bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peritoneal carcinomatosis from colorectal cancer: Not a lost cause.
Authors: Kier Y. E. , Aulakh A. S. , Furman M. , Lambert L. A. 
Published: February 2017

592 Background: Patients who present with peritoneal carcinomatosis (PC) from colorectal cancer are considered terminal, with an expected median survival of 6-8 months. Therapy is often considered palliative and aggressive treatments are nihilistically ignored. This study investigates the clinicopathologic characteristics and clinical outcomes of CRC patients who present with PC. Methods: This is a retrospective review of all patients who presented with stage IV CRC from 1/2000-12/2008 to a single, tertiary care institution. Patients with PC at the time of presentation were identified. Demographic data, clinicopathologic characteristics, treatment and survival data were collected and analyzed. Results: 591 patients who presented with stage IV colorectal cancer were identified. Complete data was available on 216 patients. PC was confirmed in 106 patients (17.9%). PC was the only site of metastatic disease in 40 patients (6.7%). Compared with patients who did not have PC, patients with PC had significantly more right-sided primary tumors (28% vs 47%) and more mucinous tumors (7% vs 22%). The median overall survival for patients with isolated PC was 11.1 months as compared with 9.1 months for PC patients with extraperitoneal metastases (p = 0.5). Conclusions: Patients with right-sided and mucinous primary colon cancers are at increased risk of developing PC. Despite a lack of aggressive therapy, patients with isolated PC achieved a 11 month median survival. Treating PC patients and patients at-risk for PC with optimal oncologic therapy, including cytoreduction and intraperitoneal chemotherapy, will improve survival and should be considered early in the management of PC patients. No significant financial relationships to disclose.
Y-90 radioembolization in the treatment of colorectal cancer that is metastatic to the liver.
Authors: Cucci A. R. , Martin E. W. , Bloomston M. , Schmidt C. R. , Mayr N. A. , Wei L. , Bekaii-Saab T. 
Published: February 2017

593 Background: Y-90 radioembolization has shown promise in the treatment of unresectable metastatic colorectal cancer (mCRC) and primary hepatocellular carcinoma (HCC). The goal of our study was to assess the efficacy in patients with refractory mCRC who underwent Y-90 radioembolization. Methods: Patients with unresectable mCRC to the liver underwent treatment at the Ohio State University with resin microspheres. Response to treatment or progression of disease was assessed by CT imaging per RECIST criteria. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan-Meier method. Log-rank test was used to compare the survival curves between the groups. The Cox-regression model was used to explore any association between time to treatment and PFS (or OS). Results: 24 patients with a mean age of 63 years old were included. 54% of patients had extrahepatic disease, 67% had hepatic bilobar involvement, and more than 80% of our patients had more than two chemotherapy regimens prior to initiation of Y-90 radioembolization. There were no objective responses radiographically. 5 patients had a CEA response. The estimated median PFS and OS were 3.9 months (CI 95%: 2.4,4.8) and 8.9 months (CI 95%: 4.2,16.7), respectively. Patients with any CEA response to treatment tended to have a significantly longer PFS (4.8 months vs. 2.7 months, p=0.088), but no significant association with OS (p=0.64). The presence of extrahepatic disease prior to initiation of treatment resulted in a significantly lower PFS (2.9 vs. 5.1 months, p=0.076) but no significant difference in OS (p=0.86). Patients older than 65 appeared to have an improvement in PFS compared to younger patients (4.6 vs. 2.4 months, p=0.052). There was no significant association between the time to initiation of treatment and PFS (p=0.63) or OS (p=1). Conclusions: Y-90 radioembolization appears to have promising activity in patients with refractory unresectable liver metastasis from mCRC. Factors such as older age and absence of extrahepatic disease may be associated with improved outcomes. CEA response may be a surrogate marker for benefit. Large randomized studies need to confirm our findings. No significant financial relationships to disclose.
Role of trimodality therapy versus dual-modality in T3N0 rectal cancer patients.
Authors: Lim H. J. , Woods R. , Johal B. S. 
Published: February 2017

597 Background: Adjuvant radiation (R) and chemotherapy (C) is generally recommended for patients (pts) with pT3N0 rectal cancer, although there is no data to support the use of adjuvant chemotherapy. This study examines the whether there is benefit with trimodality therapy vs. dual modality in this population. Methods: The BCCA Colorectal Cancer Outcomes Unit database was used to identify referred pts with pT3N0 rectal carcinoma diagnosed between 2000-2004. The data from this cohort has been previously reported (Johal et al. ASCO Annual Meeting 2007) During this period, “short course” R (25Gy/5, surgery within 10 days) was recommended for resectable cT3 tumors followed by 6 months of C. If not treated pre-operatively (pre-op), guidelines specified post-op “long course” (45Gy/25) R and C. Three treatment groups were identified: Surgery alone (S), S and R (SR), and S, R and C (SRC). Eligible pts had complete surgical resection with or without total mesorectal Excision (TME). Pts treated with “downstaging” pre-op long course R, with S and C only (13 pts) or with R2 resection were excluded. Locoregional Recurrence (LR) and Distant Recurrence (DR) rates determined. Reasons for non-treatment were determined by chart review. Due to the heterogeneity between the groups, a univariate and multivariate analysis was performed. Results: The patient characteristics have been previously reported. 5-yr LR was similar between SR and SRC (3.84 %vs. 6.34% p=0.474). 5-yr DR were 24.81% (SR), and 17.56% (SRC) p=0.0354 and 5 yr OS 68.4% (SR), and 86% (SRC) p=.0002. On multivariate analysis, chemotherapy did impact on OS with a HR of 0.532, p=0.0462. Conclusions: Treatment of pT3N0 rectal cancer was variable in clinical practice despite established guidelines. There was significant heterogeneity with respect to comorbid medical conditions between groups receiving SR and SRC which limits comparability between groups. However, those patients who received tri-modality therapy experienced less distant relapse and an increase in overall survival. No significant financial relationships to disclose.
Randomized phase II study of PEP02, irinotecan, or docetaxel as a second-line therapy in gastric or gastroesophageal junction adenocarcinoma.
Authors: Cunningham D. , Park S. , Kang Y. , Chao Y. , Chen L. , Rees C. , Lim H. , Tabernero J. , Yeh G. , De Gramont A. 
Published: February 2017

6 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11). In phase I studies, PEP02 has improved pharmacokinetics (PK) of CPT-11 and its active metabolite-SN38 with encouraging safety and tumor response in several cancer types including gastric cancer. This study evaluated the efficacy and safety of PEP02 (P), irinotecan (I) or docetaxel (D) as a single agent in gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: A randomized, 3 arms (1:1:1), Simon's 2-stage (2/21, 5/41 based on tumor response) study was conducted in Europe and Asia. Patients (pts) with locally advanced or metastatic disease, failed to one prior chemotherapy, ECOG PS ≤ 2, at least 1 measurable lesion, no prior CPT-11 or taxane, were treated with P - 120 mg/m2, I - 300 mg/m2, or D - 75 mg/m2 every 3 weeks. PK and pharmacogenetics (PGx) samples were collected for pts in P and I arms. Results: A total of 135 pts were randomized with 132 (44 per arm) treated between Jan 2008 and Jun 2010. Pts demographics (P/I/D): median age: 56/62/58, male (%): 79.5/77.3/77.3, Pts from Europe (%): 54.6/52.3/56.8, metastatic (%): 97.7/90.9/97.7, gastric adenocarcinoma (%): 84.1/79.6/68.2, and ECOG 0 + 1 (%): 93.2/93.2/90.9. The confirmed responders of P/I/D were 6 (13.6%)/3 (6.8%)/7 (15.9%) and disease control were 27 (61.4%)/27 (61.4%)/24 (54.6%). These three arms have similar progression free survival and overall survival. If stratified by region, Asian pts had longer survival than European pts. Toxicities of P/I/D were: grade 3/4 neutropenia (%): 9.1/13.6/15.9. grade 3/4 diarrhea (%): 27.3/18.2/2.3, hand-foot syndromes (%): 0.0/6.8/18.2. It was notable that symptoms related to acute cholinergic syndrome were less reported in P arm than in I arm. The PK data showed the mean T1/2, Cmax and AUC0→∞ of SN-38 in P/I arms were 88.8/22.8 hr, 8.79/44.1 ng/mL and 879/440 hr x ng/mL. Conclusions: This randomized phase II study suggests that PEP02 improves the PK profile and tumor response over irinotecan, and it is as efficacious as docetaxel in the 2nd-line treatment for gastric or GEJ adenocarcinoma. PEP02 is worthy of further evaluation as either 1st- or 2nd-line setting in future gastric cancer studies. [Table: see text]
Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.
Authors: Gutierrez J. A. , Martinez-Martinez G. , Silva A. J. , Gomez Rangel J. , Palmerin M. , Gutierrez M. , Garcia B. 
Published: February 2017

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.
Evaluation of prognostic factors in gene expression and clinicopathologic characteristics in patients with adjuvant chemotherapy for advanced gastric cancer.
Authors: Azuma M. , Ishido K. , Takeuchi A. , Naruke A. , Higuchi K. , Sasaki T. , Katada C. , Sakuramoto S. , Watanabe M. , Koizumi W. 
Published: February 2017

61 Background: We reported TS expression is an independent prognostic factor in patients with gastric cancer who received postoperative adjuvant chemotherapy with S-1 at 2010 ASCO GI (abstract 32). These pharmacogenomic finding will help for choosing chemotherapeutic agents for personalized therapy in the future. Our aim was to indicate association of TS expression with clinicopathological characteristics in the same patient population. Methods: 39 patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed. These patients received adjuvant chemotherapy with S-1 after surgery. Formalin-fixed, paraffin-embedded tumor tissues were dissected by the laser-captured microdissection technique and analyzed for target gene expressions using a quantitative real-time PCR. Results: There were no significant differences between stage II and III in TS gene expressions. TS expression (low ≤ 0.72, high > 0.72) and histological type (intestinal and diffuse) are evaluated for PFS and OS. Patients were classified as Group I (n = 5); low TS and intestinal type, Group II (n = 14); low TS and diffuse type, Group III (n = 13); high TS and diffuse type and Group IV (n = 7); high TS and intestinal type. There were significant differences between these four groups (Kaplan-Meier survival analysis, log-rank test, PFS: p = 0.0112 OS: p = 0.0128). The survival curve showed longer survival both PFS and OS in Groups 1 > 2 > 3 > 4. In low TS situation (responders as Group I and II), there is a trend in patients with intestinal type had a longer survival compared to diffuse type (Group I > II). In high TS situation (non-responders as Group III and IV), the result are opposite, there is a trend in patients with diffuse type had a longer survival compared to Intestinal type (Group III > IV). Conclusions: These data suggest that TS gene expression levels may be molecular markers of prognostic factor for patients with adjuvant chemotherapy for resectable gastric cancer. S-1 might be effect different behavior by both histological type and TS expression. Prospective studies are needed to validate these preliminary findings. No significant financial relationships to disclose.
Preoperative chemoradiotherapy for locally advanced rectal adenocarcinoma: A dosimetric comparison of intensity-modulated radiation therapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT).
Authors: Tao C. T. , Scala L. M. , Gee H. , Lim D. , Padilla B. , Rounsaville M. C. , Lee J. W. , Abendroth R. E. 
Published: February 2017

615 Background: Small bowel and bladder toxicities (bleeding, obstruction, perforation, and stricture) are rare but serious late complications of pelvic radiotherapy (RT) related to dose received by these organs. IMRT has been used effectively in other pelvic malignancies (prostate and gynecologic) to decrease the dose to normal tissues when compared to 3D-CRT. Few studies have examined the use of IMRT in rectal cancer to assess whether a similar dose reduction is feasible. Methods: Eight consecutively treated patients with T2/T3 and N0/N1 rectal adenocarcinoma underwent 5-FU based neoadjuvant chemo-RT using 7-field sliding-window IMRT between 2008 and 2010. Retrospectively, conventional 4-field 3D-CRT plans were generated for dosimetric comparison with IMRT treatment plans. Planning target volumes included the gross tumor, rectum, peri-rectal tissues, pre-sacral space, and common and internal iliac lymphatics. Organs at risk included small bowel (contoured as all small bowel identified on the planning CT plus a 1 cm symmetrical expansion), bladder, and femoral heads. Small bowel, bladder, and femoral head mean doses and volumes receiving 45 Gy (V45) were compared between conventional and IMRT plans, respectively. Paired Student's t-test was used for statistical analysis. Results: Mean prescription dose was 52.9 ± 3.3 Gy. Compared to 3D-CRT, IMRT plans had an 11% lower mean dose delivered to the bladder (38.2 ± 4.5 Gy vs 43.1 ± 1.9 Gy, p = 0.028) and 24% lower mean dose to the small bowel (24.0 ± 2.9 Gy vs 31.7 ± 7.7 Gy, p = 0.014). IMRT plans also had a 55% lower bladder V45 (27 ± 19% vs 61 ± 22%, p = 0.0077) and a 96% lower small bowel V45 (1 ± 0% vs 21± 20%, p = 0.021). The femoral heads received a nonsignificant higher mean dose (19.2 ± 3.9 Gy vs 16.6 ± 3.0 Gy, p = 0.069). Conclusions: Small bowel and bladder volume receiving 45 Gy and mean dose were significantly lower using IMRT compared with 3D-CRT planning. More stringent volumetric planning constraints may be necessary to further reduce the dose to the femoral heads. Further study is warranted to examine the clinical benefit of these dosimetric findings. No significant financial relationships to disclose.
Preliminary results of an ongoing phase II/III clinical study of the TLR9 agonist MGN1703 in patients with advanced colorectal carcinoma with disease control after first-line induction therapy (IMPACT Study).
Authors: Tschaika M. , Schmoll H. , Scheithauer W. , Mayer F. , Schroff M. , Schmidt M. , Wittig B. 
Published: February 2017

618 Background: MGN1703 is a synthetic DNA-based immunomodulator, which acts as an agonist of toll-like receptor 9. The antineoplastic activity of MGN1703 was previously shown in several in-vitro and in-vivo models. A good safety profile of MGN1703 was shown in regulatory required acute and chronic toxicity studies. A currently finished phase I study in patients with metastatic solid tumors including those with CRC provided evidence for a favorable safety profile of the investigational drug as well as demonstrated positive preliminary efficacy results. Based on these promising data, a phase II/III study was initiated in patients with advanced CRC. Methods: This international multicentric randomized placebo-controlled phase II/III clinical study is being conducted in patients with advanced CRC with disease control after first-line induction therapy with standard chemotherapy regimen in combination with bevacizumab. One hundred and twenty nine patients have to be recruited to the study and randomized to be treated ether with MGN1703 or with placebo (with a ratio of 2:1), respectively. The recruited patients are treated twice a week with subcutaneous administration of 60 mg MGN1703. This dose has been proven to be safe in the phase I clinical study. The efficacy and safety of the study treatment will be evaluated based on extensive immunological tests, radiological assessment, safety laboratory results and assessments of the quality of life. The study treatment will be continued up to occurrence of tumor progression, intolerable toxicity, exclusion criteria, and withdrawal of consent or death. [Table: see text]
The effect of chemotherapy on overall survival of stage II colon cancer.
Authors: Omaira M. , Mozayen M. , Katato K. 
Published: February 2017

625 Background: Surgical resection of local colon cancer is the only curative treatment, at the same time adjuvant chemotherapy is clearly shown to be beneficial as the standard of care for node positive disease (stage III) colon cancer. However the role of chemotherapy for stage II colon cancer treatment is still conflicting. We aim to compare the overall survival rate of stage II colon cancer patient's with and without chemotherapy. Methods: A retrospective observational study was conducted from 1990-2006. Patients with stage II colon cancer were included. Patient's characteristics including age, gender, common site of involvement, histology patterns, overall survival rate and treatment with chemotherapy were recorded. Results: A total of 138 consecutive patients were identified from 1990-2006. The median age was 68 (21-91) year, males (44%), African Americans (47.6%). The most common sites of the primary tumor were sigmoid and cecum (22.4%) each. Adenocarcinoma being the most common pathology. Majority of the patients (86.2%) were found to have T 3 tumors. Of the patients that received chemotherapy (29/44) 66% had an overall survival rate of three years or more, whereas (53/94) 57% of the patients who did not receive chemotherapy had a survival rate of three years or more. The difference of survival rates between the two groups of patients was not statistically significant. Conclusions: The role of chemotherapy in stage II colon ancer is still controversial. There was no significant difference in overall survival between the two groups who did and did not receive chemotherapy; thus more studies are warranted to explore the factors that predict the survival of stage II colon cancer. No significant financial relationships to disclose.
Circumferential resection margin (CRM) in esophageal (OC) and gastroesophageal (GOJ) cancers.
Authors: Landau D. B. , Collins C. G. , Perry E. , Suh Y. , Grieves A. , Gill B. , Botha A. , Mason R. , Jacques A. 
Published: February 2017

69 Background: We hypothesized that CRM size affect survival and local recurrence for OC and GOJ cancer. We also assessed the utility of CT in predicting margin status. Methods: A retrospective analysis of a prospective database was carried out on all patients who had esophagectomy between January 2000 and July 2008. Patients diagnosed with OC and GOJ tumors on final pathologic examination were included. Distance from the CRM was assessed by a specialist upper GI pathologist. Two radiologists, blinded to postoperative margin status, reviewed preoperative CT scans using 16 separate parameters, comparing them to measured CRM status. Results: 419 patients were assessed. 223 pts had OC or GOJ type 1 tumors, average age 62 years (range 36–80), mean follow-up 5.8 years (2-9.5). There were 125 deaths and median overall survival (OS) 3.33 years (95% CI 2.76-6.24). 76 patients had recurrence at a median of 1.3 years (0.1-4.7). For 144 patients had OC or GOJ type 1 T3 tumors. Selected results are presented in the Table. There was no CRM size above which there was no further reduction in recurrence. Postoperative chemoradiation did not improve OS (p=0.79) or recurrence (p=0.96) in patients with CRM of 0-1 mm. In 50 patients the CT parameters significantly correlated with margin status were largest axial diameter (p=0.003) and contact with adjacent structures (p=0.005). A complete statistical review with multivariate and subgroup analyses will be presented. Conclusions: CRM size is strongly correlated with survival and recurrence in OC and type 1 GOJ tumors. Prediction of a close CRM could be used to select for more intensive therapy prior to undergoing radical surgery, such as chemoradiation. Preoperative CT can help in this prediction. [Table: see text] No significant financial relationships to disclose.