Long term outcomes in patients with intracranial germinomas: a single institution experience of irradiation with or without chemotherapy

Complete remission can be achieved soon after irradiation in patients with intracranial germinoma. This study aimed to analyze the follow-up outcome of intracranial germinoma patients. About 39 intracranial germinoma patients (29 males and 10 females; average age, 15 years; range, 7–27 years) treated at Kyoto University Hospital from 1978 to 2004 were included in the study group. Six patients had multifocal disease at initial diagnosis, and 10 had human chorionic gonadotropin (HCG)-producing tumors. Thirteen patients were treated with craniospinal axis irradiation, 6 with whole-brain irradiation, 17 with whole-ventricle irradiation, and 3 with local field irradiation. Since 1997, 15 patients were treated with reduced–dose whole-ventricle irradiation (median, 23.4 Gy; range, 20.4–27 Gy) followed by a local boost (median, 40.8 Gy; range, 36–54 Gy) combined with chemotherapy. The median follow-up was 94 months (18 months to 25 years). The 5- and 10-year overall survival (OS) rates of the entire group were 97 and 90%, respectively. The 5- and 10-year progression-free survival (PFS) rates of the entire group were 91 and 87%, respectively. The 8-year OS and PFS in 15 patients treated by whole-ventricle irradiation combined with chemotherapy were 100% and 92%, respectively. Four patients had recurrences within a median period of 59.5 months (51–85 months). All relapses occurred outside the radiation fields. Tumor site, tumor size, HCG production, multifocal disease and radiation dose to the primary site or whole ventricle did not significantly affect PFS. All initial recurrences of intracranial germinoma occurred at the distant site out of the radiation field. Our data suggested that reduced doses to the whole ventricle, combined with chemotherapy, should be sufficiently effective in patients with intracranial germinoma.     

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.     

Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma

Purpose: To determine the optimal radiotherapy (RT) dose and volume for treatment of intracranial germinoma.Materials and methods: Eighty-one intracranial germinoma patients (33 pathologically-verified; 48 presumed by radiosensitivity testing) treated with RT alone between 1971 and 2002 were analyzed. The RT volume varied from focal (13) to whole brain (8), or to the entire neuraxis (60). All the cases after 1982 received craniospinal irradiation (CSI). Radiation dose was reduced gradually during the study period from 59 to 39.3 Gy for primary tumors, and from 34.2 to 19.5 Gy for the neuraxis. The median follow-up time was 120 months (48-260 months).Results: Five- and ten-year relapse-free survival rates were 98.8% and 94.1%, respectively. All the recurrences occurred in the patients who received local (4/13) or whole brain RT (1/8). None of the patients who received CSI suffered from a recurrence. Forty-six patients received 45 Gy or less to the primary site and 22 patients received less than 20 Gy to the spinal axis.Conclusion: Low-dose CSI-based RT should remain the standard treatment for intracranial germinoma. The RT dose can be reduced to 39.3 Gy for primary tumor sites and to 19.5 Gy for the spinal axis.     

Central nervous system. Experience of the Bordeaux University Hospital Center and review of the literature]

PURPOSE: Retrospective analysis of 17 patients with intracranial germ cell tumors treated in a multidisciplinary consultation at the Bordeaux University Hospital a and literature review. MATERIALS AND METHODS: Seventeen consecutive patients were treated from 1978 to 1995 for a primary intracranial germ cell tumor. Median age was 14 (range 3-29 years). There were two malignant teratoma, six proved germinoma and nine presumed germinoma (diagnostic based on biological, radiological and treatment criteria). All received radiotherapy from 30 to 60 Gy (median 40 Gy) in different volumes. Chemotherapy was administered in 15 cases, three after surgery and 12 after radiotherapy. RESULTS: All tumours were in complete remission after initial treatment. The two malignant teratomas recurred in non-irradiated area after nine and 48 months, and the patients died. None of the germinoma recurred within a follow-up period of two to 17 years (median 65 months). Five and 10 year actuarial overall survival rates were the same: 84% for all histologies and 100% for germinomas. Only two patients developed school difficulties and six presented an hypopituitarism, of which one was consecutive to radiotherapy. Chemotherapy was well tolerated. CONCLUSION: This retrospective study and literature analysis are in favor of limited dose and volume of radiation therapy associated with chemotherapy.     

SIOP CNS GCT 96: final report of outcome of a prospective,multinational nonrandomized trial for children and adults with intracranial germinoma,comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease

Background

We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s).

Methods

Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy.

Results

Patients with localized germinoma (n = 190) received either CSI alone (n = 125) or combined therapy (n = 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 ± 0.02 vs 0.88 ± 0.04; P = .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n = 45) had 0.98 ± 0.023 event-free and overall survival.

Conclusions

Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease.     

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma

PURPOSE: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. METHODS AND MATERIALS: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. RESULTS: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. CONCLUSION: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.     

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.     

Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

PURPOSE: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. METHODS AND MATERIALS: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. RESULTS: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. CONCLUSIONS: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.     

Chemotherapy trials in recurrent primary intracranial germ cell tumors

Summary Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, gern cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor — germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2⁺, 3, and 5 mos, cisplatin (120 mg/m²) in 1 of 2 patients for 2⁺ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2¹-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well the VAB6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity. Adjuvant chemotherapy should be considered in patients with newly diagnosed primary intracranial germ cell tumors whose tumors are considered unlikely to be permanently controlled with radiation alone.     

Reduction of the radiation dose for intracranial germinoma: a prospective study.

Intracranial germinoma has usually been treated with radiation doses of 50 Gy or more, but it is unclear whether such doses are actually necessary to cure this radiosensitive tumour. At our institution, the standard radiation dose for intracranial germinoma was 60 Gy in the 1960s, but the dose has prospectively been reduced stepwise to 40-45 Gy. In this paper, the treatment outcome was assessed in 84 patients (47 with histologically confirmed disease and 37 diagnosed clinically in the post-computerised tomography era) enrolled in both prospective and retrospective series. The 5 and 10 years survival rates for all 84 patients were 88% and 83% respectively, and the corresponding relapse-free survival rates were 88% and 85%. The 10-year relapse-free survival rate was 88% for 31 patients receiving 19-47 Gy (median 42 Gy) to the primary tumour, 92% for 28 patients receiving 48-52 Gy (median 50 Gy), and 83% for 25 patients receiving 54-62 Gy (median 60 Gy), and there was no significant difference among the three groups. In-field local recurrence only developed in one patient who received 40 Gy over a protracted period and one patient who received 60 Gy. A tumour size < 3 cm and treatment in the post-computerised tomography era were associated with a better prognosis according to univariate analysis, while age, sex, tumour site, treatment volume, the radiation dose to both the primary and the spinal cord and the extent of surgical resection did not influence the prognosis. In contrast, none of these factors had a significant influence in multivariate analysis. In conclusion, intracranial germinomas < or = 4 cm in size can usually be cured with 40-45 Gy of radiation, thus avoiding the major adverse effects of brain irradiation.     

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。     

Stereotactic radiotherapy for pediatric intracranial germ cell tumors

PURPOSE: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors. METHODS AND MATERIALS: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years). RESULTS: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up. CONCLUSION: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children.     

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.     

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.     

Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer

Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.     

Brain dose-sparing radiotherapy techniques for localized intracranial germinoma: Case report and literature review of modern irradiation

We examined the effects of intensity-modulated radiation therapy with dose-sparing and avoidance technique on a pediatric patient with localized intracranial germinoma. We also reviewed the literature regarding modern irradiation techniques in relation to late neurocognitive sequelae. A patient with a localized intracranial germinoma in the third ventricle anterior to the pineal gland received a dose-sparing intensity-modulated radiation therapy. The planning was compared to the radiation oncologist's guide of organs at risk and dose constraints for dosimetric analyses. The patient received radiation therapy alone. The total dose was 54 Gy delivered in 2.0 Gy fractions to the primary tumour and 37 Gy in 1.4 Gy fractions to whole ventricles using a dose-sculpting plan. Dosimetry analyses showed that dose-sparing intensity-modulated radiation therapy delivered reduced doses to the whole brain, temporal lobes, hippocampi, cochleae, and optic nerves. With a follow-up of 22 months, failure-free survival was 100% for the patient and no adverse events during radiation treatment process. Intensity-modulated radiation therapy with dose sparing and avoidance technique can spare the limbic circuit, central nervous system, and hippocampus for pineal germ cell tumours. This technique reduces the integral dose delivered to the uninvolved normal brain tissues and may reduce late neurocognitive sequelae caused by cranial radiotherapy.     

Feasibility of carbon‐ion radiotherapy for re‐irradiation of locoregionally recurrent,metastatic, or secondary lung tumors

Intrathoracic recurrence after carbon‐ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer‐related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re‐irradiation with carbon‐ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon‐ion radiotherapy who were treated with re‐irradiation with carbon‐ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy‐three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon‐ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re‐irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow‐up period after re‐irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2‐year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re‐irradiation with carbon‐ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re‐irradiation with carbon‐ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors.     

CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation

Purpose: To provide evidence that radiation therapy alone in the form of craniospinal irradiation (CSI) and a boost to the primary site of disease provides effective disease control and limited additional morbidity for patients with CNS germinoma.

Methods and Materials: Twelve patients with a median age of 12 years (range 9–16 years) with CNS germinoma were treated with CSI (median 25.6 Gy, range 23.4–32 Gy) and a boost to the primary site of disease (50.4 Gy, range 45–54 Gy) between January 1987 and June 1998. All patients were biopsied prior to radiation therapy and none received chemotherapy. No patients were lost to follow-up and the majority had long-term (> 45 month) pre- and postirradiation endocrine and psychology assessment.

Results: All 12 patients are alive and no failures have occurred with a median follow-up of 69 months (range 14–143 months). Preirradiation endocrine deficiencies were present in 6 of 6 suprasellar tumors and 1 of 6 pineal tumors; with follow-up there was no substantial difference between age and gender adjusted pre- and postirradiation stature and weight. With long-term follow-up, there were no significant differences between pre- and postirradiation full-scale, verbal, and performance IQ scores.

Conclusions: This study confirms the ability of radiation therapy alone to achieve disease control with a high rate of success in pediatric patients and demonstrates that the treatment toxicity faced by these patients may be less than anticipated. Because these patients present with substantial preexisting morbidity at diagnosis and may be of an age where the potential for radiation-related side effects is relatively small, the superiority of treatment alternatives may be difficult to prove.     

Intracranial ependymoma in children: analysis of prognostic factors

Summary Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25–36 Gy to the neuroaxis, 45–55 Gy to tumor bed), 12 received local field irradiation (29–60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had postradiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear. Address for offprints: Shiao Y. Woo, Department of Radiation Oncology, 6565 Fannin, M.S. DB1-37, Houston, Texas 77030, USA     

Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.