and 36m, resp. Medical history (12m baseline before index) included mean Charlson Comorbidity Index of 2.62, with hypertension (HTN), type 2 diabetes (T2DM), chronic liver disease (CLD), asthma/COPD, cardiovascular disease (CVD), and chronic kidney disease (CKD) present in 56, 26, 22, 18, 17 and 10% of pts, resp.; 5% had carcinoid syndrome. In total, 949 pts (47.4%) received first-line (1L) systemic Tx: somatostatin analogs (SSA; 61.6%) of either very short or long duration (median 116d vs 775d), chemotherapy (38.8%), targeted therapies (3.4%) and PRRT (0.5%). Relative to NCCN cancer surveillance guidelines, 49.5% received more and 36.8% received fewer than 4 scans in the first year of treatment. Conversely, 1053 (52.6%) did not receive any 1L systemic Tx. With the exception of CLD, pts with vs without 1L Tx had similar proportions of medical conditions during the 12m baseline and during follow-up (HTN 72.4 vs 66.5%; T2DM 34.0 vs 30.3%; asthma/COPD 16.5 vs 19.3%; CVD 27.3 vs 36.9%; CKD 18.9 vs 17.9%; however, CLD 54.0 vs 36.7%). See Table comparing both cohorts on insurance, treatments, and health care utilization during follow-up. Conclusions: This claims analysis reveals treatment differences among mGEP-NET pts that cannot be explained by the parameters assessed herein. Further research should investigate factors influencing diagnosis and treatment decision-making, applying also pt-level health record data; and analyze economic barriers to diagnosis and treatment. [Table: see text]
The factors associated with all-cause in-hospital mortality in patients with malignant well-differentiated gastroenteropancreatic neuroendocrine tumors: A retrospective analysis of National Inpatient Survey (NIS) 2020 dataset.
Authors: Obomanu Elvis , Verinumbe Tarfa , Elom Hilary
Published: July 2024

e16292

Background: Neuroendocrine tumors (NET) affect less than 200,000 (52 per 100,000) of the US population, with malignant well-differentiated gastroenteropancreatic (GEP) NETs accounting for about 65% of the cases. Owing to its rarity, the evidence on factors associated with all-cause mortality is limited. To address this gap, this study aims to identify socio-demographic and clinical factors associated with all-cause in-hospital mortality for patients with malignant well-differentiated GEP NET. Methods: We analyzed data from 2020 Nationwide Inpatient Sample survey on patients hospitalized with malignant well-differentiated GEP NET. Using ICD10 code, we identified patients hospitalized with any diagnosis of malignant well-differentiated GEP NET. In-hospital mortality was assessed based on the patient final disposition on discharge and dichotomized. Exposure variables analyzed included age, sex, tumor site, history of essential hypertension, COVID-19, hyperlipidemia, insurance status, length of hospital stay, and number of comorbidities present on the patients record. Multivariable logistic regression was used to assess for factors associated with mortality. Results: Of the 956 patients in this study, most were white (73.43%), male (48.28%) and mean age was 65 years (SD 13.59). Affected sites include small intestine (57.25%), pancreas (13.56%), colon (8.47%), appendix (8.26%), stomach (8.68%) and rectum (3.51%). Our results revealed that females were less likely to die in the hospital compared to their male counterpart hospitalized with malignant well-differentiated GEP NET (aOR = 0.42; 95% CI: 0.19 - 0.95). The presence of hyperlipidemia was significantly associated with in-hospital mortality (aOR = 0.24; 95% CI: 0.08 - 0.75). For every unit increase in the number of comorbidities, there is 12% increased risk of mortality (aOR = 1.12; 95% CI: 1.05 -1.19). The associations of age, race, tumor site, history of hypertension, insurance status or length of stay with in-hospital mortality were not statistically significant. Conclusions: Our study found significant associations of sex, hyperlipidemia, number of comorbidities and in-hospital mortality among patients with malignant well-differentiated GEP NET. Findings from this study highlight that factors such as sex, hyperlipidemia and number of comorbidities may be critical when developing prognostic tools that can be used to determine the risk of mortality among hospitalized patients hospitalized with these tumors.
Extra-adrenal paraganglioma demographic data: A NCDB study.
Authors: Peterson Michael , Ramos Brianna Eillen , Grover Jasika , Nakshbandi Noureen , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: July 2024

e16293

Background: Extra-adrenal paragangliomas are rare neuroendocrine tumors that form near blood vessels and nerves outside of adrenal glands. Despite their rare occurrence, these tumors have higher rates of malignancy and varying survival rates compared to other paragangliomas. To better understand its epidemiology, there may be clinical value in analyzing the diagnostic trends of these tumors. This study utilized information provided by the National Cancer Database (NCDB) to examine the demographic factors of patient populations diagnosed with extra-adrenal paragangliomas. Methods: A retrospective cohort analysis using the 2004–2020 National Cancer Database (NCDB) included 133 patients with a histologically-confirmed diagnosis of extra-adrenal paraganglioma (ICD-O-3 code 8693). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles/Deyo score) were analyzed by descriptive statistics. Incidence trends were interpreted via regression analysis. Results: In the NCDB, 133 patients were identified with a confirmed diagnosis of extra-adrenal paraganglioma between 2004 and 2020. This database suggested a relatively stable number of patients diagnosed per year (R² = 0.022). Men (67%) were more likely to be diagnosed than women (35%), with an average age at diagnosis of 45.7 years (SD = 17.7, range = 11-83). Patients were most commonly non-Hispanic (88%), White (68%), and had a primary site of diagnosis in the retroperitoneum (35%). Treatment was primarily surgical resection (84%) followed by radiation (17%) and chemotherapy (8%). Most patients did not receive palliative care (98%). A majority of patients (77%) had a Charlson-Deyo comorbidity score of 0, with a 2 year survival rate of 92%, a 5 year survival rate of 79%, and a 10 year survival rate of 50%. Most patients were privately insured (65%) and received treatment in an academic research facility (56%). Many individuals lived in large metropolitan counties with a population larger than 1 million (56%), and resided a mean distance of 41.6 miles (SD = 74.4, range = 0.8 - 559.3) from the treatment facility. Conclusions: To the best of our knowledge, this is the first analysis of extra-adrenal paragangliomas utilizing the NCDB, and thus addresses a significant lack of knowledge on the subject. The majority of patients are non-Hispanic White men, with a primary site of diagnosis in the retroperitoneum. This is the first time that the socioeconomic factors of extra-adrenal paraganglioma patients have been described in the literature: patients tend to be privately insured, live in large metropolitan counties, and have 10 survival rate of 50%. Continued research is necessary to gain a deeper insight on the impact of socioeconomic and demographic factors that influence the diagnosis, treatment, and survivability of extra-adrenal paraganglioma patients.
Positive psychology interventions in patients with prostate cancer: A systematic review.
Authors: Xu Eleanor , Phung Quan , Runcie Karie , Liu Michael A.
Published: July 2024

e17005

Background: Prostate cancer is the most common malignancy in men and often results in psychiatric symptoms due to the direct disease effects, hormonal treatments, functional losses, and psychological responses of patients to the cancer. Positive psychology interventions have shown promise in alleviating psychological symptoms in patients with chronic diseases but are infrequently studied in patients with prostate cancer. Therefore, our systematic review aimed to examine the benefits of positive psychology interventions for patients with prostate cancer. Methods: Using PRISMA guidelines, a systematic literature search was conducted using the Medline, PubMed/Medline, and PsycInfo databases using a combination of MeSH terms and free text words, including publications up to November 2023. Studies were eligible if they included at least one positive psychology therapy intervention and the title or abstract mentioned the inclusion of patients with prostate cancer. Two individuals independently reviewed reports identified by the search to meet the above criteria and performed a quality assessment scale of studies based on standardized criteria that were adapted from those used in prior systematic reviews. The study was pre-registered on the Open Science Framework (OSF) repository. Results: The database searches yielded 1244 initial studies, 10 of which met inclusion criteria. Of the 10 included studies, 2 were randomized clinical trials, 2 were pilot feasibility trials, 3 were single-arm interventional studies, and 3 were cross-sectional studies. Manuscripts focused on older adults, with reported mean ages ranging from 54.5 to 72.0. Positive psychology interventions consisted of mindfulness-based therapies, meditation, hope and resilience therapies, and well-being therapies. Most studies showed a positive effect on improving outcomes for patients with early to advanced stage prostate cancers, including psychological distress, mood disorders, anxiety, quality of life, happiness, and life satisfaction. However, most of the studies were limited by small sample size, qualitative findings, loss to follow-up, and observational data. Most studies also excluded patients with severe psychiatric disorders, who may potentially benefit most from these interventions. Conclusions: This systematic review demonstrates that positive psychology approaches may have benefit in patients with prostate cancer. However, further larger prospective studies and clinical trials are needed to determine whether these interventions have proven benefit in this understudied population.