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To determine the survival and prognostic factors of esophageal squamous cell carcinoma (ESCC) patients undergoing radical (chemo)radiotherapy in the era of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) in China.The Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) conducted the first nationwide survey of nine institutions. Detailed information was accumulated on 5185 patients with ESCC who received definitive 3DCRT/IMRT between 2002 and 2018. Relevant prognostic factors were evaluated to assess their influence on overall and progression-free survivals.After a median follow-up time of 47.0 (0.9-157.4) months, the 1-year, 2-year, 3-year and 5-year overall survival rates of the whole group were 69.8%, 46.6%, 37.9% and 30.1%. The 1-year, 2-year, 3-year, and 5-year progression-free survival rates were 54.1%, 36.6%, 30.5% and 24.9%. Multivariate analysis demonstrated that sex, clinical stage, treatment modality and radiation dose were prognostic factors for OS. The survival of patients who received concurrent chemoradiotherapy (CCRT) was better than that of patients who received radiotherapy alone or sequential chemoradiotherapy. Patients receiving adjuvant chemotherapy after CCRT had a better OS than patients receiving CCRT alone. Patients receiving higher radiation dose had a better OS than those patients receiving low-dose radiotherapy.The survival of ESCC patients undergoing radical (chemo)radiotherapy was relatively satisfactory in the era of 3DCRTand IMRT. As the largest-scale multicenter research on esophageal cancer radiotherapy conducted in China, this study establishes national benchmarks and helps to provide references for subsequent related researches.

Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma. Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p &lt, 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p &lt, 0.001) for DFS, and EGFR mutation type (p &lt, 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40, p = 0.036, TKIs vs. chemotherapy, HR = 0.38, p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22, p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42, p = 0.034, TKIs vs. chemotherapy, HR = 0.33, p &lt, 0.001) for DFS. No significant difference was found in the incidence of Grade 3–4 toxicities between groups (p = 0.445). Conclusions: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

BACKGROUND: To establish a nomogram for predicting the outcome of EGFR-mutated lung adenocarcinoma patients with brain metastases (BMs) and to estimate the efficacy of different therapeutic strategies. METHODS: The data of 129 cases with BM from the period between January 1st 2011 and December 31st 2014 were collected, and all of the cases were pathologically confirmed to be lung adenocarcinoma, stages I–IV and with 19 and/or 21 exon mutations of EGFR. Cox regression analysis and log-rank test were used for data analysis. The nomogram was used to establish the progression models. RESULTS: In the univariate analysis, the stage, ECOG score, interval between the diagnosis of lung cancer and BM, the number of brain metastatic lesions, and the diameter of the maximal brain metastatic lesion correlated well with overall survival (OS). In multivariate Cox proportional hazard analysis, the ECOG score, interval between the diagnosis of lung cancer and BM, and the number of brain metastatic lesions correlated well with the OS. Patients were divided into the poor prognostic group and the good prognostic group based on the nomogram prognostic model score. Subgroup analysis showed that in the poor prognostic group, the OS of patients who received radiotherapy was better than that of the patients who did not receive radiotherapy as the first-line treatment (30 vs. 19 months, P0.05). Patients in the good prognostic group who received radiotherapy had a better 3-y OS rate than the patients who received no radiotherapy as the first-line treatment (91.2% vs. 58.1%, P

Introduction This study aims to measure the air-kerma rate of 192-Ir-HDR-afterloading source with an ionization chamber in air and a solid cylindrical phantom separately and to compare the dose calibration by the American Association of Physicists in Medicine (AAPM) Task Group TG-43U1 formalism with the Abacus treatment planning system (TPS). Materials and methods The air-kerma rate of 192Ir source was measured by an ionization chamber in air and a solid cylindrical phantom separately. For the interesting point position P (8cm, 90°), the values of the dose were calculated with the TG-43U1 formula and compared with data from the Abacus TPS with single and multiple dwell positions, respectively. Results The air-kerma rate percentage deviations between the detector measurements in air and the source certificate were -1.28%, -0.91%, -0.71%, and 0.33% at the distances of 25cm, 50cm, 75cm, and 100cm, respectively. For the measurement in solid cylindrical phantom, the percent deviation from the air-kerma rate certificate was 1.85%. The percentage deviations of the dose calibration between Abacus TPS and TG-43U1 formalism at P (8cm, 90°) were -2.30%, 1.76%, and 2.10% with different distances (between the dwell positions) of 0cm, 0.5cm, and 1cm, respectively. Conclusion The in-air technique was a new attempt for clinic routine measurement. Further studies are still necessary. As a treatment planning system, the Abacus TPS should apply the AAPM TG-43U1 formulism for the development required in the future.

Background This study aimed to validate the feasibility of deformable image registration (DIR) in assessing the cumulative dose distributions in combined external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) for cervical cancer. Methods This retrospective study included 23 patients with stage IIB disease treated with combined EBRT to the whole pelvis (50.4 Gy in 28 fractions) using an intensity-modulated radiotherapy technique with 6-MV X-ray, followed by three-dimensional (3D) ICBT (28 Gy in 4 fractions). Tumor gross target volume at diagnosis (GTV-Tinit), tumor gross target volume before brachytherapy, high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV), and parametrium and organs at risk were recontoured on computed tomography images of EBRT and ICBT, respectively. The dose-volume parameters were also determined. The DIR results were reviewed using MIM Maestro (Reg Review) and modified by function (Reg Refine). To evaluate the accuracy of DIR, DIR-based cumulative dose-volume histogram (DVH) parameters and simple DVH parameter addition were compared using Wilcoxon rank-sum tests. Results The cumulative dose distributions of EBRT and four ICBT sessions were successfully illustrated using DIR. The mean tumor diameters were 68.35 cm3 at diagnosis and 29.63 cm3 at ICBT initiation. The mean tumor regression was 56.6%. The median minimum dose covering 90% (D90) of HR-CTV, GTV-Tinit, IR-CTV, and parametrium were 69.58±4.94, 68.81±7.98, 59.28±3.78, and 60.97±1.1 Gyα/β=10, respectively, for DIR and 69.11±5.68, 68.49±8.62, 58.89±3.59, and 61±1.49 Gyα/β=10, respectively, with conventional simple DVH parameter addition.No statistically significant differences in dosimetric parameters were observed between the two methods. Conclusions Although there were limitations in the DIR accuracy, DIR-based dose accumulation was significantly beneficial in visually showing the cumulative dose distribution in the target area to clinicians in combined radiotherapy for cervical cancer in routine clinical practice.

Lessons Learned Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. Background Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. Methods This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11–7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs. Conclusion Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.

Background: To investigate the effects and safety profile of radiation dose escalation utilizing computerized tomography (CT) based radiotherapy techniques (including 3-Dimensional conformal radiotherapy, intensity-modulated radiotherapy and proton therapy) in the definitive treatment of patients with esophageal carcinoma (EC) with definitive concurrent chemoradiotherapy (dCCRT). Methods: All relevant studies utilizing CT-based radiation planning, comparing high-dose (≥ 60 Gy) versus standard-dose (50.4 Gy) radiation for patients with EC were analyzed for this meta-analysis. Results: Eleven studies including 4946 patients met the inclusion criteria, with 96.5% of patients diagnosed with esophageal squamous cell carcinoma (ESCC). The high-dose group demonstrated a significant improvement in local-regional failure (LRF) (OR 2.199, 95% CI 1.487-3.253; P

Radiotherapy is the major approach and is well tolerated in locally advanced esophageal squamous cell carcinoma (ESCC). And nowadays, no effective biological markers have been identified for predicting the prognosis of patients with ESCC. Platelet-derived growth factor (PDGF) is associated with a poor prognosis of various malignancies. The present study aimed to assess the effect of PDGF-BB on radiotherapeutic responses of ESCC and the underlying mechanisms of its roles in ESCC. Serum from 68 cases that received neoadjuvant or radical radiotherapy was obtained before and during radiotherapy. Gene expression analyses were validated by enzyme linked immunosorbent assay. The prognosis of patients with significantly reduced PDGF-BB was probably better than that of the others found in the progression-free survival and overall survival groups. Depletion of PDGFB significantly suppressed the proliferation, invasion and migration of cancer cells. Inhibiting PDGFB induced cellular apoptosis and promoted the sensitivity to ionizing radiation (IR). Furthermore, IR inhibited PDGF-BB-induced migration by blocking the PI3K/AKT pathway in ESCC cells. We found that the expression of PDGF-BB provided a possible model for predicting ESCC radiotherapy. It can also be used as a prognostic indicator for locally advanced ESCC that was treated by radiotherapy.

More than 40% of patients with esophageal squamous cell carcinoma (ESCC) exhibit pathological complete responses (pCR) after neoadjuvant chemoradiotherapy (nCRT), and theoretically, these patients may be cured by CRT and omit surgery. This prospectively randomized pilot study compared definitive chemoradiotherapy (dCRT) with nCRT in patients with locally advanced ESCC who achieved clinical complete responses (cCRs) to nCRT.Single center, randomized, open phase 2 study of 256 patients with locally advanced ESCC enrolled between April 2016 and November 2018. Immediately when nCRT finished, patients enrolled underwent response evaluations within 1 week. Patients with cCR were randomly allocated to undergo surgery (arm A) or complete CRT up to the definitive radiation dose (arm B). The primary end point was 3-year disease-free survival (DFS).Finally, 71 patients were randomly assigned to the nCRT (n = 36) and dCRT (n = 35) arms. The median observation time was 35.7 months. The 3-year DFS rate was 56.43 % in arm A versus 54.73 % in arm B (hazard ratio [HR] = 0.862, 95 % confidence interval [CI] = 0.452 to 1.645, P = 0.652). The 3-year overall survival (OS) rates in arms A and B were 69.5 % and 62.3 % (HR = 0.824, 95 % CI = 403-1.688, P = 0.597), respectively.According to our treatment response evaluation criteria, survival of the patients with cCR after nCRT was not significant different between nCRT group and dCRT group. An optimized response evaluation strategy soon after nCRT may guide next therapy decisions for patients with locally advanced ESCC.

PurposeThe aim of the study was to compare the clinical outcomes of induction chemotherapy (IC) followed by definitive concurrent chemoradiotherapy (dCCRT) versus chemoradiotherapy alone in patients with esophageal squamous cell carcinoma (ESCC) on the basis of a clinical scoring model.MethodsA retrospective review of 599 patients with ESCC treated with dCCRT at our institution from 2010 to 2019 was conducted. The patients were divided into two groups based on whether they received IC. A clinical scoring model was performed using the significant variables obtained from the multivariate analysis. The PFS and OS rates were estimated using the Kaplan–Meier method.ResultsDuring the study period, 182 patients receiving IC followed by dCCRT and 417 dCCRT alone were identified. No significant differences in the PFS and OS rates were observed between the IC group (P=0.532) and the non-IC group (P=0.078). A clinical scoring model was constructed based on independent prognostic factors with scores ranging from 0 to 10.4. The patients were divided into high- and low-risk groups by using the median score as the cutoff value. The PFS rate of patients receiving IC was higher than that of patients treated without IC (P=0.034), while there was no improvement in the OS rate (P=0.794) in the high-risk group. No significant differences in the PFS (P=0.207) or OS (P=0.997) rate were found between the two treatment groups in the low-risk group.ConclusionsThe addition of IC followed by dCCRT for patients with ESCC might be associated with better PFS rates based on a clinical scoring model but has no impact on OS rates. Further prospective studies are warranted for the validation of this model.

Purpose We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT). Methods We retrospectively analyzed 252 ESCC patients treated with dCCRT in the era of intensity-modulated radiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems. Results The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P

Background Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. Methods All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. Results Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. Conclusions pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

BackgroundConcurrent chemoradiotherapy (CCRT) has become the standard of care in esophageal carcinoma patients who are not surgical candidates. The efficacy of induction chemotherapy (IC) or consolidation chemotherapy (CCT) for unresectable esophageal cancer (EC) treated with CCRT is unclear. We performed a systematic review and meta-analysis of published papers to evaluate the potential benefit of IC or CCT for patients with EC.MethodsEligible studies of IC followed by CCRT (IC-CCRT) vs. CCRT alone or CCRT followed by CCT (CCRT-CCT) vs. CCRT alone were retrieved through extensive searches of the PubMed, Science Direct, Embase, and Cochrane Library databases from the establishment of the database to July 31, 2021. Data such as 1-, 2-, 3-, and 5-year overall survival (OS), local recurrence rate (LRR), and distant metastasis rate (DMR) were collected for meta-analysis to evaluate the efficacy of IC/CCT.ResultsFour studies of IC-CCRT vs. CCRT including 836 EC patients and six studies of CCRT-CCT vs. CCRT including 1,339 patients with esophageal squamous cell carcinoma (ESCC) were finally identified in our analysis. Both IC-CCRT group [hazard ratio (HR) 0.446, 95% CI 0.286–0.693; p < 0.001] and CCRT-CCT group (HR 0.542, 95% CI 0.410–0.716; p < 0.001) exhibited statistically significant improvement in 1-year OS rate compared to that of CCRT, while the 2-year OS rate of IC-CCRT (HR 0.803, 95% CI 0.589–1.095; p = 0.166) or CCRT-CCT (HR 0.783, 95% CI 0.600–1.022; p = 0.072) was similar with that of CCRT. And the 3-year OS rate between IC-CCRT and CCRT was similar (HR 1.065, 95% CI 0.789–1.439; p = 0.680). However, comparing with CCRT alone, the CCRT-CCT group had lower DMR [odds ratio (OR) 1.562, 95% CI 1.090–2.240; p = 0.015] and higher 3-year OS rate (HR 0.786, 95% CI 0.625–0.987; p = 0.039). Besides, no differences were observed between the CCRT-CCT and CCRT groups in 5-year OS rate (HR 0.923, 95% CI 0.706–1.205; p = 0.555) and LRR (OR 0.899, 95% CI 0.686–1.179; p = 0.441).ConclusionThe study revealed the short-time survival benefit of additional IC or CCT compared to CCRT alone for patients with unresectable EC, and CCRT followed by CCT could significantly reduce the risk of distant metastases.

Objective To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT). Summary background data There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT. Methods The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified. Results A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27). Conclusions Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.

Purpose Telomerase is reactivated in non-small cell lung cancer (NSCLC), and it increases cell resistance to irradiation through protecting damaged telomeres and enhancing DNA damage repair. We investigated the radiosensitizing effect of BIBR1532, a highly selective telomerase inhibitor, and its corresponding mechanism in NSCLC. Methods and Materials Cell proliferation, telomerase activity, and telomere dysfunction-induced foci were measured with CCK-8 assay, real-time fluorescent quantitative polymerase chain reaction, and immunofluorescence. The effect of BIBR1532 on the response of NSCLC cells to radiation was analyzed using clonogenic survival and xenograft tumor assays. Cell death and cell senescence induced by BIBR1532 or ionizing radiation (IR), or both, were detected with western blotting, flow cytometry, and senescence-association β-galactosidase staining assay. Results We observed dose-dependent direct cytotoxicity of BIBR1532 at relatively high concentrations in NSCLC cells. Low concentrations of BIBR1532 did not appear toxic to NSCLC cells; however, they substantially increased the therapeutic efficacy of IR in vitro by enhancing IR-induced apoptosis, senescence, and mitotic catastrophe. Moreover, in a mouse xenograft model, BIBR1532 treatment synergized with IR at nontoxic dose levels promoted the antitumor efficacy of IR without toxicity to hematologic and internal organs. Mechanistically, lower concentrations of BIBR1532 effectively inhibited telomerase activity and increased IR-induced telomere dysfunction, resulting in disruption of chromosomal stability and inhibition of the ATM/CHK1 (ataxia-telangiectasia-mutated/Checkpoint kinase 1) pathway, which impaired DNA damage repair. Conclusions Our findings demonstrate that disturbances in telomerase function by nontoxic dose levels of BIBR1532 effectively enhance the radiosensitivity of NSCLC cells. This finding provides a rationale for the clinical assessment of BIBR1532 as a radiosensitizer.

Purpose To evaluate and analyze the efficacy and prognostic factors of intensity-modulated radiotherapy in 250 patients with cervical and upper esophageal carcinoma. Patients and methods From September 2009 to September 2016, we retrospectively analyzed 250 patients with cervical and upper esophageal carcinoma treated with intensity-modulated radiotherapy (IMRT). In our study, all patients received IMRT, 54 patients with cervical esophageal carcinoma and 196 patients with upper esophageal carcinoma. Treatment response, survival status and failure modes of treatment were observed, and prognostic factors were analyzed. Results The median survival time was 22.60 months and 3-year survival rate was 42%. The median progress-free survival time was 14.52 months and 3-year progress-free survival rate was 29.3%. The median survival time and the median progress-free survival time for cervical esophageal carcinoma were 20.40 and 15.15 months, respectively. The median survival time and the median progress-free survival time for upper esophageal carcinoma were 25.80 and 14.52 months, respectively (P>0.05). The significant clinical factors associated with survival were patient age, radiotherapy dose and T stages (P

Objective The eighth edition of the American Joint Committee on Cancer/Union of International Cancer Control esophageal cancer staging system was proposed in early 2018. The eighth edition staging system includes clinical staging, pathological staging, and neoadjuvant pathological staging, which fills in the blank of non‐operative staging of esophageal cancer. However, there are few reports on the eighth edition of clinical staging, and the purpose of the present study was to verify the prognostic value of the new American Joint Committee on Cancer clinical staging system for esophageal cancer patients who undergo radical radiation therapy. Methods A total of 544 patients with esophageal cancer from Tianjin Medical University Cancer Institute and Hospital between March 2010 and September 2016 were staged according to the eighth American Joint Committee on Cancer clinical staging system. The Kaplan–Meier method was used to calculate the survival rate of the patients. The Cox regression model was used for multivariate prognostic analysis. Results All the patients were divided into different groups by the eighth American Joint Committee on Cancer clinical tumor–node–metastasis staging system: 40 patients with T2; 157 patients with T3; 347 patients with T4; 132 patients with N0; 193 patients with N1; 172 patients with N2; 47 patients with N3; 81 patients with stage II; 102 patients with state III; and 361 patients with stage IVA. The 3‐year survival rates of stage T2, stage T3, and stage T4 were 60.1%, 45.6%, and 30.8%, respectively (P

e14006 Background: Parthenolide-derived compounds, including ACT001, achieved radiation-enhancing and normal cell protection effects in pre-clinical studies through Nrf2, STAT3 and other pathways. Safety and efficacy data from 45 cancer patients with brain metastasis in a phase 1b/2a study were presented. Methods: Eligible patients with SCLC, NSCLC and other cancers complicated with more than three metastatic brain lesions (no up limit for SCLC) were randomized to placebo (Cohort C), ACT001 200mg (Cohort A) and 400mg,bid (Cohort B). Patients were treated with ACT001 or placebo in combination with WBRT (30 Gy/10f) in first two weeks followed by continuous treatment with ACT001 or placebo till disease progression. Treatment emergent adverse events (TEAEs, the primary endpoint) and survival events were monitored. TE-SAEs and OS events that happened within 3 months (for lung cancers) or 6 months (other cancers) after end of WBRT were also assessed. MRI scans were performed and evaluated in baseline, 30 and 90 days after end of WBRT during study per iRANO and RANO-BM criteria. Results: Study enrolled 22 patients with SCLC, 14 NSCLC, 7 breast cancer and 2 with other cancers. NSCLC patients were negative for EGFR, ALK and ROS1 mutations whereas breast cancer patients are negative for HER2. Patient characteristics were balanced in age, KPS and GPA scores. All subjects finished the required WBRT. As of Dec 31st, 2021, a total of 7 (9), 13 (13) and 10 (11) patients in Cohort C, A and B respectively had post-treatment MRI scans for objective response evaluation per iRANO (or RANO-BM) criteria. Of note, the patient numbers reflected those whose tumors met radiologically evaluable lesion requirements per iRANO (> 10mm) or RANO-BM criteria (≥10mm). 3 out of 7 patients (42.9%) in Cohort C, 11 out of 13 (84.6%) in Cohort A and 9 out of 10 (90.0%) patients in Cohort B presented with partial response for intracranial lesions per iRANO criteria whereas 3 out 9 (33.3%), 11 out of 13 (84.6%) and 10 out of 11 (90.9%) patients achieved a partial response per RANO-BM criteria. The increased objective response noted in two ACT001 cohorts was also associated with decreased percentage change of median SPD (sum of the products of perpendicular diameters )as compared with data in Cohort C: -66.1% (Cohort A, baseline 969.8 mm2), -72.3% (Cohort B, baseline 445.3 mm2) and -44.7% (Cohort C, baseline 506.9 mm2). There were 41, 30 and 20 WBRT-related grade 2 and 3 adverse events in Cohorts C, A and B. respectively. In total, there were 6, 4 and 2 TE-SAEs and death events reported in non-accumulative manner in Cohorts C, A and B respectively. As of this report, one year PFS for intracranial lesions has not been determined due to limited PD events. Conclusions: ACT001 seemed to ameliorate WBRT-induced adverse events and reduce intracranial burden of tumor metastasis. A pivotal study is warranted to further evaluate these effects. Clinical trial information: ChiCTR2000037739.

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m2] plus docetaxel [25 mg/m2] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9–24.5), OS and PFS time ranged from 8.2–28.5 and 4.0–28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c+ dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.

Jing Zeng,1,2 Ziqi Liu,3 Shan Jiang,3 Qingsong Pang,1 Ping Wang1 1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Affiliated Hospital of Nankai University, Tianjin, People’s Republic of China; 3School of Mechanical Engineering, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Ping WangTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaEmail wangping2019@foxmail.comPurpose: Our previous research demonstrated that under ideal conditions, rigid registration between MRI images and US images had high accuracy for real-time image guidance. The work presented in this paper focused on the application of the previously established procedures to a new context, including preoperative CT images.Materials and Methods: We used a template to calibrate the US probe and completed the registration between preoperative CT images and US images. Marker experiments on the accuracy of real-time needle trajectories in CT images were performed using micro electromagnetic sensors. Pelvic phantom experiments were carried out to test the registration accuracy between CT and US images, in addition to registration accuracy between US images and real-time needle trajectories (real-time space model).Results: The US probe calibration error in CT images was 0.879 ± 0.149 mm. The difference of registration between US images and CT images was 0.935 ± 0.166 mm in the axial plane (n = 30) and 0.916 ± 0.143 mm in the sagittal plane (n =12). The difference of registration between US images and the needle’s real-time trajectories was 0.951 ± 0.202 mm.Conclusion: Under ideal conditions, rigid registration between CT images and US images had high accuracy for real-time image guidance.Keywords: registered ultrasound image, gynecologic brachytherapy, rigid registration, image-guidance

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are all markers of systemic inflammation response. The role of systemic inflammation in the development of esophageal fistula (EF) has yet to be defined. This study aimed to investigate the predictive value of hematologic measures of inflammation and to set up a predictive model. METHODS: The data of esophageal cancer (EC) patients who received chemoradiotherapy (CRT) in our institution between January, 2015 and January, 2018 were retrospectively collected. The NLR, PLR, and MLR of these enrolled patients were calculated. Univariate and multivariate analyses were performed to find the independent risk factors of EF. Moreover, a nomogram model was developed to predict the probability of fistula occurring in EC patients. RESULTS: For PLR, the optimal cut-off value was 153. Patients with PLR >153 had a higher probability of developing fistula than those with PLR ≤153 (P

Esophageal cancer (EC) has the seventh highest incidence and the sixth highest mortality rate of any type of cancer worldwide. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 95% of EC patients. The main treatment for EC patients is surgery and/or chemoradiotherapy (CRT). A large proportion of EC patients are already at an advanced stage of the disease by the time they are diagnosed. In these cases, CRT is left as the only treatment choice, and the treatment outcome is poor. Immune checkpoint inhibitors (ICIs) can improve clinical response and patient survival of patient with many types of tumors through reactivating antitumor immune response. The study of ICIs in ESCC is relative delayed compared with that in other solid tumors. Recent results from clinical trials have demonstrated the safety and efficacy of ICIs either alone or combined with chemotherapy or chemoradiotherapy in ESCC patients. Accumulated evidences also have shown the improved treatment outcome was associated with PD-L1 expression, tumor DNA instability-induced tumor mutational burden (TMB), and drawing lymphocytes into the tumor. Based on these findings, ICIs combined with CRT or radiotherapy (RT) are the focus of ongoing studies. This review will summarize the recent progress in this field, especially the mechanism of ICIs used in ESCC, their clinical efficacy and toxicities, and potential biomarkers.

BACKGROUND: We aimed to analyze the value of metal clip markers guided and placed by endoscopic ultrasonography (EUS) in the delineation of gross tumor volume (GTV) for thoracic esophageal squamous cell carcinoma. METHODS: From September 2016 to September 2018, patients with thoracic esophageal squamous cell carcinoma in Tianjin Medical University Cancer Institute and Hospital were recruited in the prospective trial, NCT02959385. They underwent titanium clips placement on tumor superior and inferior boundaries under EUS by a single expert endosonographer before radiotherapy computed tomography (CT) simulation. According to the clip markers, the reference GTVs were contoured by one experienced radiation oncologist. With the help of the Eclipse treatment planning system, clip markers on CT were concealed. Afterward, two other radiation oncologists with expertise in esophageal cancer delineated GTVs, defined as conventional GTVs, based on endoscopy and barium radiography findings. The two GTVs were compared and analyzed. Subgroup analysis was conducted in different T stage [early (T1 + T2) vs. advanced (T3 + T4)], focus location (upper vs. middle vs. lower segment), and tumor length (5 cm) groups. RESULTS: The trial recruited 55 patients with 60 thoracic esophageal cancer foci. A total of 111 titanium clips were guided and implanted by EUS. Before CT simulation, two titanium clips at two foci fell off. After the procedure, no case of intolerable esophageal pain, hemorrhage, or perforation occurred. Compared to reference GTVs’, discrepancies of conventional GTVs’ superior borders were 0.91±0.82 cm (P

Introduction This study aims to measure the air-kerma rate of 192-Ir-HDR-afterloading source with an ionization chamber in air and a solid cylindrical phantom separately and to compare the dose calibration by the American Association of Physicists in Medicine (AAPM) Task Group TG-43U1 formalism with the Abacus treatment planning system (TPS). Materials and Methods The air-kerma rate of 192Ir source was measured by an ionization chamber in air and a solid cylindrical phantom separately. For the interesting point position P (8cm, 90°), the values of the dose were calculated with the TG-43U1 formula and compared with data from the Abacus TPS with single and multiple dwell positions, respectively. Results The air-kerma rate percentage deviations between the detector measurements in air and the source certificate were −1.28%, −0.91%, −0.71%, and 0.33% at the distances of 25cm, 50cm, 75cm, and 100cm, respectively. For the measurement in solid cylindrical phantom, the percent deviation from the air-kerma rate certificate was 1.85%. The percentage deviations of the dose calibration between Abacus TPS and TG-43U1 formalism at P (8cm, 90°) were −2.30%, 1.76%, and 2.10% with different distances (between the dwell positions) of 0cm, 0.5cm, and 1cm, respectively. Conclusion The in-air technique was a new attempt for clinic routine measurement. Further studies are still necessary. As a treatment planning system, the Abacus TPS should apply the AAPM TG-43U1 formulism for the development required in the future.

Highlights • Lung Cancer patients are at high risk for COVID-19 infection. • All steps should be taken to protect patients and the healthcare workforce. • Shortened RT overall treatment time is an important consideration during the COVID-19 pandemic. • Twelve recommendations in the use of RT are proposed by an international panel. • The proposed recommendations require urgent consideration during this pandemic., COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. By April 2020, there are over a million two hundred thousand confirmed cases and more than sixty-five thousand deaths worldwide Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide in curbing the spread of COVID-19 while ensuring the continuity of services. In RT, shortening overall treatment time to reduce the number of patients present in the department is an important consideration. An international panel, including the majority of countries most affected by the COVID-19 pandemic, with expertise in the management of cancer in high-volume comprehensive centres from the largest societies of radiation oncology worldwide have come together to share their experience on COVID-19 preparedness in the context of lung cancer RT to deliver optimal care in such exceptional circumstances, based on the latest evidence. A comprehensive systematic review of the literature through a PubMed search was undertaken. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic.

Introduction: Intensive treatments can often not be administered to elderly patients with esophageal squamous cell carcinoma (ESCC), leading to a poorer prognosis. This multi-center phase II trial aimed to determine the toxicity profile and efficiency of S-1-based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidation chemotherapy with S-1 in elderly ESCC patients and to evaluate the usefulness of comprehensive geriatric assessment (CGA). Patients and Methods: We prospectively enrolled 46 elderly patients (age ≥ 70 years) with histopathologically proven ESCC. The patients underwent pretreatment CGA followed by SIB-RT (dose, 59.92 Gy/50.4 Gy) in 28 daily fractions administered using intensity-modulated radiotherapy or volumetric-modulated arc therapy. S-1 was orally administered (40-60 mg/m2) concurrently with radiotherapy and 4-8 weeks later, for up to four 3-week cycles at the same dose. Results: The median survival time was 22.6 months. The 1- and 2-year overall survival rates were 80.4 and 47.8%, respectively. The overall response rate was 78.3% (36/46). The incidence of grade 3-4 toxicities was 28% (13/46). The most common grade 3-4 toxicities were radiation esophagitis (5/46, 10.9%), nausea (4/46, 8.7%), anorexia (3/46, 6.5%), and radiation pneumonitis (3/46, 6.5%). There were no grade 5 toxicities. CGA identified that 48.8% of patients were at risk for depression and 65.5% had malnutrition. Conclusion: Concurrent S-1 treatment with SIB-RT followed by 4 cycles of S-1 monotherapy yielded satisfactory tumor response rates and manageable toxicities in selected elderly patients with ESCC. Pretreatment CGA uncovered numerous health problems and allowed the provision of appropriate supportive care. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02979691.

Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma. Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3–4 toxicities between groups (p = 0.445). Conclusions: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

BackgroundWe investigated the effect of miR-381 on the sensitivity of non-small cell lung cancer (NSCLC) to radiotherapy, and examined its possible mechanism.MethodsNSCLC A549 cells and miR-381 overexpression and gene silencing cell lines were treated with radiotherapy. The cell proliferation was tested by CCK-8 assay and colony formation. Flow cytometry and TUNEL were used to detect the cell apoptosis. The expression of nuclear factor kappa B (NF-κB) signaling pathway related proteins were detected by western blot. NF-κB signaling pathway activator and inhibitor cell lines were further constructed and the above experiments were repeated. Double luciferase assay was used to verify the target of miR-381. Furthermore, a nude mouse xenograft model was constructed and treated with radiotherapy. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was observed by immunohistochemistry. The apoptosis related proteins in tumor tissues were detected by western blot.ResultsThe mRNA expression of miR-381 was increased after radiotherapy treatment. Radiotherapy treatment also can inhibit the proliferation and promote apoptosis of A549 cells. Compared with radiotherapy group, cell proliferation was significantly decreased and apoptosis was significantly increased in miR-381 overexpression group (p < 0.05). Moreover, ROCK2 is a target of miR-381, and overexpression of miR-381 can down-regulate the expression of ROCK2 protein. In nude mice, miR-381 mimic interference can reduce cell tumorigenicity and proliferation, and increase the apoptosis. However, the indicators above were contrary in miR-381 silencing group. Verification experiments further verify that NF-κB signaling pathway activator can reverse the role of miR-381.ConclusionMiR-381 overexpression could enhance the sensitivity of NSCLC to radiotherapy by targeting ROCK2 to inhibit NF-κB signaling pathway.

Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m2 IV day 1, or 25 mg/m2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

Epithelia-mesenchymal transition (EMT) is critical for invasion and metastasis of esophageal carcinoma. Gli1, a transcriptional factor in Hedgehog pathway, is correlated with EMT, invasion and metastasis of tumors. However, its role in esophageal cancer is still unknown. Bioinformatics analysis revealed relationship between microRNA (miR)-361 and 3'-UTR of Gli1 gene. This study thus investigated the role of miR-361 and Gli1 in invasion and metastasis of esophageal cancer. Both tumor and adjacent tissues were collected from 58 esophageal cancer patients to test the expressions of miR-361 and Gli1, the relationship of which was confirmed by dual-luciferase reporter gene assay. Cultured esophageal cancer cells EC9706 were transfected with mimic NC, miR-361 mimic, si-NC, si-Gli1, miR-361 mimics+si-Glil, pQC or pQC-FU-Gli1. Transwell and colony formation assays were performed for cell invasion and attachment-independent growth. Expressions of Gli1, Snail, E-cadherin and N-cadherin proteins were revealed by Western blotting. The expression of Gli1 was significantly elevated in esophageal cancer tissues, along with lower miR-361 expression which was correlated with TNM stage. MiR-361 inhibited the expression of Gli1 via targeting on 3'-UTR of Gli1 gene. The transfection of miR-361 mimics and/or si-Gli1 significantly suppressed the growth of malignant cells. The over-expression of miR-361 and/or silencing of Gli1 decreased intracellular expression of Gli1, Snail and N-cadherin, and increased E-cadherin expression to suppress EMT and invasion of tumor cells while the opposite effects were obtained by over-expression of Gli1. Abnormal elevation of Gli1 and decrease of miR-361 were found in esophageal cancer tissues. MiR-361 weakened invasion of cancer cells and impeded EMT process via the inhibition of Gli1.

Importance The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival. Objective To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. Design, Setting, and Participants The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020. Interventions Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2of vinorelbine on days 1 and 8 and 75 mg/m2of cisplatin on day 1 or 25 mg/m2of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. Main Outcomes and Measures The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival. Results A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97;P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80;P Conclusions and Relevance In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC. Trial Registration ClinicalTrials.gov Identifier:NCT01216527

FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor‐dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small‐hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis. Immunofluorescence was used to detect the formation of γH2AX foci and evaluate the extent of DNA damage. Compared with corresponding adjacent noncancerous cervical tissues, the expression of FUNDC1 in cervical cancer cells was significantly increased. High expression of FUNDC1 and the prognosis of patients with cervical cancer were correlated negatively, which could be used as an independent prognostic factor for overall survival and disease‐free survival. Depletion of FUNDC1 significantly inhibited the proliferation of tumor cells, induced apoptosis, and enhanced cell sensitivity to cisplatin and ionizing radiation (IR). Our data suggested that FUNDC1 can be used as a prognostic biomarker in patients with cervical cancer, and may be a new therapeutic target to improve the antitumor effects of chemoradiotherapy.

// Xue Li 1, 2, * , Lujun Zhao 1, * , Wencheng Zhang 1 , Chengwen Yang 1 , Zhen Lian 1 , Shuai Wang 1 , Ningbo Liu 1 , Qingsong Pang 1 , Ping Wang 1 and Jinming Yu 1, 2 1 Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of Radiation Oncology, Shandong University Affiliated Shandong Cancer Hospital and Institute, Jinan 250000, China * These authors have contributed equally to this work Correspondence to: Jinming Yu, email: sdyujinming@163.com Keywords: esophageal squamous cell carcinoma, supraclavicular nodes, celiac nodes, common hepatic nodes, radiotherapy Received: February 17, 2017 Accepted: April 17, 2017 Published: May 19, 2017 ABSTRACT The purpose of this study is to assess the prognostic value of supraclavicular nodes, left gastric nodes, celiac nodes and common hepatic nodes metastasis in esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. A total of 293 ESCC patients treated with radiotherapy or chemoradiotherapy entered the study. The results showed that the presence of supraclavicular nodes (χ 2 = 0.075, P = 0.785) and left gastric nodes (χ 2 = 3.603, P = 0.058) metastasis had no significant influence on survival, while celiac nodes (χ 2 = 33.775, P < 0.001) and common hepatic nodes (χ 2 = 42.350, P < 0.001) metastasis were associated with significantly shorter survival, regardless of the sites of primary tumor. Multivariate analysis showed that celiac nodes (HR: 0.457, 95% CI: 0.256-0.816; P = 0.008) and common hepatic nodes (HR: 0.241, 95% CI: 0.092-0.630; P = 0.004) metastasis were independently adverse indicator of survival in upper ESCC. While in the middle and lower ESCC, only the common hepatic nodes (middle ESCC: HR: 0.345, 95% CI: 0.161-0.738, P = 0.006; lower ESCC: HR: 0.377, 95% CI: 0.160-0.890, P = 0.026) metastasis was an independently adverse indicator of survival. In conclusion, our study demonstrated that in ESCC treated with definitive radiotherapy, both of celiac nodes and common hepatic nodes metastasis were adverse indicator of survival in upper ESCC, and common hepatic nodes metastasis were adverse indicator of survival in middle and lower ESCC. Supraclavicular nodes an left gastric nodes metastasis is not associated with patients survival in ESCC.

// Baozhong Zhang 1 , Zhiyong Yuan 1 , Lujun Zhao 1 , Qingsong Pang 1 , Ping Wang 1 1 Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China Correspondence to: Baozhong Zhang, email: baozhongtj@163.com Keywords: non-small cell lung cancer (NSCLC), N2, post-operative chemo-radiotherapy (POCRT), nomogram Received: December 28, 2016 Accepted: March 16, 2017 Published: March 25, 2017 ABSTRACT In this retrospective study, we developed nomograms for predicting the efficacy of post-operation radiotherapy (PORT) in IIIA-N2 non-small cell lung cancer (NSCLC) patients. In total, 334 patients received post-operational chemotherapy and were included in the analysis. Of those, 115 also received either concurrent or sequential post-operational radiotherapy (PORT). Nomograms were developed using Cox proportional hazard regression models to identify clinicopathological characteristics that predicted progression free survival (PFS) and overall survival (OS), and subgroup analyses of the effects of PORT were performed using nomogram risk scores. PFS and OS predicted using the nomogram agreed well with actual PFS and OS, and patients with high PFS/OS nomogram scores had poorer prognoses. In subgroup analyses, PORT increased survival more in patients with low PFS nomogram risk scores or high OS nomogram risk scores. Thus, our novel nomogram risk score model predicted PFS, OS, and the efficacy of PORT in IIIA-N2 NSCLC patients.

// Tian Zhang 1, * , Jing Wang 1, * , Yanjun Su 2 , Xi Chen 1 , Qingna Yan 3 , Qi Li 3 , Leina Sun 3 , Yuwen Wang 1 , Puchun Er 1 , Qingsong Pang 1 and Ping Wang 1 1 Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Centre of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 2 Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 3 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China * These authors have contributed equally to this work Correspondence to: Ping Wang, email: 839159994@qq.com Qingsong Pang, email: pangqingsongtj@163.com Keywords: lung adenocarcinoma, classic EGFR mutations, micropapillary pattern, tyrosine kinase inhibitors Received: October 29, 2016 Accepted: February 22, 2017 Published: March 23, 2017 ABSTRACT Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein encoded by a gene located in the short arm of chromosome 7. This study aimed to investigate the clinicopathologic characteristics of classic EGFR exon mutation in Chinese patients with TMN stage III lung adenocarcinoma who received radical surgery. A total of 1,801 lung adenocarcinomas were analyzed for mutations in EGFR; 35% exhibited mutation of classic EGFR exons. Clinical and pathologic characteristics of patients with EGFR exon 19 mutation were compared with those who harbored EGFR exon 21 mutation. Patients with EGFR exon 19 mutation had a higher overall survival (OS, p=0.023) than those harboring EGFR exon 21 mutation. Our results demonstrated that patients with a micropapillary pattern (MPP) pathologic type in EGFR exon 19 mutation had a higher OS (p=0.022), and patients with exon 19 mutation were more sensitive to EGFR–tyrosine kinase inhibitors (p=0.032). The results of the current study can be used in decision-making regarding the treatment of patients with classic EGFR exon mutations.

The current study was to compare the efficacy and safety between concurrent and sequential chemoradiotherapy after 3-4 cycles of induction chemotherapy for limited-stage small-cell lung cancer (LS-SCLC) with bulky tumor. From July 2012 to September 2015, a total of 68 patients with stage IIIA and IIIB SCLC who had completed 3-4 cycles of etoposide plus cisplatin/carboplatin and achieved clinical complete response (cCR) or clinical partial response (cPR) were randomized into the two groups equally. The concurrent group received radiotherapy combined with oral etoposide and cisplatin and the sequential group received sequential chemoradiotherapy. Thoracic radiotherapy was performed using intensity-modulated radiation therapy (IMRT) with 95% PTV 60Gy/30 times. After completing chemoradiotherapy, patients received prophylactic cranial irradiation. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and toxicity. The median follow-up time was 63.3 months (95% confidence interval [CI], 50.8-75.8). Better PFS and OS were observed in concurrent group (median PFS, 26.0 months [95% CI, 9.0-43.0] versus 13.1 months [95%CI, 9.7-16.6], p=0.023; median OS, 35.0 months [95% CI, 25.4-44.6] versus 22.0 months [95% CI, 17.0-27.1], p=0.015). There was no significant difference in the incidence of radiation esophagitis and radiation pneumonitis between the two groups (p=0.795, p=0.525). This study demonstrated that after the completion of 3-4 cycles of chemotherapy with a remission, concurrent chemoradiotherapy with oral etoposide and cisplatin improved survival compared with sequential chemoradiotherapy in LS-SCLC with bulky tumor. ClinicalTrials.gov Identifier: NCT01745445.

BackgroundIn 1997, the Radiation Therapy Oncology Group (RTOG) put forward the recursive partitioning analysis classification for the prognosis of brain metastases (BMs), but this system does not take into account theepidermal growth factor receptor(EGFR) mutations. The aim of the study is to assess the prognosis of patients withEGFR-mutated non-small cell lung cancer (NSCLC) and BMs in the era of tyrosine kinase inhibitor (TKI) availability.MethodsThis was a retrospective study of consecutive patients withEGFR-mutated (exon 19 or 21) NSCLC diagnosed between 01/2011 and 12/2014 at the Tianjin Medical University Cancer Institute & Hospital and who were ultimately diagnosed with BMs. The patients were stage I-III at initial presentation and developed BMs as the first progression. Overall survival (OS), OS after BM diagnosis (mOS), intracranial progression-free survival (iPFS), response to treatment, and adverse reactions were analyzed.ResultsMedian survival was 35 months, and the 1- and 2- year survival rates were 95.6% (108/113) and 74.3% (84/113). The 3-month CR + PR rates of radiotherapy(R), chemotherapy(C), targeted treatment(T), and targeted treatment + radiotherapy(T+R) after BMs were 63.0% (17/27), 26.7% (4/15), 50.0% (7/14), and 89.7% (35/39), respectively. The median survival of the four treatments was 20, 9, 12, and 25 months after BMs, respectively (P = 0.001). Multivariable analysis showed that P P = 0.001) were independently associated with better prognosis.ConclusionsThe prognosis of patients with NSCLC and EGFR mutation in exon 19 or 21 after BM is associated with the number of brain metastasis and the treatment method. Targeted treatment combined with radiotherapy may have some advantages over other treatments, but further study is warranted to validate the results.

Background After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. Discussion If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). Trial registration The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).

Purpose and Objectives: Chemoradiotherapy (CRT) is an important component of treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Recent research findings support the role of CRT in activating an anti-tumor immune response. However, predictors of CRT efficacy are not fully understood. The aim of this study was to measure CRT-induced changes to lymphocyte subpopulations and to evaluate the prognostic value of lymphocyte alterations for patients with ESCC. Materials and Methods: In total, this pilot study enrolled 64 patients with ESCC who received neo-adjuvant CRT or definitive CRT. Peripheral blood samples were collected before and during treatment and were analyzed by flow cytometry for CD19, CD3, CD4, CD8, CD56, and CD16. Relationships between lymphocyte subset alterations and overall survival (OS) and progression-free survival (PFS) were evaluated using the log-rank test and a Cox regression model. Results: The median follow-up period was 11.8 months (range, 4.0-20.2 months). Compared to pre-treatment specimens, post-treatment blood samples had decreased proportions of CD19+ B-cells and increased proportions of CD3+ and CD8+ T-cells (all P < 0.05). Univariate and multivariate analysis showed that increased CD4+ T-cell ratios after CRT independently predicted superior PFS (hazard ratio [HR] = 0.383; 95% confidence interval [CI] = 0.173-0.848, P = 0.017) and that increased CD8+ T-cell ratios predicted improved OS (HR = 0.258; 95% CI = 0.083-0.802, P = 0.019). Patients with both increased CD4+ and CD8+ ratios had a superior PFS and OS, compared to patients with an increased CD4+ ratio only or CD8+ ratio only or neither (1-year PFS rate 63 vs. 25%, 1-year OS rate 80 vs. 62%, P = 0.005 and 0.025, respectively). Conclusions: CRT-induced increases in CD4+ and CD8+ T-cell ratios are reliable biomarker predictors of survival in patients with ESCC.

Baozhong Zhang, Lujun Zhao, Zhiyong Yuan, Qingsong Pang, Ping Wang Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, and Tianjin Lung Cancer Center, Tianjin, People’s Republic of China Objective: The use of postoperative radiotherapy (PORT) remains controversial for Stage IIIA-N2 non-small-cell lung cancer (NSCLC) patients, a possible reason is that IIIA-pN2 NSCLC diseases are a heterogeneous group with different clinicopathologic features. The aim of this research was to prove whether the mediastinal lymph nodes’ (LNs) skipping status could indicate the necessity of the PORT for the pN2 NSCLC patients.Methods: The skip metastasis was defined as pN0N2 (no N1 LN involved), and nonskip metastasis was pN1N2 (one or more N1 LNs involved). Patients were divided into two groups: LNs nonskip and LNs skip, and postoperative chemoradiotherapy (POCRT) and postoperative chemotherapy. Then, the LN nonskip and LN skip groups were further divided into subgroups: POCRT and point of care testing (POCT) for subgroup analysis.Results: There were 220 cases included in the analysis, and 43 of them received PORT. Onunivariate analysis, the median 3-year progression-free survival (PFS) was, respectively, 16 months (27.7%) for the LN skip group and 11 months (15.3%) for the LN nonskip group (P=0.001). The median 3-year overall survival (OS) was, respectively, 35 months (47.0%) for the LN skip group and 27 months (38.7%) for the LN nonskip group (P=0.025). The median 3-year local recurrence-free survival (LRFS) was, respectively, 25 months (41.0%) for the LN skip group and19 months (29.9%) for the LN nonskip group (P=0.014). The median 3-year distant metastasis-free survival (DMFS) was, respectively, 22 months (32.5%) for the LN skip group and 15 months (20.4%) for the LN nonskip group (P=0.013). The median 3-year PFS was, respectively, 17 months (25.6%) for the POCRT group and 12months (18.6%) for the POCT group (P=0.037). Although the POCRT group showed better OS, LRFS, and DMFS than the POCT group, the results showed no statistical significance. In subgroup analysis, there was no statistical significance in the Kaplan–Meier analysis between subgroups, but it showed that POCRT resulted in better PFS, OS, and DMFS in both LN skip and LN nonskip subgroups; this advantage was more obvious in the LN skip subgroup.Conclusion: The LN skip status is closely related to the survival of the IIIA-N2 NSCLC disease, and the LN skip patients may get more benefit in PFS and LRFS than the LN nonskip patients from PORT. Keywords: non-small-cell lung cancer (NSCLC), N2, postoperative chemoradiotherapy (POCRT), LN skip/nonskip, PFS, OS, DMFS

Dong Qian,1 Jingjing Cheng,1 Xiaofeng Ding,1 Xiuli Chen,1 Xi Chen,1 Yong Guan,1 Bin Zhang,2 Jiefu Wang,3 Puchun Er,1 Minghan Qiu,1 Xianliang Zeng,1 Yihang Guo,1 Huanhuan Wang,1 Lujun Zhao,1 Dan Xie,4 Zhiyong Yuan,1 Ping Wang,1 Qingsong Pang1 1Department of Radiotherapy, 2Department of Lung Cancer, 3Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 4State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China Abstract: PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls. PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, and the rate of PinX1 protein low/negative expression in CRC and normal tissues was 60% (52/86) and 24% (6/25), respectively (P=0.037). In addition, PinX1 downregulation was significantly associated with short overall survival (P=0.016) and disease-free survival (P=0.042) in CRC patients. Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting overall survival and disease-free survival for CRC patients. Furthermore, we demonstrated that ectopic overexpression of PinX1 in CRC cells inhibited their proliferation, promoted apoptosis, repressed telomerase activity, and induced telomere shortening. These findings suggest that PinX1 may be a prognostic biomarker for CRC patients’ survival and that it inhibits cell proliferation and promotes apoptosis by repressing telomerase activity and inducing telomere shortening. Targeting PinX1 may therefore provide a novel therapeutic strategy for CRC patients. Keywords: colorectal carcinoma, PinX1, cell proliferation, apoptosis, telomerase, telomere, prognostic biomarker

Background This report describes the clinical work in esophageal cancer radiation group at the Department of Radiotherapy, Tianjin Medical University Cancer Institute & Hospital (TJMUCH). Methods We retrospectively analyzed the clinical data of patients with esophageal cancer who received radiotherapy (RT) at TJMUCH during the 5-year period between 2015 and 2019, including RT procedures, RT methods, treatment types, treatment outcomes and complications, and clinical trials. Results In 2015-2019, 1,464 patients with esophageal cancer received RT at the Department of Radiotherapy, TJMUCH. Of these, 1,176 patients received definitive chemoradiotherapy (CRT), 100 received preoperative neoadjuvant CRT, 120 received postoperative adjuvant RT, 49 received post-relapse RT, and 19 received palliative RT for advanced esophageal cancer. Among the patients who received definitive CRT, the incidences of grade 2 and higher radiation esophagitis, radiation pneumonitis, and leukopenia were 19.4%, 3.6%, and 19.7%, respectively; the incidences of grade 3-4 radiation esophagitis, radiation pneumonitis, and leukopenia were 9.4%, 1.2%, and 5.4%, respectively; no grade 5 acute adverse events were observed. Esophageal fistula was the major side effect during the advanced stage of RT. In 2015-2018, 44 patients (5%, 44/846) developed esophageal fistula; of these, 34 cases occurred after RT, and 10 cases occurred during RT. The overall survival was based on the data of 544 patients with esophageal cancer who underwent definitive RT at TJMUCH between March 2010 and September 2016. The median follow-up time was 21.6 months. The median survival was 19.6 months; and the 1-, 3-, and 5-year overall survival rates were 69.4%, 37.2%, and 32.3%, respectively. In 2015-2019, approximately 201 patients participated in different prospective clinical trials. Conclusions RT is a crucial and effective treatment for esophageal cancer. Standardized treatment procedures, multidisciplinary cooperation, are the foundations for good treatment effects. Many promising ongoing clinical trials will be helpful to improve the prognosis and survival of esophageal cancer patients in the future.