Characteristics and patient-reported outcomes of long-term cancer survivors after apatinib-based therapy: an online survey.

BACKGROUND: Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia. METHODS: Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected. RESULTS: Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%). CONCLUSIONS: Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient's quality of life.

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

Mechanistic process understanding of the self-assembling behaviour of asymmetric bolaamphiphilic short-peptides and their templating for silica and titania nanomaterials.

Investigation of the self-assembly of peptides is critically important to clarify certain biophysical phenomena, fulfill some biological functions, and construct functional materials. However, it is still a challenge to precisely predict the self-assembled structures of peptides because of their complicated driving forces and various assembling pathways. In this work, to elucidate the effects of noncovalent interactions including hydrogen bonding, molecular geometry, and hydrophobic and electrostatic interactions on the peptide self-assembly, a series of asymmetric bolaamphiphilic short peptides consisting of Ac-EI3K-NH2 (EI3K), Ac-EI4K-NH2 (EI4K), Ac-KI3E-NH2 (KI3E) and Ac-KI4E-NH2 (KI4E) were designed and their self-assembling behaviors at different solution pH values were investigated systematically. The peptides self-assembled into twisted nanofibers under most conditions except for EI4K in a strongly alkaline solution and KI4E under a strongly acidic condition, in which they self-assembled into nanotubes via helical monolayer nanosheet intermediates. In particular, KI4E nanotubes are formed under acidic conditions, and its diameters are ∼500 nm much greater than most of the self-assembled structures from bolaamphiphilic peptides. Moreover, reversible morphological transition between the nanotubes and twisted nanofibers was observed with the change in solution pH. Such tunable self-assembled structures and switchable surface properties of the asymmetric bolaamphiphilic short-peptides allow them to be used as templates to construct advanced materials. Silica and titania nanomaterials faithful to the peptide templates in morphology were prepared at ambient temperature. This work clearly elucidates the effects of noncovalent interactions on the peptide self-assembly and also provides new insights into the design and preparation of complicated inorganic materials from tunable organic templates.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Video-assisted thoracoscopic surgery versus open surgery for Stage I thymic epithelial tumours: a propensity score-matched study.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the management of thymic epithelial tumours. However, its oncological efficacy remains to be proved. The purpose of this study is to compare the oncological outcomes following thoracoscopic versus open surgery in the case-matched groups of patients with early-stage thymic tumours from the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS: Between 1994 and 2012, a total of 1087 patients who underwent surgery for UICC (Union for International Cancer Control) pathological Stage I tumours from the ChART retrospective database were recruited for this study. A propensity score-matched analysis was used to compare the long-term outcomes in patients who received VATS or open surgery. RESULTS: VATS resection was performed in 271 patients (24.9%) and open surgery in 816 patients (75.1%). Before propensity score matching, the VATS group had a smaller tumour size (P = 0.002), lower grade histology (P = 0.034), lower T stage (P < 0.001) and less adjuvant therapy (P < 0.001). Propensity score matching by gender, myasthenia gravis, tumour size, histological classification, pathological T stage, extent of thymectomy, adjuvant radiotherapy and adjuvant chemotherapy identified 110 patients in each group. After matching, there was no significant difference in patient demographics, tumour characteristics or adjuvant therapy. All matched patients had R0 resection. Overall survival, disease-free survival and cumulative incidence of recurrence were only predicted by WHO histology, but not by surgical approach, in both univariable and multivariable analyses. There was no significant difference in the overall survival (85.7% vs 93.1%, P = 0.539), disease-free survival (92.5% vs 91.9%, P = 0.773), cumulative incidence of recurrence (7.1% vs 5.8%, P = 0.522) and improvement rate of myasthenia gravis (83.3% vs 88.2%, P = 0.589) between the 2 groups. CONCLUSIONS: This propensity score-matched study suggests that VATS and open surgeries are associated with similar oncological outcomes for Stage I thymic epithelial tumours. Minimally invasive surgery might be an acceptable surgical approach for early-stage thymic malignancies.

Lymph node metastasis in thymic malignancies: A Chinese multicenter prospective observational study.

OBJECTIVES: To study the incidence and pattern of lymph node metastases in thymic malignancies. METHODS: This multicenter prospective observational trial with intentional lymph node dissection was carried out by the Chinese Alliance for Research in Thymomas (ChART). Data on patients with thymic tumors without pretreatment were collected prospectively. Results from this prospective study were then compared with those from a previously reported ChART retrospective study. RESULTS: Among 275 patients, metastasis was detected in 41 nodes (3.04%) in 15 patients (5.5%). The rate of lymph node metastasis was 2.1% (5/238) in patients with thymomas, 25% (6/24) in those with thymic carcinomas, and 50% (4/8) in those with neuroendocrine tumors (P < .001). The rate of lymph node metastasis in category T1 to T4 tumors was 2.7% (6/222) in T1, 7.7% (1/13) in T2, 18.4% (7/38) in T3, and 50% (1/2) in T4 (P < .001). Nodal involvement was significantly higher compared with the ChART retrospective study (5.5% vs 2.2%; P = .002), although the 2 groups were comparable in terms of tumor stage and histology. Metastasis was found in N1 nodes in 13 patients (86.7%) and in N2 nodes in 8 patients (53.3%); 6 patients (40%) had simultaneous N1/N2 diseases and 6 (40%) had multistation involvement. Based on World Health Organization histological classification and Union for International Cancer Control T category, patients were divided into a low-risk group (1/192; 0.5%) with T1-2 and type A-B2 diseases and a high-risk group (14/83; 16.9%) of category T3 and above or histology B3 and above tumors for nodal metastasis (P < .001). On multivariate analysis, type B3/thymic carcinoma/neuroendocrine tumors, category T3 or above, and N2 dissection predicted a greater likelihood of finding nodal metastasis. CONCLUSIONS: Lymph node involvement in thymic malignancies is more common than previously recognized, especially in tumors with aggressive histology and advanced T category. Intentional lymph node dissection increases the detection of nodal involvement and improves accuracy of staging. In selected high-risk patients, systemic dissection of both N1and N2 nodes should be considered for accurate tumor staging.

Lymph node metastases in thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis.

OBJECTIVES: Lymphatic involvement is believed to be relatively rare in thymic epithelial tumours. The incidence and prognostic significance of nodal metastases are still unclear. The goal of this study was to define the incidence and prognostic relevance of nodal metastasis in patients with thymic epithelial tumours, using a nationwide retrospective database of the Chinese Alliance for Research in Thymomas. METHODS: Patients who underwent upfront surgical resection without preoperative therapy were enrolled for the study. The International Thymic Malignancies Interest Group proposal of a new staging system for thymic epithelial tumours was used to redefine the pathological stage. The incidence of nodal metastasis and its relationship with clinicopathological characteristics and its impact on survival were examined accordingly. RESULTS: A total of 1617 patients were enrolled in this study. Lymph node metastasis was identified in 35 patients (2.2%). No nodal involvement was found in type A, AB or B1 thymomas. The incidence of nodal metastasis in thymoma (B2/B3) and thymic carcinoma was 1.3% and 7.9%, respectively, and it was most commonly seen in patients with neuroendocrine thymic tumours (16.7%, P < 0.001). According to the primary tumour invasion stage, incidences of nodal metastasis were 0.2% in T1, 6.9% in T2, 8.5% in T3 and 7.4% in T4 tumours (P < 0.001). Gender, pleural or distant metastasis and resection status were also correlated with nodal metastasis (P < 0.05) in univariable analysis. Multivariable analysis revealed that patients with non-thymoma histological characteristics (P < 0.001) and tumours in non-T1 stage (P < 0.001) had significantly greater risk of developing nodal metastasis. The overall survival of patients without nodal metastasis was significantly higher than that of patients with nodal involvement (P < 0.001). Disease-free survival of patients after R0 resection without nodal metastasis was also significantly higher than those with nodal metastasis (P < 0.001). On multivariable analysis, overall survival was significantly associated with histology of the tumour (P = 0.019) and complete resection (P = 0.047), and there was a trend towards significance (P = 0.052) in the association between overall survival and nodal involvement. CONCLUSIONS: Lymph node metastasis in low-grade, early stage thymic tumours is a rare phenomenon. However, it is not uncommon in tumours with a higher stage or a higher histological grade, especially in neuroendocrine thymic tumours. Nodal involvement as well as tumour invasion and histological grade may denote worse prognosis. Lymph node dissection may be warranted in selected high-risk patients.

PIM1 gene silencing inhibits proliferation and promotes apoptosis of human esophageal cancer cell line Eca-109.

We aimed to study the effect of PIM1 gene silencing on the proliferation and apoptosis of human esophageal cancer cell line Eca109. Cultured Eca109 cells were transfected with the recombinant plasmids in mediation of Lipofectamine TM 2000 Reagent. The Eca109 cells in logarithmic growth phase were collected and assigned into three groups: the PIM1 siRNA group (stably transfected with PIM1-shRNA plasmids), the negative control (NC) group (transfected with vacant plasmids), and the blank group (Eca109 cells without any transfection). The PIM1 mRNA expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell cycle was analyzed by flow cytometry. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8). Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. The PIM1 mRNA expression of Eca109 cells in the PIM1 siRNA group was significantly lower than that in the NC and blank groups. Compared with the NC and blank groups, the viability and proliferation of the Eca109 cells in the PIM1 siRNA group were significantly decreased at 48 h, 72 h and 96 h after transfection. The cell growth inhibition rate of the PIM1 siRNA group was higher than that of the NC and blank groups after transfection. Furthermore, the apoptotic rate of the PIM1 siRNA group was also higher than that of the NC and blank groups. In conclusion, our preliminary findings suggest that PIM1 gene silencing could inhibit proliferation and promote apoptosis of esophageal cancer cells.

The clinical features, diagnosis and management of recurrent thymoma.

Thymoma is a disease with malignant potential, which has a recurrence rate after complete resection ranging from 5 to 50 %. Multiple studies on the risk factors, treatment or prognosis have been reported. Many of them are controversial, however. In this review, we summarized some accepted risk factors, means of diagnosis and different treatments of recurrent thymoma. The risk factors of recurrent thymoma haven't been well-studied, and its management remains controversial. We reviewed the literatures and found some key points which should be noticed during the surgery of initial thymoma. Although reoperation should be taken into account preferentially, multimodal treatments are also available. The prognosis are also been discussed.

[Postoperative Survival for Patients with Thymoma Complicating Myasthenia Gravis
- Preliminary Retrospective Results of the ChART Database].

BACKGROUND: It is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG. METHODS: The Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were followed and their survival status were analyzed. RESULTS: There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93% vs 88%; 83% vs 81%, P=0.034) respectively. The survival rate was significantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003). Among patients with advanced stage thymoma (stage III, IVa, IVb), the constituent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were significantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classification, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were significant factors, and multivariate analysis showed WHO Classification, Masaoka stage, and resectability were strong independent prognostic indicators. CONCLUSIONS: Although MG is not an independent prognostic factor, the survival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.
.

[Comparison of the Masaoka-Koga and The IASLC/ITMIG Proposal for The TNM 
Staging Systems Based on the Chinese Alliance for Research in Thymomas (ChART)
Retrospective Database].

BACKGROUND: To compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS: From 1992 to 2012, 2,370 patients in ChART database were retrospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evaluated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were first analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal. RESULTS: Based on Masaoka-Koga staging system, significant difference was detected in CIR among all stages. However, No survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was significantly lower comparing to all other T categories (P<0.05) and there is a significant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were significantly worse in N(+) than in N0 patients. Significant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb. CONCLUSIONS: Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.
.

[Preoperative Induction Therapy for Locally Advanced Thymic Tumors: A Retrospective Analysis Using the ChART Database].

BACKGROUND: To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies. METHODS: Between 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery directly after preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III-IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis. RESULTS: Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4% vs 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P<0.001). CONCLUSIONS: Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4% vs 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P<0.001).
.

[Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches].

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). METHODS: Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. RESULTS: Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs 73.9%, P=0.028), resection rate (98.8% vs 88.7%, P<0.001) and less recurrence (2.9% vs 16.0%, P<0.001). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. CONCLUSIONS: This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival.
.

[Thymectomy versus Tumor Resection for Early-stage Thymic Malignancies: A Chinese Alliance for Research in Thymomas (ChART) Retrospective Database Analysis].

BACKGROUND: To evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospective database. METHODS: Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups. RESULTS: A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomectomy group. Improvement rate of myasthenia gravis (MG) was higher after thymectomy than after thymomectomy (91.6% vs 50.0%, P<0.001). Ten-year overall survival was similar between the two groups (90.9% after thymectomy and 89.4% after thymomectomy, P=0.732). Overall, recurrence rate was 3.1% after thymectomy and 5.4% after thymomectomy, with no significant difference between the two groups (P=0.149). Stratified analysis revealed no significant difference in recurrence rates in Masaoka-Koga stage I tumors (3.2% vs 1.4%, P=0.259). However in patients with Masaoka-Koga stage II tumors, recurrence was significantly less after thymectomy group than after thymomectomy (2.9% vs 14.5%, P=0.001). CONCLUSIONS: Thymectomy, instead of tumor resection alone, should still be recommended as the surgical standard for thymic malignancies, especially for stage II tumors and those with concomitant MG.

[Role of Postoperative Radiotherapy for Stage I/II/III Thymic Tumor - Results of the ChART Retrospective Database].

BACKGROUND: Postoperative radiotherapy (PORT) for thymic tumor is still controversial. The object of the study is to evaluate the role of PORT for stage I/II/III thymic tumor. METHODS: The database of Chinese Alliance of Research for Thymomas (ChART) was retrieved for patients with stage I/II/III thymic tumor who underwent surgical therapy without neoajuvant therapy between 1994 and 2012. Univariate and multivariate survival analyses were performed. Cox proportional hazard model was used to determine the hazard ratio for death. RESULTS: 1,546 stage I/II/III patients were identified from ChART database. Among these patients, 649 (41.98%) underwent PORT. PORT was associated with gender, histologic type (World Health Organization, WHO), surgical extent, complete resection, Masaoka stage and adjuvant chemotherapy. The 5-yr and 10-yr overall survival (OS) rates and disease-free survival (DFS) rate for patients underwent surgery followed by PORT were 90% and 80%, 81% and 63%, comparing with 96% and 95%, 92% and 90% for patients underwent surgery alone (P=0.001, P<0.001) respectively. In univariate analysis, age, histologic type (WHO), Masaoka stage, completeness of resection, and PORT were associated with OS. Multivariable analysis showed that histologic type (WHO)(P=0.001), Masaoka stage (P=0.029) and completeness of resection (P=0.003) were independently prognostic factors of OS. In univariate analysis, gender, myasthenia gravis, histologic type (WHO), Masaoka stage, surgical approach, PORT and completeness of resection were associated with DFS. Multivariable analysis showed that histologic type (WHO) (P<0.001), Masaoka stage (P=0.005) and completeness of resection (P=0.006) were independently prognostic factors of DFS. Subgroup analysis showed that patients with incomplete resection underwent PORT achieved the better OS and DFS (P=0.010, 0.017, respectively). However, patients with complete resection underwent PORT had the worse OS and DFS (P<0.001, P<0.001, respectively). CONCLUSIONS: The current retrospective study indicated that PORT after incomplete resection could improve OS and DFS for patients with stage I/II/III thymic tumor. But for those after complete resection, PORT may not help improve prognosis on the whole.
.

[Application of Postoperative Chemotherapy on Thymomas and Its Prognostic Effect].

BACKGROUND: To study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors. METHODS: Between 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoajuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. The Kaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and the Cox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy. RESULTS: Two-hundred-twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed significant differences (P<0.05) regarding the incidence of myasthenia gravis, World Health Organization (WHO) histological subtypes, pathological staging, resection status and the use of postoperative radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were significantly related to increased recurrence and worse survival (P<0.05). Five-year and 10-year disease free survivals (DFS) and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy after surgery (P=0.001, P=0.001, respectively). In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy (316 patients in total) were selected and compared accordingly. Similar 5-year survival rates were detected between the two groups (P=0.332). CONCLUSIONS: Pathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present, there is no evidence to show that postoperative chemotherapy may help improve prognosis in patients with Masaoka-Koga-Koga stage III and IV thymic tumors.

Phase II study of neoadjuvant therapy with nab-paclitaxel and cisplatin followed by surgery in patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: We carried out a phase II study to evaluate the efficiency and safety of the combination of nanoparticle albumin bound-paclitaxel (nab-paclitaxel) and cisplatin as preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC)Results: From Oct 2011 to Dec 2012, 35 patients were enrolled and received neoadjuvant chemotherapy. Thirty patients underwent surgery and achieved a 100% R0 resection. Pathological complete response (pCR) rate was 13.3% and near pCR rate was 6.7%. Down-staging was achieved in 19 patients. With median follow-up of 37.8 months, 16 patients were still alive. One-, 2- and 3- year overall survival (OS) rate was 90.0%, 70.0% and 43.3%, respectively. This treatment resulted in a median disease-free survival (DFS) of 34.7 months and a median OS of 37.8 months. Median DFS and OS of down-staged patients were significantly longer than those of non-downstaged patients. The grade 4 toxicities during neoadjuvant chemotherapy were limited to neutropenia (2.9%) and vomiting (2.9%). METHODS: Patients with locally advanced ESCC (stage IIA to IIIC) and performance status 0-1 were enrolled and received two cycles of nab-paclitaxel (100 mg/m2) on day 1, 8, 22 and 29, and cisplatin (75 mg/m2) on day 1 and 22, followed by resection. Two cycles of adjuvant chemotherapy with the same regimen were given. Postoperative radiotherapy was permitted and decided by radiation therapist. CONCLUSION: Weekly nab-paclitaxel with three-weekly cisplatin seems effective and safe as a neoadjuvant chemotherapy strategy for locally advanced ESCC. Down-staged patients have favorable outcome.ClinicalTrials.gov Identifier: NCT01258192.

Preoperative induction therapy for locally advanced thymic tumors: a retrospective analysis using the ChART database.

BACKGROUND: To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies. METHODS: Between 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery directly after preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III-IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis. RESULTS: Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs. 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs. 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P=0.000), although R0 resection were similar (76.4% vs. 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P=0.000). CONCLUSIONS: Preoperative neoadjuvant therapy have been used only occasionally in locally advanced thymic malignances. Effective induction therapy leading to tumor downstaging may be beneficial for potentially unresectable diseases, especially in patients with thymomas. These findings would be helpful to related studies in the future.