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Objective: The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group., Methods: Data of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis., Results: The analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3-C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042-0.744, p = 0.018., Conclusions: Our study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C., Competing Interests: Disclosure All authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: 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., Materials and Methods: 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., Results: 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)., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The International Thymic Malignancy Interest Group (ITMIG) classifies thymoma recurrences on the basis of the topographic location, but its effectiveness in prognosis prediction has not been well investigated yet. Aims of this study are to analyze survival outcome of patients surgically treated for thymoma recurrence according to the ITMIG recurrence classification and to investigate possible alternatives., Methods: From January 1, 1990, to January 7, 2017, data on 135 surgically treated patients for thymoma recurrence from three high-volume centers were collected and retrospectively analyzed. Patients were classified according to the ITMIG classification as local, regional, and distant. The ITMIG classification and alternative classifications were correlated to overall survival (OS)., Results: According to the ITMIG classification, recurrence was local in 17 (12.5%), regional in 97 (71.8%), and distant in 21 (15.7%) patients, with single localization in 38 (28.2%) and multiple localizations in 97 (71.8%). The 5- and 10-year OS were 79.9% and 49.7% in local, 68.3% and 52.6% in regional, and 66.3% and 35.4% in distant recurrences, respectively, but differences were not statistically significant (p = 0.625). A significant difference in survival was present considering single versus multiple localizations: 5- and 10-year OS of 86.2% and 81.2% versus 61.3% and 31.5% (p = 0.005, hazard ratio = 7.22, 95% confidence interval: 0.147-0.740), respectively. Combining the localization number with the recurrence site, ITMIG locoregional single recurrence had a statistically significant better survival compared with patients with ITMIG locoregional multiple recurrence or ITMIG distant recurrence (p = 0.028). Similarly, a significant difference was present considering intrathoracic single versus intrathoracic multiple versus distant recurrence (p = 0.024)., Conclusions: The ITMIG classification for thymoma recurrence did not have significant survival differences comparing local, regional, and distant recurrences. Integrating this classification with the number of the localizations may improve its effectiveness in prognosis prediction., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Recurrence of thymoma is described in 10-30% of cases after surgical resection. Iterative surgery for thymoma pleural relapses (TPRs) is often part of a multimodal treatment. Hyperthermic intrathoracic chemotherapy (HITHOC) following macroscopic radical surgery is an option that combines the effects of mild hyperthermia with those of chemotherapeutic agents. We evaluated the effectiveness of surgery + HITHOC, compared with surgery alone, in the treatment of TPR., Methods: We retrospectively collected data of all patients who underwent surgery for TPR in our centre from 2005 to 2017. Relapses were treated by partial pleurectomy with radical intent, followed by HITHOC when not contraindicated. Patients were divided into 2 groups: surgery + HITHOC and surgery alone. We collected demographic and clinical data and analysed postoperative results together with oncological outcomes., Results: Forty patients (27: surgery + HITHOC, 13: surgery alone), mean age 49.8 (±13.7) years, were included in this study. There were no perioperative deaths. We experienced 33.3% perioperative morbidity in the surgery + HITHOC group compared with 23.1% in the surgery alone group (P = 0.71). The overall survival rate was comparable between the 2 groups (P = 0.139), whereas the local disease-free interval was 88.0 ± 15 months in the surgery + HITHOC group and 57 ± 19.5 months in the surgery alone group (P = 0.046). The analysis of factors affecting the outcomes revealed that radical surgery is related with a better survival rate whereas the local disease-free interval was significantly influenced by HITHOC., Conclusions: The safety and feasibility of HITHOC in the treatment of TPR are already known, even if it should be reserved for selected patients. Surgery + HITHOC seems to be associated with a longer local disease-free time compared to surgery alone., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Thymomas are rare neoplasms with a low recurrence rate, which are preferably surgically treated. Iterative thymoma surgery has not been well investigated yet. Study aim is to analyse prognostic factors after iterative recurrence treatment., Methods: Clinical, pathological and surgical findings of 155 patients, treated for thymoma recurrence in three high-volume centres from 01/01/1990 to 1/07/2017, were retrospectively reviewed. Recurrence patterns/treatment types (surgery or chemotherapy, radiotherapy or combined) were correlated to overall (OS) and disease free survival (DFS)., Results: Myasthenia Gravis was present in 135 (87%) patients. Surgery was performed in 135/155 (87%) patients with 109 (80.7%) complete resections. Sixty (55%)patients experienced a second recurrence surgically treated in 31/60 (52%) cases with 18 (58%) complete resections. Eleven (61%) patients experienced a third recurrence and nine underwent complete resection. Myastenia Gravis (HR: 0.45; 95% CI: 0.20-0.98, p = 0.046), DFS after the initial thymectomy >36 months (HR: 0.9; 95% CI: 0.96-0.99, p = 0.006) and complete second recurrence resection (HR: 1.45; 95% CI 2.07-10.01, p = 0.010) resulted as independent favorable prognostic survival factor. Despite patient selection bias, rewarding long-term survivals was predictable after iterative thymoma surgery (5 and 10 years survival of 79.6% and 64.6%) while a poor prognosis was observed after CT/RT (5 and 10 years OS of 56.7% and 21.5%), Masaoka stage and DFS > 36 months were risk factor for iterative recurrences., Conclusions: Myasthenia Gravis and long DFS after thymectomy are favorable survival factors for multiple thymoma recurrences. Iterative surgical treatment is a viable therapeutic option associated to long-term survival if technically and clinically feasible., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Phrenic nerve infiltration has been described in as many as 33% of advanced thymomas; en bloc resection causes diaphragmatic loss of function, with detrimental effects on pulmonary function. We report the outcomes of selected patients operated on for invasive thymoma with a nerve-sparing technique., Methods: From 1990 to 2015 we used nerve-sparing surgery with the intention to treat all patients with advanced stage thymomas without preoperative evidence of hemidiaphragmatic palsy, but with macroscopic evidence of phrenic nerve involvement. All patients underwent adjuvant radiotherapy (45 to 60 Gy) with or without chemotherapy. Long-term outcomes and the pattern of recurrence were retrospectively analyzed., Results: Among 140 patients with stage III and IVa operated on during the study period, 19 women and 18 men with a median age of 52 years received a nerve-sparing resection. Myasthenia gravis was associated in 25 cases. In 12 patients, phrenic palsy was observed postoperatively, and eventually 4 of them recovered. Recurrence was found in 10 patients (7 stage IVa, 3 stage III) requiring additional therapies. Three patients died of cancer-related causes, with an overall survival of 265.4 months and a disease-free survival of 233.2 months., Conclusions: Phrenic nerve preservation in cases of invasive thymomas is feasible and may warrant an acceptable local control of disease, if associated with radiotherapy. According to these results, this technique could be proposed to all patients with invasive thymoma, especially in those affected by severe comorbidities or with a poor performance status., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Recurrences of thymoma are described in 10-30% of cases up to 10 years after surgical resection. Herein we report our experience with surgical removal of pleural recurrences followed by hyperthermic intrathoracic perfusion chemotherapy (HITHOC)., Methods: We prospectively collected data of patients with pleural recurrence of thymoma who underwent surgery followed by HITHOC. After thoracotomy had been closed, drainages were connected to a dedicated perfusion machine, pleural space was filled with saline solution, progressively heated up to 42.5°C. At this time, chemotherapeutic agents (Doxorubicin and Cisplatin) were injected and perfusion lasted 60 min., Results: In the period 2005-2012, 13 consecutive patients have been treated (8 males, 5 females, mean age 46 years). Initial Masaoka-Koga stage was 2 IIa, 5 IIb, 5 III, 1 IVa. Disease-free interval was 47.2 months on average [standard deviation (SD): 25.5]. Nine patients presented paraneoplastic syndromes (8 myasthenia gravis and 1 red cell aplasia). Complete resection was achieved in all cases except one. HITHOC was successfully performed in all cases and no signs or symptoms of toxicity were recorded in the perioperative period. With a mean follow-up period of 64.6 months (SD: 32.5), 1 patient died for toxicity following systemic chemotherapy, another one died disease-free, 4 patients developed pleural relapses (2 ipsilateral, 2 contralateral) and 1 mediastinal and abdominal nodal metastases. Mean survival was 58 months [SD: 34.4), median survival by the Kaplan-Meier method was not reached while 5-year actuarial survival was 92%., Conclusions: HITHOC was shown to be feasible and safe. In terms of efficacy, it seems promising but multicentre studies and a longer follow-up period are required to ascertain its effectiveness., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to report a single referral centre experience in robotic extended thymectomy for clinical early-stage thymomas, evaluating its safety, feasibility and efficacy, with special regard to oncological outcomes., Methods: Between April 2002 and February 2011, we retrospectively selected all those patients who underwent robotic thymectomy for clinical early-stage thymomas. Operative time, morbidity, mortality, duration of hospitalization and overall and disease-free survival were analysed., Results: There were 14 patients (8 males, 6 females) with a mean age of 65.2 years (range 23-81). One patient suffered from myasthenia gravis. The WHO classifications were: A in two cases, AB in four cases, B1 in three cases, B2 in two cases and B3 in three cases. The Masaoka stages were: I in seven cases, IIA in four cases, IIB in two cases and III in one case. The mean operative time was 139 min. No intra-operative complication or death occurred. Conversion to open surgery was required in two cases. Minor complications occurred in two patients (14.2%) due to pleural effusion. The mean hospitalization was 4.0 days. Five patients underwent adjuvant radiotherapy. All patients were alive with no disease recurrence, with a median follow-up of 14.5 months (range 1-98)., Conclusions: Robotic thymectomy is a safe and feasible technique, with a short operative time and low morbidity. Even on a small series with short follow-up, robotic extended thymectomy for thymoma appeared to be an effective treatment for early-stage thymomas.

Aim: Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors., Methods: The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out., Results: The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages., Conclusions: The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.

Background: With the aim of evaluating the results of multidisciplinary approaches, we reviewed our experience in multimodality treatment of advanced stage (III and IVA) thymic tumors., Methods: From 1976 to 2003, 56 patients with Masaoka stage III and IVA thymic tumors underwent a multimodality treatment. Thirty-six patients underwent neoadjuvant chemotherapy, surgery, and postoperative radiotherapy; 20 patients were treated by primary surgery and postoperative radiotherapy (n = 12), chemotherapy (n = 1) or chemoradiotherapy (n = 7). The neoadjuvant or adjuvant chemotherapy consisted of three courses of cisplatin, epidoxorubicin, and etoposide every 3 weeks. Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections., Results: The preoperative diagnosis of invasive thymomas was performed in a total of 29 cases: 15 by mediastinotomy, 6 by video-assisted thoracoscopic surgery, and 8 by fine-needle aspiration. In 27 cases no diagnosis was available, but in most of them a thymus-related syndrome was present. Thirty-four patients are still alive (31 disease-free), and 22 have died (2 disease-free). Ten-year survival was 48% and 45.7% for stage III and IVA thymomas, respectively. The presence of myasthenia gravis (p = 0.04) and neoadjuvant chemotherapy (p = 0.004) affected survival significantly., Conclusions: The multimodality treatment of stage III and IVA thymic tumors allows a good long-term outcome; the neoadjuvant chemotherapy improves the resectability rate and the survival of both stages of the disease.

Objectives: Thymic carcinoma is a rare neoplasm more invasive and with a poorer prognosis than ordinary thymoma. Complete curative resection is sometimes not possible, but good response rates to chemotherapy are reported in literature. We report our experience with seven cases of thymic carcinoma, who took part to a multimodality treatment including neoadjuvant chemotherapy, surgery and post-operative radiotherapy in our center., Methods: Since June 1989, seven previously untreated patients were enrolled. The primary chemotherapy consisted of three courses of cisplatin (P; 75 mg/m(2) i.v., day 1), epidoxorubicin (E; 100 mg/m(2) i.v., day 1) and etoposide (VP16; 120 mg/m(2) i.v., days 1, 3 and 5), every 3 weeks. Surgery was performed following complete hematological recovery. After surgery, all patients underwent radiation therapy to the tumor areas, operatively marked with clips, at doses of 45 (complete resection) or 60 Gy (incomplete resection)., Results: The pre-operative diagnosis of thymic carcinoma was performed in four cases by a mediastinotomy, and in the remaining cases, by an ultrasound-guided (n=2) or a computed tompography-guided (n=1) fine needle aspiration. All patients responded (one completely) to the chemotherapy regimen. Surgical resection was complete in four cases (histological examination negative in one case). Three patients are still alive and well (62-136 months from the diagnosis), two are alive with relapse at 16 and 85 months, one patient died at 86 months from another cause, and one patient died at 18 months from local relapse and lung metastases., Conclusions: A pre-operative shrinkage of the thymic carcinoma by means of neoadjuvant multi-drug chemotherapy may improve the resectability, and therefore, the survival rate. Our experience, although preliminary, is encouraging and merits additional study in a multicenter trial with a sufficient number of patients to draw definitive conclusions.