bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients with underlying autoimmune disease (AID).
Authors: Ahmed Gulrayz , Annunzio Kaitlin , Szabo Aniko , Eastwood Daniel , Thapa Bicky , Taylor Bradley W , Tsai Susan , Christians Kathleen K. , Clarke Callisia , Evans Douglas B. , Hall William Adrian , Erickson Beth , Kamgar Mandana , George Ben
Published: June 2021

e16233

Background: Chronic inflammation from AID and the resultant immunosuppression from treatment increases the risk of various malignancies. Risk of PDAC is increased in patients (pts) with AID, however, there is paucity of cancer specific outcome data in these pts. We retrospectively reviewed the outcomes of pts with PDAC and AIDs to include Crohn’s disease (CD), ulcerative colitis (UC) and rheumatoid arthritis (RA). Methods: All pts aged 18 or older, diagnosed with PDAC in the setting of CD, UC and RA between January 2010 and December 2019 were included. Patients were identified using our institutional Clinical Research Data Warehouse (CRDW) and chart review. Clinical data was obtained by querying a cohort discovery tool (i2b2) from the CRDW with IRB approval. Pts with incomplete documentation were excluded. Descriptive statistics were used to report demographics. Overall survival (OS) was calculated from the time of diagnosis of PDAC to the date of death or last follow-up. Deaths from any cause were included in the survival analysis. OS and relapse free survival (RFS) were estimated using Kaplan-Meier methods. Results: We identified 51 pts who met inclusion criteria; 26 (51%) had RA, 15 (29.4%) had UC and 10 (19.6%) had CD. Median age at diagnosis of PDAC was 55.2 years, 49% were male (Table 1). Median duration from diagnosis of AID to PDAC for pts with CD, RA and UC was 173, 107 and 105 months, respectively. Metastatic disease at diagnosis was present in 19 (37.3%) of the 51 pts and 32 (62.7%) had localized disease (LD). Among the 17 pts with LD who underwent surgery, 6 (35.3%) experienced relapse with a median RFS of 14 months. The median OS of pts with LD who underwent surgery was 44 months compared to 8.25 months for those who did not. Among the 19 pts with metastatic disease at diagnosis, 0, 1, 2 & 3 lines of chemotherapy was received by 4 (21.1%), 8 (78.9%), 3 (36.8%) and 2 (21.1%) of pts, respectively. Median OS of patients with metastatic disease at diagnosis was 8.9 months. Conclusions: The inflammatory milieu and immunosuppression associated with AID treatment may be responsible for the early onset of PDAC in these pts. Although our sample size is small, pts with AID and PDAC who complete all planned curative intent therapy appear to have excellent outcomes, emphasizing the importance of early diagnosis and perhaps routine screening in pts with AID. Receipt of chemotherapy and OS of pts with metastatic PDAC in the setting of AID does not appear to be significantly compromised despite their exclusion from several clinical trials. Demographics.[Table: see text]
Evaluating survival in patients with pancreatic adenocarcinoma and lung metastasis.
Authors: Cham Jason , Ebrahimi Aren , Hermel David Jacob , Spierling Bagsic Samantha R. , Sigal Darren
Published: June 2021

e16237

Background: Pancreatic adenocarcinoma most commonly metastasizes to the liver and peritoneum, yet can occasionally metastasize to the lungs in an isolated fashion. Anecdotal evidence suggests that patients who have isolated metastatic disease to the lungs have improved outcomes. We sought to investigate whether pancreatic cancer lung metastasis is associated with improved survival. Methods: We conducted a retrospective review of patients within the Scripps Health system with pathologically confirmed pancreatic adenocarcinoma from 2017 to 2020. Primary sites of metastatic disease were identified with imaging, and when available, confirmed by pathology. A subgroup of 101 patients from a total cohort of 598 patients was further refined to only include patients with lung and/or liver primary metastases (N=68). Analyses were conducted on subgroups defined by metastatic sites of disease in the liver only, lung only and combined liver+lung. Primary and secondary outcome analyses compared isolated lung versus liver/liver+lung. Overall survival (OS) was defined from the date of diagnosis to date of death or most recent follow up, and recurrence free survival (RFS) from the time of diagnosis to date of recurrence. Each survival outcome was analyzed using Cox Proportional Hazards tests. Additionally, proportions of each subgroup (lung v. liver/liver+lung) that had recurrence or were deceased were reported and compared by Fisher’s exact tests. Results: No significant differences were observed in OS (HR 1.91, CI 0.66 – 3.73; p= 0.311) or RFS (HR 0.98, CI 0.42 – 2.30; p= 0.968) between patients with primary lung metastases versus those with either liver or liver+lung metastases (reported as hazard ratios of liver/liver+lung relative to lung only). Although there was no overall statistically significant difference, the kaplan-meier curve for OS appears to show improved survival for patients with primary lung metastasis initially but then ultimately shows worse survival compared to liver only metastasis at later time points. Please see Table.Conclusions: We found no difference in survival outcomes among pancreatic cancer patients with only lung metastasis at diagnosis compared to patients with hepatic metastasis. However, we do observe that patients with lung metastases seem to have improved survival initially. This study was conducted on a small set of the total number of patients with pancreatic adenocarcinoma within the Scripps Health system. Further analysis is ongoing to confirm the trend we observe in this study.[Table: see text]
Cost-effectiveness analysis of platinum-based chemotherapy treatment options for germline BRCA-mutated locally advanced/borderline resectable pancreatic cancer.
Authors: Ingram Myles , Pumpalova Yoanna S , Park Jiheum , Lim Francesca , Manji Gulam Abbas , Kong Chung Yin , Hur Chin
Published: June 2021

e16246

Background: Patients with germline BRCA1/2 mutations (gBRCAm) have an increased risk for pancreatic ductal adenocarcinoma (PDAC). The NCCN 2020 guidelines recommend platinum-based chemotherapy (FOLFIRINOX or gemcitabine plus cisplatin) in patients with gBRCAm diagnosed with borderline resectable or locally advanced (BR/LA) PDAC; for patients without progression on chemotherapy, maintenance therapy with a PAPR inhibitor (PARPi) can be considered. FOLFIRINOX and gemcitabine plus cisplatin (GemCis), with or without maintenance PARPi, have not been directly compared in this patient population. The purpose of our study was to compare treatment outcomes, toxicity, costs, and quality-of-life of the two recommended platinum-based regimens, with or without maintenance PARPi (olaparib or veliparib), in patients with gBRCAm and BR/LA PDAC. Methods: We developed a decision-analytic mathematical model comparing the total cost and health outcomes of FOLFIRINOX, FOLFIRINOX + olaparib (FOLFIRNOX-O), GemCis, and GemCis + veliparib (GCV) over twelve years. The inputs for the model were estimated using clinical trial data and published literature. Natural history was used as a comparator. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall survival (OS), progression-free survival (PFS), life-years (LYs) and total cost of care (USD). Results: Both FOLFIRINOX strategies were dominated by the GemCis strategies and thus eliminated from the efficiency frontier. GCV was the strategy that yielded the most life-years (2.05 LYs) but the ICER of $629,697.46 for this regimen far exceeded the WTP threshold. Therefore, GemCis was the cost-effective strategy, totaling incremental QALYs of 1.31 at a cost of $61,228.40 per QALY when compared to natural history. A one-way sensitivity analysis found that the GCV becomes the cost-effective strategy when the cost of maintenance PARPi is lowered to 4% of the base case. Conclusions: Our model found that GemCis is the cost-effective option for patients with gBRCAm and BR/LA PDAC. Neither of the strategies with maintenance PARPi were cost-effective. Additional clinical trial data with adequate follow-up are needed to confirm our findings.[Table: see text]
Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.
Authors: Sridharan Vishwajith , Mino-Kenudson Mari , Cleary James M. , Rahma Osama E. , Perez Kimberly , Clark Jeffrey William , Rubinson Douglas Adam , Goyal Lipika , Bazerbachi Fateh , Qadan Motaz , Parikh Aparna Raj , Ferrone Cristina R. , Casey Brenna , Fernandez Del-Castillo Carlos , Ryan David P. , Lillemoe Keith , Warshaw Andrew Louis , Krishnan Kumar , Hernandez-Barco Yasmin
Published: June 2021

e16253

Background: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. Methods: This is a retrospective study conducted at a large healthcare system from 1996-2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. Results: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery conferred OS benefit in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy provided OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). Conclusions: Pancreatic ACC patients often present with advanced disease. Surgery confers survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.
Authors: Cheng Ce , Chineke Iloabueke Gabriel , McBride Ali , Chipollini Juan , Gelmann Edward Paul , Recio-Boiles Alejandro
Published: June 2021

e16506

Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I2= 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I2= 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I2= 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I2= 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I2= 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I2= 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I2= 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I2= 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I2= 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I2= 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I2= 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.
Patient outcomes following disease progression with enfortumab-vedotin (EV) in metastatic urothelial carcinoma (mUC).
Authors: Khan Mohammed Ateeb , Szabados Bernadett , Choy Julia , Jackson-Spence Francesca , Powles Thomas , Castellano Daniel , Valderrama Begoña P.
Published: June 2021

e16516

Background: Enfortumab Vedotin (EV) is an antibody drug conjugate (ADC), licensed for use in metastatic urothelial carcinoma (mUC), following disease progression with platinum-based chemotherapy (ChT) and immune checkpoint inhibitors (ICIs). A patient cohort now exists with disease progression following EV with no guidance for subsequent treatment. This retrospective observational study assessed patient outcomes post EV progression. Methods: Patients were identified from 3 centres in Europe (St Bartholomew’s Hospital, University Hospital Virgen Del Rocio and Hospital Universitario 12 de Octubre). Data was collected regarding treatments prior to and post EV, length of EV treatment and overall survival (OS) post EV progression. Descriptive statistics and survival analyses comparing survival outcomes stratified by treatment post EV progression were performed in SPSS (Version 27). Results: All 24 patients had received both an ICI and ChT prior to receiving EV. 10 patients received further treatment following disease progression on EV. 8 patients received ChT (6 patients platinum based, 1 patient paclitaxel, 1 patient vinflunine), 1 patient received radical radiotherapy and 1 patient received derazantinib. No patient received further ICI therapy post EV progression. 2 patients had achieved complete radiological response with EV and had no evidence of disease progression. Point bi-serial correlation showed no significant association between length of EV treatment and receiving further treatment post disease progression on EV. There was also no significant association between pre EV survival length and further treatment post disease progression on EV. Survival analysis (Kaplain-Meier, Mantel-Cox Log Rank) revealed a statistically significant difference in mean OS. Mean OS was 1 month in patients who received no further treatment vs 7 months in patients who received treatment post progression on EV (Chi-Square 16.569, p = 0.000). Conclusions: Less than half of patients who progressed on EV received subsequent treatment. Patients who did receive treatment had significantly increased OS. There is a clear gap in literature and evidence-based guidance for treatment following EV progression and further studies are required with larger samples accounting for confounding factors to further evaluate best practise post disease progression on EV.
Meta analysis of arsenic exposed genes expression profiles to develop a bladder cancer predictor.
Authors: Singhal Sonalika , Ruprecht Nathan A. , Sens Donald , Sens Mary Ann , Singhal Sandeep K.
Published: June 2021

e16523

Background: IARC classified arsenic (As) as “carcinogenic to humans”, but despite the health consequences, there is no molecular signature available yet to predict when exposure may lead to the disease development. First aim of this study is to investigate the genetic changes due to the exposure to carcinogenic compounds such as As. Secondly, how accurately we can predict the disease association when exposed to toxic compounds. Methods: The entire analysis was performed in-silico fashion and data was collected from the public resources such as NCBI database. Two Asian population datasets exposed As were used to find significantly differently express genes. In addition, four cancer cell lines with exposure of As compounds were used to identify the association with cancer. The human bladder cancer biopsy datasets were used to develop a risk predictive model. As per the requirements, numerous machine learning (ML) approaches such as random forest, hierarchical clustering, were used to find the classification and association between the samples and outcome. Statistical approaches such as T-Test, and ANOVA, applied to find the differentially expressed genes associated with different conditions and logistic regression models applied to develop risk prediction models. Results: We identified a set of 1183 genes which were common between both the populations and were significantly changed in humans exposed to As. A subset of 157 genes associated with As exposure and involved in cancer progression was selected for risk prediction model development. A set of four genes (NKIRAS2, AKTIP, HLA-DQA1 and TBC1D7) shows the highest prediction ability of primary bladder tumor with AUC 0.96 (95% CI: 0.82- 0.99) and reproducibility of 0.75 (0.34-0.93) when applied on different dataset. Conclusions: This study identified a list of genes and bladder cancer predictive models that would be very helpful to forecast the outcomes of As exposed in humans.
Tolerability of axitinib in advanced renal cell carcinoma: A meta-analysis.
Authors: Chaudhry Bareia , Wu Shenhong
Published: June 2021

e16536

Background: Axitinib has been used extensively as a single agent or in combination with immunotherapy in the treatment of advanced renal cell carcinoma. It can be often discontinued due to adverse events. A meta-analysis of clinical trials was performed to evaluate the overall tolerability of axitinib in this setting. Methods: PubMed (Up to November 2020) was searched to identify clinical trials of axitinib in advanced or metastatic renal cell carcinoma. Reported data was collected to include axitinib and control discontinuation due to adverse events. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals depending on the heterogeneity of included studies. Results: A total of 11 studies including 4,056 patients (axitinib alone n = 1384, axitinib combination n = 987, control n = 1685) were included for analysis. The summary discontinuation rate for axitinib due to adverse events was 13.4% (95% CI; 11.7-15.2%) with 8.9% (95% CI: 5.3-14.6%) as a single agent and 26.6% (95% CI:17.8 –37.8%) in combination with other agents. In comparison with controls based on randomized controlled studies, axitinib overall has similar discontinuation rate due to adverse events (RR: 1.18, 95% CI: 0.77-1.80). However, there was a significantly higher discontinuation rate with axitinib in combination with other agents including immunotherapeutic agents PD-L1 inhibitors than control treatment (RR: 1.52, 95% CI: 1.24-1.86). Conclusions: The tolerability of axitinib may vary significantly with its use as a single agent or in combination in the treatment of advanced renal cell carcinoma. Further studies are needed to improve its tolerability as a part of combination therapy.
Lenvatinib (LEN) + pembrolizumab (PEMBRO) treatment in patients (pts) with metastatic clear cell renal cell carcinoma (RCC): Final results of a phase 1b/2 trial.
Authors: Lee Chung-Han , Shah Amishi Yogesh , Hsieh James J , Rao Arpit , Pinto Alvaro , Bilen Mehmet Asim , Cohn Allen Lee , DiSimone Christopher , Shaffer David R. , Gironés Sarrió Regina , Gunnestad Ribe Sara , Wu Jane , Schmidt Emmett V. , Kubiak Peter , Okpara Chinyere , Smith Alan D. , Motzer Robert J.
Published: June 2021

e16542

Background: Immune checkpoint inhibitors (ICIs) are commonly used as first-line treatment for pts with advanced RCC. In the recent phase 3 CLEAR trial, LEN + PEMBRO showed improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) vs sunitinib in first-line treatment of advanced RCC (Motzer R et al. NEJM. 2021). Additional treatment options are needed for pts with disease progression on ICIs. A phase 1b trial of LEN + PEMBRO was performed in multiple tumor types and included an expansion part into a phase 2 cohort of ICI-pretreated, treatment-naïve, or previously treated ICI-naïve pts with metastatic RCC (NCT02501096). We report the final results of the RCC cohort with an extended follow-up. Methods: Eligible pts were ≥18 years old and had measurable disease. Efficacy analyses were conducted by prior therapy grouping. The primary endpoint was ORR at week 24 (ORRwk24) per immune-related (ir) RECIST by investigator assessment. Secondary endpoints included ORR, duration of response (DOR), PFS, OS, and safety. Exploratory endpoints included tumor response assessed per RECIST v1.1 by independent review committee (IRC). Subgroup analyses of the ICI-pretreated group will be included in the poster. Results: The recommended doses determined in phase 1b were LEN 20 mg daily + PEMBRO 200 mg once every 3 weeks (Taylor M et al. JCO. 2020). The study enrolled 145 pts (efficacy analysis, n=143; safety analysis, n=145). At data cutoff (August 18, 2020), the median follow-up time was 19.8 months. The ORRwk24 was 55.8% (95% CI 45.7–65.5) for ICI-pretreated pts (n=104), 72.7% (95% CI 49.8–89.3) for treatment-naïve pts (n=22), and 41.2% (95% CI 18.4–67.1) for previously treated ICI-naïve pts (n=17). The median OS for the previously treated ICI-naïve pts was 30.3 months and was not reached in the other groups. Additional efficacy analyses are shown in the table. Treatment-related adverse events occurred in 99.3% of pts; the most common were fatigue (58.6%), diarrhea (55.2%), and hypertension (40.0%). Most pts (69%) maintained the LEN starting dose or were reduced to LEN 14 mg daily (dose level −1). Conclusions: LEN + PEMBRO demonstrated promising antitumor activity with a manageable safety profile in pts with metastatic RCC, including pts who were ICI-pretreated. Clinical trial information: NCT02501096. [Table: see text]
Clinical outcomes in metastatic renal cell carcinoma (mRCC) treated with combination of nivolumab and cabozantinib (nivo-cabo) in the salvage setting.
Authors: Ravindranathan Deepak , Liu Yuan , Martini Dylan J. , Nazha Bassel , Brown Jacqueline T , Russler Greta , Yantorni Lauren Beth , Caulfield Sarah , Master Viraj A. , Carthon Bradley Curtis , Kucuk Omer , Bilen Mehmet Asim
Published: June 2021

e16570

Background: The CheckMate 9ER trial showed that the combination of nivolumab and cabozantinib (nivo-cabo) in first line setting for treatment of mRCC was superior to sunitinib in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and led to its FDA approval. We report outcomes of cohort of patients with mRCC treated with nivo-cabo in the salvage setting. Methods: We retrospectively reviewed 17 patients with mRCC treated at Winship Cancer Institute who progressed through at least one line of prior therapy. These patients were then treated with either sequences: [1] cabozantinib and then add nivolumab upon progression (n = 8) and [2] nivolumab/ipilimumab or nivolumab and then add cabozantinib upon progression (n = 9) with two with nivolumab and ipilimumab. Median PFS and OS rates, and clinical benefit (defined as complete response or partial response, or stable disease) were described. Results: Thirteen patients had clear cell histology and four patients had non-clear cell histology. For sequence [1], the mPFS for cabozantinib alone was 9.9 months and combination of nivolumab added to cabozantinib was 8.9 months. For sequence [2], the mPFS for nivolumab with or without ipilimumab was 5.9 months and combination of cabozantinib added to nivolumab was 10.4 months. The 12-month OS rate was 88% for sequence [1] and 89% for sequence [2]. The 24-month, OS rate was 50% for sequence [1] and 89% for sequence [2]. 5/8 (63%) patients in sequence [1] and 7/9 (78%) patients in sequence [2] had clinical benefit. 3/8 (37.5%) patients in sequence [1] and 2/9 (22%) patients in sequence [2] experienced immune-related adverse effects such as hypothyroidism (grade II for two patients), pneumonitis (grade II), hepatic transaminase elevations (grade II), and pancreatitis (grade III). No patients in sequence [1] needed dose reduction in cabozantinib once nivolumab was added. 3/9 (33%) patients had dose reduction in cabozantinib in sequence [2] due to diarrhea. Conclusions: Nivo-cabo demonstrates activity in the salvage setting but there is still need to understand the optimal sequencing of both agents in the treatment of mRCC. Outcomes from this combination treatment are to be further validated from ongoing phase III trial, PDIGREE (NCT03793166).
Comparative analyses of survival differences in patients with urothelial versus non-urothelial upper tract carcinomas: Results from the National Cancer Database (NCDB).
Authors: Aragon-Ching Jeanny B. , Wang Hongkun
Published: June 2021

e16582

Background: The true incidence of upper tract cancers in the United States is not well defined, with cancers combined with kidney cancer and ureteral cancers grouped with rare urinary organ cancer. It is estimated to occur at 5% of urothelial carcinomas with a rough estimate of 3750 cases annually. Little data exists for non-urothelial variants of upper tract cancers. Methods: The primary objective of this retrospective review is to evaluate trends and differences between urothelial (UC) versus non-urothelial (nUC) histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) for upper tract cancers and compare the demographics, disease characteristics, treatment, incidence of stage and survival according to NCDB. Results: Data from diagnosis in year 2004 – 2017 were extracted from the NCDB. A total of 29743 urothelial and 561 non-urothelial cases for upper tract cancers were identified. More men were diagnosed with urothelial carcinoma, UC (62%) and non-urothelial carcinoma, nUC (58%) for non-urothelial carcinoma. The median age was similar for both groups, 73 years (UC) and 72 years (nUC). Majority were Caucasian at 92% (UC) and 91% (nUC) with incidence of 4% in the UC and 6% in the nUC cohorts for African-American patients. Primary surgery with nephroureterectomy occurred more frequently in the UC cohort (85%) compared to the nUC (58%). More patients were diagnosed with stage IV cancer based on the AJCC Clinicopathologic stage grouping in the nUC group (29%) compared to UC at 8.1%, but overall survival was not different for stage IV cancers with median OS of 8.57 mos (CI, 8.05-9.10) for UC vs 7 mos (CI, 5.62 – 9.26) nUC; logrank p = 0.283 although survival was significantly different for earlier stages of Stage 0 & 1 at 80.53 mos UC (CI, 78.13, 83.25) vs 28.98 mos nUC (CI, 20.3, 46.78), p < 0.001; and for stage II & III at median OS of 35.65 mos UC (CI, 33.38, 38.05) vs 15.75 mos nUC (CI, (11.17, 26.87) that is also significantly different though with lesser significance with longer follow-up. Conclusions: Upper tract urothelial cancers compared to non-urothelial cancers have similar poor outcomes upon diagnosis of metastatic disease though outcomes are with urothelial upper tract is better with earlier stage upon diagnosis compared to non-urothelial cancers, highlighting the importance of early diagnosis with perhaps curative intent treatment.
The genomic landscape of Chinese patients with upper tract urothelial carcinoma.
Authors: Jin Shengming , Wei Yu , Wu Junlong , Gu Chengyuan , Gao Wenqi , Li Bing , Zhu Yao , Ye Dingwei
Published: June 2021

e16583

Background: Upper tract urothelial carcinoma (UTUC) is known to have a distinct aggressive clinical phenotype and its genomic characterization is poorly understood, especially in Asian population. In this study, we aimed to characterize the genomic landscape of Chinese UTUC patients and explore the clinical relevance, which is the largest cohort of UTUC to date. Methods: Overall, 122 Chinese patients with UTUC were enrolled. Tumor and germline DNA from patients were analyzed using a targeted next-generation sequencing assay to identify somatic mutations in 520 cancer associated genes. Mutations like deletion, amplification and gene fusion were included. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also evaluated. The frequency of genomic alterations in patients with UTUC was compared with that of the Western counterpart from previous studies. Results: In total, 13 low-grade and 109 high-grade UTUC patients were included in this study. The most frequent genomic alterations were identified in genes like TERT (50.0%; 61.5% low-grade vs 48.6% high-grade), KMT2D (48.4%; 61.5% vs 46.8%), FGFR3 (41.0%; 69.2% vs 37.6%), TP53 (37.7%; 7.7% vs 41.3%), CDKN2A (22.1%; 23.1% vs 22.0%), KDM6A (20.5%; 15.4% vs 21.1%) with different mutation frequencies in the two subgroups of patients. Despite the overall similarity (including FGFR3, ARID1A and CDKN2A), the comparison between our cohort and the two Western UTUC cohorts (n = 119, 24 low-grade and 95 high-grade) revealed significant differences in mutation frequencies of KMT2D (48.4% vs 36.1%), TERT (50.0% vs 26.9%), TP53 (37.7% vs 21.9%) and KDM6A (20.5% vs 32.8%) . Chi-square analysis revealed that patients with history of other cancers (4/17 vs. 3/105, P = 0.001) were more likely to have a MSI-high status. In addition, females (9/44 vs. 6/78, P = 0.039) and patients with cancer history (6/17 vs. 9/105, P = 0.002) were more likely to have high TMB (≥20 mutations/Mb; median: 6.48 mutations/Mb). At last, the frequency of germline P/LP variants were also similar but different in the spectrum between our cohort and the Western UTUC population. Differences in mutation frequency of APC (0 vs 2.6%), BRAC2 (2.6% vs 0.9%), CHEK2 (0.3% vs 1.8%), MSH2 (2.6% vs 5.3%) and MSH6 (0 vs 1.8%) were significant. Conclusions: This study revealed that Chinese UTUC patients had a similar frequency of genomic alterations with western patients. However, there were significant differences in the prevalence of several mutated genes including KMT2D, TERT, TP53 and KDM6A, suggesting the ethnicity differences between the two populations. Our findings laid the foundation of a deeper understanding of UTUC biology and will provide potential targets for the development of precision therapies in UTUC.
Combination ozone therapy as an effective method of radiomodification in chemoradiation treatment of patients with cervical cancer.
Authors: Rodionova Olga G. , Gusareva Marina A. , Sheiko Elena A. , Voshedskiy Vitaliy I. , Sakun Pavel G. , Vasilieva Ekaterina O. , Karnaukhova Elena A. , Solntseva Anna A. , Kosheleva Natalia G , Krokhmal Yulia N. , Pustovalova Alla V. , Chalabova Tatiana G. , Dontsov Vladimir A. , Kabanov Sergey N. , Vlasov Stanislav G.
Published: June 2021

e17515

Background: The purpose of the study was to evaluate advantages of combination ozone therapy as an effective factor of radiomodification and radioprotection in the treatment of patients with cervical cancer. Methods: The study included 20 patients with stage IIIb cervical cancer T3бNхM0, the mean age 52 years. Controls (n = 10) received standard chemoradiation therapy; the main group (n = 10) received combination ozone therapy in addition to chemoradiation therapy. Systemic ozone therapy involved intravenous administration of 250 ml ozonized solution of 0.9% sodium chloride, 15 sessions during external beam radiotherapy. Local ozone therapy involved 15-minute instillations into the vagina during brachytherapy. All patients received standard chemoradiation therapy, total irradiation dose to the primary focus 80 Gy, plus weekly cisplatin 40 mg/m2. Results: In the main group, pain and discomfort in the lower abdomen were managed in 20% patients by the 5th session of ozone therapy; 30% - on the 10th day; in 50% - on the 14th day. In the control group, such symptoms in 40% of patients were reduced after 20 days. The main group showed a more rapid regression of tumor infiltration, disappearance of purulent discharge, relief of intoxication syndrome. Manifestations of gastrointestinal toxicity were observed in 10% of the main group and in 100% controls; leukopenia developed in 7 patients in the control group and was not registered in the main group. MRI showed complete clinical regression in 90% in the main group and in 65% in the control group. The treatment was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Combination ozone therapy causes a more pronounced antitumor effect, and its radioprotective effects significantly reduce the severity of chemotherapy-induced disorders. It does not aggravate concomitant pathology and shortens the treatment period.
Healthcare utilization and outcomes in cervical cancer with and without HIV: National inpatient sample analysis.
Authors: Gannamani Vedavyas , Tariq Muhammad Junaid , Sherazi Syed Ali Amir , Almani Muhammad Usman , Mudegowdra Niveditha , Usman Muhammad , Gupta Shweta
Published: June 2021

e17522

Background: Cervical cancer (CC) is an AIDS-defining malignancy and is the most common cancer in women with HIV who have a six times higher risk of developing CC than women without HIV. Compared to non-HIV-CC, HIV-CC has a reported 2-fold higher mortality. We attempted to evaluate the characteristics, outcomes and healthcare utilization of patients with CC with and without HIV from a national sample. Methods: We identified all patients of CC with and without HIV between 2016 – 2018 from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes (SO) included rates of sepsis, septic shock, pain, acute kidney injury, urinary tract infection, hydronephrosis, nephrostomy, anemia, and protein energy malnutrition (PEM). Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 755 admissions with HIV-CC and 71, 690 with non-HIV-CC were identified. Patients of HIV-CC were more likely to be younger (Mean age: 48.7 vs 53.4, p < 0.001), African American (62.8% vs 18.4%, p < 0.001), have Medicaid (52.3% vs 34.5%, p < 0.001), admitted to a teaching hospital (90.7% vs 78.7%, p < 0.01), live in lowest income ZIP codes (62.2% vs 36.2%, p < 0.01) and in Northeast region of USA (30.5% vs 17.3%, p < 0.01). HIV-CC had significantly higher rates of chronic kidney disease (CKD) and hemodialysis (HD) (p < 0.05), lower rates of hypertension (p < 0.05) with other comorbidities being similar between groups. The overall adjusted all cause mortality was significantly lower in HIV-CC (aOR = 0.15, CI 0.05-0.39, p < 0.001) but mean LOS (8.3 vs 5.6 days, p < 0.01) and THC ($86, 171 vs $63, 138, p < 0.01) was significantly higher than non-HIV-CC. The rates of anemia (70.2% vs 52.8%) and PEM (27.8% vs 20.5%) were significantly higher (p < 0.05) in HIV-CC while other SOs were non-significant. Conclusions: HIV-CC inpatients were younger, minorities from low income zip codes and, unlike historic data, had significantly lower mortality compared to non-HIV-CC. Despite lower mortality, LOS and THC were significantly higher in HIV-CC, amounting to over $17 million in 3 years. It may be related to a higher burden of CKD and HD, however more studies are needed to clarify our findings and identify causes of increased healthcare utilization in this group to save costs.
Genomic characteristics of endometrial cancer in China.
Authors: Zheng Hong , Cui Lina , Zhang Bei , Zhao Xiaochen
Published: June 2021

e17569

Background: Molecular classification of endometrial cancer has been applied in patient stratification and treatment strategy. Although the Cancer Genome Atlas project and other genomic studies have established comprehensive molecular classification, its genomic characteristics in Chinese endometrial cancer remain unclear. Methods: Tumor tissue and matched white blood cells from 316 patients with endometrial cancer underwent next-generation sequencing (NGS), which targeted the whole coding region of 733 or 381 genes. Endometrial cancer was classified into four subtypes according to genomic characteristics: polymerase (POLE) ultramutated, microsatellite instability (MSI), TP53 wild type (TP53wt), and TP53 mutant (TP53mut). Tumor mutation burden (TMB) was calculated based on the number of somatic single nucleotide variants and indels in examined coding regions. Deleterious or suspected deleterious genes were included for analysis. Genomic instability was also evaluated with Homologous Recombination Deficiency (HRD) score by over 10, 000 single-nucleotide polymorphisms distributed across human genome. HRD algorithm combined loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST). Results: The 316 endometrial cancer patients were divided into four subtypes: POLE ultramutated (16, 5.06%), MSI tumors (70, 22.2%), TP53wt (131, 41.5%), and TP53mut (99, 31.3%). Median TMB was 26.5 mut/Mb in overall cohort and POLE ultramutated subtype possessed the highest TMB (181 mut/Mb), followed by MSI (54.1 mut/Mb), TP53mut (7.11 mut/Mb) and TP53wt (6.61 mut/Mb) subtypes. POLE, PTEN, LRP1B, BRCA2 and ATRX were the top frequently mutated genes in POLE ultramutated subtype, which mutation rate are more that 80%. The most frequent mutations were detected in ARID1A, PTEN, PIK3CA in MSI subtype, TP53, PIK3CA, PTEN in TP53mut subtype, and PTEN, PIK3CA, ARID1A in TP53wt subtype. HRD score was significantly higher in TP53mut subtype, followed by TP53wt, MSI and POLE ultramutated subtype (median HRD score, 21.7, 6.15, 3.65 and 0; P < 0.001). Conclusions: Our study revealed the heterogeneous genomic characteristics of four molecular subtypes in Chinese endometrial cancer. POLE ultramutated and MSI subtypes display higher TMB. TP53mut subtype showed genome features of HRD and would likely benefit from HRD-targeted therapy.
Radiomic features in recurrent/metastatic platinum refractory head and neck squamous cell carcinoma treated with immunotherapy.
Authors: Anile Giuseppe , Bettinelli Andrea , Paiusco Marta , De Conti Giorgio , Gottardi Chiara , Conte Pierfranco , Ghi Maria Grazia
Published: June 2021

e18000

Background: Radiomics is the computerized extraction of quantitative features from medical images, beyond the level of detail accessible to an unaided human eye. Several studies on radiomic analysis have been carried out to identify predictive, prognostic and diagnostic biomarkers for diverse tumor types including HNSCC. Radiomic features proved to be effective in predicting outcomes in patients with locally advanced HNSCC. The aim of the present study was to dentify predictive and prognostic radiomic features in platinum-refractory HNSCC patients with recurrent and/or metastatic (R/M) disease treated with anti PD-1 monotherapy. Methods: We retrospectively reviewed the data of 38 patients treated with Nivolumab at our Institution between January 2018 and March 2020. Nasopharyngeal carcinomas were not eligible. CT radiomic textural features were extracted from regions of interests (ROIs) manually delineated around tumor volumes. Minimum Redundancy Maximum Relevance (mRMR) algorithm was the method of choice to rank radiomic features based on three outcomes: overall response rate (ORR); disease progression (PD) and overall survival (OS). Logistic regression was employed to build predictive/prognostic models. Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) was chosen as the metric to assess model performances. Results: Data from 29 out of 38 patients were ultimately analyzed. Nine patients were excluded due to nasopharynx as primary tumor site and/or inadequate CT scan imaging. A total of 57 ROIs were extracted and analyzed. We obtained 9 models: 3 radiomic models, 3 clinical models and 3 combined models (radiomic plus clinical) for each outcome of interest (ORR, PD, OS). In the radiomic models 2 features were identified as predictor for ORR (AUC 0.69), 1 radiomic feature was predictive for PD (AUC 0.83) and 1 predictive for OS (AUC 0.72). In the clinical models, 3 clinical characteristics were identified for both ORR (AUC 0.91) and PD (AUC 0.73) and 2 clinical features were found to be predictive for OS (AUC 0.91). The combined model identified 3 features (2 radiomics and 1 clinical) predictive for ORR (AUC 0.76). No clinical characteristics were found in the combined model for PD. No radiomics features have been shown to be related to OS. Conclusions: This is an explorative study to test the power of radiomics and the potential value of combining radiomics and clinical data as a prognostic and predictive instrument. In this small sample size, the quantitative analysis of CT images seems to be an interesting tool which has to be further explored as predictor of outcome in a larger series of patients.[Table: see text]
Development and validation of an unfolded protein response-related gene signature to predict overall survival in HNSCC.
Authors: Chen Jun , Zhang Bei
Published: June 2021

e18033

Background: Genomic expression profiles have enabled the classification of head and neck squamous cell carcinoma (HNSCC) into molecular sub-types and provide prognostic information, which have implications for the personalized treatment of HNSCC beyond clinical and pathological features. Methods: Gene-expression profiling was identified in TCGA- HNSCC (n = 492) and validated with the Gene Expression Ominibus (GEO) dataset(n = 270) for which RNA sequencing data and clinical covariates were available. A single-sample gene set enrichment analysis (ssGSEA) algorithm were used to quantified the levels of various hallmarks of cancer. And LASSO Cox regression model was used to screen robust prognostic biomarkers to identify the best set of survival-associated gene signatures in HNSCC. Statistical analyses were performed using R version 3.4.4. Results: We identified unfolded protein response as the primary risk factor for survival（cox coefficient = 17.4 [8.4-26.3], P < 0.001）among various hallmarks of cancer in TCGA- HNSCC. And unfolded protein response ssGESA scores were significantly elevated in patients who died during follow up (P = 0.009). Kaplan-Meier analysis showed that patients with low ssGSEA scores of unfolded protein response exhibited better OS (HR = 0.69, P = 0.008). And we established an unfolded protein response-related gene signature based on lasso cox. We then apply the unfolded protein response -related gene signature to classify patients into the high risk group and the low risk group with the cutoff of 0.18. Adjusted for stage，age，gender, our signature was an independent risk factor for overall survival in TCGA cohorts (HR = 0.39 [0.28-0.53],P = < 0.001). In external independent cohorts, similar results were observed. In the validation cohort GEO65858, the patients with high unfolded protein response score showed longer survival (HR = 0.62 [0.38-1.0], P = 0.049). And adjusted for stage，age，HPV state, the multivariate cox regression analysis showed that unfolded protein response-related gene signature exhibited an independent risk prediction for overall survival in 270 patients with HNSCC (HR = 0.57 [0.35-0.94], P = 0.026). Conclusions: By analyzing the gene-expression data with bioinformation approach, we developed and validated a risk prediction model with unfolded protein response -related expression scores in HNSCC, which have the potential to identify patients who could have better overall survival.
Supportive care services (SCS) during curative-intent treatment with chemoradiation for patients with locally advanced head and neck cancer (HNC).
Authors: Harris Ethan , Kacew Alec , Sreedhar Siva , Shergill Ardaman
Published: June 2021

e18041

Background: SCS assist in managing symptoms and outcomes for patients in palliative care settings. But impact of services in curative intent settings is not well defined. Here we evaluate this for head and neck cancer patients. Methods: Following IRB approval, we retrospectively reviewed charts of patients with HNC treated from 2014-2017 at the University of Illinois Hospital. Of 260 patient charts reviewed, 67 patients fit the study criteria, which included completing treatment with curative intent at University of Illinois Hospitals, not living at a skilled nursing facility, and follow-up of at least 3 months. Demographic data and treatment course data were collected. SCS included opioid use, tracheostomy use, G-tube use, prophylaxis for mucositis, speech and swallow f/u, nutritionist visits, social worker visits, and anti-emetic prophylaxis. Outcomes included number of hydration visits, number of ER visits, and number of days in the hospital. We tested the significance of correlations between continuous variables using Pearson correlation and the significance of difference in a continuous variable between two groups using the Wilcoxon ranked sum test. We used Cox proportional hazards model for analyses of overall survival (OS). Analyses were univariable. Results: 20 patients had oropharyngeal cancer. 47 had non-oropharyngeal disease. 57 patients received cisplatin and 10 patients received cetuximab, concurrently with radiation therapy. Median weight loss was 6.0kg during treatment. Highest potency opioid at end of treatment was not associated with outcomes. Among the full cohort, having a G-tube was associated with increased number of ER visits (median 1.5 vs. 0.0, p < 0.01), hospitalizations (median 2.0 vs. 0.0, p < 0.01), and number of days in the hospital (median 7.0 vs. 0.0, p < 0.01). Increased hydration appointments, meanwhile, did not predict outcomes. In subgroup analysis of patients who received G-tubes, ER visits before or after G-tube placement did not predict OS (HR 0.64, p = 0.56 for ER visits before G-tube placement, HR 1.06, p = 0.75 for ER visits after G-tube placement). Number of hydration visits after starting treatment for cetuximab vs cisplatin was significant (median 8 for cisplatin and 2 for cetuximab, p = 0.02). Conclusions: G-tube placement, even after placement, was associated with medical care needs during treatment, suggesting an unmet need for this patient population. Further studies are needed to determine how to best provide support for this vulnerable patient population.