bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss at long arm of chromosome 4 as a predictive factor for recurrence of human hepatocellular carcinoma after orthotopic living-donor liver transplantation.
Authors: Nishimura Takafumi , Mori Yukiko , Uemoto Shinji , Nishida Naoshi
Published: March 2020

e15054

Background: Living-donor liver transplantation (LDLT) is one of the curative treatments of hepatocellular carcinoma (HCC) that confined to the liver. To extend the indication of LDLT where candidate donors are more likely to be found than in liver transplantation from brain death, the Kyoto criteria (maximum tumor diameter < 5 cm, number of tumor < 10 nodules, serum PIVKA-II < 400 mAU/ml) has been proposed in addition to Millan criteria (< 5 cm for solitary nodule, or < 3 cm and < 3 nodules). The aim of this study was to identify genetic or epigenetic changes that predict recurrence in this setting. Methods: With informed consent, tumor and non-tumor tissues were obtained from 51 patients with HCC at the time of LDLT surgery. DNA copy number alterations were determined by microsatellite analysis and single nucleotide polymorphism array analysis. Mutational analyses for TP53 and CTNNB1 were performed by direct sequencing. DNA methylation status of 18 tumors was further analyzed using BeadChip Human Methylation 450. Results: Identified factors that indicate high risk for recurrence were: exceeding the Millan criteria (p = 0.0245, Log-rank test), exceeding the Kyoto criteria (p = 0.0007), hepatitis B virus infection (p = 0.0057), poorly differentiated tumor (p = 0.0245), loss of 4q34.3 (p = 0.0003), 14q (p = 0.0003), 17p (p = 0.0103), and gain of 8q24 (p = 0.0101), and high fractional allelic loss index (p < 0.0001). In patients who exceeded the Kyoto criteria for LDLT loss of 4q were associated with recurrences (5 recurrences for 6 cases with loss of 4q vs. no recurrence for 6 cases with retaining 4q). Conclusions: Genetic and epigenetic analysis combined with clinico-pathological features may help extending the indication for LDLT in patients with HCC.
Increasing stepwise expression of p16 e pRb proteins in esophageal mucosa from patients at high risk for squamous cell carcinoma.
Authors: Muller Leandro Bizarro , Antunes Luis Carlos Moreira , Lopes Antonio de Barros , Vanazzi Sara , Meurer Luise , Fagundes Renato Borges
Published: March 2020

e15067

Background: Squamous cell carcinoma of the esophagus is a lethal cancer which carries a poor prognosis due to late diagnosis. Identification of molecular markers may aid early diagnosis. We assessed the expression of p16 and pRb in esophageal mucosa and their associations with histology. Methods: Esophageal biopsies were collected from 38 patients with no esophageal lesion (group 1); from iodine-negative and normally staining areas from 108 alcoholic smokers (group 2); and from tumor and non-tumor areas from 41 patients with squamous cell carcinoma (group 3). The histological diagnoses were compared with immunoexpression of p16 and pRb (defined as positive staining in >10% of the cells). Results: In group 1, the biopsies showed only normal mucosa or mild esophagitis, and no expression of p16 or pRb. In groups 2 and 3 the diagnoses were: normal mucosa (38.4%); esophagitis (44.4%); dysplasia or carcinoma in situ (2.8%) and carcinoma (14.3%). The percentage of cases with immunoexpression of p16 and pRb increased in a stepwise fashion over the histologic spectrum from normal mucosa to esophagitis, dysplasia/carcinoma in situ and carcinoma (p for trend < 0.01). Conclusions: Esophageal mucosa exposed to alcohol and tobacco which expresses these proteins may be at risk for malignant transformation.
Long-term prognosis of patients with gastric cancer in stage UICC I without lymph-node involvement.
Authors: Treese Christoph , Sanchez Pedro , Anagnostopoulos Ioannis , Schlag Peter M. , Kruschewski Michael , Haase Oliver , Berger Gerd , Blaeker Hendrik , Hummel Michael , Daum Severin
Published: March 2020

e15068

Background: Despite radical oncologic resection with extended lymph node removal, patients with adenocarcinoma of the gastro-esophageal junction or stomach in UICC stage I show only a 5-year survival of 60-80% (Hölscher et al, 2009; Siewert et al. 1998). The aim of this retrospective study was to analyze the long-term survival of caucasian patients with early stage gastric cancer as for this population exist only sparse data. Patients with lymph-node involvement were not included as this parameter is a well-known negative prognostic marker. Methods: Tissue specimens and clinical data from patients with gastric cancer treated in the years 1993 to 2010 at the Charité, Berlin were collected retrospectively. Patients with stage T1 and T2 pN0M0 gastric cancer treated only by surgery including D1- and D2-lymphnode dissection were included in this study. Patients without relapse were followed-up for a minimum period of 24 months. Results: 97 patients (w = 36, m = 61, age 29-90 years) with a follow-up time from 6 to 208 months were identified. The 5-year survival was 94.85% (for details, see Table). Conclusions: The present data indicate a much better prognosis (5-year survival of 95%) of UICC I patients than previously described (60-80%). In harmony with other studies, our data demonstrate that R1, L1 or V1 resection seem to be a risk factor for recurrence whereas signet-ring differentiation was not found as a risk factor in our patient cohort. Ongoing work involves a broad panel of immunohistochemical markers to select prognostic expression profiles which help to identify patients with early gastric cancer at higher risk. This study was supported by the Berliner Krebsgesellschaft, grant DAFF201101. [Table: see text]
Weekly docetaxel and cisplatin with capecitabine and bevacizumab (AVDCX) in patients with advanced esophagogastric cancer: Results of a phase Ib/II study.
Authors: Purim Ofer , Kundel Yulia , Sadeh Gonik Udi , Idelevich Efraim , Medalia Gal , Gordon Noa , Sulkes Aaron , Brenner Baruch
Published: March 2020

e15078

Background: Many efforts are being made to improve treatment options for advanced esophagogastric cancer (AEGC). The aim of this phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. Methods: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). To assure regimen's safety a short phase Ib part, with three dose levels, was planned. The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX and to determine the tumor response rate. Results: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%) and these were usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. Eventually, the recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). The objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. Eighteen patients (82%) derived a clinical benefit: improvement of pain, weight or performance status without a deterioration of any of these factors, from treatment. The median overall survival was 11.3 months (range, 1.5-39.2+ months) and median progression-free survival was 8.7 months (range, 1.3–26.6 months). The 2-year OS rate reached 22.7%. Conclusions: AVDCX was associated with bevacizumab-related fatal toxicities. It seems to reproduce the efficacy of bevacizumab regimen AVAGAST trial, without a clue for significant improvement over common docetaxel regimens in AEGC.
Assessment of prognosis in hepatocellular carcinoma (HCC) using biomarkers and serum measurements.
Authors: Teng Mabel Joey , Nathavitharana Ravindhi Lakmalee , Fox Richard , Berhane Sarah , Skowronska Anna , Johnson Philip James
Published: March 2020

e15093

Background: Factors that influence prognosis in HCC are well-recognised. They include tumour size and number, the severity of liver dysfunction and the symptomology. Several staging systems combining a number of these factors offer an estimate of prognosis. Some concerned that these staging systems encompass factors that are inherently subjective, e.g. the extent of HCC in CLIP or the use of performance status in BCLC. This have led to the development BALAD score by Toyoda et al, using serum Bilirubin and Albumin and three biomarkers: alpha-fetoprotein-L3 (L3), Alpha-fetoprotein (AFP) and Des-gamma-carboxy prothrombin (DCP). This system was developed in a Japanese population which has mainly HCV-related HCC. Our aim was to develop an objective staging system using the three biomarkers for a western population and compared it to BALAD to assess its performance. Methods: 317 subjects with HCC were recruited from Birmingham, UK between 2007 and 2011. Blood samples were collected at the time of diagnosis. Liver, renal functions plus AFP, L3 and DCP were measured. L3 and DCP were measured by microchip capillary electrophoresis and liquid-phase binding assay on a uTASWako i30 auto analyzer (Wako Pure Chemical Industries Ltd, Japan). Results: Univariable and multivariable regression analyses were performed. Our scoring system (CRCTU score) was developed based on a flexible baseline hazard functions fitted using restricted cubic splines. Suitable fractional polynomials (FP) were used to explain relationship between the outcome and covariates. The level of discrimination achieved using the risk groups was assess by Harrell’s–C statistic. The CRCTU score permitted identification of 4 clearly distinct subgroups as indicated both graphically and by Harrell’s-C values. Both the CRCTU and BALAD scores return Harrell’s-C values of 0.7. Conclusions: We have shown that it is possible to use entirely objective markers to predict prognosis of HCC in a western population. Our model is comparable to the BALAD with the same variables included. However, our treatment of variables with FP is much more robust statistical technique for continuous variable as compared to having artificial categories that were seen in the BALAD system.
A phase II study of cabazitaxel in patients with previously treated metastatic gastroesophageal adenocarcinoma.
Authors: Austin Trevor Clark , Perez Kimberly , Fontes-Borts Lucia , Luppe Denise , Jean Maureen , Olszewski Adam J. , Rosati Kayla , Rathore Bharti , Safran Howard
Published: March 2020

e15095

Background: Cabazitaxel is a semi-synthetic novel taxane with activity in docetaxel refractory prostate cancer. We sought to determine the response rate of cabazitaxel in patients with advanced gastroesophageal adenocarcinoma that had progressed after at least 1 prior therapy for metastatic disease. Methods: This open label single arm phase II study followed a Simon two-stage design. The study was designed to differentiate between a 10% level of activity and a 30% level of activity and was to be terminated if the response rate was unlikely to be > 10%. Eligibility criteria included patients with gastroesophageal cancer with measurable disease after at least 1 prior regimen for metastatic disease. ECOG PS 0-2; ANC > 1,500/µL, AST/ALT ≤ 3x ULN, total bili ≤ ULN. Pts initially received cabazitaxel 25 mg/m2 IV every 21 days but after 9 patients were entered, the dose was reduced to 20 mg/m2due to toxicity. Results: The data safety monitoring board (DSMB) reviewed data after 13 pts were entered. Pt characteristics included 11 men, 2 women; median age, 70 yrs [range, 55-80]. Nine pts had ≥ 2 prior regimens. Ten pts had previous treatment with a taxane. Of 13 pts, no objective antitumor responses were observed and all 13 developed evidence of disease progression. A median of 2 cycles were given, up to a maximum of 6 cycles in 2 pts. The PFS rate at 3 months was 15%. The DSMB considered cabazitaxel ineffective and terminated the study. The probability of erroneously concluding the treatment was active (p ≥ 0.3) was < 0.0419. Grade 3 or 4 adverse events occurred in 6 pts (46.1%), in which neutropenia (n=4) and pneumonia (n=1) were grade 4. Grade 3 toxicities included ANC (n=1), anemia (n=2), nausea (n=2), weakness (n=2), diarrhea (n=1), pleural effusion (n=1), typhilitis (n=1), vomiting (n=1). Conclusions: Cabazitaxel monotherapy demonstrated no antitumor efficacy in previously treated gastroesophageal cancer. Clinical trial information: NCT01365130.
Treatment of right-sided hepatocellular carcinoma with uni-lobar y-90 radioembolisation and induction of hypertrophy in the the contralateral left lobe.
Authors: Chow Pierce K. H. , Teo Jin Yao , Allen John Carson , Ng David Chee Eng , Lo Richard H. G. , Tay Kiang Hiong , Goh Anthony , Khor Andrew Yu Keat , Goh Brian , Cheah Foong Koon
Published: March 2020

e15102

Background: Yttrium-90 microsphere (Y90) is currently used to treat locally advanced hepatocellular carcinoma (HCC) including those where resection is precluded because of inadequate future remnant liver. Hypertrophy of the contralateral lobe after Y90 treatment has been reported. This study aims to quantify this hypertrophy and identify factors predictive of this response. Methods: Radiological review of patients undergoing Y-90 with treatment delivered via right hepatic artery for advanced HCC between January 2008 – January 2012 was performed. Diagnosis of HCC was by AASLD criteria and patients must have at least one follow-up scan in our institution. Excluded were: tumour in the contralateral lobe, concomitant other treatment for HCC, patients enrolled in clinical trials. Pre- and post-treatment images were reviewed and volumes were measured using 3D software. Statistical analysis was conducted using SPSS version 16.0. Results: During this period 50 patients treated with Y90 for HCC had follow-up imaging at our institution. Of 37 patients with right-sided Y90 treatment, 11 had concomitant left-sided disease treated with TACE and RFA, 7 had follow-up scans of inadequate quality to perform accurate volumetric assessment, 2 had pre-treatment scans performed at another institution which were not accessible for study purposes. Seventeen (17) patients thus fulfilled criteria. Mean and median left-lobe hypertrophy were 34.2% (SD±35.9%) and 31.7% (range -19.0 – 106.5%) respectively at a median of 5 months post-treatment. Univariate analysis identified no specific pre-treatment factor predictive of the degree of left lobe hypertrophy. There were no cases of acute liver failure after administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions: In patients with HCC receiving SIRT to the right lobe via the right hepatic artery, a significant degree of left lobe hypertrophy results. This opens the possibility of the utilisation of SIRT as neoadjuvant therapy for borderline resectable HCC, thus increasing the pool of potentially operable and curable patients.
A prospective cohort study to reduce operative risk in stage I gastric cancer patients with metabolic syndrome: Preoperative exercise versus surgery alone.
Authors: Cho Haruhiko , Tsuburaya Akira , Hirabayashi Naoki , Shirai Junya , Aoyama Toru , Hayashi Tsutomu , Yamada Takanobu , Yoshikawa Takaki , Morita Satoshi , Sakamoto Junichi
Published: March 2020

e15112

Background: Although obesity influences the technical difficulty of surgery, a reasonable marker of abdominal obesity is not confirmed and effective intervention has never been applied to reduce the operative risk in patients with abdominal obesity. Methods: To reduce the surgical difficulty and risk in gastric cancer patients with abdominal obesity, a preoperative exercise protocol was designed for stage I gastric cancer patients who were diagnosed to have metabolic syndrome (MetS). Results: In total, 51 patients (33 who underwent surgery alone, 18 who were treated with preoperative exercise) were registered in this study. Visceral fat areas (VFA) were estimated by CT scan, and they were associated most strongly with waist, followed by HDL cholesterol, and BMI. In the exercise group, all patients completed protocol treatment, without disease progression and > grade2 exercise-associated adverse events. VFA of the exercise group were larger than that of the surgery alone group at registration (221cm2 /180cm2, p=0.028), then reduced after exercise to non-significant level with surgery alone group (201cm2 /180cm2, p=0.264). There were no significant differences of intraoperative blood loss (262mL/201mL: p=0.465) and incidence of perioperative morbidity (27.7%/29%, p=1.000) between exercise and non-exercise groups. Multivariate logistic regression analysis detected intraoperative blood loss (> 380mL) as significant risk factor (p=0.023) for perioperative morbidity. Conclusions: Waist was surrogate marker for VFA in this study, thus can be a candidate of simple indicator of abdominal obesity. Preoperative interventional exercise did not directly reduce operative risk of gastric cancer with MetS; however, it was associated indirectly with risk reduction by improving surgical difficulty.
Benefits of percutaneous ethanol injection in the treatment of advanced hepatocellular carcinoma.
Authors: Misauno Micheal Ayedima , Isichei Mercy Wakili
Published: March 2020

e15119

Background: Hepatocellular carcinoma (HCC) is a devastating disease in which survival measured in months from time of diagnosis. Incidence is highest in Asia and Africa with high prevalences of hepatitis B and hepatitis C being strong predisposing factors. HCC is screened and diagnosed early in developed countries but this is not obtainable in our practice where patients present late, with severe abdominal pain and mass and therapeutic options are limited. Percutaneous ethanol injection (PEI) introduced twenty years ago for palliation of inoperable hepatocellular carcinoma is an option we are just exploring. This study was aimed at evaluating the benefits of percutaneous ethanol injection in the management of advanced hepatocellular carcinoma. Methods: With IRB clearance, informed consent was obtained from consecutive patients diagnosed with HCC. Patients with jaundice, signs of liver failure and coma were excluded from this study. They were randomized to Ethanol treatment in form of absolute alcohol manufactured by Riedel-de Haen, Germany “Group one” or routine pain control management (DF118) “Group two”. Baseline investigations and pain score using Visual Analogue Scale (VAS) was obtained for both groups. PEI was administered via ultrasound guided intra-tumour injection of 10- 50mls of ethanol at each sitting. Investigation and pain score were obtained weekly for four weeks then monthly at follow up. Data obtained from August 2010 to July 2012 was analyzed using Epi Info. Results: “Group one” 32 patients had (PEI), “Group two” 32 (DF118) out of an initial 82; 18 patients were excluded. Mean age was 40.4+/- 14.2 yrs, range of 18 to 60 yrs. Group one had 28 (87.5%) males and 4 (12.5%) females; Group two 29 (90.6%) males and 3 (9.4%) female. All patients had Right hypochondrial pain and mass. Pre intervention pain score ranged from 6-9 for both groups while post intervention pain score a week after was 1 -2 for group 1, and group 2 required regular analgesics to control their pain. Mean survival durations were 8 months and 2.5 months for groups 1 and 2, respectively. Conclusions: We conclude that percutaneous ethanol injection significantly reduces the pain of advanced hepatocellular carcinoma.
Clinicopathologic characterization and prognostic factor in extraintestinal neuroendocrine tumors.
Authors: Leon Rodriguez Eucario , Perez Alvarez Sandra Ileana , Macedo Omar , Escobar Elizabeth
Published: March 2020

e15131

Background: The frequency, prognostic factors and long-term survival of E-NET are poorly known. Methods: A retrospective analysis of clinical, histological characteristics and survival of patients with E-NET were done. Survival analyses were assessed by the Kaplan-Meier method and prognostic factors of overall survival were tested by uni/multivariate analysis. Results: Between 1997-2010, 241 patients were identified with NET. 31 Patients were E-NET (12.8%): median age was 55 years (16-79) and 55% were females. Primary location was lung, 58%, prostate 13%, breast 10%, urinary bladder 7%, and others 12%. At diagnosis 87% patients had symptoms and 52% were localized. A functioning tumor was in 7 patients (6 ACTH). Initial treatment was surgery 61%, chemotherapy 26% (23% had objective response) and palliative care 13%. After complete resection 4/14 patients recurred. With follow-up of 15months, the cancer-specific mortality was 55%. Overall 1- and 5-year survival were 72% and 35% respectively, which were lower than survival for GEP-NET (p=0.001, Figure 1). 5 year survival differed significantly according to age at diagnosis (47% ≤50 vs 27% >50 years); location (60% lung vs 10% non-lung); extension (58% localized vs 15% metastatic/locally advanced); stage at diagnosis (59% stage I-II vs 13% III-IV); histology (52% NET/carcinoid vs 14% NEC); degree of differentiation (44% well/moderately vs 0% poorly differentiated); initial treatment (55% surgery, 25% palliative care and 0% chemotherapy); and recurrence (100% absent vs 25% present). In univariate analysis, the negative prognostic factors were age >50 years, no lung site, symptomatic, metastatic/locally advanced disease, extrahepatic metastases, NEC, poor differentiation and recurrence. In multivariate analysis, only age >50 years was an independent predictor of survival (p=0.027). Conclusions: In our experience, E-NET represent 13% of all the NET. Present symptoms with a fewer frequency, are less functional, have more frequently metastases, and a worst prognosis (5-year survival 34 vs 72%). The most important prognostic factor for overall survival was age >50 years.
Gemcitabine combined with capecitabine compared to gemcitabine with or without erlotinib as first-line chemotherapy in patients with advanced pancreatic cancer: Comparative effectiveness study.
Authors: Cho Jangho , Lim Jae Yun , Cho Jae Yong
Published: March 2020

e15132

Background: Gemcitabine is the standard treatment for advanced pancreatic cancer. Though capecitabine and erlotinib are accepted as combination agent with gemcitabine, those two combination regimens have not been compared directly in clinical trial. This study compared the efficacy and tolerability between gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM) as first-line chemotherapy in patients with advanced pancreatic cancer. Methods: We collected data ofpatients if they met the following criteria: histologically or cytologically confirmed ductal adenocarcinoma of the pancreas; unresectable/metastatic disease; treated with one of GEM, GEM-X, and GEM-T as first-line treatment; measurable or evaluable lesion; age more than 18 years; Eastern Cooperative Oncology Group performance status 0, 1, or 2; and adequate hematologic, hepatic, and renal function before first-line chemotherapy. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Results: Between January 2007 and November 2011, a total of 127 patients received one of GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved the objective response rate (21.2% vs. 12.7% and 15.9%), progression-free survival (8.9 vs. 5.2 and 3.9 months; p < 0.001) and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. The incidence of adverse events was not significantly different among groups. Conclusions: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in locally advanced and metastatic pancreatic cancers. It is worthy to further investigate which agent has clinical advantage as combination drug with gemcitabine in pancreatic cancer and to explore predictive markers for each regimen leading to personalize anti-cancer treatment.
Locally advanced or metastatic pancreatic adenocarcinoma (PA): Prognostic factors for prolonged survival.
Authors: Ploquin Anne , Cozzolino Camille , Truant Stephanie , Piessen Guillaume , Desauw Christophe , Cattan Stéphane , Hebbar Mohamed
Published: March 2020

e15134

Background: Prognosis of pts with locally advanced or metastatic PA is poor, with median survival of 6-9 months. Yet, since the use of gemcitabine, some patients survive more than one year. Recently, FOLFIRINOX regimen yielded better results in selected patients, but with more toxicity. We assessed the value of baseline predictive factors of prolonged survival in non-selected pts treated with gemcitabine. Methods: We conducted a monocentric, retrospective study (1999 to 2010) on all pts treated for locally advanced or metastatic PA. Demographical, clinical, tumoral and biological variables were included into the analysis. The primary end-point was the 12 months survival. All parameters were assessed in univariate and multivariated analyses. We then built a prognostic scoring system integrating the independent prognostic factors. Results: The study was performed on 160 pts: median age 61.1 years, sex ratio (M/F) 93/67, ECOG 0-1/2-3: 60/98, jaundice 62 (38.8%), initially resectable : 36 (22.5%), intra-pancreatic primary location: head: 110 (68.8%), body: 19 (11.9%), tail: 27 (16.9%). The adenocarcinoma was histologically document in 124 cases (77.5%). The median number of metastasis sites was 1 (71.3% liver). The median Ca 19-9 concentration was 925 IU/ml. 155 pts (96.9%) received chemotherapy, of which 124 (80.0%) with gemcitabine in first line. Fifty-two patients (32.5%) were alive 12 months after diagnosis. In univariate analysis, male gender, PS, initial stage, differentiation, primary tumor location, Ca 19-9 were prognostic factors. In multivariate analysis, male gender, head or body locations and low Ca 19-9 concentration (< 111 IU/ml) were associated with a better prognosis. The score with a cut-off between 2 and 3 points was discriminant, with positive and negative predictive values of 64.7% IC-95% [59.2-70.2] and 75.3% IC-95% [74.4-76.2], respectively. The rate of correctly classified pts was 73.6% IC-95% [72.8-74.4]. Conclusions: Male gender, pancreatic head or body location, and Ca 19-9 < 111 are independent prognostic factors for prolonged survival. Further analyses are needed to determine more accurately pts suitable for gemcitabine or the more recently validated regimen FOLFIRINOX.
A three-gene expression signature model to predict neo-chemoradiotherapy response of esophageal squamous cell carcinomas.
Authors: Wen Jing , Yang Hong , Luo Kongjia , Hu Yi , Zhang Xu , Wang Geng , Chen Yuping , Chen Zhijian , Lin Ting , Wang Huiyun , Liu Mengzhong , Fu Jianhua
Published: March 2020

e15135

Background: Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could prediction CRT response. In this study, we aim to identify mRNA markers for ESCC CRT-response prediction. Methods: Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery. Surgical specimens were assessed for the pathological response to CRT. The identified differentially expressed genes were validated by real-time quantitative polymerase chain reaction (qPCR), based on which a classifying model was built up by Fisher’s linear discriminant analysis. The predictive power of this model was further assessed in another set of 32 ESCCs. Results: The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than 2-fold changes between pathological complete responsers (pCRs) and less than pCRs (<pCRs), among which 6 genes (LIMCH1, SDPR, Clorf226, SLC9A9, GSTM3, and IGSF10) were down-regulated and 4 genes (MMP9, MMP1, MMP12 and OASL) up-regulated in pCRs versus <pCRs. A prediction model based on qPCR values of 3 genes was built up, Y=-10.388 - 0.343 × MMP1 + 0.642 × LIMCH1 + 0.921 × Clorf226 with a cut-off value of 0.607. It provided a predictive accuracy of 85.7% with leave-one-out cross-validation. Further, the predictive power of this model was validated in another set of 32 ESCCs, among which a predictive accuracy of 81.3% was achieved. Conclusions: The combination of three genes by qPCR identified by microarrays in our study provides possibility for ESCC CRT prediction, which will facilitate individualization of ESCC treatment. Further perspective validation in larger independent cohorts is warranted to fully assess the predictive power of this prediction model.
Clinical predictors of response to sorafenib in patients with hepatocellular carcinoma.
Authors: Marinelli Sara , Granito Alessandro , Terzi Eleonora , Leoni Simona , Piscaglia Fabio , Venerandi Laura , Bolondi Luigi
Published: March 2020

e15149

Background: Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). Little is known about clinical-laboratoristic parameters predicting treatment benefit. Methods: Between 2008-2012, 94 consecutiveclinically compensatedcirrhoticpatients [M/F=85/9, median age 69-years (38-88)] with advanced HCC (BCLC-C, n=57) and those with an intermediate HCC (BCLC-B, n=37) who failed to respond or not eligible to locoregional therapies, received sorafenib. Clinical-laboratoristic data were reviewed. RECIST criteria were used to assess objective benefit. Toxicities were classified using NCIC Toxicity Criteria v-3.0 and treatment managed according to drug label. Results: The median treatment duration (TD) was 3.9 months (range 0.1-48). The median survival was 9.2 months (range 0.4-45). On the basis of TD we identified two groups of patients with a significant different overall survival (OS): group A (TD>6.6 months, median-TD 11.4, 33 patients) and group B (TD<6.6 months, median-TD 2.3, 61 patients). Median OS in group A and B was 20.6 and 6.6 months, respectively (p<0.001). CPT score, BCLC stage and neoplastic portal vein thrombosis were similar in the two groups. On univariate analysis, group A showed an higher rate of ECOG-PS 0 (75% vs 50%, p=0.034), lower basal serum levels of alfa fetoprotein (best cut-off: AFP<19 ng/dl, p=0.006). Fatigue and nausea were more frequent in group B (67.2% vs 43.8%, p=0.044; 19.3% vs 3.2%, p=0.05, respectively). ECOG-PS 0, AFP serum levels and nausea were significantly associated with a longer OS (p=0.003; p=0.006; p=0.008, respectively, log-rank test). On multivariate analysis, basal AFP levels (>19 ng/ml) remained predictor of shortened OS (p=0.028, OR=4). Conclusions: Development of nausea and fatigue on sorafenib is associated with poorer OS. AFP basal levels <19 ng/ml indipendently predict a better survival. Clinical-laboratoristic parameters may be useful to identify patients more likely to benefit from sorafenib.
Baseline and dynamic plasma chromogranin A (CgA) level to predict clinical outcome and tumor response in Asian patients with gastroenteropancreatic neuroendocrine tumor (GEP-NET).
Authors: Chou Wen-Chi
Published: March 2020

e15151

Background: The plasma CgA level is a reliable biomarker in diagnosing neuroendocrine tumors.The objective of this study is to correlate both the baseline value and the dynamic changes of plasma CgA level with disease status in Asian patients with advanced GEP-NET. Methods: Fifty-four patients with advanced GEP-NET were retrospectively evaluated between April 2010 and December 2012 in a single institution. Plasma CgA level and abdominal CT scan were obtained at diagnosis as a baseline and subsequently every 3 to 6 months after starting antitumor therapy.Statistical analysis of plasma CgA level was performed to predict the hazard ratio of clinical outcomes and also to correlate antitumor therapy responses with Response Evaluation Criteria in Solid Tumors Criteria 1.1. Results: Forty-six patients (85%) had elevated baseline CgA level. Twenty-one patients (39%) died at the end of the study with the medial follow-up duration of 292 days (range 12-992 days). Patients with baseline CgA level less than 2-fold of upper normal limit (UNL) had longer overall survival time than those with more than 2-fold of UNL (not reach vs. 272 days, hazard ratio = 0.39, 95% CI 0.15-0.99). Baseline CgA level less than 2-fold of UNL was still a favorable prognostic factor after adjusted for other variables (hazard ratio = 0.30, 95% CI 0.10-0.89). Twenty-eight patients with a total of 81 measurements of serial plasma CgA were available. An increase of plasma CgA level less than 15% predicted favorable antitumor response with a sensitivity of 86% and specificity of 91% (area under curve of receiving operating characteristics curves was 0.94). Conclusions: Baseline plasma CgA level and its dynamic change are useful values to predict clinical outcomes and antitumor responses in patients with GEP-NET.Baseline CgA level and serial measurements during antitumor therapy in patients with GEP-NET should be taken to assess their clinical outcomes.
Prognostic value of baseline 18F-FDG-PET (PET) in anal cancer (AC) patients (pts): A Bologna Multidisciplinary Rectal Cancer Group analysis (BMRCG-AC01).
Authors: Pini Sara , Di Fabio Francesca , Iacopino Bruno , Guido Alessandra , Castellucci Paolo , Cuicchi Dajana , Fanti Stefano , Lecce Ferdinando , Rojas Llimpe Fabiola Lorena , Giaquinta Stefania , Adua Daniela , Mazzarotto Renzo , Pinto Carmine
Published: March 2020

e15154

Background: The incidence of AC has increased. In locally advanced disease treatment is curative radio-chemotherapy (RCT) followed by brachytherapy boost (BRT) or external beam radiotherapy (EBR). The aim of this analysis is to evaluate prognostic factors in predicting disease recurrence. Methods: We retrospectively evaluated pts with diagnosis of T2-3-4, N-/+ AC. External RT was delivered up to a dose of 4,500 cGy in 25 fr and CT consisted in 5-fluorouracil CI day 1-4 and Mitomicin-C bolus day 1 in the first and fifth weeks of radiotherapy as per Nigroregimen. BRT or EBR were performed at the end of RCT. A PET scan was performed at diagnosis before starting treatment. The standard uptake value (SUV) was determined from the most active tumor site. Results: Between March 2006 and August 2012, 50 pts with AC accessed the BMRCG. In this analysis we considered 29 pts evaluated by PET. The pt characteristics were: 8(27.6%) men, 21(72.4%) women; median age 63 (42-89) years; 17(58.6%) squamous cell carcinoma (scc), 12(41.4%) basaloid carcinoma (bc); 6(20.7%) cT2N0, 5(17.2%) cT3N0, 7(24.1%) cT3N+, 2(6.9%) cT4N0, 9(31.1%) cT4N+. Twenty-six (90%) pts received full-dose standard protocol RCT and subsequent radiotherapy boost. After a median follow-up of 25 months we observed 4 (13.8%) recurrences: 3 local and 1 lung metastasis. No disease-related death occurred. Stage at diagnosis (T2-3N0 vs T3N+T4N+/-) and tumor histotype (scc vs bc) did not relate to DFS (p=0.67 and p=0.86 respectively). ROC analysis identified a SUV cut-off of 12.5 at the baseline PET related to recurrence. In 15(51.7%) pts the baseline SUV was ≤12.5 (low SUV) and in 14 (48.3%) it was >12.5 (high SUV). Pts with high SUV had significantly worse DFS than those with low SUV (p=0.02). Multivariate Cox regression did not confirm any SUV prognostic value (p=0.95). Conclusions: These results suggest that high SUV could predict relapse in AC pts treated with curative RCT. The small number of pts rules out any definitive conclusion; a controlled trial should be conducted to explore the prognostic role of SUV to define good prognosis pts for “tailored” treatment and reduce therapy-related toxicities.
Hepatocellular carcinoma diameter and blood platelet levels in a large cohort of Chinese patients in Taiwan.
Authors: Carr Brian I. , Lin Chih-Yun , Lu Sheng-Nan
Published: March 2020

e15157

Background: Cirrhosis is often associated with thrombocytopenia and predisposes to HCC. Platelets are known to produce several HCC growth factors. Methods: A cohort of 4,139 Chinese HCC patients from Taiwan was interrogated for baseline clinical, tumor and liver function characteristics in relation to blood platelet counts. Results: Trichotomization of the cohort by tumor size after log-linearization, revealed significant relationships of tumor size to blood platelet, AFP and GGTP levels. Patients with higher platelets had larger tumors, more tumor nodules and higher AFP and GGTP levels than those with lower platelet levels. 80% of patients with larger tumors had normal platelet counts, compared to 50% of patients with smaller tumors. Analysis of the cohort according to platelet sub-sets, revealed significant relationships of platelet counts to tumor size and AFP levels. By Spearman’s correlation coefficient, platelet counts correlated moderately with tumor size (rho=0.411), but weakly with tumor numbers, PVT, AST or AFP levels. Sub-set analysis of the cohort according to platelet levels showed that 38% of patients had thrombocytopenia and they had the smallest tumors, lowest tumor numbers, lowest percent with PVT and lowest AFP levels. Conclusions: There was a significant correlation between HCC size and blood platelet counts; patients with larger tumors had higher platelet levels.
Involved field irradiation compared with prophylactic nodal irradiation to unresectable esophageal carcinoma: A retrospective study.
Authors: Zhang Xiaoli , LI Minghuan , Kong Li , Yu Jinming
Published: March 2020

e15180

Background: We retrospectively observed the failure patterns in patients of local advanced esophageal squamous cell carcinoma (ESCC) with involved field irradiation (IFI) or with intentional prophylactic nodal irradiation (PNI). Methods: The ESCC patients with unresectable lesion (length >6 cm or T4 or obvious node metastasis) were retrospectively analyzed between 2003 and 2009. All the reviewed patients received 3D-CRT with cisplatin based chemotherapy. For the IFI cases, the GTV was defined as any visible esophageal lesion(GTVe) and clinical involved node(GTVn). The CTVe was defined as the GTVe plus a 3-4cm margin superior and inferior to the primary tumor and a 1.0 cm radial margin. CTVn was defined as the GTVn plus a 0.5cm radial margin. The PTV was defined as CTV plus a 1.0cm margin. For the PNI cases, the same margins outside the primary tumor as that in IFI, and the adjacent regional lymphatics was included in the CTV according to the different location of primary tumor. The prescribed dose to PTV in IFI group was 60-64 Gy in 6-7 weeks and to PNI group was 40-50GY in 4-5weeks followed by 10-20Gy to PTVe+n. Results: Thirty-six cases received IFI and 49 cases underwent PNI. There were no difference between IFI and PNI group in tumor length and nodal status. The clinical response rates were 94.4% and 97.9% in IFI and PNI group, respectively, and no statistical difference was found ( P=0.785).The patterns of first failure in IFI and PNI group were listed as follows:(1) involved field failure, 17/36 vs 34/49 , P=0.046; (2) prophylactic nodal failure, 10/36 vs 4/49 P=0.02; (3) out field of regional nodal failure, 8/36 vs 15/49 , P=0.464; (4) distant metastasis, 17/36 vs 26/49, P=0.663. The medium PFS were 8.5m vs 12.0m( P=0.602), and the median OS were 14.0m vs 16.0m ( P=0.924)in IFI and in PNI group, respectively, and no statistical difference was found. Conclusions: Chemo-radiotherapy with PNI for unresectable ESCC showed better prophylactic field control, but had no advantage over the IFI in LC, PFS and OS.The involved field failure and distant metastasis were the main causes of failure in both groups, which suggests that the prophylactic irradiation may be not necessary for this sub-group patients.
Anal cancer in Oncólogos del Occidente from Colombia, South America 1997-2012.
Authors: Villegas Mejia Carlos Raul , Chacon Cardona Jose Arnoby , Sanchez Villegas Tomas
Published: March 2020

e15189

Background: This work describes epidemiologic characteristics in anal cancer, in the United States is 1% to 2% of bowel cancers and 3.9% of anorectal carcinomas. Statistics for anal cancer are unknown in our specific Colombia region. Methods: We performed a descriptive preliminary retrospective analysis of 50% of our total patients from Oncologos del Occidente like a private treatment cancer center from January of 1997 to June 2012. Results: 10,000 records were reviewed with 663 colorectoanal cancer and 47 were anal cancer; median age 60.064 (range 32-88. SD. 12.595), 64% female and 96% urban areas; Clinical stage II 32%, stage IIIA 14%, stage IIIB 30%, and 23% were unknown stage; Squamous cell carcinoma including basaloid 79%, adenocarcinoma 17%; Well differentiated 32%, moderately 19% and poorly 19%; 6% had Radical perineal surgery, 81% received chemoradiation (QT/RT), 13% without treatment and 2% were treated with sequential QT+RT; 19% relapsed and 70% of them were local with 87% without any treatment. Gap of RT was 1 to 14 days (11%), 15 to 30 days (23%), 31 to 106 days (15%). No gap (0 days) 51%, Gap mean 13.085 (Range 0-106 SD. 19.534); The initial QT Regimen was 5FU/mitomycin 60%, 5 FU/cisplatinum 4%, capecitabine / mitomycin C in 11%; General survival to 5 years 60% Stage II and 38% Stage III, median survival for Stage III 35%; Mean follow up 43.10 months (range 0 - 178. SD. 45.5), Gap Survival to 5 years was 36% without rest with a median of 20 months, Gap of 1 to 14 days with a median of 35 months and 40% of survival to 5 years; and 55% from 15-30 days of survival to 5 years (p> 0.05). Conclusions: These results reflect the occurrence pattern of anal cancer in a specific area of Colombia, and the importance of a multidisciplinary treatment group.
ECX as neoadjvuant chemotherapy for gastric cancer in South America.
Authors: Colli Leandro Machado , Godoy Antonio Carlos , Filardi Bruno , Figueiredo Jose Marcio Barros , Santos José Sebastião , Zola Fabio Eduardo , Rapatoni Liane , Peria Fernanda Maris
Published: March 2020

e15190

Background: Gastric cancer is a common malignant disease with a high mortality rate. Neoadjuvant treatment is efficient, but not the first option for treatment in all countries. Studies of neadjuvant chemotherapy in gastric cancer in South American countries are lacking. The aim of this retrospective analysis was to investigate the use of the ECX (epirubicin, cisplatin, and capecitabine) regimen in the neoadjuvant therapy in a Brazilian population. Methods: 25 patients (median age, 61; range 36-78 years; 14 pts >60 years) with locally advanced gastric adenocarcinoma received three courses of preoperative chemotherapy with epirubicin 50 mg/m², day 1, cisplatin 60 mg/m², day 1, and capecitabine 625 mg/m² bid, days 2-21, of a 21-day cycle. Toxicity was assessed by the Common Toxicity Criteria (CTC) after every cycle. Progression-free survival (PFS) was defined as time from diagnosis to disease progression assessed by CT. Results: 21 pts completed all three planned cycles of neoadjuvant chemotherapy. Four patients receiced surgery earlier than planned due to bleeding (1), toxicity (1), abdominal infection (1), and non-adherence to treatment (1). Three patients could not be operated due to disease progression. 70% of operated patients had curative resection with two pathologic complete response. Only six out 25 patients had disease progression and only two died after a median follow-up of 11.5 months (range 3.4-20.2). Median PFS and overall survival were not reached. Toxicities grade 3-4 were neutropenia (28%), febrile neutropenia (8%), bleeding (8%), and heart failure (6,2%). Conclusions: ECX is a efficacious neoadjuvant treatment in the Brazilian population and also well tolerated and safe. However, more studies with a larger South American population are needed.
Cisplatin and capecitabine with and without docetaxel as a first-line chemotherapy in patients with metastatic gastric carcinoma: Single clinical experience.
Authors: Narimanov Mekhty , Tryakin Alexey , Zarkua Varlam , Bazin Igor , Garin August , Tjulandin Sergei
Published: March 2020

e15194

Background: Cisplatin and capecitabine and docetaxel are active agents for treatment of metastatic gastric carcinoma. We underwent analysis of efficacy and toxicity of douplet (CX ) and triplet (DCX) regimens which were used in our department as a first-line chemotherapy in patients with metastatic gastric carcinoma. Methods: Pts with metastatic gastric carcinoma were nonrandomly allocated to DCX regimen (docetaxel 75 mg/m2 i.v. day 1, cisplatin 75 mg/m2 i.v. day 1, capecitabine 1650 mg/m2 per os days 1-14) or CX regimen (cisplatin 75 mg/m2 i.v. day 1, capecitabine 2000 mg/m2 per os days 1-14 ). Up to 6 cycles were provided every 3 weeks. G-CSF was not routinely used for primary prophylaxis. Results: From 2008 to 2012 81 pts were included in the study (DCX – 37 pts, CX – 44 pts). Pts characteristics were similar in both groups (table 1). Median number of cycles in both groups was 5 (range, 1-6). Grade 3-4 toxicity (per cycle) in DCX and CX groups were neutropenia 24,9% and 16,1%, deep venous thrombosis – 2% and 0%, diarrhea – 6.2% and 7,4%, stomatitis – 3.8% and 2,2%, infection – 11% and 0%, anemia 14% and 13,5% pts, respectively. No toxic deaths were observed. Median progression-free survival (PFS) in DCX and CX were 7,5 months (95% CI 6,1-8,9) and 5,4 months (95% CI 5,0-6,2; p=0.0009), median overall survival (OS) 14,5 months (95% CI 10,1-18,9) and 9,3 months (95% CI 9,2-10,2; p=0.0018), respectively. Conclusions: Addition of docetaxel to the combination of cisplatin and capecitabine associates with significant improvement of PFS and OS. Higher rate of infection requires use of G-CSF in primary prophylaxis. [Table: see text]
Treatment efficacy in patients with advanced biliary tract cancer receiving gemcitabine and cisplatin and 21-h infusional 5-FU: An analysis of 17 cases.
Authors: Aznab Mozaffar , Eslam pia Kiumars , Setayeshi Khosro , Rezaei Mansour , Kavianymoghadam Kaveh
Published: March 2020

e15195

Background:Biliary tract a group of tumors which only a minority of patients is eligible for curative surgery. The purpose of this study was to identify efficacy treatment of gemcitabine, cisplatin, and 21h infusional 5-FU in patients with advanced BTC receiving this therapy, and the median time to progression and OS time. Methods: The data of 17 patients with advanced biliary tract cancer who referred to clinic oncology of Kermanshah University of Medical Sciences, which received treatment from January 2009 to December 2012 were collected. Patients with gallbladder cancer with local invasion into near structures or metastatic to lymph node and or liver and or peritoneal seeding and also patients with cholangiocarcinom were randomized to recieveing chemotherapy consisting of cycles of continuous infusion of 5-FU for 21-hours (600 mg/m2) days 1, 2, 3, and 4. Gemcitabine was given at dose of 1,250 mg/m2 days 1 and 8 and cisplatin was given at dose of 60 mg/m2 day 1 with G-csf every support. Each cycle repeated every 21 days for 6-7 cycles. Results: A total of 17 patients with age range 41-61 years studied.58.8% female and 41.2% were male. The 11 patients were gallbladder cancer with only local invasion into surrounding structures in 7 pts and 2 pts with only lymph node and peritoneal involving and 2 pts with lymph node and peritoneal involving and liver metastasis, and 6 patients were cholangiocarcinoma with lymph node and peritoneal involving in 3 pts and one pts with lymph node involving and one pts with liver metastasis. Four out of the 11 patients with gallbladder cancer with local invasion survived above 29 months one pts above 20 months. Means and medians for TTP of 6 pts which disease progressed was 11.2 and 9.6 months, respectively. Means for OS Time of 17 pts was 32 months. The overall 75.5% of pts are alive. This regimen was well tolerated, with neutropenia and thrombocytopenia as the most significant toxicities. Conclusions: The triple therapy with Gemcitabine cisplatin, 5-FU showed efficacy with manageable toxicity in patients with advanced BTC and demonstrated that the addition infusional 5-FU to cisplatin and gemcitabine afforded significant PFS and OS benefits.