Surgical,Radiation, and Systemic Treatments of Patients With Thymic Epithelial Tumors: A Clinical Practice Guideline

IntroductionThe aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors.MethodsThe guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews.ResultsEvidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline.ConclusionsThis guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.     

The Impact of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma

IntroductionThe optimal role for postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Data Base to investigate the impact of PORT on overall survival (OS).MethodsPatients who underwent an operation for thymoma or thymic carcinoma were categorized into Masaoka-Koga stage groups I to IIA, IIB, III, and IV. Patients who did not undergo an operation or those who received preoperative radiation were excluded. Kaplan-Meier estimates of OS and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders.ResultsFrom 2004 to 2012, 4056 patients were eligible for inclusion, 2001 of whom (49%) received PORT. On multivariate analysis of OS in the thymoma cohort adjusted for age, WHO histologic subtype, Masaoka-Koga stage group, surgical margins, and chemotherapy administration, PORT was associated with superior OS (hazard ratio [HR] = 0.72, p = 0.001). Propensity score–matched analyses confirmed the survival advantage associated with PORT. Subset analysis indicated longer OS in association with PORT for patients with stage IIB thymoma (HR = 0.61, p = 0.035), stage III (HR = 0.69, p = 0.020), and positive margins (HR = 0.53, p < 0.001). The impact of PORT for stage I to IIA disease did not reach significance (HR = 0.76, p = 0.156).ConclusionsIn this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.     

Improved Overall Survival with Aggressive Primary Tumor Radiotherapy for Patients with Metastatic Esophageal Cancer

ObjectivesThe aim of this study was to characterize utilization and survival outcomes associated with primary tumor–directed radiotherapy (PTDRT) in patients with newly diagnosed metastatic esophageal cancer.MethodsWe conducted an observational cohort study using the National Cancer Data Base to evaluate patients with newly diagnosed metastatic esophageal cancer between 2004 and 2012. Overall survival outcomes after treatment with chemotherapy plus conventional palliative dose radiotherapy (<5040 cGy), chemotherapy plus definitive dose radiotherapy (≥5040 cGy), or chemotherapy alone were compared by using Cox proportional hazards models with inverse probability of treatment weighting using the propensity score. Potential unmeasured confounding was assessed through sensitivity analyses.ResultsThe final cohort consisted of 12,683 patients: 57% were treated with chemotherapy alone, 24% were treated with chemotherapy plus palliative dose radiotherapy, and 19% were treated with chemotherapy plus definitive dose radiotherapy. Compared with chemotherapy alone, chemotherapy plus definitive dose radiotherapy was associated with improved survival (median overall survival of 8.3 versus 11.3 months [hazard ratio = 0.72, 95% confidence interval: 0.70–0.74, p ≤ 0.001]), whereas chemotherapy plus palliative dose radiotherapy was associated with slightly inferior outcomes (median overall survival of 8.3 months versus 7.5 months (hazard ratio = 1.10, 95% confidence interval 1.07–1.13, p ≤ 0.001). These findings were robust to potential unmeasured confounding in sensitivity analyses. Additionally, landmark analyses confirmed these findings in patients surviving 12 months or longer.ConclusionsDefinitive dose, but not conventional palliative dose, PTDRT is associated with improved overall survival in metastatic esophageal cancer, suggesting that local control may be important to prognosis. These findings support integrating PTDRT into future clinical trials aimed at refining personalized treatment for patients with metastatic esophageal cancer.     

Multimodality treatment program in invasive thymic epithelial tumor

Little is known regarding malignant thymoma and thymic carcinoma optimal therapy, and a multimodality approach could therefore be proposed in an attempt to improve the survival of patients. We report our experience with 8 cases of malignant thymoma or thymic carcinoma. These patients took part in a multimodality treatment program including neoadjuvant chemotherapy, surgery, and postoperative radiotherapy in our center between December 1995 and June 2001. The induction chemotherapy consisted of 4 courses of the CAP regimen (cyclophosphamide 600 mg/m2 day 1, doxorubicin 50 mg/m2 day 1, and cisplatin 80 mg/m2 day 2), every 3 weeks. Patients underwent surgical resection after complete hematological recovery pending sufficient tumor response with a postchemotherapy resectable status. Adjuvant radiotherapy up to 60 Gy in 30 fractions was attempted postsurgically or after best chemotherapeutic response in nonsurgical patients. Among the 8 patients, 3 had a thymic carcinoma and 5 a malignant thymoma; 5 had a stage IV and 3 a stage III disease (Masaoka). Six patients partially responded to the chemotherapy regimen. Three patients were operated upon, and complete resection was performed in 2 cases. Finally, 4 patients achieved the planned radiotherapy. Four patients are still alive without evidence of tumor activity (23-77 months from the diagnosis) and 1 patient is alive with relapse at 56 months. The low compliance with the program led us to an early discontinuation. The high proportion of thymic carcinoma and advanced disease in our limited series might be an explanation for this unsatisfactory result. Optimal multimodality treatment of epithelial thymic tumor remains to be defined in multicenter trials.     

Thymoma and thymic carcinoma in children and adolescents: A report from the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT)

BackgroundThymomas and thymic carcinomas belong to a group of thymic epithelial tumours arising from the anterior mediastinum and, are extremely rare in children in which no therapeutic guidelines have been established. The aim is to describe paediatric characteristics of these tumours and give some therapeutic indications.MethodsRetrospective analysis of clinical data and therapeutic characteristics of paediatric patients less than 18 years with thymic tumours treated between 2000 and 2012 registered in the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) database of the cooperating national rare paediatric tumour working groups from France, Italy, Germany and Poland.ResultsSixteen children with thymoma, median age 11 years and 20 patients with thymic carcinoma, median age 14 years were enrolled into study. At diagnosis complete primary resection was possible in 11 patients with thymoma and one with thymic carcinoma; resection with microscopic residue was performed in three cases and incomplete resection with macroscopic residue in four patients. Chemotherapy with various regimens was administered to 22 children; 17 of them as neoadjuvant chemotherapy. Eight patients with thymic carcinoma received additional radiotherapy. Seventeen children died (15 thymic carcinoma, two thymoma). Five-year overall survival for patients with thymic carcinoma is 21.0 ± 10.0%.ConclusionsThis study confirms the possibility to perform European retrospective analysis even in very rare paediatric tumours. Thymic carcinoma is associated with paediatric patients to give a very poor prognosis independently despite multimodal management. Multidisciplinary, multicenter approach and collaboration with adults’ physician are necessary in order to propose homogenous guidelines.     

Central Nervous System Metastases in Thymic Epithelial Tumors: A Brief Report of Real-World Insight From RYTHMIC

Thymic epithelial tumors (TETs) are rare malignancies ranging from indolent thymoma A to aggressive thymic carcinomas (TCs). Brain metastases are extremely infrequent for TETs and have only been described in case reports or small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French nationwide network mandated to systematically review every TET case and prospectively includes all consecutive patients discussed by national or regional tumor boards. We analyzed patients with TETs and central nervous system (CNS) metastasis during their cancer history from this large French registry. In an 8-year period, 2909 patients were included in the database, including 248 TCs (8.5%). A total of 14 patients had CNS metastases, five (36%) at diagnosis and nine (64%) at relapse. Among them, 12 patients (86%) had a diagnosis of TC and two (14%) had thymoma A and B3. Surgical biopsies were performed, and the histologic subtype for non-TC tumors was centrally confirmed. Median overall survival was 22 months (95% confidence interval [CI]: 9.8–34.2), with longer, albeit not significant, overall survival when CNS metastases were present at diagnosis versus relapse (not reached versus 17 mo; p = 0.29); median progression-free survival was 13 versus 8 months (p = 0.06), respectively. A higher risk of death (hazard ratio = 5.34, 95% CI: 1.3–21.9, p = 0.02) and relapse (hazard ratio = 1.89, 95% CI: 0.9–3.7, p = 0.06) was observed for patients suffering from TC with brain metastases compared with those without CNS extension. CNS disease was extremely rare in our TET cohort (0.48%), reported at both diagnosis and progression, present primarily in TC, with prevalence rising to 4.9%.     

Trends in Incidence and Survival of Patients With Thymic Epithelial Tumor in a High-Incidence Asian Country: Analysis of the Korean Central Cancer Registry 1999 to 2017

IntroductionTo report the trends in incidence and survival associated with thymic epithelial tumors (TETs) in Korea.MethodsData from 1999 to 2017 were obtained from the Korean Central Cancer Registry. Age-standardized incidence rates and average annual percentage changes (AAPCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method.ResultsAmong 5812 patients diagnosed with having TETs, 58.9%, 38.1%, and 3.0% were diagnosed with having thymoma, thymic carcinoma, and thymic neuroendocrine tumor (NET), respectively. Age-standardized incidence rates were 0.50, 0.30, 0.18, and 0.02 per 100,000 for all TETs and the respective subtypes. There was an increase in incidence of all TETs (AAPC = 6.1%) and subtypes: thymoma (AAPC = 5.6%), thymic carcinoma (AAPC = 7.0%), and thymic NET (AAPC = 3.4%). Proportions of patients with thymoma, thymic carcinoma, and thymic NET were 58.9%, 38.1%, and 3.0%, respectively. For thymoma, the relative proportion of distant stage decreased (19.4% in 2005 to 8.8% in 2017) and low-grade WHO subtype (A, AB, B1) increased faster than high-grade WHO type (B2, B3) (AAPC = 19.8% versus 9.6%). For thymoma, the 5-year NS was 82.3%. This increased from 64.3% in 1999 to 2002 to 90.6% in 2013 to 2017. For thymic carcinoma, the 5-year NS was 46.2% and only slightly increased from 39.4% in 1999 to 2002 to 47.9% in 2013 to 2017.ConclusionsThis study indicates a high incidence of TET and its continuous increase in Korea. The proportion of thymic carcinoma was relatively higher than in the United States or Europe. Survival for thymoma improved during the study period, whereas this was not evident for thymic carcinoma or thymic NET.     

RELEVENT Trial: Phase II Trial of Ramucirumab,Carboplatin, and Paclitaxel in Previously Untreated Thymic Carcinoma/B3 Thymoma With Area of Carcinoma

Thymic epithelial tumors are rare malignancies. Thymic carcinoma represents about 20% of all thymic epithelial tumors and has aggressive behavior, with a greater tendency to metastatic spread. Thymic carcinoma is often diagnosed in advanced stages for which systemic treatment is the main therapeutic option. The association of chemotherapy and antiangiogenic agents in the first-line setting has never been investigated in this very rare cancer. However, preclinical and clinical evidence has suggested that inhibition of angiogenesis could be beneficial. The RELEVENT trial is a multicenter, open-label, single-arm, phase II study aimed at investigating the activity and safety of ramucirumab combined with paclitaxel and carboplatin in chemotherapy-naive patients affected by thymic carcinoma or B3 thymoma with area of carcinoma. The primary endpoint of the trial is the overall response rate. Progression-free survival, overall survival, and safety are secondary endpoints. Patient-reported outcomes will be collected at each visit. The mutational status of a subset of genes, polymorphisms, and selected micro-RNA expression will be evaluated.     

Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial

BACKGROUND: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. METHODS: From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. RESULTS: Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. CONCLUSIONS: The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease.     

RADIORYTHMIC: Phase III,Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection

IntroductionThymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway.Patients and MethodsThree hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers.ResultsThe first patient will be enrolled in January 2021, with results expected in 2028.     

Postoperative radiotherapy in stage II or IIIA completely resected non-small cell lung cancer: a systematic review and practice guideline

The Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care conducted a systematic review of literature published between 1985 and July 2003 and developed an evidence-based clinical practice guideline on postoperative radiotherapy in patients with completely resected pathologic stage II or IIIA non-small cell lung cancer (NSCLC). Forty-four Ontario clinicians reviewed the draft guideline. Evidence included one meta-analysis of individual patient data (from nine randomized controlled trials) and three randomized controlled trials (two including data reported in the meta-analysis) that compared surgery with or without postoperative radiotherapy. The meta-analysis and one trial detected a significant detriment to survival with postoperative radiotherapy. Two trials detected no survival difference. The meta-analysis detected a significant advantage in local recurrence-free survival (time to local recurrence or death) with surgery alone, although two trials detected a significant advantage in rate of local recurrence with postoperative radiotherapy. Subset analyses from the meta-analysis and one trial suggested that postoperative radiotherapy was detrimental to survival mainly in stage II disease; no benefit or detriment was evident for stage III disease. Recommendations: Postoperative radiation therapy following complete resection of stage II non-small cell lung cancer is not recommended. No definitive recommendation can be made for stage IIIA disease.     

Chemotherapy and targeted agents for thymic malignancies

Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat. Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection. However, nearly 30% of patients present with locally advanced tumors at time of diagnosis, and chemotherapy is then used to reduce the tumor burden, possibly allowing subsequent surgery and/or radiotherapy. Metastatic and recurrent thymic malignancies may similarly be treated with chemotherapy. More recently, the molecular characterization of thymoma and thymic carcinoma led to the identification of potentially druggable targets, laying the foundations to implement personalized medicine for patients.     

Clinical Outcomes of Up-front Surgery Versus Surgery After Induction Chemotherapy for Thymoma and Thymic Carcinoma: A Retrospective Study

IntroductionAlthough induction chemotherapy improves the resectability of thymic neoplasms, it is unclear whether surgery after induction chemotherapy can improve outcomes. We compared long-term outcomes of surgery with and without induction chemotherapy in patients with thymic neoplasms.Patients and MethodsWe retrospectively investigated the clinical information of patients with thymic neoplasms at the National Taiwan University Hospital between 2005 and 2013.ResultsOf 204 patients, 119 underwent direct surgery (group 1), 45 underwent surgery after induction chemotherapy (group 2), and 40 underwent no surgery (group 3). The 5-year overall survival rates of groups 1, 2, and 3 were as follows: for 204 patients, 96.3%, 76.4%, and 35.5% (P < .001); for 119 thymoma patients, 96.6%, 88.9%, and 100.0% (P = .835); for 85 thymic carcinoma patients, 94.7%, 69.7%, and 17.7% (P < .001); for 36 American Joint Committee on Cancer (AJCC) stage III-IVA thymoma patients, 92.9%, 83.3%, and 100% (P = .833); and for 28 stage III-IVA thymic carcinoma patients, 75.0%, 76.2%, and 62.5%, (P = .160). Univariate analysis showed that for group 2 (P = .0208) and group 3 (P < .0001), thymic carcinoma pathology type (P = .0010) and stage IVB disease (P < .0001) were poor prognostic factors. Multivariate analysis found thymic carcinoma (P = .0026) and stage IVB disease (P = .0449) to be poor prognostic factors.ConclusionUp-front surgery leads to best overall survival, and induction chemotherapy followed by surgery may improve resectability and outcomes. Only thymic carcinoma and stage IVB disease were poor prognostic factors in multivariate analysis.     

Routine Clinical Data Predict Survival after Palliative Radiotherapy: An Opportunity to Improve End of Life Care

AimsEstimating the prognosis of cancer patients with incurable disease remains an important and difficult task for clinicians. Radiotherapy is a commonly used modality for palliation of symptoms, and we investigated whether we could predict differences in overall survival after the first course of palliative radiotherapy using routinely available data.Materials and methodsWe examined variations in survival in 1226 patients after their first course of palliative radiotherapy in relation to cancer type, site treated, age, gender and socioeconomic status, and developed a multivariate model based on these.ResultsThe median overall survival after the first course of palliative radiotherapy was 5.2 months. Large differences in survival were seen, depending on the primary tumour and the site treated. Survival was much better in those with breast (median overall survival 11.4 months) or prostate cancer (8.4 months, hazard ratio = 1.3) than in those with oesophageal/gastro-oesophageal junctional tumours (4.6 months, hazard ratio = 2.3) or lung (3.9 months, hazard ratio = 2.5). The treated site was an important prognostic factor (primary tumour versus bone metastases, hazard ratio = 1.3; versus brain metastases, hazard ratio = 2.1).ConclusionsThe median overall survival after a first course of palliative radiotherapy was less than 6 months. Simple data, provided as part of routine radiotherapy practice, clearly discriminate between patients with very different prognoses. Such data could therefore be used to trigger appropriate end of life care.     

Postoperative Adjuvant Systemic Therapy in Completely Resected Non–Small-Cell Lung Cancer: A Systematic Review

The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non–small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016. All phase III randomized controlled trials (RCTs) and relevant systematic reviews were included. Data on overall survival (OS), disease-free survival, adverse events, and quality of life were extracted from each of the studies. Two relevant systematic reviews, 13 RCTs, and a series of pooled analyses by Lung Adjuvant Cisplatin Evaluation-Biomarker were included in the present review. Adjuvant chemotherapy statistically significantly improved OS for resected stage II-IIIA NSCLC and is recommended. For patients with stage IB NSCLC, no significant improvement was seen in OS; however, the results from subgroup analyses indicate that it would be reasonable to consider adjuvant chemotherapy for patients with larger tumors (≥ 4 cm). The present data do not support the use of adjuvant novel therapies (ie, epidermal growth factor receptor tyrosine kinase inhibitor, bevacizumab, and immunotherapy) either as an addition to, or instead of, cytotoxic chemotherapy. No predictive biomarkers are available to select patients more likely to benefit from adjuvant chemotherapy. Cytotoxic chemotherapy remains the standard of care as adjuvant therapy for patients with resected stage II-IIIA NSCLC. Additional clinical trials are needed to evaluate targeted agents in molecularly defined subgroups before these agents can be recommended in the adjuvant setting.     

Preoperative or Postoperative Therapy for Stage II or III Rectal Cancer: An Updated Practice Guideline

AimsUncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence?Materials and methodsThe MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review.ResultsSystematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice.ConclusionsPreoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy.     

Chemotherapy for thymic carcinoma

Thymic epithelial neoplasm is a quite rare malignancy arising from the thymic epithelium, and comprises thymoma, thymic carcinoma, and thymic neuroendocrine carcinoma. The incidence of thymic carcinoma and neuroendocrine carcinoma is much less than thymoma, accounting for 1-4%of anterior mediastinal tumors. These rare tumors are called"orphan tumors,"and standards of clinical management(including chemotherapeutic regimens)have not yet been determined for them yet because of their rarity. In the advanced setting, palliative-intent chemotherapy has been applied using cisplatin-based triplet or quartet chemotherapy with second-generation antitumor drugs, with reference to chemotherapeutic regimens for invasive thymoma such as ADOC, CAP, and VIP chemotherapy. However, biological plausibility is lacking for this approach, given that these tumors differ from thymoma in their expression of cellular surface proteins such as c-Kit and epidermal growth factor receptors. While limited to thymic carcinoma, platinum doublet chemotherapy with a third-generation antitumor drug as first-line chemotherapy is anticipated to offer the same clinical efficacy as multiple-agent combination chemotherapy, but with less toxicities. In second-line or later-lines of chemotherapy, single-agent chemotherapy may be optimal. Molecular biological approaches have been under investigation, but molecular targeted agents remain unavailable.     

Multidisciplinary Tumor Board Decision Making for Postoperative Radiotherapy in Thymic Epithelial Tumors: Insights from the RYTHMIC Prospective Cohort

IntroductionThymic epithelial tumors (TETs) are rare intrathoracic malignancies for which surgery represents the mainstay of the treatment. Current practice for postoperative radiotherapy (PORT) is highly variable, and there is a lack of prospective, high level evidence. Réseau Tumeurs Thymiques et Cancer (RYTHMIC) is the nationwide network for TETs in France. Established in 2012, it prospectively collects data on all TET patients, for whom management is discussed at a national multidisciplinary tumor board (MTB). We assessed whether PORT decisions at the MTB were in accordance with RYTHMIC guidelines and ultimately implemented in patients.MethodsAll consecutive patients for whom PORT was discussed at the MTB from 2012 to 2015 were identified from the RYTHMIC prospective database, and a complete review of their medical records was performed.ResultsA total of 274 patients, including 243 with thymoma (89%) and 31 with thymic carcinoma (11%), were analyzed. The decision of the MTB was in accordance with guidelines in 221 patients (92%) of the 241 with stage I or III TET. An MTB decision to deliver PORT was made for 117 patients (43%). PORT was ultimately initiated in 101 patients. The most frequent reason for not delivering PORT was excessive (>3 months) delay after surgery. Dose-volume constraints defined by the International Thymic Malignancy Interest Group were followed in all but four patients.ConclusionOur data provide a unique insight into the decision-making process for PORT in TETs, highlighting the need for systematic discussion at an expert MTB, while stressing the value of current available guidelines.     

Chemotherapy in the treatment of thymic tumors

Thymic tumors, including thymoma and thymic carcinoma, are mainly treated with surgical resection. The majority of patients with thymic tumors present with early stage and are cured with surgical excision with or without post-operative radiation. For the patients who present with unresectable stage III or IV disease, or for the patients who experience recurrence, chemotherapy can play a significant role in ensuring long-term survival and offering palliation. Thymic tumors are chemo-sensitive with optimal responses achieved with cisplatin-based combinations. A multimodality approach including chemotherapy and post-operative radiation can improve complete resection rates and long-term outcomes in locally advanced tumors. Patients with disseminated thymic tumors can have significant disease response and symptom palliation when treated with chemotherapy. Durable responses can be obtained both in metastatic and recurrent settings. Second-line treatments are available and novel therapies are currently being explored. This review provides an update of available evidence about the treatment of thymic tumors with chemotherapy.     

Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases

BACKGROUND: Thymic carcinomas are rare neoplasms, and information regarding the results of treatment and possible prognostic factors in patients with these tumors is limited. METHODS: The records of 40 patients with histologically confirmed thymic carcinoma who were treated between 1984 and 1998 were reviewed. Twenty-seven patients were treated with surgical resection followed by radiotherapy with or without chemotherapy, and the remaining 13 patients were treated with radiotherapy with or without chemotherapy. The median follow-up time for the 13 surviving patients was 87 months (range, 44-193 months). RESULTS: The 5-year and 10-year actuarial overall survival rates in all patients were 38% and 28%, respectively. On univariate analysis, complete resection, Karnofsky performance status (KPS), histology, and Masaoka stage at the time of diagnosis were found to have a significant impact on overall survival, whereas on multivariate analysis, complete resection, KPS, and histology were found to be significant prognostic factors. With regard to the degree of resection, 12 of 16 patients (75%) treated with complete resection were alive and free of disease at the time of last follow-up whereas 1 of 24 patients (4%) treated with incomplete resection or biopsy still was alive. Among 12 surviving patients treated with complete resection, 8 with resectable tumors at the time of presentation all had low-grade histology (squamous cell carcinoma) and were treated successfully with complete resection and postoperative radiotherapy with or without adjuvant chemotherapy. The remaining four patients with unresectable tumors at the time of presentation were treated successfully with neoadjuvant chemotherapy, complete resection, and postoperative radiotherapy. CONCLUSIONS: The results of the current study indicate that multimodal treatment, especially complete resection and postoperative radiotherapy with or without chemotherapy, is a curative therapy for thymic carcinomas.