Concurrent versus sequential neoadjuvant chemoradiation therapy for esophageal and gastroesophageal junction adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 395-395
Author(s):  
Robert J. Torphy ◽  
Felix Ho ◽  
Chloe Friedman ◽  
Stephen Leong ◽  
Sachin Wani ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Academic Research ◽  
Standard Of Care ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
National Database ◽  
Curative Intent

395 Background: Neoadjuvant therapy is the standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma, with most patients receiving neoadjuvant chemoradiation (CRT). CRT can be delivered concurrently or sequentially after induction chemotherapy. The purpose of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) among patients who received concurrent versus sequential CRT in the National Cancer Database (NCDB). Methods: Patients who received neoadjuvant CRT and underwent curative intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006-2015 were included. Patients with clinical T4 or metastatic disease were excluded. Concurrent CRT was defined as radiation treatment starting within 6 weeks of chemotherapy start. Sequential CRT was defined as radiation treatment starting greater than 6 weeks after chemotherapy start. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups. Results: 12,460 patients met inclusion criteria. 11,880 (95%) patients received concurrent CRT and 580 (5%) patients received sequential CRT. Patients who received sequential CRT were significantly younger (mean age: 60.7 vs 62.2 years), had higher clinical nodal stage (N2-3: 14.7% vs 10.1%), and were more often treated at academic/research hospitals (67.1 vs 55.5) (all p≤0.001). pCR was achieved in 16.2% of patients who received sequential CRT and in 14.0% of patients who received concurrent CRT (p = 0.131). Following propensity weighting, OS was significantly improved among patients who received sequential versus concurrent CRT (HR 0.82; 95% CI 0.74-0.92; p < 0.001) with a median OS for the sequential cohort of 41.4 months versus 29.4 months for those who received concurrent CRT. Conclusions: In this retrospective study from a large national database of patients who received neoadjuvant CRT for esophageal and GEJ adenocarcinoma, sequential CRT is associated with a significant OS benefit. These results merit consideration of a well powered prospective multi-institutional randomized clinical trial to further evaluate this observed difference.

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

Pathologic complete response rate after neoadjuvant chemoradiation in patients with locally advanced rectal cancer affects survival in patients with prolonged radiation-surgery interval.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3608-3608
Author(s):  
Benjamin Mitchell Motz ◽  
Patrick Daniel Lorimer ◽  
Danielle Boselli ◽  
I'sis N Perry ◽  
Joshua S. Hill ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Residual Disease ◽  
Cox Model ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Database

3608 Background: The current standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation and R0 resection. An optimal radiation-surgery interval (RSI) has not been established. A small institutional dataset showed RSI > 49 days improved pathologic complete response (pCR) rates and disease free survival. However, in a national dataset, RSI greater than 60 days was associated with increased rates of positive margins and impaired overall survival. Because pCR is associated with improved survival, we used a national database to evaluate the relationship between RSI, pCR and survival after neoadjuvant therapy for rectal cancer. Methods: The NCDB was queried for cases 2004-2013 of AJCC stage II or III rectal adenocarcinoma that underwent neoadjuvant radiation followed by radical resection. We excluded patients with missing and outlier RSI. pCR was defined as ypT0N0M0. Chi-square, univariate, multivariable Cox model, and Cochran-Armitage time trend analyses were performed. Results: 23475 patients were identified. 7901 (33.7%) had RSI ≥60 days. pCR occurred in 1766 (11.3%) of the < 60 group and 1174 (14.9%) of the ≥60 group (p < 0.001). RSI ≥60 days has increased over time, from 22.1% in 2004 to 45.4% in 2013 (p < 0.001), as have pCR rates, from 8.4% in 2004 to 14.2% in 2013 (p < 0.001). Multivariable Cox model of the total cohort showed that RSI ≥60 days (HR = 1.11, 95% CI = 1.04-1.19) and residual disease (HR = 2.04, 95% CI = 1.78-2.34) were associated with increased mortality. Subgroup analysis of patients with pCR showed RSI ≥60 days was not associated with worse survival (HR = 1.07, 95% CI = 0.82-1.41). However, analysis of patients with residual disease showed RSI ≥60 days was associated with worse survival (HR = 1.13, 95% CI = 1.06-1.21). Conclusions: In a large national database, RSI ≥60 days worsens survival in patients who have residual disease after neoadjuvant therapy for locally advanced rectal cancer, while there is no difference in those with pCR. Emphasis should be placed on identifying patients who are unlikely to have pCR and to prioritize resection in these patients within 60 days of completion of chemoradiation.

Initial experience using percutaneous irreversible electroporation (IRE) in the treatment of locally advanced pancreatic adenocarcinoma (LAPC) with vascular encasement.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 291-291 ◽  
Author(s):  
Peter Joel Hosein ◽  
Katuska J Barbery ◽  
Evelyn Perez-Rojas ◽  
Tatiana Froud ◽  
Caio Max S. Rocha Lima ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Pancreatic Tumors ◽  
Percutaneous Ablation ◽  
Initial Experience

291 Background: Neoadjuvant chemoradiation therapy can convert some patients (pts) with borderline or unresectable LAPC to resectability. Persistent vascular encasement after neoadjuvant therapy usually contraindicates resection. IRE using the Nanoknife is more versatile than other ablative modalities in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of pts referred for IRE for LAPC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was safety. Secondary endpoints included survival and resection rate after the procedure. Results: Between 12/2010 and 8/2011, 8 pts with biopsy-proven PC underwent percutaneous ablation of pancreatic tumors using IRE. The median age was 53 years (range 51-72), the median time from diagnosis to IRE was 8.8 months (range 2.4-29.2) and the median tumor size treated was 2.8cm (range 2.5-6.8). All pts had prior chemotherapy and 7 had prior radiation, with a median of 2 lines of prior therapies (range 1-4). Two pts went to surgery after IRE after 4 and 5 months respectively. Both had margin-negative (R0) resections and one had a pathologic complete response. Both remain disease-free at 1 and 5 months after resection respectively. Among the 6 remaining pts, 2 were lost to follow-up, one had progressive disease after 3 months and 3 remain under follow-up to determine resectability. One of these 3 pts had a negative follow-up PET scan and surgery is planned. The procedure was complicated by a spontaneous pneumothorax during anesthesia in one patient, and another developed pancreatitis; both recovered completely. Conclusions: Percutaneous ablation of pancreatic tumors appears to be feasible and safe using the IRE modality. In our initial experience, 2 out of 8 pts with unresectable LAPC due to persistent vascular encasement after neoadjuvant therapy achieved a margin-negative resection after IRE. One had a pathological complete response. A prospective neoadjuvant trial in LAPC incorporating IRE is planned.

Assessment of macroscopic features in relation to tumor response to neoadjuvant chemoradiation therapy in rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 507-507
Author(s):  
Amanda Kathleen Arrington ◽  
Julio Garcia-Aguilar ◽  
Marjun Philip Duldulao ◽  
Carrie Luu ◽  
Julian Sanchez ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Oncologic Outcomes ◽  
Neoadjuvant Chemoradiation Therapy ◽  
Pathologic Features

507 Background: Several studies show locally advanced rectal cancer patients with clinical complete response (cCR) have comparable oncologic outcomes to pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (NCRT). Thus, total mesorectal excision (TME) could potentially be avoided. Our objective was to validate macroscopic features of cCR. Methods: 164 patients with stage II/III rectal cancer were previously enrolled in a phase II trial and treated by NCRT and TME. Tumor response in the surgical specimens was assessed according to AJCC guidelines. A pCR was defined as absence of viable tumor cells. Gross macroscopic features by the pathologist were tabulated and our cohort was applied to previously published cCR criteria. Results: 25.0% (n = 41) had pCR; 75.0% (n = 123) had non-pCR. Descriptors were condensed into 14 macroscopic features by combining terms and excluding those rarely mentioned. Several reports affirm that scarring signifies cCR, while others suggest that fibrosis, edema, ulceration and nonpalpable tumor to be consistent with cCR. In our study, scarring was found in 6.1% of patients, 16.7% of which had pCR. We found that hyperemia, scarring, flat, smooth, and tan-pink mucosa were significantly associated with pCR (p < 0.05). In contrast, a firm lesion and ulceration were frequently observed in patients with non-pCR (p = 0.02 and 0.05 respectively). Conclusions: Our study suggests that macroscopic pathologic features do correlate with pCR. Although cCR has comparable oncologic outcomes as pCR with favorable outcomes, standard criteria of cCR should first be defined so NCRT patients can safely be selected for observation only. [Table: see text]

Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS816-TPS816
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Jian Xiao ◽  
Dianke Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

Association of adjuvant chemotherapy with improved overall survival for patients with locally advanced rectal cancer (LARC) who achieve a pathologic complete response (pCR) to neoadjuvant chemoradiation (nCRT).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 716-716
Author(s):  
Danish Shahab ◽  
Emmanuel M. Gabriel ◽  
Kristopher Attwood ◽  
Valerie Francescutti ◽  
Wen Wee Ma ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Comorbidity Score ◽  
N Stage

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.

A phase II study of neoadjuvant therapy with cisplatin, docetaxel, panitumumab plus radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4062-4062 ◽  
Author(s):  
Carolyn E Reed ◽  
Paul A. Decker ◽  
Tracey E. Schefter ◽  
Bryan F Meyers ◽  
Mark K. Ferguson ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Distal Esophagus ◽  
Tumor Control ◽  
Induction Phase

4062 Background: Multiple clinical trials have incorporated preoperative chemotherapy and radiation (RT) in an attempt to improve local tumor control, distant disease failure and overall survival rates for locally advanced but resectable adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ). This multicenter, cooperative group study combined active chemotherapy agents cisplatin (C), docetaxel (D) and the targeted EGFR agent panitumumab (P) in the induction phase followed by concurrent chemotherapy (CDP) and radiation. Pathologic complete response (pCR), a surrogate for improved survival, was the primary endpoint. Methods: From 01/15/09 to 07/22/11, 70 patients (pts) with Siewert I or II adenocarcinomas and clinical stages T3N0M0, T2-3N1M0 or T2-3N0-1M1a (celiac LN ≤ 2 cm) were accrued. Patients received cisplatin (40 mg/m2), docetaxel (40 mg/m2) and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, 9 with RT (5040 cGy, 180 cGy/day x 28d) beginning week 5. The decision rule had a 90% power with a 0.10 significance level to detect a pCR rate of at least 35%. Secondary objectives included near-pathologic complete response (near-pCR), toxicity, and overall and disease-free survival rates. Results: Five pts were ineligible. Of the remaining 65 pts (59 M, 6 F; median age 61), 12 pts did not undergo surgery (5 progressed, 4 refused, 3 other). Of the 58 evaluable pts, the pCR rate was 32.8% (90% CI: 22.6% -42.9%) and near-pCR 22.4% (90% CI: 13.4%-31.4%). Total doses of C, D, and P were achieved in 76%, 80%, and 73%, respectively (n = 70). 66 pts (94%) received the total RT dose. Sixteen pts (23%) had a grade 4+ non-heme adverse event possibly related to treatment. Venous thrombosis (5 pts) was most common. Conclusions: The CDP regimen in the neoadjuvant setting in patients with esophageal adenocarcinomas is active (pCR + near-pCR = 55.2%) and feasible. The toxicity though tolerable is substantial.

Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: A National Cancer Database (NCDB) analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 616-616 ◽  
Author(s):  
Shaakir Hasan ◽  
Paul Renz ◽  
Rodney E Wegner ◽  
Gene Grant Finley ◽  
Moses S. Raj ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Microsatellite Instability ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database

616 Background: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. We therefore utilized the national cancer database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. Methods: We analyzed 5,086 patients between 2010-2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4,450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional hazard ratios were used for survival. Results: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher grade tumors (P < 0.05). The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (OR = 0.65, 95% CI 0.43 – 0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared to 73% without it (< 0.001). Conclusions: Microsatellite instability was independently associated with a reduction in pathologic complete response for locally advanced rectal cancer following neoadjuvant chemoradiation in this NCDB-based analysis.[Table: see text]

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