bluuebunny/crossref_metadata_2025 huggingface dataset:
Health state utility assessment for low-grade glioma.
Authors: Bhanja Debarati , Wilding Hannah E. , Tuohy Kyle J. , Ozair Ahmad , Hamidi Nima , Macedo Filho Leonardo , Salmi Liz , Kwan Bethany , Xie Feng , Velásquez Carlos , Glantz Michael J. , Ahluwalia Manmeet Singh , Mansouri Alireza
Published: July 2024

e14039

Background: Low-grade gliomas (LGGs, WHO Grade II gliomas) undergo malignant transformation, portending a median survival of 5-15 years. Though resection and adjuvant therapies have significantly improved survival, there are increased risks of long-term neurological decline and treatment-related side effects. As a result, not only quantity but also quality of life (QoL) must be considered when appraising therapeutic paradigms. Health state utility assessments can quantify society’s perceptions of given health states, supporting quality-adjusted life years (QALYs) and cost-effectiveness analyses. The primary and secondary objectives were to calculate LGG health states utility values (UVs) and interpret differences between health states, respectively. Methods: Health state descriptions were developed from a comprehensive literature review, expert input, and focus groups involving neuro-oncology providers and patient advocates. Healthy, adult participants were surveyed through an online REDCap form. Two preference elicitation techniques, visual analog scale (VAS) and time trade-off (TTO), were used to derive UVs of ten LGG health states. UVs are anchored at 0 representing death and 1 for perfect health. Mann-Whitney U tests compared UVs across health states. Results: Ninety-eight participants were included. Most participants were male (52%), aged 18-29 (81.6%), and White or Asian (78%). Stable LGG had the highest UVs (Mean [SD]: VAS- 0.64 [0.21]; TTO- 0.54 [0.42]) compared to Progressive LGG (VAS- 0.44 [0.26], p<0.0001; TTO- 0.36 [0.37], p<0.0001), Stable LGG with Chemoradiation (VAS- 0.43 [0.23], p<0.0001; TTO- 0.32 [0.34], p<0.0001), and Stable LGG with Motor (VAS- 0.45 [0.23], p<0.0001; TTO- 0.23 [0.32], p<0.0001) and Language (VAS- 0.52 [0.22], p<0.0001; TTO- 0.43 [0.40], p=0.04) Deficits. Progressive LGG UVs were not statistically different from those in Progressive LGG with Motor (VAS- 0.43 [0.23], p=0.69; TTO- 0.32 [0.34], p=0.73), Language (VAS- 0.43 [0.23], p=0.62; TTO- 0.32 [0.34], p=0.60), or Visual (VAS- 0.43 [0.23], p=0.78; TTO- 0.32 [0.34], p=0.60) Deficits. Radiation negatively impacted UVs, as UVs of Stable LGG with Chemoradiation (VAS- 0.43 [0.23]; TTO- 0.32 [0.34]) were significantly lower than UVs of Stable LGG with Chemotherapy alone (VAS- 0.43 [0.23], p=0.018; TTO- 0.32 [0.34], p=0.28) on VAS. Conclusions: These are the first-ever reported LGG health state UVs. These data will enable future QALY and cost-effective analyses, which have increasing importance as new investigational therapies become available for LGG.
Hydrogenated oxide material-based hyperthermia and radiotherapy: A new treatment option for esophageal squamous carcinoma.
Authors: Yang Yuexin , Liang Jun , Jiang Jun
Published: July 2024

e16127

Background: Radiotherapy (RT) is the mainstay of esophageal squamous carcinoma (ESCC) treatment, and hyperthemia could exert synergistic effects to refractory diseases. Hydrogenated oxide material (HMO) is a newly developed photothermal agent, featured by selectively targeting tumors, high photothermal conversion efficiency under 1064 nm near-infared (NIR) illumination and safe degradation. This study aims at investigating the combination effects of HMO-based hyperthermia and RT in ESCC. Methods: mEC25 murine ESCC cells were cultured and treated with RT alone (prescribed cumulative dose of 10Gy), HMO-based hyperthermia (incubated with 100ug/ml HMO for 20min and irradiated with 1064nm NIR continuously for 15min) or combination therapy (RT followed by HMO-based hyperthermia). FLIR-One was applied to monitor temperature alterations in HMO-based hyperthermia. Flow cytometry was performed to detect apoptosis rates 24h after treatment. Results: The temperature was increased by 21.3[19.8-23.7]℃ after NIR irradiation. The apoptosis rates were 19.4%[19.4%, 19.5%], 43.8%[43.6%, 44.0%] and 61.4%[58.5%, 61.8%] in RT alone, HMO-based hyperthermia and combination therapy group respectively. Considerably low apoptosis rates were observed in HMO-incubation and NIR-irradiation only groups, which was 6.2% and 6.6% respectively, similar to that of treatment-naive cells. Conclusions: The combination of HMO-based hyperthermia and RT provided a promising treatment modality for ESCC, while its effects in rodent models and potentials in clinical practice merit further investigations.
Efficacy and safety of donafenib as adjuvant therapy for patients with hepatocellular carcinoma undergoing curative resection: A retrospective, multicenter cohort study.
Authors: Yang Xin-Rong , Zhang Sen-Quan , Chen Zhong , Yu Zheng-Ping , Wu Sheng-dong , Fan Jia , Zhou Jian
Published: July 2024

e16234

Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This multicenter, real-world study retrospectively gathered clinical data of 82 patients who had undergone radical resection of HCC and received adjuvant therapy with donafenib. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analysis was performed to evaluate RFS and OS, while the Cox proportional-hazards model was used to estimate risk factors for tumor recurrence and death. Results: A total of 82 patients with HCC who received donafenib following surgical resection were included in the study, of which were classified as high risk for tumor recurrence (with multiple or large tumor, microvascular invasion, poor tumor differentiation). The median duration of donafenib adjuvant therapy was 10.6 months (range: 0.2–26.1 months). All patients completed follow-up as required, with a median follow-up time of 19.4 months (range: 2.8–57.6 months). During the follow-up period, a totally postoperative recurrence rate was 15.9% (13/82). 1-year recurrence rate and 2-year recurrence rate were 7.3% (6/82) and 12.2% (10/82), and 1-year survival rate and 2-year survival rate were 95.1% (78/82) and 93.9% (77/82). Kaplan-Meier analysis demonstrated that patients with higher preoperative AFP level (AFP > 400ng/mL), higher preoperative PIVKA-II level (PIVKA-II > 40mAU/mL), or poor tumor differentiation (Edmondson stage III-IV) exhibited higher rate of tumor recurrence after operation (all p value < 0.05). Multivariate analysis indicated that preoperative AFP level was an independent risk factor for tumor recurrence in patients with donafenib treatment. Treatment-related adverse events (TRAEs) occurred in 67.1% (55/82) of patients, of which the most frequent were hand-foot syndrome (25.6%, 21/82), diarrhea (20.7%, 17/82), and fatigue (17.1%, 14/82). Only 8.5% (7/82) of patients had a grade ≥3 TRAEs, with the most common being hand-foot syndrome (2.4%, 2/82) and hypertension (2.4%, 2/82). No treatment-related deaths were reported. Conclusions: This study represents the largest multicenter investigation of adjuvant therapy with donafenib to date, and the findings indicate that donafenib has the potential to be an effective treatment option for preventing postoperative recurrence in HCC. Furthermore, the preoperative AFP ≤400ng/mL can serve as an effective biomarker for postoperative administration of donafenib in HCC patients.
A pilot trial of personalized neoantigen pulsed autologous dendritic cell vaccine as adjuvant treatment in hepatocellular carcinoma.
Authors: Wu Qiuji , Li Qiu
Published: July 2024

e16264

Background: The primary treatment for hepatocellular carcinoma (HCC) is radical surgery. However, HCC has a high propensity to recur postoperatively and no standard adjuvant therapies have been approved. This Phase I trial aims to evaluate the safety and efficacy of an adjuvant personalized neoantigen pulsed autologous dendritic cell vaccine (Neo-DCVac-02) in patients with HCC. Methods: Eligible patients had histologically confirmed high-risk HCC after radical surgery. After obtaining the necessary baseline biopsy specimens and PBMCs of appropriate quality for DNA and RNA sequencing, neoantigen prediction, screening and synthesis were performed. Subsequently, leukapheresis was performed and DCs were isolated and cultured. DCs were then pulsed with neoantigen peptides to produce Neo-DCVac-02. On day 0, patients were treated with cyclophosphamide at a dose of 250 mg/m2. The prepared Neo-DCVac-02 vaccine was administered subcutaneously to the axillary and inguinal regions bilaterally on day 1, followed by daily administration of GM-CSF at a dose of 0.075 mg for 5 days (days 2-6). The primary objectives of this study were to assess feasibility and safety/tolerability. Secondary objectives included evaluation of immune responses (via vaccine response: IFNγ ELISpot), relapse-free survival (RFS) and overall survival (OS). Results: A total of 32 patients provided informed consent to initiate the process of personalized neoantigen discovery, of which 26 (81%) met the requirements for successful product selection for clinical manufacturing. Feasibility was demonstrated with 13 patients receiving Neo-DCVac-02. 13 patients did not receive the neoantigen vaccine (7 due to progressive disease, 6 due to withdrawal of informed consent because of COVID-19). The treatment was well tolerated with no grade 2+ treatment-related adverse events (TRAEs). The most common Grade 1 TRAEs were injection site reactions (75%), rash (16.7%), fatigue (8.3%), neutropenia (8.3%), and headache (8.3%). Five of 13 evaluable patients showed increased antigen-specific T-cell activity and more than 50% of the neoantigen peptides in Neo-DCVac-02, and sustained cellular responses were observed up to one year. Increases in T-cell activation/co-stimulation seen after treatment with Neo-DCVac-02, as demonstrated by flow cytometric analysis, suggest immune priming. At a median follow-up of 29.7 months, median RFS was not reached, with 1- and 2-year RFS of 84.6% and 60%, respectively, and all patients are alive. Patients with a strong immune response had a longer median relapse-free survival (not reached) compared to patients with a weak immune response (17.6 months, P = 0.003). Conclusions: These data demonstrate that Neo-DCVac-02 is safe, well tolerated and capable of inducing durable antigen-specific lymphocyte immune responses that may correlate with delayed HCC recurrence. Clinical trial information: NCT04147078 .
Bi-institutional spline curve analysis of lymph node mapping in gallbladder cancer operated over 12 years: Impact of location and number of lymph nodal stations.
Authors: Patkar Shraddha , Bhargava Prabhat Ghanshyam , Ostwal Vikas S. , Ramaswamy Anant , Patel Swapnil , Goel Mahesh
Published: July 2024

e16274

Background: Current staging system for gallbladder cancers (GBC) takes into account only the number of metastatic lymph nodes without addressing their location. The current study evaluates the prognostic impact of lymph node mapping (number and location) in node positive GBCs. Methods: Prospectively maintained operative database of GBC patients with positive lymph nodes were analysed from two tertiary cancer care centers in a retrospective cohort study design between April 2010 till March 2022. Nodal burden was assessed including both, the number of metastatic nodes and the lymph node station. Impact of lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) was evaluated using regression and spline curve analysis. Results: Amongst 1312 operated GBC patients, 272 patients with node positive disease were included. The median nodal yield was 8. The median LNR and LODDS was 0.222 and -0.48 respectively. The 5-year DFS and OS for patients with only cystic node metastases was 52.3% and 50.8% respectively (median: not reached), as compared to 24.6% and 35.2% for involvement of regional nodal stations beyond cystic nodes. Higher LODDS was associated with inferior DFS and OS when compared to the LNR. On multivariate analysis, multi-station involvement was the only factor associated with inferior DFS (p < 0.001) and OS (p = 0.007). Conclusions: Station wise pathological assessment of lymph nodal involvement could potentially provide superior prognostic information, in addition to number of involved nodes. Involvement of cystic lymph node alone has relatively superior prognosis as compared to multi-station involvement.
WDR4 as a potential indicator of clinical prognosis and immunotherapy in hepatocellular carcinoma.
Authors: Lin Chi , Wang Juan , Ouyang Long , Duan Huaxin , Fan Shasha
Published: July 2024

e16275

Background: Immunotherapy has garnered increasing attention in hepatocellular carcinoma (HCC) treatment. However, there remains a pressing need for effective immunological predictive biomarkers. In our previous study, utilizing data extracted from The Cancer Genome Atlas (TCGA) database, we identified a positive correlation between WDR4 expression levels in hepatocellular carcinoma and various clinical parameters, encompassing Stage, T-stage, pathological grade, AFP level, and vascular invasion. Additionally, higher WDR4 expression was linked to poorer prognosis. Leveraging The TIMER and GEPIA databases, we further elucidated a significant association between WDR4 expression levels and the extent of immune cell infiltration, particularly macrophages, B lymphocytes, and myeloid suppressor cells, in hepatocellular carcinoma. These findings propose the potential utility of WDR4 as a biomarker for immune infiltration in hepatocellular carcinoma. As noted in the trial NCT03867084, which hypothesized that adjuvant pembrolizumab might surpass placebo efficacy, there still exists a gap in identifying the specific population benefiting from adjuvant immunotherapy. Methods: Clinical and pathological data from patients who underwent single-agent immunotherapy for HCC were additionally collected from Hunan Provincial People's Hospital between January 1, 2019, and January 31, 2024. These patients participated in the clinical trial (NCT03867084) with informed consent. The relationship between WDR4 expression levels, clinical pathological data, and patient prognosis was assessed using the Kruskal-Wallis test and Kaplan-Meier survival curve analysis. Results: WDR4 displayed significant upregulation in HCC tissues compared to para-carcinoma tissues (P < 0.001) and exhibited robust diagnostic potential. WDR4 expression showed significant associations with various immune cells, including macrophages (r = 0.278, P < 0.001). Kaplan-Meier survival analysis indicated that patients with high WDR4 expression had shorter postoperative progression-free survival in the context of immunotherapy. Data from 37 patients who underwent postoperative single-agent immunotherapy for hepatocellular carcinoma (NCT03867084) revealed a significant correlation between WDR4 expression levels and Disease-Free Survival (DFS), with notable statistical significance (Log-rank P < 0.001). Conclusions: WDR4 demonstrates elevated expression levels within HCC tissues and is associated with immune infiltration, establishing it as a prognostic biomarker in HCC. Furthermore, the positive correlation observed between WDR4 and CD68 as well as PD-L1 underscores its potential as a guiding factor in immunotherapeutic approaches for HCC.
Anatomical and demographic prognosticators of pancreatic cancer.
Authors: Desai Krishna , Pereira Kristal , Prabhakaran Sivaguha Yadunath , Ali Hassan , Thar Yu Yu , Choi Eugene , Thirumaran Rajesh
Published: July 2024

e16310

Background: Pancreatic cancer is known to have one of the poorest median of survival (mOS) of all cancers. It is now the third leading cause of cancer-related mortality after lung & colorectal cancer. With the current trends, understanding & knowing prognosticators can aid in determining outcomes of pancreatic cancer. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted pancreatic cancer cases based on primary site encoding for head, body & tail of pancreas, Islets of Langerhans (IoL), other specified parts & overlapping lesion of pancreas, pancreas, NOS (no other specific). The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 221,304 cases were extracted between 2000-2020. The median age of diagnosis was 71 years. 50.54% were males, & 49.45% were females. The incidence rates are shown below. Whites (69.99%) were commonly affected, followed by Blacks (11.05%), Hispanics (10.79%), Asians & Pacific islanders (7.41%), Alaskan natives & American-Indians (0.57%). A distribution in anatomy was notable for head of the pancreas (46.00%), followed by tail (13.20%), body (11.34%), pancreatic duct (0.49%), IoL (0.10%). A survival curves were compared on different variables. Gender showed no statistical difference. mOS for patients diagnosed >70 years was 3 months & <70 years was 8 months (p value <0.0001, CI 0.3716 to 0.3784, HR 1.731). mOS for calculated for Whites (5), Blacks (4), Asian & Pacific islanders (6), Alaskan natives & American-Indians (4), & hispanics (5) (p value <0.0001). mOS based on involved parts of pancreas were compared for: head (6), body (6), tail (5), pancreatic duct (8), IoL (59) (p <0.0001). Conclusions: Median age of diagnosis was in 71, with a slight male predilection. Overall incidence rate is trending up. It is significantly higher for males, & is significantly lower for females than that of the general population. Whites are most commonly affected, & Alaskan natives & American natives are rarely affected. Survival is significantly greater if diagnosed <70 years. Most common site involved is the head of pancreas, & the least is IoL. mOS is ~10 times greater for IoL, but it's an endocrine pancreatic cancer which is treated differently. From the exocrine pancreas, survival is the best for pancreatic duct cancer, & the worst for pancreatic duct. If anatomic & demographic prognosticators are combined with molecular, radiologic factors, it can be beneficial in predicting the outcomes of this cancer with poor prognosis. [Table: see text]
PD-1 blockade plus chemotherapy followed by concurrent SBRT with SIB as preoperative therapy for patients with potentially resectable pancreatic cancer: A single-arm phase 2 study.
Authors: Du Juan , Ni Jiayao , Sun Yi , Sha Hui-zi , Tong Fan , Mao Liang , Kong Weiwei , Shen Shanshan , Gu Qing , Wang Lei , Qiu Yudong , Liu Baorui
Published: July 2024

e16312

Background: Pancreatic cancer has 10% low rate of early diagnosis and resection due to its insidious onset and poor prognosis. We aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with Potentially Resectable Pancreatic Cancer. Methods: This is a single arm clinical trial (NCT05634564). Gemcitabine (1000 mg/m2) and nabpaclitaxel (125 mg/m2; AG) were administered to patients with LAPC or BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Concurrently, the patients underwent stereotactic body radiotherapy (SBRT) with simultaneous integrated boost (SIB)during the third cycle of treatment. Surgical intervention was reassessed after four cycles of treatment. Objective response rate (ORR) was the primary endpoint and Disease control rate (DCR), R0 resection rate, median overall survival (mOS), median progression free survival (mPFS) rate, time to progression (TTP) and safety were analyzed as secondary endpoints. Results: Between May 2020 and April 2023, 62 patients with LAPC or BRPC were enrolled. Until the last follow-up time (January 30, 2024) ,56 of them included in the intention-to-treat (ITT) analysis who completed at least three cycles of tislelizumab plus AG and underwent concurrent radiotherapy. The median age in intention-to-treat analysis was 65 years. 25 patients had a best response of partial response, the ORR was 44.6%, DCR was 100%. Thirty-one patients met the criteria for surgical resection after treatment, 9 of whom refused surgery and continued conservative treatment. 22 patients underwent resection, and the R0 resection rate was 95.45%. Two of the 22 resected patients achieved pathologic complete response (pCR) and five patients achieved major pathological response (MPR). The pathologic complete response rate was 9.10% and significant pathological response rate was 31.82%. The TTP was 19.38 months (95% CI: 12.8%-27.9%), and the mOS was 21.32 months (95% CI:15.9%-NR). The 12-months PFS rate and 12-months OS rate were 59.9% (95% CI:45.2%-71.8%) and 74.4% (95% CI:59.9%-84.3%), respectively. Grade 5 adverse events were not observed. The most common grade 3-4 hematological and non-hematological toxicities were leukopenia (17.9%), neutropenia (16.1%), anemia (8.9%), thrombocytopenia (7.1%), rash: dermatitis (7.1%), Peripheral neuropathy (3.6%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy followed by concurrent SBRT with SIB significantly prolonged mPFS rate, as well as R0 resection rate of surgical patients, and also improved the major pathological response rate. Clinical trial information: NCT05634564 .
Tislelizumab with anlotinib and chemotherapy for second-line treatment of pancreatic ductal adenocarcinoma: A pilot study early result.
Authors: Dong Xuyuan , Wu Yinying , Fan Yangwei , Shi Yu , Wang Meichen , Dong Danfeng , Li Enxiao
Published: July 2024

e16316

Background: Advanced pancreatic ductal adenocarcinoma is a malignant tumor with poor prognosis. At present, chemotherapy is still the standard treatment, however the efficacy is unsatisfied. The lack of second-line treatment options for pancreatic cancer results in progression-free survival often lasting less than 3 months. For pancreatic cancer is an immune desert type of tumor, immunotherapy has not brought breakthrough therapeutic regimen compared to the remarkable data in other tumors.There is still insufficient therapeutic evidence treated with PD1 antibody in pancreatic cancer. Anlotinib is a tyrosine kinase inhibitor (TKI) with anti-tumor effects. It has been shown the combination of PD1 and multi-target tyrosine kinase inhibitors can increase immunotherapy efficacy. The purpose of this study is to evaluate the efficacy and tolerability of Tislelizumab combined with Anlotinib, as well as chemotherapy (the choice of the investigator) in second-line treatment of patients with pancreatic ductal adenocarcinoma. Methods: In this single arm, phase II, prospective exploratory study, it was planned to recruit 30 adult patients with treated pancreatic ductal adenocarcinoma who have never received any PD (L) 1 and TKI. Eligible patients received Tislelizumab (iv, 200mg, Q3W), Anlotinib (PO, 10mg, QD), and chemotherapy (determined by the researchers) till disease progression or death. The primary endpoint was median progression-free survival (mPFS), the secondary endpoints were objective response rate (ORR), median overall survival(mOS), disease control rate (DCR), and treatment safety profile. Results: 14 eligible patients were recruited till Jan 2024, 12 patients with PFS records were included. Median follow-up time was 208 days (104 days-504 days). mPFS was 106 days, OS is not reached, BOR (best of response) was stable disease. The 3-months DCR rate was 58.3%, 6-months DCR rate was 25%. One patient was observed to have a 20% tumor shrinkage after two cycles of treatment and is still being followed up. The most common treatment-related adverse events(TRAEs) was neutropenia with level ≤grade 3, observed in 8/14 patients. The immune-related adverse event of concern was hypothyroidism(grade 1/2), which occurred in two patients. Two patients experienced grade 4 obstructive jaundice caused by the progression of the disease. Conclusions: The second-line combination regimen of Tislelizumab with Anlotinib based on chemotherapy demonstrated survival improvement trend and no new safety signals identified in pancreatic cancer. These data suggest Tislelizumab + Anlotinib+Chemo may be a promising novel treatment option for patients with pancreatic cancer. Clinical trial information: NCT05681390 .
Unfavourable carcinoma of unknown primary (CUP) with gastrointestinal profile: A retrospective study.
Authors: Guidi Lorenzo , Valenza Carmine , Battaiotto Elena , Boscolo Bielo Luca , Crimini Edoardo , Belli Carmen , Gervaso Lorenzo , Cella Chiara Alessandra , Ciardiello Davide , Venetis Konstantinos , Bottiglieri Luca , Ghioni Mariacristina , Guerini Rocco Elena , Fazio Nicola , Zampino Maria Giulia , Curigliano Giuseppe
Published: July 2024

e16374

Background: According to European Society of Medical Oncology (ESMO) guidelines, CUP are classified in favorable and unfavorable subsets. Favorable CUPs (20% of pts) have clinical aspects and either pathology highly suggestive for specific site of origin or with amenable metastases for localized treatment with curative intent; they are treated with site-specific chemotherapy (CT). All other CUPs (80%) are defined unfavorable and are treated with empiric CT regimens. There is no data about the best CT regimen for unfavourable CUPs with GI profile, i.e., those CUPs that do not meet the criteria of favourable colon-like CUP (CK7-/CK20+/CDX2+) but have a morphological/immunohistochemical profile suggestive for the digestive system. Methods: We conducted a single-center retrospective study to describe outcomes and prognostic factors of pts with unfavourable CUPs with GI profile, referred to our center from Jan 2000 to Aug 2023, who received at least one cycle of first-line CT. The definition of GI profile was: a) negativity for GATA-3, PAX-8 and TTF-1 and b) CK7+/CK20-/anyCDX2 or CK7-/CK20+/CDX2- or CK7-/CK20-/CDX2+, or c) presence of an abundant mucinous component and/or a signet ring cell component. The primary endpoint was the progression free survival (PFS) of first line chemotherapy for advanced disease. Results: 43 pts were included (characteristics in table). After a median follow-up of 43.9 months, 33 deaths were registered and the mOS was 12.6 months (95% CI, 8.7-16.5). Forty PFS events were registered and the mPFS was 6.1 months (95% CI, 3.5-8.9). At univariate analysis, male pts (p=0.034), peritoneal metastases (p=0.0282), residual tumor after surgery (p=0.002), suspected biliopancreatic origin (p=0.033), PS ECOG > 1 (p<0.001) and CDX2- status (p=0.025) were associated with shorter PFS. No CT regimen was superior in terms of PFS at both univariate (p=0.282) and multivariable analysis after adjusting for peritoneal metastases, suspected origin, gender and baseline ECOG PS. Conclusions: Although limited by the small sample size, this study showed that all CT regimens were comparable in terms of PFS among patients with unfavorable CUP with gastrointestinal profile. Keywords (3/10): cancer of unknown primary; peritoneal metastases; chemotherapy. [Table: see text]
FOLFOX as a therapeutic option in patients with hepatic failure due to liver metastasis of gastrointestinal (GI) system malignancies: A case series.
Authors: Başkurt Kadriye , Sütcüoğlu Osman , Mizrak Kaya Dilsa
Published: July 2024

e16378

Background: The treatment options for patients with hepatic metastasis presenting with liver dysfunction, particularly those experiencing severe hyperbilirubinemia, are limited. The oxaliplatin and fluorouracil/folinic acid regimen, known as FOLFOX, stands out as a viable option based on its pharmacokinetics. However, clinical data regarding the specific dosage and tolerability of this regimen are limited, and clear recommendations are not currently available. Patients and Methods: Patients who presented with severe hyperbilirubinemia immediately after the diagnosis of GI adeno cancer, and who were not eligible for drainage options, were prospectively observed in our clinic in Turkey throughout the year 2023. Severe hyperbilirubinemia was defined as a bilirubin level > 5mg/dL. The FOLFOX regimen was administered every two weeks, and the fluorouracil dose was initially reduced by 50% for the first two cycles. Subsequently, the dose was increased to the total amount if no toxicity occurred. Results: Six cases of GI cancer patients meeting the criteria were identified. Subsequent laboratory data for these six patients were collected after initiating the FOLFOX regimen. All six patients underwent the FOLFOX regimen with dose reduction for the first two cycles. Following the first cycle of chemotherapy, bilirubin levels dropped and normalized (Table 1), leading to an improvement in the patients' clinical condition. Conclusions: While our series is limited by a small number of patients, treatment with FOLFOX has proven to be feasible and may yield significant benefits in patients with severe liver dysfunction caused by GI cancer, especially when no further drainage options are available. [Table: see text]
Relugolix prescribing practices and clinical experiences at an urban academic center.
Authors: Fernandez Turizo Maria Jose , Stevens Julia , Xu Guiyu Jessie , Yankama Tuyen , Garnick Marc B. , Lichtenstein Morgan R. L. , Fein Daniel E.C.
Published: July 2024

e17008

Background: Relugolix is a novel oral GnRH antagonist that is now an alternative option for patients with prostate cancer (PC) who require androgen deprivation therapy (ADT). The potential benefits of relugolix include rapid testosterone decline and recovery, oral administration, and a possible cardiovascular (CV) benefit compared to traditional GnRH agonists. This study examines real-world data on relugolix prescribing practices and clinical experiences at a large, urban academic center. Methods: We conducted a retrospective, single-center cohort study of patients with PC prescribed relugolix from March 2021 through December 2023 at Beth Israel Deaconess Medical Center. We collected patient-related and clinical factors including demographics, comorbidities, CV risk factors, treatment history, reasons for relugolix prescription over GnRH agonists, medication compliance, adverse effects, and treatment outcomes. Descriptive statistics were used to characterize the cohort. Results: Among 267 patients who received a relugolix prescription, median age was 70 years old, 186 patients (69.6%) were Non-Hispanic White, 37 (13.9%) Non-Hispanic Black, 13 (4.9%) Asian, and 6 (2.2%) Hispanic of any race. Across all patients, 228 (85.3%) initiated relugolix with a median therapy duration of 181 days (range: 10 - 807). At the time of prescription, 88 patients (32.9%) were prescribed concurrent androgen receptor signal inhibitors (ARSI) and 186 (69.6%) had localized disease. Median CV risk factors per patient was 2 (range 0 - 7), and 4 patients (1.5%) developed major adverse CV events (MACE), including acute heart failure decompensation, sick sinus syndrome, ventricular tachycardia, and death during treatment. Among physician prescribers, the most common reasons for prescribing relugolix included concern for CV risk (90 prescriptions, 33.3%) and patient preference for oral administration (55 prescriptions, 20.4%). Forty-nine patients (18.3%) were switched from a GnRH agonist, mainly due to physician concern for CV risk (13, 4.9%) or patient preference (17, 6.4%). Conclusions: We describe real-world use of relugolix for PC in a large, diverse single center cohort. The most frequent reasons for choosing relugolix over a GnRH agonist were physician concern for CV risk and patient preference for a tablet over injection. Investigations of treatment initiation and adherence in relation to insurance coverage, adverse effects, and socioeconomic factors require further investigation.
Genomic profile of Japanese patients with rare ductal adenocarcinoma of the prostate has high grade and poor prognostic aspects.
Authors: Kosaka Takeo , Kobayashi Hiroaki , Nakamura Kohei , Baba Yuto , Yasumizu Yota , Matsumoto Kazuhiro , Ito Keiichi , Nishihara Hiroshi , Oya Mototsugu
Published: July 2024

e17046

Background: Ductal adenocarcinoma (DAC) is a rare subtype of prostate cancer with unknown etiology and poor prognosis. Genomic profile analysis using next-generation sequencing has the potential to elucidate the pathogenesis of rare cancers. To date, some studies have investigated the genetic profile of the DAC genotype; however, no definitive findings have been obtained due to the small number of patients and limited geographic coverage. The discovery of novel prognostic biomarkers and identification of new pharmacotherapeutic targets for DAC are currently of research interest. The aim of this study is to analyze the genomic profile of DAC in a Japanese population and to summarize its features. Methods: Clinical and histopathological records from our three hospitals were searched for radical prostatectomy, transurethral resection of the prostate, and prostate needle biopsy specimens containing a DAC component in the past 10 years. Twenty-eight patients diagnosed with DAC of the prostate were identified, of whom 15 were eligible for genomic profile analysis and 10 patients (66.7%) had the pure type. Genomic evaluation was performed using either the FoundationOne CDx or PleSSision testing platform. Results: At least one genomic alteration occurred in 14 patients (93.3%), and the most frequently mutated gene was tumor suppressor protein p53 ( TP53), which was found in seven cases (46.7%). Additionally, five cases (33.3%) had mutations in retinoblastoma transcriptional corepressor 1 ( RB1), and all these patients had the pure type. Four cases had both TP53 and RB1 alterations, and most of these possessed the pure type and had PSA levels of less than 4.0. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 20.0%) and Wnt-β/catenin pathway (n = 6; 40.0%) was comparable, but alterations in the DNA damage repair (DDR) pathway were few (n=1; 6.7%). None of the patients presented high tumor mutation burden or microsatellite instability. Conclusions: We found that the Japanese cohort with DAC has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1, and few DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of DAC, and further accumulation of cases is considered important.
Patient characteristics, treatment patterns and early trends of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) use by US urologists and oncologists.
Authors: Nguyen Jennifer , Patel Jeetvan , Kang Barinder , Yu Channing , Sawhney Amrita , Fallick Mark , Gorritz Magdaliz , Chen Chi-Chang , Paltanwale Queenie , Sun Kainan , Shore Neal D.
Published: July 2024

e17048

Background: 177Lu-PSMA-617 was approved by the US Food and Drug Administration in March 2022 for the treatment of patients with prostate-specific membrane antigen (PSMA) positive metastatic castration resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition (ARPI) and taxane-based chemotherapy. This study describes characteristics of patients treated with 177Lu-PSMA-617, treatment patterns and early trends in 177Lu-PSMA-617 utilization by US urologists (URO) and medical oncologists (ONC). Methods: This retrospective cohort study identified adult patients with ≥1 claim for 177Lu-PSMA-617 between 3/1/22 and 6/30/23 (first claim = index date) from the IQVIA open-source pharmacy and medical claims database. Patients were grouped by the physician specialty of the treating/referring physician. Patient characteristics were assessed within the 6 months prior to 177Lu-PSMA-617 initiation. Prior prostate cancer treatments were assessed over all available pre-index data. Results: Overall 1,394 patientstreated with 177Lu-PSMA-617 were identified during the first 16 months post-approval; 76.9% treated by an ONC and 23.1% treated by a URO. The mean age overall was 72.1 years; most patients were aged 65 and older (ONC, 83.3%; URO, 84.8%). Most patients had bone metastases (ONC, 88.0%; URO, 86.3%) and over one-third had visceral metastases (ONC, 34.6%; URO 35.7%). URO treated a higher proportion of patients with only lymph node metastases (5.9%) than oncologists (2.6%). Prior to 177Lu-PSMA-617, the vast majority of patients received ARPI and/or taxanes (ONC, 88.2%; URO, 89.4%). Use of 177Lu-PSMA-617 has steadily increased over the 16 months since approval with over five times as many patients being treated by ONC and URO in the first half of 2023. Conclusions: This is the first large-scale study describing 177Lu-PSMA-617 patient characteristics, prostatic cancer metastatic distribution, treatment patterns, and utilization trends by prescriber type (ONC and URO). This study highlights how URO are playing a pivotal role in management of post-taxane mCRPC patients receiving 177Lu-PSMA-617. As additional data with 177Lu-PSMA-617 becomes available, we anticipate the role of URO to significantly evolve with the potential for earlier use of 177Lu-PSMA-617 for pre-taxane mCRPC patients.
High-dose furmonertinib in combination with intraventricular chemotherapy for EGFR exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.
Authors: Fang Shencun , Fang Hehui , Xu Ting , Yang Liangfeng , Wang Xiaoyue , Liu Na , Zhang Xing , Zhang Bei
Published: July 2024

e20555

Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.
Impact of timing of immunotherapy in survival among patients with advanced lung adenocarcinoma treated with first-line immunochemotherapy: A propensity score matching.
Authors: Sun Yanxin , Wang Leirong , Sun Yuping , Dang Qi , Ge Yihui , Gao Aiqin , Cheng Qinglei , Sun Haifeng , Zhang Jian , Wu Jiake , Li Juan
Published: July 2024

e20560

Background: Immunochemotherapy combinations have been the mainstream first-line standard treatment of advanced non-small cell lung cancer (NSCLC), wherein concurrent chemotherapy and immunotherapy are conventionally fixed to an established dosing regimen. Few studies had suggested the remarkable impact of the timing of immunotherapy on immunochemotherapy combined therapy. However, this issue has not been addressed in advanced NSCLC cohort. Methods: This study was a retrospective analysis of 532 patients with advanced lung adenocarcinoma (LUAD) without EGFR/ALK mutations who underwent immunochemotherapy as first-line systemic treatment between June 2018 to June 2022 at 3 facilities. Patients were divided into two groups (induced and non-induced) according to the different timing of immunotherapy in combined therapy, which defined induced as receiving 1 or more cycles of full-dose chemotherapy alone before concurrent immunochemotherapy. The bias between induced and non-induced groups was minimized with Propensity Score Matching (PSM). Patients outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between the two groups by Kaplan-Meier survival curves and Cox regression analyses. Results: Survival analysis showed that both PFS and OS of the induced chemotherapy group patients were significantly longer than that of non-induced group (PFS: 14.63 months vs. 10.13 months, p = 0.004; OS: Not reached vs. 20.27 months, p = 0.0013). In the COX regression, after adjusting for confounders, induction chemotherapy was found to be a remarkable favorable factor for both PFS and OS (PFS: HR = 0.73, p= 0.018; OS: HR = 0.69, p= 0.034). After pretreatment features and treatment parameters were included in PSM, 104 patients were identified in each groups with matched characteristics, and moreover, the results of survival analysis remained consistent and showed significant difference between induced and non-induced group (PFS: 14.63 months vs. 10.23 months, p = 0.029; HR = 0.71, p= 0.030. OS: Not reached vs 18.27 months, p = 0.0013; HR = 0.52, p= 0.002). Conclusions: For advanced LUAD patients treated with first-line immunochemotherapy combinations, the timing of immunotherapy had significant impact on prognosis, which suggested notable benefit of induction chemotherapy before concurrent immunochemotherapy.
Mapping incidence and survival of non-small-cell lung cancers stratified by mutation type in southern Appalachia: A single center retrospective study.
Authors: Natarajan Arjun , Roman Hernandez Erica Marie , Ramineni SriVyshnavi , Liu Jieying , Sackfield Brad , Shastri Dipsa , Costello Patrick , Chakraborty Kanishka , Lewis Nicole
Published: July 2024

e20568

Background: Non-small cell lung cancer (NSCLC) is often a mutation-driven disease with variability in incidence and survival depending on location as seen in population-based cohort studies. Our study aims to delineate these differences based on molecular testing for these mutations in our study cohort at East Tennessee State University - Quillen College of Medicine, which is based on patients from east Tennessee, western North Carolina, and southwestern Virginia. Methods: We obtained pathology results of 294 patient samples with advanced/metastatic NSCLC from our cancer center/health system database over a 5 year period. PDL-1 was tested in all patients. Fluorescent in-situ hybridization (FISH) testing for common pathogenic driver mutations such as EGFR, ALK, ROS1, RET, MET and PTEN were performed as is standard of care. Molecular sequencing was performed and included over 40 genetic mutations and 2 biomarkers, several of which today are considered targetable for advanced NSCLC, per standard of care. Incidence of different mutations was measured in our patient population. Overall survival was calculated with date of diagnosis available based on pathology report and date of patient expiration obtained from electronic medical records. Data analysis was performed to ascertain which mutations carried an increased risk of death. Results: The TP53 mutation was very common, seen in 85% of squamous cell carcinoma (SCC) histology and 55% of adenocarcinoma. Similarly, incidence of PTEN deletion by FISH was noted to be 52% in SCC and 31% in adenocarcinoma. EGFR mutations were rare, seen in only 3% of tested patients. We had an incidence of KRAS G12C mutations at 11% overall, but it was present in up to 18% of adenocarcinomas. BRAF was seen in 4.8% of all cases, 8% of adenocarcinomas and 2% of SCC. Since there were more than 2 predictors, Cox proportional-hazards regression model was fit. Due to either having all negative values or very few positive values, the variables CCND1, CDKN2B, ERBB2, ERBB4, FGFR, FGFR2, MET, MSI, NRAS, PDGFRA, RET, RS01, SCR were excluded from analysis. A total of 156 samples were used in final analysis. After model building, it was found that BRAF and KRAS G12C mutation were significant predictors of survival by hazard ratios for death. Conclusions: In our unique patient population, there was a greater incidence of deleterious TP53 mutations and PTEN deletions compared to the general North American advanced/metastatic NSCLC population. Although BRAF and KRAS G12C mutations were not at a greater incidence in comparison to the rest of North America, they were notably significant predictors of survival, conferring nearly 3.4 and 2.7 times increased risk of death in our study. [Table: see text]
Prognostic nomogram for overall survival in patients with stage IV non-small cell lung cancer treated with chemotherapy combined with high-dose thoracic radiotherapy.
Authors: Geng YiChao , Su Shengfa , Ouyang Weiwei , Hu Yinxiang , Li Qingsong , Ma Zhu , Luo Daxian , Yang Wengang , Chen Xiaxia , Hu Cheng , Lu Bing
Published: July 2024

e20607

Background: Although the targeted therapy and immunotherapy have become the first line options for selected stage IV non-small cell lung cancer (NSCLC) patients. However, there are instances where certain patients are not administered targeted therapy or immunotherapy due to a variety of factors, chemotherapy and radiotherapy remain the main way to treat such patients. This study aimed to construct a prognostic nomogram for patients with stage IV NSCLC treated with chemotherapy combined with high-dose (≥ 60 Gy) thoracic radiotherapy. Methods: The nomogram was based on a retrospective study of 335 patients with stage IV NSCLC who treated with chemotherapy combined with high-dose (≥ 60 Gy) thoracic radiotherapy were hospitalized between January 2010 and January 2018(patient did not receive TKI therapy or immunotherapy). The patients were randomly assigned to either a primary cohort (n = 234) or a validation cohort (n = 101) at a ratio of 7 : 3. In the primary cohort, a univariate analysis of the clinical or therapeutic factors that may predict OS was performed using a Cox regression model, with P < 0.05 indicating statistical significance. The variables from the univariate analysis that affected OS significantly were included in the Cox regression model for the multivariate analysis. A nomogram was then created based on the results of multivariate analysis and using the “rms,” “foreign,” and “survival” R version 4.0.3 software packages. The discriminatory ability of the nomogram was measured using the area under the curve (AUC) of a receiver operating curve (ROC). Results: Multivariate logistic regression analysis revealed that malignant pericardial effusion, adrenal metastasis, elevated lactate dehydrogenase levels, and excessive planning target volume were independent risk factors for poorer 1–3 year overall survival (OS), while a higher radiotherapy dose for the primary lesion was associated with better OS. Nomogram prediction models were constructed using these five variables. The AUC of the ROC for 1-year, 2-year, and 3-year OS in the primary cohort were 0.685, 0.729, and 0.816, respectively. In the validation cohort, the AUC of the ROC for 1-year, 2-year, and 3-year OS were 0.706, 0.749, and 0.797, respectively. The Kaplan-Meier survival analysis showed that differentiation between the high-risk group and low-risk group using the prediction model had a direct, significant effect on survival in both the primary cohort ( P < 0.001) and validation cohort ( P = 0.004). Conclusions: The nomogram model constructed in this study may be used to objectively predict the prognosis and OS of patients with stage IV NSCLC treated with chemotherapy and high-dose thoracic radiotherapy. Identify patients who may not benefit from high-dose thoracic radiotherapy prior to treatment to avoid overtreatment.