bluuebunny/crossref_metadata_2025 huggingface dataset:
The optimal dose period of indisetron tablets for preventing chemotherapy-induced nausea and vomiting (CINV) induced by mFOLFOX6: An exploratory trial HGCSG0703.
Authors: Yuki S. , Nakatsumi H. , Tateyama M. , Uehata Y. , Kudo M. , Kato K. , Miyagishima T. , Uebayashi M. , Asaka M. , Komatsu Y.
Published: February 2017

589

Background: Indisetron is a 5-HT3 receptor antagonist which shows also 5-HT4 antagonistic activity, that had approved in 2004 by Japan's PMDA. There are no recommendations of prophylactic regimens for preventing nausea and vomiting induced by FOLFOX therapy. To explore the optimal dose period of indisetron tablets during mFOLFOX6, we designed the study to compare the antiemetic efficacy and safety of 3-day regimen of indisetron with a single dose regimen.

Methods: Advanced colorectal cancer patients who were treated with mFOLFOX6 (+/- bevacizumab) as first-line chemotherapy were enrolled in this study. They were randomly assigned to Group A (3-day of indisetron) or Group B (a single dose of indisetron). Dexamethazone (8mg) was also administered intravenously in both groups before administering of oxaliplatin. The follow-up period was 5 days from the start of chemotherapy. The primary endpoint was complete protection from vomiting, and secondary endpoints were complete protection from nausea, no use of rescue therapy, and severe adverse events.

Results: Of 45 patients enrolled in this trial, 42 (93.3%) were assessable. The proportions of patients with complete protection from vomiting were 85.7% in Group A, and 81.0% in Group B (p=1.000; Fisher's exact test). The proportions of patients with complete protection from nausea were 47.6% in each group (p=1.000; chi-square test). The no rescue therapy rates were 66.7% in Group A, and 57.1% in Group B (p=0.525; chi-square test). No severe adverse events were observed in both groups.

Conclusions: We suggested that the efficacy of a single dose of indisetron might be equivalent of 3-day regimen for preventing from nausea and vomiting induced by mFOLFOX6.

[Table: see text]
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.
A phase II study of preoperative chemotherapy with S-1 (S) and cisplatin (P) followed by D3 gastrectomy for gastric cancer (GC) with extensive lymph node metastasis (ELM): Survival results of JCOG0405.
Authors: Yoshikawa T. , Nakamura K. , Tsuburaya A. , Sano T. , Mizusawa J. , Katai H. , Kurita A. , Uyama I. , Nomura E. , Sasako M. ,   Gastric Cancer Surgical Study Group of Japan Clinical Oncology Group
Published: February 2017

70

Background: GC with ELM, especially in case of M1(LYM), is regarded unresectable in many countries, while challenge is ongoing in Japan to treat them by intensive chemotherapy followed by super extended surgery. In our previous phase II study (JCOG0001) for the same population, iritotecan plus P (IP) chemotherapy followed by surgery showed remarkable survival of 27.0% at 3 years but its toxicity led to rather high treatment related death (TRD). Development of safer and more effective treatment is urged.

Methods: Eligibility criteria included histologically proven gastric adenocarcinoma; bulky nodal involvement around major branched arteries to the stomach and/or para-aortic nodal metastases; cM0 (except para-aortic nodes); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients (pts) received two or three 28- day cycles of induction chemotherapy of S (80 mg/m2 from day 1 to 21) and P (60 mg/m2 on day 8), and then underwent D3 gastrectomy. Primary endpoint was R0 resection and key secondary endpoint was 3-year survival. Other secondary endpoints included response rate and adverse events.

Results: Between 02/2005 and 06/2007, 53 pts were enrolled and 2 pts were ineligible. Only surrogate endpoints of efficacy and feasibility were reported in ASCO-GI 2008, which included clinical response of 64.7%, R0 of 82.4%, pathological response of 51.0%, and no TRD with low toxicities. The 3-year overall survival, which we first clarified in this report, was 58.8% (95% CI, 44.1-70.9%).

Conclusions: Preoperative SP followed by D3 gastrectomy demonstrated excellent 3-year survival with low mortality compared with preoperative IP, which was far better result than expected against this unresectable population. This multimodal treatment is highly promising for GC with ELM.

[Table: see text]
Randomized controlled trial of omental bursectomy for resectable cT2-3 gastric cancer.
Authors: Kurokawa Y. , Fujiwara Y. , Takiguchi S. , Fujita J. , Imamura H. , Tsujinaka T. , Mori M. , Doki Y.
Published: February 2017

72

Background: Omental bursectomy, a traditional surgical procedure to dissect the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon, has often been performed against resectable gastric cancer. We have conducted a multi- institutional randomized controlled trial to elucidate the safety and usefulness of this procedure.

Methods: Patients with cT2 or cT3 gastric adenocarcinoma were intraoperatively randomized to radical gastrectomy plus D2 lymphadenectomy either with or without bursectomy. The primary endpoint was overall survival (OS). The planned sample size was 464, with an alpha error of 0.05 and statistical power of 80% to detect a 10% margin of non-inferiority for the non-bursectomy group. The first interim analysis was conducted on Sep 2008, and we decided the preliminary data release according to Korn's proposal (J Clin Oncol. 2005).

Results: Between Jul 2002 and Jan 2007, a total of 210 patients were randomized to either the bursectomy group or the non-bursectomy group. Background characteristics were well balanced. Intraoperative blood loss was greater in the bursectomy group than in the non-bursectomy group (median, 475 mL vs. 350 mL, p=0.047), while other surgical factors did not vary significantly. The overall morbidity rate was 14%, the same between two groups. The hospital mortality rate was 0.95%; one patient per group. In the first interim analysis, the 3-year OS were 86% in bursectomy group and 79% in non-bursectomy group, and the hazard ratio was 1.55 (95% CI: 0.84-2.84). The non-bursectomy group had more patients with peritoneal recurrences than the bursectomy group (14% vs. 8%).

Conclusions: Experienced surgeons could safely perform a D2 gastrectomy with an additional bursectomy. First interim analysis suggested the survival advantage of omental bursectomy for cT2-3 gastric cancer patients. Final analysis will be conducted in 2012.

No significant financial relationships to disclose.
Outcomes of chemoradiotherapy with a high irradiation dose using a 3D radiation treatment planning system for esophageal cancer.
Authors: Murakami Y. , Nagata Y. , Nishibuchi I. , Kimura T. , Kenjo M. , Kaneyasu Y.
Published: February 2017

89

Background: The standard irradiation dose of chemoradiotherapy (CRT) for esophageal cancer is 50.4 Gy, however, the trials in which this standard dose was originated were based on 2D radiation treatment planning. In this study we assessed the survival and toxicities of CRT with a dose of 60-66 Gy using a 3D radiation treatment planning system (3DRTPS) for esophageal cancer.

Methods: One hundred and two eligible patients with esophageal cancer treated by definitive CRT between 2000 and 2006 were assessed. Median age was 67 years old. There were stage I in 22 patients, stage II-III (without T4) in 27 and T4/M1Lymph legions in 53. There were 100 patients with squamous cell carcinoma histology and 2 with small cell carcinoma. Main tumor sites were cervical/upper/middle/lower thoracic in 15/19/43/25 patients. Treatment planning of irradiation was performed using a CT based 3DRTPS. Total irradiation dose of our protocol was 60-66 Gy. Accomplishment rate of planned irradiation was 93%. All patients received chemotherapy concurrently with radiotherapy. Fluorouracil based chemotherapy was performed in 96 patients (94%).

Results: The data was updated in August 2010. The median follow-up was 67 months. Cause-specific survival rates at 5 years for stage I, II-III (without T4) and T4/M1lymph were 100%, 49% and 17%, respectively and overall survival rates were 66%, 35% and 13%, respectively. Complete response (CR) rates were 100%, 79% and 35%, respectively and failure rates of CR cases were 5%, 43% and 42%, respectively. Late adverse effects (≥ grade 3) were observed in 11 patients (10%); pneumonitis in 4 (4%), pleural effusion in 4 (4%) and pericardial effusion in 5 (5%). Treatment related deaths were observed in 2 cases (pneumonitis developed during treatment in 1 and debility due to treatment in 1).

Conclusions: Toxicities of CRT with a high irradiation dose using 3DRTPS for esophageal cancer were acceptable and survival was promising. Dose intensification study of 50.4 Gy versus ≥ 60 Gy in CRT using a 3D-conformal radiation therapy technique for esophageal cancer should be considered.

No significant financial relationships to disclose.
Epirubicin (E) in combination with cisplatin (CDDP) and capecitabine (C) versus docetaxel (D) combined with 5-fluorouracil (5-FU) by continuous infusion as front-line therapy in patients with advanced gastric cancer (AGC): Preliminary results of a randomized phase II trial of the Gruppo Oncologico Dell'Italia Meridionale.
Authors: Maiello E. , De Vita F. , Gebbia V. , Lorusso V. , Cinieri S. , Giuliani F. , Orditura M. , Fistola E. , Filippelli G. , Colucci G.
Published: February 2017

97

Background: Combination chemotherapy regimens improve outcome of AGC patients even if there is no accepted global standard regimen. Compared with ECF, D in combination with 5-FU c.i. shown promising efficacy in a phase II randomised study (J Clin Oncol. 23:494;2005). REAL-2 trial demonstrated that C was effective as 5-FU c.i. when used as part of a triple combination regimen turning the treatment into an easier to administer regimen (N Engl J Med. 358: 36; 2008). In the present study we compare DF versus ECX as first-line therapy of AGC.

Methods: Patients with previously untreated histologically documented AGC, with at least one measurable disease, age < 18 years, ECOG PS ≤ 2, and age 18-75 years, were randomly assigned to receive E (50 mg/m2 day 1), CDDP (60 mg/m2 day 1) and C (625 mg/m2 bid, days 1-21) (ECX) or D (85 mg/m2 day 1) and 5-FU (750 mg/m2/day c.i., days 1-5) (DF) q 3 weeks. RECIST and NCI criteria were employed to determine the activity and the toxicity of these regimens.

Results: The main characteristics in ECX and DF arms were: M/F = 22/14 and 23/8, median age = 58 years (range 39-74 years) and 61 years (range 44-75 years), site of disease = liver in 29 (82.8%) and in 20 (64.5%) patients, lung in 7 (20%) and in 4 (12.9%) patients, lymph-nodes in 26 (74.2%) and in 21 (67.7%) patients, multiple 14 (20%) versus 21 (60%) and 16 (51.6%) versus 14 (48.4%). ORR (CR + PR) was 54.3% in ECX arm and 22.6% in DF arm. Nine PRO were observed in both arms (25.7% and 29.2%, respectively). Main toxicity rate (G3-4) in the evaluable patients assigned to ECX arm were neutropenia (28.5% versus 19.4%), nausea/vomiting (18.2% versus 3.2%), alopecia (22.8% versus 18.3%) and H&F syndrome (5.7% versus 0%). The worst toxicity (G3-4) in DF arm was anaemia (9.6% versus 5.7%).

Conclusions: Preliminary results of this study shown an higher ORR of ECX regimen with respect to DF with a favourable toxicity profile.

No significant financial relationships to disclose.
Single-institution experience of preoperative chemoradiotherapy for locally advanced gastric cancer.
Authors: Pepek J. M. , Chino J. P. , Willett C. G. , Tyler D. S. , Uronis H. E. , Czito B. G.
Published: February 2017

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Background: To examine acute toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer.

Methods: Patients with gastroesophageal (GE) junction (Siewert type II and III) or stomach adenocarcinoma who underwent curative intent CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Tumors were staged according to AJCC 6th edition. Local recurrence was defined as radiographic or biopsy- proven disease within the radiation treatment field. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to CTCAE v4.0.

Results: Forty-eight patients (60% stage III, 8% stage IV) were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Thirty-five percent had signet ring histology, 52% had poorly differentiated tumors and 10% had linitis plastica. Median age was 60 years and median RT dose was 45 Gy. All patients received concurrent chemotherapy (CT) with 40 (83%) receiving 5-FU-based CT. Rates of acute > grade 2 hematologic and non-hematologic toxicity were 38% and 10%, respectively. Six patients (13%) required treatment break and two (4%) were unable to complete the prescribed treatment course. Thirty-six patients (75%) underwent surgery. Patients did not undergo surgery due to distant metastases at laparotomy or restaging (n=9), patient refusal (n=2) or poor performance status (n=1). Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS for all patients was 40%. For those undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively.

Conclusions: Preoperative CRT for gastric cancer is reasonably well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with advanced disease, LC, DFS and OS rates in resected patients are comparable to similarly staged, adjuvantly treated historic controls. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.

No significant financial relationships to disclose.
Safety of proton therapy treatment for prostate cancer patients with unilateral hip replacements.
Authors: Nichols R. C. , Hoppe B. S. , Ho M. W. , Martinez H. , Henderson R. H. , Marcus R. , Mendenhall W. M. , Costa J. A. , Williams C. R. , Mendenhall N. P.
Published: February 2017

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Background: Determine the feasibility of proton therapy for prostate cancer patients who have undergone unilateral hip replacement.

Methods: From January, 2007 to March, 2008 5 patients with localized (4) or locally recurrent (1) prostate cancer and previous unilateral hip replacement underwent hip avoiding proton therapy. The median target dose was 78 Cobalt Gray Equivalent (Range 74CGE to 82CGE). All patients were treated in the supine position without a rectal balloon. Median maximum (1cc) dose to the normal femoral head was 51.47CGE (Range 43.82CGE to 64.50CGE). All patients signed informed consent and were registered to either the IRB approved UFPTI PR01, PR02 or Outcome Tracking (OTP) Protocols.

Results: With a median follow up of 28 (range 15 to 39) months, no patient experienced grade 2 or higher late rectal toxicity. No patient experienced grade 3 or higher late urinary toxicity. Two patients experienced grade 2 urinary toxicity by virtue of having been placed on medication (tamsulosin) for urinary obstructive symptoms. No patient has reported hip fracture, hip pain or other skeletal event in the normal hip.

Conclusions: Our experience suggests that patients with unilateral hip replacements can be treated with hip avoiding proton therapy without an increased risk of urinary, rectal or skeletal complications.

No significant financial relationships to disclose.
A multi-institutional study of 3,794 patients undergoing robotic-assisted laparoscopic radical prostatectomy to determine the surgical learning curve for positive margins and operating time.
Authors: Sooriakumaran P. , John M. , Leung R. , Peters D. , Lee D. , Wiklund P. , Tewari A.
Published: February 2017

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Background: The surgical learning curve for robotic assisted laparoscopic radical prostatectomy (RALP) is often cited as being shorter than for other surgical modalities. However, while this appears true with regards to surgical safety, the learning curve for more refined variables like positive surgical margin (PSM) rate and operative time (OT) is not well established. Our objective was to assess the surgical learning curve for RALP in terms of these parameters.

Methods: We performed a retrospective cohort study of 3,794 patients who underwent RALP between Jan 2003 and Sep 2009 by three surgeons (DL, PW, AKT) from three centers (UPenn, Karolinska, Cornell). Mean overall PSM rates and mean overall OT were calculated for all three surgeons at intervals of 50 RALPs per surgeon, and learning curves for these means were fit using a loess method. R version 2.71 was used for all statistical analysis.

Results: The learning curve for PSM rates for all patients demonstrated improvements that continued with greater surgeon experience, with over 1,600 cases required to get a PSM rate <10%. When only pT3 patients were evaluated, the learning curve started to plateau after 1,000-1,500 cases. Mean OT plateaued after 750 cases although with further surgical experience the OTs started to climb again.

Conclusions: The learning curve for RALP is not as short as previously thought, and a large number of cases are needed to get PSM rates and OTs to a minimum. This suggests that RALP should be performed by high volume surgeons in order to optimize patient outcomes.

[Table: see text]
Outcomes of patients with clinical lymphadenopathy treated with radical prostatectomy.
Authors: Higuchi T. T. , Breau R. H. , Umbreit E. C. , Bergstralh E. J. , Rangel L. J. , Carlson R. , Karnes R. J.
Published: February 2017

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Background: Some patients with lymph node metastases experience prolonged survival following radical prostatectomy. The purpose of this study was to determine the outcome of patients with clinically suspicious lymph nodes on preoperative imaging who underwent radical prostatectomy and lymphadenectomy.

Methods: Patients with lymph node metastases diagnosed during radical prostatectomy from 1988-2003 were reviewed. Patients with preoperative CT or MRI images were included in the study. Radiology reports were reviewed to determine if patients had clinically suspicious lymphadenopathy (cN+). For all analyses, patients with cN+ were compared to those with clinically negative nodes (cN−).

Results: Preoperative imaging was available in 202 men with lymph node metastasis at the time of prostatectomy. Of these 17% (34/202) were cN+. None had pre-operative lymph node biopsy and none had abandoned prostatectomy. At a median follow-up of 11.1 years, PSA recurrence occurred in 50% (17/34) and 49% (82/186), local recurrence in 18% (6/34) and 13% (22/186) and systemic progression in 32% (11/34) and 24% (40/186) of patients with cN+ and cN-, respectively. On multivariate analysis, cN+ was not associated with increased risk of death (HR 1.66, p=0.1).

Conclusions: cN+ patients undergoing surgical therapy for prostate cancer may experience similar outcomes to cN− patients. The presence of clinically suspicious lymph nodes on preoperative imaging should not be an absolute contraindication for surgical therapy.

No significant financial relationships to disclose.
Radical prostatectomy (RP) in extreme ages: Clinical and pathologic evaluation of localized prostate cancer (PC).
Authors: Dettino A. A. , Fonseca F. P. , Zequi S. C. , Sacomani C. A. , Rinck J. , Formiga N. , Lopes A.
Published: February 2017

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Background: Radical prostatectomy (RP) is the treatment of choice for patients with localized prostate cancer (PC). Previously, surgery was applied to patients with good clinical condition and aged <=70 years. Lately, with a better understanding of surgical technique, many centers have been performing RP in patients older than 70.

Methods: The main objective of this cohort study is to evaluate clinical evolution according to localized PC submitted to RP in patients in extreme ages. We analysed age, PSA, ASA classification,pathological stages, Gleason scores, urinary continence, D'Amico risk classification (group 1:low; 2:intermediate; 3:high), biochemical recurrence and clinical progression. Descriptive analysis of the population was performed. Fisher's exact test or chi-square tests were used to evaluate association between clinicopathologic characteristics.Biochemical recurrence was defined by PSA more than 0.2 ng/mL post-RP.

Results: In 262 patients, mean age was 63.4 years (SD 12.4; range: 41 to 83). In D'Amico's group 1 there were 96 patients (37.2%) with<=50 year old, and group 2 had 162 patients (62.8%) with age >=70. The mean follow-up in group 1 was 55.9 months (SD 41.7) and group 2 was 53.6 (SD 41.4), p=0.6770. Biochemical relapse occurred in 21 patients (15.44%) in D'Amico risk group 1, 27 (36.99%) in group 2 and 29 (59.18%) in group 3 (p<0.001). There was no difference among all the pathological variables evaluated (p>0.05). Clinical progression occurred in 2 patients (1.47%) in D'Amico risk group 1, in 3 patients (4.11%) in group 2 and in 3 patients (6.11%) in group 3 (p=0.230). There was no significant difference in relation to time to biochemical recurrence, as well as biochemical relapse rate and progression of this disease among the groups. Younger patients (in group 1) recovered earlier from urinary incontinence, as well as most were continent in final follow-up.

Conclusions: Based on our results, the differences in younger or more aged patients with PC are not related to pathological variables, or rates of biochemical recurrence and clinical disease, but better preoperative clinical features and better recovery of urinary continence are seen in younger patients.

No significant financial relationships to disclose.
A phase II study of pomegranate extract for men with rising prostate-specific antigen following primary therapy.
Authors: Carducci M. A. , Paller C. J. , Wozniak P. , Sieber P. , Greengold R. , Stockton B. , Hertzman B. , Roper R. , Liker H. , Ye X. ,   The Pom Wonderful Working Group
Published: February 2017

11

Background: Pomegranate extract (POMx) demonstrates promising antitumor effects in prostate cancer (PCA). Prior published work reveals an increase in PSA doubling time (PSADT) in a single arm study of pomegranate juice (POM) in PCA patients (pts) with a rising PSA after local therapy. We sought to determine the effects of low (1 gram) or high (3 grams) daily POMx on PSADT in a similar but broader population of men seeking to defer androgen deprivation therapy.

Methods: Our multi-center, double bind phase II trial randomized men with rising PSA and without metastases to receive high or low dose POMx, stratified by baseline PSADT and Gleason score, and with no restrictions for PSADT and no upper limit PSA value. Men were treated until progression or for 18 months. PSA levels were obtained every 3 months. This study was designed to detect a 6 month increase in PSADT from baseline.

Results: 104 patients were enrolled and treated for up to 6 (92%), 12 (70%) and 18 months (36%). Median PSADT lengthened in the Intent to treat population (96% white, median age 74.5 years, median Gleason score 7) from baseline 11.9 (range 1.6-54.6) compared to 18.5 (2-1523) months after treatment (p<.001).There was no significant treatment difference on PSADT between the dose groups (p=.920). Declining PSA levels were observed in 13 pts (13%) during the study. No significant changes occurred in testosterone in either group. Although no clinically significant toxicities were seen, mild to moderate diarrhea was seen in 8 pts (7.7%).

Conclusions: POMx treatment significantly increased the PSADT by over 6 months in both treatment arms, with no effect on testosterone. This IND-conducted study confirms slowing of PSADT after treatment with POMx as was found with POM, yet in a PCA patient population with greater high risk progression features.

[Table: see text]