Retrospective analysis of neoadjuvant chemoradiotherapy for esophageal cancer: The Knight Cancer Institute experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 126-126
Author(s):  
Faisal A Siddiqui ◽  
James P. Dolan ◽  
John G. Hunter ◽  
Miriam A. Douthit ◽  
Lisa M. Bloker ◽  
...  

126 Background: Neoadjuvant chemoradiotherapy (NAT) followed by esophagectomy has been established as standard of care for early stage (II – III), resectable esophageal cancer (EC). Patients (pts) treated with NAT are more likely to be downstaged and have a complete (R0) resection. Additionally, pts with aggressive disease are more likely to progress during NAT and, consequently, avoid unnecessary surgery. The aim of the current report was to analyze the outcomes of trimodality therapy at the Knight Cancer Institute. Methods: A retrospective study of 124 pts who underwent NAT followed by esophagectomy for EC from 1999-2010 at our institution was performed. All pts were initially staged by imaging (EUS, CT and/or PET imaging) prior to commencing treatment. After esophagectomy, pathological staging was compared to initial staging to determine the effect of NAT. Results: There were 25 women and 99 men. Initial staging is shown in the table below. Patients received cisplatin, oxaliplatin or carboplatin with 5-FU plus concurrent radiotherapy (RT). RT total dose of 45 Gy to the tumor and regional nodes was given in 1.8 Gy daily fractions, followed by a boost to the tumor for final dose 50.4-54 Gy. 27 (21.8%) of the pts had a pathologic complete response. Additionally, 54 (43.6%) pts were downstaged by chemoradiation. Of the pts that had complete remission or were downstaged, pre-treatment clinical stage was Stage II (22 pts), Stage III (55 pts), and Stage IVa (4 pts). Conclusions: NAT was effective in complete remission or downstaging of two-thirds (81) pts, including 4 pts that were initially unresectable (Stage IVa) and successfully underwent subsequent esophagectomy. As has been shown previously, NAT is effective for downstaging prior to esophagectomy making it more likely that pts will undergo R0 resection. This study also demonstrated that some pts with clinically unresectable tumors could undergo successful esophagectomy after NAT. [Table: see text]

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7561-7561 ◽  
Author(s):  
L. M. Krug ◽  
H. Pass ◽  
V. W. Rusch ◽  
H. L. Kindler ◽  
D. Sugarbaker ◽  
...  

7561 Background: The optimal management for fit patients with early stage MPM remains controversial. One approach involves neoadjuvant chemotherapy followed by EPP and hemithoracic RT and prior trials using gemcitabine and cisplatin have been reported (Weder JCO 2004, Flores JTO 2006). We administered PC, followed by EPP and RT to further assess feasibility and survival of trimodality therapy in a larger, multicenter study. Methods: Eligibility criteria: Stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 >35%) and PS 0–1. Pts received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Pts without disease progression underwent EPP followed by RT (54 Gy). The primary endpoint was pathologic complete response (pCR) rate. Enrollment was completed in March, 2006. Results: 77 patients were enrolled and 72 are evaluable. Median age 63.5 (range 34–78), M:F = 51:21, Clinical stage I:II:III:IV = 5:31:33:1, epithelial:nonepithelial = 58:15, ECOG PS 0:1:2 = 28:42:2. 83% of patients completed all four cycles of PC. Grade 3/4 events related to chemotherapy included: neutropenia (4%), febrile neutropenia (3%), nausea (1%), vomiting (3%), pneumonia (6%), pulmonary embolism (1%), and chest pain (3%). Of 73 pts assessed for radiologic response, 3 CRs, 21 PRs, 36 SDs, 3 PDs, and 10 were unevaluable; (RR= 33% [95% CI, 0.22, 0.45]). Of 54 pts who underwent surgery, EPP completion rate was 87% (47/54); that is 47/77 (61%) by ITT. Pathologic stage I:II:III:IV:NE = 4:12:24:3:11. One pCR was confirmed. 35/39 completed RT. Preliminary TTP =13.1 mo (95% CI=9.6, 15.9; 48% censored) and median survival=16.6 mo (95% CI=13.9, 19.3; 55% censored;1-yr survival = 68%). Conclusions: This multicenter trial testing trimodality therapy in MPM showed that it is feasible with a high rate of chemotherapy delivery. One pCR was observed. Preliminary survival is below that reported by single institutions for patients undergoing EPP but with a high censorship rate at this early time point. Further analyses are necessary to identify a cohort of patients most likely to benefit. This study was sponsored by Eli Lilly & Company. No significant financial relationships to disclose.


2018 ◽  
Vol 41 (2) ◽  
pp. 148-154
Author(s):  
Kodai Takahashi ◽  
Hideto Ito ◽  
Masatoshi Hashimoto ◽  
Kazuhito Mita ◽  
Hideki Asakawa ◽  
...  

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 548-548
Author(s):  
I. Marrodan ◽  
E. Azkona ◽  
S. Carrera ◽  
U. Aresti ◽  
B. Calvo ◽  
...  

548 Background: Locally advanced rectal carcinoma is associated with high rate of abdomino-perineal amputation. We analyzed a cohort of patients (pts) diagnosed of locally advanced rectal cancer, treated with neoadjuvant chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (XELOX) followed by four cycles of adjuvant XELOX after surgery. Methods: Patients with locally advanced rectal cancer (T3-T4 and/or N+) were treated with oxaliplatin (50mg/m2 day 1, 8, 22 and 29) and capecitabine (1,650mg/m2 on days 1 to 14 and 22 to 35) combined with pelvic radiotherapy (180 cGy/day; 45Gy in 25 fractions). Surgery was scheduled 4 to 6 weeks after completion QT-RT. Four cycles of adjuvant XELOX were administered (capecitabine 2,000mg/m2 on days 1 to 14 and oxaliplatin 130mg/m2 on day 1) every 3 weeks. Main end points assessed were: rate of sphincter preservation, pathologic complete response (pCR) rate and the feasibility of postoperative chemotherapy. Results: From March 2007 to April 2010, 98 pts with locally advanced rectal cancer were included. M/F: 66/32; ECOG 0/1: 19/79; median age: 64 (38-81); upper/mid/distal rectum: 13/50/35; clinical stage: cT3/N- 9, cT2-T3/N+ 72, cT4/N- 4, cT4/N+ 13. Full dose of preoperative QT-RT was administered in 93 pts (95%). Main toxicities were grade 1/2 neurotoxicity (56/4) and grade 2/3 diarrhea (23/10). After treatment 96 pts underwent surgery. Sphincter preservation, R0 resections and pCR were achieved in 57, 93 pts and 17 (18%) patients, respectively, and 65 pts (66%) received all 4 cycles of adjuvant XELOX. Grade 3/4 toxicities included diarrhea 3/0, vomiting 2/0, neurotoxicity 5/0, hand-foot syndrome 1/0, neutropenia 4/0 and thrombopenia 0/4. 3-year progression-free and overall survival were 66% and 72%, respectively. No toxic deaths were reported. Downstaging in T/N stage was achieved in 53/71 pts (55/74%) respectively. Conclusions: Combination preoperative QT-RT with capecitabine and oxaliplatin is a well tolerated regimen and achieves encouraging rates of pCR, R0 resection, sphincter preservation and tumor downstaging in patients with locally advanced rectal cancer. No significant financial relationships to disclose.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 41-41
Author(s):  
Takahiro Heishi ◽  
Hirotaka Ishida ◽  
Yu Onodera ◽  
Ken Ito ◽  
Takuro Konno ◽  
...  

Abstract Background In 1996 Akaishi et al. reported the first thoracoscopic esophagectomy (TE) in Japan. Total 650 TEs for esophageal cancer have been performed in our institute by October 2016. There are many reports about the short-term outcomes of TE compared with open esophagectomy (OE), but the long-term outcomes of TE have been under debate. The aim of this study is to investigate the survival benefits of TE and to compare with OE and long-term outcomes which other previous reports showed. Methods A total 750 cases who underwent TE (N = 650) or OE (N = 100) between 1994 and 2015 in our hospital were included in this study. They were divided into four groups; surgery without any preoperative treatments (group S, N = 414), surgery after neoadjuvant chemotherapy (Group NAC, clinical stage II or III, N = 116), surgery after neoadjuvant chemoradiotherapy (Group NACRT, clinical stage II or III, N = 68) and salvage surgery after definitive chemoradiotherapy (Group SALV, N = 76). In group S, 100 patients received OE and 314 received TE. The other 3 groups (Group NAC, NACRT and SALV) received only TE. 3-year, 5-year overall survival (OS) and progression-free survival (PFS) rates for each group were analyzed and compared. Results In group S, the 5-year OS rate of TE was 63.4% and that of OE was 68.3%, there was no significant difference (Log-Rank test P = 0.41). Stage-specific OS rates of TE and OE were also compared and there was no significant difference. PFS rates of OE and TE showed the same tendency of OS. 5-year OS rate of group NAC was 63.5%. 3-year OS of group NACRT was 61.4%. 3-year and 5-year OS of group SALV were 41.4% and 34.0%. These results were the same or better than what the previous reports showed. Conclusion The long-term outcomes of TE were almost same as those of OE. The TE procedure resulted in similar or potentially better long-term outcomes in case of NAC, NACRT and SALV. It's acceptable to say thoracoscopic approach is the standard of esophagectomy. Disclosure All authors have declared no conflicts of interest.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 390-390 ◽  
Author(s):  
Carmen Joseph Allegra ◽  
Greg Yothers ◽  
Michael J O'Connell ◽  
Mark S. Roh ◽  
Robert W. Beart ◽  
...  

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p<0.0001). Analysis of the primary endpoint showed 3-yr rates of L-R tumor control ranged from 87.4%-88.2%. 3-yr rates of L-R recurrence among pts who underwent R0 resection ranged from 2-4 % for stage II pts, and from 4-11% for stage III pts. 16% of stage II and 26% of stage III pts developed distant metastases by 5 yrs. From 84% to 97% of pts received >80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 100-100 ◽  
Author(s):  
Yusuke Sasaki ◽  
Ken Kato ◽  
Koh Furuta ◽  
Naoki Takahashi ◽  
Hirokazu Shoji ◽  
...  

100 Background: Serum α-1-acid glycoprotein (AAG) level was an independent predictor of response and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel chemotherapy. However, it has not been determined whether AAG is associated with the outcomes of esophageal cancer patients who have been treated with a combination of docetaxel, cisplatin and 5-fluorouracil (DCF) as neoadjuvant therapy. Methods: This retrospective study included a cohort of 39 patients with clinical stage II/III esophageal cancer, based on the International Union Against Cancer TNM classification system 7th edition, who were treated with neoadjuvant DCF followed by surgery. DCF consisted of docetaxel (70mg/m2) and cisplatin (70mg/m2) on day 1, and continuous infusion of 5-fluorouracil (750mg/m2/day) on days 1-5, with this regimen repeated every 3 weeks up to three cycles. Patients were divided into groups by median value of baseline AAG levels. Patient characteristics, preoperative clinical stage, chemotherapy effect, and survival were compared between the high and low AAG groups. Results: The clinical stage IIA, IIB, IIIA, IIIB and IIIC were 4, 4, 14, 17 and 0, respectively. The completion rate of three cycles of chemotherapy was 76.9% (30/39). All patients underwent surgery and the R0 resection rate was 97.4% (38/39). The best overall response rate of DCF was 48.7% with a pathological complete response of 5.1%. The 2-year progression-free survival and overall survival (OS) rates were 60.5% and 76.9%, respectively. The median serum AAG was 95 g/L, ranging from 57 to 228 g/L. A trend of lower response rate (35.0% vs. 57.9%; P = 0.20) and shorter OS (median not reached; hazard ratio [HR] 2.08; P = 0.24) was observed in patients with a high AAG level (AAG > 95 g/L) compared with a low AAG level (AAG ≦ 95 g/L). Multivariate analysis showed an AAG level hazard ratio of 1.60 (P = 0.59) for OS. Conclusions: There was a trend toward improved response and survival with low serum AAG level, for patients with esophageal cancer who received neoadjuvant DCF chemotherapy.


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 154-154
Author(s):  
Shoji Natsugoe ◽  
Ken Sasaki ◽  
Yasuto Uchikado ◽  
Hiroshi Okumura ◽  
Itaru Omoto ◽  
...  

Abstract Background In Japan, preoperative chemotherapy with cisplatin plus 5-fluorouracil (CF) followed by radical surgery has been accepted as the standard therapeutic approach for resectable esophageal squamous cell carcinoma (ESCC) result from a Japan Clinical Oncology Group randomized control trial. Whether preoperative chemoradiotherapy (CRT) followed by radical surgery is effective for Japanese ESCC patients has yet to be established. Some trials have reported usefulness of CF plus docetaxel therapy (DCF) for advanced or metastatic ESCC. Here, we have launched a randomized controlled trial to compare preoperative DCF versus DCF plus radiotherapy (DCF-RT) followed by surgery in locally advanced esophageal cancer. Methods Patients with clinical stage II/III (Japanese Classification of Esophageal Cancer, 11th Edition) are randomized to 2 groups. Patients in DCF group receive 2 courses of preoperative DCF (docetaxel, 60 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; 5-FU, 700 mg/m2/day, days 1–5) repeated every 3 weeks. Patients in DCF-RT group receive preoperative chemoradiotherapy (40Gy/20fr) with 2 courses of DCF (docetaxel, 30 mg/m2/day, day 1, 15; cisplatin, 7 mg/m2/day and 5-FU, 350 mg/m2/day, days 1–5, days 8–12, days 15–19, days 22–26). The primary endpoint is overall survival and the secondary endpoints include adverse events, response rate and pathologic complete response rate. Results Twenty-seven patients were assigned to the DCF group and 26 patients to the DCF-RT group. Grade 3/4 leukopenia and febrile neutropenia occurred 37% and 19% in the DCF group, 35% and 12% in the DCF-RT group. The clinical response rates were 16.0% and 64.0% in the DCF and DCF-RT group. Twenty patients and 23 patients underwent surgery in the DCF and DCF-RT group, and the R0 resection rate was 80.0% and 91.3%. With regard to the surgical complications, the incidence of anastomotic leakage was significantly higher in the DCF-RT group compared with the DCF group. The histological effects of DCF-RT were significantly higher than those of DCF. Two-year survival rate was 46% in the DCF group and 70% in the DCF-RT group. Conclusion The DCF and DCF-RT were found to be feasible as neoadjuvant therapy, and DCF-RT demonstrated higher efficacy than DCF in clinical stage II/III esophageal cancer patients. Disclosure All authors have declared no conflicts of interest.


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