Chemoradiotherapy For Esophageal Cancer Research Articles

Feasibility, Safety, and Factors Predicting Completion of CROSS Protocol–Based Neoadjuvant Chemoradiotherapy for Esophageal Squamous Carcinoma: Experience from an Indian Tertiary Care Cancer Center

Background Neoadjuvant chemoradiotherapy (NACRT) using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) protocol has improved esophageal cancer outcomes. This study reports the real-world experience of the CROSS regimen for esophageal squamous cell carcinoma (ESCC) regarding its feasibility, safety, and predictors of treatment completion from an Indian tertiary center. Methodology A retrospective review was conducted for patients with ESCC receiving CROSS (radiation dose: 41.4 Gy) or a modified CROSS (mCROSS; radiation dose: 45 Gy) protocol NACRT between 2015 and 2022. We studied the treatment tolerability, factors predicting NACRT completion, and the effect of completion of its chemotherapy component on the pathological outcomes. Results Of the109 patients (68.8% males; mean age, 56 ± 9 years; Charlson's comorbidity index [CCI] >2, 19.3%; stage III–IVA, 58%; mean tumor length, 5.5 ± 2.1cm; CROSS, 70.6%; mCROSS, 29.4%), all except 4 completed radiotherapy but only 58 (53.2%) patients completed ≥4 cycles of chemotherapy. Forty-nine patients belonged to the “extended” CROSS trial inclusion criteria. Among the 60 patients who fulfilled the CROSS inclusion criteria, only 51.7% were able to complete ≥4 chemotherapy cycles. The commonest reason for noncompletion of chemotherapy was the occurrence of neutropenia (60.8%). Pretreatment hemoglobin (≥12 vs. <12 g%; odds ratio [OR]: 2.76; 95% confidence interval [CI]: 1.10–6.96; p = 0.031), a low CCI (≤2 vs. >2; OR: 2.98; 95% CI: 1.02–8.73; p = 0.047), and radiation therapy techniques (conformal vs. conventional; OR: 3.29; 95% CI: 1.14–9.50; p = 0.028) were associated with completion of chemotherapy (≥4 cycles). Although there was a trend toward improved R0 resection (95.7 vs. 91.4%), reduced node positivity (17.0 vs. 31.4%), and a high pCR (57.4 vs. 48.6%) in patients completing chemotherapy (≥4 cycles) compared with those not completing chemotherapy (<4 cycles), these differences were statistically nonsignificant. Conclusion In this study, ESCC patients receiving the CROSS protocol NACRT could complete their radiotherapy component, but a significant proportion exhibited poor chemotherapy tolerance. Neutropenia was a major factor limiting chemotherapy delivery, but anemia, high CCI, and conventional radiation techniques were also associated with noncompletion of chemotherapy. The omission of a few chemotherapy cycles had no significant effect on the pathological response; however, its impact on cancer survival requires further evaluation.

Esophagectomy after definitive chemoradiation in esophageal cancer: a safe therapeutic strategy.

The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48days, P < 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P = 0.04) and anastomotic stenosis (42% vs. 17%, P < 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group.

Integrating MR radiomics and dynamic hematological factors predicts pathological response to neoadjuvant chemoradiotherapy in esophageal cancer

PurposeWe aimed to integrate MR radiomics and dynamic hematological factors to build a model to predict pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in esophageal squamous cell carcinoma (ESCC). MethodsPatients with ESCC receiving NCRT and esophagectomy between September 2014 and September 2022 were retrospectively included. All patients underwent pre-treatment T2-weighted imaging as well as pre-treatment and post-treatment blood tests. Patients were randomly divided to training set and testing set at a ratio of 7:3. Machine learning models were constructed based on MR radiomics and hematological factors to predict pCR, respectively. A nomogram model was developed to integrate MR radiomics and hematological factors. Model performances were evaluated by areas under curves (AUCs), sensitivity, specificity, positive predictive value and negative. ResultsA total of 82 patients were included, of whom 39 (47.6 %) achieved pCR. The hematological model built with four hematological factors had an AUC of 0.628 (95%CI 0.391–0.852) in the testing set. Two out of 1106 extracted features were selected to build the radiomics model with an AUC of 0.821 (95%CI 0.641–0.981). The nomogram model integrating hematological factors and MR radiomics had best predictive performance, with an AUC of 0.904 (95%CI 0.770–1.000) in the testing set. ConclusionAn integrated model using dynamic hematological factors and MR radiomics is constructed to accurately predicted pCR to NCRT in ESCC, which may be potentially useful to assist individualized preservation treatment of the esophagus.

1842: Definitive chemoradiation in esophageal cancer using VMAT technique: report on clinical outcomes

1842: Definitive chemoradiation in esophageal cancer using VMAT technique: report on clinical outcomes

Remodeling of Tumor Microenvironment Induced by Chemoradiation in Esophageal Cancer

Remodeling of Tumor Microenvironment Induced by Chemoradiation in Esophageal Cancer

S560 Advantages of the Second-Generation Photodynamic Therapy Using Talaporfin Sodium for Local Failure After Chemoradiotherapy for Esophageal Cancer

S560 Advantages of the Second-Generation Photodynamic Therapy Using Talaporfin Sodium for Local Failure After Chemoradiotherapy for Esophageal Cancer

Electrocardiogram with Artificial Intelligence Assessment as a Predictor of Cardiac Events and Overall Survival in Patients Receiving Radiotherapy for Esophageal Cancer

Neoadjuvant (chemo)radiotherapy (RT) has demonstrated an overall survival (OS) benefit in esophageal cancer and constitutes part of the standard of care trimodality therapy. Unfortunately, subsequent cardiac toxicity can reduce the benefit of treatment. Our group aimed to study whether data from electrocardiograms (ECGs) could predict clinical outcomes and cardiac events after RT for esophageal cancer, allowing for identification of and early intervention for patients at high risk for cardiac toxicity. Included patients received at least 41.4 Gy of pre-operative or definitive photon or proton RT for esophageal cancer from 2015 through July 2022. All ECGs were assessed using a previously validated artificial intelligence assessment for atrial fibrillation (AF) and reduced ejection fraction (rEF) (Noseworthy et al. Lancet 2022). The model determined propensities for the development of multiple cardiac events, including AF and heart failure (HF). Medical records were reviewed for cardiac events and conditions prior to and after RT. A cohort of 491 patients was assembled, with 301, 121, and 364 patients having an ECG prior to, during, and after RT, respectively. Of these, 84% had malignancy in the lower third of the esophagus and 48% underwent esophagectomy. At last follow-up relative to baseline assessment, patients had increased propensity for rEF (median 0.013, interquartile range (IQR): 0.001-0.038 vs. median 0.022, IQR: 0.011-0.074, p < 0.0001) and AF (median 0.16, IQR: 0.04-0.40 vs. median 0.048, IQR: 0.01-0.19, p < 0.0001). Increases in AF propensity were associated with reduced OS (hazard ratio (HR) = 1.10 per 0.1 increase, 95% confidence interval (CI): 1.03-1.17, p = 0.0071). Baseline rEF propensity was predictive of future HF events (HR = 1.14, 95% CI: 1.07-1.22, p < 0.001) for all patients or after excluding the 172 (35%) patients with baseline HF (HR = 1.45, 95% CI: 1.19-1.76, p < 0.001). Among patients who did not have HF prior to radiotherapy, the development of HF was associated with reduced OS (HR = 1.60, 95% CI: 1.10-2.32, p = 0.014). Currently available cardiac dosimetric parameters, including heart mean/max doses, did not significantly correlate with cardiac outcomes. Patients who underwent esophagectomy had improved OS (HR = 0.62, 95% CI: 0.47-0.82, p = 0.0008) and were not more likely to develop cardiac toxicity. This analysis suggests that chemoradiotherapy for esophageal cancer can have significant impacts on a patient's propensity for cardiac events, which are associated with reduced OS. ECGs carry the potential to identify patients at greater risk for such events, and baseline ECGs with artificial intelligence assessment could select patients for increased surveillance or early intervention to further optimize the therapeutic ratio of RT.

18F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction: Accuracy and Long-Term Implications

Purpose The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10–40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR.MethodsFour hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens.ResultsOf the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival.ConclusionPatients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.

Clinical impact of radiation-induced myocardial damage detected by cardiac magnetic resonance imaging and dose-volume histogram parameters of the left ventricle as prognostic factors of cardiac events after chemoradiotherapy for esophageal cancer.

This prospective study aimed to evaluate whether radiation (RT)-induced myocardial damage by cardiac magnetic resonance (CMR) imaging could be a predictor of cardiac events after chemoradiotherapy (CRT) for esophageal cancer and determine the dose-volume histogram (DVH) parameters of the left ventricle (LV) in predicting cardiac events. CMR imaging was performed before and 6months after CRT in patients receiving definitive CRT. RT-induced myocardial damage was defined as abnormal CMR findings indicating myocardial fibrosis corresponding to an isodose line of ≥30Gy. The cutoff values of the LV DVH parameters were calculated using the receiver operating characteristic curve based on the presence of RT-induced myocardial damage. The prognostic factors related to cardiac events of Grade 3 or higher were examined. Twenty-three patients were enrolled in the study. RT-induced myocardial damage by late gadolinium enhancement and/or an increase of 100ms or higher in native T1 post-CRT was detected in 10 of the 23 patients. LV V45 was the best predictive factor for RT-induced myocardial damage with a cutoff value of 2.1% and an area under the curve of 0.75. The median follow-up period was 82.1months. The 5- and 7-year cumulative incidences of cardiac events of Grade 3 or higher were 14.7 and 22.4%, respectively. RT-induced myocardial damage and LV V45 were significant risk factors (P = 0.015 and P = 0.013, respectively). RT-induced myocardial damage is a significant predictor of cardiac events. LV V45 is associated with RT-induced myocardial damage and subsequent cardiac events.

FLOT or CROSS for gastroesophageal junction cancersâ€"is the debate over yet?

In the last two decades, the incidence of gastroesophageal junction (GEJ) adenocarcinomas (AC) has increased, in part due to the increasing prevalence of obesity and untreated gastroesophageal reflux disease (GERD). Esophageal and GEJ cancers have become one of the leading causes of cancer deaths worldwide due to its aggressive nature. While the mainstay of treatment for locally advanced gastroesophageal cancers (GECs) remains surgery, several studies have now shown that multimodality approach yields better outcomes. GEJ cancers have historically been included both in esophageal cancer as well as gastric cancer trials. Therefore, both approaches, neoadjuvant chemoradiation (CRT) or perioperative chemotherapy are considered standard treatment options. thereon the same token, there yet remains a debate for the 'gold standard' treatment of locally advanced GEJ cancers. The landmark trials, fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) and ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), have shown similar improvements in overall survival (OS) and disease-free survival (DFS) for patients with resectable locoregional GEJ cancers. In this review, the authors attempt to highlight the historical evolution of current standard treatments and provide a sneak peek into the future of treatment of GEJ cancers. Several factors must be borne in mind when making the optimal choice for a patient. Some of these include surgical candidacy, tolerance to chemotherapy, eligibility for radiation (RT) as well as institutional preferences.

Chemoradiation for oesophageal cancer: the choice of treatment modality

BackgroundLocally advanced oesophageal cancer can be treated with definitive chemoradiation (dCRT) or with neoadjuvant chemoradiation followed by surgery (nCRT + S), but treatment modality choice is not always clear. The aim of this study was to investigate the factors associated with the choice of treatment modality in locally advanced oesophageal cancer.MethodsThis was a retrospective cohort study of 149 patients treated with dCRT(n = 85) or nCRT + S (n = 64) for oesophageal cancer in Helsinki University Hospital in 2008–2018. Logistic regression was used to analyse factors associated with choice of treatment modality and to compare dosimetric factors with postoperative complications. Multivariate analyses identified factors associated with survival.ResultsSurgery was performed after chemoradiation as planned on 64/91 patients (70%). 28/64 had pathological complete response (44%). Probability of nCRT + S was higher in stages I-III versus IV (OR 3.62, 95% CI 1.53–8.53; P = .003), ECOG 0–1 versus 2 (OR 6.99, 95% CI 1.81–26.96; P = .005) or in the middle/lower vs upper oesophageal tumours (OR 5.61, 95% CI 1.83–17.16, P = .003). Probability for surgery was lower, if patient had lost > 10% of body weight (OR 0.46, 95% CI 0.21–0.98, P = 0.043). Patients in the nCRT + S group had significantly better median overall survival (mOS) and local control than the dCRT group (60 vs. 10 months, P < .001 and 53 vs. 6 months, P < 0.0001, respectively). 10/85 (12%) patients died within three months after dCRT. In multivariate analysis, nCRT + S was associated with improved mOS (HR 0.28, 95% CI 0.17–0.44, P < .001). Current smokers had worse mOS (HR 2.02, 95% CI 1.04–3.92, P = .037) compared to never-smokers. No significant dosimetric factor associated with postoperative complications was found.ConclusionThe overall clinical status of the patients and the stage of the cancer guide the choice of treatment modalities, leading to overtreatment. Patients with better prognoses were more likely operated after chemoradiation, although there is no evidence of OS benefit in previous randomized trials. On the other hand, the prognosis was poor for patients with poor general health and advanced cancers, despite the chemoradiation. Thus, there are signs of overtreatment. MDT practice should be recommended to optimise the choice of treatment modalities. Smoking status is an independent factor associated with survival.

Role of (F-18) Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Prediction of Response to Neoadjuvant Therapy in Esophageal Cancer: Correlation with Pathological Response and Survival.

The purpose of this study is to assess the correlation between metabolic response with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and pathological response in patients with locally advanced esophageal cancer treated with neoadjuvant chemoradiotherapy and to study FDG-PET parameters for the prediction of pathological response and outcome. Twenty-five patients with locally advanced esophageal cancer underwent two FDG-PET/CT scans for initial staging and after neoadjuvant chemoradiotherapy. FDG uptake in the primary tumor was calculated in both scans (SUVmax, SULpeak, and TLG). Metabolic response was assessed according to the reduction of PET parameters: complete response (mCR = 100%), partial response (mPR ≥50%), and no response (mNR ≤50%). Pathological response was also classified as complete (pCR), partial (pPR), or no response (pNR). Patients were followed up (range, 8-99 months) determining free-disease interval (FDI) and overall survival (OS). Two patients were excluded due to exitus for nonesophageal-related causes. The metabolic response was observed in 18/23 remaining patients (3mCR, 15 mPR), of which 12/18 patients showed a pathological response (3 pCR, 9 pPR). A major discrepancy was observed in 2 mNR patients who achieved pPR. FDI and OS were longer in patients with metabolic response than nonresponders, but no statistical difference was found. No significant correlation was found between PET parameters and pathological response, FDI, and OS. FDG-PET/CT is a useful technique to assess response to neoadjuvant chemoradiotherapy in esophageal cancer. Although in this preliminary study, no correlation between metabolic and pathologic response was found and no statistical differences between responders and nonresponders were observed, a tendency of longer FDI and OS was apparently found in responders patients.

'CROSS'-ing into the 'Real World': a retrospective cohort study of patients receiving trimodality and bimodality therapy for esophageal cancer.

A standard of care for nonmetastatic esophageal cancer is trimodality therapy consisting of neoadjuvant chemoradiation and esophagectomy, with evidence for improved overall survival versus surgery alone in the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial. Patients who receive treatment with curative intent but are poor candidates for or decline surgery receive definitive bimodality therapy. Literature characterizing patients who receive bimodality therapy compared to trimodality therapy, and their relative outcomes, is sparse, especially among patients who are too old or too frail to qualify for clinical trials. In this study, we assess a single-institution real-world dataset of patients receiving bimodality and trimodality management. Patients treated for clinically resectable, nonmetastatic esophageal cancer between 2009 and 2019 who received bimodality or trimodality therapy were reviewed, generating a dataset of 95 patients. Clinical variables and patient characteristics were assessed for association with modality on multivariable logistic regression. Overall, relapse-free, and disease-free survival were assessed with Kaplan-Meier analyses and Cox proportional modeling. For patients nonadherent to planned esophagectomy, reasons for nonadherence were recorded. Bimodality therapy was associated with greater age-adjusted comorbidity index, worse performance status, higher N-stage, presenting symptom other than dysphagia, and held chemotherapy cycles on multivariable analysis. Compared to bimodality therapy, trimodality therapy was associated with higher overall (3-year: 62% vs. 18%, P<0.001), relapse-free (3-year: 71% vs. 18%, P<0.001), and disease-free (3-year: 58% vs. 12%, P<0.001) survival. Similar results were observed among patients who did not meet CROSS trial qualifying criteria. Only treatment modality was associated with overall survival after adjusting for covariates (HR 0.37, P<0.001, reference group: bimodality). Patient choice accounted for 40% of surgery nonadherence in our population. Patients receiving trimodality therapy were observed to have superior overall survival compared to bimodality therapy. Patient preference for organ-preserving therapies appears to impact resection rate; further characterization of patient decision-making may be helpful. Our results suggest patients who wish to prioritize overall survival should be encouraged to pursue trimodality therapy and obtain early consultation with surgery. Development of evidence-based interventions to physiologically prepare patients before and during neoadjuvant therapy as well as efforts to optimize the tolerability of the chemoradiation plan are warranted.

Primary Surgery Not Inferior to Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma

BackgroundThe current gold standard for treatment of locally advanced esophageal adenocarcinoma is neoadjuvant chemotherapy or chemoradiotherapy followed by surgery. The shift toward neoadjuvant chemoradiotherapy (nCRT) was driven by the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial. This study reassessed, in daily practice, the presumed advantage of nCRT followed by surgery on long-term survival compared with primary surgery, in a group of all adenocarcinomas treated through a transthoracic approach with extensive 2-field lymphadenectomy. MethodsThis retrospective cohort study with propensity score-matched analysis included all surgically treated patients between 2000 and 2018 with locally advanced adenocarcinoma (cT1/2 N+ or cT3/4 N0/+). For appropriate comparison, exclusion criteria of the CROSS trial were applied. Patients were matched on age, Charlson comorbidity score, clinical tumor length, and lymph node status. The primary end point was 5-year overall survival. ResultsThere were 473 eligible patients who underwent primary surgery (225 patients) or nCRT + surgery (248 patients). After propensity score-matched analysis, 149 matched cases were defined in each group for analysis. There was no significant difference after 5 years between the matched groups in median overall survival (32.5 and 35.0 months, P = .41) and median disease-free survival (14.3 and 13.5 months, P = .16). nCRT was associated with significantly more postoperative complications (mean Comprehensive Complication Index score: 21.0 vs 30.5, P < .0001) and longer mean stay in the hospital (14.0 vs 18.2 days, P = .05) and intensive care unit (11.7 vs 37.7 days, P = .05). ConclusionsOur propensity score-matched results indicate that primary surgery, performed through transthoracic approach with extensive 2-field lymphadenectomy, can offer a comparable overall and disease-free survival after 5 years, with potentially fewer postoperative complications and shorter hospital and intensive care unit stay compared with nCRT followed by surgery.

Neoadjuvant chemoradiation in elderly Irish patients with esophageal cancer: A review of the clinical outcomes and toxicity.

335 Background: In locally advanced esophageal cancer, neoadjuvant chemo-radiotherapy improves survival compared with surgery alone. In the Chemo-Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), the median age was 60. However, 1/3 of patients diagnosed with esophageal cancer are over 70 years. The CROSS outcomes are therefore limited in its application to older patients. The objective of this study is to report and compare the outcomes and tolerability in elderly patients (≥70 years), who underwent neoadjuvant chemo-radiation for esophageal cancer with younger patients &lt; 70 years. Methods: A retrospective analysis of patients treated with neoadjuvant chemo-radiation for esophageal cancer between 1st January 2015 and 1st January 2021 was completed. Baseline characteristics and haematological toxicities were reported. Pathological response was reported. Survival was estimated using the Kaplan-Meier method. Results: In total 105 patients were included; 35 (33%) were ≥ 70 years and 70 (67%) patients were &lt; 70 years. In the elderly cohort, the median age was 75 (70-86) and the younger cohort median age was 60 (29-69). 73% of patients in each cohort were male. 31 (89%) of older adults experienced any grade of anaemia compared with 45 (64%) of the younger cohort. Only one patient experienced ≥ grade 3 anaemia in each cohort. 18(51%) and 33(47%) of older and younger patients respectively experienced any grade of neutropenia. 5(14%) older and 7(10%) younger patients experienced ≥ grade 3 neutropenia. 15(43%) and 43(61%) of older and younger patients experienced any grade of thrombocytopenia. No patients experienced ≥ grade 3 thrombocytopenia. 80% of the older and 86% of the younger cohort proceeded to surgery. 3(11%) and 17(29%) of the older and younger cohorts respectively who underwent surgery achieved a complete pathological response. There was no difference in overall survival (OS) between the cohorts (p=0.48). There was also no difference in progression free survival (PFS) between the cohorts. Conclusions: In conclusion, we confirm that neoadjuvant chemo-radiation is tolerable in patients ≥ 70 when compared with patients &lt; 70 years. Both OS and PFS is similar in both cohorts. We recommend the use of neoadjuvant therapy in appropriately selected patients ≥ 70 years.

Evaluation of Exposure Doses of Elective Nodal Irradiation in Chemoradiotherapy for Advanced Esophageal Cancer.

We evaluated elective nodal irradiation (ENI) doses during radical chemoradiotherapy (CRT) for esophageal cancer (EC). A total of 79 patients (65 men and 14 women) aged 52-80 years with T1-3, N0-3, and M0 (including M1ly) who underwent CRT for EC during November 2012-September 2019 were eligible for this retrospective analysis. Patients were divided into two groups: the high-dose group (HG), including 38 patients who received ≥40 Gy as ENI; and the low-dose group (LG), including 41 patients who received <40 Gy. The median doses were 40.0 and 36.0 Gy in HG and LG, respectively. During the follow-up (median: 36.7 months), no lymph node recurrence was observed in the ENI field in all patients. Lymph node recurrence near the ENI field was observed in six patients. No significant differences were observed between the two groups in median overall survival, progression-free survival, and local control. Grade 3-4 acute and late adverse events were observed in five patients of HG and six patients of LG, respectively. No ulceration or stricture was observed in the ENI field on endoscopy examined with 58 Gy irradiation. In conclusion, an ENI dose of 36 Gy could be considered to control the elective nodes of EC.

Relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer.

The liver is the largest organ in the abdomen and is often irradiated in radiotherapy for non-hepatic malignancies. As most of the studies on changes in liver volume are on hepatocellular carcinoma based on liver dysfunction, there are few studies on healthy liver. In this study, we investigated the relationship between absorbed dose and changes in liver volume after chemoradiotherapy for esophageal cancer in patients without apparent pre-treatment liver dysfunction. Liver volume was compared between pre-treatment, acute (< 4months) and late post-treatment (≥ 4 and < 13months) phases in 12 patients using abdominal plain CT images. Volume changes were evaluated separately for the right and left lobes. We investigated the relationship between the volume change and VxGy (percentage of volume received x Gy or more dose). In addition, volume change for each absorbed dose was investigated using deformable image registration. The volume of the left lobe showed a significant decrease between pre-treatment and acute post-treatment phases (p < 0.001), while the volume of right lobe and between acute and late post-treatment phase of left lobe did not. The mean value of the volume reduction rate of the left lobe was 51.1% and equivalent to the mean value of V30Gy. As a result of the volume change for each absorbed dose, the volume reduction rate increased as the absorbed dose increased, and a significant volume loss was observed at doses above 11Gy. Volume of the liver significantly decreased only in the acute phase after chemoradiotherapy for esophageal cancer. The tolerable dose for a healthy liver is generally considered to be 30Gy, but attention should be paid to lower doses to avoid radiation-induced liver injury.

OGC O01 Delayed surgical Intervention after Chemoradiotherapy in Esophageal cancer (DICE) study

Abstract Background Chemoradiotherapy (CRT) is a core component of curative treatment for esophageal cancer for locally advanced esophageal cancer. Salvage esophagectomy is undertaken in patients who experience recurrent or residual cancer post-CRT. This study aims determine the impact of delayed surgical intervention following chemoradiotherapy on survival from oesophageal cancer. Methods This was an international, multi-center, retrospective cohort study involving seventeen tertiary international centers, including patients who received CRT followed by surgery between 2010–2020. In the main analysis patients were divided into four groups based upon the interval between chemoradiotherapy and surgery (0–50, 51–100, 101–200 and &amp;gt;200 days) to assess the impact upon 90-day mortality and 5-year overall survival (OS). Multivariable logistic and Cox regression provided hazard rations (HRs) with 95% confidence intervals (95%CI) adjusted for relevant patient, oncological and pathological confounding factors. Results 2,867 patients who underwent oesophagectomy after CRT were included. The mean age of the cohort was 63.2 (9.47) years. 79.7% were male; and 87.2% had an ASA grade ≥2. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality; compared to 0–50 (reference), 51–100 days (HR=1.54, 95%CI 1.04–2.29), 101–200 days (HR=2.14, 95%CI 1.37–3.35) and &amp;gt;200 days (HR=3.06, 95%CI 1.64–5.69). Similarly, a poorer 5-year survival was also observed with prolonged interval following CRT compared to 0–50 (reference), 101–200 days (HR=1.41, 95%CI 1.17–1.70) and &amp;gt;200 days (HR=1.64, 95%CI 1.24–2.17). Conclusions Prolonged interval following CRT and esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Patients must be carefully considered and counselled regarding surveillance and salvage esophagectomy following CRT.

Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer

Neoadjuvant chemoradiotherapy (nCRT) improves outcomes in resectable esophageal adenocarcinoma (EAC), but acquired resistance precludes long-term efficacy. Here, we delineate these resistance mechanisms. RNA sequencing on matched patient samples obtained pre-and post-neoadjuvant treatment reveal that oxidative phosphorylation was the most upregulated of all biological programs following nCRT. Analysisof patient-derived models confirms that mitochondrial content and oxygen consumption strongly increase in response to nCRT and that ionizing radiation is the causative agent. Bioinformatics identifies estrogen-related receptor alpha (ESRRA) as the transcription factor responsible for reprogramming, andoverexpression and silencing of ESRRA functionally confirm that its downstream metabolic rewiring contributes to resistance. Pharmacological inhibition of ESRRA successfully sensitizes EAC organoids and patient-derived xenografts to radiation. In conclusion, we report a profound metabolic rewiring following chemoradiation and demonstrate that its inhibition resensitizes EAC cells to radiation. These findings hold broader relevance for other cancer types treated with radiation as well.

A Deep Learning Classifier Based on Pre-Radiation Computed Tomography and Clinical Parameters to Predict Pathological Complete Response after Neoadjuvant Chemoradiation in Esophageal Cancer

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemoradiation (NCRT) followed by surgery is the standard treatment for resectable esophageal cancer. More than 30% patients achieve pathological complete response (pCR) after NCRT, who may avoid the followed surgery. However, there is no reliable method in predicting pCR yet. Artificial intelligence, especially deep learning, has made great progress in many fields including treatment response prediction. Therefore, we built up a deep learning classifier based on pre-radiation computed tomography and clinical parameters to predict pCR after NCRT for esophageal cancer. <h3>Materials/Methods</h3> Between 2009 and 2021, consecutive patients with esophageal cancer received NCRT and complete resection were retrospectively analyzed. Pathological response assessed on surgical specimen was collected. Patients were randomly assigned to the training set, validation set, and testing set as 7: 1: 2. We built a binary classification neural network based on 3D Resnet. Pre-radiation computed tomography (CT) was fed as input to build the imaging classifier. The filtered clinical parameters including gender, tumor location, clinical stage, pathological type, sequence of chemoradiation, chemotherapy regimen and radiotherapy technique were then added by encoded as fully connected layer to build the combined classifier. Area under the receiver operating characteristic curve (AUC) was calculated to evaluate the prediction performance and the optimal cut-off point was determined by Youden index. <h3>Results</h3> Totally 279 patients were enrolled, of whom 93 achieved pCR (33.3%). The performances of imaging classifier were AUC=0.989 (95% CI 0.937-0.986) with the sensitivity of 98.6% and specificity of 98.5% in the training set, and AUC=0.649 (95% CI 0.481-0.660) with the sensitivity of 66.7% and specificity of 58.9% in the testing set, respectively. After the addition of clinical parameters, the combined classifier showed AUC=0.855 (95% CI 0.797-0.986) with the sensitivity of 82.4% and specificity of 74.3% in the training set, and AUC=0.731 (95%CI 0.631-0.819) with the sensitivity of 76.6% and specificity of 65.6% in the testing set, respectively. <h3>Conclusion</h3> The combined deep learning classifier can accurately predict pCR after NCRT for esophageal cancer. Besides, addition of necessary clinical parameters can remedy the overfitting of imaging classifier. Prospective exploration based on larger data sets is needed to further improve the accuracy and generalization.