Primary anterior mediastinal seminoma

A review of the Mayo Clinic experience with primary anterior mediastinal seminomas involved 17 patients who had pure anterior mediastinal seminomas and four who had mixed germ-cell tumors containing seminomas. At follow-up, of the 17 patients with pure anterior mediastinal seminoma, nine had no evidence of disease and eight had died of metastatic disease. Of the four patients with mixed germ-cell tumor containing seminoma, two were alive at follow-up and two had died of metastatic disease. In the group with pure anterior mediastinal seminoma, these factors seemed to have been associated with a greater potential for progression of disease: older than 35 years of age, presentation with fever, superior vena caval syndrome, supraclavicular or cervical adenopathy, and roentgenographic evidence of hilar disease.     

原发于纵隔和腹膜后的生殖细胞肿瘤37例临床报告

目的 探讨原发于纵隔和腹膜后的生殖细胞肿瘤的临床特点、治疗方法、疗效以及影响预后的因素。方法 回顾性分析37例原发于纵隔和腹膜后的生殖细胞肿瘤的临床资料，其中25例原发于纵隔，12例原发于腹膜后；精原细胞瘤13例，非精原细胞瘤24例。结果 原发于纵隔的精原细胞瘤、非精原细胞瘤和原发于腹膜后的精原细胞瘤、非精原细胞瘤的5年生存率分别为40％、34％、100％和67％；相应的5年无进展生存率分别为34％、32％、100％和67％。单因素分析显示，病理类型、原发部位和国际预后评分均为有显著意义的预后因素。结论 原发于纵隔和腹膜后的生殖细胞肿瘤是1组有潜在治愈可能的疾病。影响预后的因素主要包括肿瘤原发部位、病理类型及国际预后评分。     

Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies.

Forty-nine patients with assumed extragonadal germ-cell tumors (retroperitoneum: 39, mediastinum: 8, CNS: 2) were included in the present study. The patients were treated with 'high' (40 mg cisplatin/m2 and 200 mg etoposide/m2 daily x 5) or 'conventional' (20 mg cisplatin/m2 and 100 mg etoposide/m2 daily x 5) doses of cisplatin and etoposide together with bleomycin, depending on the presence or absence of poor prognosis factors. Forty-six patients were evaluable for response and 3 patients were classified as non-responders (1 early death, 2 toxic deaths). Eighty percent obtained complete remission and 76% are alive without evidence of disease after a median observation time of 41 months (88% of patients with primary tumor in the mediastinum, 72% with tumor in the retroperitoneal area, 87% of patients with seminoma and 71% with non-seminoma, respectively). In 48 patients testicular biopsies were performed. In 42% of patients with primary retroperitoneal tumors, carcinoma in situ testis (CIS) was diagnosed. None of the patients with tumors in mediastinum or CNS had CIS in the testicles. The therapeutic outcome for patients with extragonadal germ-cell tumors is now similar to that of patients with very advanced testicular cancer when considered in relation to the presence of prognostic factors. The coexistence of CIS and retroperitoneal tumor could indicate that these tumors are not truly extragonadal or that these lesions have a common malignant progenitor.     

Primary malignant mediastinal germ cell tumors: a study of eleven cases and a review of the literature

From 1957 to 1988 eleven cases of primary mediastinal germ cell tumor were referred to the Peter MacCallum Cancer Institute (PMCI). Four were seminomas, three were mixed germ cell tumors, two were embryonal carcinomas and two were teratocarcinomas. Two of the eleven patients were female. For seminoma, surgical debulking and post-operative irradiation produced the best results. Mediastinal doses ranged from 30 to 37.5 Gy. Local control was achieved in all cases; two patients survive disease-free. The non-seminomatous germ cell tumors showed a significantly poorer survival with only one of seven patients remaining alive in remission at 15 months. One other case of non-seminomatous tumor remains alive but in relapse at 23 months. Attention is focused on the anterior position of primary germ cell tumors in the mediastinum. A review of the literature is presented.     

Testicular seminoma. Results of the Yale University experience, 1964-1984

Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma.     

The results of chemotherapy for extragonadal germ-cell tumors in the cisplatin era: the Memorial Sloan-Kettering Cancer Center experience (1975 to 1982)

Thirty-eight patients with extragonadal germ-cell tumors treated at Memorial Sloan-Kettering Cancer Center (New York) between 1975 and 1982 received high-dose cisplatin-based chemotherapy. Complete response was achieved in 89% of patients with pure seminoma and all complete responders are alive without evidence of disease (median follow-up time, 29+ months). Complete response was achieved in only 41% (12 of 29) of patients with extragonadal nonseminomatous germ-cell tumors; only four patients are alive and free of disease (median survival time, 18 months). Although patients with extragonadal seminoma respond well with current cisplatin-based chemotherapy, minimal improvement in CR rates has been achieved in patients with extragonadal nonseminomatous tumors. Patients with extragonadal nonseminomatous germ-cell tumors have a relatively poor prognosis when compared to patients with primary testicular tumors and investigational trials of innovative therapy should be considered.     

Radiocurability of microscopic disease in childhood rhabdomyosarcoma with radiation doses less than 4,000 cGy

In an attempt to evaluate the radiocurability of microscopic disease in childhood rhabdomyosarcoma (RMS) with total tumor doses of less than 4,000 cGy, we performed a retrospective analysis of all patients with microscopic residual RMS who were treated at the Memorial Sloan-Kettering Cancer Center (MSKCC) during the years 1970 to 1987. There were 32 patients ranging in age from 3 months to 22 years (median, 6 years) with microscopic residual of either (1) a localized primary tumor (MSKCC, stage IB; Intergroup Rhabdomyosarcoma Study [IRS] group IIA), 19 patients; or (2) an involved lymph node region with the primary tumor completely resected (MSKCC stage III; IRS group IIC), 13 patients. Twenty-nine of the 32 patients presented with embryonal histology. All patients were treated with combination chemotherapy (CT) and megavoltage external beam radiotherapy (RT). The RT was delivered in either conventional fractionation of 180 to 200 cGy daily (30 patients) or hyperfractionation of 150 cGy twice daily (two patients). Fifteen patients received RT doses of less than 4,000 cGy with a range of 3,000 to 3,600 cGy and a median value of 3,100 cGy; 17 patients received 4,000 cGy or more with a range of 4,000 to 6,000 cGy and a median value of 4,600 cGy. With a median follow-up of 11 years, the relapse-free survival was 25 of 32 patients (less than 4,000 cGy, 12 of 15; greater than or equal to 4,000 cGy, 13 of 17). The RT local control rate was 30 of 32 (less than 4,000 cGy, 14 of 15; greater than or equal to 4,000 cGy, 16 of 17 [P = .94]). Our results suggest that radiation doses of below 4,000 cGy, when combined with effective multiagent CT, may be sufficient for local control of microscopic disease in childhood embryonal RMS.     

26例原发性纵隔恶性生殖细胞瘤的诊治

目的:探讨原发性纵隔恶性生殖细胞瘤的诊治及外科手术的作用.方法:对26例收治的原发性纵隔恶性生殖细胞瘤的临床资料进行回顾性分析.结果:22例手术治疗患者中,11例根治性切除,10例姑息性切除,1例探查,手术并发症发生率及死亡率分别为18.2%和9.1%,其中12例术后给予以顺铂为主的联合化疗,4例予以放疗.手术治疗患者术后病理为无性生殖细胞瘤12例,精原细胞瘤5例,未成熟畸胎瘤5例.3例未成熟畸胎瘤及1例胚胎癌患者明确诊断后未手术而给予放疗或放、化疗.本组26例患者中仅2例精原细胞瘤生存满5年,17例已证实死亡,除2例手术死亡外均死于肿瘤复发转移.结论:原发性纵隔恶性生殖细胞瘤的治疗应强调以化疗为主的综合治疗,外科切除只宜做为阶段性的辅助手段,手术时机把握应以具体患者情况而定.     

Iodine125 interstitial brachytherapy in the treatment of carcinoma of the lung.

In a prospective study, 14 patients with primary non-oat cell lung carcinoma were treated with intraoperative Iodine125 (I125) implantation of the lung tumor via lateral thoracotomy or median sternotomy. Staging mediastinal node dissection was performed in each case. Patients were selected when wedge or segmental resections were not technically feasible, such that lobectomy or completion pneumonectomy would have been required or pulmonary function studies were poor. Doses ranged from 8,000 cGy at the periphery to 20,000 cGy at the center. With a minimum 12 month follow-up, mean and median survivals were 16.7 and 15.1 months, respectively. Local control was achieved in 10 of 14 patients (71%) with all local failures occurring in pathologic stage III patients. When separated according to tumor size, local control was obtained in six of seven tumors of less than 3 cm and four of five tumors of 3-5 cm. Both cases with masses greater than 5 cm failed locally. There was one operative mortality and two postoperative complications. All other patients were discharged within one week of surgery. There was no radiation pneumonitis. I125 lung brachytherapy is an excellent alternative treatment for T1 and T2 tumors when medical conditions preclude curative resection.     

原发恶性纵隔生殖细胞瘤的治疗与预后

目的:探讨纵隔原发恶性生殖细胞肿瘤的临床特征、治疗及预后.方法:回顾性分析四川大学华西医院2008年至2013年收治的生殖细胞瘤患者,筛选纵隔原发恶性生殖细胞肿瘤,采集临床病理资料分析预后.结果:经病理确诊生殖细胞瘤患者共1 523例,原发于纵隔163例,其中恶性14例,包括精原细胞瘤6例,非精原细胞瘤8例.病人接受手术、放疗及化疗的综合治疗.精原细胞瘤患者生存时间优于非精原细胞瘤患者(P=0.015).结论:精原细胞瘤患者生存优于非精原细胞瘤患者.手术对纵隔原发恶性GCT的价值仍难以断定,需要仔细评估疾病的具体情况.放化疗的综合治疗应当是此类病人的主要治疗模式.     

Primary malignant germinal tumors of the mediastinum. A study of 24 cases.

The malignant germinal tumors found in the testis (seminoma, teratocarcinoma, embryonal carcinoma, choriocarcinoma, and mixtures of these) can originate in the anterior mediastinum. An occult testicular tumor must be sought, but primary mediastinal germinal tumors constitute a true entity. The details of 24 such patients treated at Walter Reed General Hospital are presented. Of 19 patients who died, 2 were women; postmortem examination of the testes of 13 men failed to reveal a primary tumor. Five patients are alive and well with no testicular abnormality. It is important to distinguish the histopathologic types. Seminomas are readily controlled with modest doses of irradiation. Embryonal carcinomas are also radiocurable with somewhat higher doses; 2 long-term disease-free survivors are reported. Teratocarcinomas are highly malignant and require higher doses for control. Choriocarcinomas progress so rapidly that chemotherapy is necessary.     

Primary seminoma of the mediastinum. Cancer Control Agency of British Columbia experience

Six patients with primary seminoma of the mediastinum were treated at the Cancer Control Agency of British Columbia during the period from 1970 to 1982. Primary treatment used was external beam radiotherapy. Only one patient received both radiotherapy and chemotherapy. Tumor dose ranged from 3000 cGy in 16 daily fractions in 3 weeks to 3500 cGy in 20 daily fractions in 4 weeks using parallel opposed fields on megavoltage machines. Two patients received additional small-volume boost to the superior mediastinum, delivering 500 cGy and 1000 cGy, respectively. All patients had complete resolution of the mediastinal mass after treatment and are alive and free of disease. One patient developed a metastasis to the fifth lumbar vertebra 1 year after treatment. This metastatic lesion was treated with radiotherapy and the patient is alive and free of clinical disease. Mediastinal seminoma is radiosensitive and radiocurable.     

Metachronous Gonadal and Extragonadal Primary Germ Cell Tumors: Two Case Reports

Bilateral synchronous or metachronous germ cell tumors (GCT) of the testis are recognized in 2-3% of patients. Extragonadal GCT in the mediastinum or the retroperitoneum have been rarely reported in patients with primary GCT of the testes. Two patients were observed with two separate primary GCT; in 1 a retroperitoneal embryonal carcinoma was successfully treated with chemotherapy and surgery and a new primary developed 14 years later in the testicle as a seminoma. A second patient had a primary teratocarcinoma of the testes treated with surgery only; 4 years later he developed a mediastinal endodermal sinus tumor, which was fatal. These cases suggest that not only is the remaining testicle at risk for a second primary GCT, but also that extragonadal sites impose a similar risk and monitoring of patients should consider all potential sites for the development of GCT.     

Primary lymphoma of the central nervous system. A report of 20 cases and a review of the literature

Twenty patients with primary non-Hodgkin's lymphoma of the central nervous system (CNS) were seen at Vanderbilt and its affiliated hospitals between 1974 and 1986. Histologically, the most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. However, multiple histologies were identified. Lesions most commonly involved the frontal lobes and/or deep nuclei. Positive cerebrospinal fluid cytology was rare at initial presentation. Seventeen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 5,000 cGy (range: 3,000-5,600 cGy). Seven patients have been followed for less than 12 months since diagnosis. Of the remaining patients, 7 (54%) survived at least 1 year. The extent of surgery performed, dose of radiotherapy administered, subclass of lymphoma diagnosed, or location(s) of involvement within the CNS did not influence survival. Treatment rarely caused a dramatic improvement in performance status despite objective signs of response. New treatment strategies are needed to improve the management of these tumors.     

Primary tumors of the mediastinum

BACKGROUND AND OBJECTIVES: Diagnostic and therapeutic approaches to mediastinal tumors have changed over the past three decades. We reviewed our recent experience with these tumors and assessed the role of a multidisciplinary treatment approach. METHODS: A retrospective review of 124 patients with primary mediastinal tumors over a 25-year period. RESULTS: Median age was 35 years. Symptoms were present in 86 of 124 (69%) patients. One hundred and eleven of 124 (90%) tumors were malignant. Distant metastases were present at diagnosis in 14 of 124 (11%) patients. The most common tumor was thymoma (38/124, 31%), followed by germ-cell tumor (29/124, 23%), lymphoma (24/124, 19%), and neurogenic tumors (15/124, 12%). Seventy-four of 124 (60%) patients underwent resection, 88 (71%) received chemotherapy, and 97 (78%) received radiation therapy. Tumor recurrence occurred in 52% (47/91) of patients who initially had a complete resection or response to treatment. Median time to recurrence was 10 months. Overall median survival was 44 months. Metastatic disease at presentation (P = 0.02) and tumor recurrence (P = 0.00001) were the only significant independent predictors of survival on multivariate analysis. CONCLUSIONS: Malignant primary mediastinal tumors often require multimodality treatment. Despite improvements in survival with multimodality treatment, death from recurrent disease remains a problem.     

Impact of tumor control on survival in carcinoma of the lung treated with irradiation

The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1-3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course (p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000-6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure (p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled (p = 0.001). In patients surviving 12 months after treatment with 5000-6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 29 months, in contrast to 18 months, if they developed intrathoracic failure (p = 0.05). In patients treated with 4000 cGy, the median survival was 23 months with control and 18 months without control of the intrathoracic tumor [corrected] (p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant (p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)     

Palliative radiation treatment of cutaneous mycosis fungoides--a dose response

Between 1966 and 1981, 20 patients (191 lesions) underwent palliative radiation therapy for control of biopsy-proven cutaneous mycosis fungoides. Six patients (47 lesions) and an additional 34 lesions from the remaining 14 patients with complete response to treatment were excluded from the study because of follow-up of less than one year. Included in the remaining 110 lesions were all recurrences and all partial responses. The modalities for treatment included superficial X rays, Cobalt-60 or electron beam irradiation. The total tumor doses employed ranged from 600-4000 cGy. The 110 lesions (14 patients) were retrospectively analyzed to determine the dose required for local control of the lesions. Fifty-three percent of the lesions were classified as plaques, 20% as tumors less than or equal to 3 cm in diameter, and 27% as tumors greater than 3 cm in diameter. Complete response to treatment was observed in 95% of the plaque lesions, 95% of the tumors less than or equal to 3 cm in diameter and 93% of tumor greater than 3 cm in diameter. A complete response to treatment was noted in all lesions receiving greater than 2000 cGy. In the total population of lesions having a complete response, a local infield recurrence rate of 42% was noted in the group receiving less than or equal to 1000 cGy, 32% in those receiving 1001-2000 cGy, 21% in those receiving 2001-3000 cGy, and 0% in the group receiving greater than 3000 cGy. No infield recurrence was seen when the treated lesion received a total tumor dose greater than or equal to TDF of 49. Of those lesions which recurred, the mean time to recurrence for the first three dose ranges above were 5 months, 10 months and 16 months respectively. Eighty-three percent of the 30 recurrences were seen within one year of treatment; 100% of the recurrences occurred within two years of treatment. The data from this study indicate that tumor doses equivalent to at least 3000 cGy at 200 cGy per fraction, five fractions per week (TDF greater than or equal to 49) are needed for adequate local control of cutaneous mycosis fungoides lesions.     

Endodermal sinus (yolk sac) tumor elements in testicular germ-cell tumors in adults: comparison of prospective and retrospective studies

The incidence of endodermal sinus tumor (EST) or yolk sac tumor (YST) elements has been studied in two series of testicular germ-cell neoplasms in adults. One series, consisting of 200 germ-cell neoplasms seen from 1053 through 1968, was studied retrospectively, and the other, consisting of 147 cases seen from May 1974 through February 1979, was studied prospectively. Excluding the cases of pure seminoma, EST(YST) elements were found in 21 (28.7%) of 73 cases in the retrospective series and in 27 (44.4%) of 61 cases in the prospective series. The EST(YST) elements were in all cases admixed with other neoplastic germ-cell elements and varied from microscopic foci to being the predominant element within a tumor. The EST(YST) elements were histologically similar to infantile EST(YST) and EST(YST) in other locations. Serum alphafetoprotein (AFP) was determined in the majority of patients in the prospective series, and there was good correlation between the presence of EST(YST) elements within the tumor and elevated levels of AFP. The results of the present study indicate that EST(YST) elements occur quite frequently in testicular germ-cell neoplasms in adults and provide an explanation for the raised levels of serum AFP found in many adults with testicular germ-cell tumors. The results emphasize the importance of a thorough and careful pathologic examination of testicular germ-cell tumors, and the value of AFP as a tumor marker in patients with EST(YST). The results also lend further support to the view that EST(YST) elements found in testicular germ-cell tumors in adults are homologous with infantile EST(YST) and that EST(YST) is a distinctive and specific type of germ-cell neoplasm and should be included as such in the classification of testicular tumors.     

Outcome following resection for patients with primary mediastinal nonseminomatous germ-cell tumors and rising serum tumor markers post-chemotherapy

BackgroundTo assess the outcome of surgical resection in patients with primary mediastinal nonseminomatous germ-cell tumors (PMNSGCT) with rising serum tumor markers (STM) following standard platinum-based chemotherapy.Patients and methodsA total of 158 consecutive patients with PMNSGCT who received platinum-based chemotherapy followed by complete surgical extirpation of residual disease at Indiana University from 1982 to 2007 were retrospectively reviewed. Thirty-five of these 158 patients had rising STM at time of resection.ResultsThirty-five patients (34 males and 1 female) comprise the basis of this report. Three patients had rising human chorionic gonadotropin, and the remaining 32 patients had rising alpha-fetoprotein at the time of thoracic surgery. Twenty-four of the 35 (69%) pathologically demonstrated viable germ-cell tumor, while 8 patients had teratoma and 3 patients had necrosis only at time of resection, despite the presence of rising STM. Twenty-seven patients normalized their tumor markers postoperatively. Twenty-one of 35 died, 5 were lost to follow-up, and 9 are alive. Of the nine patients alive, seven are continuously disease free with median follow-up of 64 months (range 25–220 months).ConclusionThe presence of rising STM doesn’t preclude successful therapy with surgical resection, especially if carried out by experienced thoracic surgical oncologists.