Chemoradiotherapy For Esophageal Cancer Research Articles

Definitive radiochemotherapy in esophageal cancer - a single institution experience.

BackgroundDefinitive radiochemotherapy is the preferred treatment option in patients with the cancer of the cervical esophagus and a viable treatment option in patients with the cancer of lower two thirds of the esophagus, who decline proposed surgical treatment. The purpose of the study was to evaluate the treatment results with definitive radiochemotherapy of patients with esophageal cancer, treated in a single institution in the period from 2010 to 2017.Patients and methodsAll available medical data for 55 patients with esophageal cancer, who were treated with definitive radiochemotherapy with curative intent, were analyzed retrospectively. Patients were irradiated to a total dose to the tumor of 70 Gy (2 Gy per fraction) in upper third (cervical) tumors or to the mean total dose of 57.6 Gy (1.8 Gy per fraction) in middle third (intrathoracic) tumors. All but one patient received concomitant chemotherapy, with the majority of them (41 patients; 74.5%) receiving concomitant chemotherapy with 5-fluorouracil in continuous 96 hours infusion and cisplatin. The main endpoints of the study were overall survival (OS; death of any cause), locoregional control (LRC; local and/or regional disease recurrence) and disease-free survival (DFS; recurrence of any kind and/or new primary malignoma). Univariate analysis testing the impact of different parameters on survivals and analysis of treatment related side effects were performed as well.ResultsThe mean age of patients was 62 years (SD 9 years; range: 29–80 years). Majority of them had squamous cell cancer (53 patients; 96.4%) in the stage T3 or T4 (47 patients; 85.5%) and/or N+ disease (35 patients; 63.6%). Median follow-up time for the whole group of patients was 16.8 months (range: 0.3–81.8 months). At the time of analysis 14 (25.5%) patients were still alive. Rates for OS, LRC and DFS at two and five years were as follows: 47% and 19.4%; 43.7% and 41%; 32.1% and 11.5%, respectively.ConclusionsThe study results of treatment with definitive radiochemotherapy in patients with esophageal cancer are similar to the results of other studies. Majority of patients ended the treatment according to the protocol, which at least in part can be attributed to the adequate and well organized supportive treatment in our institution.

Outcome of Weekly Carboplatin–Paclitaxel-based Definitive Chemoradiation in Oesophageal Cancer in Patients Not Considered to be Suitable for Platinum–Fluoropyrimidine-based Treatment: A Multicentre, Retrospective Review

AimsAlthough cisplatin–fluoropyrimidine-based definitive chemoradiotherapy (dCRT) is a standard of care for oesophageal cancer, toxicity is significant and limits its use in elderly and frail patients. Weekly carboplatin–paclitaxel-based dCRT provides a viable alternative, although prospective data are lacking in the dCRT setting. Here we report the results of a national, multicentre retrospective review of outcome in patients treated with weekly carboplatin–paclitaxel-based dCRT. Materials and methodsIn this multicentre retrospective study of nine radiotherapy centres across the UK we evaluated the outcome of patients who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous cell or undifferentiated; World Health Organization performance status 0–2; stage I–III disease) and had been selected to receive weekly carboplatin–paclitaxel-based dCRT as they were considered not suitable for cisplatin–fluoropyrimidine-based dCRT. dCRT consisted of carboplatin AUC 2 and paclitaxel 50 mg/m2 (days 1, 8, 15, 22, 29) and the recommended radiation dose was 50 Gy in 25 daily fractions. We assessed overall survival, progression-free survival (PFS; overall, local and distant), proportion of patients who were failure free at the response assessment (12 weeks after dCRT), treatment compliance and toxicity. ResultsIn total, 214 patients from nine UK centres were treated between 15 February 2013 and 19 March 2019: 39.7% of patients were ≥75 years; 18.7% ≥ 80 years. Indications for weekly carboplatin–paclitaxel-based dCRT were comorbidities (47.2%), clinician choice (36.4%) and poor tolerance/progression on cisplatin–fluoropyrimidine induction chemotherapy (15.8%). The median overall survival was 24.28 months (95% confidence interval 20.07–30.09) and the median PFS was 16.33 months (95% confidence interval 14.29–20.96). Following treatment, 69.1% (96/139) had a combined complete response on endoscopy with non-progression (complete response/partial response/stable disease) on imaging. The 1- and 2-year overall survival rates for this patient group were 81.9% (95% confidence interval 75.6–86.8%) and 50.6% (95% confidence interval 40.5–60.0%), respectively. Thirty-three per cent (n = 70) of patients experienced at least one grade 3 + acute toxicity (grade 3/4 haematological: 10%; grade 3/4 non-haematological: 32%) and there were no treatment-related deaths. 86.9% of patients completed at least four cycles of concomitant weekly carboplatin–paclitaxel-based chemotherapy and planned radiotherapy was completed in 97.7% (209/214). ConclusionWeekly carboplatin–paclitaxel-based CRT seems to be well tolerated in elderly patients and in those with comorbidities, where cisplatin–fluoropyrimidine-based dCRT is contraindicated. Survival outcomes are comparable with cisplatin–fluoropyrimidine-based dCRT.

CT radiomic features for predicting resectability of oesophageal squamous cell carcinoma as given by feature analysis: a case control study

BackgroundComputed tomography (CT) is commonly used in all stages of oesophageal squamous cell carcinoma (SCC) management. Compared to basic CT features, CT radiomic features can objectively obtain more information about intratumour heterogeneity. Although CT radiomics has been proved useful for predicting treatment response to chemoradiotherapy in oesophageal cancer, the best way to use CT radiomic biomarkers as predictive markers for determining resectability of oesophageal SCC remains to be developed. This study aimed to develop CT radiomic features related to resectability of oesophageal SCC with five predictive models and to determine the most predictive model.MethodsFive hundred ninety-one patients with oesophageal SCC undergoing contrast-enhanced CT were enrolled in this study, and were composed by 270 resectable cases and 321 unresectable cases. Of the 270 resectable oesophageal SCCs, 91 cases were primary resectable tumours; and the remained 179 cases received neoadjuvant therapy after CT, shrank on therapy, and changed to resectable tumours. Four hundred thirteen oesophageal SCCs including 189 resectable cancers and 224 unresectable cancers were randomly allocated to the training cohort; and 178 oesophageal SCCs including 81 resectable tumours and 97 unresectable tumours were allocated to the validation group. Four hundred ninety-five radiomic features were extracted from CT data for identifying resectability of oesophageal SCC. Useful radiomic features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomic features were chosen using multivariable logistic regression, random forest, support vector machine, X-Gradient boost and decision tree classifiers. Discriminating performance was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1score.ResultsEight radiomic features were selected to create radiomic models related to resectability of oesophageal SCC (P-values < 0.01 for both cohorts). Multivariable logistic regression model showed the best performance (AUC = 0.92 ± 0.04 and 0.87 ± 0.02, accuracy = 0.87 and 0.86, and F-1score = 0.93 and 0.86 in training and validation cohorts, respectively) in comparison with any other model (P-value < 0.001). Good calibration was observed for multivariable logistic regression model.ConclusionCT radiomic models could help predict resectability of oesophageal SCC, and multivariable logistic regression model is the most predictive model.

Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer

Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer

Mean Cardiopulmonary Dose and Vertebral Marrow Dose Differentially Predict Lineage-Specific Cytopenia Kinetics During Radiotherapy for Esophageal Cancer

Lymphopenia is associated with poor outcomes in esophageal cancer (EC) patients (pts) undergoing chemoradiotherapy (CRT). While dose to vertebral marrow is implicated in lymphopenia, cytopenic effects of RT on non-marrow compartments are not well described. We hypothesized that dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) has unique effects on WBC counts and clinical outcomes. We identified clinical and dosimetric factors associated with cytopenias in EC pts undergoing CRT, and temporally characterized dose-dependent effects on central and peripheral hematological compartments during therapy. Weekly and 90-day post-CRT cell counts (lymphocyte [Lym], neutrophil [Neu], hemoglobin [Hgb], and platelet [Plt]) were retrospectively collected for 49 pts treated with CRT (definitive or neoadjuvant) for locoregional EC. Dose volume histogram data for thoracic vertebral (TV) volumes receiving 10-40 Gy (TV10-4010-40 Gy (TVS10-40 Gy) was calculated by subtracting TV10-TV40 from total TV volume. Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels, excluding marrow, as a surrogate for circulating blood pool. We used linear and logistic regression to examine associations between absolute (Abs) and normalized (Nml) cell count nadirs and grade 3 (Gr3) and 4 (Gr4) cell count toxicities by CTCAE v5.0. Repeated measures ANOVA tested for associations between cell count trends and clinical predictors. WBC and Plt counts reached nadir at week 6 of CRT and Hgb at 90 days post-CRT. Abs WBC and Nml Lym declined more rapidly in diabetic pts (p=.02, p=.05); Nml Lym also declined more rapidly with age >66 (p=.047). mCPD was strongly associated with lower Abs and Nml WBC nadir (p=.0003, p=.0006), and Abs and Nml Neu nadir (p<0.01, p=.02), but not Lym nadirs (p>.27). In contrast, TVS10-30 and TV10-20 were associated with Abs Lym nadir (all p<.03, p≤.01) and Nml Lym nadir (all p≤.01, all p≤.001). mCPD was associated with Gr3+ leukopenia (p=.04) and Gr3+ neutropenia (p=0.01). In multivariate analysis, mCPD remained associated with Abs WBC nadir (p=.0018) Nml Neu nadir (p=.0392) and Abs Neu nadir (p=.0053), and TVS10-40 remained associated with Nml Lym nadir (all p≤.042). Mean cardiopulmonary dose and TV marrow dose differentially predict lineage-specific cytopenias during CRT for EC. mCPD is significantly associated with lower Abs and Nml nadirs of multiple cell lines, with the exception of Lym. In contrast, TV dose is significantly associated with lower Lym nadirs but not with other cytopenias. Diabetes and age are associated with a more rapid decline in WBC and Lym counts. Further studies are needed to confirm mechanisms of mCPD-associated count suppression, and to prospectively evaluate the influence of these factors on pt outcomes.

Is Concurrent Chemotherapy With Radiotherapy for Esophageal Cancer Beneficial in Patients Aged 80 Years or Older?

To determine whether concurrent chemotherapy with radiotherapy should be performed in elderly patients with esophageal cancer. A total of 185 patients aged 80 years or older who were treated with definitive radiotherapy alone or combined with chemoradiotherapy for esophageal cancer at seven institutions were enrolled. In order to compare survival rates of patients treated with chemoradiotherapy with those of patients treated with radiotherapy alone, propensity score matching was performed to homogenize the two populations. For the whole patient cohort, the 3-year overall survival (OS) rate was 52.6% and the median survival was 42.5 months. After propensity score matching, the 3-year OS rate for the chemoradiotherapy group was not significantly better than that for the group treated with radiotherapy alone (53.7% vs. 59.9%, p=0.876). Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older did not have significant OS benefit over radiotherapy alone.

Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer

Combination of Toripalimab and Chemoradiotherapy in Esophageal Cancer

P-124 - Definitive chemoradiotherapy in oesophageal cancer: treatment outcomes from a regional cancer centre

P-124 - Definitive chemoradiotherapy in oesophageal cancer: treatment outcomes from a regional cancer centre

Su1123 – Added Value of Mri to Endoscopic and Endosonographic Response Assessment After Neoadjuvant Chemoradiotherapy in Esophageal Cancer: A Pilot Study

Su1123 – Added Value of Mri to Endoscopic and Endosonographic Response Assessment After Neoadjuvant Chemoradiotherapy in Esophageal Cancer: A Pilot Study

1031 – Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Cancer: is More Better?

1031 – Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Cancer: is More Better?

Prediction of response after chemoradiation for esophageal cancer using a combination of dosimetry and CT radiomics.

To investigate the treatment response prediction feasibility and accuracy of an integrated model combining computed tomography (CT) radiomic features and dosimetric parameters for patients with esophageal cancer (EC) who underwent concurrent chemoradiation (CRT) using machine learning. The radiomic features and dosimetric parameters of 94 EC patients were extracted and modeled using Support Vector Classification (SVM) and Extreme Gradient Boosting algorithm (XGBoost). The 94-sample dataset was randomly divided into a 70-sample training subset and a 24-sample independent test set while keeping the class proportions intact via stratification. A receiver operating characteristic (ROC) curve was used to assess the performance of models using radiomic features alone and using combined radiomic features and dosimetric parameters. A total of 42 radiomic features and 18 dosimetric parameters plus the patients' characteristic parameters were extracted for these 94 cases (58 responders and 36 non-responders). XGBoost plus principal component analysis (PCA) achieved an accuracy and area under the curve of 0.708 and 0.541, respectively, for models with radiomic features combined with dosimetric parameters, and 0.689 and 0.479, respectively, for radiomic features alone. Image features of GlobalMean X.333.1, Coarseness, Skewness, and GlobalStd contributed most to the model. The dosimetric parameters of gross tumor volume (GTV) homogeneity index (HI), Cord Dmax, Prescription dose, Heart-Dmean, and Heart-V50 also had a strong contribution to the model. The model with radiomic features combined with dosimetric parameters is promising and outperforms that with radiomic features alone in predicting the treatment response of patients with EC who underwent CRT. • The model with radiomic features combined with dosimetric parameters is promising in predicting the treatment response of patients with EC who underwent CRT. • The model with radiomic features combined with dosimetric parameters (prediction accuracy of 0.708 and AUC of 0.689) outperforms that with radiomic features alone (best prediction accuracy of 0.625 and AUC of 0.412). • The image features of GlobalMean X.333.1, Coarseness, Skewness, and GlobalStd contributed most to the treatment response prediction model. The dosimetric parameters of GTV HI, Cord Dmax, Prescription dose, Heart-Dmean, and Heart-V50 also had a strong contribution to the model.

PO-0795 Prediction of severe lymphopenia during chemoradiotherapy for esophageal cancer

PO-0795 Prediction of severe lymphopenia during chemoradiotherapy for esophageal cancer

PV-0623 Tumor-stroma ratio for predicting pathologic response after chemoradiotherapy in esophageal cancer

PV-0623 Tumor-stroma ratio for predicting pathologic response after chemoradiotherapy in esophageal cancer

PO-0798 Response assessment to neoadjuvant chemoradiotherapy for esophageal cancer using PET/CT and DW-MRI

PO-0798 Response assessment to neoadjuvant chemoradiotherapy for esophageal cancer using PET/CT and DW-MRI

Neoadjuvant treatment strategy for locally advanced thoracic esophageal cancer.

Multimodal treatment combining surgery with chemotherapy and/or radiotherapy is necessary to improve the chances of survival in patients with locally advanced thoracic esophageal cancer. Based on the results of the Japan Clinical Oncology Group 9907 (JCOG9907) trial, neoadjuvant chemotherapy, two courses of cisplatin and 5‐fluorouracil (5‐FU), followed by esophagectomy with D2 lymphadenectomy is the recommended treatment in Japan. Alternatively, neoadjuvant chemoradiotherapy (NACRT) typified by carboplatin and paclitaxel plus concurrent radiotherapy with 41.4 Gy (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study [CROSS]) has shown promising outcomes in some Western countries. Currently, several clinical trials are being conducted within and outside of Japan to confirm the best neoadjuvant treatment regimen. For instance, a three‐arm phase III randomized controlled trial (JCOG1109) is ongoing in Japan. The three arms comprise a doublet regimen (two courses of cisplatin 80 mg/m2 day 1 and 5‐FU 800 mg/m2 days 1‐5; repeated every 3 weeks) versus a triplet regimen (three courses of docetaxel, 70 mg/m2 day 1; cisplatin 70 mg/m2 day 1; and 5‐FU 750 mg/m2 days 1‐5; repeated every 3 weeks) versus a chemoradiotherapy (CRT) regimen (radiotherapy of 41.4 Gy/23 fractions with two courses of cisplatin 75 mg/m2 day 1 and 5‐FU 1000 mg/m2 days 1‐4; repeated every 4 weeks). Development of a multimodal strategy for neoadjuvant therapy is expected to receive the continuous focus of research in the hope of achieving better outcomes from treatment of patients with advanced thoracic esophageal cancer.

Diagnostic performance of MRI for assessment of response to neoadjuvant chemoradiotherapy in oesophageal cancer.

BackgroundPatients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non‐surgical management. The aim of this study was to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2‐weighted (T2W) and diffusion‐weighted (DW) MRI.MethodsPatients with locally advanced oesophageal cancer who underwent T2W‐ and DW‐MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five‐point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW‐MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated.ResultsTwelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W‐MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW‐MRI were 90–97 and 42–50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W‐MRI, and 0·71, 0·70 and 0·70 on T2W + DW‐MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24–0·55 on T2W‐MRI to 0·55–0·71 with DW‐MRI.ConclusionPreoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.

Active surveillance versus surgery in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal cancer: a propensity-matched study

Active surveillance versus surgery in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal cancer: a propensity-matched study

Radiochemotherapy in esophageal cancer

Esophageal cancer is one of the ten most frequent tumors worldwide. There are two major histologies: squamous cell carcinomas, which appear more frequently in the upper part of the esophagus, and adenocarcinomas, which are predominantly found in the distal part and at the gastroesophageal junction. Most patients suffer from locally advanced tumors, for which the prognosis is still poor with a 5-year survival rate of 15–25%. Treatment is based on histology, tumor stage, location of the tumor, performance status, age, and comorbidities and it consists of surgery, chemotherapy, or radiotherapy or a combination of these. Over the past decades, neoadjuvant radiochemotherapy followed by surgery became standard of care in patients with locally advanced squamous cell carcinomas suitable for surgery. The treatment of locally advanced adenocarcinomas and junctional tumors is still under debate and consists of either perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. In patients not suitable for surgery, definitive radiochemotherapy is considered the treatment of choice. Modern radiotherapy in esophageal cancer is increasingly conformal and the dose at organs-at-risk could be reduced over the years to lower the rate of treatment-related side effects. Individualization of treatment and new combinations of systemic agents are under investigation to improve treatment outcome.

Comparative study of dual energy CT iodine imaging and standardized concentrations before and after chemoradiotherapy for esophageal cancer

BackgroundTo compare dual energy CT iodine imaging and standardized iodine concentration before and after chemoradiotherapy (CRT) for esophageal cancer and evaluate the efficacy of CRT for EC by examining DECT iodine maps and standard CT values.MethodsThe clinical data of 45 patients confirmed by pathology with newly diagnosed esophageal cancer who underwent concurrent CRT from February 2012 to January 2017 in our department of radiology were collected. All patients underwent dual-source dual-energy CT (DECT) before and after CRT. Normalized iodine concentration (NIC) and normalized CT (NCT) corresponding to the overall cancer lesion and its maximum cross-sectional area were observed and compared. Additionally, 30 healthy individuals were compared as control group. After treatment, the patients were divided into two groups according to RECIST1.1: treatment effective group and ineffective group.ResultsThere were 33 patients (CR 9, PR 24) in the effective group and 12 patients (SD 12, PD 0) in the ineffective group. There was no significant difference in the NIC-A, NIC-V, NCT-A and NCT-A indexes between the effective group (B group) and the ineffective group (C group) before treatment (P > 0.05). After the treatment, the above-mentioned indexes in the effective group of patients were significantly lower than before treatment, and compared with the ineffective group, the NIC-A, NIC-V, NCT-A and NCT-V values of the effective group were significantly lower than those of ineffective group (P < 0.05). After treatment, the NIC-V and NCT-V in the ineffective group were lower than before treatment, and the difference was statistically significant (P < 0.05). However, their NIC-A and NCT-A were not statistically different from those before treatment (P > 0.05).ConclusionUsing DECT iodine map, the changes of NIC and NIC before and after CRT in patients with esophageal cancer can evaluate the effect of CRT, and does not increase the radiation dose, so it is suitable for clinical use.

Preoperative chemoradiation may be more effective for esophageal squamous cell carcinoma compared with adenocarcinoma: results from 15 randomized controlled trials of 2,250 patients

Background: Although preoperative chemoradiation (CRT) is considered a standard treatment for patients with esophageal cancer, the results obtained from a variety studies concerning this treatment type still do not completely concur. The purpose of this study is to evaluate the efficacy of preoperative CRT on different histological types in the treatment of esophageal cancer, and to clarify the benefits of preoperative CRT for esophageal cancer. Methods: PubMed, EMBASE, Web of science and Cochrane library were searched for eligible studies published up to December 2017. Three primary out-comes were analyzed. Pooled hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated using a random effects or fixed effects. Heterogeneity of included studies was assessed using the I2 test. Publication bias was examined by the Begg’s funnel plot. Results: Fifteen RCTs totaling 2,250 patients were included, compared with surgery alone (SA), the HR (95% CI) for the overall survival (OS) was 0.88 (0.81–0.97), the disease-free survival (DFS) rate was 0.78 (0.64–0.96), and the progression-free survival (PFS) rate was 0.72 (0.56–0.91). To clarify the effect of histological differences on CRT, a subgroup analysis was performed, and the results showed that there was no statistically significant difference in the HR of the OS in squamous cell carcinoma (SCC) and adenocarcinoma (AC) for those treated with preoperative CRT compared with SA [HR of SCC =0.92 (0.83–1.01), P=0.085; HR of AC =0.77 (0.55–1.08), P=0.135]. There was however a statistically significant difference in the HR of the PFS in SCC and AC for those treated with preoperative CRT compared with SA [HR =0.48 (0.32–0.71) for SCC and =0.83 (0.57–1.21) for the AC]. The indirect compare results show there was no statistically significant difference between SCC and AC in OS, ROR (=1.19, 95% CI: 0.84–1.70), but have a statistically significant difference in PFS, ROR (=0.58, 95% CI: 0.33–1.00). Conclusions: Preoperative CRT can improve the OS, PFS and DFS of esophageal cancer. The results of subgroup analyses show that preoperative CRT can improve the PFS of esophageal SCC, but not esophageal AC. However, there was no significant difference in the OS of SCC and AC. And the indirect comparison results confirmed it.