bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected gallbladder cancer as the source of some unknown primary cancers.
Authors: Zhang Xiaowei , Liu Xin , Luo Zhiguo , Hu Xichun , WANG Qifeng , Hu Silong , Zhou Liangping , Jiang Shiyu
Published: June 2021

e16177

Background: CUP (Cancer of Unknown Primary) represents a frequent cancer type causing incomparable difficulties in pathological diagnosis as compared to other tumor types. To explore and analyze the causes of CUP (Cancer of Unkown Primary) patients with misdiagnosis in patients after laparoscopic cholecystectomy with cholecystitis or cholecystolithiasis. Methods: 13 patients with CUP (Cancer of Unkown Primary) were recruited in this research, who accepted the multidisciplinary discussion of the CMUP (Cancer of Multiple or Unknown Primary) multidisciplinary team. Our team analyzed the clinical data and pathological characteristics of these patients, and tried to find the common characteristics of the CUP patients whose primary site is the gallbladder that has been already removed. Results: 13 patients were received laparoscopic cholecystectomy because of previously considered cholecystitis or cholecystolithiasis. The gallbladder is considered as the primary organ supported by the pathological features of the metastatic sites. Importantly, all these patients have local abdominal wall and/or local perigallbladder lymph node metastases. Among them, 3 cases were diagnosed as gallbladder cancer, and 1 case was considered as high-grade intraepithelial neoplasia after pathological consultation, which were recognized as benign disease. Among the 13 cases, 9 cases showed local thickening of the gallbladder wall by preoperative CT or B-ultrasound. The median recurrence time was 16.4 months (9-48 months). Of the 13 patients, 5 received radical resection again, and received GP (gemcitabine plus platinum) chemotherapy after surgery. Of the 8 patients who were unable to undergo radical surgery, 5 received first-line GP based chemotherapy, 2 received first-line PD-1 immunotherapy combined with anti-vascular targeted drugs, and 1 received tegafur monotherapy due to poor physical condition. Till now, these patients are still under follow-up. Conclusions: Unexpected gallbladder cancer is the source of some unknown primary cancers. For these patients with cholecystitis or cholecystolithiasis, B-ultrasound examination should not be performed alone, and CT or MRI examination should be performed when necessary. We should pay high attention to the patients with cholecystitis or gallstone thickening of the gallbladder wall or other high-risk gallbladder cancer. Before surgery, clinical data should be analyzed comprehensively, and rapid frozen examination should be performed on patients suspected of having cancer. In order to avoid misdiagnosis, we should pay attention to the principle of none tumor and avoid the risk of incision implantation. If unexpected gallbladder cancer is found, radical operation should be performed as soon as possible.
Neoadjuvant radiotherapy to improve overall survival in resectable hepatocellular carcinoma.
Authors: Luo Zhiwen , Che Xu , Cai Jianqiang , Zhao Hong , Jin Jing , Tang Yuan , Chen Bo , Bi Xinyu
Published: June 2021

e16178

Background: There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. Methods: We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. Results: We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Conclusions: Patients with resectable HCCs may derive a survival benefit from NRT. Younger age ( < 65 years) with a positive AFP level at N0 status could be indicators for NRT. These findings enlighten current guidelines to consider NRT in patients with resectable HCCs. The present study establishes a reasonable basis for further prospective studies.
Anchored matching-adjusted indirect comparison (MAIC) of regorafenib (REG) versus cabozantinib (CAB) in advanced hepatocellular carcinoma (HCC).
Authors: Proskorovsky Irina , Krotneva Mira , Ozgurdal Kirhan , Jaeger Savina , Su Yun
Published: June 2021

e16188

Background: REG and CAB, two therapies for second-line (2L) advanced HCC, have been evaluated vs. placebo (PBO) in randomized phase III trials, RESORCE (NCT01774344) and CELESTIAL (NCT01908426), respectively. In the absence of head-to-head studies, indirect treatment comparison (ITC) is needed to compare the efficacy and safety of REG vs. CAB. Anchored MAIC is an ITC method adjusting for cross-trial heterogeneity using PBO as the common comparator or anchor. Methods: Patient-level data from RESORCE were available to match the inclusion criteria and published baseline characteristics of CELESTIAL. 2L patients with prior sorafenib exposure of >3 months were included in the analyses. Overall survival (OS), progression-free survival (PFS), and Grade 3/4 treatment-emerging adverse events (TEAEs) occurring in > 10% of patients were compared. Matching was conducted for the following covariates, which were either imbalanced across trials or likely treatment effect modifiers (EMs): gender, region, Eastern Cooperative Oncology Group (ECOG), prior sorafenib duration, extrahepatic spread, macrovascular invasion, hepatitis B (HBV), hepatitis C (HCV), alcohol use, and alpha-fetoprotein (AFP) ≥400 ng/mL. Anchored MAIC were used to compare the relative effect of each treatment. To account for violation of the proportional hazards assumption, in addition to hazard ratios (HRs), restricted mean survival time (RMST) was estimated to quantify differences in OS and PFS. For safety, the relative effects were expressed as risk differences (RDs) (REG – CAB). Results: After matching, the effective sample sizes of REG and its PBO arm were 214 and 82, respectively. For OS, REG showed favorable although not statistically significant HR, and 30% longer mean survival with an RMST ratio approaching statistical significance. For PFS, there was no numerical difference in HR and no clinically meaningful difference based on RMST analyses (Table). REG showed lower incidence of diarrhea [RD of -7.1% (NE, NE)] and fatigue [RD of -6.3% (-14.6, 2.0)]. Conclusions: In this anchored MAIC, REG showed favorable OS and safety profile, especially for diarrhea and fatigue. No clinically meaningful difference was observed for PFS. The analysis could be limited by reduced sample size after matching and unobserved or missing EMs that could not be adjusted.[Table: see text]
Efficacy of immunotherapy in hepatocholangiocarcinoma (HCC-CC): Proof of concept.
Authors: Diab Osama , Khan Maloree , Abbasi Saqib , Saeed Anwaar , Kasi Anup , Baranda Joaquina Celebre , Sun Weijing , Al-Rajabi Raed Moh'd Taiseer
Published: June 2021

e16194

Background: Hepatocholangiocarcinoma (HCC-CC) is a rare form of cancer with a poor prognosis. Of all primary liver cancers, the incidence of HCC-CC ranges from 0.4 to 14.2%. HCC-CC is a mixed carcinoma with findings of both hepatocellular carcinoma and cholangiocarcinoma. Immune checkpoint inhibitors are a potent first line treatment in hepatocellular carcinoma with multiple clinical trial showing effectiveness in cholangiocarcinoma. HCC-CC has limited proven treatment options as patients are generally excluded from clinical trials. In this study we reviewed outcomes of patients with HCC-CC who received immune checkpoint inhibitor in a single center. Methods: Records of patients who had a pathological confirmed HCC-CC by a subspecialized hepatic pathologist at the University of Kansas medical center were reviewed. We identified 6 patients with locally advanced unresectable or metastatic HCC-CC that received immune checkpoint inhibitor between February 2017 and January 2021. Baseline characteristics were obtained, as well as best response, line of therapy, and duration of response. Results: Of the six patients 4 (66%) received PD-1 inhibitor alone and 2 (34%) received combination therapy with CTLA-4 inhibitor for the treatment of HCC-CC. There were 3 (50%) females and 6 (100%) with prior hepatitis C infection. four (66%) patients had metastatic disease and 2 had locally unresectable advanced disease. Objective response rate was 83.3%. One patient achieved complete response and had a treatment holiday after receiving treatment for 2 years, and restarted immunotherapy upon relapse. Four patients had a partial response, of which two passed away after disease progression. One patient had stable disease on 2 different lines of immunotherapy then progressed. Of those who responded, one patient received immunotherapy, 3 (50%) received liver directed therapy and two received chemotherapy or Lenvatinib as first line treatment (Table). Conclusions: Immune checkpoint inhibitors demonstrate potential activity in patients with HCC-CC without unexpected side effect in this unmet need high-risk population. Larger studies are needed to confirm activity and efficacy in this setting.[Table: see text]
Clinical outcomes and efficacy of endoscopic ultrasound guided ablation of pancreatic cancer a systematic review and a meta-analysis.
Authors: Ehsan Hamid , Yousaf Muhammad Nadeem , Wahab Ahsan , Neupane Karun , Sana Muhammad Khawar , Rafae Abdul , Masood Adeel , Ahmed Zahoor , Muneeb Ahmed , Tayyeb Muhammad
Published: June 2021

e16261

Background: Endoscopic ultrasound-guided ablation therapy (EUS-A) is a minimally invasive technique increasingly used for the management of surgically unresectable pancreatic cancer. The data on the efficacy and clinical outcome of EUS-A for unresectable pancreatic cancer is lacking. We conducted this systematic review and meta-analysis to evaluate the safety, technical and clinical success of EUS-A therapies specifically for unresectable pancreatic cancer. Methods: Studies were identified with a comprehensive search for EUS-A and pancreatic cancer on PubMed, Google Scholar, Web of Science and Embase data search as of October 2020. The technical and clinical success rates of EUS-A were primary outcomes while adverse events (AEs) rate was secondary outcome. We defined technical success as successful placement of probe within tumor and able to perform ablation regardless of tumor outcome. Clinical success was defined as symptomatic improvement and/or any reduction in tumor size or evidence of necrosis on radiological imaging after EUS-A. A compute pooled analysis was performed using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.0.2) using random effect model. Results: Nineteen studies including 192 patients (54% females) were included. Common pancreatic tumors were nonfunctional neuroendocrine tumor (NNET) 43.5% (97), followed by locally advanced pancreatic ductal adenocarcinoma (LAPDAC) 27.3% (61), insulinoma 17.9% (40), cystic neoplastic lesions 8.5% (19). The pancreatic head was the most common site of tumor 49.8% (111), followed by body, neck and tail 44.8% (100). EUS-RFA was the most commonly used ablative therapy 63% (12/19 studies), followed by EUS-EA (ethanol ablation) 26% (5/19 studies) while EUS-A using laser and lauromacrogol injection was used in one study each. The mean number of ablation sessions per patient was 1.4 based on the total 243 sessions in 176 patients. The pooled technical success rate of EUS-A was 99.5% [95% CI = 0.90-0.97, I2 = 0%]. The pooled clinical success rate calculated out of total number of pancreatic lesions was 91.1% [95% CI = 0.79-0.92, I2 = 16%]. Clinical improvement in symptoms was reported in 11 studies and a complete resolution or decrease in tumor size was reported in 16 studies. The pooled AEs rate was 22.9% [95% CI = 0.17-0.37, I2 = 43%]. Common AEs were abdominal pain 7.8% (15), pancreatitis 5.2% (10) and pancreatic pseudocyst 2.1% (4). The median follow-up was 9.5 months. Conclusions: EUS-A is a safe and promising modality in the management of unresectable pancreatic cancer with a high technical and clinical success rate. Large prospective studies and clinical trials are required for comparison of clinical outcome of different EUS-A therapies and its widespread application for unresectable pancreatic cancer.
The role of selective internal radiation therapy for liver metastases from pancreatic adenocarcinoma after progression on prior chemotherapy.
Authors: Hackett Jonathan O , Crothers Rebecca S , Shaughnessy Emma , Cardaci Giuseppe , Kaard Alaar , Dean Andrew Peter
Published: June 2021

e16272

Background: Selective internal radiation therapy (SIRT) has established benefit for liver metastases in colorectal cancer. Very little data exists on the use of SIRT for liver dominant metastatic pancreatic cancer. A 2015 phase II trial by Gibbs et al suggested that SIRT at diagnosis may be beneficial in liver metastases in pancreatic cancer, particularly in those who have had a previous primary resection. Methods: In this single-institute retrospective audit we identified eleven patients who had liver predominant metastatic adenocarcinoma of the pancreas who received SIRT at any stage of their treatment. Data was analysed from our electronic patient databases. Results: 11 patients with adenocarcinoma of the pancreas, who had SIRT following progression on chemotherapy were identified. 3 had a primary surgical resection. All patients had received a minimum of one line of chemotherapy and had ECOG performance status of 2 or less. The median time from diagnosis to SIRT was 13 months (range 5-24 months). Patients received Yttrium-90 microspheres with a median activity of 2.1GBq with all eleven receiving concurrent infusional 5-FU 225mg/m2/day for 7 days prior and 14 days after. The median survival after SIRT therapy was 6 months (range 2-19 months). The median overall survival from diagnosis was 20 months (range 12-31 months). SIRT appeared safe and well-tolerated with no associated 30 day all-cause mortality. One patient developed radiation induced asymptomatic portal hypertension and liver cirrhosis. Conclusions: This is the first report of the use of SIRT with radiosensitising concurrent infusional 5FU for metastatic pancreatic cancer after failure of prior chemotherapy. We conclude that SIRT with concurrent infusional 5FU offers an additional treatment option for patients with liver dominant metastatic pancreatic cancer, who maintain a good PS who have progressed on prior lines of chemotherapy. This can provide a durable treatment response and requires further exploration.
A multicenter, prospective evaluation of a urine-based assay for bladder cancer diagnosis.
Authors: Wang Liang , Liang Yiming , Shi Min , Ma Tonghui , Deng Jianhua , Ding Degang
Published: June 2021

e16509

Background: At present, bladder cancer is diagnosed mainly through cystoscopy as the "gold standard" method, which is invasive, costly, and painful for patients. Meanwhile, the current non-invasive liquid biopsy approaches, such as FISH or cytology, still do not show adequate performance in the diagnosis of bladder cancer because of the unsatisfactory sensitivity. Therefore, developing a novel method that performs higher sensitivity and specificity, especially negative predictive value(NPV) is an urgent issue to be addressed and will be very helpful for the clinical application. Methods: From October 2019 to October 2020, we designed a multicenter, prospective study, in which 321 hematuria patients were enrolled, including 218 males and 103 females, and their average age was 56. Based on the final pathological diagnosis, 121 patients were confirmed as bladder cancer and 200 samples were benign urinary diseases. 100ml urine samples were collected from each patient before the endoscopy examination. The Genetron Uro-18 assay, which included a 17 gene mutation panel and the methylation test on ONECUT2, was used in this study. The regions in the panel were selected based on the TCGA database, as well as previous publications. 321 urine DNA libraries were generated using multiplex PCR methods and then sequenced on the Ion S5 System. The CpG-sites on the ONECUT2 gene were detected by bisulfite-specific real-time PCR. Results: In these samples, a total of 205 oncogenic mutations were found in 13 genes in the panel. Mutations on TERT, PIK3CA, FGFR3, and TP53 genes showed significantly higher occurrence. 103 samples were found to be mutation-positive, 92 of which were pathologically confirmed as bladder cancers. When only gene mutations were considered, the sensitivity and specificity of this assay were 76.0% and 94.5%, respectively. The methylation of ONECUT2 had a performance in the test with a sensitivity of 74.4% and specificity of 93.0%. Combining the mutation panel with the ONECUT2 methylation test will improve the sensitivity (86.0%) of this assay, but slightly hampered the specificity (91.0%). The positive predictive value(PPV) and negative predictive value(NPV) of the combination were 85.2% and 91.5%. The sensitivity was as high as 91.5% when low-grade bladder cancer samples were excluded. In contrast, the sensitivity of cytology and FISH tests were only 48.4% and 62.0%. Conclusions: The novel urine-based liquid biopsy assay has excellent performances in the diagnosis of bladder cancer, with sensitivity and NPV reaching 86.0% and 91.5%, which improved significantly than cytology and FISH tests. Thus this assay will be more beneficial for patients with urinary diseases which significantly reduces the current burden of repeat cystoscopies and cytology tests.
Three versus four cycles of neoadjuvant gemcitabine cisplatin for muscle invasive bladder cancer (MIBC).
Authors: Major Catherine Kendall , Williams Michael Brandon , Fleming Mark T.
Published: June 2021

e16524

Background: The standard of care for MIBC is neoadjuvant (NAC) cisplatin-based chemotherapy with either 3-4 cycles of dose dense MVAC or 4 cycles of gemcitabine/cisplatin (GC) followed by radical cystectomy. However, due to toxicity some patients are unable to complete intention to treat full course chemotherapy. We aim to identify any variation in overall survival (OS) and progression-free survival (PFS) with 3 vs 4 cycles of neoadjuvant GC in the setting of miUCB. We hypothesize that there will be a statistically significant difference in OS and PFS with three vs four cycles of neoadjuvant GC. Methods: A consecutive retrospective chart review of patients with MIBC treated with three or four cycles of neoadjuvant cisplatin-based chemotherapy from 2009-2020 was performed. R Studio was used to generate Kaplan-Meier curves representing OS and PFS with p-values. Results: One hundred and twenty-one patients were identified. Patient characteristics are described in the table below. Eighty-six patients received 4 cycles of GC and thirty-five patients received 3 cycles. Ninety-five patients proceeded to cystectomy: 93 received a radical cystectomy, 1 received a partial cystectomy, and 1 was aborted due to positive lymph nodes. There was a statistically significant difference in OS between those who got 3 or 4 cycles (p=0.03) and PFS (p=0.014). Median OS for those who got 3 cycles and 4 cycles was 52 months and 92 months respectively. Conclusions: Toxicity can preclude patients from receiving four cycles of GC and this study demonstrates a significant difference in overall OS and PFS between those who receive 3 vs 4 cycles of GC.[Table: see text]
RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.
Authors: Li Liping , Yang Mengmei , Huang Mengli
Published: June 2021

e16528

Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.
Baseline modified Glasgow prognostic score (mGPS) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI).
Authors: Brown Jacqueline T , Liu Yuan , Martini Dylan J. , Shabto Julie M. , Russler Greta , Caulfield Sarah , Yantorni Lauren Beth , Joshi Shreyas S. , Kissick Haydn , Ogan Kenneth , Nazha Bassel , Carthon Bradley Curtis , Kucuk Omer , Harris Wayne , Master Viraj A. , Bilen Mehmet Asim
Published: June 2021

e16546

Background: The IMDC and MSKCC risk models for mRCC were validated before the era of ICI. The mGPS incorporates albumin and C-reactive protein and reflects systemic inflammation. mGPS may be a useful prognostic biomarker of particular relevance in mRCC given the current, largely ICI-based treatment paradigm and hypothesis that systemic inflammation may contribute to ICI resistance. Methods: We retrospectively assessed mRCC patients treated with ICI (including anti-PD-1 and anti-PD-L1 agents) in any line of therapy at Winship Cancer Institute of Emory University from 2015-2018. Primary outcomes assessed included overall survival (OS) and progression-free survival (PFS). mGPS was calculated by giving 1 point for CRP > 10 mg/L and/or albumin < 3.5 g/dL with 0 points awarded for solitary low albumin. The relationship between mGPS and survival outcomes was assessed in UVA and MVA using Cox proportional hazard model and in Kaplan-Meier analysis. Results: We assessed 156 eligible patients. Median follow up was 24.2 months. Median age was 64 years, 69% were male, 20% were Black, and 78% had clear cell histology. 57.1% received anti-PD-1 monotherapy whereas all others received dual ICI or ICI combined with an antiangiogenic agent or experimental therapy in trial. Higher baseline mGPS was significantly associated with worse OS and PFS (Table). The median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (CI 27.3, NA), 15.3 (CI 11, 24.2) and 10 (CI 4.6, 17.5) months, respectively (p<0.0001), while the median PFS of these three cohorts was 6.7 (CI 3.6, 13.1), 4.2 (CI 2.9, 6.2) and 2.6 (CI 2, 5.6) months, respectively (p=0.0216). Conclusions: A higher mGPS at the start of therapy was negatively prognostic in patients with mRCC receiving ICI. These results should be validated in a larger, prospective study. [Table: see text]
TIVO-3: Age-related tolerability outcomes of tivozanib versus sorafenib in metastatic relapsed or refractory renal cell carcinoma, a subgroup analysis of the TIVO-3 clinical trial.
Authors: Escudier Bernard , Rini Brian I. , Pal Sumanta K. , McDermott David F. , Porta Camillo , Verzoni Elena , Atkins Michael B. , Needle Michael N. , Hutson Thomas E.
Published: June 2021

e16553

Background: Tivozanib (TIVO) is a potent and selective VEGF receptor (R) tyrosine kinase inhibitor with a long half-life designed to optimize the VEGF blockade while minimizing off-target toxicities. The TIVO-3 trial demonstrated improved progression-free survival (PFS) when compared to sorafenib (SOR; 5.6 mo. vs 3.9 mo., respectively) with a hazard ratio (HR) of 0.73. TIVO showed better tolerability with reduced need for dose interruptions (p = 0.0164) and dose reductions (p = 0.0147) as compared to SOR. Methods: Data was analyzed to identify relationships between and age or prior use of immune checkpoint inhibitors (CPI). Results: Of the 343 patients treated on study, 120 (35%) were between age 65 and 75 and 34 (10%) were over 75. Adverse events were less frequent for TIVO compared to SOR in all age groups and drug exposure was consistently greater in the TIVO arm. Of particular interest, the tolerability advantages noted in the total population are also observed in the patients 75 and over with almost half the rate of the adverse drug reactions leading to dose reduction or discontinuation compared to SOR. Patients treated with prior CPI had an increased need for dose adjustment, but dose adjustments were less common with TIVO than SOR in CPI exposed and naïve patients. Conclusions: Tivozanib was better tolerated than sorafenib regardless of age or prior CPI treatment. Dose adjustments and interruptions are more common after prior CPI. Clinical trial information: NCT02627963. [Table: see text]
Clinicopathologic features of Xp11.2 translocation renal cell carcinoma and its response to target therapy.
Authors: Yan Xieqiao , Chi Zhihong , Si Lu , Cui Chuanliang , Kong Yan , Tang Bixia , Mao Lili , Wang Xuan , Lian Bin , Li Siming , Bai Xue , Zhou Li , Dai Jie , Sheng Xinan , Guo Jun
Published: June 2021

e16559

Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 translocation RCC was found in 41 cases. The median PFS and Median OS was 6.3 months (4.4 - 8.8) and 17.3 months (12.4 - 21.8) for the whole cohort, respectively. First-line treatment mainly included sunitinib (n = 12), sorafenib (n = 13), axitinib (n = 6), and pazopanib (n = 4), and the median PFS of these regimens was 5.4 months, 5.1 months, 9.4 months, 8.3 months, respectively. Twenty-three patients received subsequent therapies, the median PFS and the median OS was 4.3 months and 12 months for the second-line therapy(n = 21), 4.3 months and 14.1 months for the third-line therapy(n = 11), 2.4 months and 9.6 months for the fourth-line therapy(n = 6). Conclusions: Metastatic Xp11.2 translocation RCC is an aggressive disease. Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) agents appeared to demonstrate some efficacy, the combination of VEGFR-TKI and immune checkpoint inhibitor (ICI) might be a useful tool for the treatment of metastatic Xp11.2 translocation RCC.
Prostate-specific antigen testing in the disabled population: A cross-sectional analysis of the Health Information National Trends Survey (HINTS).
Authors: Leong Joon Yau , Pinkhasov Ruben , Chandrasekar Thenappan , Shapiro Oleg , Daneshvar Michael , Sanford Thomas , Bratslavsky Gennady , Goldberg Hanan
Published: June 2021

e17000

Background: Disabled patients are a unique minority population that may have lower literacy levels and difficulty communicating with physicians. Furthermore, their knowledge for cancer prevention recommendations is unknown. Herein, we aim to compare prostate-specific antigen (PSA) testing rates and associated predictors among disabled men and non-disabled men in the USA. Methods: We performed a cross-sectional study utilizing the Health Information National Trends Survey (HINTS) to analyze factors predicting PSA testing rates in men with disabilities (disabled, deaf, blind). Multivariable logistic regression models were used to determine clinically significant predictors of PSA testing in men with disabilities compared to that of the healthy cohort. Results: A total of 782 (14.6%) disabled men were compared to 4,569 (85.4%) non-disabled men. Disabled men were older with a mean age of 65.0 ± 14.2 vs. 55.0 ± 15.9 years (p < 0.001). On multivariable analysis, after adjusting for all available confounders including race, age, geographical region, survey year, marital status, health insurance, healthcare provider, amongst others, men with any disability were less likely to undergo PSA screening (OR 0.772, 95% CI 0.623-0.956, p = 0.018). Variables associated with increased PSA screening rates included age, having a healthcare provider or health insurance, and living with a partner. Although prostate cancer detection rates were shown to be higher among disabled men, this did not reach statistical significance. Conclusions: Our data suggests that significant inequalities in PSA screening exist among men with disabilities in the USA, with disabled men, especially the deaf and the blind, being less likely to be offered PSA screening. There is a clear need to implement strategies to reduce existing gaps in the care of disabled men and strive to reach equality in PSA screening in this unique population.
Sub-centimeter lymphadenopathy in germ cell testicular cancer: An ongoing surveillance challenge.
Authors: Kieran Ruth , Browne Iseult , McCaffrey John
Published: June 2021

e17011

Background: Correct identification of retroperitoneal disease is essential for proper staging and management in germ cell tumors. A size threshold of a 10mm diameter has high specificity in assessing nodal metastases, but sensitivity can be poor at this level and many patients have sub-centimeter lymphadenopathy on post-orchidectomy staging. As many staging scans are done soon after surgery, these may represent reactive lymph nodes. We aimed to assess the prevalence of sub-centimeter lymphadenopathy on baseline imaging in our patients, and its association with recurrence. Methods: Records of patients diagnosed with testicular germ cell cancer in a tertiary cancer center (n = 55, 2015-2020) were reviewed (median followup of 26 months, range 1-59). Lymphadenopathy size measurements were taken from the scan report, which had been authorized by a radiology consultant. Results: Patients had a median age of 34 (range 19-63). 37 (67%) had pure seminomas, 2 (4%) pure embryonal tumors, 12 (22%) mixed tumors with a primarily (> 50%) embryonal component, and 4 (7%) other mixed types. 48 (87%) had stage 1 disease, 3 (6%) stage 2 and 4 (7%) stage 3 disease. 26 (47%) had CT staging preoperatively, of the remainder 69% (n = 20) were staged in the first 48 postoperative hours. 28 (51%) had no lymphadenopathy, 15 (27%) had sub-centimeter lymphadenopathy within the landing zone, 8 (15%) had lymphadenopathy measuring > 1 cm within the landing zone, 4 (7%) had lymphadenopathy elsewhere. 7 had immediate chemotherapy, 48 entered surveillance. For the 14 with sub-centimeter lymphadenopathy within the landing zone who did not have immediate chemotherapy, 3 regressed, 8 were stable. 2 underwent a PET for further assessment, 1 a biopsy. 3 increased in size. 6 patients on surveillance had a recurrence – of these 2 had seminomas with no baseline lymphadenopathy, 4 had mixed primarily embryonal tumors (3 with sub-centimeter lymphadenopathy (0.6, 0.7 and 0.9 cm each), one with a 1.3cm para-aortic lymph node). Of those 4, only 1 had significantly elevated HCG pre-operatively, all recurred in the sites of previously noted lymphadenopathy. Those with mixed, primarily embryonal disease with lymphadenopathy (representing 50% of such patients on surveillance) had a higher recurrence risk than other patients on surveillance (OR: 153, 95% CI 6-3709, p= 0.002) Those undergoing preoperative/delayed postoperative imaging (n = 28) were equally likely to have lymphadenopathy to those having imaging in the first 7 postoperative days ( X2 (3, N= 27) = 2.9, p= 0.4). 1 patient had died (unrelated causes), all others were disease-free at most recent followup. Conclusions: Sub-centimeter lymphadenopathy is more likely to be benign in those with seminomas, but even small volume lymphadenopathy in those with mixed tumors with a primarily embryonal component may represent metastatic disease, and should be monitored closely.
PTEN loss as a potential biomarker in patients with castration resistant prostate cancer M0.
Authors: Puente Javier , Castro Elena , Sánchez García María , Vidal Natalia , Moreno Jesús , Hernández David , Senovilla Jose Luis , Herrera Bernardo , Montesa Alvaro , Carles Joan , Planas Jacques , Alonso Gordoa Teresa , Vazquez-Estevez Sergio , Álvarez Sara , Casas Francisco Javier , Paz Cabezas Mateo , de Torres Ines , Olmos David
Published: June 2021

e17043

Background: Until 2018, there were no approved agents for high risk non-metastatic castration-resistant prostate cancer (nmCRPC). Recently, three second-generation anti-androgens (apalutamide, enzalutamide and darolutamide), in combination with ADT, have demonstrated a significant benefit in metastasis-free survival (MFS) and overall survival.According to conventional imaging, nmCRPC state is the opposite to mCRPC. Nevertheless, CRPC is a continuous in which nmCRPC may share similar biology and biomarkers such as PTEN loss, which has proven to be a useful and targetable biomarker in mCRPC. Methods: We performed a prospective and multicenter analysis of 77 patients (pts) with nmCRPC. We collected blood samples as well as prostate cancer diagnostic biopsy whenever they were available. The aim of this study is to find potential biomarkers that could identify pts at a higher risk of metastasis development. Here we report preliminary results according to PTEN status. Results: We have analyzed 32 patients for PTEN loss. We report preliminary results using an IHC assay based on the IPATENTIAL150 PTEN score. Median age was 66 years and 50% of patients had a Gleason score > 8 irrespectively of PTEN status. We identified 24 patients (75%) with PTEN loss with a median PSA at diagnosis of 13,1 ng/ml, and a PSA doubling time (PSA-DT) of 6,3 months vs. 37,35 ng/ml and 3,5 months respectively in the PTEN non-loss pts. In the PTEN loss population, 9 pts (37,5%) did not receive any local treatment vs. 2 pts in the PTEN non-loss (25%). Mediantime from diagnosis to CRPC was 11.5 vs 8.0 yrs in PTEN loss vs. non-loss pts. In the PTEN loss population 2 patients received apalutamide plus ADT and 2 darolutamide plus ADT, these patients were excluded for the MFS analysis. Median MFS was 37 months in the PTEN loss population vs. 23 months in the PTEN non-loss. However, with a median follow-up of 38 months, 54% of PTEN loss pts had developed metastasis and 50% of PTEN non-loss pts. Skeleton was by far the first site of metastasis in PTEN non-loss pts (75%), while PTEN loss pts developed metastasis in lymph nodes (38,5%) nearly as much as in the skeleton (46%). Conclusions: To our knowledge, this is the first data of PTEN loss as a biomarker in nmCRPC. In our study, PTEN loss in primary tumor is more frequent than previously documented for mCRPC. PTEN loss appears to provide a better prognosis and higher lymph node involvement. Further analysis will be performed to corroborate these results and identify other factors involved.
Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.
Authors: Kaur Anahat , Wang Shuai , Elrafei Tarek N. , Steinberg Lewis , Kumar Abhishek
Published: June 2021

e17502

Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]
Global line-1 hypomethylation as novel biomarker for cervical cancer in Nigerian women living with HIV.
Authors: Zheng Yinan , Musa Jonah , Joyce Brian Thomas , Wang Jun , Gursel Demirkan , Silas Olugbenga A. , Abdulkareem Fatimah Biade , Imade Godwin , Akanmu Alani , Wei Jian-Jun , Kocherginsky Masha , Kim Kwnag-Youn , Wehbe Firas Hazem , Achenbach Chad , Anorlu Rose , Simon Melissa A. , Sagay Atiene , Ogunsola Folasade , Murphy Robert , Hou Lifang
Published: June 2021

e17513

Background: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria. Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value. Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72). Conclusions: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries.
L-MOCA: An open-label study of olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer.
Authors: Gao Qing-lei , Zhu Jianqing , Zhao Weidong , Huang Yi , An Ruifang , Zheng Hong , Qu Pengpeng , Wang Li , Zhou Qi , Wang Danbo , Lou Ge , Wang Jing , Low John , Kong Beihua , Yin Rutie , Xie Xing , Liu Jihong , Sun Wei , Zang Rongyu , Ma Ding
Published: June 2021

e17526

Background: In patients with platinum-sensitive recurrent serous ovarian cancer, maintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib, significantly improves progression-free survival (PFS) versus placebo. This is the first study to evaluate the efficacy and tolerability of the olaparib (Lynparza), an oral PARPi, in patients with platinum-sensitive relapsed (PSR) ovarian cancer, carried out exclusively in Asia. Methods: In this open-label, single arm trial, patients with PSR high grade epithelial ovarian cancer who had received ≥2 previous lines of platinum-based chemotherapy with a response, were enrolled from 28 centres in China and Malaysia. All patients received oral olaparib (300 mg) tablet twice daily until disease progression or unacceptable toxicity. The primary endpoint was PFS assessed by investigator according to RECIST 1.1 criteria. Secondary endpoints included time to TFST, PFS2, TSST, OS, and safety endpoints included adverse events (AEs). Subgroup analysis of PFS was examined by BRCA status. Data were summarized by descriptive statistics; time-to-event endpoints were analyzed using Kaplan-Meier method. Primary analysis was performed when 60% of PFS events had been achieved. Results: Between 2018 and 2020, the 224 patients recruited into this study received oral olaparib (full analysis set). 224 patients (91.5% from China and 8.5% from Malaysia) provided BRCA mutation status by blood and tissue testing. 47.3% patients were BRCAm, 41.1% patients were gBRCAm,52.2% patients were BRCAwt and 0.4% patients were BRCA unknown. 35.7% patients had received ＞2 lines of chemotherapy. At data cut-off (Dec 25th, 2020), 139 patients had disease progression; median PFS (mPFS) was 16.1 (95% CI 13.3-18.3) m in all patients. The mPFS was 21.2m, 21.4m and 11.0m in BRCAm, gBRCA and BRCAwt subgroups, respectively. The overall incidence of any AE and SAE was 99.1% and 25.4%, respectively. There were 9.4% patients who discontinued therapy due to the treatment related AE. The most common AEs were anemia, nausea and vomiting. Conclusions: The L-MOCA study demonstrates olaparib maintenance treatment is effective and well tolerated in Asian PSR ovarian cancer patients regardless of BRCA status. Clinical trial information: NCT03534453. [Table: see text]
Preliminary results of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer.
Authors: Liu Guochen , Liu Jihong , Xian Bingna , Li Jing , Feng Yanling , Huang He , Wan Ting , Huang Qidan , Tu Hua , Gu Haifeng , Liu Zhimin
Published: June 2021

e17532

Background: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. Combination of PARP inhibitors and antiangiogenic therapy is reported as an effective antitumor strategy. In this study (ANNIE), we evaluate the activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian carcinoma. Methods: The ANNIE trial (ClinicalTrials.gov identifier NCT04376073) was a multicentre, single-arm, phase 2 study that evaluated the safety and activity of niraparib combined with anlotinib in patients (≥18 & ≤70 years, an Eastern Cooperative Oncology Group performance status of 0 or 1) with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer cancer whose disease recurred in less than 6 months after the last administered platinum therapy, and with measurable disease according to the Response Evaluation Criteria in Solid Tumors. Patients received oral niraparib 300mg/200mg once daily continuously and anlotinib 12mg (The initial dose was reduced to 10mg on November 1, 2020) on day 1-14 of each 21-day cycle thereafter until disease progression or intolerable toxicity. The primary objective was to assess objective response rate (ORR; complete plus partial responses) according to RECIST version 1.1. 40 cases are planned to be enrolled. Results: Between May 22, 2020 and February 6, 2021, we enrolled 33 patients (median age, 56 years [range, 37-69 years]). Patients had received a median of six (range, 2-9) previous lines of therapy. The cut-off date of analysis was February 4, 2021, the median follow-up was 4.1 months (range, 0.1–8.1). At data cutoff, all but seven (2 voluntarily withdrew, 5 with progressive disease) of the patients were still on treatment. Twenty-five patients underwent imaging evaluation. The confirmed best overall response assessment showed 12 with partial responses, 12 with stable disease, yielding the ORR of 48.0% (95% CI, 27.0%̃69.0%). The median duration of response and the median PFS were not reached. Drug-related grade 3 or worse treatment-emergent adverse events were occurred in 39.4% patients, including hand-foot skin reaction (3 pts), thrombocytopenia (2 pts), hypertriglyceridemia (2 pts), neutropenia (2 pts), anemia (1 pts) and hypertension (1 pts). The most common treatment emergent adverse events were hand-foot skin reaction (36.4%), hypertension (36.4%), and thrombocytopenia (33.3%). No treatment-related death was recorded. Enrollment was ongoing so far. Conclusions: Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum resistant recurrent ovarian cancer. The conclusion can be clarified after the research is completed. Clinical trial information: NCT04376073.