bluuebunny/crossref_metadata_2025_split huggingface dataset:
A reassessment of the clinical utility of 68Ga-DOTATATE PET/CT in patients with gastroenteropancreatic neuroendocrine tumors.
Authors: Prela Orjola , Caveney Brennen , Strawderman Myla S. , Carpizo Darren R. 
Published: July 2024

e16294 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and biologically diverse group of tumors that can be challenging to image. Gallium-68 (Ga-68) DOTATATE positron emission tomography/computed tomography (PET/CT) is the most sensitive imaging tool for these tumors and has now been in clinical practice for over a decade. While its use has increased over time, its clinical impact remains unclear for specific stages of disease and indications for imaging. We sought to investigate this to provide information to guide its future use in clinical management. Methods: This retrospective cohort study identified adults with pathologically confirmed GEP-NETs between 1/1/2020 and 9/1/2022 at a tertiary care academic medical center. The electronic medical record was reviewed for demographic, clinical, and radiographic data. The primary objective was to determine if the use of 68Ga-DOTATATE PET/CT was associated with a change in clinical management, medical or surgical. The secondary objective was to determine if 68Ga-DOTATATE PET/CT was more effective in identifying primary or metastatic lesions compared to traditional imaging such as CT or magnetic resonance imaging (MRI) performed less than 90 days of the PET/CT scan. Percentages are reported with 95% Confidence Intervals (CI). Results: Overall, 124 patients with pathologically confirmed GEP NETs underwent a total of 207 68Ga-DOTATATE PET/CT scans. The majority (92.7%) of GEP NETs were moderately/well differentiated and the primary sites included the small intestine (50%), pancreas (23.4%), appendix/colon (8.9%), gastric (8.1%), mesentery (2.4%), and unknown (7.3%). Following PET/CT scan, 51 patients (41.1%; 95% CI = 32.4-49.8) had a change in clinical management, with the proportion of patients who had a change being higher among those with metastatic disease (44.9% vs 14.5%). Of the 124, 72 patients had traditional imaging 90 days or less prior to PET/CT available for comparison. In this subgroup, 34 patients (47.2%; 95% CI = 35.7-58.7) had new lesions identified on PET/CT that were not identified using traditional imaging and of the 34 patients with new lesions identified, 79.4% (95% CI = 66-93) had a change in their clinical management. The majority of these patients had M1 disease (50% vs 15.4%). Conclusions: This study highlights the impact of 68Ga-DOTATATE PET/CT imaging in the clinical management of patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Notably this imaging technique resulted in a change in clinical management for 41% of these patients, particularly benefiting those with metastatic (M1) disease, where the change in management was more pronounced (44.9% vs. 14.5%). Furthermore, 68Ga-DOTATATE PET/CT proved superior to traditional imaging revealing new lesions in 47.2% of the patients, with the majority being patients with metastatic disease.
Impact of EOB-MRI on the outcome of patients with pancreatic cancer in real-world settings.
Authors: Oba Atsushi , Taguchi Tomoyuki , Fujikawa Naoto , Okami Suguru , Tsuji Takashi , Michel Alexander , Kado Yuki , Goshima Satoshi 
Published: July 2024

e16298 Background: Contrast-enhanced computed tomography (CE-CT) is a commonly used imaging modality for the preoperative detection of local extension and distant metastasis in patients (pts) with pancreatic cancer (PaC). There have been cases where surgical treatment was deemed unsuitable due to unexpected distant metastases discovered during surgery, which had not been detected by CE-CT. While studies have reported gadoxetate disodium-enhanced MRI (EOB-MRI) improves the detection of liver metastases, it is not clear whether adding EOB-MRI to CE-CT provides clinical benefits, e.g. improved outcomes through the early access to appropriate treatments by avoiding unnecessary surgery (open-close surgery) in pts with PaC. This study aimed to assess the effectiveness of adding EOB-MRI before surgical or non-surgical treatment on overall survival (OS) in pts with PaC in real world settings. Methods: This was a retrospective cohort study using a nationwide hospital-claims database in Japan. Pts aged ≥18 years diagnosed with PaC with a record of surgery, radiotherapy, or chemotherapy, who had an imaging modality were identified between January 1, 2011 to October 31, 2021. Pts were grouped into EOB-MRI and no EOB-MRI groups, and further grouped into surgery, no surgery and open-close laparotomy. OS was compared between propensity-score matched EOB-MRI and no EOB-MRI groups using the Cox regression model. Results: 39,624 pts were included in the study, of them, 4,477 (11.3%) underwent EOB-MRI prior to the initial treatment. 2,061 (46.0%) pts in EOB-MRI group underwent surgery, 2,346 (52.4%) had no surgery and 70 (1.6%) had open-close laparotomy. In 35,147 (88.7%) pts in no EOB-MRI group, 13,182 (37.5%) underwent surgery, 21,506 (61.2%) had no surgery, and 459 (1.3%) had open-close laparotomy. The OS results in subgroups are shown in the Table. Conclusions: In real-world settings, EOB-MRI performed prior to the initial treatment was associated with significantly higher OS than those without EOB-MRI in pts who did not undergo surgery, but there was no difference in OS in pts who underwent surgery. These results suggest that the early detection of micro hepatic metastases through EOB-MRI and multidisciplinary treatment that enables EOB-MRI may contribute to improved outcomes in pts with PaC. [Table: see text]
Unveiling the nexus: Use of e-frailty index in predicting chemotherapy tolerance in older patients with pancreatic cancer.
Authors: Al-Jumayli Mohammed , Sehovic Marina , Vonnes Cassandra , Extermann Martine 
Published: July 2024

e16315 Background: Pancreatic cancer prevalence is on the rise, particularly among octogenarians—individuals aged 80 years and above. This age group, however, remains notably underrepresented in clinical trials, hindering the applicability of findings to this growing demographic. Methods: We conducted a retrospective study investigating the predictive potential of the E-frailty Index (EFI) in relation to chemotherapy tolerance in octogenarian patients with unresectable/metastatic pancreatic adenocarcinoma. Drawing from EFI's developmental insights in a prior study¹, our cohort comprised 72 octogenarians undergoing chemotherapy. Results: Despite a modest statistical correlation (R = 0.038, p = 0.751), our study revealed a weak, but positive association between EFI and chemotherapy toxicity. Conclusions: Our findings, while subtle, highlight the potential relevance of EFI in predicting chemotherapy outcomes among octogenarians. The non-significant correlation underscores the need for larger-scale, prospective trials to confirm these insights. Inconclusion, This study, rooted in the developmental continuum of EFI, offers a glimpse into its potential significance in predicting chemotherapy tolerance in octogenarian pancreatic cancer patients. The call for prospective trials is evident, especially considering the underrepresentation of this demographic in current research.
A preliminary enrichment analysis of tumor genes in patients suffering from rectal cancer with and without CNS metastasis.
Authors: Polyak Andrew , Cholankeril Michelle 
Published: July 2024

e16381 Background: Colorectal cancers have been touted as the third most common cancer and the third leading cause of cancer death worldwide. Of these, rectal cancers often have a more favorable outcome, and are generally responsive to chemotherapy and radiation, due to metastasis limited to local tissues via lymphatics. However, in recent years, cases of rectal cancer with distant metastasis to the CNS have been noted at an urban community hospital serving a primarily Hispanic population in central New Jersey. Methods: We used genetic data from 51 patients at our local cancer center over 5 years to delineate risk factors associated with CNS metastasis. Of these patients, two had CNS metastasis with available tumor genetic information. We performed a gene enrichment analysis to determine phenotypic terms and molecular pathways associated with each gene set using Enrichr. Results: Of 51 patients, genetic data was available on 20, of which 18 had rectal cancer without CNS metastasis. Mutations involving 23 genes were found in this cohort, analysis of which found enrichment of the terms “Lynch Syndrome” and “Constitutional mismatch repair deficiency syndrome”, which are classically implicated in CRCs. In addition, enrichment of the terms “rectal cancer childhood”, “colorectal cancer childhood”, and “Familial colorectal cancer” were found. Of the two patients who had metastasis to the CNS, mutations involving 14 genes were found. Interestingly, both patients had mutations involving KRAS. Analysis of these genes found enrichment of the terms “pilomyxoid astrocytoma”, “giant cell glioblastoma” and “gliosarcoma”. Interestingly, common to both cohorts were the classic CRC-associated genes KRAS, APC and TP53, further solidifying their role in general CRCs. Conclusions: While this study is ongoing, preliminary data suggest that genetic analysis of tumors in patients with rectal cancer can determine whether a patient is susceptible to CNS metastasis. Given the heterogeneity of these cancers, further studies involving tumor and germ-line genetic analysis, which follow patients longitudinally may benefit in predicting which tumors are prone to CNS metastasis before they metastasize.
Lutetium-177–PSMA-617 experience in Appalachian patients with advanced prostate cancer at West Virginia University Health Science Center.
Authors: Yu Stephen Lee , Holler Seth , Wen Sijin , Wang Xiaofei , Hogan Thomas F. 
Published: July 2024

e17045 Background: Lutetium Lu-177 vipivotide tetraxetan (Lu-177) allowed for improved biochemical and radiographic response rate with relatively low toxicity for metastatic castration-resistant prostate cancer (PC) after multiple lines of therapy. In the 2021 VISION study (DOI: 10.1056/NEJMoa2107322), Lu-177 was reported to have a median overall survival (OS) of 15.3 months in patients (pts) with advanced prostate cancer (PC). We reviewed the result with Lu-177 for the treatment of advanced PC at a rural tertiary academic center at West Virginia University Health Science Center (WVU-HSC). Methods: All PC pts receiving one or more doses of Lu-177 at WVU-HSC were retrospectively reviewed. Pts were followed until death or the last clinic visit. All pts were established patients at WVU-HSC for management of the advanced PC between July 2022 and February 2024. Data was tabulated with descriptive statistics and median survival was calculated from Kaplan-Meier method. Results: Over an eighteen months period 34 pts received 126 doses of Lu-177. 26 pts were referred from outside the WVU-HSC specifically for Lu-177. Demographics from data collection showed predominantly Caucasian pts (91% Caucasian). The time from the initial PC diagnosis to the first dose of Lu-177 was a median of 67 months (range: 10 months-367 months). The median age at the first dose of Lu-177 was 65 years (range: 45-80). 18 patients (53%) remain alive as of Feb 2024. 14 pts (41%) completed 6 cycles of Lu-177 and 11 pts (32%) remain alive. The Kaplan-Meier median OS for these 34 pts starting from the first cycle of Lu-177 was 10 months. Conclusions: A 2022 estimated cost for Lu-177 was $42,500 per dose (excludes administration) so “payors” may have been charged more than $5,000,000 for the Lu-177 for these patients. Lu-177 may be of more benefit earlier in the PC disease spectrum, or perhaps pre-treatment PSMA imaging can better target patients who will benefit from Lu-177. Our observed median OS of 10 months did not match the 15.3 reported in the VISION study (DOI: 10.1056/NEJMoa2107322). Further data evaluation and collection are warranted from different communities to investigate the differences observed in the survival data reported in the literature and observed in the clinic setting. [Table: see text]
Quality metrics analysis in patients who received Lutetium-177 PSMA-617 (177Lu–PSMA) therapy in a real-world practice setting.
Authors: Yazdanpanah Omid , Dwabe Sami , Warnecke Brian , Benjamin David Joseph , Srinivas Shyam M. , Rezazadeh Arash , Mar Nataliya 
Published: July 2024

e17049 Background: 177Lu–PSMA is a radiolabeled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA). It has been approved for use in metastatic castration-resistant prostate cancer (mCPRC) in 3/2022, based on VISION study. The Food and Drug Administration (FDA) label for 177Lu–PSMA requires prior therapy with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy as well as presence of at least one PSMA-positive tumor with uptake greater than normal liver and no PSMA-negative lesions on a PSMA positron emission tomography (PET) scan. In the VISION study, PSMA PET was performed within 4 weeks of therapy start. Further, patient received either 177Lu–PSMA plus protocol permitted standard of care (SOC), including ARPI, or SOC alone. Given the relatively recent approval of this therapy, real-world familiarity with administration of this agent may not be optimal. Methods: A retrospective analysis of 25 patients with mCRPC who received 177Lu–PSMA therapy since 3/2022 at the University of California Irvine (24/25) and Hoag Hospital (1/25) was performed. Multiple variables were analyzed and compared to the FDA label for this agent as well as design of the VISION study. Results: All patients in this study had received an ARPI and at least one taxane chemotherapy prior to 177Lu–PSMA. A PSMA-PET scan was obtained prior to 177Lu–PSMA therapy in all patients. The timing of the scan was within 4 weeks of starting 177Lu–PSMA therapy in only 5/25 (20.0%) patients. The average time from PSMA PET scan to 177Lu–PSMA therapy start was 66 days [range: 18 - 326 days]. None of the PSMA PET scan reports included a baseline liver standardized uptake value (SUV) or mentioned whether any lesions were non PSMA-avid. All reports provided SUV values for some, but not all, PSMA-avid lesions. The average maximum SUV of the most PSMA-avid lesion noted on the reports was 34.7. All PSMA PET scans were retrospectively reviewed by a nuclear medicine specialist and the average maximum SUV of the most PSMA-avid lesion on re-review was 42.0 (p <0.05). During 177Lu–PSMA therapy, co-administration of ARPI occurred in 10/24 (23.8%) of patients. Conclusions: This study highlights the differences in quality metrics between patients who received 177Lu–PSMA therapy in a real-world practice setting compared to the FDA label for this agent and VISION study design. Differences included lack of uniform PSMA PET scan reporting, timing of obtaining pre-treatment PSMA PET imaging, and co-administration of ARPI. Development of institutional algorithms around administration of 177Lu–PSMA therapy may be needed.
Urinary-based detection of MSL, HE4, and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.
Authors: Wimberger Pauline , Schwarz Franziska Maria , Klotz Daniel , Kuhlmann Jan Dominik 
Published: July 2024

e17567 Background: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified by Lumipulse G chemiluminescent enzyme immunoassay (Fujirebio). In total, this study was based on 1080 biomarker detection runs from 188 serum and 172 urine samples from 192 ovarian cancer patients. Results: While absolute concentrations of MSL and CA125 were higher in serum than in urine, serum HE4 concentrations were considerably lower than urinary HE4 concentrations. Nonetheless, relative intra-patient levels of all three biomarkers strongly correlated between matched serum vs. urinary samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity in predicting surgical outcome and relapse/death among both body fluid types (urinary HE4: AUC=0.854; AUC=0.750, respectively). All clinically relevant findings of urinary MSL, HE4 and CA125 were reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis. Conclusions: We report that the capacity of MSL, HE4 and CA125 for predicting surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.
Ovarian-Adnexal Reporting & Data System (O-RADS) versus modified benign descriptors and IOTA ADNEX (two-step strategy) in classification of ovarian masses.
Authors: Rodríguez Nadiezhda , Pérez Sophia , Rodríguez Juan Nicolás , Cantor Nicolás , Ardila Fabian , Esquivel Alba Liliana , Segovia Javier 
Published: July 2024

e17569 Background: The use of a single and common language in the diagnosis of ovarian tumors is a multidisciplinary effort spanning several decades that has allowed the global adoption of the Ovarian-Adnexal Reporting & Data System (O-RADS) and the International Ovarian Tumor Analysis (IOTA). The objective is to determine the diagnostic accuracy of O-RADS versus modified benign descriptors and IOTA ADNEX in the classification of adnexal masses. Methods: Ambispective diagnostic accuracy study based on ultrasound data collected at a university hospital with a gynecologic oncology unit between 2012 and 2022. Two IOTA-certified level III sonographers classified adnexal masses using modified benign descriptors (MBD). The main outcome was the classification of the masses as benign or malignant for each strategy. Histopathology was used as the diagnostic reference standard. A diagnostic test analysis was performed. Results: 876 patients with 902 adnexal masses were included in the study for both analysis strategies. For the two-step analysis, 573 (64%) met the classification criteria for their evaluation based on MBD (first step) and 329 (36%) were assessed using IOTA ADNEX. 99% (567/573) of the masses classified according to the MBD, were benign by histopathology. The diagnostic performance of IOTA ADNEX (second step) had a sensibility of 93%, specificity of 64%, positive predictive value of 48%, negative predictive value of 96%, AUC (0,880). Regarding the analysis of the O-RADS system to stratify malignancy risk, we observed a prevalence of 58% for O-RADS 2, 22% for O-RADS 3, 11% for O-RADS 4, and 9% for O-RADS 5. Sensibility was 92%, specificity 88%, positive predictive value 48%, negative predictive value del 99%, AUC (0,886). Conclusions: In our experience, the diagnostic accuracy of the two-step strategy or the O-RADS system is similar. However, the ORADS system had a lower proportion of false negatives.
Outcomes in STK11-, KEAP1-, and KRAS-mutant lung squamous cell carcinoma (LSCC) with use of immune checkpoint inhibitors (ICIs).
Authors: Marin-Acevedo Julian A. A. , Shi Justin Wang , Han Yan , Tran Mya , Karkash Ahmad , He Weston , Shields Misty Dawn , Hanna Nasser H. 
Published: July 2024

e20504 Background: Studies have suggested that STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with lung adenocarcinoma. The effect of these mutations in LSCC is unknown. Methods: We conducted a retrospective analysis from January 1, 2018 through December 31, 2023 evaluating individuals seen in the Indiana University Health System with STK11, KEAP1, or KRAS-mutant advanced LSCC treated with ICI-based therapy. Demographic information and baseline PD-L1 levels were collected. Response to therapy was assessed using standardized real-world criteria. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared using a log-rank test. Results: Thirty-one of 316 evaluable patients with LSCC had a mutation in KEAP1, STK11, or KRAS. Twenty-one of those individuals had advanced disease treated with ICIs. Nine of 21 had tumors harboring KEAP1 and/or STK11, 10 had tumors harboring KRAS, and 2 had KRAS + STK11-mutant tumors. The median age was 67 years, 71% (15/21) were male, 86% (18/21) were White, 83% (15/18) had PD-L1 levels ≥1%, and 81% (17/21) were evaluable for response including 11 treated with ICIs + chemotherapy and 6 who received ICIs alone. The overall response rate (ORR) was 65% with 5 individuals having progressive disease (PD), 1 with stable disease (SD), and 11 exhibiting partial response (PR). Those receiving ICIs + chemotherapy had an ORR of 73% (3 PD, 8 PR). The ORR was 50% (2 PD, 1 SD, 3 PR) in the cohort treated with ICIs alone. Among those with KEAP1 and/or STK11 mutations, the ORR was 43% (4 PD, 3 PR). The ORR was 88% for the KRAS-mutant cohort (1 SD, 7 PR) and 50% in the KRAS + STK11 subgroup (1 PD, 1PR). The median PFS was 6.4 months for the entire population, 6.0 months for those treated with ICIs + chemotherapy, and 8.1 months for those receiving ICIs alone. Although the cohort size was limited, individuals with KRAS mutations appeared to have improved PFS compared to those with STK11, KEAP1, or KRAS + STK11 mutations treated with ICI-based therapy (Table 1). Conclusions: STK11, KEAP1, and KRAS mutations impact response to ICIs in individuals with LSCC. There was a trend toward improved ORR and PFS in those with KRAS-mutant LSCC treated with ICI-based therapy compared to those with STK11, KEAP1, or KRAS + STK11-mutations. [Table: see text]