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B Hero

Publications and source records attributed to B Hero.

At least 19 recordsLinked to original sources
PubMed2006

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004.

AIM: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy has been used in neuroblastoma treatment for many years but its value in high intensive first line treatment protocols is not exactly known. PATIENTS, METHODS: Stage 4 neuroblastoma patients >1 year with (123)I-MIBG positive residual disease (primary tumour and/or metastasis) after complete induction chemotherapy according to the German neuroblastoma trial NB97 were retrospectively analyzed. RESULTS: One-hundred-eleven patients had (123)I-MIBG positive residual disease after complete induction chemotherapy. Forty patients received (131)I-MIBG therapy using a median activity of 0.44 GBq/kg body weight. By univariate analysis, patients who underwent (131)I-MIBG therapy had a better 3-year event free survival (3-y-EFS 46 +/- 8%) and 3-year overall survival (3-y-OS 58 +/- 9%) than 71 patients without (131)I-MIBG therapy (3-y-EFS 19 +/- 5%, p = 0.003; 3-y-OS 43 +/- 6%, p = 0.037). However, subgroup analysis of 66 patients who underwent high dose chemotherapy with autologous stem cell transplantation (ASCT) during treatment found a very similar outcome with (131)I-MIBG therapy (3-y-EFS 49 +/- 9%, 3-y-OS 59 +/- 10%) and without (131)I-MIBG therapy (3-y-EFS 33 +/- 9%, p = 0.171; 3-y-OS 59 +/- 9%, p = 0.285) due to the dominating effect of ASCT. By multivariate analysis, (131)I-MIBG therapy had no impact on EFS (p = 0.494) and OS (p = 0.891). Only ASCT, external beam radiation therapy and MYCN amplification were important for EFS and OS. CONCLUSIONS: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG therapy with emphasis on tumour dosimetry.

3-Iodobenzylguanidine↗
PubMed2006

[Dosimetry for therapeutic treatment of neuroblastoma by 131I-mIBG].

AIM: Targeted radiotherapies using iodine-131 meta-iodobenzylguanidin have long been in use for treatment of stage IV neuroblastoma but reliable dosimetric data are scarce. METHOD: This work presents an approach to determine the whole body exposure and tumour doses delivered during therapy. Dosimetric data are reported and discussed for six treatments carried out according to the trial protocol NB2004 as it is in use in our study in the last two years. RESULTS: Whole body exposures are found to be in the range of 1.75 to 2.5 Gy whereas tumour doses vary between 15 and 55 Gy. CONCLUSION: The course of action prescribed by the trial protocol allows whole body exposure as well as tumour doses to be determined routinely.

3-Iodobenzylguanidine↗
PubMed2004

MYCN-status in neuroblastoma: characteristics of tumours showing amplification, gain, and non-amplification.

While the role of MYCN-amplification (MNA) for risk assessment in neuroblastoma is undisputed, the phenomenon of gene copy excess below the amplification threshold is rarely described. To discuss biological characteristics and the clinical impact of the so-called MYCN-gain versus amplified or non-amplified cases, we investigated the MYCN status of 659 patients uniformly analysed by fluorescence in situ hybridisation. The number of MYCN-amplified tumours in our cohort was 18% (116/659); an additional 38 tumours (6%) displayed MYCN-gain. Both alterations were associated with an advanced stage disease, an increased patient age and further chromosomal alterations. Most of the amplified neuroblastomas displayed 1p aberrations, whereas MYCN-gain tumours correlated with 11q alterations. In contrast to the amplified cases, tumours with gain displayed no increased MYCN RNA levels. MNA versus non-amplification discriminated between good and poor outcomes, independent of stage, age and the degree of amplification. However, patients with amplified tumours showed a significantly better outcome when this was combined with non-stage 4 disease and age <1 year versus stage 4 and age < 1 year. Although MYCN-gain was associated with poor event-free-survival (EFS) in stages 1-3, 4S (P=0.005), this might be related to associated genetic aberrations and not to the MYCN-gain itself. A survival difference between neuroblastomas with gain and single copy MYCN could not be delineated. In conclusion, MNA predicts a poor outcome for neuroblastoma patients of all stages and age. MYCN-gain is also a characteristic feature of advanced stage tumours and older patients, but is not associated with higher MYCN expression and appears not to be discriminative in predicting patient outcome.

Blotting, Southern↗
PubMed2003

Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age.

During the last two decades new diagnostic and therapeutic tools have been utilized to improve the poor survival chances of children with stage 4 neuroblastoma. This study reviews the risk profiles and the long-term outcome of patients from five consecutive German neuroblastoma trials. A total of 96% of all German patients registered at the German childhood cancer registry with neuroblastoma stage 4 over 1 year of age at diagnosis entered one of the trials during 1979-2001. Eight hundred and twenty-eight consecutive children were analyzed retrospectively. In spite of having significantly improved diagnostic tools like bone marrow superstaging and mIBG scintigraphy the stage 4 incidence did not increase after reaching completeness of the registry (5.4 cases/100,000 children at 1-14 years of age; P=0.52). The distribution of the primary tumors and of metastases was constant over the periods. The amount of bone marrow infiltration did not change with time. The risk factors lactate dehydrogenase, ferritin and MYCN, and the clinical risk groups 4A, 4B, 4C also remained constant over the trials with a few exceptions for NB97. The 5-year event free survival increased from 0.01+/-0.01 (NB79) to 0.14+/-0.03 (NB85), 0.16+/-0.04 (NB82), 0.27+/-0.02 (NB90), and 0.33+/-0.04 (NB97). The overall survival rates improved similarly from 0.04 (NB79) to 0.44 (NB97). In conclusion, the improved survival was associated with better treatment and not caused by lower risk profiles in stage 4 neuroblastoma patients.

Adolescent↗
PubMed2003

Tumour markers are poor predictors for relapse or progression in neuroblastoma.

The value of the tumour markers vanillylmandelic acid (VMA) and homovanillic acid (HVA) in urine (u) and serum (s), neurone-specific enolase (NSE), and lactate dehydrogenase (LDH) in the early prediction of relapse/progression in neuroblastoma is not known. We analysed the data of neuroblastoma patients who had successfully completed first-line treatment and had laboratory results available from their initial diagnosis and from relapse/progression (n=196). Patients' overall survival from relapse or progression was 21.5+/-4.2% (mean+/-standard deviation). At diagnosis, we found abnormal results in 75% for VMA and/or HVA (s), 92% for VMA and/or HVA (u), 90% for NSE, and 81% for LDH. We found a lower incidence of abnormal results at relapse or progression with 40% for VMA and/or HVA (s), 54% for HVA and/or VMA (u), 61% for NSE, and 48% for LDH. Sensitivity of all markers was higher for metastatic compared with local recurrence. NSE was the best, being able to detect 42% of the localised relapses, 77% of the combined local/metastatic relapses, and 69% of the metastatic recurrences. Relapse or progression in neuroblastoma cannot be detected reliably by monitoring tumour markers alone. Therefore, follow-up of neuroblastoma patients must include clinical assessment and imaging studies.

Adolescent↗
PubMed2002

Isolation and transplantation of highly purified autologous peripheral CD34(+) progenitor cells: purging efficacy, hematopoietic reconstitution and long-term outcome in children with high-risk neuroblastoma.

We have investigated the purging efficacy of positive selection of autologous mobilized CD34(+) peripheral stem cells in 22 children with high-risk neuroblastoma. CD34(+) cell selection was performed using the method of magnetic-activated cell sorting (MACS). The median purity of the CD34(+) cells post selection was 97.6% (range 81.7-99.7). For detection of contaminating neuroblastoma cells before and after CD34(+) selection, the chimeric anti-disialoganglioside GD2 antibody delta ch 14.18 was used. Prior to positive selection, various numbers of contaminating neuroblastoma cells were found in 17 patients. After positive CD34(+) cell selection, low numbers of neuroblastoma cells were only detectable in four patients. In 18 patients, high-dose chemotherapy was performed and the isolated CD34(+) cells were reinfused. In all patients, a rapid neutrophil recovery was seen with a median time to reach 0.5 x 10(9)/l neutrophils of 12 days (range 8-24 days). Nine of the 18 patients are free of progression with a median follow-up of 55 months (range 45-70 months). Two patients are alive with relapse, six patients died due to progression or relapse and one patient died due to secondary AML 10 months after transplant while in remission from neuroblastoma. In summary, we show that, through a highly effective positive selection method, a high purging efficacy can be obtained without compromising the hematopoietic reconstitution capacity of the graft.

Antigens, CD34↗
PubMed2002

High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma.

Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. From April 1992 to December 1998, 23 evaluable patients received HDC within the German Cooperative Wilms Tumor Studies. Nineteen were given melphalan, etoposide and carboplatin (MEC); the others received different regimens. The dose of carboplatin was adjusted according to renal function. Indications for HDC were high-risk relapse in 20 patients, bone metastases in two patients and no response in one patient. Fourteen of 23 patients are alive after a median observation time of 41 months, 11 of 14 in continuous complete remission, three in CR after relapse post HDC. The estimated survival and event-free survival for these patients are 60.9% and 48.2%. Twelve children relapsed after HDC; nine of them died within 12 months and three are surviving from 20 to 33 months after relapse. The main toxicities were hematologic, mucositis and renal (tubular dysfunction; intermittent hemodialysis in one patient). There were no toxic deaths. About half of the children suffering from Wilms tumor with very unfavorable prognostic factors survive disease-free after HDC for over 3 years. Besides hematological toxicity, mucositis and infections, renal function is at risk during HDC. With dose adjustment on glomerular filtration rate, however, no permanent renal failure was observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Characteristics and outcome of thoracic neuroblastoma.

It has been reported by several groups that thoracic neuroblastoma (NB) are associated with a better outcome than NB of other localisation. Concerning the reason for this phenomenon, however, the findings have diverged and therefore therapeutic recommendations are not uniform. We performed a retrospective analysis of the prognostic factors and surgical results of 113 thoracic NB and compared these to 556 NB of other sites, all treated according to the protocol of the German Cooperative Study NB90. Compared to non-thoracic NB, thoracic NB showed a female preponderance (P = 0.018), more often with localised disease stages 1 - 3 (P < 0.001), lower LDH serum levels (P = 0.027), and less often with MYCN amplification (P = 0.04), while there was no statistically significant difference in the patients' ages and histological grades. In a separate analysis of localised (stages 1 - 3), stage 4 and stage 4 S NB, there were no differences between thoracic and non-thoracic NB in LDH secretion. MYCN amplification was different only in localised NB (P = 0.037). In a multivariate analysis, tumour stage (P < 0.0001), MYCN-status (P < 0.001) and serum-LDH (P = 0.008), but not thoracic localisation, were independent prognostic factors. A complete resection was achieved in 73/104 (70 %) operated thoracic NB, while 25 (24 %) were partially resected and 6 (6 %) only biopsied. Patients with thoracic NB had a better outcome only in stage 4, but not in stages 1 - 3 and 4 S (EFS; P = 0.028). There was no difference for all stages in the event-free survival between completely and incompletely resected tumours. Surgical complications occurred in 34 (20 %) of all operations, some of them severe, although there were no surgical deaths. Our results suggest that although thoracic NB has a relatively favourable prognosis, it should be treated in the same way as NB with non-thoracic localisation, with stratification according to tumour stage and biological properties, such as MYCN status. Radical surgery is only indicated if mutilation and life-threatening complications can be avoided.

Antineoplastic Agents↗
PubMed2002

The impact of surgical radicality on outcome in childhood neuroblastoma.

AIM: Improvement of treatment results for neuroblastoma (NB) has been achieved during recent years, especially by intensifying therapy for advanced NB. Surgery, however, has not contributed very much to this progress and there is still controversy regarding the best approach for high-risk NB. We therefore attempted to find criteria for a differentiated strategy for tumour resection in NB. METHODS: We retrospectively analysed the data of 2251 NB patients treated in the German Cooperative NB Studies NB79 - NB97 (1979 - 1999) including patients' age, tumour stage, MYCN oncogene status, surgical intervention, completeness of resection, surgical complications and outcome. RESULTS: 1148 patients had a localised NB (stage 1 - 3), 878 had stage 4, and 225 had stage 4 S disease. 2112 patients underwent surgery. Tumour resection as the final result of primary or delayed operation was complete in 1403 (66.4 %), incomplete in 449 (21.3 %), and only a biopsy was carried out in 260 (12.3 %) cases. Complete resection was performed most often in localised NB (73.5 %), less often in stage 4 NB (59.2 %) and in stage 4 S (54.5 %). Clinically relevant complications occurred in 19.2 % of all operations independent of the time of resection during treatment, patients' age, tumour stage, tumour site and MYCN status. For 1787 patients from the studies NB79 - NB90 the probability of 5-year event-free survival (EFS) could be analysed and correlated with surgical radicality. In localised NB of patients aged > 1 year there was a significant difference in 5-year EFS between complete, incomplete, and no substantial resection ( P < 0.0001), while this was not the case in infants < 1 year. In the early study period (NB79 - NB85) patients with stage 4 NB had a significantly better 5-year EFS after complete excision of the primary tumour. In contrast, this difference was not confirmed during the later period (NB90) with intensified drug therapy. Timing of surgery did not influence prognosis. For infants with stage 4 S NB there was no difference in outcome after complete or incomplete resection of the primary tumour. MYCN status did not alter the significant relevance of tumour resection for outcome in localised NB. In contrast to MYCN non-amplified stage 4 NB, however, stage 4 NB with MYCN amplification had a significantly better outcome if the primary tumour could be completely or incompletely resected, compared to a biopsy only. CONCLUSIONS: Radical tumour resections with the risk of surgical complications are only justified in children > 1 year with a localised NB. In stage 4 NB, the primary tumour may be resected during intensive multimodal treatment without risky complications. Complete or incomplete resection of the primary tumour improves prognosis only in MYCN-amplified stage 4 NB. Stage 4 S NB with non-amplified MYCN are subject to spontaneous regression; a resection after chemotherapy may be indicated in cases of non-sufficient regression or growth of the primary tumour.

Clinical Trials as Topic↗
PubMed2001

Metabolic activity and clinical features of primary ganglioneuromas.

BACKGROUND: Ganglioneuroma (GN) is considered by most to be a benign tumor of neural crest origin. It may evolve from differentiating neuroblastoma or may be diagnosed as primary ganglioneuroma. The rarity of this tumor and the lack of understanding of its biology often lead to inaccurate diagnosis and treatment. METHODS: The authors analyzed clinical features and biologic behavior of primary ganglioneuroma in 49 patients who were registered with but were not part of the national neuroblastoma trials. Data included age and symptoms at diagnosis, gender, tumor localization and size, (123)I-metaiodobenzylguanidine (mIBG) scintigraphy, secretion of catecholamines, histology, treatment, and outcome, whenever available. RESULTS: Patients with primary ganglioneuroma were significantly older than patients with neuroblastoma. Median age at diagnosis was 79 months compared with 16 months (P < 0.0001). Ganglioneuroma were equally distributed between males and females (1.13:1). A preference of thoracic (41.5%) and abdominal, nonadrenal tumors (37.5%) was observed compared with adrenal GN (21%). At diagnosis, thoracic tumors appeared larger than nonthoracic ones. Local lymph node metastases occurred in two patients. One ganglioneuroma had metastasized to soft tissues. (123)I-mIBG scintigraphy detected mIBG uptake at tumor site in 57% of the GN tumors. Levels of catecholamines in plasma and/or urine were increased in 39%. Slight immaturity of ganglion cells was observed in 93% of all ganglioneuroma tumors. None of the 22 tumors analyzed exhibited MYCN gene alterations. Although 12 patients had macroscopic residuals, no tumor progression or recurrence was observed in a median follow-up of 25 months. CONCLUSIONS: Ganglioneuroma may present with metabolic activity such as increased secretion of catecholamines and/or mIBG uptake. There are no specific diagnostic signs or symptoms discriminating ganglioneuroma and neuroblastoma tumors. Therefore, ganglioneuroma requires tissue investigation for diagnosis. Prognosis after surgical resection without further therapy seems to be excellent.

3-Iodobenzylguanidine↗
PubMed2001

Evidence of chromaffin oxygen sensing in neuroblastoma.

With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.

Animals↗
PubMed2001

Preclinical and clinical aspects on the use of amifostine as chemoprotector in neuroblastoma patients.

BACKGROUND: In several studies in adults, amifostine (WR-2721) and its active metabolite WR-1065 have shown protection against myelo- and nephrotoxicity of chemotherapeutic agents without compromising cytotoxic efficacy to the tumor. PROCEDURE: In the present study, the effect of amifostine and WR-1065 on neuroblastoma tumor growth and its protective potential for hematotoxicity were investigated. Neither amifostine nor WR-1065 reduced the cytotoxic effect of six drugs commonly used for this tumor when tested on neuroblastoma cells in vitro. RESULTS: In mice carrying human xeno-transplanted neuroblastoma, tumor growth and antitumor activity of chemotherapy were unaffected by amifostine. In addition, hematotoxicity of alkylators was relieved in some cases. In patients with neuroblastoma, amifostine only slightly reduced bone marrow toxicity and was highly emetogenic. CONCLUSIONS: Therefore, amifostine warrants further investigation before its widespread clinical use in the treatment of children with neuroblastoma.

Adolescent↗
PubMed2001

Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as response markers in stage 4 neuroblastoma.

BACKGROUND: The early biological response has been proved an excellent predictor in acute lymphoblastic leukemia and nephroblastoma. We asked whether catecholamine metabolites, mIBG scan, and bone marrow evaluation might be relevant response markers in disseminated neuroblastoma. PROCEDURE: Three hundred sixty-seven unselected stage 4 neuroblastoma patients treated according the German cooperative trial NB90 were entered into the study. Catecholamine plasma and urine levels were centrally determined by gas chromatography/ mass spectrometry. Bone marrow cytology and mIBG scans were evaluated by local investigators. RESULTS: At diagnosis, mIBG scan was positive in 306 patients (92%), borderline in seven patients (2%), and negative in 19 patients (6%). Bone marrow aspirates were cytologically positive in 292 patients (84%) and negative in 57 patients (16%). Plasma catecholamine levels were elevated in 79% (206 of 260 patients.), urinary levels in 91% (307 of 338 patients). The outcome of patients with normalized mIBG scan after four courses of chemotherapy [5 year EFS (event free survival) 0.22 +/- 0.07] was not superior to the outcome of patients with still abnormal uptake (5 year EFS 0.30 +/- 0.05). The event free survival of patients with still positive bone marrow aspirates after four courses (0.16 +/- 0.06) was inferior to the EFS of patients with negative bone marrow aspirates (0.26 +/- 0.04, P = 0.0054). Urinary catecholamine normalization after four cycles of chemotherapy (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10) had no influence on outcome, whereas plasma catecholamine normalization after the first (5 year EFS 0.40 +/- 0.09 versus 0.14 +/- 0.07, P= 0.0364) or the fourth cycle (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10, P = 0.0242) indicated a better outcome. CONCLUSIONS: These data show that serial plasma catecholamine levels and bone marrow aspirates in the course of the disease are useful tools in predicting outcome.

3-Iodobenzylguanidine↗
PubMed2000

Testicular and paratesticular involvement by metastatic neuroblastoma.

BACKGROUND: Testicular and paratesticular involvement is a less familiar feature in neuroblastoma and its prognostic impact is unclear. METHODS: The records of 1076 male patients in the German cooperative neuroblastoma treatment trials were searched for patients with testicular or paratesticular involvement. RESULTS: The authors found 11 children with paratesticular or testicular involvement at the time of manifestation of the disease, 3 children with testicular involvement at the time of relapse, and 1 infant with testicular involvement at the time of progression of neuroblastoma from International Neuroblastoma Staging System (INSS) Stage 4S to Stage 4. In de novo disease, the age of manifestation did not exceed 12 months. Two children had paratesticular involvement per continuitatem by growth of a primary tumor through the inguinal channel. All others had distant primary tumor. Prognosis appeared more favorable for infants (3 of 9 died) than for older children (5 of 6 died), for children with involvement of testes and < 10% involvement of bone marrow (2 of 8 died) than for children with other distant metastasis (6 of 7 died), and for children with intrascrotal involvement at first diagnosis (4 of 11 died) than for children with intrascrotal involvement during relapse of the disease (all 4 children died). CONCLUSIONS: Paratesticular or testicular metastasis does not per se indicate unfavorable outcome and is compatible with INSS Stage 4S in infants. The age at diagnosis and the time of manifestation during disease contributed to the prognosis in those patients.

Abdominal Neoplasms↗
PubMed2000

Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas.

BACKGROUND: As traditional parameters do not ensure completely accurate prognostic grouping in neuroblastoma (NB), new molecular markers are needed for assessing the individual patient's prognosis more precisely. PROCEDURE, RESULTS, AND CONCLUSIONS: Based on 133 NB, we show that telomerase activity (TA) is a powerful, independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative 'favorable' clinical or biological subgroups of NB patients. Analysis of gene and protein expression of telomerase subunits suggests that the presence or absence of TA in NB is strongly correlated with expression levels of both the catalytic subunit hTERT and the internal RNA component (hTR).

Disease Progression↗
PubMed2000

Metastatic neuroblastoma in infancy: what does the pattern of metastases contribute to prognosis?

BACKGROUND: The purpose was to investigate the influence of metastatic pattern and primary extension over midline on prognosis of infants with metastatic neuroblastoma. PROCEDURE: Data of 317 consecutive infants with metastatic neuroblastoma were analyzed. RESULTS: The amount of bone marrow infiltration (<10% vs. >10%) proved to be the most important factor and was more important than the presence of bone metastases. A disadvantage in outcome for patients with distant lymph node, intracranial, or atypical metastases or for patients with primary extension over midline could not be demonstrated. However, in the subgroup of patients treated with limited treatment, primary extension over midline proved a risk factor. CONCLUSION: A redefinition of Stage 4S on an international basis is suggested.

Follow-Up Studies↗
PubMed2000

Telomerase activity and telomerase subunits gene expression patterns in neuroblastoma: a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues.

PURPOSE: We have recently demonstrated that telomerase activity (TA) is an independent prognostic factor in neuroblastomas. In the present study, the prognostic impact of TA and gene expression of the three major telomerase subunits is evaluated by molecular and immunohistochemical techniques in fresh-frozen and paraffin-embedded tissues. PATIENTS AND METHODS: One hundred thirty-three neuroblastomas of all stages were analyzed for TA. The TA levels of 75 neuroblastoma cases were correlated with gene expression of telomerase subunits hTRT, human telomerase RNA (hTR), and telomerase protein 1 (TP1) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), using an innovative approach on the LightCycler instrument (Roche Diagnostics, Mannheim, Germany). For selected cases, the applicability of RT-PCR and immunohistochemistry for hTRT expression analysis was investigated in paraffin-embedded tissues. TA and subunit expression patterns were correlated with traditional prognostic indicators and disease outcome. RESULTS: TA was present in a total of 39 (29.3%) of 133 neuroblastomas and in 31 (29.8%) of 104 initial neuroblastomas without cytotoxic pretreatment. TA was significantly correlated with both event-free and overall survival (P <.0001). Furthermore, we found a significant correlation between expression levels of TA and hTRT (P <.0001) as well as hTR (P <.001). Multivariate analysis revealed only TA and tumor stage but not serum lactate dehydrogenase, MYCN amplification, or age at diagnosis as independent prognostic factors. CONCLUSION: The significant correlation with clinical outcome strongly recommends that analysis of TA be incorporated into the clinical investigation of each individual neuroblastoma at the time of diagnosis. Because the mere presence or absence of TA without further quantification is sufficient basis for predicting disease outcome, the telomeric repeat amplification protocol assay could be complemented with but not replaced by analysis of hTRT or hTR expression.

Biomarkers, Tumor↗