Supplementary Figure 1 from Potential Role of Jun Activation Domain–Binding Protein 1 as a Negative Regulator of p27^kip1 in Pancreatic Adenocarcinoma

Supplementary Figure 1 from Potential Role of Jun Activation Domain–Binding Protein 1 as a Negative Regulator of p27kip1 in Pancreatic Adenocarcinoma

Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS), pts > 75 yrs old were excluded from this study. The purpose of this study was to assess the safety and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in this population. Methods: We retrospectively analyzed unresectable PC pts, age >= 75, treated with mFOLFIRINOX at MD Anderson from 2011 to 2017. Primary outcome was rate of grade 3 or 4 hematologic toxicity (HT). Results: 24 pts were included. Grade 3 or 4 HT occurred in 11 pts 6 pts required hospitalization for any toxicity, and 10 stopped mFOLFIRINOX due to toxicity. The most frequently used starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m(2), respectively. Median PFS was 3.7 months (95% CI: 3.0-5.7) with a median OS of 11.6 months (95% CI: 6.14-15.7). For first line pts, median PFS and OS were 5.1 (95% CI: 2.0-12.8) and 12.2 months (95% CI: 4.8-30.8), respectively. Conclusions: In this single-center retrospective analysis of unresectable PC pts age 75 or older given mFOLFIRINOX, toxicities and survival outcomes were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar toxicity and efficacy when compared to younger pts. (C) 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.

OBJECTIVESNeoadjuvant therapy (NT) is used for advanced pancreatic ductal adenocarcinoma (PDAC). No clear guidelines exist for switching therapies when patients do not respond to initial NT. We sought to characterize patients who underwent early switch from FOLFIRINOX to gemcitabine/nab-paclitaxel (GA) as NT for PDAC.METHODSWe identified patients at a single institution switched from FOLFIRINOX to GA within the first 4 months of NT for PDAC during 2012-2017. We compared clinicopathologic data and oncologic outcomes.RESULTSOf 25 patients who met the criteria, 21 showed a serologic or radiographic response to GA; 11 (52%) reached resection. Responders had decreased carbohydrate antigen (CA) 19-9 levels from pretreatment to post-GA (P = 0.036). Resected responders had significantly decreased CA 19-9 comparing preswitch to post-GA (P = 0.048). The only predictor of GA response was prechemotherapy CA 19-9 of less than1000 U/mL (P = 0.021). Predictors of reaching resection were head/uncinate tumor (P = 0.010) and presenting stage lower than locally advanced (P = 0.041).CONCLUSIONSWhen patients do not respond to neoadjuvant FOLFIRINOX, early switch to GA should be considered. Future efforts should be directed toward identifying markers that will allow correct choice of initial therapy rather than attempting to rescue patients who respond poorly to first-line therapy.

362 Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS) (11.1 vs 6.8 months [m] with gemcitabine, P < 0.001), pts > 75 yrs old were excluded from this study. As per SEER 2011-2015 data, 38% of new PC cases are diagnosed in pts age > 75. The purpose of this study was to assess the safety and efficacy of FOLFIRINOX in this group of pts. Methods: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with FOLFIRINOX at MD Anderson since 2011. Data obtained include demographics, line of treatment (tx), starting dose, progression free survival (PFS), OS and toxicities. Response was determined by chart documentation. Primary outcomes were mOS and rates of grade 3/4 hematologic toxicity (HT). Results: A total of 24 pts (19 male) were included with median age of 76 (range 75 to 84). 18 had metastatic disease, and FOLFIRINOX was the 1st line of tx for 18 of the 24 pts. The median number of cycles administered was 4 (range 1 to 12). The most frequent starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m2, respectively. Bolus 5-FU and leucovorin were omitted in all but 3 pts. Median PFS was 3.7 m (95% CI: 3.0-5.7) with mOS of 11.6 m (95% CI: 6.14-15.7). 16 pts (67%) experienced disease control (response to tx or stable disease). Grade 3 or 4 HT occurred in 11 pts (46%), and 9 (38%) were supported with granulocyte colony-stimulating factor at some point during tx. 6 pts (25%) required hospital admission for any toxicity, most commonly infection (3 pts), and 10 (42%) stopped FOLFIRINOX due to toxicity, most commonly fatigue (6 pts). Conclusions: In this single-center retrospective analysis of 24 unresectable PC pts age 75 or older given FOLFIRINOX, OS outcomes were similar to those reported by Conroy et al in the original trial which excluded pts older than 75. In our review, toxicities including incidences of grade 3 or 4 HT were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar efficacy and toxicity when compared to younger pts.

Abstract Background: More than half of patients (pts) with pancreatic cancer (PC) initially present with unresectable, locally advanced disease (LAPC). Data on management of these pts after systemic chemotherapy are scarce. Many clinicians utilize a strategy of induction chemotherapy followed by consolidative concurrent chemoradiation (CRT) for pts not progressing on initial chemotherapy. How to manage pts after CRT is controversial. We sought to evaluate the role of maintenance chemotherapy (MCT) after CRT in pts with LAPC. Methods: We retrospectively analyzed LAPC pts treated with CRT at MD Anderson from 2005-2018. Pts who were taken for curative-intent surgery were excluded. Primary and secondary outcomes were median progression-free survival (mPFS) and median overall survival (mOS), respectively, as measured from the start date of CRT. Data were also obtained on pt demographics, response, and duration of induction chemotherapy as well as MCT regimens. Results: We included 165 pts with LAPC treated with CRT in our analysis. Median age was 66 (range 39 – 84), and 97 (59%) pts were male. Median follow-up was 12.9 months. The median duration from initiation of induction chemotherapy to start of CRT was 4.4 months. Most pts (84%) received 1 line of induction chemotherapy prior to CRT. Ten pts (6%) did not receive induction chemotherapy and 17 pts (10%) received at least 2 lines prior to CRT. All but 9 pts (94%) developed disease progression (PD) after CRT, and 49 pts (33%) had PD within 3 months of CRT. On univariate analysis, PD on the induction chemotherapy regimen immediately prior to CRT was associated with shortened PFS (HR 2.46, p < 0.001) and OS (HR 2.96, p < 0.001) after CRT. Most pts (78%) did not receive MCT after CRT. 69% of pts who received MCT were male, compared to 56% of those who did not receive MCT. The percentages of pts who had PD on the chemotherapy regimen immediately prior to CRT in the MCT and no-MCT groups were 9% and 12%, respectively. Sixteen pts who received MCT were treated with either gemcitabine alone or a gemcitabine-containing regimen, while 14 pts received capecitabine monotherapy. On univariate analysis, the use of MCT after CRT was associated with prolonged mPFS (9.0 vs. 4.2 months, p = 0.01), but was not associated with an increase in mOS (15.5 vs. 12.5 months, p = 0.14). On multivariable analysis controlling for race, radiation dose, age, and whether there was progression on the chemotherapy regimen prior to CRT, the use of MCT was significantly associated with both prolonged PFS (HR 0.45, p < 0.001) and OS (HR 0.66, p = 0.047). Conclusions: In this single-institution retrospective analysis of 165 pts with LAPC treated with CRT, treatment with post-CRT MCT was associated with a significant improvement in both PFS and OS as measured from the start date of CRT. Based on these results, MCT may be an appropriate option for pts with LAPC who have not progressed following consolidative CRT, and a prospective trial should be performed to better address this knowledge gap. Citation Format: Jonathan D. Mizrahi, Shalini Moningi, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Milind M. Javle, Gauri R. Varadhachary, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Christopher H. Crane, Joseph M. Herman, Albert C. Koong, Eugene J. Koay, Jane E. Rogers, Shubham Pant. Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B36.

To develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk.

During neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients.

OBJECTIVE:To determine the impact of histology on pathologic response, survival outcomes, and recurrence patterns in patients with esophageal cancer (EC) who received neoadjuvant chemoradiotherapy (CRT).SUMMARY OF BACKGROUND DATA:There is a paucity of data regarding comparative outcomes after neoadjuvant CRT between esophageal squamous cell carcinoma (SCC) and adenocarcinoma.METHODS:Between 2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by esophagectomy at 3 academic institutions were retrospectively reviewed, including 207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%). Pathologic response, survival, recurrence pattern, and potential prognostic factors were compared.RESULTS:Pathologic complete response (pCR) rate was significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P < 0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P = 0.023). For patients who achieved a pCR, no significant differences were found in recurrence pattern, sites, or survival end-points between the 2 histology groups. For non-pCR patients, the SCC group demonstrated significantly higher regional and supraclavicular recurrence rates but a lower hematogenous metastasis rate than adenocarcinoma patients, whereas the adenocarcinoma patients had a more favorable locoregional failure-free survival (P = 0.005) and worse distant metastasis-free survival (P = 0.024). No differences were found in overall survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups.CONCLUSIONS:SCC was associated with a significantly higher pCR rate than adenocarcinoma. Recurrence pattern and survival outcomes were significantly different between the 2 histology subtypes in non-pCR patients.

TPS533 Background: Checkpoint inhibitors such as pembrolizumab are active against a variety of tumor types; however, pancreatic cancer patients generally do not see improvements in their disease from single agent treatment. Blocking CXCR4 may potentiate the activity of checkpoint inhibitors by (1) increasing mobilization of lymphocytes from bone marrow, (2) blocking production of SDF-1, in turn allowing better penetration of immune cells into the tumor, (3) reducing the entry of suppressor T cells into tumor, and (4) upregulating CCL20 in the tumor microenvironment, which may help attract dendritic cells into the tumor. We have launched a study combining BL8040, a CXCR4 antagonist, with pembrolizumab in order to determine the efficacy of this combination. Methods: Major inclusion criteria require patients with pancreatic adenocarcinoma whose tumors have progressed through at least one line of therapy. There must be sufficient disease to allow for pre- and post-treatment biopsy as well as measurement of response by RECIST criteria. Patients must be age 18 or older and ECOG 0-1. Liver function, renal, and hematologic criteria are fairly rigorous. Major exclusion criteria include patients with viral infections or those who require supraphysiologic steroid use. Treatment includes a two week cycle of single agent BL-8040 given on days 1-5 and 8-12. Cycles 2 and beyond include treatment on day 1 with pembrolizumab, 200 mg flat dose, plus BL-8040 given SQ on days 1,4,8, and 11 of a two week cycle. The primary endpoint is response rate; other major clinical objectives include progression free and overall survival. Scientific correlates include assessments of immune cell infiltrates into tumor via histology and immunoflourescence, histological assessment of stromal components, and gene expression signatures. Blood is likewise being collected for serum cytokine analysis, circulating free DNA analysis, circulating tumor cells, and exosome analysis. Clinical trial information: NCT02907099.

S52 ESTRO 37Rescheduled QA and service reduced the fraction of treatment course time violations according to guidelines to less than 20 % for accelerated treatments and to less than 40 % for the non-accelerated treatments after 2011 (fig.2).The introduction of the systematic review of treatment schedule reduced the fractions of treatment course time violations to 4 % for accelerated treatments, and to 13 % for the non-accelerated treatments (fig.2).The surveillance alternates between two radiation therapists and takes approximately 5-15 minutes per week. ConclusionAwareness and continual review of treatment schedules of head and neck cancer patients reduced the treatment course duration.

e23565 Background: Sarcomatoid carcinoma is a rare histologic subtype of cancer of unknown primary (SCUP) characterized by poorly differentiated carcinoma with a component of sarcoma-like differentiation or a true mixed lineage neoplasm. There is limited data regarding the presentation, diagnostic algorithm and natural history of patients (pts) with SCUP. Methods: We retrospectively reviewed the MD Anderson CUP database and tumor registry from 2012-2015 and identified 26 pts with SCUP. Data regarding pathologic nomenclature, immunohistochemistry (IHC), molecular diagnostics, treatments, and outcomes were obtained. Kaplan Meier method was used for survival analyses (OS). Results: The most common nomenclature was sarcomatoid carcinoma, followed by sarcomatoid malignant neoplasm, and carcinoma with sarcomatoid features. Median age at diagnosis was 61 years (range 33-77). 54% of pts were female. Majority of pts presented with more than 3 metastatic sites, commonly lung, liver, and bone. 22 pts (85%) received chemotherapy, most commonly gemcitabine + docetaxel (10 [38%]) and carboplatin + paclitaxel (4 [15%]). Epithelial IHC markers included Pankeratin (AE1/AE3), CK7, BerEp4, Low Molecular Weight keratin and mesenchymal IHC markers included Calretinin, SMA, Vimentin, Mesothelin. Median OS for entire cohort was 7 months (m) (95% CI: 2.1-11.9). Pts who underwent definitive multimodality management did significantly better compared to pts with palliative therapy alone (median OS 26 vs 7 m: HR 0.25; 95% CI: 0.11-0.58, P = 0.003). Poor PS (HR 3.49; 95% CI 1.28-9.53, P = 0.0005), elevated LDH (HR 2.81; 95% CI 0.68-11.63; P = 0.03), and elevated neutrophil-to-lymphocyte ratio (NLR) (HR 3.18; 95% CI: 1.07-9.48, P = 0.002) were associated with poor OS. 5 pts underwent NGS which demonstrated p53 (3), BRAF V600E (2) and EGFR amplification (1). Conclusions: SCUP is a rare presentation with an aggressive course and limited survival. The diagnosis is difficult to make and requires a careful review and synthesis of histology, IHC, and molecular diagnostics. Further research is needed to better understand the optimal use of molecular diagnostics in order to more optimally diagnose and treat this disease.

Abstract Background: We aimed to categorize the most common comorbid medical conditions in pancreatic cancer (PC) patients and to determine whether these conditions have impact on the overall survival (OS). Methods: Between January 2000 and 2014, 2165 patients with pathologically confirmed adenocarcinoma of the pancreas consented to participate in a clinico-epidemiological study at the University of Texas MD Anderson Cancer Center. We reviewed the electronic medical records of all patients to identify the prevalence of four chronic medical conditions, including systemic hypertension, hyperlipidemia, type 2 diabetes, and altered morphology of the pancreas. Prevalence of each chronic disease was assessed and median survival was estimated by using the Kaplan-Meier product-limit method, and significant differences between the survival times were determined by using the log-rank test. Results: Among all patients, 950 (43.9%) had history of hypertension, 516 (23.8%) had hyperlipidemia, 585 (27%) had type 2 diabetes. Radiological and pathological records indicted presence of steatosis (0.4%), fibrosis (1.9%), and pancreatitis (9.9%). The prevalence of hyperlipidemia and diabetes was significantly higher in men (27.9%, 30.2%) than in women (18.2%, 22.8%) respectively; P value <.01. We found no significant variation in the prevalence of hypertension and altered pancreatic morphology between men and women. Hypertension was more frequent among African American patients while diabetes was more common among Hispanics and African Americans. No significant variations in the distribution of other conditions by ethnicity. Median survivals of PC patients by comorbidities are presented in table 1. Conclusion: Chronic medical conditions are commonly reported by PC patients and the prevalence of these conditions may vary by gender. However, the impact of these conditions may not significantly affect the survival of the patients. The interaction treatment choices with these conditions still needs to be elaborated in future studies. OS (months), 95%CI of PC patients by comorbiditiesComorbidityYesNoP valueHypertension10.9 (10-11.7)11.6 (10.7-12.4).09Hyperlipidemia12 (11.8-13.1)10.9 (10.2-11.6).4Diabetes Mellitus9.7 (8.4-11.1)11.4 (10.7-12.1).1 Note: This abstract was not presented at the meeting. Citation Format: Ahmed O. Abousamra, David Fogelman, Vijayashri Rallapalli, Akram Shalaby, Milind Javle, Renato Lenzi, Linus Ho, Donghui Li, Manal Hassan. Common chronic medical conditions in pancreatic cancer: impact on overall survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3282. doi:10.1158/1538-7445.AM2017-3282

Chemoradiation plays a key role in the treatment of esophageal cancer (EC). While Platinum-based/5-fluorouracil (5FU) (PF) is a commonly used concurrent chemotherapy doublet with radiotherapy, taxane-based/5FU (TF) has frequently been employed as an alternative regimen at our institution. This study is to compare the toxicities and clinical outcomes of these two regimens in combination with radiotherapy for EC. A total of 687 EC patients who received concurrent chemoradiotherapy without induction chemotherapy between 1998 and 2016 were identified, of whom 194 received PF, and 493 received TF. We conducted a propensity score analysis comparing PF (n=105) and TF (n=103) matched on a number of patient and tumor characteristics. Treatment related toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Differences in continuous variables and categorical variables were examined with independent-sample t tests and Chi-square tests. The rates of overall survival (OS), recurrence free survival (RFS), loco-regional control (LRC), and distant metastasis free survival (DMFS) were calculated with the Kaplan-Meier method. Statistical analysis was performed using SPSS version 23.0. The overall severe toxicities (grade ≥ 3) were 41% vs. 45% for PF vs. TF, respectively (P>0.05). Compared to TF, the risk of severe hematologic toxicity was comparable (P >0.05). The incidence of severe non-hematologic toxicities, such as esophagitis and pneumonitis, were also comparable (P >0.05). The median and 5 year OS were comparable between PF and TF at 35.3 vs. 28.2 months and 35% vs. 28.1%, respectively (P >0.05). There were also no differences in RFS, LRC or DMFS between the two groups. Concurrent TF with radiotherapy appears comparable to PF in clinical outcomes and toxicities. Understanding the specific toxicities of these two chemotherapy regimen may help better individualize concurrent chemoradiotherapy for EC.

This study aimed to determine whether 18F-FDG PET response after induction chemotherapy before concurrent chemoradiotherapy can identify patients with esophageal adenocarcinoma who may benefit from subsequent esophagectomy. Methods: We identified and analyzed 220 patients with esophageal adenocarcinoma who had received induction chemotherapy before chemoradiotherapy, with or without surgery, with curative intent; all underwent 18F-FDG PET scanning before and after induction chemotherapy. 18F-FDG PET responders were defined as patients who achieved complete response (CR) after induction chemotherapy (maximum SUV ≤ 3.0). The predictive value of 18F-FDG PET response for patient outcomes was evaluated. Results: Overall, 86 patients had bimodality therapy (BMT; induction chemotherapy + chemoradiotherapy) and 134 had trimodality therapy (TMT; induction chemotherapy + chemoradiotherapy with surgery). Forty-eight patients (21.8%) achieved an 18F-FDG PET CR after induction chemotherapy. 18F-FDG PET CR was found to correlate with overall survival (OS) and progression-free survival (PFS) in BMT patients. For TMT patients, 18F-FDG PET CR predicted pathologic response (P = 0.003) but not survival. Among 18F-FDG PET nonresponders, TMT patients had significantly better survival than did BMT patients (P < 0.001). However, among 18F-FDG PET responders, BMT patients had OS (P = 0.201) and PFS (P = 0.269) similar to that of TMT patients. After propensity score-matched analysis, 18F-FDG PET responders treated with BMT versus TMT still had comparable OS and PFS, but TMT was associated with better locoregional control. Conclusion: 18F-FDG PET response to induction chemotherapy could be a useful imaging biomarker to identify patients with esophageal adenocarcinoma who could benefit from subsequent esophagectomy after chemoradiotherapy. Compared with BMT, TMT can significantly improve survival in 18F-FDG PET nonresponders. However, outcomes for 18F-FDG PET responders were similar after either treatment (BMT or TMT). Prospective validation of these findings is warranted.

The purpose of our study was to determine the value of 18F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).

Purpose: In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC. Methods and materials: This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications. Results: The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%). Conclusions: This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.

Purpose: To assess the contribution of induction chemotherapy (IC) before definitive chemoradiation therapy (dCRT) in patients with esophageal cancer (EC) based on recursive partitioning analysis (RPA).Methods and Materials: A total of 496 eligible patients with EC staged by positron emission tomography (PET) who received dCRT from 1998 to 2015 were included, 162 (32.7%) of whom underwent IC before dCRT. RPA was used to risk-stratify patients on the basis of independent prognostic factors to predict progression-free survival (PFS). Outcomes were compared between treatment groups.Results: The median follow-up time was 49.1 months (range, 7.0-155.9 months) for survivors. Compared with the non-IC group, the IC group had a comparable 5-year PFS rate (21.0% vs 23.4%; P=.726) in the whole cohort. Multivariate analysis identified age, performance status, primary tumor length, baseline PET maximum standard uptake value (SUVmax), and maximum lymph node diameter as independent prognostic factors for PFS. RPA segregated patients into 3 prognostic groups: low-risk group (PET SUVmax <9.7 and tumor length <= 5 cm), intermediate-risk group (PET SUVmax >= 9.7 and age >= 67), and high-risk group (PET SUVmax <9.7 and tumor length >5 cm, or PET SUVmax >= 9.7 and age <67). Significant improvements in PFS (P=.006) and locoregional failureefree survival (P=.028) in the IC group in comparison with the non-IC group were observed in high-risk patients, whereas no differences in survival were found between the 2 treatment groups in low-risk or intermediate-risk patients. After propensity score matching, the high-risk group still demonstrated a significantly improved PFS with IC (P=.009).Conclusions: The RPA prognostic grouping provides a useful method of selecting high-risk EC patients who may benefit from IC before receiving dCRT. Prospective validation is warranted. (C) 2017 Elsevier Inc. All rights reserved.

Objective: To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT). Background: Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce. Methods: Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients. Results: A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort. Conclusions: We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

Objectives: The aim of this study was to identify patients with esophageal cancer who may benefit from induction chemotherapy (IC) before neoadjuvant chemoradiotherapy (nCRT) on the basis of a prognostic scoring model.Methods: Between 1998 and 2015, 535 patients with esophageal cancer who underwent nCRT were included for analysis, including 218 patients who received IC before nCRT (IC group) and 317 patients who did not receive IC (non-IC group). A prognostic scoring model was developed to predict disease-free survival (DFS) on the basis of a Cox proportional hazards model.Results: The median follow-up time was 63.5 months (range 8.0-178.5) for survivors. The 5-year DFS rates were similar between the IC and non-IC groups (53.7% vs. 45.1%, p = 0.196). Multivariate analysis determined that histologic grade, tumor location, baseline positron emission tomography maximum standard uptake value, and lymph node size were independent prognostic factors for DFS. A prognostic scoring system was constructed by using these four factors, with the total score ranging from 0 to 6.2. When the median value was used as a cutoff, low-risk (<= 3.5) and high-risk (>3.5) groups were identified. In the high-risk group, patients who received IC had a nonsignificantly higher pathologic complete response rate (p = 0.272) and a significantly better DFS (p = 0.03) than patients who did not receive IC. After propensity score matching, the high-risk group demonstrated a significantly improved DFS with IC, a benefit that was not observed in the low-risk group.Conclusions: On the basis of the prognostic scoring model, the addition of IC to nCRT may provide a DFS benefit in high-risk patients with a risk score higher than 3.5. Prospective validation is warranted. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.