Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors

BACKGROUND: The aim of this study was to determine the effects of independent prognostic variables, such as prechemotherapy tumor markers, the extent of disease at diagnosis, the tumor markers postchemotherapy (PC), and the pathology of the PC residual mass on the overall survival of patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT). METHODS: The authors undertook a retrospective review of 39 patients with PMNSGCT between 1983 and 1997 who received their initial chemotherapy at Indiana University and 36 additional patients referred for PC resection. All patients received chemotherapy based on the combination of cisplatin and etoposide. The median follow-up was 22 months (range, 12-144 months). RESULTS: The prechemotherapy tumor markers did not affect overall survival. Extent of disease (mediastinal only vs. visceral metastases) was an important prognostic factor for survival in univariate analysis (P = 0.042). Sixty-two of 75 patients underwent PC resection of residual disease. Fifteen of the 62 patients achieved a CR with chemotherapy alone, as the PC resection revealed only necrosis. Fourteen of these 15 patients continuously had no evidence of disease (NED). Forty-seven of the 62 patients had NED with chemotherapy and PC resection, including 31 with teratoma and 16 with carcinoma. However, 11 of 31 with teratoma and 11 of 16 with carcinoma subsequently relapsed. Although 18 patients had elevated tumor markers at the time of PC resection, 6 of 18 had only necrosis and 4 had teratoma. The PC tumor markers did not affect survival. The pathology of the resected specimen was the most significant predictor of survival in multivariate analysis (P < 0.001). CONCLUSIONS: Twenty-eight of 39 patients (71.8%) with PMNSGCT treated at Indiana University achieved NED status, but only 16 (41%) continuously had NED. Twenty of 36 (55.5%) referred for resection continuously had NED. Disease confined to the mediastinum and necrosis in the PC specimen were important prognostic factors for survival.     

Outcome of patients with residual germ cell or non-germ cell malignancy after resection of primary mediastinal nonseminomatous germ cell cancer.

PURPOSE: To identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer. PATIENTS AND METHODS: Forty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed. RESULTS: At diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively. CONCLUSION: The presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.     

Osteosarcoma of the mobile spine

BackgroundThe aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine.Patients and methodsSince 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome.ResultsThe median age was 29 years (range 5–58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1–22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05).ConclusionsOsteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas.     

Hepatic arterial infusion and systemic chemotherapy after multiple metastasectomy in patients with colorectal carcinoma metastatic to the liver: a North Central Cancer Treatment Group (NCCTG) phase II study, 92-46-52

BackgroundPatients with multiple liver metastases from colorectal cancer are at high risk of recurrence after resection. Hepatic artery infusion (HAI) alternating with systemic therapy after surgical resection may improve survival after surgery.MethodsPatients with liver-only metastases from colorectal cancer amenable to resection/cryoablation were eligible. Previous adjuvant chemotherapy for a completely resected primary tumor was allowed. Alternating courses of HAI and systemic therapy included floxuridine (FUDR) by HAI. Systemic chemotherapy consisted of bolus leucovorin (LV) plus 5-fluorouracil (5-FU).ResultsForty-nine patients had complete resection of their liver metastases, with 44% having more than 4 hepatic metastases and 78% having bilobar disease. Thirty-six patients had HAI FUDR alternating with systemic therapy. Patients received a median of 3.5 cycles (range, 1-4) and 3 cycles (range, 0-6) of therapy with HAI FUDR and systemic therapy, respectively. At the time of final analysis the estimated median disease-free survival and hepatic disease-free survival was 1.2 years (95% confidence interval [CI], 0.9-2.1) and 1.8 years (95% CI, 1.8-not available), respectively. Eleven patients (31%) were alive at this writing. All surviving patients had a minimum of 5.5 years of follow-up.ConclusionThis trial of adjuvant chemotherapy in patients who underwent complete resection with unfavorable characteristics demonstrates apparent improvement in outcome compared with historical series treated with surgery alone. However the results of this trial and other randomized trials of HAI do not appear to support its use at this time because of the development of more effective systemic options.     

EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy

IntroductionIn classical EGFR mutant non-small-cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitor (TKI) therapy yields better outcomes than platinum-based chemotherapy. However, EGFR exon 20 insertion (ex20ins) NSCLC is relatively resistant to currently available EGFR TKIs. Though platinum-based chemotherapy is the frontline standard of care for EGFR ex20ins NSCLC, its efficacy is not fully described.Study DesignA retrospective, single-center, case seriesMethodsPatients were identified through an electronic research database at a single institution and included if they had advanced EGFR ex20ins NSCLC, received platinum-based chemotherapy for metastatic disease, and had scans evaluable for response. Each patient's demographics, tumor characteristics, and clinical course were recorded. Treatment response was evaluated using RECIST v1.1 criteria, and the PFS was calculated by the Kaplan-Meier method.ResultsAmong 27 patients identified with EGFR ex20ins NSCLC at our institution, 18 (67%) received platinum-based chemotherapy for metastatic disease and had scans evaluable for response. These patients received platinum-based chemotherapy in the first-line (N = 17, 94%) and second-line settings (N = 1, 6%). The objective response rate (ORR) to platinum-based chemotherapy was 39% (7 of 18 patients; 95% confidence interval [CI] 16-61). The median PFS with platinum-based chemotherapy was 7.1 months (95% CI, 6.3 -13.7), and the median overall survival was 3.2 years (95% CI, 1.92 – NR).ConclusionsThe efficacy of platinum-based chemotherapy in EGFR ex20ins NSCLC is similar to that expected for TKI sensitive EGFR mutant NSCLC. Novel agents designed to specifically target ex20ins mutant EGFR should additionally improve outcomes.     

Late relapse of testicular cancer

The complete response (CR) rate of disseminated germ-cell tumors with current aggressive chemotherapy and surgical resection of localized residual disease is between 70%-80%. Most patients who relapse do so within the first year of therapy. We have observed seven patients with germ-cell tumors treated with a variety of modalities who relapsed after more than two years in CR (45-87 months). Five patients are alive after salvage therapy with follow-up too short to assess the durability of second remission. There were no features distinguishing late relapse patients from all patients treated with chemotherapy for germ-cell tumors. Follow-up in patients treated for germ-cell tumors with chemotherapy should be extended to five years before curability can be established.     

Prognostic factors in patients with poor-risk germ-cell tumors: a retrospective analysis of the Indiana University experience from 1990 to 2014

BackgroundBased on the risk stratification from the International Germ Cell Cancer Collaborative Group (IGCCCG), only 14% of patients with metastatic germ-cell tumors (GCT) had poor-risk disease with a 5-year progression-free survival (PFS) rate of 41% and a 5-year overall survival (OS) rate of only 48%. This analysis attempts to identify prognostic factors for patients with poor-risk disease.Patients and methodsWe conducted a retrospective analysis of all patients with GCT diagnosed and treated at Indiana University from 1990 to 2014. Clinical and pathological characteristics were available for all patients and all of them were treated with cisplatin–etoposide-based chemotherapy. Cox proportional hazards models were used to target significant predictors of disease progression and mortality. A significance level of 5% was used in the analysis.ResultsWe identified 273 consecutive patients with poor-risk GCT (PRGCT). Median follow-up time was 8 years (range 0.03–24.5). The 5-year PFS and OS rates were 58% [95% confidence interval (CI) 51% to 63%] and 73% (95% CI 67% to 78%), respectively. In multivariate survival analyses, multiple risk factors were associated with disease progression, including liver metastasis, brain metastasis, primary mediastinal nonseminomatous GCT (PMNSGCT), and elevation in logarithmic β-hCG. Significant predictors of mortality were PMNSGCT [hazard ratio (HR) 4.63, 95% CI 2.25–9.56; P < 0.001], brain metastasis (HR 3.30, 95% CI 1.74–6.23; P < 0.001), and increasing age (HR 1.03, 95% CI 1.01–1.06; P = 0.02).ConclusionsPatients with PMNSGCT, brain metastasis, or with increasing age are at higher risk of death than their counterparts. This contemporary cohort (1990–2014) of 273 patients with PRGCT had improved PFS and OS outcomes than those from the historical IGCCCG group of patients (1975–1990).     

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.     

Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor

BackgroundThe emergence of a primitive neuroectodermal tumor (PNET) within a germ-cell tumor (GCT) is rare. We assess the prognosis and response to treatment.Patients and methodsEighty-one patients were identified. Selected patients were treated with cyclophosphamide 1200 mg/m², doxorubicin 75 mg/m², and vincristine 2 mg i.v. alternating with ifosfamide 1.8 g/m² × 5 days plus etoposide 100 mg/m² × 5 days (CAV/IE). Ewing's sarcoma (EWS) translocation was assessed using a FISH-based method.ResultsMedian follow-up was 41 months. Seventy-six patients had PNET in the primary tumor or in initial metastasis. Five harbored PNET only at relapse. Twenty-six of 76 underwent primary retroperitoneal lymph node dissection, 13 of whom had retroperitoneal PNET and four are dead of disease (DOD). Fifty of 76 were initially treated with GCT chemotherapy (n = 49) or CAV/IE (n = 1). Twenty-seven of these 50 underwent complete postchemotherapy resection of residual PNET and 17 are DOD. Ten patients received CAV/IE. Eight achieved an objective response, and five are currently alive. One of the 14 specimens examined carried the EWS translocation.ConclusionsPNET of GCT origin is associated with an adverse outcome. For low-volume disease, surgery is the optimal initial therapy. CAV/IE may have a role in patients with unresectable disease.     

Adrenocortical carcinoma: is adjuvant therapy indicated? A single institution experience

Background. Adrenocortical carcinomas are rare tumors with an aggressive natural history. Complete surgical resection of the tumor is possible only in few patients, and even after complete resection many patients develop local recurrence of tumor or distant metastases. The role of adjuvant chemotherapy is not established, and there are no published series on the probable benefit of adjuvant cisplatin-based chemotherapy. Methods. In this retrospective study, 17 patients with completely excised adrenocortical carcinoma were given adjuvant treatment (n = 7) or placed on observation (n = 10). Adjuvant treatment included chemotherapy, using a combination of cisplatin and etoposide, and/or tumor bed irradiation. Results. All 4 patients who received adjuvant chemotherapy are alive and disease-free at a median follow-up period of 28 months. None of the 3 patients who received local radiotherapy showed evidence of local recurrence. Seven of the 10 patients placed on observation alone had disease recurrence at local (n = 2), distant (n = 1), or both local and distant sites (n = 4). Conclusion. Adjuvant chemotherapy or radiotherapy appeared to delay both local and distant relapses in completely resected adrenocortical carcinoma in this small retrospective series. Initial results of adjuvant therapy with cisplatin and etoposide in adrenocortical carcinoma are promising and warrant further studies. Received: March 11, 1999 / Accepted: December 24, 1999     

Bladder preservation in small cell carcinoma of the urinary bladder: an institutional experience and review of the literature

AimsPrimary small cell carcinoma (SCC) of the urinary bladder is rare, accounting for less than 1% of all primary bladder malignancies. Metastases are often present at the time of diagnosis, prognosis is poor and there is no established optimum treatment strategy. Small cell carcinoma of the lung (SCLC) shares many clinicopathological features with SCC of the bladder, and there is good evidence supporting the use of combination chemotherapy in SCLC. In addition, consolidation thoracic irradiation and prophylactic cranial irradiation (PCI) both increase 3-year absolute survival by 5.4% in SCLC patients with limited disease and a complete response to chemotherapy. Therefore, we adopted a similar staging and treatment strategy for SCC of the bladder. We report our clinical experience using this strategy, and review published studies.Materials and methodsAll cases of SCC of the bladder referred to Velindre Hospital between 1998 and 2005 were identified and data collected retrospectively on demographic details, stage, performance status, treatment and response to treatment. For the review, the electronic databases MEDLINE, EMBASE and Cancerlit were searched, along with hand searching of journals, relevant books and review papers.ResultsSeven patients were identified. In total, six out of seven had platinum-based chemotherapy. Four patients received consolidation radiotherapy (CRT) to the bladder after a complete response to chemotherapy, and none have locally relapsed to date. The three patients with limited disease remain alive and disease free 14, 30 and 36 months after diagnosis.ConclusionsCombined modality therapy using platinum-based combination chemotherapy and consolidation radiotherapy may provide effective local control and allow a bladder-preserving approach to the management of SCC of the bladder. The role of PCI is controversial, and should be discussed with patients on an individual basis.     

What is the Role of Enlarged Lymph Node Resection Alone in Patients With Nonseminomatous Germ Cell Tumor Who Had Stage II or III Disease?

BackgroundRetroperitoneal lymph node dissection is an important treatment modality in nonseminomatous germ cell tumors of the testis. However, the role of more limited surgical approaches such as resection of enlarged lymph nodes only is still controversial.Patients and MethodsBetween January 1991 and December 2010, charts of 94 patients who underwent resection of enlarged retroperitoneal lymph nodes alone were reviewed. Pathologic findings, local recurrence, and adverse effects were noted after this surgical approach.ResultsThe median age was 25.5 years. Twenty-one (22.6%) patients had lung metastasis, and 5 (5.4%) patients had nonregional lymph node metastasis at the initial visit. Eighty-seven (91.6%) patients received chemotherapy after inguinal orchiectomy, and the other patients had mass resection only for enlarged lymph nodes without prior chemotherapy. In patients who had chemotherapy before surgery, the median retroperitoneal lymph node size before and after chemotherapy cycles was 55 mm and 32.5 mm, respectively. The pathologic assessment of retroperitoneal masses revealed mature teratoma in 51.6% (n = 47) of patients, viable carcinoma in 20.9% (n = 19) of patients, and necrosis or fibrosis in 27.5% (n = 25) of patients. The median follow-up time was 60.2 months (range, 2.7-334.8 months). During follow-up, 5 (5.4%) patients had radiologic relapse at the retroperitoneal area, and 3 patients developed systemic metastases. Six (6.4%) patients died of their disease, 2 (2.1%) patients were alive with disease, 86 (91.5%) patients were healthy at the last follow-up. Ejaculation status was recorded in 56 patients. Antegrade ejaculation had preserved in 53 (94.6%) of these patients.ConclusionsResection of enlarged lymph node metastases alone is a reasonable treatment option for patients with nonseminomatous germ cell tumors.     

Effectiveness of craniotomy and long-term survival in 35 patients with gestational trophoblastic neoplasia with brain metastases: a clinical retrospective analysis

ObjectiveTo investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy.MethodsThirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed.ResultsAll 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55–85.15; p=0.017).ConclusionDecompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.     

SEOM clinical guidelines for the treatment of non-small-cell lung cancer: an updated edition

The purpose of this article is to provide updated recommendations for the diagnosis and treatment of patients non-small-cell lung cancer (NSCLC). The staging system for lung cancer has recently been revised by the International Association for Study of Lung Cancer and patients with NSCLC shall now be staged according to the UICC system 7th edition. Recommendations for treatment were based on treatment strategies that improve overall survival. In functionally fit patients with stage I–II disease surgical resection is recommended. Four cycles of adjuvant cisplatin-based chemotherapy is recommended in patients with pathologic stage II-III. For patients with stage IIIA and non-bulky mediastinal lymph node survival was significantly improved with induction chemotherapy plus surgical resection. Patients with unresectable or bulky stage IIIA and those with stage IIIB, should be treated with platinum-based chemotherapy and thoracic radiotherapy. For patients with metastatic disease and performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For elderly patients and those with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with platinum-based chemotherapy, except for patients with certain clinical characteristics. Maintenance therapy with pemetrexed or erlotinib increases survival in patients who did not progress after 4 cycles of a platinum based chemotherapy. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs.     

Adjuvant Chemotherapy Increases Programmed Death-Ligand 1 (PD-L1) Expression in Non–small Cell Lung Cancer Recurrence

BackgroundDespite recent studies, the effect of chemotherapy on programmed death-ligand 1 (PD-L1) expression remains controversial. In this study, we investigated whether PD-L1 expression is affected by platinum-based chemotherapy. Furthermore, we evaluated correlation of PD-L1 expression with oncogenic driver alterations.Materials and MethodsWe retrospectively evaluated changes in PD-L1 expression by immunohistochemical (IHC) analysis in resected specimens and in biopsies at non–small cell lung cancer recurrence in patients receiving or not adjuvant chemotherapy after surgical resection. Four IHC score groups were defined: TC0 < 1%, T ≥ 1% and < 5%, TC2 ≥ 5% and < 50%, and TC3 ≥ 50%.ResultsThirty-six patients with adenocarcinoma were included. Twenty (56%) patients underwent adjuvant chemotherapy, and 16 (44%) patients did not receive adjuvant chemotherapy. PD-L1 expression was present in 10 (28%) of 36 initial tumor specimens. From patients receiving adjuvant chemotherapy, 7 (35%) of 20 tumor biopsies showed significant upregulation in PD-L1 expression at recurrence. In contrast, from patients with no adjuvant therapy, only 2 (12.5%) of 16 showed a change in PD-L1 expression. Six (17%) of 36 patients were PD-L1-negative in the primary tumor and turned positive at recurrence. KRAS mutation was present in 70% of patients expressing PD-L1.ConclusionPD-L1 expression in non–small cell lung cancer can change from primary to recurrence, implicating the need for re-biopsy at recurrence. Moreover, chemotherapy might increase expression of PD-L1, supporting a combinatorial therapy with chemotherapy and anti-PD(L)1 treatment.     

Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy

The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy. © 1996 Wiley-Liss, Inc.     

The Role of Surgery in the Management of Recurrent or Persistent Non-seminomatous Germ Cell Tumors

ObjectiveTo review the management of patients with non-seminomatous germ cell tumors (NSGCTs) with persistent or recurrent disease following primary or secondary therapy, with particular attention devoted to the role of surgery.MethodsA non-structured review of the literature until January 2007 was performed using the PubMed database.ResultsThe management of persistent or recurrent disease among patients with NSGCT depends on stage at presentation and relapse, serum tumor marker levels at relapse, prior therapy, and timing of relapse. Clinical stage I patients who relapse following active surveillance are usually treated with induction chemotherapy. Likewise, patients who relapse following primary retroperitoneal lymph node dissection (RPLND) are treated with induction chemotherapy based on the systemic pattern of recurrence. Advanced cases with residual radiographic disease >1 cm and normal tumor markers following induction chemotherapy are generally recommended for postchemotherapy surgical resection, whereas those with persistently elevated markers undergo salvage chemotherapy. Select patients with resectable disease and elevated serum tumor markers may be appropriate candidates for surgery. Based on intrinsic chemoresistance, the treatment of patients with advanced disease who relapse >2 yr (late relapse) following successful chemotherapy is primarily surgery.ConclusionPatients with NSGCTs with persistent disease or recurrence within 2 yr of initial therapy remain highly curable. The prognosis of patients with late relapse is compromised based on tumor chemoresistance. The role of surgery in the management of recurrent disease is primarily limited to the postchemotherapy setting; however, in the context of late relapse it often represents the primary treatment.     

Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free.     

Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label,single-arm,phase 2 Pazotest trial

BackgroundTherapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT.Patients and methodsIn the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%,α = 5%,β = 20%).ResultsForty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%–28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%–33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%–69.6%). The small sample size was the major limitation.ConclusionsDespite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.     

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols

BackgroundLocal recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins.Patients and methodsWe analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR.ResultsMedian follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery.ConclusionsPatient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.