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Radiotherapy and Oncology : Journal of... Jun 2024To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial...
PURPOSE
To assess the prognostic factors and patterns of failure of patients consecutively treated with surgery and postoperative radiation therapy (PORT) for thymic epithelial tumours (TET).
PATIENTS AND METHODS
Data from 192 TET patients who were operated and received PORT at a single centre from 1990 to 2019 was retrospectively analysed.
RESULTS
Most patients had thymoma (77 %, B247%), were classified Masaoka-Koga stage III (35 %) or IV (32 %) and had a R0 (75 %) resection. Radiotherapy was delivered at a median dose of 50.4 Gy (range, 42-66 Gy; ≥ 60 Gy in 17 %), 63 (33 %) patients were treated by intensity-modulated radiation therapy and elective nodal radiotherapy was used for 37 %. At a median follow-up of 10.9 years, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 62 % (95 % CI: 54-70 %) and 47 % (95 % CI: 39-55 %), respectively. Locoregional recurrence (LRR) occurred in 72/192 (38 %) patients, distributed as 6 local, 45 regional and 21 both local and regional. LRR were mainly located to the pleura: 66/72 (92 %) and 16/72 (22 %; 16/192 in total, 8 %) were in-field. Distant relapse (DR) were observed in 30 patients (16 %), resulting in 10-year locoregional (LRC) and distant control rates of 58 % (95 % CI: 50-66 %) and 82 % (95 % CI: 77-88 %), respectively. In the multivariate analysis, Masaoka-Koga stage (HR [hazard ratio]: 1.9; p = 0.001), thymic carcinomas/neuroendocrine tumours (TC) (HR: 1.6; p = 0.045) and ECOG PS > 1 (HR: 1.9; p = 0.02) correlated with poorer OS. Higher Masaoka-Koga stage (HR: 2.6; p < 0.001) associated with a decreased LRC but not R1 status (HR: 1.2; p = 0.5) or WHO histology classification. TC (HR: 3.4; p < 0.001) and a younger age (HR: 2.5; p = 0.02) correlated with DR.
CONCLUSION
Approximately one-third of the TET in our study experienced a LRR, mainly to the pleura, and 8% in total were in-field. The place of radiotherapy should be better defined in higher risk thymoma patients within prospective randomized studies.
Topics: Humans; Thymus Neoplasms; Male; Female; Middle Aged; Aged; Adult; Retrospective Studies; Follow-Up Studies; Neoplasms, Glandular and Epithelial; Aged, 80 and over; Young Adult; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Radiotherapy, Intensity-Modulated; Adolescent; Thymoma; Prognosis; Survival Rate
PubMed: 38614283
DOI: 10.1016/j.radonc.2024.110272 -
Cancers Mar 2024Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low... (Review)
Review
Thymic epithelial tumors are a histologically diverse group of cancers arising from the epithelial compartment of the thymus. These tumors are characterized by a low tumor mutation burden, a lack of actionable genomic changes, and, especially with thymomas, defects in immune tolerance. Surgery is the mainstay of the management of resectable disease, whereas advanced, unresectable tumors are treated with platinum-based chemotherapy. Disease recurrence can occur months to years after frontline treatment. Although several options are available for conventional treatment of recurrent thymic tumors, response rates are generally low, and treatment-related toxicity can affect quality of life. A subset of patients benefit from biologic therapies, but there remains an unmet need for the development of new treatments. Immune checkpoint inhibitors are safe, clinically active, and have contributed to an improvement in survival for patients with a wide variety of cancers. However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers.
PubMed: 38611047
DOI: 10.3390/cancers16071369 -
Journal of Thoracic Oncology : Official... Apr 2024The aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the...
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.
PubMed: 38608933
DOI: 10.1016/j.jtho.2024.04.004 -
Journal of Thoracic Oncology : Official... Apr 2024Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains...
INTRODUCTION
Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative RadioTherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT.
METHODS
A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI method was used to question 24 national experts, with 115 questions regarding the following: (1) imaging techniques, (2) clinical target volume (CTV) and margins, (3) dose constraints to organs at risk, (4) dose and fractionation, and (5) follow-up and records. Consensus was defined when opinions reached more than or equal to 80% agreement.
RESULTS
We established the following recommendations: preoperative contrast-enhanced computed tomography (CT) scan is recommended (94% agreement); optimization of radiation delivery includes either a four-dimensional CT-based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT imaging (81% agreement); imaging fusion based on cardiovascular structures of preoperative and planning CT scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/volumetric modulated arc therapy is recommended (88% agreement); total dose is 50 Gy (81% agreement) with 1.8 to 2 Gy per fraction (94% agreement); cardiac evaluation and follow-up for patients with history of cardiovascular disease are recommended (88% agreement) with electrocardiogram and evaluation of left ventricular ejection fraction at 5 years and 10 years.
CONCLUSION
This is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.
PubMed: 38608932
DOI: 10.1016/j.jtho.2024.04.003 -
Pneumologie (Stuttgart, Germany) Apr 2024
Topics: Humans; Inpatients; Lung Neoplasms; Thymoma; Mesothelioma; Thymus Neoplasms
PubMed: 38608657
DOI: 10.1055/a-2227-3775 -
International Journal of Cancer Aug 2024Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC.... (Comparative Study)
Comparative Study
Thymic carcinoma (TC) is a rare malignant tumor with a poor prognosis, and there is currently limited data on the use of immunotherapy in patients with unresectable TC. In this study, data of patients with unresectable TC diagnosed from January 2017 were retrospectively collected from multiple centers. Treatment response, progression-free survival (PFS), overall survival (OS), survival-independent prognostic factor, and adverse events (AEs) were further analyzed. As a result, a total of 93 patients with unresectable TC were enrolled, of which 54 received first-line chemotherapy, and 39 received chemotherapy plus immune checkpoint inhibitors (ICIs). The objective response rate was 50% (27/54) in the chemotherapy group and 76.9% (30/39) in the chemotherapy plus ICIs group. The chemotherapy plus ICIs group achieved significant median PFS benefit (8.8 vs. 34.9 months, p < .001) and median OS benefit (41.8 months vs. not reached, p = .025). Multivariate analysis showed that ICIs and local therapy were independent prognostic factors for PFS. In addition, 17 patients developed immune-related AEs (IRAEs), of which 15 (38.5%) had Grade 1 or 2 IRAEs and 2 (5.1%) had Grade 3 IRAEs in the chemotherapy plus ICIs group. In conclusion, the efficacy of chemotherapy plus ICIs is superior to chemotherapy, and the adverse effects are manageable in patients with unresectable TC.
Topics: Humans; Male; Retrospective Studies; Female; Middle Aged; Immune Checkpoint Inhibitors; Aged; Thymus Neoplasms; Adult; Antineoplastic Combined Chemotherapy Protocols; Thymoma; Prognosis; Progression-Free Survival
PubMed: 38608177
DOI: 10.1002/ijc.34948 -
BMC Cancer Apr 2024Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two...
PURPOSE
Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.
METHODS
We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro.
RESULTS
In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration.
CONCLUSIONS
In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.
Topics: Humans; Acetyltransferases; Adenocarcinoma; Adenocarcinoma of Lung; Adrenal Cortex Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Chromosomal Proteins, Non-Histone; Colonic Neoplasms; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Thymus Neoplasms
PubMed: 38605349
DOI: 10.1186/s12885-024-12213-w -
Radiographics : a Review Publication of... May 2024Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality...
Thymic imaging is challenging because the imaging appearance of a variety of benign and malignant thymic conditions are similar. CT is the most commonly used modality for mediastinal imaging, while MRI and fluorine 18 fluorodeoxyglucose (FDG) PET/CT are helpful when they are tailored to the correct indication. Each of these imaging modalities has limitations and technical pitfalls that may lead to an incorrect diagnosis and mismanagement. CT may not be sufficient for the characterization of cystic thymic processes and differentiation between thymic hyperplasia and thymic tumors. MRI can be used to overcome these limitations but is subject to other potential pitfalls such as an equivocal decrease in signal intensity at chemical shift imaging, size limitations, unusual signal intensity for cysts, subtraction artifacts, pseudonodularity on T2-weighted MR images, early imaging misinterpretation, flow and spatial resolution issues hampering assessment of local invasion, and the overlap of apparent diffusion coefficients between malignant and benign thymic entities. FDG PET/CT is not routinely indicated due to some overlap in FDG uptake between thymomas and benign thymic processes. However, it is useful for staging and follow-up of aggressive tumors (eg, thymic carcinoma), particularly for detection of occult metastatic disease. Pitfalls in imaging after treatment of thymic malignancies relate to technical challenges such as postthymectomy sternotomy streak metal artifacts, differentiation of postsurgical thymic bed changes from tumor recurrence, or human error with typical "blind spots" for identification of metastatic disease. Understanding these pitfalls enables appropriate selection of imaging modalities, improves diagnostic accuracy, and guides patient treatment. RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Neoplasm Recurrence, Local; Thymus Neoplasms; Thymoma; Positron-Emission Tomography; Magnetic Resonance Imaging; Radiopharmaceuticals
PubMed: 38602866
DOI: 10.1148/rg.230091 -
Blood Apr 2024
Topics: Humans; Thymoma; Thymus Neoplasms; Lymphoma, B-Cell
PubMed: 38602694
DOI: 10.1182/blood.2023022586 -
Journal of Cardiothoracic Surgery Apr 2024This case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such...
This case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such tumors. A 71-year-old female presented with an asymptomatic anterior mediastinal tumor discovered incidentally during a routine health examination. Surgical intervention, followed by pathological and immunohistochemical analysis including CK-pan, p63, p40, and CD117 molecules, led to a definitive diagnosis of basaloid carcinoma of the thymus. This case highlights the critical importance of differential diagnosis in mediastinal lesions, especially those presenting with multilocular thymic cysts on chest CT. The subxiphoid video-assisted thoracoscopic surgery enabled complete tumor resection with minimal trauma and favorable postoperative outcomes. The patient opted against further radiotherapy or chemotherapy and she has survived for over eight months without recurrence. This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists.
Topics: Female; Humans; Aged; Mediastinal Neoplasms; Thymus Neoplasms; Mediastinal Cyst; Thymoma; Carcinoma, Squamous Cell; Teratoma
PubMed: 38600577
DOI: 10.1186/s13019-024-02712-z