Comparison of Neoadjuvant Chemotherapy Followed by Surgery to Upfront Surgery for Thymic Malignancy

doi:10.1016/j.athoracsur.2018.08.055

The Annals of Thoracic Surgery

Volume 107, Issue 2, February 2019, Pages 355-362

Presented at the Fifty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 27–31, 2018.

https://doi.org/10.1016/j.athoracsur.2018.08.055 Get rights and content

Background

The oncologic benefit of neoadjuvant chemotherapy in thymic malignancies remains unclear. Postoperative oncologic outcomes of curative resection after neoadjuvant chemotherapy were compared with those of upfront surgery.

Methods

Based on records from a multicenter database, 1,486 patients with surgically resected thymic malignancies between 2000 and 2013 were included in the final study cohort. Of these, 110 patients (7.4%) underwent surgical resection after neoadjuvant chemotherapy, and 1,376 patients (92.6%) underwent upfront surgery. A propensity score-matched analysis was performed to minimize differences in preoperative and intraoperative variables. Postoperative outcomes and survivals were compared between the two groups.

Results

In the matched cohort, there were no significant differences in postoperative mortality (p value not calculated), postoperative complications (p = 0.405), and hospital length of stay (p = 0.821) between the two groups. However, the neoadjuvant chemotherapy group showed significantly higher transfusion rates (p = 0.003) and longer operation times (p < 0.001) than the upfront surgery group. Pathologically complete resection rates (p = 0.382) and tumor sizes (p = 0.286) were similar between the two groups. The 5-year overall survival rates were 77.4% and 76.7%, respectively (p = 0.596). The 3-year recurrence-free survival rates were 62.9% and 71.5%, respectively (p = 0.070).

Conclusions

Neoadjuvant chemotherapy, followed by resection, obtained similar resectability and long-term survival rates to those of upfront surgery. Therefore, the role of neoadjuvant chemotherapy should be refined in randomized controlled trials.

Section snippets

Material and Methods

The Korean Association for Research on the Thymus recently set up a database of patients who were surgically treated for thymic malignancies at 4 institutions in Korea. From January 2000 to December 2013, 1,663 patients were identified in the database. Among them, we excluded patients with (1) incomplete data regarding pathologic variables and survival, (2) noncurative resection (ie, biopsy only), (3) surgical resection for recurrence after primary treatment, and (4) missing data. Radiologic

Patient Characteristics

The final study cohort included 1,486 patients. We divided the cohort into two groups according to the treatment strategy: 110 (7.4%) underwent surgical resection after neoadjuvant chemotherapy (NC group), and 1,376 (92.6%) underwent upfront surgery (US group). Supplemental Tables 1 and 2 summarize the patient characteristics and surgical procedures in the unmatched cohorts. Median follow-up duration was 52.3 months. Table 2 describes the patient characteristics and surgical procedures in the

Comment

We used records from a multiinstitutional database to compare postoperative outcomes and long-term survival between neoadjuvant chemotherapy, followed by resection, versus upfront surgery. Although more frequent transfusion, higher blood loss, and longer operation times were required for patient who underwent resection after neoadjuvant chemotherapy compared with upfront surgery, complete resection rates were similar. The results showed similar long-term survival rates between the two groups

References (20)

K. Kondo et al.
Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan
Ann Thorac Surg
(2003)
F.C. Detterbeck et al.
Thymic tumors
Ann Thorac Surg
(2004)
S. Park et al.
A prospective phase II trial of induction chemotherapy with docetaxel/cisplatin for Masaoka stage III/IV thymic epithelial tumors
J Thorac Oncol
(2013)
F. Rea et al.
Multidisciplinary approach for advanced stage thymic tumors: long-term outcome
Lung Cancer
(2011)
F. Venuta et al.
Long-term outcome after multimodality treatment for stage III thymic tumors
Ann Thorac Surg
(2003)
M. Lucchi et al.
Advanced stage thymomas and thymic carcinomas: results of multimodality treatments
Ann Thorac Surg
(2005)
M. Hamaji et al.
A meta-analysis of induction therapy for advanced thymic epithelial tumors
Ann Thorac Surg
(2015)
E.S. Kim et al.
Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report
Lung Cancer
(2004)
S.A. Hayes et al.
Preoperative computed tomography findings predict surgical resectability of thymoma
J Thorac Oncol
(2014)
Y. Yamada et al.
Surgical outcomes of patients with stage iii thymoma in the Japanese Nationwide Database
Ann Thorac Surg
(2015)

There are more references available in the full text version of this article.

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Unradical Surgery for Locally-Advanced Thymoma: Is it time to evolve Perspectives?
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Nearly-one-third of thymomas are locally-advanced at diagnosis. The traditional dogma that surgery is justified in case a complete resection can be achieved has remained unmovable until today. This study aimed to investigate feasibility and oncologic efficacy of incomplete resection for locally-advanced thymomas in a contest of multimodality therapy.
A retrospective analysis was conducted using data of prospectively maintained thymomas database in a single high-volume centre. Data on 285 consecutive patients undergoing surgery for stage III and IVa thymomas between 1995 and 2019 were reviewed. Patients who underwent incomplete resection with curative-intent (removal of at least 90% of tumour burden) were included. Long-term outcomes and predictors of cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed. Secondary endpoint was to assess adjuvant therapy efficacy.
The study included 79 patients, 60 with microscopic residual tumour (76%, R1) and 19 with macroscopic residual disease (24%, R2). Masaoka-Koga stage was: III in 41 patients (52%) and IVa in 38 (48%). Histology was B2-thymomas (n = 31, 39.2%) followed by B3 (n = 27, 34.2%). Five- and 10-years CSS was 88% and 80%. Seventy patients (90%) underwent adjuvant treatment; they showed CSS comparable to radical resected patients (5-years: 89.1% vs 98.9%, respectively; 10-years: 81.8% vs 92.7%, respectively, p = 0.43). The site of residual disease, Masaoka-Koga stage and WHO histology did not affect prognosis. Stepwise multivariable analysis confirmed adjuvant therapy as a favourable CSS prognostic factor (HR, 0.51; 95% CI, 0.33–0.79, p = 0.003). Stratifying by subgroups, R2-patients who received postoperative chemo(radio)therapy (pCRT) showed a significantly better prognosis than R2-patients treated by consolidation radiotherapy alone (10-years CSS: 60%, p < 0.001).
In locally-advanced thymomas, whenever a radical surgery cannot be achieved, incomplete resection has proved to be effective in a contest of multimodality strategy, independently of WHO histology, Masaoka-Koga stage and site of residual disease.
Outcomes of extended resection for locally advanced thymic malignancies
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Thymic malignancies are rare tumors about which data are limited. Our objective here was to evaluate the outcomes and risk factors for complications and death in patients who underwent extended surgery to remove thymic malignancies.
We retrospectively included patients who underwent extended resection of locally advanced, nonmetastatic thymic malignancies at our institution. Patients were deemed eligible for resection by a multidisciplinary team. During surgery, priority was given to achieving complete resection rather than to sparing organs.
The 108 patients had a mean age of 53 ± 15 years (range, 9–83); among them, 91 had thymoma, 12 thymic carcinoma, and 5 neuroendocrine tumor. The Masaoka stage was III or higher in 86 patients; examination of operative specimens resulted in downstaging of 22 patients. Tumor-free resection margins were achieved in 98 patients. Overall 5- and 10-year survival rates were 80% and 68%, respectively. Myasthenia gravis, present in 36 patients, was the only independent significant risk factor for major postoperative complications. Age older than 70 years, thymic carcinoma or neuroendocrine tumor, pT3 or pT4 stage, and R1 or R2 resection margins independently predicted death. The number of resected structures was not associated with survival. Thymic carcinoma or neuroendocrine tumor was independently associated with shorter disease-free survival.
In an expert center, extended resection targeting complete resection rather than organ preservation provided good outcomes in patients with locally advanced thymic malignancies. The risk/benefit ratio of surgery should be assessed with special care in patients who are elderly or have myasthenia gravis.
Superior Vena Cava Reconstruction in Masaoka Stage III and IVa Thymic Epithelial Tumors
2022, Annals of Thoracic Surgery
Citation Excerpt :
We did not experience any complete pathologic response in our population. The Korean Association for Research on the Thymus studied complete resection rate, OS, and DFS among patients with upfront surgery or with induction therapy plus surgery and found no difference.28 Similarly, the European Society of Thoracic Surgeons showed no association between induction treatment and cancer-specific or recurrence-free survival.29
We present here a case series of patients who underwent resection for Masaoka stage III and IVa thymic epithelial tumors (TETs) with invasion into the superior vena cava (SVC).
A total of 29 patients with stage III and IVa TETs were treated surgically in 3 institutions. Operative resections involved replacing the SVC from one of the innominate veins (n = 18) or via reconstruction by truncal replacement (n = 2) or patch plasty (n = 9).
Fifteen patients underwent neoadjuvant treatment. Thirty- and 90-day mortality rates were 3.4% and 10.3%, respectively. For stage III patients, the median overall survival and disease-free survival (DFS) were 39 and 30 months, respectively. The median overall survival and DFS in patients with Masaoka stage IVa disease were 67 and 21 months, respectively. Undergoing only preoperative chemotherapy (P = .007) or receiving no chemotherapy (P = .009) had a DFS that was significantly higher than receiving both preoperative and postoperative chemotherapy.
SVC resection and reconstruction in Masoaka stage III and IVa TETs can be performed with acceptable morbidity and mortality. Stage IVa patients with SVC involvement can be treated with similar results as stage III patients with multimodality treatment.
CT Radiomic Features for Predicting Resectability and TNM Staging in Thymic Epithelial Tumors
2022, Annals of Thoracic Surgery
To explore the performance of a computed tomography based radiomics model in the preoperative prediction of resectability status and TNM staging in thymic epithelial tumors.
We reviewed the last preoperative computed tomography scan of patients with thymic epithelial tumors prior to resection and pathology evaluation at our institution between February 2008 and June 2019. A total of 101 quantitative features were extracted and a radiomics model was trained using elastic net penalized logistic regressions for each aim. In the set-aside testing sets, discriminating performance of each model was assessed with area under receiver operating characteristic curve.
Our final population consisted of 243 patients with: 153 (87%) thymomas, 23 (9%) thymic carcinomas, and 9 (4%) thymic carcinoids. Incomplete resections (R1 or R2) occurred in 38 (16%) patients, and 67 (28%) patients had more advanced stage tumors (stage III or IV). In the set-aside testing sets, the radiomics model achieved good performance in preoperatively predicting incomplete resections (area under receiver operating characteristic curve: 0.80) and advanced stage tumors (area under receiver operating characteristic curve: 0.70).
Our computed tomography radiomics model achieved good performance to predict resectability status and staging in thymic epithelial tumors, suggesting a potential value for the evaluation of radiomic features in the preoperative prediction of surgical outcomes in thymic malignancies.
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2021, Radiologic Clinics of North America
Citation Excerpt :
With incomplete surgical resection confirmed by microscopic disease at the surgical site, multimodality therapy, including chemotherapy and postoperative radiotherapy, is recommended to achieve complete disease eradication.33,36,37 Neoadjuvant chemotherapy is recommended for potentially resectable locally advanced thymic malignancies.38,39 Following surgical resection, postoperative radiation therapy is recommended, as these patients are at higher risk of recurrence.40
Thymic Epithelial Neoplasms: Radiologic-Pathologic Correlation
2021, Radiologic Clinics of North America
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The ITMIG recommends extended thymectomy including resection of prevascular mediastinal lymph nodes for all thymomas and sampling of deep lymph nodes when thymomas invade adjacent structures.39 Because achieving complete surgical resection improves survival regardless of stage or histologic classification, neoadjuvant chemotherapy may be used to convert unresectable tumors into resectable tumors.40 When there are positive margins or evidence of microscopic invasion into surrounding tissue on the pathologic specimen, adjuvant radiation therapy is indicated.

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Original articleGeneral thoracicComparison of Neoadjuvant Chemotherapy Followed by Surgery to Upfront Surgery for Thymic Malignancy

Background

Methods

Results

Conclusions

Section snippets

Material and Methods

Patient Characteristics

Comment

Ann Thorac Surg

Ann Thorac Surg

J Thorac Oncol

Lung Cancer

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Lung Cancer

J Thorac Oncol

Ann Thorac Surg

Original article
General thoracic
Comparison of Neoadjuvant Chemotherapy Followed by Surgery to Upfront Surgery for Thymic Malignancy