bluuebunny/crossref_metadata_2025 huggingface dataset:
Various clinical outcomes in patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma undergoing trimodality therapy: Prognostic implications.
Authors: Suzuki Akihiro , Xiao Lianchun , Taketa Takashi , Sudo Kazuki , Blum Mariela A. , Komaki Ritsuko , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Hofstetter Wayne Lewis , Swisher Stephen , Ajani Jaffer A.
Published: March 2020

e15053

Background: Preoperative chemoradiation (trimodality therapy) has the strongest evidence in trimodality-eligible patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma. Pathological complete response (pathCR) and clinical complete response (clinCR) are independent prognostic factors. We hypothesized that pathCR is associated with best prognosis. Methods: Patients with E-GEJ adenocarcinoma undergoing trimodality therapy were identified from the prospectively maintained database at our institution. The Log rank test, univariate and multivariate Cox proportional hazards regression analysis were applied for the survival analysis. Variables with p value < 0.15 in the univariate analysis were included in the multivariate analysis, the backward selection procedure was used for the model selection. Variables with P value < 0.05 were considered statistically significant. Results: For 314 esophageal cancer patients, the median follow-up time was 44.0 months (95% CI; 34.2-50.9). 107 of 314 patients died at this analysis. 80 patients (25.5%) had a pathCR. 160 patients (51.0%) had a clinCR prior to surgery but did not have pathCR. The remaining 74 (23.6%) had <pathCR and <clinCR. Median OS were: not achieved in pathCR patients, 82.8 months (95% CI; 63.9, NA) in clinCR patients and 27. 6 months (95% CI; 19.4, NA) <pathCR/<clinCR (p<0.001). The median recurrence-free survival (RFS) were: 79.6 months (95% CI; 37.4, NA) in pathCR patients, 67.4 months (95% CI; 31.8, NA) in clinCR patients and 13.5 months (95% CI; 10.4, 21.4) in <pathCR/<clinCR (p<0.001). In multivariate analysis, no lymph node metastasis (p<0.001), not poorly differentiated adenocarcinoma (p=0.002) and pathCR (p=0.02), and cCR (p<0.001) were independent prognosticators of OS and RFS. Conclusions: pathCR and clinCR are associated with a better survival ourtcome compared to patients without pathCR/clinCRand may be helpful in devising new therapeutic and surveillance strategies.
Use of cardiopulmonary exercise testing (CPET) to identify patients at high risk for adverse outcome after pancreaticoduodenectomy.
Authors: Siriwardena Ajith K. , Junejo Muneer
Published: March 2020

e15072

Background: Pancreaticoduodenectomy is the standard of care for tumours confined to the head of pancreas and can be undertaken with low operative mortality. However, the procedure has a high morbidity, particularly in older patient populations with pre-existing co-morbidities. Many of the currently available methods for assessment of pre-operative risk rely on either scoring systems or indirect measures of cardiopulmonary function. In contrast, pre-operative cardiopulmonary exercise testing (CPET) provides a direct functional assessment of integrated cardiac and respiratory performance. This study evaluates the role of pre-operative cardiopulmonary exercise testing (CPET) for prediction of post-operative morbidity and outcome after pancreaticoduodenectomy. Methods: In a prospective cohort undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with co-morbidity) were categorized as high-risk and underwent preoperative assessment by CPET according to pre-defined protocol. Data were collected on functional status, postoperative complications and survival. The predictive potential of CPET-derived markers was assessed. Results: 143 patients underwent preoperative assessment of whom 50 were deemed low-risk for surgery per protocol. Of 93 high-risk patients 64 proceeded to surgery after preoperative CPET. CPET-derived ventilatory equivalent of carbon dioxide (VE/VCO2) at anaerobic threshold (AT) was a predictive marker of postoperative mortality with an AUC of 0.85 (95% CI 0.63 to 1.07, p = 0.020); a threshold of 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). Above this threshold, raised VE/VCO2 was a predictor of poor long-term survival (HR 1.90, 95%CI: 1.02 to 3.57, p = 0.045). Conclusions: CPET is a useful adjunctive test for predicting post-operative outcome in patients being assessed for pancreaticoduodenectomy. CPET-derived VE/VCO2 above a threshold of 41 predicts early post-operative death and poor long-term survival. CPET should be considered in the pre-operative work-up prior to pancreaticoduodenectomy.
Evaluation of a nonbiologic nanoparticle form of paclitaxel in metastatic pancreatic cancer.
Authors: Motamed Kouros , Hwang Larn , Hsiao Chao , Trieu Vuong N.
Published: March 2020

e15076

Background: The (nab-Pac)/Gemcitabine (Gem) combination has recently been shown to impart a significant survival advantage over Gem alone in patients with metastatic pancreatic cancer. The goal of this study was to define a non-biologic, nanoparticle paclitaxel (NBN-Pac) which has a similar toxicity profile and utilizes the same albumin-mediated transport mechanism. Herein, we report in vitro, preclinical and phase I clinical results for this NBN-Pac in metastatic pancreatic cancer. Methods: In vitro drug cytotoxicity was measured as mean IC50 values following a 72-h exposure in four pancreatic cell lines (MIA Paca-2 and Capan-1 and multi-drug resistant cell lines PANC-1 and ASPC-1). In vivo anti-tumor activities were assessed in xenografted MIA PaCa-2 and PANC-1 models in nude mice treated with three i.v. doses of NBN-Pac (20, 50 mg/kg) and Taxol (20 mg/kg) on days 0, 3, and 6 (q3dx3), and twelve i.v. doses of Gem (140 mg/kg) on every 3 days (q3dx12). A phase I clinical trial (N=18) was conducted to determine the MTD and the recommended phase II dose of the combination therapy with NBN-Pac (220-300 mg/m2, q3w) and Gem (1250 mg/m2) as primary endpoints in first line treatment of subjects with advanced pancreatic cancer. Reduction in the plasma levels of CA19-9 was measured as a PD biomarker. Results: The mean IC50 value of NBN-Pac in four pancreatic cell lines was approximately 30-fold lower than that of Gem. NBN-Pac formulation (50 mg/kg) produced superior anti-tumor activity in the two xenograft models tested over Taxol and Gem at clinically equivalent doses. Our phase I trial established the MTD of this NBN-Pac formulation as 300mg/m2. Moreover, 5 out of 16 subjects (31.3%) were CR or PR with 95% exact confidence interval of (11.0%, 58.7%). The median PFS time was 5.6 month (95% C.I = 2.9). The median OS time could not be estimated as the survival rate did not fall below 50%. Other safety variables revealed no significant abnormality that may have affected the result of the study. Conclusions: NBN-Paclitaxel formulation has superior anti-tumor activity vs. Taxol and Gem in in vitro toxicity assays, preclinical models of pancreatic cancer, as well in a phase I clinical study in patients with advanced pancreatic cancer.
Chemoembolization with super absorbent polymer microspheres (SAP-MS) loaded with doxorubicin (D) using escalating doses and adverse events (AE) in resectable hepatocellular carcinoma.
Authors: Peixoto Renata D'Alpino , Lim Howard John , Ibrahim Fady , Wasan Ellen , Ford Jo-Ann , Liu David M.
Published: March 2020

e15084

Background: SAP-MS have demonstrated utility in the treatment of hepatocellular carcinoma (HCC) as a bland embolic and have demonstrated the ability to load and release D in vivo. Little is known about its toxicity profile. We aimed to determine if the dose and maximum plasma concentration (Cmax) of D were correlated with occurrence of AE. Methods: A phase II dose-escalation study was performed to systematically evaluate AEs relating to outpatient-based D/ SAP-MS embolization in HCC using a D dose of 0-75 mg. D plasma levels were assessed at multiple time points (0.5, 2, 24 and 675h), in addition to standard analyses of liver and hematologic function. All AEs were reported following the Common Toxicity Criteria Version 3.0. A Pearson product-moment correlation was run to determine the relationship between Cmax and AE. Results: Of 25 patients enrolled, 24 were evaluable (6 = 0mg, 6 = 25mg, 6 = 50mg, 6 = 75mg). The side-effect profile was similar to other abdominal embolization procedures, with abdominal pain (62.5%), fatigue-like symptoms (41.7%), and nausea (41.7%) being the most common AE. There were no correlation between the administered doses of D and all grade AE (r = .209, p .328) or between Cmax's of D and all grade AE (r = .321, p .127). All patients were discharged on the same day. There were no grade 4 or 5 AE and no hepatic decompensation. One patient required hospitalization 7 days post-procedure for groin puncture related complication. Conclusions: In our phase II dose-escalation study, patients experienced minimal post-embolization syndrome, which was not correlated with the amount of doxorubicin administered. The toxicities relating to SAP-MS delivery likely result from the embolic effect as opposed to dose response relating to the use of doxorubicin and can be managed on an outpatient basis. Clinical trial information: NCT01116635.
Factors affecting the administration of adjuvant therapy in patients with pancreatic adenocarcinoma.
Authors: Serrano Aybar Pablo Emilio , Kim Peter Tae Wan , Leung Kenneth , Cleary Sean P. , Gallinger Steven , Greig Paul David , Moulton Carol-anne , Wei Alice Chia-chi
Published: March 2020

e15087

Background: Adjuvant therapy for pancreatic adenocarcinoma is now considered standard of care. The proportion of patients receiving adjuvant therapy (ADT) following pancreatic resection is a good quality indicator of cancer care. The aim of this study was to evaluate factors associated with receiving ADT in patients with pancreatic cancer. Methods: Between years 2000-2010, all patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma at a single high-volume hepatotopancreatobiliary center were evaluated. The impact of demographic, peri-operative and pathological risk factors affecting the administration of ADT were analyzed using univariate and multivariate logistic regression analysis. Results: There were 258 patients identified. Median age was 65 (37-84) years, 54% were females. There was a 15% margin positivity rate, 14% pancreatic leak rate, 14.7% major complication rate, and 1.2% 90 day/in-hospital mortality rate. Overall, 160/258 (70%) of patients received adjuvant therapy. On multivariate analysis; age, presence of major complications, node-negative disease and earlier era (2000-2004) were significantly associated with a lower probability of receiving ADT. Reasons for not receiving ADT were; patient preference: 20/67 (32%), not recommended: 14/67 (23%), disease recurrence: 12/67 (9.5%) and being medically unfit for ADT: 18/67 (11.5%). None of these reasons were different between time-periods except for fewer patients being offered ADT from 2000-2005 (15.4% vs. 2.5%, p <0.001). Conclusions: Thirty percent of patients do not receive ADT following pancreatectomy. Those with advanced age; node-negative disease and those who had major complications after pancreaticoduodenectomy were less likely to receive ADT. The impact of these factors should be taken into account when considering the administration of ADT.
Clinicopathologic features predicting HER2 overexpression in gastric cancer.
Authors: Park Ji Soo , Jung Minkyu , Kim Hye Ryun , Rha Sun Young , Chung Hyun Cheol , Kim Hyo Song
Published: March 2020

e15098

Background: HER2-based therapy was found to improve survival outcome of patients with HER2-positive advanced gastric cancer. In gastric cancer, HER2 overexpression is commonly defined as IHC 3+ or IHC 2+/FISH amplification. Because positivity of HER2 overexpression is reported in below 20%, identifying the predictive clinical factors for the HER2 overexpression before the pathologic analysis may be helpful and cost-effective. Methods: From JAN 2005 to DEC 2010, 517 gastric cancer patients performed with HER2 IHC and/or FISH tests at Yonsei University College of Medicine were enrolled. Results: Among the 517 patients, 61 patients (11.8%) were confirmed as HER2 overexpression. Forty three out of stage IV, 258 patients (16.7%) and 18 out of 259 (6.9%) localized gastric cancer patients had HER2 overexpression (p <0.001). HER2 overexpression was more common in male (14.2% vs. 7.5% in female, p-value 0.024), moderately differentiated (26.4% vs. 11.1%, 8.9%, 4.9% and 5.9% in well differentiated, poorly differentiated, signet ring cell, and mucinous, retrospectively, p <0.001). Patients with elevated CEA (> 5.0 ng/mL vs. ≤ 5.0 ng/mL: 24.3% vs. 8.4%, p <0.001), metastasis to distant lymph node (with vs. without: 28.6% vs. 14.8%, p-value 0.042), without carcinomatosis (without vs. with: 21.2% vs. 11.6%, p-value 0.039) and pulmonary metastasis (with vs. without: 47.4% vs. 14.2%, p <0.001) also frequently had HER2-positive disease. In addition, high risk patients with 4 or more of the 7 features (metastatic disease, male, moderate differentiated adenocarcinoma, elevated CEA level, metastasis to distant lymph node, pulmonary metastasis, and without carcinomatosis) had 32.9% of HER2 positivity. (p <0.001). Conclusions: Those clinicopathologic factors may be helpful to predict the high likelihood of HER2 positive cases prior to pathologic confirmation in gastric cancer. Further molecular study for the HER2 overexpression is needed to clarify and explain this clinical phenomenon.
The inflammation based index (IBI) predicts survival advantage after transarterial chemoembolization in hepatocellular carcinoma.
Authors: Adjogatse Delali Akosua , Karamanakos George , Pinato David James , Sharma Rohini
Published: March 2020

e15101

Background: Transarterial chemoembolization (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting for therapeutic outcome. The inflammation based index (IBI) has previously been shown to independently predict overall survival in all stages of HCC. This retrospective study explored the prognostic ability of the IBI as a predictor of survival after TACE. Methods: Sixty three eligible patients who had undergone TACE for intermediate stage HCC were selected. The IBI was calculated using serum albumin and CRP levels as previously described; giving a score of 0-2, equating to low, intermediate and high risk respectively. Survival was calculated from the date of TACE to date of death. Dynamic changes in the IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model. Results: Patients with a normal IBI prior to TACE had a significant improvement in survival in comparison to those with an intermediate or high-risk score (p=0.02). Other predictors of survival on univariate analysis were radiological response to TACE (p<0.001), pre-TACE CLIP score (p<0.01), initial tumour diameter >5 cm (p=0.049) and AFP > 400 (p<0.001). On multivariate analysis; normalisation of IBI post TACE was associated with improved overall survival, compared to patients showing a persistently abnormal index (p<0.001; HR 5.5, 95% CI 1.9 – 16.5). Conclusions: Normalisation of IBI after TACE is shown to be an independent predictor of survival. Patients with a persistently raised IBI following TACE have a worse survival outcome. As a simple and accessible stratifying biomarker, IBI aides the identification of patients with a significant survival advantage following TACE.
Survival analysis of linitis plastica advanced gastric cancer patients receiving S-1 plus cisplatin.
Authors: Kumekawa Yosuke , Chin Keisho , Osumi Hiroki , Ogura Mariko , Ozaka Masato , Suenaga Mitsukuni , Shinozaki Eiji , Matsusaka Satoshi , Sano Takeshi , Mizunuma Nobuyuki
Published: March 2020

e15105

Background: Linitis plastica gastric cancer (LPGC) has been known to have worse prognosis than non-LPGC. Clinical trial using molecular targeting agent has been ongoing for LPGC. However it remains unknown whether to be better to change the chemotherapy for the patients. S-1 plus cisplatin (SP) is the standard chemotherapy for previously untreated Japanese advanced gastric cancer (AGC). Methods: To clarify the clinical feature and outcome of LPGC treated with chemotherapy, we retrospectively compared the patients with unresectable or metastatic LPGC and non-LPGC who received SP as the first-line chemotherapy in Cancer Institute Hospital of JFCR between 2007 and 2011. Results: In the period there were 687 patients with AGC who received systemic chemotherapy and 223 (LPGC 63 and non- LPGC 160) patients received SP as first-line chemotherapy. LPGC patients were more frequent in female (44.0% vs. 26.9%; P=0.016). LPGC was more likely to have non-measurable disease (39.7% vs. 14.4%; P<0.001), peritoneal metastasis (73% vs. 35.6% P<0.001), and diffuse type histology (diffuse type 85.7% vs. 56.3%, intestinal type 7.9% vs. 27.5%; P<0.001). LPGC was less likely to have liver metastasis (7.9% vs. 27.5%; P<0.001), and no evaluable distant metastasis in computed tomography (81.0% vs. 93.8%; P=0.010). Other clinicopathological characteristics were follows (LPGC patients vs. non-LPGC patients): median age (57 vs. 62 years), disease status (recurrent 11.1% vs. 18.8%), ECOG PS 0 (81.0% vs. 81.9%), number of metastatic sites (1: 52.4% vs. 46.9, 2: 39.7% vs. 46.9%, ³a3: 7.9% vs. 6.2%), lymph node metastasis (63.5% vs. 70.6%), prior gastrectomy (31.7% vs. 35.6%). They were not significantly different. Median overall survival time is 383 days (95% CI 332-564) in LPGC patients and 473 days (95% CI 412-555) in non-LPGC patients (P=0.363). Median time to treatment failure is 229 days (95% CI 155 - 280) in LPGC patients and 189 days (95% CI 156 -219) in non-LPGC patients (P=0.245). Conclusions: Although clinicopathological backgrounds were not identical, it was suggested that the prognosis of the patients treated with SP was not different between advanced or metastatic LPGC and non-LPGC.
Prevalence of gene amplifications of SOX-2, c-MET, and FGFR1 in Asian patients with esophageal squamous cell carcinoma.
Authors: Huang Ta-Chen , Chen Wei-Wu , Hsu Ta-Wen , Lin Chia-Chi J. , Yeh Kun-Huei , Cheng Ann-Lii , Hsu Chih-Hung
Published: March 2020

e15127

Background: Amplifications of SOX-2, c-MET, and FGFR1 have recently been recognized as important molecular derangements with therapeutic implication in squamous cell carcinoma of lung. We investigated the significance of these molecular derangements in esophageal squamous cell carcinoma (ESCC). Methods: Locally advanced ESCC patients who had received curative- intent loco-regional therapy and had available pre-treatment endoscopic biopsy tissues at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. DNA was extracted from formalin-fixed paraffin-embedded tissues. Amplifications of SOX-2, c-MET, and FGFR1 were evaluated by quantitative PCR (TaqMan Copy Number Assay, Applied Biosystems, CA, USA), using TERT as a reference gene. Amplification of specific gene was defined as a copy number more than 4. Results: Forty locally advanced ESCC patients, M: F= 39: 1 with a median age of 56 years (range: 37 to 80), were included. The primary tumors located at cervical, upper thoracic, middle thoracic, and lower thoracic esophagus in 2, 9, 23, and 6 patients, respectively; the tumor staging according to AJCC 2002 version was T3N0, AnyTN1, and M1a in 1, 37, and 2 patients, respectively. Amplifications of SOX-2 and c-MET were identified in 14 (35%) and 7 (17.5%) patients, respectively. No FGFR1 amplification was detected. The amplifications of SOX-2 and c-MET were not associated with any known clinical features of the patients, including gender, age (<60 vs ≧60), primary tumor location, clinical stage, and performance status (ECOG 0, 1). Conclusions: Amplifications of SOX-2 and c-MET, existing in significant portions of Asian patients with ESCC, are worthy of exploration as therapeutic targets of ESCC.
Long-term survival after multidisciplinary treatment of small-bowel neuroendocrine tumors with synchronous liver metastases: A single-institute experience.
Authors: Bertani Emilio , Fazio Nicola , Chiappa Antonio , Botteri Edoardo , Spada Francesca , Grana Chiara , Ravizza Davide , Cossu Laura , Bonomo Guido , Andreoni Bruno
Published: March 2020

e15147

Background: Neuroendocrine tumors (NETs) that originate in the distal jejunum and ileum are commonly diagnosed in stage IV, with liver metastases in 50%-75% of cases. The aim of this study was to ascertain the impact of surgery in a consecutive series of patients with small bowel NET and synchronous liver metastases treated at a single institute. Methods: Ninety-one patients managed between 1995 and 2011 were extracted from the institutional tumor registry. All patients had diagnosis by histology of small bowel NET and synchronous liver metastases. Results: Among the 91 patients 28 (30.8%) underwent primary tumor removal and liver metastases resection or intraoperative termal ablation (Group 1), 54 (59.3%) underwent resection of only the primary tumor (Group 2), and the remaining 9 (9.9%) did not receive any surgery (Group 3). After a median follow-up of 64 months an overall survival (OS) of 93.1%, 81.8% and 76.2% at 3, 5 and 8 years was registered for the whole group. Cancer-specific survival (CSS) was 93.1%, 83.3% and 77.6% at 3, 5 and 8 years, respectively. Five-years OS differed significantly according to the surgical approach (96.0% for Group 1 vs 79.8% for Group 2 vs 48.6% for Group 3, p=0.02). During the course of the illness octreotide was administered in 78 patients (85.7%), peptide receptor radiotherapy in 61 (67.0%), systemic chemotherapy in 21 (23.1%), hepatic artery embolization in 17 (18.7%), interferon in 11 (12.1%), molecular targeted agents in 2 (2.2%). For patients who underwent any surgery (Group 1 and Group 2) the multidisciplinary approach was associated with a better OS (85.7% vs 77.2% 5-years OS, p=0.04). In the multivariate analysis only age was associated with OS, HR: 1.05 (C. I.: 1.01-1.10). The results of CSS were comparable to those of OS. Conclusions: In this metastatic setting of small bowel NETs the 5 year OS was as high as 82% with a maximum benefit achievable for patients who had primary tumor resection and liver disease amenable to surgical or thermal ablation. However, the potential impact of age in prognosis should be carefully considered when choosing the treatment to be delivered in such patients.
Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.
Authors: Takada Ryoji , Ioka Tatsuya , Ishida Nobuko , Yamai Takuo , Fukutake Nobuyasu , Ashida Reiko , Uehara Hiroyuki , Katayama Kazuhiro
Published: March 2020

e15150

Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.
The influence of human papilloma virus (HPV) infection on the outcome of subjects with anal squamous cell carcinoma.
Authors: Batra Anu , Hennings Leah J , James Jennifer D , Siegel Eric R , Govindarajan Rangaswamy
Published: March 2020

e15152

Background: HPV infection is a risk factor for the development of anal cancer. P16 expression correlates highly with HPV infection. The influence of HPV infection on the outcome of these subjects has not been well defined. To evaluate the influence of HPV infection on prognosis of subjects with anal squamous cell cancer, a retrospective analysis was conducted. Methods: Subjects with anal squamous cell cancer diagnosed at the University of Arkansas for Medical Sciences between 1992 and 2010, were identified from the tumor registry. The charts were reviewed to confirm the diagnosis, stage, treatment and outcome of the subjects. Paraffin tissue blocks of the subjects were stained for p16 expression using the immunoperoxidase method using mouse monoclonal antibody (Clone E6H4) and CINTek Histology VKit. Slides were scanned to digital file (Aperio CS, Aperio, Vista, CA). Neoplastic regions were analyzed using a color deconvolution algorithm (Aperio). Based on the percentage of pixels with weak, moderate, strong, and negative staining, each slide was given a score between 0-300. Score of 150 and above was designated as positive. P16 positive and negative groups were compared for differences in recurrence-free survival (RFS) and overall survival (OS) via log-rank test. Results: There were 19 deaths observed among 33 study-eligible subjects during 103.2 person-years of follow-up. The median age (quartiles) was 53 (45-61) years. Males were 55%; Caucasians were 94%. All subjects were treated with chemotherapy and radiation. 26 subjects were p16 positive and 7 were p16 negative. The median RFS was 2.99 years for the p16-positive group vs. 1.90 years for the p16-negative group (p = 0.32). The median OS was 3.14 years for p16-positives vs. 2.00 years for p16-negatives, (p = 0.52). Conclusions: 78% of the patients with anal squamous cell cancer in our study were p16-positive. The RFS and OS tended to be longer for patients with p16-positive cancer, but the lack of statistical significance might be explained by the small number of p16-negative subjects. A larger study needs to be conducted to further evaluate the difference. [Table: see text]
Experience with perioperative chemotherapy (ECC or ECF) for gastroesophageal cancer in British Columbia: A multicenter experience.
Authors: Lim Howard John , Al-Barrak Jasem , Cheung Winson Y. , Peixoto Renata D'Alpino
Published: March 2020

e15153

Background: In 2006, the MAGIC trial demonstrated a significant overall survival benefit for perioperative ECF among patients with resectable gastro-esophageal cancer when compared to surgery alone. Since 2008, perioperative chemotherapy has become the standard of care for resectable gastro-esophageal cancer in our institution. We report the results of our experience with this protocol. Methods: The BC Cancer Agency is a multi-centre institution treating the majority of oncology patients for the province. A total of 83 consecutive patients with localized gastric, gastro-esophageal junction (GEJ) or lower esophageal cancer who initiated ECC/ECF perioperative chemotherapy from March 2008 to June 2011 were identified using the pharmacy database. Patient’s characteristics were abstracted to an anonymous database and analyzed. Results: In our cohort, 83 patients (66 males and 17 females) with a median age of 62 years (range 37 – 79) began preoperative chemotherapy, of whom 73 (87.9%) completed 3 cycles. The response rate was 49.3%. Among the 83 patients, 78 (93.9%) underwent surgery (2 patients died of chemotherapy toxicities, 1 refused surgery and 2 developed disease progression before surgery), of whom 11 (14.1%) could not have their tumors resected (1 unresectable, 1 with liver metastasis and 9 with peritoneal carcinomatosis). Only one patient died of surgical complications. Six patients (7.69%) achieved pathologic complete response (ypCR) and all of them are alive and recurrence-free. Forty-eight patients (57.8%) subsequently began postoperative chemotherapy, of whom 37 (44.5%) completed 3 cycles. Thirty-nine patients have died as of December 4th, 2012. The observed median survival was 38 months. Conclusions: In our multi-center experience, the results reported in the MAGIC trial were reproduced.
Changes in pulse pressure upon exposure to electromagnetic fields modulated at specific frequencies in healthy individuals, HBsAg positive cancer-free patients (HBsAg+), and patients with advanced hepatocellular carcinoma (HCC).
Authors: Costa Frederico , Parise Edison Roberto , Gumz Brenda Pires , Zanesco Tatiana , Iemma Antonio Francisco , Barbault Alexandre , Pasche Boris
Published: March 2020

e15155

Background: Werecently described the antiproliferative effects of low levels of electromagnetic fields, amplitude-modulated at disease-specific frequencies (AM EMF) in patients with HCC (Br J Cancer, 2011,105:640) and on HCC cells (Br J Cancer, 2012,106:307). We identified HCC-specific modulation frequencies using a patient based biofeedback approach (J Exp Clin Cancer Res, 2009,28:51). Specific frequencies cause changes in pulse pressure in patients with HCC but not in healthy individuals. The effects of AM EMF in HBsAg+ patients, a pre-malignant condition, are unknown. Methods: 17 healthy individuals and 17 patients (5 HCC and 12 HBsAg+) were exposed to 206 HCC-specific modulation frequencies ranging from 100 Hz to 21 kHz (HCC-frequencies) and 237 random chosen frequencies (non-specific frequencies) within the same frequency range. All participants were exposed to both AM EMF and each frequency was tested separately. Changes in pulse pressure were recorded as previously described (J Exp Clin Cancer Res, 2009, 28:51). Results: HCC-frequencies caused changes in pulse pressure in all HBsAg+ and patients with HCC but no changes were observed in healthy individuals. The median number of frequencies causing changes in pulse pressure in patients with HCC was 175 (range: 97-206) and 7 (range: 3-16) in HBsAg+ patients. The non-specific frequencies did not cause changes in pulse pressure in patients with HCC but it caused changes in pulse pressure in 9 HBsAg+ (75%) with a median number of responding frequencies of 2 (range: 1-6). Non-specific frequencies also caused changes in pulse pressure in 11 healthy individuals (64%) with a median number of responding frequencies of 11 (range: 1-15). The pattern of changes in pulse pressure were significant between the 3 groups (p=0.0001). Conclusions: EMF modulated at specific frequencies cause a significantly different pattern of changes in pulse pressure in the three groups. These findings provide support for the development of EMF as a new diagnostic procedure. Clinical trial information: NCT01641276.
The prognostic VALUE of Ki-67 in gastric cancer.
Authors: Fradique Antonio Caldeira , Bruno Da Costa Ligia , Pupo Alexandra , Quaresma Luisa , Silva Gualdino , Cabrita Fernanda , Marques Mateus , Esteves Jorge , Pina Filomena , Da Silva Guedes , Oliveira Mario
Published: March 2020

e15172

Background: Gastric carcinoma is the second cause of cancer mortality worldwide. In Portugal, a country with a high incidence of the disease, it is also the second leading cause of cancer mortality. The gravity of this situation and the advanced stage of disease at presentation warrants a search of a new prognostic indicator. We studied in patients (pts) with gastric cancer, both diffuse and intestinal types, several possible prognostic indicators, such as: weight, nutrition status, Ki-67, p53, Cerb2, and cadherin E. The results showed that Ki-67, an indicator of cell proliferation, may play an important role as a prognostic indicator because it is easily assessed by immunohistochemistry, is observed in both intestinal and in diffuse tumor types, and is related with tumor size, depth of invasion and the pattern of lymphatic spread. Methods: A total of 50 pts with gastric carcinoma (25 diffuse and 25 intestinal types) undergoing radical gastrectomy with extended lymphadenectomy (D2 and a few D3 types ) were prospectively studied by immunohistochemistry for the determination of Ki-67 in biopsied tissue and gastrectomy specimens. A relationship between the Ki-67 and various other prognostic factors, like histological tumor type, tumor location, number of involved lymph nodes, depth of invasion, sex and stage was established. Results: A total of 50 tumor specimens and an equal number of biopsies were evaluated for Ki-67 overexpression. Ten tumors (20%) presented a Ki-67 < 50%, 13 tumors (26%) showed a Ki-67 >50% < 74%, and 27 tumors (54%) had a Ki-67 > 75%. It was found that tumors with a low Ki-67 expression have a more proximal location, the histological type was either mixed or diffuse, tend to invade superficially the gastric wall, they don’t have metastases in distal lymph nodes, and are diagnosed in early stages of the disease. Conclusions: In this study, the Ki-67 overexpression showed prognostic value in both diffuse and intestinal type gastric cancer patients.
Efficacy of paclitaxel plus cisplatin in advanced esophageal squamous cell cancer: Further analysis of single center, prospective study.
Authors: Gong Jifang , Zhang Xiaodong , Lu Ming , Li Yan , Li Jie , Li Jian , Zhang Xiaotian , Zhou Jun , Lu Zhihao , Shen Lin
Published: March 2020

e15174

Background: To evaluate efficacy and toxicity of paclitaxel plus cisplatin in advanced esophageal squamous cell carcinoma (ESCC). Methods: In this single-center, prospective study, chemo-naïve patients with metastastic and recurred ESCC received paclitaxel 175mg/m2 d1 and cisplatin was given on day 1, 2, at a total dose of 75 mg/m2 over 60 minutes, repeated every 21 days. Efficacy was evaluated every 2 cycles. Results: 133 patients were enrolled between June 2006 and November 2010. The median cycles of chemotherapy accepted were only 3. The objective response rate(RR) of paclitaxel and cisplatin in ESCC patients was 34.2%. After a median follow-up of 24.2 months, the progression free survival (PFS) was limited to 7.0 months (95%CI 5.68-8.32), meanwhile the median overall survival (mOS) was 12.0 months (95%CI 9.93-14.07). In the multivariate Cox regression analysis, distant organ metastasis remained an independent predictor of OS with a hazard ratio of 1.460 (95% CI 0.871-2.446, P = 0.041). 31 patients received radiotherapy after chemotherapy with significantly longer PFS than those without (6.8 months vs. 10 months, p = 0.037), but no difference in OS was observed (12.0 vs. 13.0 months, p = 0.23).Adverse events were tolerable. Conclusions: The efficacy of paclitaxel plus cisplatin in esophageal squamous cell carcinoma is promising. Sequencial chemoradiotherapy could release local progression but no help to overall survival.
Retrospective review of modified dose docetaxel, cisplatin, and 5-flourouracil (DCF) for the treatment of first-line metastatic gastric carcinomas.
Authors: Özdemir Nuriye , Aksoy Sercan , Eren Tulay , Abali Huseyin , Oksuzoglu Omur Berna , Zengin Nurullah
Published: March 2020

e15175

Background: Docetaxel, cisplatin, and 5FU (DCF) has been shown to be an effective regimen for metastatic gastric carcinomas. However, treatment-related adverse events is quite high with original dose DCF. We evaluated the outcomes of the metastatic gastric carcinomas who treated with modified dose DCF (mDCF) in our institution. Methods: A single institution retrospective review of patients with metastatic gastric cancer treated with three weekly mDCF from 1/2006 to 1/2013 was evaluated. Over this time period a standard order-set was in place in which cisplatin 60 mg/m2, 5FU 600 mg/m2 and docetaxel 60 mg/m2 was given three weekly. Tumor response was calculated retrospectively using RECIST criteria. Results: One hundred and ninety-one patients were included the study. The median age was 55 years (23 to 76), 74% were male, and 82% were chemo-naive. Eighty percent of the patients were metastatic at the time of diagnosis. The median number of cycles administered was 6 (2-10). Hematological toxicity was mild with grade 3/4 granulocytopenia in 25% of the patients, grade 3/4 thrombocytopenia in 4% of the patients, and grade 3/4 anemia in 9% of the patients. Neutropenic infection occurred in 9 (%5) patients. Grade 3/4 nausea/vomiting was reported by 10% of the patients, and diarrhea by 7%. A total of 19 (10%) patients had dose delays or dose reductions related to toxicity. Six (3%) patients had complete response and 43 (23%) patients had partial response. Stable disease were occurred in 83 (45%) patients and 56 (23%) progressive disease. Ninety percent of the patients have died with median follow-up of 8 months. Progression-free survival was 7 months (95% CI 6 to 7.8 m) and overall survival was 10 months (95% CI 8.7 to 11.2 m). Conclusions: mDCF has mild hematological toxicity and overall excellent tolerance in first line metastatic gastric cancer patients. Response rate and the survival of these patients with a minimal toxicity are comparable with the original dose DCF.
Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma.
Authors: Alessandretti Matheus Bongers , Brandao Erika Pereira , Abrahão Carina Meira , Lino Aline Rocha , Junior Rodnei Macambira , Costa Marcos André , Cruz Marcelo Rocha
Published: March 2020

e15176

Background: Few data regard efficacy and safety of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, fluorouracil bolus of 400 mg/m2 and continuous infusion of 2400 mg/m2 over 46 hours and leucovorin 400 mg/m2) in patients over 65 years with advanced pancreatic adenocarcinoma. Methods: After Ethical Committee approval, consecutive patients age over 65 with biopsy proven pancreatic adenocarcinoma that received at least one cycle of modified dose-attenuated FOLFIRINOX (no bolus FU and reduced dose of at least one agent since first cycle) were selected (São José Hospital database) for a retrospective review for safety, response, and survival. Results: Nineteen consecutive patients were selected from our database. Patients characteristics included 12 (63,1%) males, 7 (36,9 %) females, median age 72,7 (range 66-79). Tumor location was 11 (57,8 %) head of the pancreas, 6 (31,57 %) body and 2 (11 %) in other sites. Grade 3/4 toxicities were reported in 10 patients (52,6 %): nausea/vomiting 1 (5,2 %), diarrhea 1 (5,2 %), fatigue 3 (15,7%), neutropenia 4 (21 %), thrombocytopenia 1 (5,2%) and febrile neutropenia 3 (15,6 %). Elevations in AST and ALT above the upper limit of normality were identified in 5 (26,31%). No deaths reported due to toxicity. Prophylactic granulocyte colony stimulator factor (G-CSF) was given to 14 (73 %). Seventeen patients completed at least four cycles; disease control was obtained in 15 (83, 3 %) with 1 complete response, 5 partial response and 9 stable diseases. Median reductions in doses in the first cycle of chemotherapy by drugs were: oxaliplatin 23,3 % (10%-30%), irinotecan 24,6 % (0%-60%), fluorouracil 20,6% (0%-40%). Median reductions in doses in the fourth cycle of chemotherapy by drugs were: oxaliplatin 20,8 % (0%-42%), irinotecan 24,9 % (0%-75%), fluorouracil 17,6% (0%-40%).With a median follow up of 4.5 months, median overall or progression free survival is not reached. Conclusions: Modified dose-attenuated FOLFIRINOX is a therapeutic option to elderly with advanced pancreatic adenocarcinoma. Although grade 3 and 4 toxicities were reported, they were manageable. Modified attenuated-dose of FOLFIRINOX needs further investigated.
TACE plus sorafenib for the treatment of advanced hepatocellular carcinoma.
Authors: Palwe Vijay Sukhdeo , Nagarkar Rajnish Vasant
Published: March 2020

e15178

Background: Hepatocellular carcinoma (HCC) is considered to be a hypervascular tumor. Therefore, Trans Arterial Chemo Embolization (TACE) and inhibition of angiogenesis appear rational treatment strategies for those patients who have localised disease not amenable to surgical resection. TACE causes increased hypoxia leading to an up regulation in hypoxia inducible factor-1α (HIF-1α), which in turn up regulates vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor, and increases tumor angiogenesis. The present study investigated for the combination of TACE and Sorafenib, a multikinase inhibitor with anti-angiogenic activities approved for the treatment of HCC. Methods: Patients included histologically confirmed, unresectable hepatocellular carcinoma beyond Milan criteria, no extrahepatic spread, Child Pugh score ≤8, ECOG PS 0-2, platelets >100K/µl, and bilirubin <2.5 mg/dl. We present our experience with 42 patients of HCC treated with Trans Arterial Chemo Embolisation (TACE) with Cisplatin, Lipodol and PVA of which 14 pts received TACE along with Sorafenib. Results: Between May 2007 to Jan 2013, 42 patients were enrolled. Patients received a mean of 1.45 TACE interventions (range 1-4). The longest survival was 53 months after 1stTACE and median overall survival was 443 days. Grade 3 and 4 toxicities were noted in 18% and 7% of patients. Conclusions: TACE is a very good method for palliation of unresectable hepatocellular carcinoma (HCC) with improved survival and quality of life.The combination of TACE with sorafenib is tolerable for most patients and associated with a promising rate of radiographic response and OS.
Health care utilization and treatment patterns for patients (pts) with gastric cancer (GC) in China.
Authors: Jianfei Jeff , Du Wenmin , Chu Laura , Wang Xiaopei , Pruemer Jane
Published: March 2020

e15185

Background: GC is the third most common cancer in China with ~0.3 million deaths and 0.4 million new cases annually. Objective: To describe treatment patterns and survival for pts with GC, and to assess treatment outcomes and associated factors including health insurance coverage, gastric-intestinal disease, clinical comorbidities and family genetic or demographic factors. Methods: A retrospective cohort study was conducted. Primary data sources were medical records collected from multiple major Shanghai medical centers with timeframe of Jan2004 - Mar2010. Treatment outcomes included ‘improvement’ and ‘recovery or cure’ (as documented in the pts’ record), and death. Classical logistic regression and COX proportional hazard regression analysis were performed to assess the relationship between health outcomes and associated factors. Results: A total of 2249 GC pts were identified with mean age 65.9 and 36% female. Average follow-up was 26.3 months since GC index date (1stGC diagnosis date). During the study period, 518 (23%) pts died. GC treatments included surgical procedure (28%), radiation (2%), chemotherapy (14%), and traditional Chinese medicine/herbal regimens (21%). Major chemotherapy included 5-FU, cisplatin, etoposide, leucovorin, mitomycin, oxaliplatin, and semustine. From multivariable models, pts more likely to achieve recovery or cure were those who received surgical procedures (OR=15.0, 95% CI 11.3-19.9), radiation (OR=2.4, 95% CI 1.2-4.9), any chemotherapy (OR=2.7, 95% CI 1.9-3.9), and were covered by public health insurance (OR=3.5, 95% CI 2.3-5.3) or collaborative insurance (OR=3.5, 95% CI 2.1-5.8). Higher risk of mortality was significantly associated with key factors like advanced age (OR=1.0, 95% CI 1.0-1.0), late-stage cancer (OR=9.8, 95% CI 5.1-19.0), and liver disease (OR=1.9, 95% CI 1.4-2.6). A lower risk of mortality was associated with surgical procedure treatment (OR=0.6, 95% CI 0.5-0.7) and chemotherapy (OR=0.6, 95% CI 0.4-0.9). Conclusions: Multiple treatment regimens for GC are available in China. Surgical procedure, chemotherapy, TCM/herbal, and health insurance coverage are associated with positive treatment outcome and survival duration.
Sequential neoadjuvant chemotherpy with nab-paclitaxel plus gemcitabine and FOLFIRINOX in locally advanced pancreatic cancer (LAPC): A PILOT study.
Authors: Kunzmann Volker , Hartlapp Ingo , Scheurlen Michael , Einsele Hermann , Mueller Justus , Kenn Werner , Steger Ulrich , Germer Christoph T.
Published: March 2020

e15193

Background: Nab-Paclitaxel (nab-P) + Gemcitabin (G) and FOLFIRINOX have both shown promising activity in metastatic pancreatic cancer (mPC). Our group has developed sequential usage of both regimens in order to exploit the stromal depletion effects of nab-P and increase global efficacy of chemotherapy in the neoadjuvant setting of LAPC. Methods: This pilot study evaluated patients with cytological/histological confirmed diagnosis of locally advanced pancreatic ductal adenocarcinoma without evidence of metastatic disease (stage III). nab-P+G was administered for 2 cycles (nab-P 125 mg/m2, G 1000 mg/ 2; on days 1, 8, 15; every 28 days) followed by 2 cycles of FOLFIRINOX (as reported by Conroy et al., NEJM 2011). Results: We report the preliminary analysis of 8 pts treated in our institution. Patients characteristics were M/F: 5/3; median age 63 (46-79); PS 0/1: 6/2. 3 pts (37%) had a biliary stent before starting treatment. All pts received the planned 4 cycles of neoadjuvant chemotherapy without dose reductions. There were no treatment-related deaths and none of pts stopped treatment due to toxicity. Grade 3-4 toxicities were neutropenia (50 %), nausea (12%), diarrhea (12%) and thrombopenia (25%). Grade 2-3 sensory neuropathy occured in 25% of pts. Prior nab-P+G did not result in increased hematological or non-hematological toxicity of FOLFIRINOX. Among the 8 patients evaluable so far, 5 partial responses (63%) and 3 stable disease (37%) have been observed, resulting in a disease control rate of 100%. After sequential chemotherapy 3 pts (37%) underwent radical surgical resection. Of note, all resected patients pts showed regression of the tumor (Evans Regression Score 2-4) with 1 patient fullfilling the criteria of a complete pathological remission (pCR). 4 pts received concomitant chemo-radiotherapy and 1 pt underwent an explorative laparotomy with evidence of occult (micronodular) peritoneal metastasis. Conclusions: Sequential neoadjuvant chemotherapy with nab-P+G and FOLFIRINOX seems to be highly active with manageable toxicity profile and may allow to achieve pCR in LAPC. These results are encouraging to test this approach in a prospective phase II trial.