Bevacizumab in combination with paclitaxel and platinum for previously treated advanced thymic epithelial tumors.

There are no optimal regimens for advanced thymic epithelial tumors (TETs) when frontline chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with a routine chemotherapeutic regimen. Patients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160 mg/m2) and cisplatin (70 mg/m2) or carboplatin (area under the curve, 6) plus Bevacizumab (7.5 mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred. Between March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years). The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression-free survival for thymoma and thymic carcinoma was 6 and 8 months, respectively. Hematological toxicities were the main side effects. Paclitaxel and platinum plus Bevacizumab showed promising effects in refractory or relapsed advanced TETs without severe toxicity. Even when applied as salvage therapy, this regimen resulted in a better ORR than frontline chemotherapy.

Adjuvant chemotherapy improves survival outcomes after complete resection of thymic squamous cell carcinoma: a retrospective study of 116 patients.

OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy (ACT) for thymic squamous cell carcinoma after completely resection. METHODS: Patients with thymic squamous cell carcinoma treated with complete resection between January 2009 and December 2016 were retrospectively identified. Kaplan-Meier analysis was used to summarize the time-to-event variables. Univariable and multivariable Cox proportional hazards regression analyses were performed. RESULTS: A total of 116 patients were analysed with 44 patients in the non-ACT group and 72 patients in the ACT group. No significant difference was found in the 5-year recurrence-free survival (RFS) rate (58.1% vs 51%, P = 0.33) or the 5-year overall survival (OS) rate (77.7% vs 67.1%, P = 0.26) between the ACT group and the non-ACT group. Masaoka stage was the only independent prognostic factor for both RFS and OS. Subgroup analysis showed significant improvement in 5-year RFS for Masaoka stage II patients (P = 0.035) and 5-year OS (P = 0.036) for Masaoka stage III patients when comparing ACT with non-ACT. No chemotherapy-related death occurred. The most frequent adverse effect higher than grade 3 was neutropenia. CONCLUSIONS: For completely resected thymic squamous cell carcinoma, ACT significantly improved the 5-year RFS in Masaoka stage II patients and the 5-year OS in Masaoka stage III patients.

Long-term follow-up of a phase I/II trial of radiation dose escalation by simultaneous integrated boost for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: To observe the long-term survival and late adverse events in a phase Ⅰ/Ⅱ trial (NCT01843049) of dose escalation for thoracic esophageal squamous cell carcinoma (ESCC) with simultaneous integrated boost (SIB) technique. METHODS: Patients with ESCC were treated with escalating radiation dose of four predefined levels. Dose of 62.5-64 Gy/25-32 fractions was delivered to the gross tumor volume (GTV), with (Level 3&4) or without (Level 1&2) a SIB up to 70 Gy for pre-treatment 50% SUVmax area of GTV. Patients also received 2 cycles of chemotherapy of cisplatin and fluorouracil concurrently and 2 more cycles after radiotherapy. RESULTS: Median follow-up duration was 17.2 (2.5-83.4) months for all 44 patients and 47.2 (3.9-83.4) months for 25 survivors. The 3-year overall survival and progression-free survival rates were 57.6% and 41.0%, respectively. One, one, four and twelve severe (grade≥3) esophageal late adverse events (SEAE) occurred in patients of Level 1/2/3/4 (n = 5/10/16/13), with median occurrence time of 6.5 months. In univariable and multivariable competing risk models, maximal dose of the esophagus (Dmax) was found to have significant impact on the incidence of SEAE, and the cutoff distinguishing patients who developed SEAE or not was 77 Gy. CONCLUSION: Boosting the gross tumor to 63 Gy while delivering 50.4 Gy to subclinical diseases in 28 fractions in locally advanced ESCC is well tolerated with promising long-term survival. Intenser dose regimen should be considered with caution before further toxicity assessment. Esophageal Dmax was significantly associated with severe late esophageal injury, while more findings of dose-volume predictors need larger-sample investigation.

Intensity Modulated Radiation Therapy for Pleural Recurrence of Thymoma: A Prospective Phase 2 Study.

PURPOSE: This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable for surgery and had progressed after chemotherapy. MATERIALS AND METHODS: From February 2012, consecutive patients with pleural recurrence of thymoma were prospectively enrolled. Due to dose restrictions to normal tissue (lung, liver, and kidney), 3 different levels of radiation doses (30 Gy, 40 Gy, and 50 Gy) were prescribed for pleural lesions of different sizes and locations, with a daily fraction dose of 2 Gy. The objective response rate, local control time (LCT), overall survival time, and toxicity were recorded, respectively. RESULTS: By August 2016, 31 patients had completed the IMRT treatment. There were 21 male and 10 female patients, with a median age of 49 (range, 22-70) years. B3 thymoma was the major (62%) tumor subtype observed. During the median follow-up of 48 (24-70) months, the objective response rate was 97%, and the median LCT was 49 (95% confidence interval, 40.4-58.1) months. However, 29 (93.5%) patients developed out-of-field recurrence, among whom 10 (32%; 30 Gy, n = 7; 40 Gy, n = 3) developed both out-of-field and in-field recurrence. The median progression-free survival was 19 months, and no in-field recurrence occurred in the 50 Gy group. Moreover, a higher dose was related to a longer LCT. No toxicities higher than a grade 4 occurred after IMRT within the normal-tissue dose limitation. The 5-year overall survival of the patients was 81%. CONCLUSIONS: IMRT for pleural recurrence may act as an alternative treatment when surgery is not feasible, with a higher dose resulting in a longer LCT. In this study, out-of-field recurrence was considerably common, but repeated IMRT for new recurrence should be cautiously carried out due to the high risk of radiation-induced pneumonitis.

Clinical significance of age at diagnosis among patients with thymic epithelial tumors: a population-based study.

BACKGROUND: To investigate the clinicopathologic characteristics and survival outcomes of patients with thymic epithelial tumors (TET) according to age at diagnosis. RESULTS: A total of 4431 patients were analyzed. Gender, race, tumor histology and surgery were similar between different age groups. The 0-18 group was associated with a higher risk of distant metastasis. Compared to patients aged above 80, the hazard ratios (HR) for patients aged 0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80 were 1.079, 0.739, 0.614, 0.621, 0.633, 0.673, 0.861, respectively. From the subgroup analysis for the adult patients who were above 19 years old, we found that the 19-70 group had significant better cancer specific survival (CSS) and overall survival (OS) than the above 70 group. CONCLUSIONS: Age is a strong independent prognostic factor for survival in TET. Pediatric TET has a higher risk of distant metastasis and an inferior CSS. For the adults who were above 19, patients older than 70-year-old were associated with a shorter CSS. METHODS: Information of 4431 TET patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic features, clinicopathologic characteristics and survival outcomes were compared between patients diagnosed at different age groups (0-18, 19-30, 31-40, 41-50, 51-60, 61-70, 71-80, above 80).

S-1 salvage chemotherapy for stage IV thymic carcinoma: a study of 44 cases.

BACKGROUND: Thymic carcinoma (TC) is a rare mediastinal tumor, and patients with stage IV TC have a poor prognosis. No optimal chemotherapeutic regimen has yet been established. In this study, we evaluated the efficacy and safety of S-1 as a salvage mono-therapy in stage IV TC. METHODS: Patients with histologically confirmed stage IV TC were enrolled in this study when front-lined chemotherapy failed. S-1 capsules were orally taken twice a day. The daily dose was prescribed in three levels (80, 100, 120 mg) based on body surface area (BSA). One cycle of treatment consists of 4 weeks of drug use and 2 weeks of rest. The cycle was repeated until tumor progressed or intolerable toxicity occurred. The response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. RESULTS: Forty-four patients with stage IV TC were included between January 2013 and July 2017. Squamous cell carcinoma accounted for 84% of cases (37/44). There were 22 males and 22 females with a median age of 57 years (27-78 years). S-1 was prescribed at a dose of 80 mg for 18 (41%) patients, 100 mg for 17 patients (38%), and 120 mg for 9 patients (21%). The median number of cycles of administrated per patient was 3 [1-32]. Among 44 patients, 13 (30%) achieved a partial response, 22 (50%) remained stable disease, and 9 (20%) showed a rapid progression. With a median follow-up time of 14 months, the median PFS and OS of the whole group were 6 (95% CI, 7.0-13.9) months and 15 (95% CI, 13.2-21.6) months, respectively. For the 13 patients who showed response to S-1, the median PFS was 22 (95% CI, 15.5-30) months. Anorexia was the most common side effect, but all cases were mild. Other toxicities of grade ≥3 were bone marrow suppression (n=6) and rash (n=1). No drug-related deaths occurred. CONCLUSIONS: S-1 is a safe and effective treatment for stage IV TC as a salvage monotherapy. It is especially effective in disease control when the tumor shows response to S-1.

Radiotherapy for stage IVa thymoma-Shanghai Chest experience.

To investigate the effect of two modalities, radiotherapy (RT) and surgery plus entire hemithoracic radiotherapy (EHRT), on stage IVa thymoma. Patients enrolled in this study meet the following criteria: histologically proven thymoma; primary stage IVa or pleural dissemination after initial curative treatment. One treatment modality is intensity-modulated radiotherapy (IMRT) for pleural lesions with a dose ranging from 30-50 Gy, the other is macroscopically surgical resection plus EHRT with a dose of 13 Gy in 13 fractions. From July 2012 to April 2018, there were totally 56 patients enrolled in this study. The median age was 45 years old (range, 20-75 years old). There were 35 male and 21 female patients. The histology subtype distribution was 1 AB, 8 B1, 20 B2 and 27 B3, respectively. Thirty-one patients received IMRT for pleural dissemination and the response rate (CR + PR) was 97%. The mean local control time was 40 months (95% CI, 32.6-47.3 months). The in-field and out-field recurrence were 32% and 94%, respectively. The 2-year progression free survival (PFS) was 18%. While for patients who were treated by surgery plus EHRT, the in- and out-field recurrence were 8% and 16%, respectively. The 2-year PFS was 40%. The 2-year PFS for B1, B2 and B3 were 20%, 50% and 23%, respectively (P=0.255). Major toxicity occurred in IMRT group, 5 died of radiation-induced pneumonitis. Both IMRT and surgery plus EHRT showed good local control for stage IVa thymoma. Since stage IVa thymoma has a tendency to involve the whole hemithorax, surgery plus EHRT has a potential to produce longer PFS.

A nomogram to predict long-time survival for patients with M1 diseases of esophageal cancer.

Objective: To evaluate the clinicopathologic characteristics of the long-time survivals and construct a clinical nomogram using the Surveilance, Epidemiology, and End Results (SEER) database. Materials and Methods: Information of patients diagnosed with M1 stage esophageal cancer from 2010-2014 was retrieved from SEER database. Patients with unknown information of AJCC TNM stage or metastatic sites or marital status or surgery or survival were excluded. Demographic and clinicopathologic characteristics were compared between LTS (long time survivals: patients who have survived for no less than 2 years) and STS (shorter time survivals: patients who have survived for less than 2 years). Cox regression analysis was performed to evaluate prognostic factors. A nomogram comprising demographic and clinicopathologic factors was established to predict 1-year survival and 2-year survival for patients with M1 diseases. Results: A total of 2981 patients from the SEER database were included for analysis. Compared with the STS, married people and patients with well differentiated tumors or oligometastatic site were more likely to be LTS. Also, LTS were associated with significantly less bone metastasis and more surgery. The OS nomogram, which had a c-index of 0.633, was based on the eleven variables: gender, age, marital status, T stage, N stage, histology, grade, number of important metastatic organs and primary surgery. Conclusions: Married patients, patients with well differentiated tumors, patients with oligometastatic site, patients without bone metastasis or liver metastasis and those who underwent surgery are associated with long time survivals. We developed a nomogram predicting 1- and 2-year OS and CSS for M1 stage esophageal cancer. The prognostic model may improve clinicians' abilities to predict individualized survival and to make treatment recommendations.

[Outcome of Nonsurgical Treatment for Locally Advanced Thymic Tumors].

BACKGROUND: Surgical resection remains the mainstay of treatment for patients with early-staged thymic tumors, while chemotherapy is most commonly used in stage IV cases. As for locally advanced thymic tumors, especially those unsuitable for surgery, the optimal therapy is still controversial. Thus, we conducted this retrospective study by comparing three nonsurgical treatment modalities to find some clues. METHODS: Three treatment modalities were used in 42 patients from October 2000 to December 2010, including radiotherapy (RT) alone, sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT). Objective response rate (ORR), overall survival (OS) and toxicity of the three regimens were compared accordingly. RESULTS: The ORR in all 42 patients was 61.9%, and 5-year OS was 46%. The ORR of RT, SCRT and CCRT were 43.8%, 50% and 87.5%, respectively (RT vs SCRT, P=0.692; RT vs CCRT, P=0.009; SCRT vs CCRT, P=0.051). The 5-year OS of RT, SCRT and CCRT were 30%, 50% and 61.9%, respectively (RT vs SCRT, P=0.230; RT vs CCRT, P=0.011; SCRT vs CCRT, P=0.282). Eleven patients developed neutropenia of grade 3-4, with 7 in CCRT group and 4 in SCRT, respectively. Nine patients experienced esophagitis of grade 3 with 2 in RT, 3 in SCRT and 4 in CCRT. There were also two cases of grade 3 radiation induced pneumonitis in CCRT group. No life-threatening side effects were noted. CONCLUSIONS: When used to treat locally advanced thymic tumors unsuitable for surgery, CCRT performed more favorably than RT alone or SCRT in both tumor response and long time survival, but probably with the increasing risk of pulmonary damage. CCRT may offer the best chance of disease control in the management of locally advanced disease.

Outcome of nonsurgical treatment for locally advanced thymic tumors.

BACKGROUND: Surgical resection remains the mainstay of treatment for patients with early-staged thymic tumors, while chemotherapy is most commonly used in stage IV cases. As for locally advanced thymic tumors, especially those unsuitable for surgery, the optimal therapy is still controversial. Thus, we conducted this retrospective study by comparing three nonsurgical treatment modalities to find some clues. METHODS: Three treatment modalities were used in 42 patients from October 2000 to December 2010, including radiotherapy (RT) alone, sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT). Objective response rate (ORR), overall survival (OS) and toxicity of the three regimens were compared accordingly. RESULTS: The ORR in all 42 patients was 61.9%, and 5-year OS was 46%. The ORR of RT, SCRT and CCRT were 43.8%, 50% and 87.5%, respectively (RT vs. SCRT, P=0.692; RT vs. CCRT, P=0.009; SCRT vs. CCRT, P=0.051). The 5-year OS of RT, SCRT and CCRT were 30%, 50% and 61.9%, respectively. (RT vs. SCRT, P=0.230; RT vs. CCRT, P=0.011; SCRT vs. CCRT, P=0.282). Eleven patients developed neutropenia of grade 3-4, with 7 in CCRT group and 4 in SCRT, respectively. Nine patients experienced esophagitis of grade 3 with 2 in RT, 3 in SCRT and 4 in CCRT. There were also two cases of grade 3 radiation induced pneumonitis in CCRT group. No life-threatening side effects were noted. CONCLUSIONS: When used to treat locally advanced thymic tumors unsuitable for surgery, CCRT performed more favorably than RT alone or SCRT in both tumor response and long time survival, but probably with the increasing risk of pulmonary damage. CCRT may offer the best chance of disease control in the management of locally advanced disease.

Outcome of multimodality treatment for 188 cases of type B3 thymoma.

INTRODUCTION: This study aimed to evaluate the long-term efficacy of multimodality therapy for patients with type B3 thymoma. METHODS: A total of 188 consecutive patients with type B3 were treated in our hospital from January 2001 to December 2010. One hundred seventy-seven patients who had been treated with curative intent were retrospectively analyzed. According to World Health Organization Classification, all patients were pathologically confirmed as type B3. Distribution of Masaoka stages I, II, III, and IV was 35 (19.8%), 20(11.3%), 78 (44.1%), and 44 (24.8%), respectively. Myasthenia gravis coexisted in 34% of patients. RESULTS: After a mean follow-up of 49 months (7-135 months), the 10-year overall survival (OS) rates were 65% (89%, 86%, 61%, and 42% in stage I, II, III, and IV, respectively). One hundred five patients patients (102 patients with R0 resection and 3 with complete response after radiotherapy) were analyzed for freedom from recurrence (FFR). The 5- and 10-year FFR rates were 91% and 73% (100%, 94%, 84%, 71% and 100%, 94%, 56%, N/A in stages I, II, III, and IV, respectively. We have no data of stage IV.) TTP was calculated on 72 patients including 57 patients with R+ resection and 15 with partial response or stable disease after radiotherapy. The 5-year time-to-progression (TTP) rates were 33% (41%, 24% in stage III and IV, respectively). Multivariate analysis showed that prognostic factors for OS were the Masaoka stage and adjuvant radiation for patients with stage III and IV. The Masaoka stage and resection margin after surgery had significant effects on FFR and TTP. CONCLUSION: The type B3 thymoma often presented with the later stages at the diagnosis. The Masaoka stage was closely associated with OS, FFR, and TTP. Resection margin after surgery was related to TTP. Adjuvant radiotherapy may be beneficial to stage III and IV patients in this clinical setting.