PS02.162: THREE-YEAR OVERALL SURVIVAL UPDATE FROM PHASE II STUDY OF CHEMOSELECTION WITH DCF AND SUBSEQUENT CONVERSION SURGERY FOR LOCALLY ADVANCED UNRESECTABLE ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 167-168
Author(s):  
Tomoya Yokota ◽  
Ken Kato ◽  
Yasuo Hamamoto ◽  
Yasuhiro Tsubosa ◽  
Hirofumi Ogawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
R0 Resection ◽  
Conversion Surgery ◽  
Significant Difference ◽  
Subsequent Conversion ◽  
The Impact

Abstract Background A multicenter phase II trial revealed that docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (IC) and subsequent conversion surgery (CS) was tolerable and effective in patients with locally advanced unresectable esophageal cancer (LAUEC) (Br J Cancer 2016;115:1328–1334). Here, we report updated 3-year analyses to further characterize the impact of DCF-IC followed by CS. Methods Esophageal cancer patients with clinical T4 disease and/or unresectable supraclavicular lymph node metastasis were eligible. The treatment starts with 3 cycles of DCF-IC, followed by CS if resectable, or by concurrent radiation plus chemotherapy with 5-fluorouracil and cisplatin (CF-RT) if not resectable. This updated analysis represents 3-year overall survival (OS), 3-year progression free survival (PFS), location of relapse, and subsequent therapy. Results As of October 11, 2017, 25 patients were dead. The median follow-up period in patients surviving without death was 39.3 months (95%CI: 38.7 - 41.7months). The estimated 1-year OS was 66.7% and lower limit of 95% confidence interval was 54.6%. The estimated 3-year OS was 46.6% (95% CI; 34.2 - 63.5%). The OS for patients who underwent R0 resection (n = 19) was significantly longer than those who did not undergo R0 resection (3-year OS: 71.4% vs. 30.1%). The estimated 1-year PFS was 50.6% (95%CI: 38.1 - 67.3%) and the estimated 3-year PFS was 39.6% (95%CI: 27.7 - 56.6%). The PFS for patients who underwent R0 resection (n = 19) was significantly longer than those who did not undergo R0 resection (3-year PFS: 61.3% vs. 25%). The recurrence or progression in primary site was observed in 31% of non R0 group. There was no significant difference in the rates of distant metastasis between the two groups (non R0 group vs. R0 group; 21% vs. 16%). The subsequent therapy after protocol therapy included chemotherapy (n = 18), radiotherapy (n = 11), and surgery (n = 5). Conclusion This longer follow up of DCF-IC followed by CS strategy for patients with LAUEC revealed promising OS and PFS. Based on this phase 2 trial, JCOG1510, a prospective randomized controlled trial to compare chemoselection with DCF-IC followed by CS versus CF-RT as a standard treatment is in preparation for LAUEC. Disclosure All authors have declared no conflicts of interest.

scholarly journals Long-term outcomes of omentum-preserving versus resecting gastrectomy for locally advanced gastric cancer with propensity score analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yusuke Sakimura ◽  
Noriyuki Inaki ◽  
Toshikatsu Tsuji ◽  
Shinichi Kadoya ◽  
Hiroyuki Bando
Keyword(s):  
Gastric Cancer ◽  
Propensity Score ◽  
Advanced Gastric Cancer ◽  
Missing Values ◽  
Propensity Score Analysis ◽  
Locally Advanced ◽  
R0 Resection ◽  
Significant Difference ◽  
First Recurrence ◽  
The Impact

Abstract Omentectomy is conducted for advanced gastric cancer (AGC) patients as radical surgery without an adequate discussion of the effect. This study was conducted to reveal the impact of omentum-preserving gastrectomy on postoperative outcomes. AGC patients with cT3 and 4 disease who underwent total or distal gastrectomy with R0 resection were identified retrospectively. They were divided into the omentum-preserved group (OPG) and the omentum-resected group (ORG) and matched with propensity score matching with multiple imputation for missing values. Three-year overall survival (OS) and 3-year relapse-free survival (RFS) were compared, and the first recurrence site and complications were analysed. The numbers of eligible patients were 94 in the OPG and 144 in the ORG, and after matching, the number was 73 in each group. No significant difference was found in the 3-year OS rate (OPG: 78.9 vs. ORG: 78.9, P = 0.54) or the 3-year RFS rate (OPG: 77.8 vs. ORG: 68.2, P = 0.24). The proportions of peritoneal carcinomatosis and peritoneal dissemination as the first recurrence site and the rate and severity of complications were similar in the two groups. Omentectomy is not required for radical gastrectomy for AGC.

Hemangiogenic response after pre-operative COX2 inhibition predicts recurrence in esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15077-15077
Author(s):  
D. Jin ◽  
J. L. Port ◽  
P. Lee ◽  
L. Zhang ◽  
C. A. Ferrara ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Tumor Recurrence ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Angiogenic Activity ◽  
Angiogenic Therapy ◽  
Men 2 ◽  
Promising Tool ◽  
Significant Difference ◽  
The Impact

15077 Background: Growth of esophageal cancer involves a proliferative hemangiogenic component. Biomarkers that predict this propensity in esophageal cancer and the impact of anti-angiogenic strategy on their levels as well as clinical response remain unknown. Methods: A multimodular approach was devised to assess hemangiogenic parameters in a cohort of chemotherapy naïve patients with locally advanced (T2-T3N0, T1-T3N1M0M1a) esophageal cancer pre- and 4 days post-celecoxib neoadjuvant treatment. Patients went on to receive neoadjuvant therapy with celecoxib, paclitaxel and carboplatin for 3 cycles, followed by surgical resection. This bioassay panel consists of 5 components: i) HUVEC-based angiogenic scale for functional plasma angiogenic activity, ii) flow cytometry to quantify CD133+VEGFR2+ circulating endothelial progenitors (CEPs), iii) hematopoietic colony-forming assay to quantify circulating hematopoietic progenitors (CHPs), iv) plasma SDF-1 level, and v) platelet VEGF-A level. Results: The cohort consists of 8 consecutive patients (6 men, 2 women) with median age of 58. After 18 months of followup, 6 patients remained alive and without evidence of recurrence, while 2 had tumor recurrence and metastasis. Analysis of the positive responders (pre-celecoxib baseline versus 4 days post treatment) revealed a global suppression of hemangiogenic parameters with reduction of the functional HUVEC-based angiogenic scale (mean score of 3.3 versus 1.8; p<0.05), 2.2-fold decrease in CEPs (p<0.05), and 3-fold decrease in CHPs (p<0.05). This trend also correlated with decreased plasma SDF-1 and platelet VEGF-A levels . However, in the 2 cases of tumor recurrence, the initial hemangiogenic response was blunted with no significant difference in all parameters tested during the celecoxib monotherapy period. Conclusion: Esophageal cancer development involved a hemangiogenic switch toward increased CEPs, CHPs, and functional plasma pro-angiogenic activity. COX2 inhibition with celecoxib normalized the hemangiogenic profile. Collective assessment of hemangiogenic biomarkers during neoadjuvant setting may be a promising tool in predicting clinical outcomes, recurrence, and for validating impact of anti-angiogenic therapy on esophageal cancer. No significant financial relationships to disclose.

Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14714-e14714
Author(s):  
Olugbenga Olanrele Olowokure ◽  
Ivan Dario Bedoya ◽  
Michelle Lynn Mierzwa ◽  
Maria Patricia Torregroza ◽  
Alok kumar Dwivedi ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Categorical Variables ◽  
Rank Test ◽  
Nccn Guidelines ◽  
Prior Therapy ◽  
Significant Difference ◽  
Ecog Ps ◽  
The Impact

e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m2 and nab-P=100mg/m2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline <1 (R<1-12,861), CA19-9 decrease > 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.

Long-term cardiopulmonary mortality after radiation for locally advanced esophageal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Abigail Berman Milby ◽  
Andrzej Pawel Wojcieszynski ◽  
Smith Apisarnthanarax ◽  
James M. Metz ◽  
John Peter Plastaras
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Carcinoma ◽  
Background Radiation ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Rank Test ◽  
Trimodality Therapy ◽  
Significant Difference

99 Background: Radiation (RT) is considered an integral component of trimodality therapy for locally-advanced esophageal carcinoma to improve locoregional control and potentially survival. However, the long-term risk of cardiopulmonary mortality (CPM) is not well-understood in this population. Methods: Patients age 20-85 with esophageal carcinoma with T3, T4 or node positive (N+) disease who underwent esophagectomy were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988-2006. Patients with metastatic disease or <6 mo follow up were excluded. CPM was calculated for patients receiving vs not receiving RT and compared by the Kaplan-Meier method. The log-rank test was used for univariate associations and Cox proportional hazards model was used for multivariate analysis (MVA). Results: A total of 4,079 patients met the defined selection criteria of whom 2,408 were treated with RT, and 1,671 were not. Median age was 62.2 yrs (22-84) and follow-up was 22 mos (6-248). There was no significant difference in CPM in patients who received RT versus those who did not (p=0.8). At 10 yr, the majority of deaths were from esophageal cancer (73 with vs 78% without RT) compared to CPM (13.7 with vs 11.6% without RT). On univariate analysis ( table ), age <60, diagnosis era, and histology were significant independent predictors of CPM. On MVA, age <60 (HR 0.36) and diagnosis era (0.63 for 1994-2000 and 0.55 for 2000-2006) remained statistically significant for CPM. Conclusions: RT for esophageal cancer is not associated with an increased long-term risk of CPM in the overall population. Older age and earlier diagnosis era predict for CPM. Although survival in esophageal cancer is dominated by cancer deaths, advances in RT are still needed to prevent excess treatment-related mortality. [Table: see text]

Impact of lung and heart dose on survival after radiotherapy for esophageal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Patrick Oh ◽  
Minsi Zhang ◽  
Paul Brady ◽  
Ellen Yorke ◽  
Elizabeth Won ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Independent Predictor ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Lung Cancer ◽  
Lung Dose ◽  
Cardiac Dose ◽  
The Impact

3 Background: Chemoradiation is an essential tool in treatment of localized esophageal cancer. Recent data indicates that cardiac dose is an independent predictor of survival after chemoradiation for locally advanced lung cancer. However, the impact of normal tissue dose in esophageal cancer has not been well characterized. We investigated cardiac and pulmonary dose-volume histogram (DVH) metrics as potential predictors of overall survival (OS) after chemoradiation for esophageal cancer. Methods: We reviewed 453 consecutive patients with stage I-III esophageal cancer treated with definitive or preoperative chemoradiation (median dose 50.4 Gy in 28 fractions) between 2007 and 2015 at our center. Most (n = 442) received intensity-modulated radiation therapy. Radiation plans were reviewed and multiple DVH metrics for heart (max and mean dose, V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy) and lung (mean dose, V5Gy, and V20Gy) were extracted for analysis. Other clinical covariates (surgery, performance status, stage, and histology) were recorded. Cox univariate (UVA) and multivariate (MVA) regression was used to analyze the association of these factors with overall survival. Results: Median follow-up for surviving patients was 28.4 months. On UVA, older age, lower performance status, Stage III disease, lack of surgery, heart V40Gy, lung V5Gy, lung V20Gy, and lung mean dose were significantly associated with decreased survival. On MVA, surgery (p = 0.008), stage III disease (p < 0.0002) and lung V20Gy (p = 0.0389) remained significant, while heart V40Gy did not (p = 0.211). Patients with lung V20Gy< 20% had a median survival of 44.0 months, compared to 24.0 months for patients with lung V20Gy≥20%. Conclusions: This comprehensive dosimetric analysis of heart and lung dose in a large cohort of esophageal cancer patients suggests that lung dose is a significant independent predictor of survival. Cardiac dose was not independently predictive after adjusting for lung dose and other clinical factors. This data suggests that esophageal cancer outcomes may be improved by minimizing lung dose, particularly the volume receiving 20Gy or more, and provides further rationale for pursuing new techniques to reduce lung dose, such as proton therapy.

Neoadjuvant therapy for localized gastrointestinal stromal tumors (GISTs): A propensity score weighted analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Kathryn E. Marqueen ◽  
Erin Moshier ◽  
Michael Buckstein ◽  
Celina Ang
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Propensity Score ◽  
Survival Benefit ◽  
Postoperative Mortality ◽  
Phase Iii ◽  
R0 Resection ◽  
Treatment Groups ◽  
Significant Difference ◽  
The Impact

e23516 Background: Retrospective and single-arm prospective studies have reported clinical benefit associated with receipt of neoadjuvant imatinib for GISTs. In the absence of randomized phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival, in comparison to upfront resection, remains unknown. Methods: We identified N = 14,402 patients with complete clinical, demographic, treatment and pathologic data within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel, and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalance among treatment groups, with the propensity score estimated by logistic regression. The effect of NAT on overall survival was estimated with a weighted time-dependent Cox proportional hazards model. A weighted logistic regression was used to estimate the effect of NAT on 90-day postoperative mortality and R0 resection. Results: 759 (5.3%) patients received NAT followed by resection, compared to 13,643 (94.7%) who underwent upfront resection. Median length of NAT was 6.3 months. 53% of NAT patients were male vs. 49% of UR patients, 68% vs. 66% had primary gastric GIST, and 73% vs 49% were high risk. Patients receiving NAT had larger tumors (p < 0.001) and higher mitotic index (p = 0.003). There was a significant survival benefit associated with receipt of NAT (table). 90-day postoperative mortality rate was 3/759 (0.4%) among NAT patients vs. 307/13,643 (2.3%) UR patients. Receipt of NAT was significantly associated with lower odds of 90-day postoperative mortality (table). Of the 13,562 patients with information on margin status, the R0 resection rate was 635/716 (88.7%) for the neoadjuvant group vs. 11,823/12,846 (92%), with no significant difference between treatment groups (table). Conclusions: After adjustment for imbalance in prognostic and demographic factors, this analysis demonstrates that receipt of NAT for localized GIST is associated with a modest overall survival benefit. Although NAT patients had higher risk features, NAT was associated with a lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection. [Table: see text]

Effect of Margin Status on Survival After Resection of Hilar Cholangiocarcinoma in the Modern Era of Adjuvant Therapies

2020 ◽  
pp. 000313482097340
Author(s):  
Michael D. Watson ◽  
Maria R. Baimas-George ◽  
Michael J. Passeri ◽  
Jesse K. Sulzer ◽  
Erin H. Baker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hilar Cholangiocarcinoma ◽  
Demographic Data ◽  
Locally Advanced ◽  
Resection Margins ◽  
R0 Resection ◽  
Complication Rates ◽  
Curative Intent ◽  
Adjuvant Therapies

Introduction Studies have shown that for patients with hilar cholangiocarcinoma (HC), survival is associated with negative resection margins (R0). This requires increasingly proximal resection, putting patients at higher risk for complications, which may delay chemotherapy. For patients with microscopically positive resection margins (R1), the use of modern adjuvant therapies may offset the effect of R1 resection. Methods Patients at our institution with HC undergoing curative-intent resection between January 2008 and July 2019 were identified by retrospective record review. Demographic data, operative details, tumor characteristics, postoperative outcomes, recurrence, survival, and follow-up were recorded. Patients with R0 margin were compared to those with R1 margin. Patients with R2 resection were excluded. Results Seventy-five patients underwent attempted resection with 34 (45.3%) cases aborted due to metastatic disease or locally advanced disease. Forty-one (54.7%) patients underwent curative-intent resection with R1 rate of 43.9%. Both groups had similar rates of adjuvant therapy (56.5% vs. 61.1%, P = .7672). Complication rates and 30 mortality were similar between groups (all P > .05). Both groups had similar median recurrence-free survival (R0 29.2 months vs. R1 27.8 months, P = .540) and median overall survival (R0 31.2 months vs. R1 38.8 months, P = .736) with similar median follow-up time (R0 29.9 months vs. R1 28.5 months, P = .8864). Conclusions At our institution, patients undergoing hepatic resection for HC with R1 margins have similar recurrence-free and overall survival to those with R0 margins. Complications and short-term mortality were similar. This may indicate that with use of modern adjuvant therapies obtaining an R0 resection is not an absolute mandate.

Triple induction chemotherapy and chemoradiotherapy in locally advanced esophageal cancer: Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4568-4568
Author(s):  
W. M. Eisterer ◽  
A. De Vries ◽  
B. Spechtenhauser ◽  
D. Kendler ◽  
A. Königsrainer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
R0 Resection ◽  
Ecog Performance Status ◽  
Blurred Vision ◽  
Hyperfractionated Radiotherapy

4568 Background: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but 5-year survival rates rarely exceed 20%. Neoadjuvant chemoradiotherapy (CRT) may lead to downstaging of the tumor and thus improve the possibility of complete oncologic resection. Docetaxel (Dx) showed considerable activity in combination with hyperfractionated radiotherapy and only moderate toxicity. We evaluated a triple neoadjuvant regime including Dx in patients with locally advanced esophageal adenocarcinoma (AC) or squamos cell carcinoma (SCC). Methods: 24 patients (pts) with AC (n=8) or SCC (n=16) medically fit, no prior therapy, ECOG-performance status = 2 were included. Pts received 2 cycles of cisplatin (Cis) 15mg/ms2 d1–5, 5-fluorouracil (5-FU) 750mg/m2 continuous infusion (CI) d1–5, and Dx 75mg/m2 d1 repeated every 29 days followed by radiotherapy (RT) 39.6 Gy total dose (daily fraction 1.8Gy) concomitant to Dx 15mg/m2 on days 1, 8, 15, 22 and 5-FU 300mg/m2 CI on the days of RT followed by resection or definitive RT up to 59.6 Gy in case of inoperability. Results: See table . Grade 3/4 toxicity (n/%): neutropenia 10/43%, diarrhea 4/18%, alopecia 2/9%; deep vein thrombosis 1/5%, blurred vision 1/5%, fever 1/5%, pulmonary embolus 1/5%, arterial hypertension 1/5%. 1 pt died 39 days post resection due to fatal anastomical bleeding. 6/16 operated pts (37%) showed morbidity (anastomical stenosis/insufficiency, fistula, nervus recurrens palsy). 4/22 pts (18%) died 7- 25 months after therapy due to metastatic disease. At a median follow-up of 12 months 18 pts (82%) are alive, median survival has not been reached yet. Conclusions: Triple induction CT and CRT with Dx, Cis, and 5-FU is safe, feasible, and effective with CPR in 31%, downstaging in 81% and R0-resection in 100% of pts. Main toxicities are neutropenia (43%) and postoperative morbidity (37%). A follow-up phase II trial of triple induction therapy in combination with an EGFR-directed antibody is planned. [Table: see text] No significant financial relationships to disclose.

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