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.

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.

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.

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.