The value of lymphadenectomy in esophageal cancer after neoadjuvant chemoradiation.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 79-79
Author(s):  
Basem Azab ◽  
Francisco Igor Macedo ◽  
Omar Picado ◽  
Caroline Ripat ◽  
Dido Franceschi ◽  
...  

79 Background: There are conflicting reports on the value of the extent of post neoadjuvant chemoradiation (NCRT) lymphadenectomy (LND) in locally advanced esophageal adenocarcinoma (E-ADC) and squamous cell carcinoma (E-SCC). We sought to study the impact of LND variables [positive and total lymph node (LN) number and LN ratio (LNR)] on oncological outcomes in these patients. Methods: The National Cancer Data Base 2004-2014 was queried for patients with NCRT followed by esophagectomy. The median examined LN number was used to divide the patients into a higher (> 12) and lower (≤ 12) LND groups. The primary outcome was overall survival (OS) and secondary outcomes were 30- and 90-day postoperative mortality. Results: A total 4708 patients were included. The median of positive, negative LN, and LNR were and (0, 11, 0%). The median and 5-year OS for higher LND group were higher than the lower LND group (39 vs. 32 months, 38% vs. 34%), p < 0.0001. OS was not significantly different among E-SCC subset or among those who achieved pathological complete response (pCR). The higher LND group had better 30- and 90-day postoperative mortality rates (61/2335 = 2.6%, 141/2308 = 6.1%) than lower LND group (86/2262 = 3.8%, 184/2251 = 8.2%), p = 0.01 and 0.001, respectively . In multivariate Cox regression analysis, higher LND group (HR 0.88, 95% CI 0.81-0.96, p = 0.004) and LNR (per 10% increase: 1.11, 95% CI 1.09-1.13, p < 0.0001) were significant predictor of OS. Conclusions: The LND (> 12 examined LN) remains as a crucial treatment goal after NCRT with potential survival benefit, especially among E-ADC and those did not achieve pCR.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 2-2
Author(s):  
Basem Azab ◽  
Omar Picado ◽  
Caroline Ripat ◽  
Francisco Igor Macedo ◽  
Alan S Livingstone ◽  
...  

2 Background: The association of the interval between neoadjuvant chemo-radiation and surgery (CRT-S), and cancer outcomes in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR), short and long overall survival (OS). Methods: Patients listed on the National Cancer Data Base from 2004 to 2013 were studied. We included patients with CRT followed by surgery in 15-90 days. All patients had reported pT, pN cancer stages and survival status. CRT-S interval was studied as continuous (weeks) and categorical variables (quintiles). Results: A total of 5181 patients were included; 81% were adenocarcinomas, 84% were males and mean age was 62 years. They were divided into CRT-S interval quintiles (15 to 37, 38 to 45, 46 to 53, 54 to 64 and 65 to 90 days) (n = 1016, 1063, 1081, 1083 and 938 patients), respectively. There was a significant increase of pCR rate across the CRT-S quintiles (18%, 21%, 24%, 25% and 29%, p < 0.001). This advantage persisted when CRT-S was measured as continuous variable in weeks (OR: 1.11, 95% CI = 1.078-1.143, p < 0.001). However, 90-day mortality significantly increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5% and 8.2%, p = 0.02) and through weeks (OR = 1.05, 95%CI = 1.005-1.106, p = 0.03). Mean OS across CRT-S quintiles was 59.2, 58.8, 55.4, 56.6 and 51.5 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval (HR 1.02, 95% 1.003-1.037, p = 0.02), especially among the last quintile (CRT-S = 65-90 days: HR 1.2, 95% CI 1.04-1.32, p = 0.009). Those with no-pCR had worse OS as time to surgery increased (p < 0.001), while pCR group had similar OS across CTR-S intervals. Conclusions: Despite higher pCR rate as CRT-S interval increasing, surgery is preferred to be done in less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. Further randomized studies are needed to consolidate our findings.


2017 ◽  
Vol 27 (6) ◽  
pp. 1171-1177 ◽  
Author(s):  
Andrew T. Wong ◽  
Yi-Chun Lee ◽  
David Schwartz ◽  
Anna Lee ◽  
Meng Shao ◽  
...  

ObjectiveClinical outcomes for patients with uterine carcinosarcoma are poor after surgical management alone. Adjuvant therapies including chemotherapy (CT) and/or radiation therapy (RT) have been previously investigated, but the optimal management of this disease remains controversial. The purposes of this study were to analyze the patterns of use of adjuvant CT and RT and to assess the impact on survival of each of these treatment regimens using the National Cancer Data Base.Methods/MaterialsThe National Cancer Data Base was queried for patients given a diagnosis of uterine carcinosarcoma confined to the pelvis who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011. Patients were excluded if they survived less than 4 months after diagnosis. Data regarding CT and RT use were collected. Overall survival (OS) was analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to evaluate the effect of covariates on OS.ResultsA total of 4906 patients were included in this study. Median age was 67 years (interquartile range, 60–75 years). Median follow-up was 28.9 months (interquartile range, 15.4–52.9 months). There were 1777 patients (36.2%) who received no adjuvant treatment, 971 (19.8%) who received CT alone, 1060 (21.6%) who received RT alone, and 1098 (22.4%) who received both RT and CT. The 5-year OS for patients receiving no adjuvant therapy, adjuvant RT alone, adjuvant CT alone, and combined CT and RT were 44.9%, 47.1%, 47.5%, and 62.9%, respectively. On pairwise analysis, combined CT and RT was associated with improved survival compared with all other subgroups (P < 0.001). On multivariable Cox regression analysis, combined CT and RT (hazard ratio, 0.50; 95% confidence interval, 0.44–0.57; P < 0.001) and CT alone (hazard ratio, 0.78; 95% confidence interval, 0.69–0.88; P < 0.001) were significantly associated with improved OS, whereas RT alone was not.ConclusionsCombination therapy with CT and RT was associated with significantly improved 5-year OS compared with no further therapy, RT alone, or CT alone.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19022-e19022
Author(s):  
Alaa Altahan ◽  
Eric Vick ◽  
Upama Giri ◽  
Eric Wiedower ◽  
Michael Gary Martin

e19022 Background: There has been some improvement in overall survival (OS) for patients with MCL over the past years [Gordon 2014]. However, side effects of treatment remain a major concern. With introduction of novel therapies like IT, it is imperative to optimize treatment regimens to improve survival while minimizing toxicity. Methods: MCL patients (pts) who were diagnosed in 2013 or later with information available about chemotherapy (CT) and IT and did not receive transplant were extracted from NCDB. Pts were assigned to age categories and were sorted into six groups based on different combinations of CT (none, single agent (SA), and multi-agent (MA)) with or without IT. Cox regression analysis was used to perform multivariate analysis that included age category, sex, race, clinical stage, Charlson/Deyo score, CT, radiation, and IT for each group. Multivariate p values (p) were used to analyze statistical significance. Kaplan Meier method was utilized to analyze OS. T-test was used to compare means (t-p). Results: 1438 total pts were identified with a mean age of 70 (range 24-90); 71% male; 93% white, 4% black, 3% others; 42% with stage III/IV disease. 667 pts did not receive CT or IT, and 40 received IT alone and both of these groups were excluded from further analysis. 52 pts received SA- (without) IT, 206 received SA+(with) IT and 260 pts received MA-IT and 213 MA+IT. Mean age was 72 and 66 for SA and MA groups, respectively (t-p<0.01). Mean OS for SA+IT was 27 months (m) vs SA-IT 16 m (p < 0.01). MA+IT v MA-IT showed no difference in mean OS (25 vs 26 m, respectively, p =0.49). Although there was a significant difference in OS between SA and MA groups without IT (16 vs 25 months, p < 0.01). SA + IT group showed comparable mean OS time to MA + IT (27 vs 26 m, p =0.145). Conclusions: For MCL pts, MA has superior OS to SA group. However, adding IT significantly improves OS for SA group and makes it comparable to MA. Adding IT to MA did not provide significant difference in OS. These results highlight the possibility of achieving same OS with less toxic regimens. Hence further evaluation in a prospective study to optimize treatment while reducing toxicity is warranted.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 187-187
Author(s):  
Jan-Binne Hulshoff ◽  
Ellen C. de Heer ◽  
Daphne H. Klerk ◽  
Derk Jan De Groot ◽  
John Theodorus Plukker ◽  
...  

187 Background: Patients with curable esophageal cancer (EC) which proceed beyond the original CROSS eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect of extending the CROSS eligibility criteria for nCRT on treatment related toxicity and overall survival (OS) in EC. Methods: Included were 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0), treated with the CROSS schedule followed by esophagectomy. Group 1 (N = 90) consisted of patients which met the CROSS criteria and patients in group 2 (N = 71) met the extended eligibility criteria, i.e. including a tumor length of > 8 cm (N = 23), > 10% weight loss (N = 35), > 2 – 4 cm extension in the stomach (N = 21), celiac lymph node metastasis (N = 13), and/or age > 75 years (N = 2). We assessed the differences in hematologic toxicity (≥ grade 3) and 90-day postoperative mortality. Moreover, we assessed the prognostic value on OS with multivariate Cox regression analysis. Results: No difference was found in hematologic toxicity and 90-day mortality. The OS differed significantly (P = 0.003), with a median of 37.3 (95% CI 10.56 – 64.0) and 17.2 (95% CI 13.8 – 20.6) months in group I and II, respectively. Pathological N-stage (P = 0.024), ypT-stage (P = 0.044), and group II (P = 0.006) were independent prognostic factors for OS. Conclusions: Extension of the CROSS study eligibility criteria for nCRT did not affect hematologic toxicity and postoperative mortality, but was prognostic for OS.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 78-78
Author(s):  
Basem Azab ◽  
Francisco Igor Macedo ◽  
Omar Picado ◽  
Dido Franceschi ◽  
Alan S Livingstone ◽  
...  

78 Background: There is little consensus on the use of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) in gastric carcinoma (GC) patients. We sought to compare the outcomes of these two approaches in a large national data base. Methods: National Cancer Data Base PUF (2004-2014) of GC patients who underwent NCRT/NCT followed by resection were included. Primary outcome was overall survival (OS), secondary outcomes were pathological complete response (pCR), R0 resection and postoperative mortality. Results: A total of 4204 GC patients with NCT were included, 62% of them had additional neoadjuvant radiotherapy (NRT). NCRT had higher pCR and R0 rates [551/2613 (21%), 2314/2561 (90%)] than NCT group [148/1573 (9%), 1242/1543 (80%)], p < 0.0001. Multivariate logistic regression showed similar higher odds of pCR (OR 2.8, 95% CI 1.65-4.60, p < 0.0001) and R0 (OR 1.5, 95% CI 1.14-1.99, p = 0.004) among NCRT versus NCT. There was no significant difference in length of hospital stay, 30-day readmission rate, 30- and 90-day postoperative mortality. Median, 3- and 5-year OS for NCRT versus NCT were: (20.4 months, 24% and 11%) versus (18.3 months, 19% and 6%), p < 0.001. Univariate cox regression analysis showed superior OS with NRT (HR 0.9, 95% CI 0.80-0.91, p < 0.001). After adjusting for confounding variables, pCR (HR 0.2, 95% CI 0.18-0.24, p < 0.001) and R0 (HR 0.7, 95% CI 0.61-0.75, p < 0.001) had better OS, while NRT was not. Conclusions: NRT improved pCR and R0 rates in GC without increase in surgical morbidity/mortality. The long-term OS benefit of NRT is likely secondary to higher pCR and R0 resection.


Author(s):  
Helena Hong Wang ◽  
◽  
Ellen C. de Heer ◽  
Jan Binne Hulshoff ◽  
Gursah Kats-Ugurlu ◽  
...  

Abstract Background Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome. Patients and Methods Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality. Results Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS. Conclusion Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 331-331
Author(s):  
Nawar Hanna ◽  
Quoc-Dien Trinh ◽  
Jesse Sammon ◽  
Thomas Seisen ◽  
Malte Vetterlein ◽  
...  

331 Background: The use of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is supported by results from several randomized control trials, including SWOG-8710. We sought to test the applicability of the SWOG-8710 study in the general population. Methods: We used the National Cancer Data Base (NCDB) to identify patients with non-metastatic muscle-invasive urothelial carcinoma of the bladder who underwent RC between 2004 and 2012. The primary endpoint was overall survival (OS). Secondary endpoints were rates of downstaging (pT0), positive pathologic lymph nodes (pN+), margin status, postoperative readmission, length of hospital stay (LOS), and 30 and 90-day postoperative mortality rates. OS comparison using Cox regression analysis was conducted. Furthermore, logistic regression models examining secondary outcomes were fitted. To adjust for potential selection bias, propensity score weighted analyses were performed. Results: Of 8732 patients who underwent RC, 1619 (19%) received NAC. Compared to the SWOG-8710 cohort, our population was older, more commonly female (p=0.002), and had higher clinical stage (p<0.001). Following propensity score adjustment, receipt of NAC was associated with an OS benefit (Hazard Ratio [HR]: 0.88, p=0.017). On secondary outcome analysis, higher downstaging rates (Odds Ratio [OR]: 5.03, p<0.001) and lower 30-day (OR: 0.49, p=0.019) and 90-day (OR: 0.61, p=0.009) postoperative mortality rates were recorded in patients who received NAC. Conclusions: Despite baseline differences between patients from the SWOG-8710 trial and general urologic practice, NAC is associated with an OS advantage relative to RC alone. Continued efforts should focus on promoting the use of NAC in appropriate patients.


Author(s):  
Sivesh K. Kamarajah ◽  
Steven A. White ◽  
Samer A. Naffouje ◽  
George I Salti ◽  
Fadi Dahdaleh

Abstract Background Data supporting the routine use of adjuvant chemotherapy (AC) compared with no AC (noAC) following neoadjuvant chemotherapy (NAC) and resection for pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to determine whether AC improves long-term survival in patients receiving NAC and resection. Methods Patients receiving resection for PDAC following NAC from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). Patients with a survival rate of < 6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression analysis were performed to account for selection bias and analyze the impact of AC on overall survival. Results Of 4449 (68%) noAC patients and 2111 (32%) AC patients, 2016 noAC patients and 2016 AC patients remained after PSM. After matching, AC was associated with improved survival (median 29.4 vs. 24.9 months; p < 0.001), which remained after multivariable adjustment (HR 0.81, 95% confidence interval [CI] 0.75–0.88; p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (hazard ratio [HR] 0.80, 95% CI 0.72–0.90; p < 0.001), N1 (HR 0.76, 95% CI 0.67–0.86; p < 0.001), R0 margin status (HR 0.82, 95% CI 0.75–0.89; p < 0.001), R1 margin status (HR 0.77, 95% CI 0.64–0.93; p = 0.007), no neoadjuvant radiotherapy (NART; HR 0.84, 95% CI 0.74–0.96; p = 0.009), and use of NART (HR 0.80, 95% CI 0.73–0.88; p < 0.001). Stratified analysis by nodal, margin, and NART status demonstrated consistent results. Conclusion AC following NAC and resection is associated with improved survival, even in margin-negative and node-negative disease. These findings suggest completing planned systemic treatment should be considered in all resected PDACs previously treated with NAC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20641-e20641
Author(s):  
J. P. Plastaras ◽  
J. C. Haynes ◽  
R. Mick ◽  
L. M. Hertan ◽  
A. I. Urdaneta ◽  
...  

e20641 Background: Baseline nutritional status is associated with clinical outcomes in esophageal cancer. Moreover, nutritional support during chemoradiation has been shown to improve outcomes in other disease sites. This retrospective study evaluated the impact of nutritional interventions and baseline nutritional status on outcomes in patients (pts) with locally advanced esophageal cancer. Methods: A retrospective review was performed of 132 pts treated with curative intent using radiation (RT) between 1986 and 2007 at the Hospital of the University of Pennsylvania. The median age of the population was 60 years (range: 33–86). Esophagectomy was performed in 70%, with adjuvant RT in 60% and neoadjuvant RT in 40%. Concurrent chemotherapy was given to 85% of the group. Nutritional counseling was provided to 83% of pts. During RT, oral or enteral nutritional supplements were provided to 77% of pts and intravenous fluids (IVF) were given to 38%. Median follow-up was 14.1 months. Results: Median survival from end of radiation was 1.5 yrs. Median absolute and percentage weight loss during RT were 6.2 lbs and 3.8%, respectively. Median percentage decrease in hemoglobin and albumin were 5.7% and 9.1%, respectively. Univariable Cox regression analysis demonstrated a statistically significant association between weight loss of ≥5 lbs during RT and worse survival (HR 1.74, 95% CI 1.09 - 2.79, p=0.02). Decrease in hemoglobin of 5% or more (HR 1.22, 95% CI 0.59 - 2.54) and decrease in albumin of 10% or more (HR 1.09, 95% CI 0.48 - 2.48) were not associated with survival. Patients who received only nutritional supplements during RT survived significantly longer (p=0.03) than pts who received IVF regardless of nutritional supplementation (HR 2.12, 95% CI 1.12 - 4.01) or pts who received neither nutritional supplements nor IVF (HR 1.8, 95% CI 1.03 - 3.14). Conclusions: Weight loss during RT predicted for worse survival. Nutritional factors before and during RT may be important in outcomes in patients with esophageal cancer and may be modifiable. The use of IVF may be a potential indicator of worse prognosis. Future prospective studies should consider these factors in trial design. No significant financial relationships to disclose.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Francesco Sclafani ◽  
Ian Chau ◽  
David Cunningham ◽  
Andrea Lampis ◽  
Jens Hahne ◽  
...  

581 Background: An association between rs4919510, a SNP of mir-608, and prognosis of patients with colorectal cancer has been reported. However, no studies have analysed the role of this SNP in LARC. We conducted a pharmacogenomic analysis of rs4919510 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in high-risk LARC. Methods: SNP analysis was performed on DNA extracted from tumour tissue. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients had tumours assessable for rs4919510 genotyping. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG with no deviation from the Hardy-Weinberg equilibrium (p=0.379). Genotypes were evenly distributed in the two treatment groups and no association with baseline clinico-pathological characteristics or tumour molecular status (including RAS) was observed. Complete response did not differ according to the tumour genotype in the entire population (14.7% for CC, 13.3% for CG/GG) and was not influenced by treatment (12.0% for CC and 14.3% for CG/GG in CAPOX, 17.8% for CC and 12.5% for CG/GG in CAPOX-C) (all p values>0.05). Median follow-up was 64.9 months. In the CAPOX arm the 5-yr PFS and OS rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, p=0.02, HR OS 0.38, 95% CI: 0.14-1.01, p=0.05). In the CAPOX-C arm the same survival figures were 73.2% and 82.2% for CC and 64.6% and 73.1% for CG/GG (HR PFS 1.38, 95% CI: 0.61-3.13, p=0.44, HR OS 1.34, 95% CI: 0.52-3.48, p=0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (p=0.02) and OS (p=0.07). Conclusions: This is the first study investigating rs4919510 in LARC. We found that the CC genotype was associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy alone but not in those treated with cetuximab. The addition of cetuximab to chemotherapy may mitigate the unfavourable prognostic associated with the CC genotype.


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