Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

Phase 2 Clinical Trial of Simultaneous Boost Intensity Modulated Radiation Therapy With 3 Dose Gradients in Patients With Stage I-II Nasal Type Natural Killer/T-Cell Lymphoma: Long-Term Outcomes of Survival and Quality of Life.

PURPOSE: The aim of this study was to investigate the treatment results and long-term quality of life in patients with early-stage extranodal natural killer/T-cell lymphoma who were prospectively treated with simultaneous boost intensity modulated radiation therapy (SIB-IMRT) with 3 dose gradients. METHODS AND MATERIALS: Sixty patients with stage I-II nasal cavity natural killer/T-cell lymphoma (NKTCL) and Waldeyer's ring NKTCL were enrolled in a single-arm, prospective, phase 2 clinical trial from August 2011 to April 2015. All patients were treated with definitive radiation therapy combined with short-course induction chemotherapy. A newly designed SIB-IMRT scheme was uniformly adopted, with 54.6 Gy for the gross tumor volume (GTV) of the primary tumor and GTV of the positive lymph nodes, 50.7 Gy for the high-risk clinical target volume (CTV), and 45.5 Gy for the low-risk CTV, all delivered in 26 daily fractions. Before SIB-IMRT, L-asparaginase-based induction chemotherapy was used in 95.0% (57/60) of patients. RESULTS: With a median follow-up time of 95.8 months, the 5-year locoregional recurrence-free survival, progression-free survival, and overall survival rates were 83.3%, 81.7%, and 88.3%, respectively. Dosimetric analysis in the first 21 patients showed satisfying conformality for planning target volume of GTV, high-risk CTV, and low-risk CTV, while the organs at risk were well protected. The results of long-term quality-of-life investigations in patients without progression were favorable, and nasal discomfort was the most common symptom. No grade 3 or 4 acute or late toxicities were observed. CONCLUSIONS: The scheme of target volume delineation and dose setting that we designed has favorable clinical effects with mild side effects in treating patients with stage I-II nasal cavity NKTCL and Waldeyer's ring NKTCL.

Role of dynamic contrast-enhanced MRI in predicting severe acute radiation-induced rectal injury in patients with rectal cancer.

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min-1 vs 0.054 min-1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. CONCLUSION: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

The role of MRI after neochemoradiotherapy in predicting pathological tumor regression grade and clinical outcome in patients with locally advanced rectal adenocarcinoma.

Objective: To evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC). Materials and methods: This was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test. Results: From January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p<0.05). In multivariate analysis, downstaging N was an independent prognostic factor for OS. Meanwhile, downstaging T and downstaging N remained independent prognostic factors for PFS. Conclusions: Although the consistency between mrTRG and pTRG is only fair, favorable mrTRG after neo-CRT may be used as a potential prognostic factor for LARC patients.

Corrigendum: OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism.

[This corrects the article DOI: 10.3389/fonc.2022.977348.].

OIT3 serves as a novel biomarker of hepatocellular carcinoma by mediating ferroptosis via regulating the arachidonic acid metabolism.

Background: Oncoprotein-Induced Transcript 3 Protein (OIT3) was identified as a liver-specific gene with abnormal expression in hepatocellular carcinoma (HCC). Herein, we aimed to examine the function and specific mechanism of OIT3 in HCC. Methods: Bioinformatic analyses and tissue microarray via immunohistochemistry were used to validate the expression of OIT3 in HCC. The biofunctions of OIT3 in HCC were determined in vitro and in vivo. The mechanism was confirmed by RNA-Sequence and Western blotting. The uni- and multivariate analyses were used to identify the independent predictors for HCC. Results: Low expression of OIT3 was observed in HCC and predicted a poor clinical outcome. Ectopic expression of OIT3 could inhibit the proliferation, migration, and invasion abilities of HCC cells. Mechanistically, OIT3 upregulated the expression of ALOX15 and CYP4F3, thus inducing arachidonic acid increase, ROS accumulation, and lipid peroxidation, and eventually causing ferroptosis. OIT3 was validated as a prognostic predictor for HCC patients. Conclusions: Our findings revealed a novel role of OIT3 in the process of tumorigenesis of HCC. OIT3 inhibited reproliferation, migration, and invasion of HCC cells by triggering ferroptosis, which indicates that OIT3 could serve as a potential biomarker in HCC.

Characteristics and trends of globally registered glioma clinical trials in the past 16 years.

Background: Advancement in the treatment of glioma has been vacant since temozolomide has proved its therapeutic value in glioblastoma in 2005. Aim: To help investigators understand the landscape of glioma clinical research, we analyzed the characteristics and trends of globally registered glioma trials in the past decades. Methods: This is a cross-sectional analysis of glioma trials registered on ClinicalTrials.gov between January 2006 and December 2021. Characteristics regarding phase, enrollment number, study design and type, funding source, tumor site, pathology, patient status, age of population, trial purpose, and participating country were abstracted, and chronological shifts were analyzed. Results: There were 1531 registered glioma trials involved 58 participating countries. The trial purpose concerning surgery, radiotherapy, chemotherapy, targeted therapy, tumor-treating fields, immunotherapy, other antiglioma therapy and non-antiglioma research trial accounts for 3.5%, 6.5%, 9.5%, 28.9%, 2.0%, 16.4%, 12.5%, and 20.6%, respectively. In the past 16 years, the numbers of chemotherapy and targeted therapy trials declined; tumor-treating fields and immune checkpoint inhibitor application trials sprang at the latter half period; Immunotherapy, other antiglioma therapy and non-antiglioma research trials escalated (all above p trend < 0.005). The trend also showed the phased trials registered diminishingly and that the trials which focused on glioblastoma registered incrementally (those two p trend < 0.05). Among 784 drug therapy trials, it was included 45 cytotoxic drugs, 186 targeted drugs, 19 immune checkpoint inhibitors, 78 other drugs, and five immunomodulatory drugs. Two trials belonged to Bayesian adaptive randomized design. By the end of December 2021, 309 trials had publications. Only everolimus and tumor-treating fields exhibited meaningful survival benefit in specific glioma patients in phase 3 trials. Conclusion: Meaningful effective treatments regarding drugs or methods for glioma were difficult to be found. Bayesian adaptive platform trials may accelerate clinical research in glioma. Development of novel treatment modalities for glioma is still challenged.

Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma.

BACKGROUND: Epstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS: We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups. RESULTS: Patients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077-3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392-3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072-2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987-3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis. CONCLUSIONS: Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.

Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation in stage IV rectal cancer patients with potentially resectable metastases.

BACKGROUND: The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. METHODS: Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. RESULTS: A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P < 0.001) and 3-year PFS (45.5% vs 30.5%, P = 0.004) were significantly improved compared those who did not finish the treatment. Grade 3-4 chem-radiotherapy treatment toxicities were observed in 51 (22.4%) of all patients and surgical complications occurred in 22 (9.6%) of 142 patients who underwent surgery, respectively. CONCLUSIONS: Neoadjuvant chemotherapy and radiotherapy followed by resection/ablation and subsequent adjuvant chemotherapy offered chances of long-term survival with tolerable toxicities for selected patients with potentially resectable stage IV rectal cancer, and could be considered as an option in clinical practice.

Neoadjuvant chemoradiotherapy in patients with unresectable locally advanced sigmoid colon cancer: clinical feasibility and outcome.

BACKGROUND: Patients with locally advanced sigmoid colon cancer (LASCC) have limited treatment options and a dismal prognosis with poor quality of life. This retrospective study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery as treatment for select patients with unresectable LASCC. METHODS: We studied patients with unresectable LASCC who received NACRT between November 2010 and April 2019. The NACRT regimen consisted of intensity modulated radiotherapy (IMRT) of 50 Gy to the gross tumor and positive lymphoma node and 45 Gy to the clinical target volume. Capecitabine­based chemotherapy was administered every 2 (mFOLFOX6) or 3 weeks (CAPEOX). Surgery was scheduled 6-8 weeks after radiotherapy. RESULTS: Seventy­two patients were enrolled in this study. Patients had a regular follow-up (median, 41.1 months; range, 8.3-116.5 months). Seventy­one patients completed NACRT, and sixty-five completed surgery. Resection with microscopically negative margins (R0 resection) was achieved in 64 patients (88.9%). Pathologic complete response was observed in 15 patients (23.1%), and multivisceral resection was necessary in 38 patients (58.3%). The cumulative probability of 3-year overall survival (OS) and progression-free survival (PFS) were 75.8 and 70.7%, respectively. CONCLUSIONS: For patients with unresectable LASCC, neoadjuvant chemoradiotherapy is feasible, surgery can be performed safely and may result in increased survival and organ preservation rates.

Colorectal cancer under 20 years old: a retrospective analysis from three tertiary hospitals.

PURPOSE: Colorectal cancer (CRC) rarely occurs in children and adolescents. This study aimed to perform a retrospective analysis and disclose more detailed information about CRC in patients under 20 years old. METHODS: Medical records of CRCs in patients under 20 years old referred to three tertiary hospitals in China from September 2000 to July 2019 were retrospectively reviewed. Clinicopathological characteristics, treatment processes and laboratory findings were summarized and treatment outcomes and prognostic factors were analyzed. RESULTS: A total of 33,394 CRC medical records were analyzed, and we identified seventy (0.21%) CRCs in patients under 20. The most common primary tumor location was the left hemicolon (35.7%). The prominent pathological types were mucinous adenocarcinoma (22.9%) and signet ring cell carcinoma (22.9%). Nearly half (47.1%) of the patients presented with distant metastasis at diagnosis. The fractions of patients with deficient mismatch repair (dMMR) protein expression and microsatellite instability-high (MSI-H) were 23.8% (5/21) and 71.4% (5/7), respectively. Forty-four patients underwent radical surgery. Fifty-five patients received chemotherapy and six patients received radiotherapy. One dMMR/MSI-H rectal cancer patient received immunotherapy and achieved a clinically complete response. The median overall survival (OS) time was 80 months. The 3-year and 5-year OS rates were 61.8% and 57.2%, respectively. An absence of distant metastasis was a favorable factor for OS. For stage II/III CRCs, classic adenocarcinoma and radical surgery were favorable factors for OS. For stage IV CRCs, primary location at the colon was a favorable factor for OS. CONCLUSION: Child and adolescent CRC patients are likely to have distant metastasis, undifferentiated, left hemicolon location, and a dMMR/MSI-H phenotype at diagnosis. Additional efforts are needed to improve their survival outcomes.

Long-Term Survival and Prognostic Factors in Locoregionally Advanced Nasopharyngeal Carcinoma Patients Treated with TPF Induction Chemotherapy followed by Cisplatin-Combined Concurrent Chemoradiotherapy.

Purpose: The objective of this study was to report long-term results of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and identify prognostic factors for this group of patients. Materials and Methods: From December 2010 to January 2015, 109 patients with locoregionally advanced (III-IVB) NPC were included. Patients were scheduled to complete TPF induction chemotherapy followed by cisplatin based CCRT. Failure-free survival (FFS), overall survival (OS), locoregional failure-free survival (LRFFS) and distant failure-free survival (DFFS) served as clinical outcomes. Kaplan-Meier method, Cox proportional hazards model and receiver operating characteristic (ROC) curves were used for analyzing. Results: With a median follow-up of 60.2 months (range, 7.9-91.6 months), 3-year FFS, OS, LRFFS, and DFFS were 76.8%, 85.1%, 88.3%, and 84.1%, respectively. The highest incidence rate of recurrence and metastasis were in the first year after treatment. Multivariate analyses showed that age, total time of radiation therapy (RTT), and total time of therapy (TTT) were independent prognostic factors for FFS and OS. Body mass index (BMI), RTT and TTT were significant variables predicting DFFS. TTT was the only independent prognostic factor for LRFFS. Conclusion: This study indicated that TPF regimen produced encouraging results in Asian patients with locoregionally advanced nasopharyngeal carcinoma. Toxicity was tolerable and reversible. However, overall treatment time is an important factor that we should take into consideration when make plans of induction chemotherapy related treatment.

ZWINT is the next potential target for lung cancer therapy.

PURPOSE: We aimed to analyze the expression of ZWINT, NUSAP1, DLGAP5, and PRC1 in tumor tissues and adjacent tissues with public data. METHODS: The expression patterns of four genes were detected in cancer tissues and adjacent tissues by qRT-PCR. The overall survival analysis was used to explore these genes in lung adenocarcinoma and squamous cell carcinoma patients. Knockdown assays were used to select the most suitable gene among these four genes. Cell function assays with the knockdown gene were conducted in A549 and NCL H226 cells. The role of the knockdown gene in lung cancer was dissected in a mice tumor model. Transcriptome sequencing analyses with the knockdown gene were analyzed. RESULTS: Overexpression of these genes was significantly detected in cancer tissues (P < 0.01). Overall survival revealed that high expression of these genes is closely related with poor prognosis of lung adenocarcinoma patients (P < 0.05). Knockdown of ZWINT reduced proliferation in NCI H226 and A549 cells (P < 0.05). Knockdown also inhibited cell migration, invasion, apoptosis, and colony formation (P < 0.05). ZWINT knockdown reduced tumor volume (P < 0.05). Transcriptome sequencing of ZWINT knockdown-treated A549 and NCI H226 cells indicated that 100 and 426 differentially expressed genes were obtained, respectively. Gene ontology analysis suggested that binding, biological regulation, and multicellular organismal processes were the most enriched. KEGG analysis revealed that TNF, P53, and PI3K signal networks would be the most potential ZWINT-related pathways and were identified by Western blot analysis. CONCLUSIONS: ZWINT may be a novel target for lung cancer therapy.

Promising clinical outcomes of sequential and "Sandwich" chemotherapy and extended involved-field intensity-modulated radiotherapy in patients with stage IE /IIE extranodal natural killer/T-cell lymphoma.

BACKGROUND: The optimal treatment for the rare subtype of non-Hodgkin lymphoma, extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, has not been clearly defined. The purpose of the study was to investigate the efficacy of sequential and "Sandwich" chemotherapy and extended involved-field intensity-modulated radiotherapy (IMRT) in patients with stage IE /IIE extranodal ENKTL, nasal-type. METHODS: One hundred and fifty-five patients with stage IE /IIE nasal-type ENKTL were enrolled in the study, including 99 patients treated with sequential chemotherapy and extended involved-field IMRT (SCRT) and 56 patients with "Sandwich" chemotherapy and extended involved-field IMRT and chemotherapy (SCRCT). All patients were treated with extended involved-field IMRT with median dose of 54.6 Gy to the primary tumor and positive lymph nodes. Ninety-four patients had Ann Arbor stage IE disease, and 61 patients had stage IIE disease. RESULTS: The 5-year rates of loco-regional recurrence (LRR), progression-free survival (PFS), and overall survival (OS) were 17.0%, 78.5%, and 84.7%, respectively. Univariate analysis revealed that EBV DNA copy after treatment (normal vs elevated level) was significant prognostic factor for LRR, PFS, and OS (P < 0.001); therapeutic method (SCRT vs SCRCT) was significant prognostic factor for PFS (71.0% vs 91.8%, P = 0.011), but there was no significant effect on 5-year LRR and OS (22.2% vs 8.2%, P = 0.051 for LRR; 80.9% vs 91.8%, P = 0.199 for OS). CONCLUSIONS: Compared with SCRT, SCRCT was significantly associated with higher PFS rates and showed a trend toward improved loco-regional control. EBV DNA copy after treatment is a good index for recurrence and prognosis for stage IE /IIE ENKTL patients.

Exploration of the optimal treatment regimes for Esthesioneuroblastoma: a single center experience in China.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon neoplasm arising from the olfactory mucosa. The optimal treatment regimen for ENB remains unclear. This study aims to evaluate its clinical features, long-term outcomes and explore optimal treatment patterns. METHODS: Clinical data of consecutive 44 ENB patients were reviewed retrospectively. The correlation between clinical features and treatment approaches were analyzed, with several prognostic factors explored meanwhile. RESULTS: The age of onset of ENB showed a bimodal distribution, with peaks at 10~20 and 50~60 years. The median follow-up time was 84 months (range, 27~198 months).The 5-year overall and progression free survival rates were 42.7% and 39.1%, respectively, with 10-year rates of 28.9% and 21.7% respectively. Overall, 19 patients developed recurrent disease. Patients undergoing surgery combined with adjuvant radiotherapy had significantly higher 5-year overall survival (67.5% vs. 33.3%, P=0.043) and progress-free survival (60.0%vs. 18.7%, P=0.008) than those receiving other treatment approaches. No-Skin-involved ENB was associated with markedly better 5-year overall survival (45.5%vs.0 %, P=0.038) and progress-free survival (31.3% vs. 0 %, P=0.001) compared with skin-involved tumor. CONCLUSIONS: ENB is a rarely malignant tumor with high probability of locoregional recurrence and poor survival. Surgical resection followed by radiotherapy has been shown to achieve optimal local control and overall survival.

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients.

OBJECTIVE: To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy (RT) in the management of extramedullary plasmacytoma (EMP). METHODS: Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51 (range, 22-77) years. The median tumor size was 3.5 (range, 1.0-15.0) cm. The median applied dose was 50.0 (range, 30.0-70.0) Gy. Thirty-nine patients (70.9%) presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery (S) alone, 3 received chemotherapy (CT) alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients. RESULTS: The median follow-up duration was 56 months. The 5-year local recurrence-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) rates were 79.8%, 78.6%, 65.2% and 76.0%, respectively. Univariate analysis revealed that RT was a favourable factor for all examined endpoints. Furthermore, head and neck EMPs were associated with superior LRFS, MMFS and PFS. Tumor size <4 cm was associated with superior MMFS, PFS and OS; serum M protein negativity was associated with superior MMFS and PFS; age ≥50 years and local recurrence were associated with poor MMFS. The dose ≥45 Gy group exhibited superior 5-year LRFS, MMFS and PFS rates (94.7%, 94.4%, 90.0%, respectively), while the corresponding values for the dose <45 Gy group were 62.5% (P=0.008), 53.3% (P=0.036) and 41.7% (P<0.001). CONCLUSIONS: Involved-site RT of at least 45 Gy should be considered for EMP. Furthermore, patients with head and neck EMP, tumor size <4 cm, age <50 years and serum M protein negativity had better outcomes.

Intensity-modulated radiotherapy has superior outcomes to three-dimensional conformal radiotherapy in patients with stage IE-IIE extranodal nasal-type natural killer/T-cell lymphoma.

We compared the treatment outcomes, toxicities and prognoses of patients with stage IE-IIE extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT). Newly diagnosed early-stage ENKTL patients (N = 173) were enrolled and received extended involved-field radiotherapy following induction chemotherapy. Patients were treated with 3DCRT (n = 98) or IMRT (n = 75). One-to-one matching of the IMRT and 3DCRT groups was performed through propensity score matching, which yielded 23 pairs of patients. The two groups achieved similar complete remission rates before and after radiotherapy (P > 0.05). All patients were followed up for a median of 41 months. The rates of local recurrence-free survival (LRFS, P < 0.001), progression-free survival (PFS, P = 0.003) and overall survival (OS, P = 0.003) were longer in the IMRT than 3DCRT group. In the matched patients, IMRT was still associated with superior LRFS (P = 0.024), but not with improved PFS (P = 0.113) or OS (P = 0.115). Multivariate analysis also suggested IMRT was a favorable independent factor for LRFS (HR = 2.230, P = 0.043), but not for PFS (P = 0.195) or OS (P = 0.116). Equivalent acute toxicities were observed for 3DCRT and IMRT; however, among stage II patients who had received cervical irradiation, the rate of late xerostomia was lower in the IMRT than 3DCRT group (38.5% vs. 66.7%, P = 0.046). Overall, IMRT yielded a better treatment response and local control than 3DCRT, and tended to reduce late xerostomia in patients with cervical irradiation, but failed to enhance OS. Thus, IMRT is recommended for the treatment of stage IE-IIE ENKTL patients.

Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy. Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT1-2N1M0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR. Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites. Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

Radiotherapy improves survival in early stage extranodal natural killer/T cell lymphoma patients receiving asparaginase-based chemotherapy.

This study retrospectively investigated asparaginase-based chemotherapy treatment outcomes with or without radiotherapy in 143 patients with stage IE-IIE extranodal natural killer/T cell lymphoma (ENKTCL). All patients received a median of three cycles of asparaginase-based chemotherapy, while 121 patients received radiotherapy following the chemotherapy. The complete remission (CR) rate for all patients post-chemotherapy was 58.7%, and rose to 73.4% by the end of treatment. Patients who received radiotherapy achieved better survival outcomes than those who did not (89.7% vs. 49.0% for 2-year overall survival (OS), P<0.001; 86.8% vs. 37.4% for 2-year progression-free survival (PFS), P<0.001). Additionally, even patients who achieved CR post-chemotherapy exhibited differential survival rates with or without radiotherapy (90.8% vs. 60% for 2-year OS, P=0.006; 86.1% vs. 60% for 2-year PFS, P=0.044). Multivariate analysis revealed that radiotherapy was an independent factor favoring OS (HR=0.098, 95%CI=0.031-0.314, P=0.001) and PFS (HR=0.156, 95%CI=0.062-0.396, P=0.001). Thus, radiotherapy is recommended for stage IE-IIE ENKTCL patients treated with asparaginase-based chemotherapy, even in cases of CR following chemotherapy.