Treatment of colorectal carcinoma in adolescents and young adults with surgery, 5-fluorouracil/leucovorin/interferon-alpha 2a and radiation therapy.
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Adolescent↗
Biomedical subjects
T E Merchant
Publications and source records attributed to T E Merchant.
Effect of low-dose radiation therapy when combined with surgical resection for Ewing sarcoma.
BACKGROUND: As an alternative to high-dose irradiation, limited surgery and low-dose irradiation have been investigated as a means to achieve local control. We retrospectively examined the clinical characteristics, treatment, and outcome for 25 patients with Ewing sarcoma treated with limited surgery and low-dose irradiation. PROCEDURE: The records of 25 patients (age 4-48 years) were reviewed who were treated between 1979 and 1996 at Memorial Sloan-Kettering Cancer Center. At the time of diagnosis, 21 of the 25 patients had prognostically unfavorable tumors including the presence of metastatic disease (n = 12), an axial primary (n = 17), and a tumor measuring greater than 8 cm (n = 18). The primary tumor was completely resected (wide local excision) in 13 patients, incompletely resected (marginal excision) in 7 patients, and biopsied only in the remaining 5 patients. The median dose of irradiation to the primary site was 30 Gy. RESULTS: With a median follow-up of 67 months (range 16-189 months) for the surviving patients, 28% failed distantly, and an additional 28% suffered from the progression of previously established metastatic disease. No patient failed locally. The median overall survival was 43 months. The actuarial overall survival at 5 years was 39% (+/-11%) for all patients and 60% (+/-14%) for patients with localized disease. CONCLUSIONS: Limited surgery and postoperative irradiation are one strategy that promises to balance the goal of achieving local control with the goal of diminishing late effects. Apart from the scenario in which radiation therapy is absolutely unnecessary, low-dose irradiation may be appropriate after considering the risk for local recurrence and overall prognosis.
Adolescent↗
Esophageal cancer phospholipids correlated with histopathologic findings: a 31P NMR study.
We analyzed 36 esophageal tumor specimens for phospholipid content using phosphorus nuclear magnetic resonance spectroscopy (31P NMR) and correlated the individual phospholipid profiles with specific clinical and histopathologic features. Among the 18 phospholipids identified in the esophageal tumor specimens, the mean mole percentage concentration of dimethylphosphatidylethanolamine, lysoalkylacylphosphatidylcholine, lysophosphatidic acid, lysophosphatidylcholine (deacylated at the glycerol-1 carbon), and lysoethanolamine plasmalogen correlated with pathologic T stage, nuclear grade, or the presence of lymphatic invasion. 31P NMR produces well-dispersed phospholipid spectra and a precise determination of phospholipid relative mole percentages. These data provide a statistical correlation between histopathologic features and molecules known to play an important role in cellular activities and processes unique to malignant tissues.
Esophageal Neoplasms↗
The impact of margin of resection on outcome in pediatric nonrhabdomyosarcoma soft tissue sarcoma.
BACKGROUND/PURPOSE: Because the management of pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) is determined by extrapolation from adult studies, the effect of margin of tumor resection and postoperative radiation therapy (RT) on local tumor recurrence in children has not been assessed. METHODS: Records of NRSTS patients from a single institution were reviewed with regard to demographic data, TNM staging, grade, histological type and site of primary tumor, RT, and local tumor recurrence. The margin of resection was determined by pathological review and did not necessarily reflect operative margins. RESULTS: Eighty-eight clinical group I patients were treated over a 30-year period. The most common histological tumor subtypes were synovial cell sarcoma (n = 26), malignant fibrous histiocytoma (n = 17), and fibrosarcoma (n = 7). The mean age was 9.4 years (range, 0 to 29 years). Thirty-four patients had high-grade tumors. Two of ten patients with low-grade tumors and margins less than 1 cm, including one of five who had received RT, had a local recurrence. Patients with low-grade tumors and margins greater than 1 cm (n = 44) had a lower recurrence rate (2 of 44, 4.5%). None of these patients had received RT. Fourteen patients with high-grade tumors had margins less than 1 cm. Seven of these had RT and had no recurrence. Three of the seven patients who received no RT had a recurrence (42.9%). None of the 20 patients with high-grade tumors and margins greater than 1 cm received RT; four of these patients had recurrences (20%). Seven of the 12 irradiated patients (58.3%) had serious radiation-associated complications (wound dehiscence, fracture, growth retardation, and joint dysfunction). CONCLUSIONS: Grade alone does not determine the rate of local recurrence. In both low- and high-grade tumors, a pathological margin of resection greater than 1 cm reduced local recurrence. Radiotherapy provided no advantage in low grade tumors but did decrease local recurrence rates in high-grade tumors with less than 1 cm pathological margins.
Adolescent↗
Preliminary results of conformal radiation therapy for medulloblastoma.
Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n = 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring.
Adult↗
High-grade pediatric spinal cord tumors.
Our institutional experience with high-grade pediatric spinal cord tumors includes 11 children treated during the period of 1981-1997. All patients underwent a biopsy or an attempt at resection and received postoperative radiation therapy. Three patients had a gross-total resection of their primary tumor, 6 patients had a subtotal resection and the remaining 2 were biopsied. Histologically, these tumors were characterized as anaplastic astrocytoma (n = 6), glioblastoma multiforme (n = 3) or anaplastic oligodendroglioma (n = 2). Three patients were treated with craniospinal irradiation (38-48 Gy) in addition to a boost to the residual tumor. The median dose to the primary site for all patients was 48.6 Gy (range 38-55 Gy). The median overall survival was 13 months (range 8-149 months). Only 2 patients were alive at 138 and 149 months following radiation therapy. The median progression-free survival following radiation therapy was 10 months (range 2-80 months). There was no difference in progression-free or overall survival for those diagnosed with glioblastoma multiforme when compared to patients diagnosed with anaplastic astrocytoma or anaplastic oligodendroglioma. The pattern of failure was either diffuse or local. For the patients who failed diffusely (n = 6), the median progression-free survival was 2 months compared to 23 months for those whose failure was entirely local (p < 0.01). The median overall survival was significantly shorter for those who failed diffusely compared to those who failed locally (10 vs. 37 months, p < 0.01). High-grade spinal cord tumors in children have a poor prognosis based on this report. It is important to document the extent of disease accurately prior to the initiation of radiation therapy, since a subset of these patients progress rapidly outside of the field of irradiation.
Child↗
Malignant evolution of choroid plexus papilloma.
Choroid plexus tumors are rare CNS neoplasms. The distinction between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC) is made on the basis of clinical and histological criteria. Malignant evolution of CPP may occur, and the presence of mitotic figures in CPP may predict the likelihood of recurrence or malignant evolution. Close surveillance is mandated for these patients. We report on two such cases of CPP that transformed to CPC at the time of recurrence.
Cell Transformation, Neoplastic↗
Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor.
PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Examination of CSF for malignant cells, detection of LMD on spinal magnetic resonance imaging (MRI), or both are the methods routinely used to diagnose LMD. A recent study suggested 100% correlation between CSF and MRI findings in children with medulloblastoma. To determine the validity of this hypothesis, we compared the rate of detection of LMD between concurrent lumbar CSF cytology and spinal MRI performed at diagnosis in patients with medulloblastoma or PNET. PATIENTS AND METHODS: As a part of diagnostic staging, 106 consecutive patients newly diagnosed with medulloblastoma or PNET were evaluated with concurrent lumbar CSF cytology and spinal MRI. CSF cytology was examined for the presence of malignant cells and spinal MRI was reviewed independently for the presence of LMD. RESULTS: Thirty-four patients (32%) were diagnosed with LMD based on CSF cytology, spinal MRI, or both. There were 21 discordant results. Nine patients (8.5%) with positive MRI had negative CSF cytology. Twelve patients (11.3%) with positive CSF cytology had negative MRIs. The exact 95% upper bounds on the proportion of patients with LMD whose disease would have gone undetected using either CSF cytology or MRI as the only diagnostic modality were calculated at 14.4% and 17.7%, respectively. CONCLUSION: With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET. Thus, both CSF cytology and spinal MRI should routinely be used to diagnose LMD in patients with medulloblastoma or PNET.
Adolescent↗
Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital.
PURPOSE: The rarity and heterogeneity of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) has precluded meaningful analysis of prognostic factors associated with surgically resected disease. To define a population of patients at high risk of treatment failure who might benefit from adjuvant therapies, we evaluated the relationship between various clinicopathologic factors and clinical outcome of children and adolescents with resected NRSTS over a 27-year period at our institution. PATIENTS AND METHODS: We analyzed the records of 121 consecutive patients with NRSTS who underwent surgical resection between August 1969 and December 1996. Demographic data, tumor characteristics, treatment, and outcomes were recorded. Univariate and multivariate analyses of prognostic factors for survival, event-free survival (EFS), and local and distant recurrence were performed. RESULTS: At a median follow-up of 9.2 years, 5-year survival and EFS rates for the entire cohort were 89% +/- 3% and 77% +/- 4%, respectively. In univariate models, positive surgical margins (P =.004), tumor size > or = 5 cm (P <.001), invasivene (P =.002), high grade (P =.028), and intra-abdominal primary tumor site (P =.055) adversely affected EFS. All of these factors except invasiveness remained prognostic of EFS and survival in multivariate models. Positive surgical margins (P =.003), intra-abdominal primary tumor site (P =.028), and the omission of radiation therapy (P =.043) predicted local recurrence, whereas tumor size > or = 5 cm (P <.001), invasiveness (P <.001), and high grade (P =.004) predicted distant recurrence. CONCLUSION: In this largest single-institution analysis of pediatric patients with surgically resected NRSTS, we identified clinicopathologic features predictive of poor outcome. These variables should be prospectively evaluated as risk-adapted therapies are developed.
Adolescent↗
Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors.
PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.
Adolescent↗
High-dose rate intraoperative radiation therapy for pediatric solid tumors.
BACKGROUND: Sixteen pediatric patients with solid tumors received treatment on a protocol designed to test the feasibility and safety of high-dose rate intraoperative radiation therapy (IOHDR) via a remote afterloader. PATIENTS AND METHODS: Patients with Ewing's sarcoma (n = 5), rhabdomyosarcoma (n = 3), synovial cell sarcoma (n = 2), Wilms tumor (n = 2), osteosarcoma, immature teratoma, desmoplastic small round cell tumor, and inflammatory fibrosclerosis were included. IOHDR was used in the initial management of nine patients and at the time of recurrence in seven. Indications for treatment included gross residual disease in 5 and suspected microscopic disease in 11. The general sites treated were the abdomen (n = 3), chest-wall/thoracic cavity (n = 7), and pelvis (n = 6). All of the patients received multiagent chemotherapy prior to the IOHDR procedure, and 5 had been previously treated with external beam radiation therapy. Separate from the procedure during which IORT was performed, 9 patients underwent an attempt at resection at the time of their initial presentation. A dose of 1200 cGy was prescribed to a depth of 0.5 cm from the surface of a multichannel tissue-equivalent applicator. Complications ascribed to IOHDR included an abscess, delayed wound healing, and cytopenia. Four patients received supplemental external beam radiation therapy to the IOHDR site. At the time of IOHDR, 3 patients had disseminated disease within the pleural cavity and one had pulmonary metastases. RESULTS: With a median follow-up of 18 months, the actuarial rates of local control, metastasis-free, and overall survival at 2 years were 61%, 51%, and 54%, respectively. The patterns of failure were local (n = 1), distant (n = 1), and local + distant (n = 1). Two patients are alive with active disease. Nine are alive with no evidence of disease and the remaining 5 are dead from disease (n = 2), other causes (n = 1), or treatment (n = 2). CONCLUSIONS: The potential to improve local control with high doses of radiation should be balanced against the risk of late effects. The ability to confine the dose of radiation to the primary site and decrease the dose to normal tissues makes IOHDR an important adjunct to external beam radiation therapy. IOHDR can be a safe and integral component in the management of pediatric solid tumors.
Child↗
Results of alternating chemotherapy and hyperfractionated radiation therapy in childhood rhabdomyosarcoma.
BACKGROUND: A regimen of multi-drug chemotherapy alternating with split course hyperfractionated radiation therapy (HFRT) was adopted for the treatment of patients with rhabdomyosarcoma (RMS). The purpose of this treatment regimen was to allow for the timely delivery of radiation and chemotherapy, reduce treatment-related toxicity, and improve compliance. PROCEDURE: Forty-four patients with stages II-IV RMS were treated with HFRT and received 5,400 cGy. The treatment was administered in two courses (3,000 and 2,400 cGy) and separated by a 4-week interval. HFRT consisted of 150 cGy delivered twice a day, 5 days a week with an interfraction interval of 4-6 hours. A limited comparison was made between the HFRT patients and 42 historical patients with comparable clinical characteristics who were treated with similar chemotherapy and conventionally fractionated radiation therapy (CFRT) (median 4,800 cGy, range 4,000-5,680 cGy). RESULTS: HFRT patients completed radiation therapy in 59.1 +/- 9.4 days (mean +/- SD) and CFRT patients completed treatment in 56.6 +/- 10.5 days compared to an expected 52 and 40 days, respectively. With a median follow-up of 55 months for the HFRT patients and 104 months for the CFRT patients, no differences in local control or survival were noted. Nine of 44 (21%) HFRT and 8/42 (19%) CFRT patients experienced local failure. The median time to local failure was 15 months for patients in the HFRT group and 11 months for patients in the CFRT group. CONCLUSIONS: The results of the HFRT regimen were acceptable in terms of toxicity and compliance. No improvement in local control was obtained by alternating radiation and chemotherapy. The lack of difference between patients treated with HFRT and CFRT may be related to the lengthened treatment time of the split course regimen, the small difference in total dose, and tumor repopulation.
Adolescent↗
A hybrid neural network analysis of subtle brain volume differences in children surviving brain tumors.
In the treatment of children with brain tumors, balancing the efficacy of treatment against commonly observed side effects is difficult because of a lack of quantitative measures of brain damage that can be correlated with the intensity of treatment. We quantitatively assessed volumes of brain parenchyma on magnetic resonance (MR) images using a hybrid combination of the Kohonen self-organizing map for segmentation and a multilayer backpropagation neural network for tissue classification. Initially, we analyzed the relationship between volumetric differences and radiologists' grading of atrophy in 80 subjects. This investigation revealed that brain parenchyma and white matter volumes significantly decreased as atrophy increased, whereas gray matter volumes had no relationship with atrophy. Next, we compared 37 medulloblastoma patients treated with surgery, irradiation, and chemotherapy to 19 patients treated with surgery and irradiation alone. This study demonstrated that, in these patients, chemotherapy had no significant effect on brain parenchyma, white matter, or gray matter volumes. We then investigated volumetric differences due to cranial irradiation in 15 medulloblastoma patients treated with surgery and radiation therapy, and compared these with a group of 15 age-matched patients with low-grade astrocytoma treated with surgery alone. With a minimum follow-up of one year after irradiation, all radiation-treated patients demonstrated significantly reduced white matter volumes, whereas gray matter volumes were relatively unchanged compared with those of age-matched patients treated with surgery alone. These results indicate that reductions in cerebral white matter: 1) are correlated significantly with atrophy; 2) are not related to chemotherapy; and 3) are correlated significantly with irradiation. This hybrid neural network analysis of subtle brain volume differences with magnetic resonance may constitute a direct measure of treatment-induced brain damage.
Adolescent↗
Bithalamic involvement predicts poor outcome among children with thalamic glial tumors.
Clinical features and treatment of 36 consecutive pediatric patients with thalamic glial tumors confirmed by histology and characterized by neuroimaging were reviewed to identify prognostic factors. The median age at diagnosis was 10 years (range 1-18 years). Twenty-four patients had low-grade tumors (juvenile pilocytic astrocytoma n = 9, fibrillary astrocytoma n = 6, astrocytomas not otherwise specified n = 6, ganglioglioma n = 2 and oligodendroglioma n = 1) and 12 patients had high-grade tumors (glioblastoma multiforme n = 7, anaplastic astrocytoma n = 4 and unclassified malignant tumor n = 1). With a median follow-up of 4.3 years among survivors, estimates of 4-year progression-free survival (PFS) and overall survival (OS) for the entire group are 28+/-10 and 37 +/- 10%, respectively. Low-grade tumors were associated with a significantly better 4-year PFS (36 +/- 12 vs. 0% for the high-grade group; p = 0.03) and OS (52 +/- 12 vs. 0%; p < 0.001). This review identified that bithalamic involvement, characterized by neuroimaging, exerted an independent and significant negative impact on PFS and OS for patients with low-grade tumors. Estimates of 4-year PFS and OS among patients with tow-grade bithalamic versus monothalamic tumors were 58 +/- 15 vs. 0% and 85 +/- 11 vs. 0% (p < 0.00001), respectively. The presence of bithalamic involvement did not affect outcome among patients with high-grade tumors. Additionally, age at diagnosis, enhancement with neuroimaging contrast, extension beyond the thalamus and extent of surgical resection did not correlate with overall outcome. Because treatment approaches varied during the study period, the impact of radiation therapy or chemotherapy could not be assessed. This contemporary, single-institution series of pediatric thalamic glial tumors demonstrates, for the First time, the statistical significance of bithalamic involvement as a marker of poor prognosis among patients with low-grade glial lesions.
Adolescent↗
Radiation therapy for relapsed CNS germinoma after primary chemotherapy.
PURPOSE: To retrospectively evaluate the ability of radiation therapy to salvage patients with CNS germinoma who relapsed after treatment with primary chemotherapy on a multiinstitution trial that included carboplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Eight patients with CNS germinoma received carboplatin, etoposide, and bleomycin as their only nonsurgical treatment following their initial diagnosis. At the time of relapse each patient received high-dose cyclophosphamide (one to three cycles) followed by craniospinal irradiation (25.2 to 36 Gy) and a boost to the site of recurrent disease (45 to 54 Gy). Six of eight patients had disease at relapse that was more extensive than at diagnosis. One patient had magnetic resonance imaging (MRI) evidence of leptomeningeal enhancement in the cauda equina although CSF cytology was negative, and one patient had cytologic evidence of CSF involvement. The median time to relapse following primary chemotherapy was 17 months. RESULTS: Although myelosuppression was prolonged following the administration of preirradiation chemotherapy, all patients completed a continuous course of radiation therapy. With a median follow-up after radiation therapy of 32 months (range, 16 to 47 months), no failures have occurred. CONCLUSION: Radiation therapy has a proven record of efficacy in the treatment of intracranial germinoma and it remains the standard therapy with which others are compared for treatment response, local control, and overall survival. Arguments can be made for alternative approaches when patients face hormonal or neurocognitive dysfunction as a result of radiation therapy; however, any reduction in late effects will have to be weighed against the probability of survival if alternative approaches prove to be inferior.
Adolescent↗
Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.
PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.
Antineoplastic Combined Chemotherapy Protocols↗
Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors.
PURPOSE: This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue (ABMR) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation. PATIENTS AND METHODS: Patients underwent surgery and/or conventional chemotherapy at the time of recurrence to achieve minimal residual disease (two of these patients also underwent local single-fraction gamma-knife radiosurgery). Myeloablative chemotherapy was then administered with carboplatin, thiotepa, and etoposide (16 patients), thiotepa and etoposide (three patients), or thiotepa, etoposide, and carmustine (BCNU; one patient). Autologous bone marrow was re-infused 72 hours after chemotherapy. Twelve patients received external-beam irradiation after recovery from ABMR. RESULTS: Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years (median, 2.9 years) at ABMR were evaluated. Two patients died of toxicity related to myeloablative therapy. Eight patients died of progressive disease. Ten of 20 (50%) patients (primitive neuroectodermal tumor (PNET)/medulloblastoma, three patients; cerebral PNET, three patients; glioblastoma multiforme, two patients; anaplastic astrocytoma, one patient; pineal PNET, one patient) are alive and disease free at a median of 37.9 months (range, 9.7 to 98.2 months) from ABMR (3-year overall survival [OS] rate of 43% +/- 13% and event-free survival [EFS] rate of 47% +/- 14%]. Seven of these 10 patients also received irradiation post-ABMR. CONCLUSION: Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors.
Antineoplastic Combined Chemotherapy Protocols↗
Delayed-accelerated hyperfractionated radiation therapy for advanced-stage or high-risk rhabdomyosarcoma.
The treatment of six patients with advanced-stage or high-risk rhabdomyosarcoma (RMS) is described. These patients were treated with a delayed-accelerated hyperfractionated radiation therapy (DAHFRT) regimen which delivers 5200 cGy over 20 treatment days. Acceptable early toxicity was noted when radiation therapy was given after a full course of chemotherapy and major attempts at resection of the primary tumor. The DAHFRT regimen has inherent biological and time-intensity advantages compared to other fractionation schemes which may be exploited to improve local control. The DAHFRT regimen should be considered as an alternate fractionation scheme for RMS patients and a possible foundation from which dose-escalation of radiation therapy may be attempted using advanced treatment planning technology. Late effects of high-dose radiation therapy, although a major concern, should assume less priority given the high local failure rates of advanced-stage patients and the advent of conformed radiation therapy treatment planning and delivery which can be used to reduce treatment-related toxicity.
Adolescent↗