Neoadjuvant Chemoradiotherapy For Esophageal Cancer Research Articles

Intratreatment Response Assessment With 18F-FDG PET: Correlation of Semiquantitative PET Features With Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy

This prospective study seeks to extract semiquantitative positron emission tomography (PET) features from 18F-fluorodeoxyglucose PET scans performed before and during neoadjuvant chemoradiotherapy for esophageal cancer and to compare their accuracy in predicting histopathologic response. From 2012 to 2016, 26 patients with esophageal cancer underwent pretreatment and intratreatment PET scans during chemoradiotherapy followed by surgery. Median patient age was 63years (interquartile range, 58-68years); 26 patients had esophageal adenocarcinoma, and 3 had esophageal squamous cell carcinoma. The intratreatment PET scan was performed at a median of 32.4Gy (interquartile range, 30.6-32.4Gy). PET features of the primary site including maximum standardized uptake value (SUV), SUV mean, metabolic tumor volume, and total lesion glycolysis were extracted from the pretreatment and intratreatment PET scans. Patients were histopathologic responders if there was complete or near-complete tumor response by modified Ryan scheme. Mean values of PET features were compared between histopathologic responders and nonresponders. The area under the receiver operating characteristic curve (AUC) was used to compare the accuracy of PET features in predicting histopathologic response. Eleven patients (42%) were histopathologic responders. PET features most discriminatory of histopathologic response on AUC analysis were volumetric PET features from the intratreatment PET including metabolic tumor volume based on manual contour (AUC, 0.73; 95% confidence interval, 0.52-0.93) and total lesion glycolysis based on semiautomatic 40% SUV threshold (AUC, 0.73; 95% confidence interval, 0.53-0.94). Volumetric PET features from the intratreatment PET were the most accurate predictors of histopathologic response.

Impact of pathological complete response following neoadjuvant chemoradiotherapy in esophageal cancer.

Neoadjuvant radiochemotherapy (nRCT) followed by surgery has become the gold standard treatment in patients with locally advanced esophageal cancer. The pathological response is an important predictor in such patients. This work represents a single-center analysis investigating the impact of pathological complete response (pCR) on treatment outcome. All patients treated with nRCT followed by surgery between January 2005 and December 2015 were reviewed. The patients were categorized into two groups according to the pathological response following nRCT: pCR group and non-pCR group. Fifty-six patients with invasive cancer, 23 patients (41.1%) achieved pCR and 33 patients had non-pCR (58.9%) following nRCT. The average age was 62 years (±9.1), and most patients were males (83.9%). Histological types included squamous cell carcinoma (75%) and adenocarcinoma (25%). The total radiation dose was 45 Gy in 76.8% of the patients and 50.4 Gy in 23.2%. The median overall survival (OS) of the entire group was 3.5±1.2 years, and the 5-year OS rate was 38.2%, while the median disease-free survival (DFS) was 2.1±0.4 years and the 5-year DFS rate was 33.1%. The patients who achieved pCR had significantly higher 5-year OS and 5-year DFS rates: 47.2% and 48% compared to 27.3% and 21% for the non-pCR patients respectively (P=0.04, 0.03). The median time of local recurrence was 3.8±0.4 years in pCR group and 1.8±0.2 years in non-pCR group (P=0.01), while the median time of distant metastases in pCR group was 1.2±0.5 years and 1.1±0.2 years in non-pCR group (P=0.6). Complete pathological response predicts significantly higher rates of OS and DFS in patients with locally advanced esophageal cancer treated with nRCT followed by surgery.

Patients' preferences for treatment after neoadjuvant chemoradiotherapy for oesophageal cancer.

After neoadjuvant chemoradiotherapy (nCRT) plus surgery for oesophageal cancer, 29 per cent of patients have a pathologically complete response in the resection specimen. Active surveillance after nCRT (instead of standard oesophagectomy) may improve health-related quality of life (HRQoL), but patients need to undergo frequent diagnostic tests and it is unknown whether survival is worse than that after standard oesophagectomy. Factors that influence patients' preferences, and trade-offs that patients are willing to make in their choice between surgery and active surveillance were investigated here. A prospective discrete-choice experiment was conducted. Patients with oesophageal cancer completed questionnaires 4-6 weeks after nCRT, before surgery. Patients' preferences were quantified using scenarios based on five aspects: 5-year overall survival, short-term HRQoL, long-term HRQoL, the risk that oesophagectomy is still necessary, and the frequency of clinical examinations using endoscopy and PET-CT. Panel latent class analysis was used. Some 100 of 104 patients (96·2 per cent) responded. All aspects, except the frequency of clinical examinations, influenced patients' preferences. Five-year overall survival, the chance that oesophagectomy is still necessary and long-term HRQoL were the most important attributes. On average, based on calculation of the indifference point between standard surgery and active surveillance, patients were willing to trade off 16 per cent 5-year overall survival to reduce the risk that oesophagectomy is necessary from 100 per cent (standard surgery) to 35 per cent (active surveillance). Patients are willing to trade off substantial 5-year survival to achieve a reduction in the risk that oesophagectomy is necessary.

Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study

After neoadjuvant chemoradiotherapy for oesophageal cancer, roughly half of the patients with squamous cell carcinoma and a quarter of those with adenocarcinoma have a pathological complete response of the primary tumour before surgery. Thus, the necessity of standard oesophagectomy after neoadjuvant chemoradiotherapy should be reconsidered for patients who respond sufficiently to neoadjuvant treatment. In this study, we aimed to establish the accuracy of detection of residual disease after neoadjuvant chemoradiotherapy with different diagnostic approaches, and the optimal combination of diagnostic techniques for clinical response evaluations. The preSANO trial was a prospective, multicentre, diagnostic cohort study at six centres in the Netherlands. Eligible patients were aged 18 years or older, had histologically proven, resectable, squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction, and were eligible for potential curative therapy with neoadjuvant chemoradiotherapy (five weekly cycles of carboplatin [area under the curve 2 mg/mL per min] plus paclitaxel [50 mg/m2 of body-surface area] combined with 41·4 Gy radiotherapy in 23 fractions) followed by oesophagectomy. 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients had oesophagogastroduodenoscopy with biopsies and endoscopic ultrasonography with measurement of maximum tumour thickness. Patients with histologically proven locoregional residual disease or no-pass during endoscopy and without distant metastases underwent immediate surgical resection. In the remaining patients a second clinical response evaluation was done (PET-CT, oesophagogastroduodenoscopy with biopsies, endoscopic ultrasonography with measurement of maximum tumour thickness, and fine-needle aspiration of suspicious lymph nodes), followed by surgery 12-14 weeks after completion of neoadjuvant chemoradiotherapy. The primary endpoint was the correlation between clinical response during clinical response evaluations and the final pathological response in resection specimens, as shown by the proportion of tumour regression grade (TRG) 3 or 4 (>10% residual carcinoma in the resection specimen) residual tumours that was missed during clinical response evaluations. This study was registered with the Netherlands Trial Register (NTR4834), and has been completed. Between July 22, 2013, and Dec 28, 2016, 219 patients were included, 207 of whom were included in the analyses. Eight of 26 TRG3 or TRG4 tumours (31% [95% CI 17-50]) were missed by endoscopy with regular biopsies and fine-needle aspiration. Four of 41 TRG3 or TRG4 tumours (10% [95% CI 4-23]) were missed with bite-on-bite biopsies and fine-needle aspiration. Endoscopic ultrasonography with maximum tumour thickness measurement missed TRG3 or TRG4 residual tumours in 11 of 39 patients (28% [95% CI 17-44]). PET-CT missed six of 41 TRG3 or TRG4 tumours (15% [95% CI 7-28]). PET-CT detected interval distant histologically proven metastases in 18 (9%) of 190 patients (one squamous cell carcinoma, 17 adenocarcinomas). After neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Dutch Cancer Society.

Organ-preserving approaches in oesophageal cancer

Oesophagectomy is part of the mainstay of treatment for oesophageal cancer. Because most affected patients are elderly and have associated comorbidities, surgery is challenging. Furthermore, recovery from surgery can take up to a year and, in view of the poor survival associated with this cancer type, many patients will not regain their preoperative quality of life. 1 Smyth EC Lagergren J Fitzgerald RC et al. Oesophageal cancer. Nat Rev Dis Primers. 2017; 3: 17048 Crossref PubMed Scopus (294) Google Scholar Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort studyAfter neoadjuvant chemoradiotherapy for oesophageal cancer, clinical response evaluation with endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET–CT for detection of interval metastases. Active surveillance with this combination of diagnostic modalities is now being assessed in a phase 3 randomised controlled trial (SANO trial; Netherlands Trial Register NTR6803). Full-Text PDF

DW-MRI and DCE-MRI are of complementary value in predicting pathologic response to neoadjuvant chemoradiotherapy for esophageal cancer

Purpose To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. Material and methods Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2–3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated. Results GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADCpost-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUCper-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89). Conclusions Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

ObjectiveDuring 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.MethodsIn total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis.ResultsOf 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3–83.4%) and 93.7% (95% CI: 91.6–95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration.Conclusions18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.

EP-1419: Outcomes according to radiation fields of neoadjuvant chemoradiotherapy for esophageal cancer

EP-1419: Outcomes according to radiation fields of neoadjuvant chemoradiotherapy for esophageal cancer

Totally minimally invasive esophagectomy after neoadjuvant chemoradiotherapy: Long-term oncologic outcomes.

Minimally invasive esophagectomy is emerging with comparable short-term outcomes as open esophagectomies. Neoadjuvant chemoradiotherapy followed by surgery is considered standard of care in the Netherlands for patients with esophageal cancer. The aim of this study was to analyze the long-term oncologic outcome after neoadjuvant chemoradiotherapy followed by totally minimally invasive esophagectomy. Neoadjuvant carboplatin and paclitaxel based chemotherapy was concomitantly given with 41.4 Gy radiotherapy. Six weeks after neoadjuvant treatment, totally minimally invasive esophagectomy was performed. From December 2010 until December 2015 161 patients received this combination of treatment. In 128 male and 33 female patients with median age of 65 years (58-71), 88 minimally invasive esophagectomies with intrathoracic anastomosis and 73 minimally invasive esophagectomies with cervical anastomosis were carried out. Radical (R0) resection was confirmed in 156 patients (97%). In hospital mortality occurred in 6 patients (3.7%). Overall survival was 79% and 51% at 1 and 5 years, respectively, with a median follow-up of 24.5 months (13-38). Disease-free survival was, respectively, 76% and 55%. Totally minimally invasive esophagectomy after neoadjuvant chemoradiotherapy for esophageal cancer is a safe treatment with low postoperative mortality rates and favorable overall and disease-free survival.

Development of a radiomic signature for prediction of pathological complete response following neoadjuvant chemoradiotherapy in esophageal cancer.

106 Background: Pivotal to personalized therapy is accurate pre-treatment patient selection based on predictive biomarkers. We developed a radiomic signature model to predict pathological complete response (pCR) following neoadjuvant chemo-radiotherapy (NACRT) in esophageal cancers. Methods: We retrospectively identified 68 patients with esophageal cancer, treated with NACRT followed by esophagectomy, with baseline 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and computed tomography (CT) scans performed at our institution. In-house data-characterization algorithm was used to extract 3D radiomics features from the segmented primary disease. Prediction models were constructed and internally validated (2/3rd training, 1/3rd validation) using machine learning software. Cox regression hazard used to assess association with relapse free survival (RFS). Results: pCR was observed in 34 (50%) patients. A total of 126 features were extracted individually from PET and CT scans. On univariate analysis, 16 PET and 14 CT features were found to independently predict pCR. Three separate predictive models were built for CT, PET and combined CT+PET. Individually, both CT and PET had a good predictive power with AUC 0.74 and 0.730, respectively. Combined CT+PET radiomic features resulted in a significant improvement of predicting power, with AUC 0.856. Good discrimination (82.6%) was observed in validation dataset. Final model was: 13.439-34.632(CT-eccentricity)-2.469(CT-LRLGE)+10.626(CT-Gnorm_HIE)-2.094(CT-SD_Lac2)-19.337(CT-FD_SD)-0.344(PET-Contrast), where eccentricity is shape feature, LRLGE a gray level run length feature, Gnorm_HIE gray-level size zone feature, SD_Lac2 a fractal dimension feature. Stratifying patients with low vs. high radiomic signature score predicted RFS: median RFS 80.1 vs. 40.1 months; and 2-year RFS 77.4% vs. 52.6% [Hazard Ratio: 2.24, 95% CI 1.01-5.58], respectively. Conclusions: The developed radiomics signature models were highly predictive of pCR following NACRT. Further validation in larger data sets is needed to determine whether the model can predict clinical outcomes.

The Implications of the Introduction of Neoadjuvant Chemoradiotherapy for Oesophageal Cancer in a Low Volume Centre

Background: Oesophagectomy is the standard treatment for oesophageal cancer in medically fit patients, but is associated with significant morbidity and mortality. Neoadjuvant chemoradiotherapy has been included in the management of this disease with the aim to improve prognosis, and has been shown to improve survival without an associated increase in operative complications. This study included patients who underwent oesophagectomy at the Canberra Hospital, to determine if neoadjuvant therapy was associated with an increase in perioperative morbidity and mortality. Methods: Patients who underwent oesophagectomy at Canberra Hospital between January 2001 and December 2012 were reviewed retrospectively. Statistical analysis was performed using Chi-Squared tests, time to disease recurrence was estimated using Kaplan-Meier methods. Results: Of 98 patients (73 men, 25 women; median age 63 years) who underwent oesophagectomy, 39 (40%) received neoadjuvant therapy. Perioperative complications of grades III (67%) and IV (100%), occurred in the surgery alone group. Perioperative mortality rate was 3.8%, with all deaths occurring in the surgery alone group (P=0.05). Complete resection was possible in 87 patients (89%), 100% in the neoadjuvant therapy group, 82% in the surgery alone group (P=0.10). Median disease free survival was 49.2 months (CI 25.2, 73.2), with no significant difference between patient groups (P=0.53). Neoadjuvant therapy was associated with lower perioperative morbidity, with no statistically significant increase in perioperative mortality. It was also associated with improved rates of complete resection; however this did not appear to have translated into improved disease free survival.

Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer : Aretrospective study and literature review.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F‑18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Asystematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. Aliterature review of RILI was also performed. Of 205 patients undergoing nCRT, 6cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11-46months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe. FDG accumulation in the caudate or left liver lobe after CRT in the area that received ahigh radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

Inclusion of PET-CT into planning of primary or neoadjuvant chemoradiotherapy of esophageal cancer improves prognosis.

PET-CT is widely used for both the staging and planning of primary or neoadjuvant chemoradiotherapy for esophageal cancer. Inclusion of PET-CT information into radiotherapy planning often leads to substantial modifications of the target volume. In the case of detection of distant metastases, it may also result in aswitch to apalliative treatment approach. This spares patients from therapy-related toxicities that provide no clinical benefit. However, due to alack of studies, it is currently unclear whether the advantages of PET-CT also translate into ameasurable improvement in patient survival. Aretrospective analysis assessed the survival data of 145 patients with esophageal carcinoma stagesI (eight patients; 5%), II (45; 31%), III (79; 55%), IV (8; 5%) and unknown (5; 4%). Patients were treated between 1999 and 2014 either with primary chemoradiation (n= 101) or neoadjuvant chemoradiation at the Department of Radiation Oncology, University Medical Center Mainz, followed by transabdominal or transthoracic tumor resection (n= 44). Of the 145 patients, 64(44%) had undergone PET-CT. Univariate analysis showed the use of PET-CT to be associated with significantly longer local recurrence-free survival (p= 0.006) and tended to translate into ameasurable improvement of overall survival (p= 0.071). Since more patients underwent surgery in the group planned using PET-CT (20% vs. 44%; p= 0.002), we carried out amultivariate Cox regression analysis to adjust for this possible confounding factor. Surgery (p= 0.042; HR 0.55; 95% confidence interval: 0.31-0.98) as well as the use of PET-CT (p= 0.048; HR 0.60; 95% confidence interval: 0.36-0.99) nearly halved the risk of local recurrence. It was only in the group of patients with PET-CT that atrend towards ashorter overall survival was evident in lymph node-positive patients (p= 0.16), whereas nodal stage did not impact on survival in patients staged without PET-CT (p= 0.97). To the best of our knowledge these data suggest for the first time that the use of PET-CT in the framework of staging and planning of primary or neoadjuvant chemoradiotherapy for esophageal cancer has afavorable impact on patient survival.

A Prognostic Scoring Model for the Utility of Induction Chemotherapy Prior to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

ObjectivesThe 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. MethodsBetween 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. ResultsThe 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. ConclusionsOn 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.

Outcomes of adjuvant chemotherapy after neoadjuvant chemoradiotherapy for esophageal cancer.

92 Background: The use of adjuvant chemotherapy (AC) after neoadjuvant Chemoradiotherapy (NCR) and surgery for esophageal cancer is controversial. The purpose of this study is determine if AC is associated with an overall survival (OS) benefit after NCR. Methods: The National Cancer Database was queried to identify esophageal cancer patients who underwent NCR and surgery between 2006 and 2013 and stratified by treatment with AC. Propensity score matching was utilized against age, pathologic tumor and nodal stage, histology, and margin status. Kaplan-Meier and log-rank analysis was used to determine OS benefit. Univariate (UVA) and multivariate (MVA) was performed with Cox proportional hazard ratio analysis. Results: We identified 1816 patients. AC was associated with improved OS. The median and 3-year OS for AC versus none was 36.4 months and 50% versus 30.9 months and 45%, respectively, (p = 0.02), however, the benefit was restricted to node positive (N+) patients. The median and 3-year OS for AC versus none in N+ patients was 31 months and 44% versus 26 months and 36%, respectively, (p = 0.03). UVA revealed that AC only benefitted patients with N+, R0 resection, and adenocarcinoma. UVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of > 10 nodes and AC was associated with decreased mortality. MVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of > 10 nodes was associated with decreased mortality. MVA revealed that AC was not prognostic for OS in all patients nor in N+ patients. Conclusions: This is the largest analysis on the use of AC after NCR and surgery for esophageal cancer. While there is an OS benefit favoring AC, the benefit is restricted to N+ patients. However, no benefit to AC was seen on MVA. Clinical trials are needed to address the role of AC after NCR in esophageal cancer.

Interim FDG-PET imaging during neoadjuvant chemoradiotherapy for esophageal cancer: Correlation with pathologic response.

175 Background: In this prospective study we evaluated whether changes in metabolic tumor parameters on interim flurodeoxyglucose positron emission tomography (FDG-PET) performed during neoadjuvant chemoradiotherapy (CRT) for esophageal cancer correlates with histopathologic tumor response. Methods: From February 2012 to February 2016, 60 patients with esophageal cancer underwent PET scans before therapy and after 30-36 Gy. Patients who underwent surgery after carboplatin/paclitaxel CRT were eligible for the current analysis. PET metrics of the primary site including maximum standardized uptake value (SUVmax), SUV mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the pre-treatment and interim PET based on a manual contour and SUV 2.5 threshold. Patients were called histopathologic responders if they had a complete or near complete tumor response based on the modified Ryan scheme. Relative changes in PET metrics between pre-treatment and interim PET were compared between histopathologic responders and non-responders using the Mann-Whitney test and binary logistic regression. Results: Twenty-six patients were included in the analysis. Adenocarcinoma was the most common histology (n = 23). Eleven patients (42%) had a complete or near complete pathologic response to CRT (histopathologic responders). Changes in PET metrics from pre-treatment to interim PET based on the manual contour were not significantly different between responding and nonresponding tumors. The relative reduction of SUVmax (Mean ± SD) was 38.2% ± 28.4% for histopathologic responders and 27.9% ± 31.4% for non-responders. The relative reduction in MTV, SUV mean and TLG was 36.1% ± 26.2%, 23.5% ± 21.3%, and 49.3% ± 28.3% for histopathologic responders and 28.6% ± 32.0%, 11.8% ± 19.1%, and 33.1% ± 38.5% for histopathologic non-responders, respectively. When analyzed based on the SUV 2.5 threshold there continued to be no significant difference in PET metrics. Conclusions: In this pilot study we observed changes in metabolic tumor parameters on PET performed during CRT for esophageal cancer. However, these changes did not predict for histopathologic responders.

Does Neutrophil Lymphocyte Ratio Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer?

Does Neutrophil Lymphocyte Ratio Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer?

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUVmax in 18F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18F-FDG PET and CT. The current most accurate prediction model with SUVmax as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUVmax model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUVmax). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery.

Characterization of residual tumours at the primary site in patients with a near pathological complete response after neoadjuvant chemoradiotherapy for oesophageal cancer

A 'surgery as needed' strategy has been proposed for patients with oesophageal cancer who truly achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT). However, the ability to detect residual disease remains problematic. This study investigated the anatomical locations and pathological characteristics of residual cancer in patients with oesophageal squamous cell carcinoma (SCC) who achieved a near pCR following nCRT. Patients with oesophageal SCC who achieved a near pCR after nCRT were eligible. Near pCR was defined as residual cancer in the resection specimen representing less than 10 per cent of the apparent original tumour area. Detailed histopathological reassessment of 76 consecutive patients (mean age 54·4 years) with a near pCR was undertaken. Some 32 patients (42 per cent) with a near pCR had no detectable mucosal lesions. Residual tumour was identified most frequently in the submucosal layer (54, 71 per cent), followed by the mucosa (44, 58 per cent), muscle layer (36, 47 per cent) and adventitia (22, 29 per cent) (P < 0·001). Among patients without ypT1a disease, increasing depth of tumour invasion correlated negatively with the likelihood of mucosal involvement. Of patients with ypT3 disease, 16 of 22 had no detectable cancer located in the mucosa, compared with six of 29 with ypT1b disease (P < 0·001). Better tools for predicting pCR are required before considering a 'surgery as needed' approach in the management of oesophageal cancer.

Predicting response to neoadjuvant chemoradiotherapy in esophageal cancer by textural features derived from pretreatment FDG-PET scans.

93 Background: 18-F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is currently the imaging method of choice in assessing response of neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients. PET/CT derived texture analysis is potentially more useful than common PET/CT measurements in response assessment and might also be of predictive value in different cancer types. The aim of this study was to develop a model to predict response to nCRT in EC based on pretreatment FDG-PET derived textural features in combination with clinical parameters. Methods: We reviewed 80 locally advanced EC patients who underwent pretreatment FDG-PET/CT and radiation planning CT scans between 2009 and 2015. Patients received nCRT according to the CROSS regimen (carboplatin/paclitaxel/41.4Gy) followed by esophagectomy. We analyzed 7 clinical, 16 geometry-based, and 87 different texture features derived from pretreatment FDG-PET images of the radiotherapy gross tumor volume. Ordinal logistic regression analysis was performed to construct a prediction model for treatment response, which was pathologically classified in complete, partial and no response on the Mandard tumor regression grade (1 vs. 2-3 vs. 4-5). The performance of this model was estimated by comparison with clinical outcome. Results: Pathologic examination revealed 16 (20.0%) complete, 46 (57.5%) partial, and 18 (22.5%) non- responders. Response analysis yielded the following independent predictive textural features: SUVmin, small zone low gray level emphasis, and contrast; and the independent predictive clinical parameters: nodal stage, endoscopic tumor length, and gender. The model has a sensitivity/specificity, positive/negative predictive value, and accuracy of 69%/97%, 85%/93%, and 91% for the prediction of complete response and 61%/79%, 46%/88%, and 75% for non-response, respectively. Conclusions: The prediction model constructed in this study, shows a good overall performance level in predicting response to nCRT in EC patients, but requires further external validation and refinement before it can be used for clinical decision making.