Search

Purpose: The aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC)., Methods: All patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60-74 Gy in 30-37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18 F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP)., Results: The median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 - 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 - 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 - 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24-0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16-4.28; p = 0.02), also irrespective of allocation., Conclusion: Mediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [MM reports consultant fees from Novartis, Roche, Telix, and Veraxa. The other authors have no relevant financial or non-financial interests to disclose.]., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Mediastinal germ cell tumors are rare and few large-scale studies on mediastinal germ cell tumors are reported. We aimed to investigate the clinical characteristics and survival outcomes of patients with mediastinum germ cell tumors in Japan., Methods: A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with mediastinal germ cell tumors in 2012-2013. The datasets were registered from 80 institutions., Results: The selection criteria were met by 123 patients, the majority of whom were male. The median age at diagnosis was 39 years (range 25-89 years) and the most common age groups at diagnosis was 30-39 years, followed by 40-49 years and ≥ 50 years. The histology of non-seminoma (55.3%) was slightly more frequent than that of seminoma (44.7%). The most common histological subtype in non-seminoma was yolk sac tumor, followed by mixed germ cell tumor. The 5-year survival of seminoma and non-seminoma were 96.4% and 57.3%, respectively (p < 0.001). Non-seminomatous mediastinal germ cell tumors, malignant teratomas, mixed germ cell tumors, and yolk sac tumors had comparable survival rates, while those with choriocarcinoma showed the worst prognosis., Conclusions: This is the first report showing the clinical characteristics and survival outcomes of mediastinal germ cell tumors in Japan using a real-world large cohort database., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University., Methods: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m 2 carboplatin and 750 mg/m 2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% confidence intervals were also calculated along with 2-year probabilities., Results: The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths., Conclusions: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: To report the complications and outcomes associated with thoracoscopic cranial mediastinal mass resection in dogs., Animals: 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal., Methods: This was a retrospective cohort study (January 1, 2014, to July 31, 2023), and the medical records of 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal were reviewed. The signalment, history, clinicopathologic features, perioperative complications, and long-term outcome were recorded., Results: Preoperative myasthenia gravis (MG) and megaesophagus (ME) were identified in 17 of 49 (35%) dogs and 11 of 49 (22%) dogs, respectively. The median maximal tumor diameter on CT images was 4.7 cm (range, 2.7 to 8.5 cm). Nonemergent conversion to an open procedure was necessary in 4 of 49 (8%) dogs, and dogs with conversion to an open procedure had a significantly larger median maximal CT tumor diameter than dogs without conversion (P = .03). The most common tumor type was thymoma (37/49 [76%]). The overall median survival time for dogs with thymoma was 1,102 days (95% CI, 482 to upper bound not reached). The median survival time for dogs with thymoma and concurrent presurgical MG was 182 days (95% CI, 14 to upper bound not reached). Presurgical diagnosis of MG (P = .44) or ME (P = .69) was not associated with survival time., Clinical Relevance: Thoracoscopic removal of cranial mediastinal masses was associated with low conversion and complication rates. Long-term survival is possible, and thoracoscopic removal should be considered for select cases.

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis., Competing Interests: Declaration of competing interest None of the authors has any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190). Median follow-up time for infused patients was 12.17 months (IQR 5.53,22.73). The overall (complete + partial) response rate (ORR,CR + PR) after bridging was 41% for PMBCL and 28% for other LBCL, p = 0.0102. Thirty days ORR was 78% (53/68) with 50% (34) CR in PMBCL, and 75% (141/187) with 53% (100) CR in other LBCL, p = 0.5457. Ninety days ORR was 69% (45/65) with 65% (42) CR in PMBCL, and 54% (87/162) with 47% (76) CR in other LBCL; progressive disease was 21% in PMBCL and 45% in other LBCL, p = 0.0336. Twelve months progression-free survival was 62% (95% CI: 51-75) in PMBCL versus 48% (95% CI: 41-57) in other LBCL, p = 0.0386. Twelve months overall survival was 86% (95% CI: 78-95) in PMBCL versus 71% (95% CI: 64-79) in other LBCL, p = 0.0034. All grade cytokine release syndrome was 88% (228/260); all grade neurotoxicity was 34% (88/260), with 6% of fatal events in PMBCL. Non-relapse mortality was 3%. In conclusion, PMBCLs achieved significantly better response and survival rates than other LBCLs., (© 2024. The Author(s).)

The ideal therapeutic regimen in primary mediastinal B-cell lymphoma (PMBCL) is controversial and may include consolidation radiotherapy (RT). An adequate strategy is essential in a population where long-term effects of RT are significant. We evaluated the prognostic value of end-of-treatment (EOT) FDG-PET in 50 patients receiving rituximab and anthracycline-containing chemotherapy and its implications for consolidative RT. Thirty patients (60%) obtained complete metabolic response (CMR), five received consolidation RT. The remaining patients had partial response (14) and progression (6). Of these, 12 received mediastinal RT, six salvage chemotherapy, and two no further treatment. Five-year progression free survival was 100% and 48% (95% CI 30%-77%) in patients with negative and positive EOT FDG-PET, respectively (P < .001). Five-year overall survival for negative and positive EOT FDG-PET was 100% and 67% (95% CI 48%-93%) respectively (P = .001). Within positive EOT FDG-PET cases, an association was found between Deauville score and survival. The negative predictive value (NPV) of EOT FDG-PET for disease relapse/progression was 100% (95% CI 0.88-1.00); the positive predictive value was 47% (95% CI 0.24-0.71). This study demonstrates the importance of metabolic assessment in PMBCL and is relevant for its high NPV. Our data favor the use of EOT FDG-PET for decisions concerning RT., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Despite its aggressive course, PMBCL is considered curable. While in recent years dose-adjusted (DA) EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) has become widely endorsed as first-line therapy for newly-diagnosed PMBCL, the optimal treatment for this disease and the role of radiotherapy (RT) remains unclear. DA-EPOCH-R provides good clinical outcomes, albeit is associated with short- and long-term toxicity. To address this issue, the current retrospective bi-icenter analysis compared efficacy and toxicity of DA-EPOCH-R and a less toxic R-CHOP/R-ICE regimen used for the treatment of newly-diagnosed PMBCL., Patients and Methods: The study included all patients with a histologically confirmed PMBCL diagnosis treated with DA-EPOCH-R or R-CHOP/R-ICE between 01/2013-12/2020 at two tertiary medical centers. Patient demographic and clinical data were derived from institutional electronic medical records. The analysis included 56 patients: 31 received DA-EPOCH-R and 25 - R-CHOP/R-ICE., Results: At a median follow-up of 1.9 years (IQR 3.1 years), similar progression-free survival (2.1 versus 2.4 years; p = 0.7667), overall survival (2.5 versus 2.7 years; p = 0.8047) and complete response (80%) were observed in both groups. However, DA-EPOCH-R was associated with significantly longer hospitalization required for its administration (p < 0.001) and a trend for higher frequency of infections, stomatitis, thrombotic complications and febrile neutropenia-related hospitalizations., Conclusion: DA-EPOCH-R and R-CHOP/R-ICE provide similarly encouraging outcomes in newly-diagnosed PMBCL patients. R-CHOP/R-ICE is associated with lower toxicity and significantly reduced hospitalization. Our findings suggest that this regimen may be considered as an alternative to DA-EPOCH-R in this patient population., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Data on composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma (LBCL) and classical Hodgkin lymphoma (cHL) are rare., Methods: We identified 25 cases with composite lymphoma (CL), 116 cases developing LBCL as a second primary cancer after cHL (cHL-LBCL), and 74 cases developing cHL as a second primary cancer after LBCL (LBCL-cHL) from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Comparisons of overall survival (OS) and lymphoma cause-specific survival (CSS) between patients with cHL-LBCL or cHL-LBCL and their de novo counterparts were performed., Results: The 5-year OS of patients with CL was 74.8 %. No significant difference in unadjusted OS and lymphoma CSS were observed between patients with de novo LBCL (LBCL-1 group) and patients with cHL-LBCL. However, the age- and stage-adjusted cHL-LBCL group had inferior OS and lymphoma CSS compared with that in the LBCL-1 group. The unadjusted and adjusted OS and lymphoma CSS in the LBCL-cHL group were significantly worse than patients with de novo cHL., Conclusions: CL between LBCL and cHL may have good outcomes. cHL survivors had poorer outcomes after a LBCL diagnosis versus patients with LBCL-1. Significantly poor outcomes were observed in patients with LBCL-cHL compared with patients with de novo cHL., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Primary mediastinal yolk sac tumors (PMYSTs) are a rare occurrence. As such, the clinicopathological features, treatment, and prognosis, of this disease still remain unclear. In this study, we aimed to provide further information relating to this rare malignancy in order to facilitate the creation of more specific clinical guidelines for the diagnosis and treatment of patients with PMYSTs.In this retrospective study, we recruited 15 patients who had been diagnosed with PMYST from four medical institutions to create a population-based cohort. We then used Kaplan-Meier analysis and the log-rank test to investigate and compare overall survival (OS) and progression-free survival (PFS).A total of 15 cases were identified. The mean age was 27.3 years (range: 19-34 years). The estimated 1- and 2-year PFS rates were 66.7% and 60.0%, respectively. The 1- and 2-year OS rates were both 73.3%. Computer tomography scans revealed tumors were located in the anterior middle mediastinum (5 cases), the anterior superior mediastinum (1 case), the left anterior mediastinum (3 cases), and the right anterior mediastinum (6 cases). Of the 15 patients receiving extended resections, the majority (40.0%) underwent tumor resection, partial pericardiotomy, pulmonary wedge resection, and mediastinal lymphadenectomy. R0 resections were achieved in eleven patients. Four patients underwent R2 resection and experienced postoperative complications, including pneumonia (2 cases), atelectasis (1 case), and bronchopleural fistula (1 case). Four patients developed postoperative lung metastasis. Three patients died due to progressive diseases. Disease recurred in all patients at a median of 8.0 months (range: 6.0-11.0 months).PMYST is a rare but highly malignant tumor with a poor prognosis. Tumor resection, with optimal extended surgical management, may provide patients with the best chance of a cure although postoperative complications relating to the pulmonary systems should be treated with caution., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020., Materials and Methods: We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes., Results: The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy., Conclusion: It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients.

Background: Surgery is still the mainstay of radical treatment for resectable esophageal cancer (EC). It is apparent that the presence or spread of lymph node metastasis (LNM) is a powerful prognostic factor in patients with EC who are eligible for curative treatment. Although the importance and efficacy of lymph node dissection in radical esophagectomy have been reported, the clinical or prognostic relevance of specific metastatic patterns within the mediastinal cavity and abdomen remains unclear., Methods: We retrospectively analyzed the association of postoperative survival with clinical mediastinal LNM (cMLNM) and abdominal LNM (cALNM) in 157 patients who underwent radical EC surgery at our hospital between May 2012 and March 2018., Results: A significant difference in cause-specific survival (CSS) was observed between patients with and without cALNM (log-rank p = 0.000). A multivariate Cox regression analysis revealed that cALNM and thoracic surgery (mediastinal lymphadenectomy via conventional open right thoracotomy or video-assisted thoracoscopic surgery) independently predicted CSS (p = 0.0007 and 0.021, respectively). Moreover, a significant difference in systemic recurrence-free survival was observed between those with and without cALNM (log-rank p = 0.000). Multivariate Cox regression analysis revealed that cALNM and sex independently predicted systemic recurrence-free survival (p = 0.000 and 0.015, respectively)., Conclusion: cALNM was an independent poor prognostic factor for CSS after EC surgery. It may also be an independent prognostic factor for postoperative systemic recurrence, which can shorten the CSS. For patients with cALNM-positive EC who have a high potential risk of systemic metastases, more extensive treatment besides the conventional perioperative systemic chemotherapy may be necessary.

Objective: Treatment of primary mediastinal nonseminomatous germ cell tumors involves cisplatin-based chemotherapy followed by surgery to remove residual disease. We undertook a study to determine short and long-term outcomes., Methods: A retrospective analysis of patients with primary mediastinal nonseminomatous germ cell tumors who underwent surgery at our institution from 1982 to 2017 was performed., Results: A total of 255 patients (mean age, 29.2 years) were identified. Acute respiratory distress syndrome occurred postoperatively in 27 patients (10.9%), which was responsible for all 11 (4.3%) postoperative deaths. Of patients who developed acute respiratory distress syndrome, more patients received bleomycin-containing chemotherapy (25 out of 169; 14.8%) than non-bleomycin regimens (2 out of 77; 2.6%) (P = .004). With respect to variables independently predictive of long-term survival, evidence of choriocarcinoma before chemotherapy (n = 12) was determined to be an adverse factor (P = .006). In contrast, biopsy-proven elements of seminoma (n = 34) were predictive of improved survival (P = .04). The worst pathology identified in the residual mediastinal mass after chemotherapy was necrosis in 61 patients (25.0%), teratoma in 84 patients (34.4%), and malignant (persistent germ cell or non-germ cell cancer) in 97 patients (39.8%), which influenced overall survival (P < .001). Additionally, teratoma with stromal atypia (n = 18) demonstrated decreased survival compared with teratoma without atypia (n = 66; P = .031). Patients with malignancy involving >50% of the residual mass (n = 47) had a 2.3-fold increased risk of death compared with ≤50% malignancy (n = 45; P = .008). Finally, elevated postoperative serum tumor markers (n = 40) was significantly predictive of adverse survival (P < .001)., Conclusions: In the treatment of primary mediastinal nonseminomatous germ cell tumors, avoiding bleomycin-containing chemotherapy is important. Pre- and postchemotherapy pathology and postoperative serum tumor markers are independent predictors of long-term survival., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Men with metastatic nonseminomatous germ cell tumors (NSGCTs) often present with residual chest tumors after chemotherapy. We examined the pathologic concordance of intrathoracic disease and outcomes based on the worst pathology of disease resected at first thoracic surgery., Methods: A retrospective analysis was performed of consecutive patients undergoing thoracic resection for metastatic NSGCT in our institution between 2005 and 2018., Results: Eighty-nine patients (all men) were included. The median age was 29 years (interquartile range [IQR], 23-35 years). Primary sites were testis (n = 84; 94.4%) and retroperitoneum (n = 5; 5.6%). Eighty-seven patients received chemotherapy before undergoing surgery. Nineteen patients (21.3%; group 1) had malignancy resected at first surgery (OR1), and the other 70 patients had benign disease at OR1 (78.7%; group 2). Concordant pathology between lungs was 85.2% in group 1 and 91% in group 2, and between lung and mediastinum was 50% in group 1 and 72.7% in group 2. Despite no teratoma at OR1, 3 patients (15.8%) in group 2 had resection of teratoma (n = 2) or malignancy (n = 1) at future surgery. After a mean follow-up of 65.5 months (IQR, 23.1-89.2 months) for group 1 and 47.7 months (IQR, 13.0-75.1 months) for group 2, overall survival was significantly worse for group 1 (68.4% vs 92.9%; P = .03)., Conclusions: The wide range of pathology resected in patients with intrathoracic NSGCT metastases requires careful decision making regarding treatment. Pathologic concordance between lungs is better than that between lung and mediastinum in patients with intrathoracic NSGCT metastases. Aggressive surgical management should be considered for all residual disease due to the low concordance between sites and the potential for excellent long-term survival even in patients with chemotherapy-refractory disease., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center., Methods and Materials: Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS)., Results: Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5)., Conclusions: In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Malignant mediastinal germ cell tumor (MGCT) is rare and has poor outcomes even after multimodality treatment. Data from resource-poor countries are scarce in the literature., Aims: To evaluate the clinicopathologic features and treatment outcome of primary malignant MGCT at our center., Methods and Results: Single institutional data review of patients aged ≥18 years, treated with a diagnosis of malignant MGCT between Nov'2013 and Nov'2019. Risk stratification was done as per International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Patients were treated with platinum based chemotherapy and surgical resection for the residual disease was performed in non-seminomatous histology.28 patients had MGCT with a median age of 25 years (range:18-36) and all were male. Seven patients had superior vena cava obstruction (SVCO) at diagnosis and pre-treatment histological diagnosis was available in 23 (82%) patients. Seven (25%) patients had seminoma histology, all were of good risk as per IGCCCG risk criteria, whereas others had non-seminoma histology with poor-risk group. Seven patients with seminoma histology achieved a complete response after initial treatment. Six patients with non-seminoma histology underwent complete resection of residual disease post-chemotherapy and five revealed residual viable tumors. After a median follow-up of 10.8 months (range:2.9-75), 3-year progression-free survival (PFS) and overall survival (OS) estimate was 61.2% and 94.7% in the whole cohort, respectively and 3-year PFS and OS estimate was 100% in patients with seminoma histology., Conclusions: This is the largest data set of MGCT patients' outcomes reported from India with multi-modality treatment. All patients were male and one-fourth had SVCO at presentation. Seminoma histology patients had a 100% outcome after initial platinum based chemotherapy. But, those with non-seminoma histology had a poor outcome even with chemotherapy and surgery., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment., (© 2020 by The American Society of Hematology.)

Purpose: To investigate local control and survival after bronchial artery embolization (BAE) using N-butyl-2-cyanoacrylate (NBCA) for pulmonary hilar or mediastinal tumors that are refractory to chemotherapy or chemoradiotherapy., Method: This is a single center retrospective study involving 42 patients treated between 2015 and 2018 for pulmonary hilar or mediastinal tumors (primary tumors in 5 and metastatic ones in 37). Tumor histology was sarcoma in 22 and carcinoma in 20 patients. All patients had shown tumor progression regardless of previous chemotherapy (n = 37) or chemoradiotherapy (n = 5). Thirty-seven patients (88 %) had respiratory symptoms, such as cough, dyspnea, and hemoptysis. BAE was performed using NBCA to shrink tumors for extending life expectancy. Target tumors were followed with computed tomography at 1,3, and 6 months after BAE. Endpoints included the best tumor response within 6 months as well as overall survivals in patients with and without tumor responses., Results: Best local responses within 6 months were complete response (CR) in 1 patient, partial response (PR) in 16, stable disease (SD) in 24, and progressive disease (PD) in 1; the CR/PR rate was 40 % (17/42). Median follow-up period was 13 months (range:1-43). Overall survival in patients with CR/PR was significantly better than in those with SD/PD (p = 0.006); with 3-year survival rates of 45 % (8/17) and 0% (0/25), respectively., Conclusions: BAE using NBCA has potential promise for shrinking hilar and/or mediastinal tumors that are refractory to chemotherapy or chemoradiotherapy, and may also improve overall survival in patients who respond., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Unexpected N2 involvement occurs in approximately 10% to 20% of patients with non-small-cell lung cancer (NSCLC) and patients' prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients., Methods: From January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis., Results: Regarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P = .009), proposed N2 classification subgroups (P = .014), age <66 (P < .001), and pT (P = .005); for DFS: NR <17% (P = .003), adjuvant treatment (P = .026), and pT (P = .026); and for CSS: NR <17% (P = .008), grading (P = .001), and adjuvant treatment (P < .001)., Conclusion: Our study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis., Patients and Methods: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. Patients received chemo-immunotherapy every 3 weeks until the second confirmed complete response (CR) or up to 12 cycles, followed by camrelizumab monotherapy for up to 1 year. The primary endpoints were objective response rate (ORR) and safety., Results: Twenty-seven response evaluable patients were enrolled, who received a median of three first-line therapies, 59% with bulky disease. The ORR was 74%, including 56% with a CR. A median time of 1.7 months to response was observed, with 78% exhibiting tumor shrinkage at the first evaluation. After 24.8 months median follow-up, the median duration of response was not reached, with a 65% 2-year estimated response rate. Thirteen responders remained in sustained complete remission. Estimated 24-month progression-free survival and overall survival rates were 48.2% and 81.5%, respectively. Any grade and grade 3 treatment-related adverse events (AE) occurred in 93% and 33% of patients, respectively; with no grade 4 or 5 AEs. Baseline levels of IL10, IFNγ, and soluble Fas were associated with objective response., Conclusions: Camrelizumab plus GVD chemotherapy offers a potent option as life-saving chemo-immunotherapy with promising efficacy and a manageable safety profile for patients with rrPMBCL, especially with bulky aggressive disease., (©2020 American Association for Cancer Research.)

Diffuse large B-cell lymphoma (DLBCL) encompasses a group of aggressive B-cell non-Hodgkin lymphomas with striking genetic heterogeneity and variable clinical presentations. Among these is primary mediastinal B-cell lymphoma (PMBL), which has unique clinical and molecular features resembling Hodgkin lymphoma. Treatment of DLBCL is usually curative, but identifiable subsets at highest risk for treatment failure may benefit from intensified chemotherapy regimens and/or targeted agents added to frontline therapy. Recent comprehensive genomic analyses have identified distinct genetic subtypes of DLBCL with characteristic genetic drivers and signaling pathways that are targetable. Immune therapy with chimeric antigen receptor T cells and checkpoint inhibitors has revolutionized the treatment of relapsed or refractory disease, and antibody drug conjugates have weaponized otherwise intolerable cytotoxic agents. Ongoing clinical trials are further refining the specificity of these approaches in different genetic subtypes and moving them from the setting of recurrent disease to frontline treatment in high-risk patient populations.

Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Background : Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma. Approximately 10-30% of patients experience refractory or relapsed PMBCL (rrPMBCL) after first-line therapy. Data and treatment guidelines for rrPMBCL are scarce, and management is based on clinical experience. Methods : Two structured literature reviews were undertaken to determine the incidence, prevalence, and mortality rates associated with rrPMBCL, and to identify clinical practice guidelines and real-world patterns of care. Results : Epidemiology studies included reported lymphomas ( n = 1), non-Hodgkin lymphoma ( n = 1), lymphoid neoplasm ( n = 1), PMBCL ( n = 6), and rrPMBCL ( n = 1). Of 12 published treatment guidelines, only four provided recommendations for rrPMBCL. Sixteen studies provided data on real-world treatment patterns, but most were single-center studies with small patient numbers. Chemotherapy/immunochemotherapy, followed by high-dose treatment (HDT) and stem cell transplantation, was a mainstay of salvage therapy in most studies; real-world care generally followed treatment guidelines. Conclusions : Salvage chemotherapy (often with rituximab and radiotherapy), followed by HDT and stem cell transplantation, appears to be the standard real-world treatment for rrPMBCL. However, large prospective and retrospective studies are warranted to improve our knowledge of real-world treatment patterns.

Background: The standard first-line treatment for primary mediastinal B-cell lymphoma (PMBCL) patients is rituximab-based immunochemotherapy; however, this is not due to the result of randomized clinical trials., Aims: We retrospectively investigated 53 PMBCL patient outcomes treated either with R-CHOP-21 or DA-EPOCH-R-28. The primary endpoint was overall survival (OS). Secondary endpoints were complete remission (CR), overall response rate (ORR), progression-free survival (PFS), and treatment-related complications., Results: Treatment with R-CHOP-21 resulted in a 92.0% ORR (60% CR), while DA-EPOCH-R yielded a 92.6% ORR (70.4% CR). There were no differences in the occurrence of grade 3-4 hematological adverse events, but grade 1-2 cardiologic complications (P = .003) were observed more frequently in the DA-EPOCH-R arm. Median PFS and OS were not achieved. The differences in estimated 12-month PFS in R-CHOP and DA-EPOCH-R group (87% vs 73.9%) and OS (100% vs 92%) were insignificant. Patients treated with R-CHOP-21 and autologous hematopoietic stem cell transplantation (auto-HSCT) had an improved OS (P = .03) but not PFS (P = .43) compared to those treated solely with R-CHOP-21. No differences in PFS or OS were observed between patients treated with R-CHOP-21/auto-HSCT and DA-EPOCH-R., Conclusion: The results of this study suggest that R-CHOP-21 may be an alternative to DA-EPOCH-R treatment for PMBCL patients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade., Methods: In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity., Results: The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival., Conclusion: Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.

Standard therapy for relapsed or refractory (rel/ref) primary mediastinal large B cell lymphoma (PMBCL) is salvage therapy followed by autologous (auto) hematopoietic stem cell transplantation (HSCT). However, many patients have refractory disease and are unable to undergo autoHSCT, and a sizeable proportion of patients will relapse after autoHSCT. By analogy to diffuse large B cell lymphoma, these patients may be treated with allogeneic (allo) HSCT with curative intent, but at the risk of significant morbidity and mortality. Given the advent of effective immunotherapy approaches for rel/ref PMBCL, it is important to better understand the toxicity and efficacy of alloHSCT in these patients, to which these new approaches could be an alternative. Therefore, we retrospectively studied the outcomes of alloHSCT in a multicenter cohort of 28 patients with rel/ref PMBCL who underwent transplantation at 4 centers. Most patients (79%) were sensitive to pretransplantation therapy and 86% received reduced-intensity conditioning. The overall progression-free survival (PFS), overall survival (OS), and cumulative incidences of nonrelapse mortality and relapse in the cohort at 5 years were 34%, 45%, 32%, and 33%, respectively. Outcomes were significantly better in patients with pretransplantation responsive disease (2-year PFS and OS of 50% and 58%, respectively) compared with refractory patients (2-year PFS and OS of 0%). In our multicenter retrospective study, alloHSCT produced durable remissions in a proportion of patients with treatment-sensitive disease before transplantation (5-year PFS of 44%) and should be considered in the treatment of patients with rel/ref PMBCL., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate safety and efficacy of image guided-hypofractionated radiation therapy (IG-HRT) in patients with thoracic nodes oligometastases., Methods: The present study is a multicenter analysis. Oligometastatic patients, affected by a maximum of five active lesions in three or less different organs, treated with IG-HRT to thoracic nodes metastases between 2012 and 2017 were included in the analysis. Primary end point was local control (LC), secondary end points were overall survival (OS), progression-free survival, acute and late toxicity. Univariate and multivariate analysis were performed to identify possible prognostic factors for the survival end points., Results: 76 patients were included in the analysis. Different RT dose and fractionation schedules were prescribed according to site, number, size of the lymph node(s) and to respect dose constraints for relevant organs at risk. Median biologically effective dose delivered was 75 Gy (interquartile range: 59-86 Gy). Treatment was optimal; one G1 acute toxicity and seven G1 late toxicities of any grade were recorded. Median follow-up time was 23.16 months. 16 patients (21.05%) had a local progression, while 52 patients progressed in distant sites (68.42 %).Median local relapse free survival was not reached, LC at 6, 12 and 24 months was 96.05% [confidence interval (CI) 88.26 - 98.71%], 86.68% (CI 75.86 - 92.87) and 68.21% (CI 51.89 - 80.00%), respectively. Median OS was 28.3 months (interquartile range 16.1 - 47.2). Median progression-freesurvival was 9.2 months (interquartile range 4.1 - 17.93).At multivariate analysis, RT dose, colorectal histology, systemic therapies were correlated with LC. Performance status and the presence of metastatic sites other than the thoracic nodes were correlated with OS. Local response was a predictor of OS., Conclusion: IG-HRT for thoracic nodes was safe and feasible. Higher RT doses were correlated to better LC and should be taken in consideration at least in patients with isolated nodal metastases and colorectal histology., Advances in Knowledge: Radiotherapy is safe and effective treatment for thoracic nodes metastases, higher radiotherapy doses are correlated to better LC. Oligometastatic patients can receive IG-HRT also for thoracic nodes metastases.

Purpose: In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT., Methods: Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed., Results: Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status ( P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status ( P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01)., Conclusion: The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.

Objective: The aim of this study was to compare survival outcomes between non-small cell lung cancer (NSCLC) patients with or without 4L node dissection (4LND) and to evaluate the potential patient population who will particularly benefit from 4LND., Methods: Between January 2009 and December 2015, a total of 2063 patients with primary left-sided NSCLC in the Western China Lung Cancer Database were initially reviewed. After exclusion, 1064 patients were enrolled in this study. A total of 460 patients with 4LND (4LND + group) were matched with 460 patients without 4LND (4LND - group) using propensity-matched analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed., Results: The metastasis rate of station 4L was 14.6%. Patients with 4LND showed higher DFS (5-year DFS 52.6% vs. 46.7%; hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.03-1.50; p = 0.022) and OS (5-year OS 65.8% vs. 56.3%; HR 1.36, 95% CI 1.10-1.69; p = 0.006) than patients without 4LND. In the multivariate analysis, patients without 4LND (HR 1.33, 95% CI 1.07-1.66; p = 0.011), tumor size > 3 cm, lymph node metastasis, and pathologic stage higher than stage I were independent prognostic factors for poor OS. Subgroup analysis according to pathologic TNM stage and N stage showed that stage II, IIIA, and N2 disease indicated better survival outcomes in the 4LND + group (p = 0.050, p = 0.016, and p = 0.008, respectively)., Conclusions: Performing 4LND may bring survival benefits to patients with left-sided NSCLC. We suggest 4LND as a standard procedure for left-sided NSCLC patients with stage II or advanced stage disease.

Objectives: The goals of retrocrural metastasectomy are complete resection with preservation of the diaphragmatic function while avoiding phrenic nerve injury and spinal cord ischemia. We describe 2 approaches for metastasectomy depending on the pattern of metastases., Methods: Between 1999 and 2017, 44 patients underwent 50 retrocrural metastasectomies. In case of lower retrocrural, bilateral retrocrural, and or additional retroperitoneal and abdominal metastases, an abdominal approach with mobilization of the liver and the kidney followed by longitudinal incision of the diaphragmatic crus was performed. In case of upper retrocrural metastases and additional thoracic disease, a thoracic approach was performed. The Kaplan-Meier method and log-rank test were used to analyze survival and prognosticators., Results: The minor morbidity, major morbidity, and mortality were 16.6%, 0%, and 0% for the abdominal approach, respectively, and 15.4%, 3.8%, and 0% for the thoracic approach. There was no phrenic nerve palsy, diaphragmatic hernia, or spinal cord ischemia. Additional retroperitoneal, mediastinal, pulmonary, or further resection was necessary in 10, 25, 9, and 6 cases, respectively. In all cases, a R0 resection was achieved. The 15-year survival rate was 95%., Conclusions: Depending on the pattern of metastases, a complete retrocrural metastasectomy with low morbidity and without mortality by thoracic or abdominal approach is possible. Both approaches preserve diaphragmatic function. Furthermore, the lateral abdominal approach provides a good view and might lead to less tension at the spinal arteries and therefore might reduce the risk of paresis. Good long-term survival is achievable. These patients should be operated on in specialized centers., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Prior to the introduction of rituximab, primary mediastinal B-cell lymphoma (PMBCL) had high rates of treatment failure with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), prompting the use of consolidative mediastinal radiation or more intensive chemotherapy regimens. Cure rates improved dramatically with rituximab, but mediastinal radiation was still commonly employed with R-CHOP. We performed a retrospective review of patients treated with R-CHOP alone without radiation for PMBCL. Of 43 patients with PMBCL, 16 received R-CHOP alone. High-risk factors included 56% with bulky disease, 75% with elevated LDH, 25% with SVC syndrome, and 13% with stage IV disease. Three-year progression-free survival (PFS) and overall survival (OS) were 93% and 100% respectively. These results suggest that R-CHOP alone has a high cure rate in PMBCL while avoiding the side effects of mediastinal radiation.

Background: Low-risk neuroblastomas have favorable biologic characteristics. Children Oncology Group (COG) proposed that surgical resection of the primary tumor was sufficient. We evaluated the long-term prognosis of surgery alone for patients with low-risk neuroblastoma in China., Methods: A total of 34 patients with low-risk neuroblastoma were treated in our center between Jan 2009 and Dec 2013. The medical records of these patients were reviewed., Results: The primary lesion was located in the adrenal gland in 19 patients, the retroperitoneum in 5, the posterior mediastinum in 9 and the neck in 1. The tumor diameters and volumes were 1.80-10.0 cm (average 5.5 ± 2.3 cm) and 1.28-424.10 cm 3 (average 58.81 ± 92.00 cm 3 ), respectively. The stages of the patients were as follows: stage I in 25, stage II in 7, and stage IVs in 2. All patients were in the low-risk group according to COG risk stratification criteria. No patients showed MYCN amplification. The primary tumors of all patients were completely resected. Nine adrenal tumors were completely resected by laparoscopy. All patients were successfully followed for 66-115 (average 89.71 ± 16.17) months. Recurrence was observed in 4 patients. In addition to one local recurrence, another three recurrences were metastases. The lesions were effectively controlled in all patients with recurrences. All patients survived, including 28 cases of tumor-free survival; the 4-year overall and event-free survival rates were both 100%., Conclusions: Surgery alone is a safe and effective treatment strategy for low-risk neuroblastoma. Recurrent lesions may be controlled and treated by rescue chemotherapy and surgery.

Purpose: Intrathoracic sarcomas (ITS) are considered rare tumors and have a dismal prognosis. We investigated outcomes and risk factors for local control (LC), disease-free survival (DFS), and overall survival (OS) in patients with resected nonmetastatic ITS treated with or without adjuvant radiation therapy (RT) and/or chemotherapy., Methods and Materials: Patients from the Rare Cancer Network database were studied. A Kaplan-Meier estimate was used to assess survival curves, and Cox proportional hazards regression was used to assess risk factors for LC, DFS, and OS., Results: Between 2000 and 2017, 121 patients met inclusion criteria. The primary site was lung in 30%, mediastinum in 34%, and pleura in 36%. Thirty-nine percent and 32% received RT and chemotherapy. Median follow-up was 34 months (range, 2-141). LC, DFS, and OS at 10 years were 52%, 18.7%, and 7.2%, respectively. In multivariate analysis, RT (P = .003) and R1 margin status (P = .041) retained a significant association with LC. Only R1 resection (P = .002) remained associated with an increased risk of death in multivariate analysis. Overall, 7 patients (6%) developed grade 3 treatment-related chronic toxicity events., Conclusions: This joint analysis revealed that OS remains modest in this group of patients, mainly given by the high risk of local and distant failure. Our results suggest that resected ITS can benefit from adjuvant RT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Accurate staging of the mediastinal lymph nodes is of great importance to determine optimal treatment options in non-small cell lung cancer (NSCLC). In case of suspected mediastinal metastases, endoscopic/endobronchial ultrasound combined with mediastinoscopy is the gold standard. The diagnostic value of these procedures stands or falls by how they are technically performed. This study used data from the Dutch Lung Cancer Audit for Surgery to evaluate surgical performance of mediastinoscopies in The Netherlands., Methods: The study included all patients with a mediastinoscopy for staging of NSCLC and subsequent resection from 2012 to 2016. Complete case analysis was performed, excluding patients with missing data on biopsies or tumor side. Location and number of biopsied stations and adherence to guidelines for performing mediastinoscopy were analyzed. The proportion of unforeseen mediastinal lymph node metastases (unforeseen N2) was compared between mediastinoscopies that did or did not comply with the Dutch guideline., Results: The analysis included 1,729 patients. Mediastinoscopies were performed according to the Dutch guideline (requirements: biopsies of 2 ipsilateral stations, 1 contralateral station, and N7) in 51.4% (n = 888) and according to the European Society of Thoracic Surgeons guideline (N4 left, N4 right, and N7) in 75.4% (n = 1,303). Overall, unforeseen N2 was present in 10.2% (n = 140). In mediastinoscopies performed according to the Dutch guideline, unforeseen N2 occurred less often (8.6%) than in the nonadherence group (11.9%; p = 0.043)., Conclusions: There is improvement potential in surgical performance of mediastinoscopy in The Netherlands, which is reflected by the percentage of guideline adherence and the occurrence of unforeseen N2., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Liposarcoma has been subclassified histologically into well-differentiated, myxoid, pleomorphic, and dedifferentiated types. The dedifferentiated type generally shows poorer prognosis than the well-differentiated type. Because of its rarity, the clinicopathological features and clinical outcomes of primary mediastinal dedifferentiated liposarcoma remain unclear., Methods: Five patients with primary mediastinal dedifferentiated liposarcoma were treated at Shinshu University Hospital between January 2012 and August 2017. We investigated the clinical characteristics, including age, gender, radiographic findings, pathological status, and clinical and treatment outcomes., Results: Four of the five patients initially underwent radical surgical resection. One patient was disease-free after surgery, but the remaining three patients developed local recurrence in the mediastinum after surgical resection. Two of these patients underwent repeat surgical resection, resulting in long survival (60 and 40 months, respectively), while the other underwent proton beam therapy and showed no evidence of recurrence as of 17 months after treatment. The remaining patient was treated with chemotherapy using doxorubicin because of advanced inoperable disease, but failed to show a response and died within a month of the initiation of chemotherapy. Although the maximum standardized uptake values on fluorodeoxyglucose-computed tomography were relatively low, there was a slight positive relation between these values and the Ki-67-positive ratio in the tumor., Conclusion: Aggressive treatment by surgical resection should be considered for mediastinal dedifferentiated liposarcoma, even in cases with local recurrence., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Mediastinal teratomas are enigmatic; those in children and women are almost invariably benign but in men they may be benign or malignant. There are few data on the chromosome 12p status of mediastinal germ cell tumors (GCT), whereas increased 12p copy number is virtually uniform in malignant testicular GCTs. We therefore studied chromosome 12p copy number in 34 diverse mediastinal GCTs and correlated the results with morphology and follow-up to gain insight into possible pathogenesis. Four prepubertal (below 12 y) children (3 females and 1 male), 7 postpubertal females (14 to 52 y) and 6 postpubertal males (12 to 40 y old) had pure, previously untreated teratomas; 15 were mature and 2 had low-grade immaturity. All lacked 12p copy number increase and cytologic atypia, and most (14/17) showed organoid morphology. On follow-up of 16, 1 died of postoperative complications and the remaining 15 were disease free (1 to 119 mo, mean: 39 mo). Eight postpubertal males (19 to 44 y old) had pure teratomas in postchemotherapy resections; 5/8 showed 12p copy number increase. All 8 had distinct cytologic atypia, with organoid morphology in 3. On follow-up, 6 were disease free after surgical resection (1.5 to 94 mo, mean 38 mo); 1 died of disease at 14.5 months, and 1 was alive with metastases at 176 months. Two postpubertal patients, 1 male (29 y) and 1 female (31 y), had teratoma with secondary somatic-type malignancies, with positive 12p copy number increase in the former but not the latter. The man's tumor occurred after chemotherapy and was a nonorganoid teratoma with primitive neuroectodermal tumor and malignant glioma; the woman's was a previously untreated organoid teratoma with an undifferentiated carcinoma component. The man died of disease (16 mo) and the woman was alive with metastases (27 mo). Seven patients had resections for mixed GCTs (4) or pure nonteratomatous tumors, all after chemotherapy; 5/7 had positive 12p copy number increase. The teratoma component of the 2 cases having one showed distinct cytologic atypia and lacked organoid morphology. On follow-up, 1 died of disease (5 mo), 2 were alive with disease (1, 1.5 mo), 3 were disease free (1 to 43 mo; mean: 18 mo), and 1 was alive with unknown status (31 mo). Our results support that mediastinal teratomas likely develop from 2 separate pathways. Those in children, women and some men arise as pure neoplasms from a nontransformed precursor cell and, therefore, lack 12p copy number increase, show no cytologic atypia, often have organoid morphology and are benign. Common 12p copy number increase, uniform atypia, infrequent organoid structures and malignant behavior support that pure teratomas after chemotherapy in postpubertal males derive from a malignantly transformed precursor cell. Interestingly, we identified organoid pancreatic differentiation only in the benign group and neuroglia more commonly in the malignant teratomas.

Primary mediastinal (thymic) large B cell lymphoma is a subtype of diffuse large B cell lymphoma with distinct clinical, molecular, and genetic features, many of which overlap with Hodgkin lymphoma. Increasingly, initial therapy for these patients has used dose-dense chemotherapy with or without radiation with excellent results. In patients with relapsed and primary refractory disease, outcomes of second-line therapy followed by consolidation with high-dose therapy and autologous stem cell transplantation remains largely undefined. We reviewed the outcomes of 60 transplant-eligible patients with relapsed or refractory primary mediastinal (thymic) large B cell lymphoma enrolled on sequential protocols with uniform second-line therapy with intent to consolidate with autologous stem cell transplant. The estimated 3-year overall and event-free survivals for all patients were 61% and 57%, respectively, and 68% and 65%, respectively, for patients proceeding to stem cell transplant. Multivariable analysis of risk factors before transplant revealed that an incomplete response to initial therapy, advanced Ann Arbor stage at disease progression, and failure to achieve a partial remission or better to second-line therapy to be independently associated with inferior event-free and overall survival. A risk score based on these variables was able to identify patients who are unlikely to respond to conventional second-line strategies. These results suggest that salvage chemoradiotherapy with intent of subsequent high-dose therapy and autologous stem cell transplant is successful in most patients with relapsed and refractory primary mediastinal (thymic) large B cell lymphoma. Alternative strategies are warranted for a significant subset of patients with high-risk disease who are unlikely to be cured with this strategy., (Copyright © 2018. Published by Elsevier Inc.)

The World Health Organization now recognizes primary mediastinal B-cell lymphoma (PMBCL) as a unique clinical and biologic entity. PMBCL is distinct from other B-cell non-Hodgkin lymphoma subtypes and has features that overlap with classical Hodgkin lymphoma, including a peak incidence in the adolescent and young adult population, mediastinal presentation of disease, and molecular alterations in JAK2 and programmed death ligands. Because PMBCL is rare, there are few prospective clinical trials to guide therapy, resulting in no single standard of care. Given the long life expectancy of survivors of PMBCL, treatment approaches must balance maximizing cure while minimizing long-term toxicity. In this article, I review my approach to the treatment of PMBCL, incorporating data from adult and pediatric studies, as well as recent advances in our understanding of the molecular basis of PMBCL., (© 2018 by The American Society of Hematology.)

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUV max in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUV max was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R ( clinicaltrials.gov identifier 00001337 )., (Copyright© 2018 Ferrata Storti Foundation.)

Mediastinal germ cell tumor (MGCT), which accounts for 1% to 3% of extragonadal germ cell tumors, has unique manifestations; it is associated with several types of hematologic malignancy, particularly myeloid neoplasm. The aim of this study was to report the 10-year incidence, clinical characteristics, and outcomes of MGCT at Thailand's national pediatric tertiary referral center. This retrospective study included patients diagnosed with MGCT at the Department of Pediatrics, Siriraj Hospital during 2005 to 2014. Eight patients (all male) were diagnosed with MGCT. Five of 8 patients were found to have hematologic abnormalities. Three patients were diagnosed with acute myeloid leukemia (AML) (one patient with M1, another having M7, and the other with M0). Another patient had mixed MGCT with mediastinal myeloid sarcoma (MMS). The other patient had malignancy-associated hemophagocytic lymphohistiocytosis syndrome (M-HLH). Isochromosome 12p was detected in 3 patients (AML [2], mixed MGCT/MMS [1]). Four of 5 patients with hematologic abnormalities died of hematologic abnormalities or treatment complication (AML [3], M-HLH [1]). One patient with mixed MGCT/MMS survived with chemotherapy. All patients with AML and MMS were nonseminomatous MGCT and the onset of myeloid malignancies were within 1 year after the diagnosis of MGCT. Associated hematologic malignancies should be suspected in MGCT with abnormal blood count or hematologic symptoms. Isochromosome 12p was the most common cytogenetic finding in MGCT-associated myeloid malignancies patients. Those with nonseminomatous MGCT should have their blood count carefully monitored especially during the first year after the diagnosis of MGCT. Better treatment alternatives for MGCT with associated hematologic malignancies are warranted to ameliorate adverse outcomes.

Background: Primary mediastinal sarcomas are rare and deadly. Our objective was to describe the clinicopathological features, treatment strategies, and overall survival outcomes for a contemporary cohort of patients diagnosed with primary mediastinal sarcoma in the United States., Methods: We queried the National Cancer Database for cases of mediastinal sarcoma diagnosed from 2004 to 2012. Five-year overall survival (OS) was examined using the Kaplan-Meier method. Differences in OS were assessed using log-rank analysis and Cox proportional hazards regression., Results: The mean age of diagnosis was 53 years (range, 0 to 90) with a male predominance (59.2%). The most common histological subtype was hemangiosarcoma (27.1%). Fewer than half of patients underwent surgery (48.9%), and 19.7% of patients had no treatment. For all patients, OS was 14.8%. The best unadjusted OS was seen in patients treated with surgery and radiation (40.1%); untreated patients had the worst unadjusted OS (4.2%). Of those who underwent surgery (n = 477, 48.9%), OS was significantly better for those who achieved an R0 resection (30.1% versus 18.9%; p = 0.002). In multivariable analysis, surgery combined with radiation therapy was again associated with the best survival (HR, 0.24; 95% CI, 0.16 to 0.36). Other factors associated with improved OS included younger age, fewer comorbidities, and leiomyosarcoma histology. Worse OS was associated with poorly differentiated or undifferentiated grade, metastases, treatment in the New England region, and having Medicaid or no insurance. Sex and tumor size had no effect on OS., Conclusions: The 5-year OS for primary mediastinal sarcoma is poor. Surgical resection can be successful and should be considered whenever possible., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The nationwide Dutch Lung Surgery Audit (DLSA) started in 2012 to monitor and evaluate the quality of lung operations in The Netherlands as an improvement tool. This outline describes the establishment, structure, and organization of the audit by the Dutch Society of Lung Surgeons (NVvL) and the Dutch Society of Cardiothoracic Surgeons (NVT), in collaboration with the Dutch Institute for Clinical Auditing. In addition, the first 4-year results are presented., Methods: The NVvL and NVT initiated a web-based registration, including weekly updated online feedback for participating hospitals. Data verification by external data managers is performed on regular basis. The audit is incorporated in national quality improvement programs, and participation in the DLSA is mandatory by health insurance organizations and the National Healthcare Inspectorate., Results: Between January 1, 2012, and December 31, 2015, all hospitals performing lung operations participated, and a total of 19,557 patients were registered from which almost half comprised lung cancer patients. Nationwide the guideline adherence increased over the years, and 96.5% of lung cancer patients were discussed in preoperative multidisciplinary teams. Overall postoperative complications and mortality after non-small cell lung cancer operations were 15.5% and 2.0%, respectively., Conclusions: The audit provides reliable benchmarked information for caregivers and hospital management with potential to start local, regional, or national improvement initiatives. Currently, the audit is further completed with data from nonsurgical lung cancer patients, including treatment data from pulmonary oncologists and radiation oncologists. This will ultimately provide a comprehensive overview of lung cancer treatment in The Netherlands., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

An important unmet need in the management of primary mediastinal B-cell lymphoma (PMBCL) is to identify the patients for whom first-line therapy will fail to intervene before the lymphoma becomes refractory. High heterogeneity of intratumoral 18 F-fluorodeoxyglucose (18FDG) uptake distribution on positron emission tomography/computed tomography (PET/CT) scans has been suggested as a possible marker of chemoresistance in solid tumors. In the present study, we investigated the prognostic value of metabolic heterogeneity (MH) in 103 patients with PMBCL prospectively enrolled in the International Extranodal Lymphoma Study Group (IELSG) 26 study, aimed at clarifying the role of PET in this lymphoma subtype. MH was estimated using the area under curve of cumulative standardized uptake value-volume histogram (AUC-CSH) method. Progression-free survival at 5 years was 94% vs 73% in low- and high-MH groups, respectively ( P = .0001). In a Cox model of progression-free survival including dichotomized MH, metabolic tumor volume, total lesion glycolysis (TLG), international prognostic index, and tumor bulk (mediastinal mass > 10 cm), as well as age as a continuous variable, only TLG ( P < .001) and MH ( P < .001) retained statistical significance. Using these 2 features to construct a simple prognostic model resulted in early and accurate (positive predictive value, 89%; negative predictive value, ≥90%) identification of patients at high risk for progression at a point that would allow the use of risk-adapted treatments. This may provide an important opportunity for the design of future trials aimed at helping the minority of patients who harbor chemorefractory PMBCL. The study is registered at ClinicalTrials.gov as NCT00944567., (© 2018 by The American Society of Hematology.)

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance ( P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis ( P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression., (© 2018 by The American Society of Hematology.)

Synovial sarcoma (SS), a translocation-associated sarcoma characterized by SS18-SSX1/2 fusion, presents most often in the extremities of young adults. While SS regularly occurs in the pleuropulmonary parenchyma, the mediastinum is an exceedingly rare primary site; the literature on this subject is predominantly composed of case reports and small series, mostly without molecular confirmation. Cases of mediastinal SS were selected from our institutional and consultation archives. Diagnoses were confirmed by either SS18 fluorescence in situ hybridization (n=6) or reverse transcription polymerase chain reaction for SS18-SSX1/2 (n=15). Mediastinal SSs occurred in 21 patients (15 men; mean age, 38 y; range, 21 to 75). Only 1 patient was older than 50 years. Average tumor size was 13.5 cm (range: 6.4 to 23 cm). One tumor was biphasic and the rest were monophasic, 11 of which were poorly differentiated (52%). Of 10 cases with known fusion transcripts, 6 had SS18-SSX2 and 4 had SS18-SSX1. Follow-up was known for 16 patients (mean: 18.9 mo; range: 5 to 45): 14 had local disease progression or recurrence, and 6 had metastasis. Death from disease occurred in 11 of 16 patients (69%) at 5 to 32 months, and 5 (36%) were alive with disease at last follow-up (6 to 45 mo). Mediastinal SS is a rare and aggressive malignancy most common in patients younger than 50 years. Most are monophasic and reach large size before detection. Poorly differentiated morphology is common. SS should be included in the differential diagnosis of spindle cell, biphasic and poorly differentiated mediastinal tumors. Because of the rarity of SS at this site, molecular testing is recommended to confirm the diagnosis.

Objectives: We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network., Methods: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH)., Results: Twenty-one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed staining to PD-L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10 PMBL (50%), and 3 GZL (23%) cases were not stained by PD-L1 antibodies. Patients over 40 years old manifest more frequent expression of PD-L1 in cHL. Proportion of tumors stained by PD-L2 antibody was increased in PMBL. FISH analyses with a PD-L1/PD-L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL, 1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case., Conclusion: We identified increased staining of PD-L1 in cHL and that of PD-L2 in PMBL. GZL had a pattern similar to that of cHL., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)