bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative concomitant chemoradiotherapy with capecitabine in locally advanced rectal carcinoma
Authors: Larbaoui B.
Published: August 2020

e15134

Background: Preoperative concomitant chemoradiotherapy has shown to improve local control and sphincter preservation with decreased acute toxicity compared with postoperative treatment in locally advanced rectal carcinoma. The primary endpoint of this phase II trial was pathologic tumor response. Secondary endpoint was sphincter preservation and toxicity. Methods: Inclusion criteria: rectal adenocarcinoma <12 cms from anal verge, clinical stage T3–4, adequate renal, hematological and liver function. Planned sample for this trial was 40 patients. Treatment schedule: Pelvic radiotherapy (45 Gy : 2 Gy /day ) and chemotherapy: Capecitabine 850 mg/m2 b.i.d p.o: day 1 to 14 (2weeks of treatment followed by 1 week rest period (cycle repeated every 3 weeks). Surgery with TME was performed after the end of the second cycle of chemotherapy. Adjuvant chemotherapy with 5FULV2 was administered after surgery Results: 15 patients have been recruited between January and October 2007: 12 males/3 females. Median age 40 years (range 22–70). Clinical stage (determined by CT or RMI): T3: 70% and T4: 30%. Tumor location (from anal verge): < 6 cm in 8pts, >6 cm in 7pts. Surgery (performed in 14 patients) consisted of low anterior resection in 7pts and abdominal-perineal resection in 8pts. Tumor down staging was observed in 9pts (60%), including 5pts with complete pathological response (33.3%). Main adverse effects (NCI-CTC): diarrhea G3–4: 15.2%, nausea/vomiting G3–4: 13%, Anemia G3- 4: 8.5%, neutropenia G3–4: 12.5%. Conclusions: Preliminary results show that preoperative concomitant chemoradiotherapy with Capecitabine is an effective regimen with an acceptable safety profile for locally advanced rectal cancer, leading to a high probability of tumor downstaging.

No significant financial relationships to disclose.
Rectal prognostic index (RPI) to predict outcome of patients with locally advanced rectal cancer (LARC) treated with preoperative chemo-radiation (preop-CRT)
Authors: Piperdi M. , Velagapudi V. , Ayata G. , Simons J. , Tseng J. F. , Piperdi B.
Published: August 2020

e15139

Background: Preop-CRT followed by surgical resection is the standard for LARC. LARC patients (pts) treated with preop-CRT have 60–70% 5-year survival. Several pathologic features including T stage (yT), lymph node (N) ratio (# of positive N (Np) / # of N examined (Ne)) and tumor regression grade (TRG) have been shown to be independent prognostic markers. We developed a prognostic score to determine pts with low risk of recurrence after preop-CRT. Methods: Our sample set consists of 20 pts treated on in house trial of preop-CRT with paclitaxel. All pts had R0 resections and received 4 months of 5-FU based adjuvant chemotherapy. All pathology slides were independently reviewed by GI pathologist. RPI scale of -4 to 14 was developed based on the formula: RPI = T (1–4) + (Np/Ne x 10) - TRG (0–4). The low, intermediate and high risk for recurrence were predefined as RPI (≤1), (>1 and <5), (≥5). Results: Between 1999–2003, 20 pts were treated on the trial and had R0 resection. The data is summarized in table 1 . The 5yr disease-free (DFS) and overall survival (OS) rate of all pts were 62 and 77%. Two pts (10%) achieved complete pathological response. Low, intermediate and high risk RPI was noted in 50, 35, and 15 % of pts. The 5yr DFS and OS for low, intermediate and high risk groups were 75, 42, 33 % and 86, 71 and 33% respectively.Conclusions: RPI can accurately predict a subset of pts with low risk of recurrence after preop-CRT. Majority of pts in this cohort have low risk RPI and have a favorable outcome (5yr survival rate of 86%). RPI could be very helpful in designing future trials tailoring adjuvant chemotherapy based on risk of recurrence. We are validating this data with a larger, independent group of LARC patients from our cancer registry (N=30) and this data will be available for presentation. Since RPI only requires the final pathology after CRT, it should be readily reproducible in future prospective studies across different institutions.

[Table: see text]

No significant financial relationships to disclose.
Inter- and intra-criteria reproducibility of RECIST ver 1.1 and modified EASL (European Association for the Study of the Liver) tumor response criteria to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC): From the dataset of JIVROSG (Japan Interventional Radiology in Oncology Study Group) 0401
Authors: Sato Y. , Watanabe H. , Sone M. , Onaya H. , Sakamoto N. , Osuga K. , Takahashi M. , Yamamoto S. , Arai Y.
Published: August 2020

e15501

Background: In spite of systemic response evaluation criteria, RECIST is widely used for evaluating the tumor response (TR) in local therapy. As a result, there are double standard criteria (RECIST ver 1.1 and modified EASL) in the evaluation for TR of HCC treated by TACE. Tumor size is evaluated by measurement of the entire lesion including necrotic part in RECIST ver 1.1 (EJC 2009;45:228), whereas the only contrast-enhanced part on radiological images is measured when the modified EASL are used (JNCI 2008;100:698). Both criteria adopt the unidimensional measurement. Methods: This is a study of the radiological findings of patients who underwent TACE for multiple HCCs in the JIVORSG 0401 study. The subjects were 65 lesions in 21 patients treated by pan- hepatic TACE using cisplatin and gelatin particles without mixing iodized-oil. Five radiologists measured independently each lesion twice, therefore 130 measurements were performed per radiologist according to the 2 criteria (RECIST ver 1.1 and modified EASL). To compare the inter- and intra- criteria reproducibility of TR for each lesion, CR rate, response rate, proportion of agreement, and the kappa statistics for response categories were calculated. Results: Results are shown in the table. CR rate and response rate obtained using the modified EASL were higher than those obtained using RECIST ver 1.1. The inter-criteria reproducibility between RECIST ver 1.1 and modified EASL were poor. The intra-criteria reproducibility of RECIST ver 1.1 indicated substantial agreement, while that of modified EASL indicated almost perfect agreement. Conclusions: For a precise interpretation of the tumor response in clinical trials of TACE for HCCs, appropriate attention must be paid to the criteria employed for the evaluation.

[Table: see text]

No significant financial relationships to disclose.
Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)
Authors: Campos L. T. , Nemunaitis J. , Stephenson J. , Richards D. , Barve M. , Gardner L. , Niecestro R. , Sportelli P.
Published: August 2020

e15505

Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD > 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received > 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent < 30 days, 4 toxicity < 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease > 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment < 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities > 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration.

[Table: see text]
A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC)
Authors: Saif M. W. , Li J. , Lamb L. , Rosenberg A. , Elligers K. , Ruta S. , Mezes M. , Grant N. , Liu S. H. , Chu E. , Cheng Y.
Published: August 2020

e15508

Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC. However, a standard second-line chemotherapy regimen has yet to be defined after G. PHY906, a 4-herb traditional Chinese medicine has a history of > 1,800 yrs of human use to treat GI symptoms including diarrhea. Preclinical studies showed that PHY906 may potentiate antitumor activity of CAP in human PANC-1 xenograft (ASCO 2007). A phase I study showed that CAP can be escalated up to 1750 mg/m2 PO BID on d1- 7 and PHY906 800mg PO BID on d1–4 q 2 wks with no DLTs (ASCO, 2008). Delivered dose-intensity of CAP was similar at 1750mg/m2 dose level as 1500mg/m2. Therefore, 1500mg/m2 of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC. Methods: Pts with G-refractory APC with ECOG PS <2 were treated with CAP 1500mg/m2 d1–7 with PHY906 800mg d1–4 q 2 wks. Response was assessed by CT scan according to RECIST q 6 wks and toxicity according to NCI-CTC v3.0. Primary objective is overall survival. Secondary objectives include overall RR, PFS and measurement of cytokines to assess inhibition of NF-kappa B, a possible mechanism responsible for PHY906's pharmacological activity. Results: As of January 5, 2009, 25 pts have been enrolled. Baseline characteristics include median age, 65 (range, 40–85); male/female,15/10; ECOG PS 0/1, 4/19; median cycles: 3 (r: 0.5–15). At this point 5 pts are still in active treatment. 4 pts have confirmed OS > 6 ms (1 still on study) with 2 further pts approaching 6 ms. Among evaluable pts, 1 had PR (5.3%), 11 SD (57.9%) and 7 PD (36.8%) after initial restaging scan. 36 % pts had >30% reduction in CA19–9 as biochemical response. There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI. G3/4 toxicities diarrhea 3/25 (12%), fatigue, 1/25 (4%), HFS 1/25 (4%) and mucositis 1/25 (4%). 1 pt was removed from study due to G3 HFS. Biomarker studies (IL4, GM-CSF, TNF-alpha, IL10, MCP-1, IL2, IL6) are ongoing. Conclusions: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts. CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation. In addition, PHY906 may have a cytoprotective antidiarrheal and anti-HFS effect, making treatment with CAP more tolerable.

[Table: see text]
Prognostic significance of preoperative serum tumor markers in the patients with curatively resected advanced gastric cancers
Authors: Yoon S. , Yoo C. , Park I. , Chang H. , Kim T. , Lee J. , Yook J. , Oh S. , Kim B. , Kang Y.
Published: August 2020

e15515

Background: We evaluated the prognostic significance of preoperative tumor markers, carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA19–9), and carbohydrate antigen 72–4 (CA72–4), in the patients with curatively resected advanced gastric cancers (AGC). Methods: Preoperative serum tumor markers were available for 667 patients who had been enrolled in a phase III trial of adjuvant chemotherapy (AMC0201). We compared the relapse free survival (RFS) and overall survival (OS) according to patient's pre-treatment clinical characteristics and serum tumor markers by using log rank test and Cox proportional hazard model. Results: Of total 667 patients, 3 year RFS rate and OS rate were 67.4% and 75.0%, respectively. Postoperative pathologic stage was II in 353 (52.9%), IIIA in 202 (30.3%), IIIB in 61 (9.1%), and IV (M0) in 51 (7.6%). CEA, CA19–9, CA72–4 were elevated pre-operatively in 64 of 665 patients (9.6%), 75 of 664 patients (11.3%), and 121 of 639 patients (18.9%), respectively. After the median follow-up of 38.4 months, 209 patients (31.3%) had recurrence, and 164 patients (24.6%) died. In the univariate analysis, location of tumor, type of surgery, Borrmann type, TNM stage, the elevation of CEA and CA72–4 level were significant prognostic factors for RFS and OS. In the multivariate analysis, serum CA72–4 was independent significant prognostic factor for RFS and OS as well as tumor location, Borrmann type, and stage Conclusions: Pre-operative serum CEA and CA72–4 levels were independent prognostic factors as well as clinical characteristics of pathologic stage, tumor location and Borrmann type in patients with curatively resected AGC.

No significant financial relationships to disclose.
Combined chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 for malignant ascites due to advanced gastric cancer with peritoneal dissemination
Authors: Kitayama J. , Ishigami H. , Kaisaki S. , Hidemura A. , Kato M. , Nagawa H.
Published: August 2020

e15524

Background: Malignant ascites caused by peritoneal metastasis the most life-threatening mode of metastasis and recurrence and seriously impair the quality of life in patients with gastric cancer. However, none of the treatment protocols have proved satisfactory clinical outcome. Methods: Twenty one patients with malignant ascites due to the peritoneal dissemination of gastric cancer were enrolled. Intraperitoneal catheter with infusing port was placed subcutaneously in all patients, and Paclitaxel was administered intraperitoneally at 20 mg/m2, together with intravenously at 50 mg/m2, on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. The change of the ascetic volume was prospectively investigated as the primary endopoint of the response rate. The volume of malignant ascites was objectively measured with the calculation of the consecutive computed tomography (CT) images using NIH image J software. Peritoneal cytology and mRNA of CEA in acitic fluid were also evaluated in 17 and 16 cases, respectively. Results: The volume of malignant ascites before the treatment was more than 500ml in 8 patients and less than 300ml in 13 patients. The average course of the treatment was 9 (2–19). The ascetic volume was markedly (more than 33%) reduced in 8 patients and totally disappeared in 5 cases with CT image, and thus the response rate was 62%. Malignant cells in peritoneal cytology disappeared in 13 cases while CEA mRNA became negative only in 2 cases. The one year overall survival was 71% in all patients and 85% in patients with reduced ascites. Conclusions: Combined chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was a useful protocol for malignant ascites caused by peritoneal dissemination of gastric cancer.

No significant financial relationships to disclose.
Analysis of signal pathway activation in hepatocellular carcinoma: Association with clinical outcomes to sorafenib in Chinese patients
Authors: Ji Y. , Fan J. , Zhang L. , Tan Y. , Zhou J. , Zeng H. , Ren Z. , Xu J.
Published: August 2020

e15529

Background: The pathogenesis of hepatocellular carcinoma invovles multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. Treatment strategies have focused on inhibition of the Ras effector pathway with inhibitors of Raf, such as sorafenib in HCC. Greater understanding of the cellular response to sorafenib is needed to tailor targeted therapy for individual patients and identify those more likely to benefit. Methods: We performed immunohistochemistry on a tissue microarray of tumor and adjacent liver tissue from 40 HBV-infected HCC patients who were treated with sorafenib, and 20 normal liver. We compared the levels of 8 signaling proteins including growth factor receptors (PDGFRa, VEGFR1, VEGFR2, VEGFR3, c-kit, c-met, IGF-R, EGFR), tumor suppressors (PTEN) and their downstream phosphorylated (p-) signal transducers (p-RAF, p-MEK1/2, p-ERK1/2; PI3K, p-AKT, NFkB, axin, β-catenin,p-GSK3β, p-mTOR, p-S6, p-70S6K, p-JNK, p-SRC, p-STAT3, c-fos, c-jun) in cancer cells and endothelial cells of HCC to those in non-neoplastic liver. Results: The overall profiles of signalling protein expression levels, activation states and subcellular distribution in HCC cells and endothelial cells were distinguishable from non-neoplastic hepatocytes. The ERK pathway activation was correlated with low level of nuclear β-cat and high level of p-mTOR (p<0.05). Long survival (>6m) patients were characterized by high level of nuclear pERK and low level of p-AKT, p-GSK3β (p<0.05) in tumor cells. The high microvessel density and the presence of micrometastases correlated with high level of VEGFR, p-ERK and p-SRC in endothelial cells. Conclusions: Sorafenib may affect signalling through the Ras/Raf/MAPK/ERK pathway. HBV-related HCC patients with. overactivation of signal transduction cascade MAPK/ERK and PI3K/AKT pathways in tumor cells and/or endothelial cells may benefit from the targeted treatment.

No significant financial relationships to disclose.
Application of a time-varying covariate model to the analysis of CA 19–9 as a biomarker for time-to-progression (TTP) and overall survival (OS) in patients with advanced pancreatic cancer
Authors: Boeck S. , Laubender R. P. , Haas M. , Klose C. , Kullmann F. , Buchner H. , Bruns C. J. , Stieber P. , Mansmann U. , Heinemann V.
Published: August 2020

e15545

Background: It remains unclear whether baseline CA 19–9 or CA 19–9 kinetics during chemotherapy may serve as predictive biomarker in patients (pts) with pancreatic cancer (PC). Methods: Main inclusion criteria for this retrospective multicenter analysis: histologically confirmed diagnosis of PC, treatment with first-line therapy, pre-treatment CA 19–9 level of > 5.2 U/ml. Analysis of CA 19–9 was exclusively performed using the Elecsys® assay (Roche Diagnostics). The effect of the pre- treatment CA 19–9 level on TTP and OS was modelled by Cox proportional hazards regression. The effect of CA 19–9 kinetics was also modelled by Cox proportional hazards regression where CA 19–9 was treated as time-varying covariate. When modelling CA 19–9 we developed univariate and multivariate Cox models where we selected additional predictors (e.g. performance status) using backward elimination performing likelihood ratio tests on a significance level of 0.05. Results: One-hundred and fifteen pts from 5 German centers were included. Median age was 63 years, 12% had locally advanced and 88% metastatic disease; 73 % of the pts were treated within prospective clinical trials. Median baseline CA 19–9 was 1059 U/ml (range 9.5–100000), median pre- treatment bilirubin 0.6 mg/dl. The median TTP in the study population was 4.4 months, median OS 9.4 months. Univariate analysis showed that the pre-treatment CA 19–9 level (as continuous variable, log [CA 19–9]) was significantly associated with TTP (HR 1.24, 95% CI 1.12–1.37, p<0.001) and OS (HR 1.16, 95% CI 1.06–1.28, p=0.002). These associations remained significant also within a multivariate analysis. For CA 19–9 kinetics during chemotherapy, data from 69 pts (TTP) and 84 pts (OS) were available, respectively; log [CA 19–9] kinetics were found to be a significant predictor for TTP in univariate (HR 1.44, 95% CI 1.25–1.67, p<0.001) and multivariate (HR 1.39, 95% CI 1.19–1.62, p<0.001) analyses, and also for OS (univariate: HR 1.34, 95% CI 1.20–1.49, p<0.001; multivariate: HR 1.39, 95% CI 1.23–1.57, p<0.001). Conclusions: According to this new statistical model, CA 19–9 may serve as a useful predictive biomarker in advanced PC.

[Table: see text]
Impact of lymph node metastases on outcome following treatment with sorafenib in patients with hepatocellular carcinoma (HCC): Subset analysis from the phase III SHARP trial
Authors: Raoul J. , Craxi A. , Porta C. , Lentini G. , Nadel A. , Voliotis D. , Bruix J. , Llovet J. M.
Published: August 2020

e15547

Background: Results from the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, a multinational, randomized, placebo-controlled, phase III trial, demonstrated that sorafenib is effective and safe for patients with advanced HCC (Llovet et al, N Engl J Med, 2008). As lymph nodes are among the most common sites of metastasis in patients with HCC, we performed subset analyses to evaluate the efficacy and safety of sorafenib in patients with or without lymph node metastases at baseline. Methods: Patients (N=602) with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy for HCC were randomized 1:1 to receive either sorafenib 400 mg BID or placebo. End points included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 d from first demonstration of response), time to progression (TTP), and safety. Results: Median TTP, OS, and DCR by subset are shown in the table. The incidence of grade 3/4 drug-related adverse events across subgroups was consistent with that reported for the overall population. The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib prolonged OS and TTP in patients with advanced HCC, whether or not lymph node metastases were present at baseline. The safety profile of sorafenib in patients with lymph node metastases was comparable with that for the overall study population.

[Table: see text]

[Table: see text]
Phase II trial of neoadjuvant fixed dose rate (FDR) gemcitabine with capecitabine (GX) combination chemotherapy in locally advanced pancreatic adenocarcinoma (LAPA)
Authors: Lee J. , Lee S. , Kim T. , Lee J. , Park D. , Seo D. , Lee S. , Kim M. , Han D. , Kim S.
Published: August 2020

e15553

Background: To determine the efficacy and safety of fixed dose rate (FDR) gemcitabine and capecitaibne (GX) combination chemotherapy for locally advanced pancreatic adenocarcinoma Methods: Patients with histologically confirmed LAPA were eligible for this prospective phase II trial. Dynamic pancreas/pelvic CT, MRI and FDG-PET were undertaken to assess the resectability. EUS was also performed as needed basis. ‘Borderline resectable (BR)’ and ‘unresectable (UR)’ criteria developed by our pancreatico-biliary multidisciplinary management team (PBMMT) and NCCN criteria were used. After confirmation of resectability, patients received 3 cycles of FDR gemcitabine 1,250 mg/m2 on D1 and D8 and capecitabine 950 mg/m2 from D1-D14 every 3 weeks. Thereafter, staging was repeated and patients underwent surgery if the disease was not unresectable. For patients with R0 resection, additional 6 cycles of GX were administered. For patients with R1 resection, chemoradiotherapy (CRT) (54 Gy over 5 weeks with concurrent 5-FU and leucovorin or capecitabine) followed by FDR-GX was administered. Patients with stable or better response to chemotherapy but assessed unresectable at reassessment received additional chemotherapy up to 9 cycles followed by CRT. Results: Between August 2006 and July 2008, 38 eligible patients (14 with BR and 24 with UR based on NCCN criteria; 29 with BR and 9 with UR based on our PBMMT criteria) entered on this study. The median age was 61 yo (42–76) and 71% had cT4 disease. The response to neoadjuvant chemotherapy was PR in 6 (16%), SD in 26 (68%) and PD in 3 (8%). Metabolic response was achieved in 20 patients (53%) with 2 metabolic CR out of 31 evaluable patients. Grade 3 or worse adverse effects were mainly HFS (n=5) and gastrointestinal (n=3) with no grade 4 in severity. Surgery was performed in 9 patients (24.0%, R0=8, R1=1, 6 in NCCN-BR and 3 in NCCN-UR, 9 in PBMMT-BR) and five patients refused surgery although their diseases seemed not to be unresectable. The median PFS was 9.4 months (95% CI, 8.3–10.4) and estimated median OS was 13.5 months (95% CI, 12.4- 14.5). Conclusions: FDR-GX was effective as neoadjuvnat chemotherapy in LAPA with favorable toxicity profile.

No significant financial relationships to disclose.
Definitive chemoradiation therapy with capecitabine in locally advanced pancreatic cancer
Authors: Yi S. , Kim H. S. , Lee J. , Park S. , Park Y. , Lim H. , Kang W. , Park H. , Lim D. , Park J. O.
Published: August 2020

e15558

Background: We evaluated safety and efficacy of concurrent chemoradiotherapy (CCRT) with capecitabine in patients with locally advanced pancreatic cancer (LAPC). We also tried to devise a prognostic model for LAPC undergoing definitive CCRT. Methods: Between January 2004 and January 2008, 39 patients with LAPC treated with capecitabine CCRT were reviewed. Capecitabine was administered at 850 mg/m2 bid every day for 5 weeks. Radiotherapy was given 5 days per week, at 1.8 Gy fractions, over the 5 weeks. Results: Thirty seven (94.8%) patients completed CCRT, and 2 patients removed during the treatment for toxicity issues. Of the 36 evaluable patients, 15 (41.7 %) patients achieved partial response, and 13 (36.1 %) had a stable disease with 77.8% of disease control rate. Among the 28 patients who had achieved disease control after CCRT, 8 patients (21.6 %) received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay. With median 1.8 years of follow- up, the overall survival was 14.3 months (95% confidence interval [CI]; 10.6–17.9 months). Median progression free survival was 11.1 (95% CI 7.2–15.1) for all patients, and 7.9 months (95% CI 6.6–9.2) for those not received post-CCRT chemotherapy. No patient had grade 4 hematologic or non-hematologic toxicity. Eight patients (21.6%) had severe grade 3 toxicities, 7 (18.9%) with gastrointestinal toxicity and 1 (2.7%) with hematologic toxicity. Prognostic factors for survival were serum albumin (P=0.014; relative risk [RR], 3.4; 95% CI, 1.4, 8.6), and adjuvant gemcitabine treatment (P = 0.005; RR, 3.5; 95% CI, 1.2, 10.6). The prognostic grouping resulted in three groups with significantly different prognosis: group 1 (0 adverse factor; n=8; 1-year survival, 87.5%), group 2 (1 adverse factor; n=23; 1-year survival, 52.9%) and group 3 (2 adverse factors; n=8; 1-year survival, 25.0%). Conclusions: Combined therapy with capecitabine CCRT was well tolerated. Capecitabine seems to be a promising regimen in the treatment of LAPC, in terms of response, survival, and tolerable adverse effects.

No significant financial relationships to disclose.
Use of PET SUV for primary tumor to predict outcome in locally advanced esophageal cancer treated with trimodality therapy
Authors: Videtic G. M. , Macley H. M. , Reddy C. , Adelstein D. J. , Rice T. W. , Saxton J. P. , Venigalla N. , Srinivas S.
Published: August 2020

e15559

Background: To assess the value of the primary tumor's SUVmax (PT-SUVmax) from the staging FDG-PET as a predictor of clinical and pathologic outcomes in patients undergoing trimodality therapy for locally advanced esophageal cancer. Methods: A retrospective chart review was conducted on patients with T3/4 and/or node positive esophageal carcinoma treated at the Cleveland Clinic between 7/1/03 and 5/31/06. All patients were managed with an institutional regimen consisting of preoperative radiotherapy [30 Gy @ 1.5 Gy twice daily over two weeks] with concurrent cisplatin and 5-fluorouracil during the first week. Following resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered. Pretreatment patient and tumor characteristics including PT-SUVmax were analyzed with respect to response and survival. Results: 141 patients completed preoperative CRT: 125 (88.7%) were male, median age was 60 years, 73.8% had adenocarcinoma, 79.4% had N1 disease, 81.6% underwent surgery and 63.8% completed the full regimen. Median follow-up was 17.2 months [range 0.7–75.1]. Median PT-SUVmax was 9.43 [range 0 to 47.7]. Increasing clinical stage was associated with increasing PT-SUVmaxs: for cT2 vs. cT3 and cN0 vs. cN1, PT-SUVmax cutoffs were 8 (p=0.03) and 11 (p=0.02), respectively. Median (MST) and 5-year overall survivals were 20.7 months and 27.4%, respectively. A PT-SUVmax of < vs. > 7 was a significant predictor for T downstaging (p=0.0502) and N downstaging (p=0.0467). A PT-SUVmax cutoff of 7.6 was associated with a significant difference in MST, at 29.1 and 13.0 months for PT-SUVmax< 7.6 and >7.6, respectively (p=0.0158, HR=1.82, 95%CI=1.19–2.94). On multivariate analysis, PT-SUVmax was the only significant factor associated with survival (p=0.0.314, HR=1.71, 95%CI=1.05–2.79). Conclusions: The pretreatment SUVmax of a primary esophageal cancer appears to correlate with clinical stage, pathologic response to therapy and survival. This finding could play a role in the design of clinical trials and in adapting treatment strategies.

No significant financial relationships to disclose.
A phase II study of gemcitabine-based chemoradiotherapy (CCRT) after triplet induction chemotherapy (ICT) for locally advanced pancreatic cancer (LAPC): A Taiwan Cooperative Oncology Group (TCOG) study
Authors: Ch’ang H. , Hwang T. , Wang H. , Chang M. , Tien Y. , Chen J. , Hsieh R. , Lin P. , Shan Y. , Cheng A. , Chen L.
Published: August 2020

e15562

The optimal management of LAPC remains controversial. The efficacy of CCRT is hampered by early systemic dissemination. To treat undetectable metastases and to select patients who are likely to benefit from CCRT, ICT followed by CCRT has recently been extensively evaluated in LAPC. Recently, we showed that triplet chemotherapy consisting of gemcitabine 800 mg/m2 (10 mg/m2/min) followed by oxaliplatin 85 mg/m2 and 48-hour infusion of 5-FU/LV 3,000 and 150 mg/m2 Q 2 weeks, the GOFL regimen, is feasible and active for pts with APC. Chemo-naïve pts with histo- /cytologically proven unresectable LAPC, and bi-dimensionally measurable diseases were eligible. Patients who did not experience disease progression (PD) after 6 cycles of GOFL would had CCRT consisting of weekly gemcitabine 400mg/m2 plus 50.4Gy/28 fractions of radiation 4–6 weeks later. After CCRT, pts were re-evaluated for surgical intervention and those with unresectable disease would continue GOFL until PD, unacceptable toxicity, patient's refusal or death. Among the 50 enrolled pts (24F/26M, median age 58.5 years), 48 had definitively unresectable diseases. After induction GOFL, 16 (32%) pts were off-studied because of PD in 12 (24%) and ICT-related toxicity in 4 (8%, PD/UE group). Among the 34 (68%) with objective response or stable disease after 6 cycles of ICT, 27 (54%) who completed the assigned multimodality treatment are categorized as CCRT group; whiles 7 (14%) who either declined CCRT (in 5) or still on ICT (in 2) are categorized as non-CCRT group. The median PFS and OS for the ITT population were 9.1 and 14.5 months, respectively. The median PFS for PD/UE, non-CCRT and CCRT groups were 2.1, 8.2 and 12.8 months, respectively; whiles the OS were 8.5, 15.0 and 18.3 months, respectively. The most common grade 3–4 toxicities were neutropenia (40%), anemia (14%), infection (16%), nausea (26%), vomiting (20%). Grade 2–3 peripheral neuropathy was observed in 7 of 29 who received post-CCRT GOFL. Conclusion: Three months of triplet ICT followed by gemcitabine-based CCRT is feasible and likely to prolong the survival of selected LAPC pts. Prospective, randomization study is warranted to validate the findings.

No significant financial relationships to disclose.
Hepatic arterial infusion chemotherapy using low-dose cisplatin and 5-fluorouracil (5-FU) in the treatment of patients with advanced hepatocellular carcinoma with portal vein tumor thrombus or refractory to transarterial chemoembolization: A single institute outcome analysis
Authors: Nishimura T. , Matsumoto S. , Kanai M. , Ishiguro H. , Kitano T. , Yanagihara K. , Fukushima M.
Published: August 2020

e15563

Background: Although sorafenib has been reported to prolong survival of patients with advanced hepatocellular carcinoma (HCC), the prognosis of those who did not respond to or are not candidate to transarterial chemoembolization (TACE) remains poor. The aim of this outcome analysis is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted injection port in the treatment of such patients. Methods: From the prospective cohot database of Outpatient Oncology Unit, Kyoto University Hospital, patients with HCC who had been treated with HAIC using low dose cisplatin and 5-FU (cisplatin 10mg and 5-FU 250mg for day 1–5, repeated serially for three or four weeks, then repeated once weekly) between October 2003 and December 2008 were searched for. All adverse events were assessed according to Common Terminology Criteria for Adverse Events v3.0. Survival analysis was performed by using Kaplan-Meier method. Prognostic factors were assessed using Log-rank test. Results: Forty-one patients were identified. The indications of HAIC were: (1) the presence of portal vein tumor thrombus (20/41 cases, 49%), (2) failure to TAE (19/41, 46%) or (3) not candidate for TAE due to the presence of extrahepatic disease (2/41 case, 5%). One complete response and 7 partial responses were observed, overall response rate being 19.5% (95%CI, 7.4–31.6%). Median overall survival was 26.1 month (95%CI: 9.6–45.6). Commonly observed grade 3/4 adverse events were thrombocytopenia (10 cases, 16.3%) and neutropenia (10 cases, 16.3%). There was a trend that fewer death occur in patients who responded to HAIC (1/8 cases, 12.5%) as compared to patients who did not (11/33, 33.3%), but log-rank test failed to detect a statistical significance (P=.145). Conclusions: HAIC for patients with advanced HCC who are not candidate for TACE warrants randomized controlled trial.

No significant financial relationships to disclose.
Effect of understaging of early oesophageal tumors on treatment
Authors: Rohatgi A. , Naji S. , Hamouda A. , Ross P. J. , Mason R. C.
Published: August 2020

e15572

Background: Early and node negative oesophageal cancers do not undergo chemotherapy as it is felt that as the risk of lymph node metastasis is small, early operative intervention is considered the best option. We analysed a prospective database in a tertiary referral centre to see, with current preoperative staging modalities, if a significant number of patients were under staged and hence under treated preoperatively. Methods: Four hundred and fifteen patients underwent esophagectomies for cancer in our unit between March 2000 and December 2006. 117 were preoperatively staged as either T1/T2 N0. Pre-operative staging was by gastroscopy, endoscopic ultrasound (EUS), CT scan and PET-CT. These were discussed in a multi-disciplinary meeting and as per current evidence did not undergo preoperative chemotherapy. Results: 115 patients were analysed as two were excluded. Preoperatively there were 35 T0N0, 30 T1N0, and 50 T2N0. There were 42 (36.5%) patients who were under staged utilising the standard preoperative staging protocol. These were preoperatively staged as T0N0 –2, T1N0 –6, T2N0 –34. 6 did not have EUS, only 4 had a PET- CT and 1 had a staging laparoscopy. Gastroscopy, CT scan and EUS was the staging protocol in 87%. Post op staging was T1N1–7, T2N1–12, T2N2–1, T3N0–10, T3N1–11, T3N2–1. Conclusions: Utilising current preoperative staging methods one third of patients were under staged. Looking specifically at T2N0 68% were under staged. We feel that early oesophageal cancer especially T2N0 disease may benefit from neoadjuvant chemotherapy based on the current staging protocols.

No significant financial relationships to disclose.
Changes in cardiopulmonary reserves associated with neoadjuvant therapy in patients with esophageal cancer
Authors: Hofstetter W. L. , Hightower C. E. , Morris G. S. , Sun X. G. , Riedel B. J. , Mehran R. J. , Hearon C. M.
Published: August 2020

e15589

Background: Recent treatment trends for resectable esophageal cancer have moved toward the addition of neoadjuvant chemoradiotherapy. This additional therapy, however, places these patients at increased risk for loss of physiologic/functional capacity. If present, such declines can delay resection of the primary tumor until the patient has physiologically recovered from this insult. To determine whether physiological reserves decline, peak exercise performance was assessed before and after completing neoadjuvant therapy Methods: In this prospective study seventeen male patients (60.5 + 7.1 years) with esophageal cancers underwent a symptom limited, standard ramp bicycle ergometer cardiopulmonary exercise test (CPET) before and after completing neoadjuvant therapy. The exercise protocol sequentially entailed 3 minutes of quiet resting, 3 minutes of unloaded cycling, ramp protocol to peak exercise tolerance, and 3 minutes of recovery. Ramp rates (5–25 watts/.min) were individually chosen to achieve test durations of 8–12 minutes. Expired gases were measured for volume and gas fractions via breath-by-breath analysis (Medical Graphics CardiO2/CP system). STATISTICAL ANALYSIS: Physiological data were analyzed by paired t-tests (α=0.05). Data are presented as mean + standard deviation. Results: Pre treatment exercise testing occurred immediately before onset of treatment. Post treatment exercise testing typically occurred 45 + 17 days after neoadjuvant ended and 11 + 10 days before surgery. Peak exercise capacity (VO2peak) and anaerobic threshold declined 11.9 % and 10.5 % respectively (p < 0.01) over the neoadjuvant therapy treatment period. Both oxygen pulse (VO2/HR) and pulse pressure product (HR X SP) at VO2peak also significantly declined (p< 0.01) over the treatment period. Conclusions: These results suggest 1) both systemic and peripheral changes contribute to an overall physiological and functional decline in patients undergoing neoadjuvant therapy and 2) efforts aimed at preserving optimal physiological/functional capacity may be warranted during this period.

No significant financial relationships to disclose.
Elucidating genetic events in human hepatocellular carcinoma
Authors: Rosario C. , Gladdy R. , Ko M. , Pollett A. , Dennis J. , Swallow C.
Published: August 2020

e15590

Background: Hepatocellular carcinoma (HCC) is prevalent world wide with increasing incidence in North America. 4q is a commonly deleted region in HCC and is lost in 32% of premalignant cirrhotic nodules but the precise molecular lesion involved in tumor initiation remains unknown. Human Plk4, a member of the polo family of cell cycle regulating serine /threonine kinases is located on 4q28. Plk4 is a haploinsufficient tumor suppressor in mice, with 50% of animals developing spontaneous tumors, most commonly multifocal primary HCC. We hypothesize that Plk4 plays a role in the initiation of human HCC. Our purpose was to determine the levels of Plk4 in human HCC and investigate possible genetic interactions with the tumor suppressor p53. Methods: Formalin-fixed paraffin-embedded sections of human HCCs, adjacent non-neoplastic liver tissue and gallbladder tissue were microdissected. DNA was extracted and manual LOH analysis was performed. To asses Plk4 expression, RNA from the hepatoma cases was used for real time RT-PCR. To elucidate a genetic interaction, Plk4 p53 compound mutant mice were generated and murine embryonic fibroblasts (MEFs) were derived and cultured. Results: In HCC Plk4 LOH rates varied from 57% for the marker closest to Plk4 to 8% for the marker furthest away (n=32). Using an intragenic marker the rate of LOH was 45% (n=24). Studies in CRC (n=46) and pancreas cancer specimens (n=40) showed only background levels of LOH. Expression of Plk4 in HCC tumor samples that displayed LOH at the Plk4 locus was reduced compared to non-neoplastic liver. Plk4±p53−/− mice showed acceleration of tumor formation compared to Plk4+/+p53−/− mice. Plk4±p53−/− MEFs had increased levels multinucleation, centrosome amplification and aneuploidy compared to Plk4+/+p53−/− cells. In addition these cells were tumorigenic in vivo whereas Plk4+/+p53−/− cells were not. Conclusions: Our results demonstrate significant rates of LOH at the Plk4 locus specifically in human HCC and indicate that this is associated with decreased Plk4 expression. In addition, our studies of compound mutant mice suggest a possible genetic interaction of Plk4 and p53 in tumor development.

No significant financial relationships to disclose.
Clinical significances of preoperative serum IL-6 and CRP level in operable gastric cancer
Authors: Lee S. , Kim D. , Oh S. , Kwon H. , Jang J. , Kim S. , Kim M. , Kim K. , Han J. , Kim H.
Published: August 2020

e15591

Background: The interleukin (IL)-6 pathway is one of the mechanisms liking inflammation and angiogenesis to malignancy. As the C-reactive protein (CRP) is representative marker of inflammation, recently CRP has been reported to be associated with processing of disease in many cancers. This study aims to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and correlate them with disease status and prognosis. Methods: A total of 115 patients receiving gastrectomy entered this study. Serum level of IL-6 was measured by using Enzyme-Linked Immuno-Sorbent Assay (ELISA) and CRP was measured by using immunoturbidimetry. Histological findings were included depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (AJCC Stage Groupings The staging systems; Primary tumor, regional LN, metastasis). Results: The more cancer invasion and stage are high, the more preoperative serum IL-6 levels are high. IL-6 level was correlated with depth of invasion (P=0.006) and TNM stage (P<0.001). Preoperative CRP level also correlated with depth of invasion (P<0.001), TNM stage (P=0.001), and presence of peritoneal seeding metastasis (positive 0.66 ± 0.69 mg/dL, negative 0.20 ± 0.29 mg/dL; P<0.001). When we put cutoff value of IL-6 level (6.77 pg/dL) by ROC curve, although patients’ survival did not reach the median value, it shows significant difference in time to progression (TTP; P<0.001) and overall survival (OS; P<0.010). But, CRP did not show significance to patients’ TTP and OS. Conclusions: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion and TNM stage. Preoperative high IL- 6 level was a poor prognostic factor of disease recurrence and overall survival in patients with gastric cancers.

No significant financial relationships to disclose.
Cetuximab plus docetaxel-cisplatin (DC) as first-line treatment for locally advanced or metastatic gastric cancer: Preliminary results of a phase II study
Authors: Fahlke J. , Ridwelski K. , Florschuetz A. , Kettner E. , Leithaeuser M. , Kroehning H. , Stuebs P. , Zierau K. , Lippert H.
Published: August 2020

e15592

Background: Based on promising published data, this multicenter, phase II study was initiated to investigate a combined treatment using DC and cetuximab in the first-line setting for patients with gastric cancer. Methods: Patients aged 18–75 years with stage III (T4, nonresectable) or stage IV gastric cancer, ECOG performance status (PS) ≤2, and life expectancy ≥3 months were recruited to receive cetuximab (400 mg/m2 on day 1 then 250 mg/m2 q1w) and DC (D 75 mg/m2 and C 75 mg/m2; both as 1-h infusions on day 1 and then q3w). Treatment was stopped in the event of disease progression, intolerable toxicity, or consent withdrawal. Tumor staging was performed after cycle 3 and then every 12 weeks. The primary endpoint was overall response rate and secondary endpoints included time to progression, overall survival and toxicity. Planned accrual was 79 patients. A per-protocol interim response analysis was planned for the initial 20 evaluable patients. Results: Preliminary data are available for 30 patients; median age 64 [range: 40–73] years; median ECOG PS 1 [range: 0–2]; adenocarcinoma 87%. Median cycles administered were 3 [range: 1–14] and the median follow-up was 1.63 months. The overall response rate was 27.3% (complete response, n=1; partial response, n=5). Stable disease was observed in 10 patients, and disease progression in 6 patients. The most relevant NCI-CTC grade 3–4 hematologic events per patient were leukopenia and neutropenia (73%), anemia (13%), and febrile neutropenia (10%). Major grade 3–4 nonhematologic toxicities were nausea (30%), vomiting (20%), diarrhea (13%), acne (13%), and fatigue (13%). Conclusions: DC and cetuximab were well tolerated and resulted in promising response rates and a predictable toxicity profile. The study is ongoing.

No significant financial relationships to disclose.
Usefulness of PET/CT in the diagnosis of distant metastases of potentially operable gastric adenocarcinoma
Authors: Gallego R. , Fuster D. , Ginés A. , Ortín J. , Ayuso J. R. , Momblan D. , Arguis P. , Conill C. , Pons F. , Maurel J.
Published: August 2020

e15598

Background: 1) To evaluate the usefulness of Positron Emission Tomography with combined 18F-Fluorodeoxyglucose with Computed Tomography (PET/CT) in the diagnosis of distant metastases in patients with gastric adenocarcinoma (GAC) compared to spiral double contrast thoracoabdominal Computed Tomography (CT); 2) To establish the utility of PET/CT in the detection of peritoneal carcinomatosis compared to laparoscopy. Methods: Thirty prospective patients (22 men, 8 women; mean age 67±11) who underwent endoscopic ultrasound and were classified as T2–3N1 or T3Nx GAC were included in this study. Whole body images were obtained 1 hour after injection of 370 MBq of 18F-Fluorodeoxyglucose. CT was performed within 2 weeks of PET/CT. Laparoscopy was performed without remarkable incidences. All findings were confirmed by histopathology examination and/or by at least 6 months follow- up. Results: Distant metastases were found in 9/30 cases: carcinomatosis (3), retroperitoneal (3) or mediastinal (2) pathological lymph nodes and one case of bone metastases (1). PET/CT diagnosed unsuspected distant metastases by CT in 4/9 patients (retroperitoneal (1) or mediastinal (2) pathological lymph nodes and 1 case of bone metastasis in the spine). In 1/3 patients with histopathological confirmed diagnosis of peritoneal carcinomatosis by laparoscopic findings was negative by PET/CT, and considered as a false negative case. On the other hand, 3 patients with initially positive peritoneal carcinomatosis by invasive laparoscopy were finally diagnosed as benign lesions. These lesions did not show significant uptake in PET/CT and were considered as true negative cases. Conclusions: 1) PET/CT is useful in the diagnosis of distant metastases in patients with GAC 2) Further studies are needed to establish the role of PET/CT to detect peritoneal carcinomatosis.

No significant financial relationships to disclose.