Long-term results of radiotherapy for intracranial germinoma: a multi-institutional retrospective review of 126 patients

PURPOSE: Optimal management of radiotherapy (RT) for intracranial germinoma remains controversial. This study was conducted to evaluate the long-term results of RT in patients with these tumors. METHODS AND MATERIALS: The study group consisted of 126 patients with intracranial germinoma (50 patients with pathologically verified germinoma and 76 clinically diagnosed with germinoma by clinical and neuroradiologic signs) who were treated by RT alone between 1980 and 2001. The median age at diagnosis was 17 years (range, 2-47), and various radiation doses and treatment fields were used. Serum human chorionic gonadotropin (hCG) levels were elevated in 18 patients. The median follow-up of the 114 surviving patients was 122 months (range, 13-263). RESULTS: The 10-year actuarial overall survival and cause-specific survival rate for all patients was 90% and 95%, respectively. The 10-year actuarial cause-specific survival rate for patients with and without elevated hCG levels was 94%. Relapses were noted in 10 patients, 7 of whom died of the disease. No in-field relapses at primary sites were observed in 72 patients treated with total doses of 40-50 Gy. The incidence of spinal relapses was 4% (2 of 56) for patients treated with spinal irradiation and 3% (2 of 70) for those without spinal irradiation. After a median 10-year follow-up, 54 (92%) of 59 patients with tumors not involving the neurohypophyseal region and 42 (76%) of 55 patients with tumors involving the neurohypophyseal region had Karnofsky performance status scores of 90-100%. With regard to school education and occupation, 54 (92%) of 59 patients with tumors not involving the neurohypophyseal region and 39 (71%) of 55 patients with tumors involving the neurohypophyseal region were attending school or undertaking occupations. Hormonal replacement therapy was required in 50 (44%) of 114 surviving patients before RT; only 4 patients (4%), all with neurohypophyseal tumors, required hormonal replacement therapy after RT. Clinically evident severe neurocognitive dysfunctions were documented in 10 patients before RT, and no patients treated with total doses of <55 Gy developed apparent neurocognitive dysfunctions or other complications after RT. CONCLUSION: RT was a curative treatment for intracranial germinoma, and elevated serum hCG levels did not affect the prognosis of patients treated by RT alone. A total dose of 40-50 Gy to adequate treatment fields was effective in preventing intracranial relapse, and the incidence of spinal relapses was too low to warrant routine spinal irradiation. Karnofsky performance status scores, educational achievement, and the ability to work were generally good, particularly in patients with tumors that did not involve the neurohypophyseal region. Because most complications, such as hormonal deficiency and neurocognitive dysfunction, were documented before RT and newly diagnosed complications after RT were infrequent, the treatment toxicity faced by germinoma patients appears to be less than anticipated.     

41例原发鞍上+松果体区生殖细胞瘤治疗分析及策略探讨

目的 分析颅内原发鞍上+松果体区生殖细胞瘤患者的治疗结果及治疗策略的探讨。方法 1996—2013年放疗鞍上+松果体区生殖细胞瘤患者 41例,男 35例、女 6例,年龄 5~39岁。经病灶活检病理诊断 5例,其余为临床诊断。采用常规放疗 33例、IMRT 8例;5例病理诊断者进行化放疗。放疗采用6 MV X线,照射野有全脑室照射+瘤区补量 6例,全脑照射+瘤区补量 16例,全脑脊髓照射+瘤区补量 19例。肿瘤区照射剂量 37.8~50.0 Gy,预防照射区剂量 17.8~35.0 Gy。Kaplan-Meier法进行生存率计算。结果 5年样本数 26例。5年OS率为95%、RFS率为85%。复发转移 8例,其中脊髓转移 4例、脑室播散 1例、脑室周边复发 3例。22例未进行脊髓照射者脊髓转移 4例,19例进行脊髓照射者无脊髓转移。8例IMRT者及 5例化放疗者随访期内均未出现治疗失败。结论 颅内生殖细胞瘤放疗效果好,双部位生殖细胞瘤不进行脊髓照射者失败率较高,建议对双部位病灶的患者进行脊髓照射。     

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.     

Limited-field radiation for bifocal germinoma

PURPOSE: To report the incidence, characteristics, treatment, and outcomes of bifocal germinomas treated with chemotherapy followed by focal radiation. METHODS AND MATERIALS: This was a retrospective review. Inclusion criteria included radiologic diagnosis of bifocal germinoma involving the pineal and neurohypophyseal region, no evidence of dissemination on spinal MRI, negative results from cerebrospinal fluid cytologic evaluation, and negative tumor markers. RESULTS: Between 1995 and 2004, 6 patients (5 male, 1 female; median age, 12.8 years) fulfilled the inclusion criteria. All had symptoms of diabetes insipidus at presentation. On MRI, 4 patients had a pineal and suprasellar mass, and 2 had a pineal mass associated with abnormal neurohypophyseal enhancement. All patients received chemotherapy followed by limited-field radiation and achieved complete remission after chemotherapy. The radiation field involved the whole ventricular system (range, 2,400-4,000 cGy) with or without a boost to the primary lesions. All patients remain in complete remission at a median follow-up of 48.1 months (range, 9-73.4 months). CONCLUSIONS: This experience suggests that bifocal germinoma can be considered a locoregional rather than a metastatic disease. Chemotherapy and focal radiotherapy might be sufficient to provide excellent outcomes. Staging refinement with new diagnostic tools will likely increase the incidence of the entity.     

低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤中的价值

背景与目的：颅内生殖细胞肿瘤（intracranial germ cell tumors）经积极放化疗常可获得令人满意的局部控制率和生存率，然而对部分无法取得病理诊断的颅内生殖细胞肿瘤的治疗，研究者们至今无法达成一致意见。该研究探讨低剂量诊断性放疗联合化疗在诊治颅内生殖细胞肿瘤的可行性及临床意义。方法：该研究分析了贵州省人民医院及北京天坛医院收治的28例（16例男性，12例女性，中位年龄14.5岁）高度怀疑为颅内生殖细胞肿瘤的患者。患者血浆和（或）脑脊液人绒毛膜促性腺激素（β-human chorionic gonadotropin，β-HCG）和甲胎蛋白（α-fetoprotein，AFP）均为阴性，头颅MRI诊断提示鞍区和（或）松果体区呈典型生殖细胞肿瘤影像特征，临床表现高度提示可能为生殖细胞瘤（germinoma）。这些患者因无法通过手术及立体定向活检明确病理诊断，或患者本身不同意手术或活检，因此我们建议实施诊断性低剂量放疗联合化疗方案，诊断性放疗剂量为3.4 Gy，1.7 Gy/2次。经低剂量诊断性放疗后行MRI复查。随后根据MRI复查结果采用以下治疗：⑴ 影像学为进展（progression disease，PD）或稳定（stable disease，SD），建议手术治疗。⑵ 影像学达完全缓解（complete response，CR）或部分缓解（partial release，PR），再予以2个周期化疗，顺铂+足叶乙甙（DDP+VP16）方案2个周期，化疗后再次行MRI复查，如果患者影像学检测结果显示达CR，随即按生殖细胞瘤进行调强放疗（intensity-modulated radiation therapy，IMRT）及三维适形放疗（three-dimensional conformal radiotherapy，3D-CRT)。放疗方案根据患者情况进行选择：① 局部放疗；② 全脑全脊髓+局部加量放疗；③ 全脑+局部加量放疗（松果体区病变总剂量小于等于50.4 Gy；鞍区病变总剂量小于等于41.0 Gy）。⑶ 经低剂量诊断性放疗联合化疗后行MRI复查，如果患者影像学仍未达CR，建议患者立即接受手术治疗。参考WHO实体瘤疗效评价标准判断放化疗效果。结果：经诊断性放疗后显示为SD的患者1例，被随后的手术证实为垂体瘤。经低剂量诊断性放化疗后，病灶影像学诊断结果显示26例达CR，考虑临床诊断为颅内生殖细胞肿瘤，随即予患者行IMRT及3D-CRT；治疗后影像学复查均为CR，以上患者随访时间1~8年，所有患者均无瘤生存，无复发，未见放射性坏死。经诊断性放疗及2个周期化疗后仍有1例患者影像学诊断结果显示未达到CR，后经手术证实为混合性生殖细胞肿瘤。结论：低剂量诊断性放疗联合化疗具备区分颅内生殖细胞瘤与非生殖细胞瘤的能力，对高度怀疑为颅内生殖细胞肿瘤的患者, 在没有病理证实的情况下，可参考此方案进行诊断性治疗和临床处理。     

Neoadjuvant chemotherapy followed by radiotherapy adapted to the tumor response in the primary germinoma of the central nervous system: experience of the Pitié-Salpêtrière Hospital and review of literature]

PURPOSE: Retrospective analysis of ten cases of germinoma of the central nervous system treated in Pitié-Salpêtrière Hospital, Paris. PATIENTS AND METHODS: Ten male patients were treated from 1997 to 2005 for histologically verified primary seminoma of the central nervous system. The median age was 27 years (range 18-40 years). Our option for the treatment was the association of 3-4 cycles of neoadjuvant chemotherapy (cisplatin and etoposide) to radiotherapy. Five patients received a craniospinal radiotherapy of 30 Gy (for one patient 36 Gy) followed by a tumoral boost from 20 to 24 Gy. For five patients, irradiated volume was limited to the tumour, total dose from 24 to 54 Gy (for three patients the total dose was from 24 to 30 Gy). Surgery was used for five patients, but only in one case was macroscopic complete. RESULTS: Six patients were in situation of complete remission after neoadjuvant chemotherapy. All the patients were in situation of complete remission after the irradiation. All the patients were alive free of disease with a median follow-up 46 months (range 13-90 months). CONCLUSION: In spite of the fact that the intracranial germinal tumours are not the subject of a consensual treatment strategy, this retrospective analysis pleads in favour of chemotherapy followed by limited dose and volume irradiation.     

Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors.

PURPOSE: To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-beta)-secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomas, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). RESULTS: Disease-related, overall, and relapse-free survival rates at 5 years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-beta-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-beta-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the last follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. CONCLUSION: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas.     

Salvage Radiation Therapy for Intracranial Germinoma Recurring After Primary Chemotherapy

Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7–24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61–129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40–47 Gy.     

The treatment of cranial germ cell tumours

Germ cell tumours of the central nervous system (CNS) include many subtypes whose response to treatment varies, even though the symptoms and radiological appearances are similar. Five-year survival rates are 96% for germinomas, 100% for mature teratomas, 67% for immature teratomas and 69% for immature teratomas mixed with germinomas; for beta-HCG secreting germinomas the rate is only 38%. Patients with choriocarcinoma, embryonal carcinoma, or yolk sac tumour have the lowest survival rates; patients with germinoma or mature teratoma have longer survival rates.Although a wider resection is associated with a higher rate of survival for patients with non-germinomatous germ cell (NGGC) tumours, to date an aggressive surgical approach has been advocated only for pineal region tumours, but not for hypothalamic/neurohypophyseal tumours. Beside the delayed injury induced by radiotherapy, the late injury induced by chemotherapy is becoming increasingly evident. Cisplatin is considered an indispensable drug, but it may cause renal damage, ototoxicity, peripheral neuropathy and sterility, while etoposide is associated with an excess frequency of second neoplasms.Taking into account all of the published literature, the following therapeutic options are suggested: in pure germinoma tumours (GT) radiotherapy alone will usually ensure adequate control of the disease, and the long-term sequelae may be limited by reducing the dose delivered, as was proposed for germ cell testicular tumours, to 30 Gy to limited fields plus 25-30 Gy to the spinal axis if there is disseminated disease. In cases of recurrence, which should be uncommon, patients may be rescued with both radiotherapy and chemotherapy.In NGGC tumours, the prognosis is more unfavourable and there is often dissemination to the spine at diagnosis; however, the tumour's high chemosensitivity suggests neoadjuvant treatment chemotherapy with cisplatin and etoposide for three cycles followed by consolidation radiotherapy with 40 Gy to the limited fields plus 30 Gy to the spinal axis if disseminated.In our opinion, a higher dose of radiotherapy in cases in which chemotherapy does not achieve a radiological complete remission is not advisable, because very often the residual radiological abnormality does not represent biologically active tumour but differentiated forms such as mature teratoma.The challenge for 2000 is to both cure these patients, and avoid the late and permanent sequelae of radiation and/or chemotherapy that may subsequently impair quality of life.     

Combined chemotherapy and radiotherapy for intracranial germinomas in adultpatients: a single-institution study

We report on our experience in the treatment of intracranial germinomas (18 pure germinomas and two germinomas with syncytiotrophoblastic giant cells) according to a strategy of radiotherapy doses and fields reduction after a neoadjuvant chemotherapy (Cisplatin-vinblastine and bleomycin combination). Radiation therapy was delivered after the completion of the third and last course of chemotherapy. For the solitary germinoma the target volume was the gross tumour volume. In the five multifocal germinoma patients the whole ventricle volume was irradiated. For the single disseminated germinoma patient we treated the whole central nervous system. The cumulative doses were 30 Gy for the pure germinomas. For the STGCs, a cumulative dose of 35 Gy was used. The median follow-up was 55 months (range 12–120). 18 patients were alive without recurrence of disease. In the two patients with STGCs the death took place 16 and 35 months after diagnosis.     

Pineal region tumors: Analysis of treatment results

This article represents a review of 32 patients with pineal region tumors seen and treated at the University of Michigan Medical Center from January 1950 to December 1980. All patients presented with manifestations of increased intracranial pressure: limitation of the upward gaze (Parinaud's syndrome), hydrocephalus and a mass in the posterior aspect of the third ventricle. The tumor was demonstrated by pneumoencephalography, ventric ulography, angiography or CT scans. Ventricular decompression was performed in all patients. Eighteen of the 32 patients (56%) had a histological diagnosis of germinoma, one patient had a diagnosis of hamartoma; no histological diagnosis was obtained in the remainder of the patients. Twenty-seven patients received post-operative irradiation. Irradiation dosage ranged between 30 and 55 Gy. The overall 10 year survival for evaluable patients was $\text{16}\text{24}$ (67%). The low incidence of spinal cord metastasis in these patients does not justify routine use of spinal irradiation.     

Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91.

PURPOSE: To evaluate the outcome of children with supratentorial primitive neuroectodermal tumors after surgery, irradiation, and chemotherapy and to identify factors predictive for survival. PATIENTS AND METHODS: Sixty-three children in the prospective trials HIT 88/89 and HIT 91 were eligible. Complete resection was performed in 21 patients. Patients were randomized for preirradiation chemotherapy, consisting of two cycles of ifosfamide, etoposide, methotrexate, cisplatin, and cytarabine (n = 40), or chemotherapy after irradiation, consisting of eight cycles with cisplatin, vincristine, and lomustine (n = 23). Irradiation volume was recommended to encompass the neuraxis with 35.2-Gy total dose followed by a boost (20.0 Gy) to the primary tumor site (n = 54). Seven patients were irradiated to the tumor region only with a total dose of 54.0 Gy. RESULTS: Overall survival at 3 years was 48.4%. Progression occurred in 38 children, with local recurrences in 27 patients. The only significant prognostic factor was dose and volume of radiotherapy (progression-free survival after 3 years was 49.3% with correct treatment compared with 6.7% for 15 children with major violations of radiotherapy). Ten early progressions occurred during adjuvant therapy (eight before and two during radiotherapy), nine of them treated with preirradiation chemotherapy. There was a positive trend in outcome for nonmetastatic and pineal tumors. CONCLUSION: Significant predictive factors were dose and volume of radiotherapy. Volume of irradiation should encompass the whole CNS with additional boost to the tumor region. Local doses of at least 54 Gy and a craniospinal dose of 35 Gy are necessary. Preirradiation chemotherapy seems to increase risk of early progression.     

Radiation therapy for intracranial germ cell tumors: Predictive value of tumor response as evaluated by computed tomography

Background This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response during radiation therapy can predict achievement of primary local control with radiation therapy alone. Methods Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy). Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years. Results Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and 100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone and initial tumor volume. The rate of tumor volume response to irradiation assesed by CT was significantly different in those patients who relapsed compared to those who did not relapse Conclusion Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy alone.     

Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987

A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma.     

Can elective nodal irradiation be omitted in stage III non-small-cell lung cancer? Analysis of recurrences in a phase II study of induction chemotherapy and involved-field radiotherapy

PURPOSE: To establish the recurrence patterns when elective mediastinal irradiation was omitted, patients with Stage III non-small-cell lung cancer were treated with sequential chemotherapy (CHT) and involved-field radiotherapy (RT). METHODS AND MATERIALS: Fifty patients were treated with either two or four cycles of induction CHT, followed by once-daily involved-field RT to 70 Gy, delivered using three-dimensional treatment planning. The contoured gross tumor volume consisted of the pre-CHT tumor volume and nodes with a short-axis diameter of > or = 1 cm. Patients were reevaluated at 3 and 6 months after RT using bronchoscopy and chest CT. Elective nodal failure was defined as recurrence in the regional nodes outside the clinical target volume, in the absence of in-field failure. RESULTS: Of 43 patients who received doses > or = 50 Gy, 35% were disease free at last follow-up; in-field recurrences developed in 27% (of whom 16% had exclusively in-field recurrences); 18% had distant metastases exclusively. No elective nodal failure was observed. The median actuarial overall survival was 18 months (95% confidence interval 14-22) and the median progression-free survival was 12 months (95% confidence interval 6-18). CONCLUSION: Omitting elective mediastinal irradiation did not result in isolated nodal failure. Future studies of concurrent CHT and RT for Stage III non-small-cell lung cancer should use involved-field RT to limit toxicity.     

Central nervous system germinoma: retrospective study of six cases]

PURPOSE: Retrospective analysis of six patients with intracranial germinoma treated in INO and a literature review. MATERIALS AND METHODS: Six patients were treated from 1993 to 1998, for histologically verified primary intracranial germinoma. Median age was 18 years (range: 14-26 years). All patients received chemo-radiotherapy (4FP + radiotherapy from 30 to 50 Gy). RESULTS: 4 tumours were in complete remission. Two patients have kept non-evolutive residual cyst. Five patients are alive with non-evolutive disease after 15-40 months of follow-up (average: 27 months). One patient was lost to follow-up, 14 months after treatment, without disease. CONCLUSION: The treatment of intracranial germinoma is currently first line chemotherapy followed by low-dose and limited irradiation.     

Continuous hyperfractionated accelerated radiation therapy week-end less in combination with neoadjuvant chemotherapy for the treatment of stage III non-small-cell lung cancer

PURPOSE: Current treatment for unresectable stage III lung cancer includes standard radiotherapy with chemotherapy. Continuous hyperfractionated radiotherapy has been shown to be more effective than standard radiotherapy but may be associated with increased toxicity. In this study, we evaluated the feasibility and outcomes of patients treated with a hyperfractionated accelerated regimen in combination with neoadjuvant chemotherapy. METHODS AND MATERIALS: We prospectively studied 61 consecutive patients with unresectable stage III non-small-cell lung cancer. All patients received three dimensional conformal radiotherapy using three daily fractions of 1.5 Gy to a total dose of 54-60 Gy omitting elective mediastinal irradiation. Approximately two-thirds of the patients also received platinum-based neoadjuvant chemotherapy. The primary outcome was locoregional disease-free survival. Secondary analyses were performed to assess tolerability, response rates, and overall and disease-free survival among study participants. RESULTS: Overall, 56% of patients had a complete response. Locoregional recurrence was observed in 55% of patients with only a 3% rate of dissemination to non-irradiated mediastinal lymph nodes. Median locoregional disease-free survival, disease-free survival, and overall survival were 16 months (95% CI: 12-20), 15 months (95% CI: 12-18), and 19 months (95% CI: 15-30), respectively. Additionally, no episodes of severe toxicity were reported among study participants. Poor performance status and radiation response were independent predictors of survival. CONCLUSIONS: This study suggests that conformal three-dimensional hyperfractionated accelerated radiotherapy omitting elective node irradiation can be used in combination with neoadjuvant chemotherapy to treat patients with stage III lung cancer. Future studies should compare this approach with the standard treatments for patients with stage III lung cancer.     

Upfront chemotherapy and involved-field radiotherapy results in more relapses than extended radiotherapy for intracranial germinomas: modification in radiotherapy volume might be needed

PURPOSE: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma. METHODS AND MATERIALS: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months. RESULTS: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106). CONCLUSIONS: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.     

The role of chemotherapy in intracranial germinoma: A case report

Background: The case of a 29-year-old man with histologically proven simultaneous germinoma (seminoma) of the pineal gland and a stage I embryonal carcinoma of the testis is reported. An intradural metastatic lesion from the pineal germinoma was diagnosed at the level of the first thoracic vertebra. Treatment, after inguinal orchiectomy, was chemotherapy only, rather than conventional radiotherapy for the pineal germinoma.Methods: Therapy consisted of bleomycin (B), etoposide (E) and cisplatin (P). MRI was used to assess the effectiveness of BEP chemotherapy.Results: A complete remission of the pineal gland germinoma and the epidural metastasis was documented after two cycles of BEP chemotherapy and after 15 months of follow-up the patient remains free of relapse.Discussion: The pathogenesis of simultaneously occurring germinoma of the pineal gland and embryonal cell carcinoma of the testis is discussed.The choice of therapy in these circumstances is a matter of debate and the good result of chemotherapy alone in this patient suggest that primary chemotherapy may be the therapy of choice in patients with pineal germinomas.     

Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients

BACKGROUND: The current study assessed the contribution of spinal irradiation to the treatment outcome of patients with intracranial germinoma. METHODS: Clinical data from 180 patients with intracranial germinoma, who were treated with radiotherapy and/or chemotherapy from 1980 to 2001, were collected from 6 institutions. The patients' median age was 16 years (range, 1-47 yrs), and the male-to-female ratio was 133:47. Pathologic verification was obtained in 88 patients. A solitary tumor was seen in 129 patients, and multifocal or disseminated tumors were detected in 51 patients. The median tumor size was 2.5 cm (range, 0.6-7.0 cm). Local field and/or whole brain irradiation was performed in 114 patients, and craniospinal irradiation was performed in 66 patients. Fifty-five patients were treated with chemotherapy. The median follow-up time was 89 months (range, 3-297 mos). RESULTS: Eight-year overall and event-free survival rates were 91% and 89%, respectively. The 8-year recurrence rates at the primary site, intracranial space, and the spinal space were 1%, 6%, and 6%, respectively. Cox regression analysis showed that spinal irradiation (hazard ratio, 1.050; 95% confidence interval [CI], 0.355-3.170) did not contribute to a favorable event-free survival. CONCLUSIONS: Spinal irradiation did not contribute to favorable event-free survival in patients with intracranial germinoma.