bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.
Authors: Dean Andrew Peter , Mulligan Fiona , Kelly Geena , Shaughnessy Emma , Wilson Kate 
Published: June 2021

e16274 Background: In our phase I trial of the first-in-class agent CEND-1 with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer, we reported a preliminary overall RR of 59% in 29 patients across 3 institutions. Our site enrolled 19 of these patients and we present updated outcome data from this institution. CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. Methods: We reviewed our updated outcome data from the first in human CEND-1 trial in pancreatic cancer. Patients received a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Data was analysed to determine response rate, progression free survival and ongoing benefit. Results: Of the 19 patients that were enrolled at this institution; 13 (69%) showed partial response, 5 (26) % had stable disease, and 1 (3.4%) had progressive disease. Median progression free survival for this cohort was 8.8 months. 4 patients (21%) remain on the trial without disease progression to date. Median treatment duration for these patients is 20 months (range 17.1 – 24.6 months). Adverse events were as previously described¹ with no new significant events or toxicities. Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial with notable progression free survival. No new safety signals or adverse events have been detected with this prolonged follow-up. The randomised phase 2 trial of this combination will be proceeding later this year. Clinical trial information: ACTRN12618000804280.
Frequency and risk factors for metastasis in newly diagnosed appendiceal carcinoma.
Authors: Minhas Ahmed , Minhas Sohail A. 
Published: June 2021

e16281 Background: Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using ICD-O-3 histology/behavior codes between 2010-2015. Logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, grade, and tumor and nodal stage using the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Results: We identified a total of 3, 447 patients with known metastatic status. 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) was associated with significantly higher odds of presenting with metastasis at diagnosis in unadjusted (OR 3.55; 95% CI [2.97-4.24]) and adjusted (OR 2.97 [2.26-3.89]) regression. Signet ring cell carcinoma (SC) also had higher odds in unadjusted (OR 3.91 [2.99-5.12]) and adjusted (OR 2.05 [1.33-3.15]) regression. Goblet cell carcinoma (GC) was associated with lower odds in unadjusted (OR 0.28 [0.21-0.37]) and adjusted (OR 0.58 [0.36-0.94]) regression. The table describes the association of tumor and nodal stage with metastasis at diagnosis. Women had higher odds in unadjusted (OR 1.59 [1.39-1.82]) and adjusted (OR 1.93 [1.55-2.39]) regression. 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions: A significant proportion of patients with appendiceal carcinoma had metastasis at diagnosis. Compared to CA, MA and SC were much more likely to present with metastasis at diagnosis, while GC was less likely. Women had almost twice the odds of presenting with metastatic disease as men. T4 and N2 stages showed much higher odds of metastasis at diagnosis compared to T1 and N0 stages, respectively. Surprisingly, T2 and T3 stages were associated with lower odds of metastasis at diagnosis than T1 stage.[Table: see text]
Primary urachal carcinoma: A systematic review.
Authors: Findakly Dawood , Wang Jue 
Published: June 2021

e16502 Background: Primary urachal carcinoma (PUC) is a rare cancer of unknown definite cause, and various treatment approaches given its very low incidence and the scarcity of prospective studies. This review aimed to assess the clinicopathologic findings, treatment, and outcomes of PUC cases reported in the literature. Methods: We performed PubMed, Medline, ScienceDirect, and Scopus literature search for "urachus cancer" in adults (19+ years) from data inception through 2020, pooled with six cases from our institution. Results: We included 152 patients with a male: female ratio of 1.61:1 and mean age at diagnosis (±SD, range) of 50.0 (±13.5, 20–86) years. Most common presenting symptoms were hematuria, irritative voiding, abdominal pain, mucinuria, and a palpable mass in 49.5%, 17.3%, 10.2%, 8.7%, and 6.6% of patients, respectively, with a median duration of symptoms of 3 (range 0.25-240) months. Most common locations were the urinary bladder dome (83.6%), supero-anterior (7.03%), and the anterior wall (3.9%), with a median size of 4.9 (range 0.5–96) cm. Subgroups, according to tumor size, were divided into < 4 cm (n = 54, 35.5%) vs ≥4 cm (n = 98, 64.5%) with a significant survival differences according to a log-rank test (p-value < 0.0001). Histologically, the most common diagnoses were urachal adenocarcinoma (43.4%), followed by mucinous adenocarcinoma (24.1%), adenocarcinoma of enteric type (8.9%), and adenocarcinoma with signet ring cell (6.9%). 17.5% and 72.2% of patients were diagnosed at an early stage (stage I and II) while 82.5% and 27.8% were diagnosed at an advanced stage ( III and IV) using Sheldon staging system and Mayo staging system, respectively. Only 9.9% of patients lived for more than five years after their diagnosis. Early Sheldon stage is associated with a high survival probability based on a log-rank test (p-value: 0.003). Overall, most common treatment modalities included surgery alone (71.0%), followed by surgery with chemotherapy (18.6%), and surgery with chemoradiation (4.1%). Patients underwent partial cystectomy (65.4%), en bloc radical resection/exenteration (25.7%), local resection (8.8%), pelvic lymphadenectomy (38.2%), and umbilectomy (16.9%). Almost 79% of patients were alive with an average duration of follow-up of 12 (range 0.9-240) months, and 20.9% were deceased with an average time to death of 23.9 (range 5-139) months. Conclusions: Early Sheldon stage and smaller tumor size were notable predictors of higher survival probability in PUC patients. Hence, early and correct diagnosis is crucial in improving outcomes. This review serves as real-world evidence to promote our understanding of this rare entity and shed light on future clinical trial design.
Clinical safety and activity of cabozantinib (CABO) plus durvalumab (DURVA) in patients (pts) with advanced urothelial carcinoma (UC) after platinum chemotherapy (ARCADIA): Preliminary results from a nonrandomized, open-label, phase 2 trial.
Authors: Giannatempo Patrizia , Franza Andrea , Marandino Laura , Raggi Daniele , Calareso Giuseppina , Alessi Alessandra , Colecchia Maurizio , Bevilacqua Liana , Russo Giusy , Del Re Marzia , Anichini Andrea , Sgambelluri Francesco , Sepe Pierangela , Zimatore Matteo , Claps Melanie , Verzoni Elena , Guadalupi Valentina , Ottini Arianna , Procopio Giuseppe , Necchi Andrea 
Published: June 2021

e16529 Background: Combining anti-VEGFR drugs with checkpoint inhibitors have shown synergistic effect in pts with UC. ARCADIA is a phase 2 trial evaluating the safety and efficacy of combination of CABO, a multikinase inhibitor, with the anti-PDL1 DURVA in pts with platinum-refractory advanced UC or variant histology (NCT03824691). Herein we report the preliminary results. Methods: Pts received CABO 40 mg daily, orally, in combination with DURVA 1500 mg, intravenously, every 28 days, until disease progression or unacceptable toxicity. Key inclusion criteria were: ECOG-PS 0-1, UC or variant histology, failure of 1 or 2 platinum-based regimen for metastatic disease, non-measurable disease was permitted. Response was evaluated by RECIST criteria v.1.1 every 2 cycles by CT and 18FDG PET/CT scans. The primary endpoint of the study was overall survival (OS). Other endpoints included safety, objective response-rate (ORR), duration of response, progression-free survival (PFS). PD-L1 expression was assessed by Ventana SP142 assay. Next-generation sequencing tests (FoundationOne) on pre-therapy tumor samples were performed. Results: From September 2019 to February 2021, 26 pts were enrolled with a median follow-up of 5 mo. Median age was 64 yrs (range 44-74), 69% were male, and 23% had ECOG PS 1. 8 pts presented variant histology. Five pts (19%) had received 2 prior systemic anticancer therapies. In pts evaluable for efficacy analyses, 3 (11.5%) complete responses (CR) and 6 (23.1%) partial responses (PR) were observed. The ORR and DCR were 34.6% and 57.7% respectively. Treatment-related AEs (TRAEs) occurred in 17 pts (65%), including 2 (8%) grade 3 TRAEs, within the first 2 cycles. 7 pts (27%) discontinued CABO due to toxicity, no interruption of DURVA was observed. The most common AEs by any grade were transaminase increase (35.7%), asthenia (27%), diarrhea (27%), and hypertension (15%). Conclusions: Combination of CABO and DURVA demonstrated promising preliminary activity and a manageable safety profile in pts with advanced UC and variant histology. More mature results according to biomarkers and histology will be presented. Clinical trial information: NCT03824691.
Retrospective analysis of multiparametric MRI to predict complete pathologic response after neo-adjuvant chemotherapy for muscle invasive bladder cancer.
Authors: De Maeseneer Daan , De Visschere Pieter , Van den Broecke Mats , Villeirs Geert , Verbeke Sofie , Decaestecker Karel , Rottey Sylvie 
Published: June 2021

e16535 Background: Muscle invasive bladder cancer (MIBC) is a life-threatening disease. Treatment is multimodal combining neo-adjuvant cisplatin-based chemotherapy (NAC) and radical cystectomy (RC). Accurately predicting complete pathologic response (pCR) using multiparametric MRI (mpMRI) could impact peri-operatively treatment. Methods: MIBC patients receiving NAC were evaluated at our institution with mpMRI before, after 2 cycles and after 4 cycles of dose dense MVAC (ddMVAC). Response after 4 cycles was retrospectively assessed using the method earlier described by Necchi et al with blinding of the readers for the pathological result of RC. Two radiologists independently evaluated 3 questions: residual disease at T1/T2-weighted images, presence of spots of restrictive diffusion within the bladder wall on diffusion-weighted imaging, and presence of focal contrast enhancement in the bladder wall on dynamic contrast enhanced images. Radiographic complete response (rCR) was defined as “No” on all three questions. Results: A total of 46 patients were identified having received ddMVAC for urothelial MIBC. Six patients did not undergo RC after NAC and were excluded from this analysis. Eleven out of 40 (28%) patients showed a complete pathologic response (ypT0). Baseline characteristics were similar compared to non-complete pathologic responders ( > ypT0), with the exception of hydronephrosis (9% in ypT0 vs. 52% in > ypT0). mpMRI questions could be assessed in 37 of 40 patients (93%). rCR was seen in 5 patients and was significantly associated with pCR (1-sided p value 0.021). Although sensitivity was low (36%), specificity was very high (96%) of this 3-step assessment. Positive likelihood ratio was 9.45, negative likelihood ratio 0.66. Concordance of assessment was very high. Conclusions: Using the 3-step imaging approach of Necchi et al, mpMRI can predict pCR after neo-adjuvant cisplatin-based chemotherapy with high specificity but low sensitivity. mpMRI should be included in future trials of multimodal management of MIBC and is an important predictive asset in routine clinical management.[Table: see text]
Association of BMI, body composition and outcomes in Chinese patients with metastatic renal cell carcinoma treated with immunotherapy: A retrospective, multicohort analysis.
Authors: Wang Jun , Qu Yuanyuan , Xu Wenhao , Yu Chunping , Zhang Zhiling , Ye Dingwei , Zhou Fangjian 
Published: June 2021

e16563 Association of BMI, body composition and outcomes in Chinese patients with metastatic renal cell carcinoma treated with immunotherapy: a retrospective, multicohort analysis. Background: Obesity (body-mass index [BMI] ≥30 kg/m) is associated with a higher risk of developing clear cell renal cell carcinoma (RCC) but, paradoxically, obesity is also associated with better outcome in renal cell carcinoma (RCC) patients treated with immunotherapy. Whether BMI associate outcomes in Chinese RCC patients treated with immunotherapy considering Asian population has a lower BMI? In this study, we aimed to investigate the relationship between BMI, body composition and outcomes of Chinese patients with RCC treated with immunotherapy. Methods: We evaluated clinical data of metastatic RCC patients treated with immunotherapy from five major centers in China. Despite using the Chinese standard, only 6 people met the obese standard (BMI ≥28 kg/m, as per WHO's BMI categories), so we divided the patients into high BMI gourps (BMI ≥24.0 kg/m), and normal weight groups (BMI 18.5-23·9 kg/m). We assessed overall survival, defined as the time from treatment initiation to the date of any-cause death or of censoring on the day of the last follow-up, in high BMI patients and in patients with a normal weight. We also investigative the relationship between body composition (skeletal muscle index (SMI = skeletal muscle area/height2), skeletal muscle density (SMD), and subcutaneous adipose distribution index (SADI = subcutaneous adipose tissue area / subcutaneous adipose tissue area + visceral adipose tissue area) of each patient at the third lumbar vertebrae) and overall survival using CT or MRI scan at the treatment initiation. Results: Out of a total of 222 patients, 203 had evaluable CT or MRI radiographs, pretreatment BMI measurements, and overall survival data for analyses, and we excluded 4 (1.7%) underwetight patients, leaving a final cohort of 199 patients from this study for our analyses. There were 79 (39.7%) high BMI patients and 120 (65.3%) normal weight patients. There was no difference in overall survival between the high BMI and normal weight groups (HR:1.36, CI 0.83-2.21). In addition, SMI and SMD were not associated with outcome of patients. Interestingly, although there was no statistical difference, subcutaneous fat was associated with better outcomes, while visceral fat was associated with poor outcomes. Thus, the combination of the two indicators, SADI, showed a significant prognostic correlation after adjustment for International Metastatic RCC Database risk score (aHR:0.314, CI 0.19-0.51). Conclusions: BMI is not a good predictor of the outcome of immunotherapy in Chinese patients with RCC. Evaluation of body composition may be a better tool for predicting prognosis in RCC patients treated with immunotherapy.
What happened to the preserved renal parenchyma after partial nephrectomy?
Authors: Campbell Steven , Xiong Longbin , Jane Nguyen , Zhou Fangjian , Zhang Zhiling , Peng Yulu 
Published: June 2021

e16581 Background: Partial nephrectomy (PN) is the standard therapy for small renal mass, despite various degree of ischemia reperfusion injury (IRI) is always inevitable as the renal artery is usually clamped during PN. In mouse IRI model, unilateral renal artery clamped for 21 minutes results to sever kidney fibrosis in one year. However, what happened to the preserved renal parenchyma after several years since PN is still a mystery. The aim of the study is to compare the pathological chronic kidney disease (CKD) score of normal renal parenchyma before and several years after PN, as well as to explore the factors that associated with CKD score increase and GFR decline. Methods: We retrospectively collected the clinicopathologic data of 114 renal cell carcinoma (RCC) patients who underwent PN and subsequent radical nephrectomy (RN) due to tumor recurrence in 19 Chinese centers and Cleveland clinic. Macroscopic normal renal parenchyma was sampled at least 5 mm away from the tumor border in PN specimen and at distal portion of the kidney in RN specimen. Pathological CKD score is a summary of glomerular, tubular, interstitial, and vascular score. MDRD2 equation was used to estimate the glomerular filtration rate (GFR). Predictive factors for CKD score increase were evaluated by logistic regression. Results: A total of 64 patients that have all the required data were included in the analysis. The median duration warm ischemia (n = 41) and hypothermia (n = 23) were both 23 min. In a median interval of 2.44 years, the CKD score arose in 73.4% (47/64) patients, with 45.3% (29/64) cases increased by ≥3. Even so, no kidney fibrosis was observed in this cohort including in those with extend warm ischemia (≥45min). There was no significant difference in the change of CKD score during patients with different ischemia time and type. However, patients with comorbidities such as hypertension, diabetes mellitus or CKD (HTN/DM/CKD) showed higher rate and extent of CKD score increase. In multivariate analysis, HTN/DM/CKD was found to be an independent predictor for the CKD score increase [OR:4.24 (1.23-14.64)]. However, the decline of GFR was mild and analogous between patients with or without CKD score increase (23.03±22.53ml/min/1.73m2 vs. 24.27±21.79ml/min/1.73m2, p = 0.856). Conclusions: In majority, preserved renal parenchyma after PN suffered pathological deterioration. Ischemia time and type seem to have limited impact on the change of CKD score of preserved renal parenchyma during PN. Patients with HTN/DM/CKD have higher risk of CKD score increase in despite of similar mild GFR deterioration.
Post radical prostatectomy prostate-specific antigen doubling-time kinetics: Observations of increasing versus decreasing doubling times.
Authors: Huynh Linda My , Huang Erica , Skarecky Douglas , Ahlering Tom Edward 
Published: June 2021

e17002 Background: Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of distant metastatic progression or prostate cancer (PC) death, consequently resulting in overtreatment. Further, little has been published about active surveillance (AS) specific management recommendations. Herein, we validate the practicality of using the kinetics (change) of PSA doubling time (PSADT) to direct continued observation versus intervention. Methods: In a retrospective cohort analysis of 406 men with BCR (defined as adjuvant therapy or PSA > 0.2 ng/dl, x2), 284 men were monitored post RP with PSADT graphs for all patients, and the PSADT was characterized as increasing vs decreasing. Receiver-operator characteristic (ROC) curves were generated to assess the sensitivity/specificity/positive predictive value/negative predictive value of PSADT progression on treatment and prostate cancer specific mortality at 10 years post-RARP, respectively. Results: The median follow-up was 7.6 (IQR: 4.6-10.6) years. Of 284 men, 109 (38%) and 175 (62%) were in the no treatment versus treatment groups, respectively. 87% of men receiving treatment had a decreasing PSADT and 100% men with PCSM had a decreasing PSADT. ROC analysis showed 0.870 sensitivity and 1.0 specificity when predicting secondary treatment (AUC = 0.935) and 0.857 sensitivity and 0.50 specificity when predicting PCSM (AUC = 0.679). Conclusions: A decreasing PSADT is a sensitive and specific metric for predicting the need for secondary intervention. We also found all men who died of PC had a decreasing PSADT. Lastly an increasing DT predicts a benign course without need for treatment. The current findings suggest that the kinetics of PSADT, increasing versus decreasing, is an accurate metric for the need of treatment. A direct comparison between PSADT kinetics and PSADT is needed.
Genomic characteristics of homologous recombination deficiency in prostate cancer.
Authors: Wei Yu , Yao Zhu , Cui Lina , Zhao Xiaochen , Bai Yuezong , Ye Dingwei 
Published: June 2021

e17004 Background: PARP inhibitors (PARPi) have been approved in the treatment of metastatic castration-resistant prostate cancer with deleterious or suspected deleterious alterations in homologous recombination repair (HRR) genes. Patients carrying alterations of different HRR genes showed diverse response to PARPi, while the underlying mechanism is unrevealed. Homologous recombination deficiency (HRD) score serves as a promising way to interpret the genomic instability by targeted next-generation sequencing (NGS). In this study, we analyzed HRD score and its relationship to genomic characteristics in a prostate cancer (PC) cohort. Methods: Tumor tissue and matched white blood cells from 295 PC patients were analyzed by NGS-based assays, which target over 10,000 single-nucleotide polymorphisms distributed across human genome to characterize genomic instability, as well as the whole coding region of 733 or 233 genes. HRD score was derived by the sum of three indexes, including loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions. Deleterious or suspected deleterious mutations were included for analysis. Tumor mutation burden (TMB) was calculated by the number of somatic single nucleotide variants and indels in examined coding regions, with driver mutations excluded. An ovarian and fallopian tube cancer cohort, carrying deleterious or suspected deleterious mutations in BRCA1/2, was also included. Results: In PC cohort, 25 patients (8.47%) had BRCA1/2 mutations, with additional 39 patients (13.2%) carrying mutations in HRR genes other than BRCA1/2. HRD score was similar among tumors with germline BRCA1/2 mutation (n = 9), somatic BRCA1/2 mutation (n = 14) or both (n = 2) (median HRD score 38.0, 32.5 and 49.5; P = 0.281). In BRCA1/2 mutation carriers, HRD score in PC cohort was lower than ovarian cancer (n = 222) and fallopian tube cancer (n = 8) (median HRD score 36, 54 and 67; P < 0.001). PC samples with CDK12 (n = 35), ATM (n = 13) and PALB2 (n = 2) mutations had lower HRD score compared with BRCA1/2 mutants (median HRD score 24, 14, 11 and 36; P < 0.001). In PC patients without HRR mutation, HRD score was higher in TP53 mutants compared with TP53 wildtype (median HRD score 25 and 14; P < 0.001), while tumors with ERG fusion had lower HRD score than ERG fusion absent tumors (median HRD score 8 and 18.5; P = 0.029). In four TP53 mutated PC patients treated with PARPi in our center, three patients achieved PSA response. Furthermore, no linear correlation was discovered between TMB and HRD score, while tumors with higher HRD score (HRD score ≥ 30) had a bit lower TMB (median TMB 3.07 vs 3.91, P = 0.002). Conclusions: HRD score was affected by alterations in different HRR genes, TP53 mutation and ERG fusion, which should be taken into consideration of the future clinical trials and research on intrinsic mechanisms. Patients carrying alterations other than HRR genes might benefit from PARPi. Further studies are needed.