bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of bilateral supraclavicular lymph nodes irradiation in stage III lower thoracic esophageal squamous cell carcinoma after radical surgery.
Authors: Deng Min , Gong Youling 
Published: September 2018

e15555 Background: Surgery is the most important treatment for patients with lower thoracic esophageal squamous cell carcinoma (LT-ESCC) at stage III, but the locoregional failure is common, especially mediastinal and supraclavicular lymph nodes metastases. Postopearative radiotherapy (PORT) is benefit for those patients. However, the clinic target volume (CTV) remains controversial, especially whether or not including bilateral supraclavicular lymph nodes radiotherapy. Methods:79 patients of lower LT-ESCC at stage III who had undergone radical surgery and PORT were enrolled. 51 patients received the PORT CTV without bilateral suparclavicular lymph nodes region (group A), while 28 patients received the CTV with suparclavicular region (group B). Results: Totally, 26 patients had the tumor recurrences of supraclavicular lymph nodes. Among them, 23(45.1%) patients had the metastasis in group A, 3(10.7%) patients had the metastasis in group B. Univariate analysis showed the bilateral supraclavicular region RT can decrease of supraclavicular lymph nodes recurrence (p = 0.007). However, it could not prolong the overall survival (p = 0.273) or control the distant metastasis (p = 0.760).The Cox analysis revealed it was independent factor to control supraclavicular lymph node recurrence (HR = 0.027; 95 % CI 0.068-0.757; p = 0.016). PORT includingsupraclavicular region didn’t increase the radiotherapy complications, such as radiation pneumonia (p = 0.354), radiation esophagitis (p = 0.456), gastrointestinal reaction (p = 0.809), neutropenia (p = 0.470), thrombocytopenia (p = 0.137) and anemia (p = 0.642). Conclusions:PORT including bilateral supraclavicular region can reduce the metastasis of supraclavicular lymph nodes in LT-ESCC at stage III, and it does not increase radiotherapy complications. However, it can’t prolong OS or control the distant metastasis. Chemotherapy is essential to control distant metastasis and prolong OS.
Nimotuzumab plus paclitaxel and cisplatin as 1st line treatment for unresectable esophageal squamous cell carcinoma: Long term follow-up of survival in a phase II study.
Authors: Zhang Xiaodong , Jia Jun , Lu Ming , Wang Xicheng , Gong Jifang , Li Jie , Li Jian , Li Yan , Zhang Xiaotian , Lu Zhihao , Yu Jing , Sun Zhiwei , Yang Ying , Shen Lin 
Published: September 2018

e15573 Background: The role of anti-epidermal growth factor receptor (EGFR) targeting treatment in esophageal squamous cell carcinoma (ESCC) is still uncertain. We conducted a prospective phase 2 study of paclitaxel, cisplatin, and nimotuzumab (TPN) as first-line treatment in unresectable or metastatic ESCC (NCT01336049). The objective response rate was 51.8%. Here we reported long-term follow-up results of that initial trial. Methods: 59 patients were enrolled from Mar 2011 to Apr 2013 and treated with the TPN regimen (nimotuzumab 200mg weekly, paclitaxel 175mg/m2 on day1, and cisplatin 30mg/m2 on day1 and 2, repeat every 3 weeks for total six cycles). Patients were allowed to receive sequential radiotherapy in case of local-regional disease or controlling symptom. Results: 56 of 59 patients were eligible for evaluation. After a median follow-up of 32.2months, the median progression-free survival (PFS) and overall survival (OS) were 18.1±4.2 months (95% Confidence: 9.8-26.4) and 26.2±10.0 months (95% Confidence: 6.6-45.8) in 29 patients with unresectable local-regional disease, while those were 6.6±0.4 months (95% Confidence: 5.8-7.5) and 11.5±3.7 months (95% Confidence: 4.2-18.8) respectively in 27 patients with metastatic disease. Patients of male, with multiple lymph node station metastasis, visceral metastasis, no response to TPN treatment, and without radiotherapy had worse OS. Even in some patients with multiple stations lymph node metastasis or recurrent disease of local-regional lymph node metastasis, TPN with sequential radiation seemed could bring longer survival time. But multivariate cox-regression analysis only confirmed that the TPN treatment was associations with OS. Compared with those of complete and partial response, patients of stable disease and progression had poor OS (HR = 2.32, 95% CI: 1.03-5.05, p = 0.03). Conclusions: the combination of nimotuzumab, paclitaxel, and cisplatin is effective as first-line treatment for patients with unresectable and metastatic ESCC, especially those with sequential radiotherapy. Clinical trial information: NCT01336049.
Erythropoietin and hepatocellular carcinoma: What is patients survival outcome?
Authors: Abdel-Wahab Reham , Hassan Manal , Lacin Sahin , Shalaby Ahmed S , Afshar-Kharghan Vahid , Kaseb Ahmed Omar 
Published: September 2018

e15660 Background: Erythropoietin (Epo) is a glycoprotein that stimulates cell proliferation and angiogenesis. Both, hypoxia and anemia are triggering factors that induce Epo overproduction. Although, previous studies reported that Epo induces angiogenesis in hepatocellular cancer (HCC), the relationship between Epo and HCC remains unclear .Our study aims to assess Epo level in HCC patients and evaluate its prognostic roles. Methods: We enrolled 766 HCC patients from MD Anderson Cancer Center Between 2001 and 2014. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. Based on the plasma level of Epo, we classified our patients into two groups: group 1 (N = 407) had normal serum level ( < 20mIU/ml) and group 2 (N = 359) had higher level (≥20mIU/ml). Median overall survival (OS) was estimated by kaplan meier curve and log rank test. We used multivariate hazard ratio (HR) and 95% Confidence interval (CI) to determine the independent effect of Epo on the prognosis of HCC patients. Results: Univariate analysis showed that higher level of Epo had a statistically significant association to a higher Child Pugh Score (CTP), and an advanced stage in Barcelona clinic liver cancer (BCLC) and Cancer of the Liver Italian Program (CLIP). Median OS and 95%CI was 16.1 months (12.7 – 19.4) in group 1 compared to 11.4 months (8.6 – 14.3) in group 2 ( P< .0001). The same significant difference was achieved among HCC patients with cirrhosis ( P = .005) and without cirrhosis ( P= .002). The estimated multivariate HR and 95%CI for elevated Epo level was 1.4 (1.04 – 1.9) (P = .03) in the absence of cirrhosis, while it was 0.97 (0.79 – 1.2) (P = .8) in the presence of cirrhosis after adjustment for several confounding factors. Conclusions: Abnormal Epo level in the plasma is significantly associated with a worse clinico-pathological characteristics and a shorter OS. Previous studies showed that HCC stimulates erythrocytosis and increases Epo production. Although, our study concluded that Epo is an independent prognostic factor among non-cirrhotic HCC patients only. Future studies are warranted to understand the mechanistic pathways of Epo effect in HCC patients and its variation in the presence and absence of cirrhosis.
A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) as a bridge to transplant in hepatocellular carcinoma (HCC).
Authors: Nugent Francis Warren , Gunturu Krishna , Stuart Keith E. , Flacke Sebastian , Molgaard Chris , Hunter Klaudia , Qamar Amir , Iqbal Shams , Gordon Frederick , Galuski Kari , Hartnett Erin 
Published: September 2018

e15677 Background: For HCC pts undergoing LT, local treatment as a "bridge" is standard to decrease likelihood of tumor progression. The most common treatment is TACE, but the safest and most effective bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts are planned for accrual. Pts with C-P < 9 and HCC within Milan Criteria were randomized between two arms. TACE pts received 2 treatments one month apart using DEBDOX beads. TACE pts were hospitalized after each treatment. Pts randomized to SBRT, after fiducial placement, received a median total dose of 45 Gy delivered over 5 fractions. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life (QOL) were assessed before treatment, during treatment, 2 weeks post-treatment, and then every 3 months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was need for retreatment of the previously treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, QOL, and cost. Results: From 9/2014-1/17, 33 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE (n = 18) vs. SBRT (15). Data on evaluable pts is summarized in the table below. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears at least equally effective as TACE as a bridge to liver transplantation. SBRT may engender less toxicity, better maintain QOL, and eliminate the need for hospitalization. An update along with a full cost analysis will be presented in June. Clinical trial information: nct02182687. [Table: see text]
IL-8 as PD biomarker for TGF-b antisense (OT-101) therapy: Results of a phase II trial.
Authors: Trieu Vuong N. , Wang Wen , Qazi Sanjive , Ng Kevin , D'Cruz Osmond , Nam David , Hwang Larn 
Published: September 2018

e15742 Background: Trabedersen (OT-101) is a phosphorothioate antisense specific for human TGF-β2 mRNA. In a Phase I/II study of OT-101 in patients with advanced pancreatic cancer (PAC) treated second line and beyond, improved Overall Survival (OS) was observed when OT-101 was followed with chemotherapy. Here, we examined the association between plasma levels of cyto-/chemokines and OS outcomes and identified IL-8 as a biomarker for improved OS. Methods: 37 patients with PAC were treated with OT-101 by IV infusion in escalating doses of 2 treatment schedules (7-days on, 7-days off and 4-days on, 10-days off). Plasma levels of 31 cyto-/chemokine were measured over 8 time points during 3 cycles of OT-101 therapy (140 mg/m2/day on a 4-days on, 10-days off cycle). IL-8 levels were measured in 12 patients before and during 3 cycles of treatment on Days 2 and 5. Maximum levels of IL-8 on Day 2 were subtracted from levels on Day 5 and these standardized scores were correlated with log10 transformed OS values. Feedback interactions with PK parameters were also investigated utilizing an ANCOVA model. Results: We observed OS of 14.5 months and 2.6 months for those treated with and without subsequent chemotherapies, respectively (p = 0.0009). Peak IL-8 levels were apparent after 2 days of OT-101 treatment. A significant regression and 95% CI was evident, whereby increasing difference of IL-8 following Day 2 vs Day 5 was positively correlated with OS (R2 = 0.58, F1,9 = 12.32, P = 0.0066). R- squared increased from 0.4955, p < 0.0001, for all patients to 0.8524, p < 0.0001, for patients without subsequent chemo and 0.9744, p < 0.0001, for patients with subsequent chemo. The ANCOVA model for two PK parameters exhibited significant model fits (F3,7 = 7.89, P = 0.012 for Simulated Vz Mean; F3,7 = 8.18, P = 0.011 for Simulated Cl Mean) and the interaction effects resulted in lower p-values for the correlation of OS vs IL-8 levels. Conclusions: Peak of IL-8 response on Day 2 of OT-101 treatment was correlated with OS in PAC patients. The correlation existed between OS whether patients received subsequent chemo or not suggesting that the IL-8 spike is a PD biomarker for OT-101. Clinical trial information: NCT00844064.
Comparison of guidelines, BRCAPRO, and genetic counsellors estimates for the identification of BRCA1 and BRCA2 mutations in pancreatic cancer.
Authors: Grant Robert C , Holter Spring , Borgida Ayelet , Pintile Melania , Akbari Mohammad R , Zogopoulos George , Gallinger Steven 
Published: September 2018

e15784 Background: Germline BRCA1 and BRCA2 (BRCA) mutation carriers with pancreatic adenocarcinoma (PDAC) are eligible for precision therapy trials and their relatives should undergo genetic testing and tailored cancer prevention. We assessed the performance of strategies to identify BRCA mutation carriers in PDAC. Methods: Incident cases of PDAC were prospectively recruited for BRCA sequencing in a multidisciplinary PDAC clinic. Probands were evaluated according to the National Comprehensive Cancer Network 2017 (NCCN) and the Ontario Ministry of Health and Long-Term Care (MOHLTC) guidelines for BRCA testing. The probability of each proband carrying a BRCA mutation was estimated using BRCAPRO and by surveying genetic counsellors. Guidelines were compared across sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Estimates from BRCAPRO and the genetic counsellors were compared using the area-under-the-curve (AUC) for discrimination and the Hosmer-Lemeshow test for calibration. Results: 22/484 (4.5%) of probands carried a BRCA mutation. The mutation rate was higher in probands with Ashkenazi Jewish ancestry (7/57, p=0.009) or a first-degree relative with breast cancer (8/83, p=0.036). 119 genetic counsellors responded to the survey and each proband was assessed by a mean of 5.9 genetic counsellors. The Table displays the performance of the guidelines. Discrimination was similar for the estimates from genetic counsellors and BRCAPRO (AUC 0.755 and 0.775, respectively, p=0.701). Genetic counsellors generally overestimated (p=0.008), whereas BRCAPRO severely underestimated (p<0.001), the probability that each proband carried a mutation. Conclusions: The NCCN 2017 guidelines and estimates from genetic counsellors accurately identify BRCA mutations in PDAC. The MOHLTC guidelines and BRCAPRO should be updated to account for the association between PDAC and BRCA mutations. [Table: see text]
Phase II study of panitumumab in KRAS wild-type metastatic adenocarcinoma of the small bowel or ampulla of vater.
Authors: Gulhati Pat , Raghav Kanwal Pratap Singh , Shroff Rachna T. , Varadhachary Gauri R. , Javle Milind M. , Qiao Wei , Wang Huamin , Morris Jeffrey , Wolff Robert A. , Overman Michael J. 
Published: September 2018

e15799 Background: Given the benefit noted with epidermal growth factor receptor (EGFR) antibodies in KRAS wild-type colorectal cancer, we conducted a phase II trial to evaluate the efficacy of panitumumab in metastatic small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Methods: This is a single-center open-label single arm two-stage phase II study. The primary objective was response rate (RR). Secondary objectives included overall progression-free survival (PFS), overall survival (OS) and toxicity. Eligibility included: KRAS exon 2 wild-type, ECOG PS 0-1, metastatic disease, adequate organ function and prior progression or intolerance to fluoropyrimidine with oxaliplatin. Panitumumab was administered at a dose of 6mg/kg IV every 14 days. Next generation sequencing panels were used for genomic analysis. Results: 9 patients [M/F 7/2, median age: 61 yrs (range: 40-74), ECOG PS 0/1: 2/7] were enrolled from September 2013 to October 2015. 1 pt had AAC (pancreaticobiliary subtype) and 8 pts had SBA (duodenal in 3, jejunal/ileal in 5). The most common toxicity was grade 1 acneiform rash in all patients. The most common grade 2/3 toxicities were anemia (33%), fatigue (22%), hypomagnesemia (22%) and skin infection (22%). None of the patients had a response, 2 patients had SD while the remaining 7 patients had PD. At a median follow-up time of 16.6 months, the median PFS and median OS were 2.4 months and 5.6 months, respectively. Extended RAS mutational testing identified 0/9 patients with mutations in extended KRAS or NRAS. Further genomic analysis of genes relevant to anti-EGFR activity (BRAF, PIK3CA and ERBB2) identified 2/9 patients with BRAF G469A mutation, 1/9 patients with PIK3CA H1047R mutation, and 0/9 patients with ERRB2 mutations. Conclusions: Although well tolerated, panitumumab had minimal clinical activity in patients with metastatic SBA and AAC. Given recent findings suggesting that right-sided colon cancers (hindgut derivation) benefit less from anti-EGFR therapy compared to left-sided colon cancers (midgut derivation), we propose that our findings may relate to the primarily foregut (proximal duodenum) and midgut (distal duodenum to ileum) derivation of the small bowel. Clinical trial information: NCT01202409.
Correlation of next generation sequencing (NGS) of urine with tumor and plasma in patients with non-muscle invasive bladder cancer (NMIBC).
Authors: Raymond Chris , Lahdya Alexandria , Hernandez Jenny , Garg Kavita , Henderson Samantha , Vakar-Lopez Funda , Li Mark , Montgomery Robert B. , Wright Jonathan Lawrence 
Published: September 2018

e16002 Background: The current standard-of-care surveillance protocols for post-treatment NMIBC patients involve invasive procedures that result in poor patient compliance. Detection of recurrent NMIBC tumor DNA in plasma or urine would provide a less invasive alternative, and here we examine the feasibility of this approach by performing targeted NGS on tumor, plasma, and urine samples from NMIBC patients. Methods: 5 patients with untreated NMIBC (histology: Ta(n = 3), T1(n = 2)) have been analyzed to date. Urine and plasma samples were taken just prior to tumor resection. Samples were analyzed using a capture panel that includes common mutations found in > 80% of NMIBC patients. Coverage includes the promoter region of the TERT gene, the entire coding regions of KDM6A and FGFR3, and copy number variation in PD-L1 and JAK2. Results: Mutations were observed in all tumor samples, with the TERT -124C > T promoter mutation found in 4 patients (AF:16-84%) and the TERT -146C > T promoter mutation found in the other (AF:19%). Deleterious mutations were found in KDM6A for 4 patients, and FGFR3 activating mutations were found in 2 patients. Amplification of FGFR3 was seen in one sample. When the 4 matched pairs of urine and tumor samples were examined, all of the called mutations in tumor were also found in urine at similar allele frequencies. This includes the detection of gene copy alterations. No such mutations were observed in plasma samples despite extensive sequencing ( > 2000 unique read coverage). Conclusions: These data show that canonical NMIBC mutations are readily detectable in urine and correlate well with tumor, suggesting that NMIBC tumors shed prolifically into urine, and indicate that further investigation of NGS sequencing of urine as a means of detecting NMIBC recurrence is warranted.
Responses to chemotherapy in patients with metastatic urothelial cancer (MUC) after frontline immunotherapy.
Authors: Szabados Bernadett , Van Der Heijden Michiel Simon , Gomez De Liano Lista Alfonso , Tang Yen Zhi , Powles Thomas 
Published: September 2018

e16004 Background: The effect of prior immune checkpoint inhibition therapy (CI) on the efficacy of subsequent chemotherapy is largely unknown in MUC. The identification of the optimal sequence of chemotherapy and IO is yet to be determined, but may influence outcomes. Methods: A retrospective audit and comparison of patients who progressed after first and second line CI and received subsequent standard chemotherapy was performed. Date was collected across a broad spectrum of CI. We report on patient’s characteristics and response rates of 28 sequential patients collected from two institutions who received chemotherapy after CI. Patients were separated into 2 cohorts. Cohort A had not previously received chemotherapy (n = 14), cohort B had previously received at least 1 chemotherapy regimen (n = 14). Central radiology review was performed. We assessed objective response rate by RECIST v 1.1. Kaplan Meier method was used. Results: Median age for the whole cohort was 64 yrs (45-80). ECOG was 0/1 in 89,3% and 2 in 10,7% at the time of starting chemotherapy. The commonest chemotherapy regimen in cohort A and B were carboplatin-gemcitabine (71%) and carboplatin paclitaxel (50%) respectively. 75% of the patients were intermediate risk group. In Cohort A 63% responded to chemotherapy whereas in cohort B only 3 patients showed response. The median change in target lesions in the front line immunotherapy cohort was -60% (-81 to +1%). Both patients who responded to 2nd line chemotherapy after CI had a long interval between first and 2nd line chemotherapy (9-24 months). Conclusions: Chemotherapy maintains its efficacy after front line CI with deep responses. Although numbers are modest, results strongly suggest patients should be offered chemotherapy in this setting.
Title: A real-world study of chemotherapy treatment and costs in metastatic urothelial cancer (mUC) patients in the United States.
Authors: Malangone-Monaco Elisabetta , Wilson Kathleen , Varker Helen , Stetsovsky Diana , Shih-Wen Lin , Tayama Darren , Ogale Sarika 
Published: September 2018

e16009 Background: Cisplatin (CIS)-based regimens are recommended for first-line (1L) treatment of mUC. Carboplatin (CAR) serves as an alternative for patients unfit to receive CIS. This study examined treatment patterns and costs for patients treated with CIS, CAR, and other treatment (OT). Methods: This was a retrospective cohort study of 9,436 patients from a U.S. insurance claims database between 1/1/2005-6/30/2015. Adult patients with ≥ 2 diagnosis codes for UC, ≥ 2 diagnosis codes for metastasis (first metastasis = index date), ≥ 6 months of continuous enrollment pre-index and no evidence of cystectomy were included. Results: The population was majority male (74%); with a mean age of 70. Sixty percent of the mUC patients did not receive 1L chemotherapy during the study period. Among the 3,750 who received treatment, 935 (25%) received 1L CIS, 1,505 (40%) received 1L CAR, and the remaining patients received OT. Patients treated with CIS were younger (62 vs. 69 and 68) and healthier (NCI comorbidity score 0.7 vs. 1.1, and 1.0) vs. patients treated with CAR and OT, respectively. Among CAR patients, 87% received it as combination therapy (CT), with GEM being the most common agent used with CAR. Only 16% of OT patients received CT. Per-patient-per-month (PPPM) 1L all-cause healthcare costs were similar across 1L regimens ($16,540 CIS, $15,739 CAR, and $16,443 OT) and 1L mUC-related healthcare costs were $9,043, $6,975 and $6,191 for CIS, CAR, and OT, respectively. Conclusions: In this real-world study, the majority of mUC patients did not receive 1L chemotherapy, and only a small fraction of those treated received CIS. The remaining patients were treated with CAR or OT, often as monotherapy, which tend to have poorer outcomes compared with CIS. Despite CAR and OT treated patients being younger and healthier, their total health care costs were similar to CIS patients. Newer therapies may provide safer and more efficacious treatment alternatives for patients who are not considered a good fit for CIS therapy.