The addition of pembrolizumab to neoadjuvant chemoradiotherapy did not increase the risk of developing postoperative anastomotic leakage for ESCC: an analysis from a prospective cohort.

BACKGROUND: To compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC). MATERIALS AND METHODS: The GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. RESULTS: A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy. CONCLUSION: Based on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

A machine learning approach using 18F-FDG PET and enhanced CT scan-based radiomics combined with clinical model to predict pathological complete response in ESCC patients after neoadjuvant chemoradiotherapy and anti-PD-1 inhibitors.

Background: We aim to evaluate the value of an integrated multimodal radiomics with machine learning model to predict the pathological complete response (pCR) of primary tumor in a prospective cohort of esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) and anti-PD-1 inhibitors. Materials and methods: Clinical information of 126 ESCC patients were included for analysis. Radiomics features were extracted from 18F-FDG PET and enhanced plan CT images. Four machine learning algorithms, including SVM (Support Vector Machine), Random Forest (RF), and eXtreme Gradient Boosting (XGB) and logistic regression (LR), were applied using k-fold cross-validation to predict pCR after nCRT. The predictive ability of the models was assessed using receiver operating characteristics (ROC) curve analysis. Results: A total of 842 features were extracted. Among the four machine learning algorithms, SVM achieved the most promising performance on the test set for PET(AUC:0.775), CT (AUC:0.710) and clinical model (AUC:0.722). For all combinations of various modalities-based models, the combination model of 18 F-FDG PET, CT and clinical features with SVM machine learning had the highest AUC of 0.852 in the test set when compared to single-modality models in various algorithms. The other combined models had AUC ranged 0.716 to 0.775. Conclusion: Machine learning models utilizing radiomics features from 18F-FDG PET and enhanced plan CT exhibit promising performance in predicting pCR in ESCC after nCRT and anti-PD-1 inhibitors. The fusion of features from multiple modalities radiomics and clinical features enhances the better predictive performance compared to using a single modality alone.

Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01).

This randomized phase II trial (NCT05978193) combines low-dose radiotherapy (LDRT) and conventionally fractionated radiotherapy (CFRT) with immunochemotherapy for metastatic esophageal squamous cell carcinoma, aiming to assess the potential enhanced effect of radiotherapy on immunotherapy. Patients are administered a PD-1 inhibitor along with paclitaxel and platinum-based chemotherapy (arm B), or combined with LDRT and CFRT (arm A). Immunotherapy is given every 3 weeks with chemotherapy for 4 cycles, followed by immunotherapy maintenance therapy for up to 24 months. In arm A, LDRT (2 Gy, 2 fractions; delivered to the primary and all metastatic tumors) precedes each immunochemotherapy cycle for 4 cycles, followed by CFRT (40-50 Gy, 20-25 fractions; delivered to the primary tumor) starting from the fifth immunotherapy cycle. The primary end point is median progression-free survival. Clinical Trial Registration: NCT05978193 (clinicaltrials.gov).

Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

BACKGROUND: The aim of the study was to analyze the relationship between pretreatment inflammatory biomarkers (IBs) and survival outcomes for patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (neo-CRT) and pembrolizumab. METHODS: Clinical variables and IBs (absolute monocyte count [AMC], absolute lymphocyte count [ALC], platelet count [PLT], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], pan-immune inflammation value [PIV], systemic immunoinflammatory index [SII], systemic immunoreactivity index [SIRI] and prognostic nutritional index [PNI]) were collected. Univariate and multivariate analysis were performed to identify the independent factors for outcomes of ESCC. RESULTS: A total of 51 patients were included. Of these, 35 patients achieved pathological complete response (pCR) after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (overall response [OR] 4.4, p = 0.051) and PLT (OR 6.7, p = 0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p = 0.028) and SIRI (HR 3.13, p = 0.048) were two independent predictors associated with PFS. Kaplan Meier analysis demonstrated that the PFS of ESCC with high baseline ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p = 0.027), but not for overall survival (2-year OS: 96% vs. 87%, p = 0.46). CONCLUSIONS: This retrospective analysis based on a prospective cohort for the first time demonstrates that pretreatment ALC is an independent predictor for achieving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab.

No survival benefit could be obtained from adjuvant radiotherapy in esophageal cancer treated with neoadjuvant chemotherapy followed by surgery: A SEER-based analysis.

Background: The aim of this study is to assess the clinical benefit of postoperative radiotherapy (PORT) in patients with esophageal cancer (EC) who treated with neoadjuvant chemotherapy (NAC) and surgery via a national population-based database. Methods: Patients diagnosed with EC between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was used to compare the overall survival (OS) and cause-specific survival (CSS) difference between PORT vs. no-radiotherapy (RT) groups before and after propensity score matching (PSM). After PSM for baseline characteristics, Cox proportional hazard regression was performed to investigate the factors associated with OS. Results: A total of 321 patients were included in the analysis. Of them, 91 patients (28%) received PORT. In the unmatched population, the no-RT group had improved OS compared with PORT (44 vs. 25 months, p = 0.002), and CSS was similar in patients undergoing NAC with or without PORT (42 vs. 71 months, p = 0.17). After PSM for baseline characteristics, the OS benefit of the no-RT group over the PORT group remained significant with a median OS of 46 vs. 27 months (p = 0.02), and CSS remained comparable between groups (83 vs. 81 months, p = 0.49). In subgroup analyses, PORT did not improve the OS among patients with adenocarcinoma in the subgroups of cN0, cN1, and cN2-3 (all p > 0.05). In Cox regression, aged ≥71 years old, cT3-4, cN2-3, and receiving PORT were independent predictors of worse OS, whereas cT4 and cN2-3 were independent predictors of worse CSS (all p < 0.05). Conclusions: The present study demonstrated that no survival benefit could be obtained from the additional use of PORT after NAC and surgery in patients with EC. Well-designed prospective trials are needed to confirm our findings.

Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial design.

Objective: The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response rate of 55.6% after PPCT. We will conduct the multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (ClinicalTrials.gov ID: NCT04435197). Methods: A total of 143 patients with previously untreated, locally advanced, and surgically resectable esophageal squamous cell carcinoma (T2 through T4a, N0 through N+, M0) will be enrolled in PALACE-2. Main exclusion criteria are autoimmune disease, interstitial lung disease, ongoing immunosuppressive therapy, and having received chemotherapy, radiotherapy, target therapy, or immune therapy for this or any other malignancies. Positive programmed cell death ligand 1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (area under the curve = 2, once a week for 5 weeks), nab-paclitaxel (50 mg/m2, once a week for 5 weeks), and radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week). Esophagectomy will be performed within 4 to 6 weeks after the completion of PPCT. Results: The primary end point is the rate of pathologic complete response. Secondary outcome measures are 3-year disease-free survival rate, 3-year overall survival rate, R0 resection rate, and adverse events during neoadjuvant and perioperative periods. Conclusions: PPCT was preliminarily demonstrated to be safe, feasible, and to provide potential therapeutic benefits by the PALACE-1 trial. The subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable esophageal squamous cell carcinoma.

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of locally advanced esophageal cancer: a population-based analysis.

AIM: Currently, the optimal treatment strategy for locally advanced esophageal cancer (LAEC) remains controversial. We perform the present study to compare the outcomes of LAEC treated with neoadjuvant chemotherapy (neo-CT) or chemoradiotherapy (neo-CRT). MATERIALS AND METHODS: A population cohort with histologically diagnosed of esophageal cancer was identified from SEER database between 2004 and 2015. The Kaplan-Meier method and Cox-regression proportional hazards model were used to assess the impact of neoadjuvant treatment regimens on the cause-specific survival (CSS) and overall survival (OS) of LAEC. A propensity score model was utilized to balance baseline covariates. RESULTS: After propensity score matching, a total of 1986 LAEC patients were included for analysis, 1,655 patients treated with neo-CRT and 331 with neo-CT, respectively. The survival outcomes of LAEC treated with neo-CRT were comparable to those treated with neo-CT in terms of 5-year OS (39% vs. 36%, p = 0.63) and CSS (51% vs. 51%, p = 0.77). In the multivariate Cox analyses, sex, histological grade, ypT stage, ypN( +), and number of LN examined were independent factors for predicting OS and CSS among LAEC treated with neoadjuvant treatment. CONCLUSION: The present study based on large cohort demonstrated that no significant survival difference was observed between LAEC patients treated with neo-CRT versus neo-CT. However, the results needed to be confirmed in well-designed prospective trials.

Established and Validated Novel Nomogram for Predicting Prognosis of Post-Mastectomy pN0-1 Breast Cancer without Adjuvant Radiotherapy.

AIM: To establish and validate a nomogram for predicting prognosis of breast cancer patients with pN0-1 who were treated with mastectomy and without adjuvant radiotherapy. MATERIAL AND METHODS: The LASSO regression was performed to identify predictors of breast cancer-specific survival (BCSS), local regional recurrence (LRR) and distant metastasis (DM). Model performance was evaluated by the concordance index (C-index) and calibration plot. RESULTS: The 5-year BCSS, LRR and DM rates for the entire cohort were 98%, 2% and 4%, respectively. LASSO regression analysis found that pathological T stage, number of positive LN, grade and Ki-67 were significant predictors for both BCSS and DM-free survival, while number of resected LN and PR status were predictors for DM-free survival. In addition, number of positive LN was the only significant predictor for developing LRR. The C-indexes for the 5-year BCSS and DM nomograms were 0.81 and 0.78 in the training data set, 0.65 and 0.70 in the testing set and 0.72 and 0.69 in the external validation set, respectively. CONCLUSION: Our prognostic nomograms accurately predict 5-year BCSS and DM-free survival in post-mastectomy breast cancer without adjuvant radiotherapy, which provides a useful tool to identify high-risk patients who could benefit from additional adjuvant therapy.

Prognostic role of pretreatment lung immune prognostic index in extensive-stage small-cell lung cancer treated with platinum plus etoposide chemotherapy.

BACKGROUND: To investigate the prognostic role of lung immune prognostic index (LIPI) in extensive-stage small-cell lung cancer (ES-SCLC) patients treated with platinum plus etoposide chemotherapy. METHODS: Data were obtained from two randomized controlled trials (NCT00119613 and NCT00363415). Overall survival (OS) and progression-free survival (PFS) was assessed according to LIPI score through Kaplan-Meier analysis. Univariate and multivariate Cox-regression analysis were performed to investigate predictors for OS and PFS. RESULTS: A total of 911 patients with ES-SCLC treated with platinum plus etoposide chemotherapy (CT) were included for analysis. The median age at diagnosis was 62 years, and 760 (83.4%) had performance status of 1 or less. 1-year OS for ES-SCLC with poor, intermediate, and good LIPI was 20%, 30% and 31%, respectively, and 1-year PFS was 7%, 15% and 21%, respectively. Cox-regression analysis showed that the PFS and OS of ES-SCLC with a poor LIPI score was significantly worse than those with good LIPI scores (HR 1.81, 95% CI: 1.38-2.36; p< 0.001 and HR 1.35, 95% CI: 1.07-1.72, p= 0.012), while no significant difference was observed between intermediate and poor LIPI groups in terms of OS (HR 1.01, 95% CI: 0.82-1.23, p= 0.82), but not for PFS (HR 1.27, 95% CI: 1.00-1.61, p= 0.048). In addition, LIPI score was significantly associated with disease control rate and objective response rate (both p< 0.0001). CONCLUSION: Prognosis of patients with pretreatment LIPI score of 2 is poorer than those with LIPI score of 0-1 among ES-SCLC who received first-line platinum plus etoposide chemotherapy; Further studies are still recommended to confirm our findings in prospective studies.

Epidemiology and prognosis of lymphoepithelioma-like carcinoma: a comprehensive analysis of surveillance, epidemiology, and end results (SEER) database.

AIM: Lymphoepithelioma-like carcinoma (LELC) is a rare histological types of solid tumors. The present study aims to comprehensively describe the demographic and clinical features of LELC using surveillance, epidemiology, and end results (SEER) database, with an emphasis on the prognostic difference according to primary tumor sites of LELC. MATERIALS AND METHODS: A population cohort with histologically diagnosed LELC were identified from SEER database between 1973 and 2016. Age-adjusted incidence rates and cancer-specific survival (CSS) were determined. Cox-regression proportional hazards model was used for both univariate and multivariate analyses. RESULTS: In total, 2106 patients with LELC were identified, with the most common diagnosed primary tumor site of nasopharyngeal LELC (56.22%), followed by non-nasopharyngeal head and neck LELC (21.32%) and respiratory system (7.83%). The overall age-adjusted incidence of LELC was 0.091 per 100,000. The CSS rates of LELC patients at 5, 10, 15, and 20 years were 76%, 69%, 65%, and 61%, respectively. A tendency of decreasing incidence of LELC was observed in the past decade. Univariate analysis indicated that sex [hazard ratio (HR) 1.21, p = 0.031], year of diagnosis (HR 0.60 and 0.63, p < 0.001), race (HR 1.29, p = 0.0021), age (HR 1.25, p = 0.0072), summary tumor stage (HR 1.97, and 4.57, both p < 0.001), number of positive LN(HR2.21, p < 0.001), surgery (HR 0.58, p = 0.0033), chemotherapy (HR 1.19, p = 0.037) and primary tumor site (p < 0.001) were significant factors associated with prognosis of LELC. In multivariate analysis, age (HR 1.75, p = 0.03), distant stage (HR 6.57, p = 0.0001), number of positive LN (HR 2.63, p = 0.0015) and non-nasopharyngeal head and neck LELC (HR 0.37, p = 0.0031) were significantly independent predictors for CSS of LELC. In sub-group analysis, radiotherapy significantly improves CSS for nasopharyngeal LELC (HR 0.57, p = 0.0002), while surgery significantly improve CSS for non-nasopharyngeal LELC (HR 0.33, p < 0.0001). CONCLUSION: Based on SEER data analysis, age older than 50 years, distant stage and more than three positive LN are significantly associated with worse CSS for LELC, while the prognosis of non-nasopharyngeal head and neck LELC is significantly better than nasopharyngeal LELC. Local treatments for LELC could be recommended according to primary tumor sites.

Assessment of systematic inflammatory and nutritional indexes in extensive-stage small-cell lung cancer treated with first-line chemotherapy and atezolizumab.

BACKGROUND: The present study aims to investigate the prognostic role of systematic inflammatory and nutritional indexes in extensive-stage small-cell lung cancer (ES-SCLC) treated with first-line chemotherapy and atezolizumab. MATERIALS AND METHODS: Prospective cohort population involving 53 patients were identified from NCT03041311 trial. The following peripheral blood-derived inflammatory and nutritional indexes, including neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutrition index (PNI), advanced lung cancer inflammation index (ALI), and lung immune prognostic index (LIPI) were evaluated. RESULTS: The optimal cut-off values of the ALI, LMR, NLR, PLR, PNI, SII and SIRI were 323.23, 2.73, 2.57, 119.23, 48, 533.28 and 2.32, respectively. With a median follow-up of 17.1 months, the 1-year OS and PFS were 56% and 8%, respectively. Multivariate analysis showed that PLR was the only independent prognostic factors for OS among ES-SCLC patients treated with chemotherapy and atezolizumab (HR 4.63, 95%CI: 1.00-21.46, p = 0.05). K-M analysis showed that the OS and PFS for patients with high PLR (> 119.23) were significantly poorer than these with low PLR (≤ 119.23) (p = 0.0004 for OS and p = 0.014 for PFS). In external validation set, prognosis of patients with high PLR was also significantly poorer than these with low PLR in terms of OS (p = 0.038) and PFS (p = 0.028). CONCLUSION: Pre-treatment PLR could serve as a valuable independent prognostic factor for ES-SCLC who receive chemotherapy and immune checkpoint inhibitors. Further, prospective studies are still needed to confirm our findings.

Simultaneous integrated boost for mediastinal lymph node recurrence after radical surgery for esophageal cancer: Interim results from a phase I/II prospective study.

BACKGROUND: This was a single institute, phase I/II study of salvage chemoradiotherapy (CRT) with simultaneous integrated boost in patients with mediastinal lymph node (LN) recurrence after esophagectomy. METHODS: Patients who presented with a clinical diagnosis of ≤5 mediastinal LN recurrence received three consecutive levels of radiotherapy dose for the recurrences. Level 1: 58.8 Gy/2.1 Gy/28 fractions, Level 2: 64.4 Gy/2.3 Gy/28 fractions and Level 3: 70 Gy/2.5 Gy/28 fractions. RESULTS: A total of 17 patients (10 patients in phase I and 7 patients in phase II) were enrolled in the present study between June 2019 and July 2020. The median duration from surgery to initial recurrence was four months (range: 3-43 months). The most common site of recurrence according to JES was 106recR, accounting for 35%. Dose-limiting toxicity was not observed during three-month follow-up after completion of irradiation. The most common hematological toxicities were leukocytopenia and anemia. The most common nonhematological toxicity was esophagitis. The ORR according to RECIST was 58.8% (CR: seven patients; PR: three patients). With a median follow-up of 15 months (95% CI: 7-16 months), all patients were still alive. Among them, two patients who received a level 1 dose and one patient who received a level III dose developed multiple lung metastases after salvage CRT, and another patient who received a level 1 dose developed an out-of-field recurrence in the left cervical lymph node area. Another patient who received a level III dose developed chest wall recurrence after salvage CRT. CONCLUSIONS: The regimen of salvage CRT using the simultaneous integrated boost (SIB) technique (70 Gy/2.5 Gy/28F) for mediastinal lymph node recurrence in ESCC patients after esophagectomy is feasible and well tolerated.

Perioperative alectinib in a patient with locally advanced anaplastic lymphoma kinase positive non-small cell lung cancer (NSCLC): a case report.

We reported a case of locally advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient who received neoadjuvant alectinib therapy. Enhanced computed tomography (CT) scan was performed after the first cycle of alectinib therapy to evaluate the efficacy of neoadjuvant alectinib. Surprisingly, the tumor shrunk 42.2% after one cycle treatment. Partial remission (PR) was achieved without any side effects, although the tumor stage didn't degrade. Then right upper lobectomy and mediastinal lymph node dissection by video assistant thoracoscopic surgery (VATS) were successfully performed after multi-disciplinary team meeting with the department of respiratory, thoracic surgery, radiotherapy (RT), pathology and radiology. Pathologic evaluation about tumor was assessed by hematoxylin and eosin staining. However, the residual viable tumor cells were 15%, which indicated that major pathologic response (MPR) was not achieved. Next, continually adjuvant alectinib and RT were given because mediastinal station 4R lymphadenectomy excluded with serious tissue adhesion and MPR status was not met. In this case, we presented neoadjuvant alectinib therapy was feasible and well tolerated in locally advanced ALK positive NSCLC, inspiring clinical studies to further assess its clinical implication in treating patients with locally advanced ALK-positive NSCLC. And we also discussed the necessary time of neoadjuvant and adjuvant alectinib in advanced ALK-positive NSCLC.

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1).

BACKGROUND: To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable oesophageal squamous cell carcinoma (ESCC) (ClinicalTrials.gov number, NCT03792347). METHODS: Twenty resectable ESCC patients, regardless of programmed death ligand-1 status, received preoperative pembrolizumab with concurrent chemoradiotherapy (PPCT). Preoperative therapy includes carboplatin (area under the curve of 2 mg per milliliter per minute, once a week for 5 weeks), paclitaxel (50 mg/m2, once a week for 5 weeks), radiotherapy (23 fractions of 1.8 Gy, 5 fraction a week) and pembrolizumab (2 mg/kg) on days 1 and 22. Within 4-6 weeks after preoperative therapy, patients underwent surgery. The primary end-point was safety and secondary outcome measures were feasibility, pathologic complete response (pCR) rate and radiographic response. Immune signature of CD8+ T cells was evaluated in surgical specimens using immunohistochemistry and immunofluorescence. RESULTS: All patients have received PPCT successfully, except one patient who missed the last dose of chemotherapy due to leukopenia. Grade III and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and one patient had a grade V AE. The most frequent grade III AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18). The percentage of transcription factor 1 positive cells was significantly higher in specimens of pCR group than those of non-pCR group (p value = 0.010). CONCLUSIONS: PPCT was safe, did not delay surgery, and induced a pCR in 55.6% of resected tumours. A phase II multicentre study is undergoing for further confirmation of efficacy (NCT04435197).

Role of a multidisciplinary team in administering radiotherapy for esophageal cancer.

BACKGROUND: Radiotherapy (RT) is the major part of the treatment strategy set by a multidisciplinary team (MDT) for patients diagnosed with esophageal cancer (EC). The effect of an MDT collaboration on patients with EC who underwent RT is unclear. METHODS: We retrospectively collected all patients diagnosed with EC in the radiation oncology department at our institution from January 2015 to May 2017. The patients were divided into groups based on if they had their cases presented or not presented at the MDT meeting (with MDT and non-MDT, respectively). Propensity score matching (PSM) was applied at a ratio of 1:1 and the nearest neighbor matching method to compare the two groups. RESULTS: A total of 212 consecutive patients were analyzed, including 157 with MDT and 55 non-MDT. In the unmatched population, the patients with MDT were more likely to received chemotherapy than the non-MDT patients (84.7% vs. 69.1%; × 2 = 6.373; P = 0.012).MDT-patients had significantly improved overall survival compared with non-MDT patients (p = 0.025). In the multivariate analysis, MDT was an independent prognostic factor for OS in patients with EC who underwent RT (P = 0.019, HR 0.59, 95% CI 0.38-0.92). After PSM for baseline characteristics, the benefit of MDT for OS became more obvious. Additionally, we also found that MDT was an independent predictor of receiving chemotherapy by using logistic regression analysis. CONCLUSION: In patients who underwent radiotherapy for esophageal cancer, MDT was an independent factor for overall survival, which probably due to the selection of multimodality treatment when compared to non-MDT setting.

Risk factors for developing cardiac toxicities in cancer patients treated with panitumumab combination therapy.

Aim: To evaluate the incidence and risk of cardiac toxicities associated with panitumumab in advanced cancer of Caucasian patients. Materials & methods: The incidence of cardiac toxicity was assessed by simple incidence rates and rates per 100 person-years. Univariate and multivariate Cox regression was conducted. Results: Panitumumab-containing therapy significantly increased the risk of developing cardiac arrhythmias (p = 0.036), but not for any cardiac event (p = 0.24) or ischemic event (p = 0.087). The absolute rate of developing cardiac arrhythmia was 10.0 events versus 7.5 events per 100 person-years. Pre-existing hypertension (p = 0.033), history of cardiac disease (p = 0.055) or panitumumab usage (p = 0.046) were risk factors for cardiac arrhythmias. Conclusion: The addition of panitumumab to chemotherapy increases the risk of developing cardiac arrhythmia, but not for any cardiac toxicity or ischemic events.

Competing risk nomogram to predict cancer-specific survival in esophageal cancer during the intensity-modulated radiation therapy era: A single institute analysis.

The present study aimed to investigate the probability of cancer-associated mortality of patients with esophageal cancer undergoing intensity-modulated radiation therapy (IMRT), and to establish a competing risk nomogram to predict the esophageal cancer-specific survival (EC-SS) of these patients. A total of 213 patients with EC who underwent IMRT between January 2014 and May 2017 were selected to establish nomograms according to Fine and Gray's competing risk analysis. Predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index), calibration curves and the area under receiver operating characteristic curves. Decision tree analysis was also constructed for patient grouping. With a median follow-up of 19 months (range, 3-50), the 2-year EC-specific mortality (EC-SM) and the non-esophageal cancer specific mortality (NEC-SM) of the cohort were 35.4 and 3.51%, respectively. Furthermore, an elevated 2-year EC-SM was observed in patients with tumor length ≥4.5 cm compared with patients with tumor length <4.5 cm (45.8% vs. 21.4%; P<0.001), patients with non-squamous cell carcinoma compared with patients with squamous cell carcinoma (49.9 vs. 33.7%; P=0.025) and patients with N3 stage (43.2%; P=0.005). The 2-year NEC-SM of patients with tumor length ≥4.5 cm was 6% vs. 0% in patients with tumor length <4.5 cm (P=0.016). Three independent risk factors for survival, including tumor length, histological type and N stage, were integrated to build competing nomograms for the EC-SS model (C-index=0.72; 95% confidence interval, 0.66-0.77). In addition, the nomograms displayed better discrimination power than the 7th edition of the Tumor-Node-Metastasis staging system for predicting EC-SS (area under the curve=0.707 vs. 0.634). Furthermore, the results from the classification tree analysis demonstrated that N stage was the initial node and that primary tumor length was a determinant for EC-SM in these patients. In conclusion, NEC-SM represented a competing event for patients with EC with a tumor length ≥4.5 cm. The competing risk nomograms may therefore be considered as convenient individualized predictive tools for cancer-specific survival in patients with EC undergoing IMRT treatment.

Adjuvant regional nodal irradiation did not improve outcomes in T1-2N1 breast cancer after breast-conserving surgery: A propensity score matching analysis of BIG02/98 and BCIRG005 trials.

AIM: To determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy. METHODS: Data were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias. RESULTS: With median follow-up 80 months (range: 3-155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone. CONCLUSION: The addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population.