Intensity modulated radiotherapy might be effective for locally advanced esophageal carcinosarcoma: A single center's experience and review of literature.

Esophageal carcinosarcoma is a rare type of esophageal cancer; however, few studies have investigated the effects of radiotherapy in locally advanced patients. This study aimed to report experience of the safety and efficacy of intensity-modulated radiotherapy for locally advanced esophageal carcinosarcoma and review the literature. By searching the institutional database between January 2010 and December 2020, along with the literature review, 25 patients were eligible for the study. The clinical and radiologic information of all patients with esophageal carcinosarcoma who underwent radiotherapy were collected. Survival outcomes were calculated using Kaplan-Meier plots. In our series, 5 patients were in the curative/neoadjuvant radiotherapy group and 10 patients were in the adjuvant group. Most tumors were protruding (n = 10, 66.7%). All patients underwent intensity-modulated radiotherapy. In the curative/neoadjuvant radiotherapy group, 2 patients underwent concurrent chemoradiotherapy before surgery, and the other three received radiotherapy alone as the initial treatment. The median follow-up time was 43.1 months. All patients showed a partial response at the efficacy evaluation. The median time of overall survival and progression-free survival were 40.2 months (95% confidence interval [CI], 13.1-67.3 months) and 19.0 months (95% CI, 13.9 months-24.1 months) for the entire cohort, but were not reached for curative/neoadjuvant radiotherapy group. Overall survival (hazard ratio [HR] 0.81, 95% CI, 0.15-4.43; P = .805) and progression-free survival (HR 1.68, 95% CI, 0.35-8.19; P = .514) did not differ significantly between the 2 groups. When considering the literature review data in the final analysis, overall survival (HR 0.84, 95% CI, 0.25-2.81; P = .779) and progression-free survival (HR, 0.68; 95% CI, 0.26-1.76; P = .425) were also not different between the 2 groups. Treatment based on intensity-modulated radiotherapy with neoadjuvant or curative intent may be an option for patients with unresectable esophageal carcinosarcoma. Further research with a larger sample size is needed to validate the reliability.

Local Therapy Combined With First-Line EGFR Tyrosine Kinase Inhibitor Achieves Favorable Survival in Patients With EGFR-Mutant Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: EGFR tyrosine kinase inhibitor (TKI) is recommended as the first-line therapy for patients with EGFR-mutant metastatic non-small cell lung cancer (NSCLC). Yet, resistance often occurs in 1 year after therapy and most progressions occur at the initial sites of disease. Addition of local therapy to the first-line TKI therapy may delay the progression and provide survival benefit to the patients. METHODS: From 2010 to 2017, metastatic NSCLC patients with EGFR activating mutations who received first-line TKI and relatively radical local therapy (RRLT) were reviewed. RRLT was defined as local curative therapy to the main site or any intensity of local therapy to all sites of disease. The Kaplan-Meier method and log-rank test were used for survival estimation and comparison. RESULTS: A total of 45 patients were included in this retrospective study with a median follow-up of 48.0 months. The median progression-free survival (PFS) and overall survival (OS) was 17.0 months (95% confidence interval [CI]: 14.6-19.3) and 55.0 months (95% CI: 49.3-60.6), respectively. Univariate analysis indicated that age ⩽ 60 years (P = .019), first-line TKI duration ⩾ 10 months (P = .028), and accumulated TKI duration ⩾ 20 months (P = .016) were significantly associated with favorable OS. Among the 36 patients who progressed during the follow-up, 55.8% of the progressions occurred at the new sites. RRLT combined with TKI did not show any severe toxicity to the patients. CONCLUSIONS: Combined application of RRLT and first-line TKI may improve the survival and alter the pattern of failure for metastatic NSCLC patients with EGFR activating mutations.

Clinical outcomes and radiation pneumonitis after concurrent EGFR-tyrosine kinase inhibitors and radiotherapy for unresectable stage III non-small cell lung cancer.

BACKGROUND: Concurrent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with radiotherapy in patients with EGFR-mutant unresectable stage III non-small cell lung cancer (NSCLC) might improve survival. However, both treatments carry a potential risk of pneumonitis. METHODS: Between May 2012 and December 2017, patients with unresectable stage III NSCLC treated with concurrent radiotherapy and EGFR-TKI were enrolled in this retrospective study. The baseline characteristics were evaluated to determine correlations with toxicity development. RESULTS: Among 45 eligible patients, 20 (44.4%) had an EGFR mutation and 44 (97.8%) received 50-66 Gy of radiotherapy. The median follow-up was 62.7 months. The median progression free survival (PFS) and overall survival (OS) for patients with EGFR-mutations were 27.9 (95% CI: 18.7-37.2) and 49.7 (95% CI: 27.7-71.8) months, and 13.8 (95% CI: 8.8-18.9) and 31.1 (95% CI: 9.8-52.4) months for EGFR wild-type/unknown patients. A total of 17 patients (37.7%) developed radiation pneumonitis/pneumonitis (14 grade 2, 3 grade 3). In 16 patients, pneumonitis occurred within the radiation field and one patient had bilateral pneumonitis. The median time from the initial radiotherapy to pneumonitis was 74 days. Logistic regression analysis revealed a trend between the time of EGFR-TKI and the development of G2+ pneumonitis. For late toxicity, only two patients had G2+ fibrosis. The daily dyspnea symptoms of patients with G2+ pneumonitis recovered significantly after the phase of pneumonitis (P = 0.007). CONCLUSIONS: Combined EGFR-TKI and radiotherapy showed favorable survival in EGFR-mutant patients with inoperable stage III NSCLC, with a 6.7% incidence of grade 3 radiation pneumonitis/pneumonitis, despite a higher incidence of mild-to-moderate radiation pneumonitis. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We evaluated the outcomes and radiation pneumonitis after EGFR-TKI during interval radiotherapy. EGFR-TKI plus radiotherapy increased survival in patients with EGFR-mutant inoperable stage III NSCLC. The mild-to-moderate radiation pneumonitis incidence increased but no grade 4--5 adverse events occurred. WHAT THIS STUDY ADDS: The combination of EGFR-TKI and radiotherapy might carry a risk of pneumonitis; however, there are limited data concerning dose constraints. Our results showed a slightly higher incidence of mild or moderate radiation pneumonitis by strict dose limitation.

[Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer].

OBJECTIVE: To compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Five hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy. RESULTS: The 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups. CONCLUSIONS: The results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.

Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution.

BACKGROUND: For patients with resected pathological stage IIIA-N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. In this single-institutional study, we re-evaluated the effect of PORT on overall survival (OS) as well as tumor control in this subgroup of patients. METHODS: In 2003-2005, 221 consecutive patients with resected pathological stage IIIA-N2 NSCLC at our institution were retrospectively analyzed in an institutional review board-approved study. The effect of PORT on OS, cancer-specific survival (CSS), and disease-free survival (DFS) was evaluated using the Kaplan-Meier method and log-rank tests. The impact of PORT on locoregional control and distant metastasis was also analyzed. Results. Compared with the control, patients treated with PORT had a significantly longer OS time (χ2, 3.966; p = .046) and DFS interval (χ2, 6.891; p = .009), as well as a trend toward a longer CSS duration (χ2, 3.486; p = .062). Patients treated with PORT also had a significantly higher locoregional recurrence-free survival rate (χ2, 5.048; p = .025) as well as distant metastasis-free survival rate (χ2, 11.248; p = .001). Multivariate analyses showed that PORT was significantly associated with a longer OS duration (p = .000). CONCLUSIONS: PORT can significantly improve the survival of patients with resected pathological stage IIIA-N2 NSCLC. A prospective randomized multicenter clinical trial is ongoing.

[Clinical analysis of 126 patients with primary small cell carcinoma of the esophagus].

OBJECTIVE: To investigate the prognostic factors and the principles of treatment of primary esophageal small cell carcinoma (SCEC) retrospectively. METHODS: The data of 126 patients with histologically confirmed SCEC treated in our department between May 1985 and June 2005 were retrospectively analyzed. 85 patients were in limited disease stage (LD) and 41 patients as extensive disease stage (ED) according to the Veterans Administration Lung Study Group staging system. Among the 84 patients treated with esophagectomy, 8 cases were in stage I, 16 in stage IIa, 10 in stage IIb, 40 in stage III, 4 in stage IVa and 6 in stage IVb, according to the TNM system (6(th) edition, AJCC). Cox's hazard regression model was used to identify the prognostic factors, and Chi-square test to detect the difference of frequencies among different groups. Kaplan-Meier and log-rank methods were used to estimate and compare the survival rates. RESULTS: The median follow-up duration of this series was 13 months. One hundred and eight patients died of the disease during the follow-up, 10 were still alive and 8 were lost to follow-up. The 1-, 3-, and 5-year overall survival rates (OS) were 52.2%, 15.9%, and 12.2%, respectively, with a median survival time (MST) of 12.5 months. The 1-, 2-, and 3-year OS were 62.1%, 30.8%, and 22.4% with a MST of 14.0 months for LD, and 29.3%, 13.6% and 2.7% with a MST of 7.0 months for ED, respectively. There was a statistically significant difference in OS between LD and ED (P = 0.0001). The MST of the patients treated with chemotherapy was 14.5 months, significantly longer than the 5.2 months of the patients without (P = 0.0001). Multivariate analysis showed that stage (HR 1.91, 95% CI 1.26 approximately 2.91, P = 0.002), length of the primary lesion (HR 1.75, 95% CI 1.17 approximately 2.63, P = 0.007), and chemotherapy (HR 0.42, 95% CI 0.28 approximately 0.65, P = 0.000) were independent prognostic factors. CONCLUSION: Esophageal small cell carcinoma is a systemic disease. The tumor stage (LD or ED), length of the primary lesion and chemotherapy are independent prognostic factors. Therefore, a systemic therapy based on chemotherapy should be recommended.

[Effect of different chemotherapy regimens for concurrent chemoradiotherapy on locally advanced non-small cell lung cancer].

OBJECTIVE: To retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC). METHODS: The data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed. RESULTS: The median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis. CONCLUSION: There is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.

[Postoperative three-dimensional conformal radiotherapy for resected non-small cell lung cancer].

OBJECTIVE: To investigate the association between survival and postoperative three-dimensional conformal radiotherapy (3DCRT) in patients with resected non-small cell lung cancer (NSCLC). METHODS: Eighty-four patients were treated with surgery and postoperative 3DCRT for NSCLC. Sixty-five (77.4%) patients received lobectomy, and 19 (22.6%) received pneumonectomy. Fifty-four (64.3%) patients achieved R0 resection and 30 cases (35.8%) received R1/R2 resection. Fifty-two patients were of stage IIIA and 24 patients were of stage IIIB. Photon energy of 6 MV was used for all the patients. The median 3DCRT dose was 60 Gy (40 - 70 Gy) with a fraction size of 2 Gy. Thirty-seven patients received median 3 cycles of adjuvant chemotherapy. The median follow-up was 35.5 months for survivors. RESULTS: The overall 3-year survival rate was 58.6%, and the 4-year overall survival rate was 43.9%. Of the 43 patients who had treatment failure, only 8 (9.9%) patients showed intrathoracic recurrence, but 38 (46.9%) patients had distant metastasis. The univariate analysis for all patients showed that sex, age, weight loss, tumor size, pathology and stage were not correlated with prognosis. R1/R2 resection was associated with a significantly worse survival. Toxicities were acceptable, with 9 (11.1%) patients appeared higher than NCI CTC grade 2 radiation pneumonitis. CONCLUSION: In a population-based cohort, postoperative 3DCRT for NSCLC provides a good prognosis, and the radiation-related pneumonitis is acceptable.

[Three-dimensional conformal radiotherapy for locoregionally recurrent non-small cell lung cancer after initial radiotherapy].

OBJECTIVE: To evaluate the feasibility, therapeutic effects and normal tissue complications of three-dimensional conformal radiotherapy (3DCRT) for locoregionally recurrent non-small cell lung cancer after initial radiotherapy. METHODS: Between August 1999 and August 2003, 27 such patients were treated with 3DCRT after initial radiotherapy. This series consisted of 25 men and 2 women with a median age of 64 years. Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week, to a median dose of 50 Gy. Treatment results and normal tissue complications were assessed with WHO and RTOG/EORTC criteria. RESULTS: Based upon a median follow-up time of 20.6 months, 25 patients (92.6%) completed the planned 3DCRT treatment. Their clinical symptom relief rate was 79.1%, and the response rate was 59.3% with a complete remission rate of 14.8% (4/27), partial remission rate of 44.4% (12/27). The overall 1- and 2-year survival (OS) rates were 73.8% and 25.4% with a median survival time (MST) of 20 months. The 1- and 2-year local progression free survival (LPFS) rates were both 88.8%. Grade 2 and grade 3 acute radiation pneumonitis developed in 7.4% (2/27) and 11.1% (3/27). Grade 2 late radiation pneumonitis developed in 11.1% (3/27). CONCLUSION: 3DCRT is feasible and advisable for locoregionally recurrent non-small-cell lung cancer, giving a good immediate tumor response and acceptable normal tissue complications.