PubMed Health⌕ Search

Biomedical subjects

J F Delemarre

Publications and source records attributed to J F Delemarre.

At least 19 recordsLinked to original sources
PubMed1999

New definitions of focal and diffuse anaplasia in Wilms tumor: the International Society of Paediatric Oncology (SIOP) experience.

BACKGROUND: Unlike the original definitions of focal (FA) and diffuse anaplasia (DA) in Wilms tumor (WT), recently redefined FA and DA proved to be of prognostic significance. The aim of the study was to analyze WT from the SIOP file, the majority of which were treated with preoperative chemotherapy, in order to investigate whether chemotherapy influenced the presence of anaplasia, whether the new definitions were applicable to these tumors, and whether they were of prognostic significance. PROCEDURE: The unilateral anaplastic WT of children up to 16 years of age from the SIOP 6 and 9 nephroblastoma trials and studies were first classified according to the original definitions and analyzed. Then they were reclassified and analyzed according to the new definitions. RESULTS: Anaplasia was diagnosed in 86 (5.5%) of 1,554 unilateral WT. The age at diagnosis ranged from 9 to 175 months (median, 63) and more than half of children were over 5 years of age. From 15% to 85% of the tumor mass showed chemotherapy-induced changes. Blastemal anaplasia was seen in 74, stromal in 23, and epithelial in 22 cases. According to the original definitions, FA was diagnosed in 55 (64%) and DA in 31 (36%) cases. In total, 48% children were alive and well, including 53% with FA and 39% with DA (P = 0.23). When reclassified, 39 old FA cases were moved to the new DA group, resulting in 70 (81%) DA and 16 (19%) FA cases. The female-to-male ratio for FA changed from 1.9:1 to 1:1 while remained unchanged for DA. The percentage of FA stage I cases increased from 31% to 44%, while it decreased from 25% to 6% for stage III. For other stages it remained virtually unchanged. The overall 4-year actual survival was 75% for FA and 41% for DA (P = 0.03). CONCLUSIONS: Preoperative chemotherapy did not obliterate or produce anaplasia. The new definitions were applicable to pretreated cases and they were of prognostic significance.

Adolescent↗
PubMed1999

Misstaging in nephroblastoma. Causes and consequences. A report of the Sixth Nephroblastoma Trial and Study of the International Society of Paediatric Oncology.

In the Wilms tumour trials and studies of the International Society of Paediatric Oncology (SIOP), the postoperative treatment is based on the extension (stage) and the histological type. Incorrect staging results in under- or overtreatment. The authors studied the causes and consequences of misstaging in SIOP 6. In this study, the final stage was defined by a central panel of pathologists after review of the surgical and histopathological forms and study of representative microscopical sections. In 46 out of 509 trial patients there was a discrepancy between the final stage and the stage determined at the participating centres: 33 patients were understaged of whom 27 survived more than 5 years (18% died) and 13 patients were overstaged of whom 11 survived more than 5 years (15.3% died). All children with tumour extension into the renal pelvis and treated as stage I instead of stage II survived without evidence of disease. Therefore, it was decided to treat these children in the next study as a stage I. In 17 cases the treatment was based on the surgical stage before the pathological stage was known or the treatment was given according to the stage determined by the local pathologist without waiting for the panel review. The numbers are too small to conclude on the consequences of overtreatment on late effects. For all clinicians the main and most important conclusion of this study is: wait for the final pathology report before initiating postoperative therapy.

Adolescent↗
PubMed1998

Is partial nephrectomy appropriate treatment for unilateral Wilms' tumor?

PURPOSE: After nephrectomy for unilateral Wilms' tumor (WT), two potential hazards threaten the remaining kidney. The development of a metachronous WT (2% to 3%), and decrease in renal function after chemotherapy. Our study aims included: (1) to clarify how many WT patients could benefit from partial nephrectomy (PN) without jeopardizing the high cure rate, (2) to establish the function of the kidney remnant, and (3) to test the radiological criteria for preoperative selection of PN candidates. METHODS: A retrospective analysis of 90 consecutive cases of histologically verified WT (1982 to 1992) was carried out. Data were studied independently by the surgeon, the radiologist, and the pathologist. The preoperative selection criteria for PN were functioning kidney, tumor confined to upper or lower pole leaving two thirds of the kidney tumor free, and no hilar or vascular structures involved. After PN, renal function was estimated by a calculated creatinine clearance (CC) combined with the assessment of the relative function of each kidney by renal scintigraphy. RESULTS: There were 46 boys and 44 girls with median age at diagnosis of 3 years 6 months (range, 3 months to 16 years 7 months). Stage I disease occurred in 40 patients, stage II in 23, stage III in 16, and stage IV occurred in 11 patients. Nearly all patients received preoperative chemotherapy. Radiological analysis of 85 available data sets (5 missing) suggested that PN was possible in 13 patients, and data were inconclusive in two. All 13 patients selected by the radiologist appeared to be in agreement with the pathological criteria for resectability. Of these cases, complete resection by PN was performed in five, could have been possible in retrospect in two, and appeared impossible in six. In two more patients, PN was performed; in both cases the radiologist had predicted PN to be impossible. Median follow-up after PN was 61 months, range, 45 to 167 months. Two patients died of distant metastasis, and no local recurrence occurred. Five are in remission with a median CC level of 110 mL/min, range, 85 to 124. Relative functions of the kidney remnants were 20% to 50%. Contralateral nephrectomy for progressive obstruction was performed in one, but CC level remained normal (85 mL/min). Comparing the preoperative radiological prediction with the combined surgical and pathological findings in a 2 x 2 frequency table, the sensitivity of the radiological findings could be calculated to be 80%, the specificity 97%, and the accuracy 87%. CONCLUSIONS: (1) Partial nephrectomy is safe in approximately 10% of Wilms' tumor patients. (2) The function of the kidney remnant remains well, and even permits contralateral nephrectomy. (3) Preoperative imaging shows an accuracy of 87% to predict the possibility for partial nephrectomy.

Child, Preschool↗
PubMed1997

Second malignant neoplasms in patients treated on SIOP Wilms tumour studies and trials 1, 2, 5, and 6.

The incidence of second malignant neoplasms (SMNs) was investigated among 1,988 patients with complete data, enrolled in the SIOP Wilms tumor trials and studies 1, 2, 5, and 6, treated between September 1971 and October 1987. By the end of 1992, eight SMNs were documented, whereas only 1.3 were expected (standardized incidence ratio [SIR] = 4.15; 95% CI = 1.79, 8.17). The risk increases in the first 10 years from diagnosis, while no apparent excess of risk is observed in the subsequent periods. This finding however is difficult to interpretdue to the low statistical power. The cumulative incidence of a second cancer observed at 15 years after Wilms tumor diagnosis was 0.65%. Six SMNs were registered in the cohort of patients treated in the SIOP studies 1, 2 and 5 (999 cases) compared to the two cases observed in the SIOP6 cohort (989 cases). If the suggested reduced incidence of second cancers between SIOP1-5 and SIOP6 patient cohorts is confirmed by longer follow-up, it might reflect changes in the treatment protocols.

Adolescent↗
PubMed1997

Ewing's sarcoma of the pelvis: changes over 25 years in treatment and results.

The pelvic localisations of Ewing's sarcoma have the worst prognosis due to large size at diagnosis, frequent distant metastases, radiosensitive organs next to the tumour and difficult surgery. The purpose of the present study was to analyse treatment results over a period of 25 years and to investigate the impact of newer chemotherapy schedules, improved radiotherapy techniques and newer surgical methods on the prognosis. 35 children and young adults were identified from 1967 to 1994 for whom diagnosis, presentation, performed treatment and outcome were available. Tumour size, as measured from CT scans, response to chemotherapy and radiotherapy target volume, could be reviewed in the later years. Actuarial 5-year survival for the whole group was 31% and for the 24 non-metastatic patients 40%, with a disease-free interval of 19%. Tumour size could be measured in 27 patients and ranged from 36 to 1540 cm3. There were 12 local recurrences, 1 in the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients developed local failure. 3 patients had adequate fields and one a close field which did not cover completely the prechemotherapy extent and 3 of these recurred. All 4 patients with stable disease after neoadjuvant CT failed locally, not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended to be shorter in patients without local relapse. There was no significant difference in survival before and after 1983.

Adolescent↗
PubMed1996

Rhabdoid tumour of the kidney: a clinicopathological study of 22 patients from the International Society of Paediatric Oncology (SIOP) nephroblastoma file.

We present 22 (0.9%) cases of rhabdoid tumour of the kidney diagnosed amongst 2392 renal tumours in children. The patients ages ranged from 3 weeks to 94 months (median 7 months) and the female:male ration was 1.2:1. Clinically, they presented with an abdominal mass but four (18%) children also had hypercalcaemia and one (4.5%) developed a brain tumour (primitive neuroectodermal tumour). None of the children presented with stage I disease, five (23%) had stage II, ten (46%) stage III, and five (23%) stage IV disease. Two (9%) patients had bilateral tumours. Histologically, the vast majority (20/22) of the tumours exhibited a classical pattern but other histological patterns were also noted. Immunohistochemical studies performed in 12 cases showed vimentin positivity in all cases, CAM 5.2 in eight, epithelial membrane antigen in six, neuron specific enolase in four, S-100 protein in eight, and desmin in one case. In only 12 of the 22 tumours was there agreement between the reporting pathologist and the panel on a diagnosis of rhabdoid tumour of the kidney. Eight tumours originally diagnosed as rhabdoid tumour of the kidney were found to be other renal tumours and in another ten cases the initial diagnosis was changed by the panel to rhabdoid tumour. Metastases developed in 18 (82%) of the children--in eight they were present at the time of diagnosis and in 10 they developed from 2 weeks to 9 months after initial diagnosis. Metastases were found in the lung, abdomen, lymph nodes, liver, bone and brain. Of the 19 children with adequate follow-up, only two (10.5%) with stage II disease are alive, while 17 (89.5%) died 2 weeks to 20 months after the diagnosis.

Adolescent↗
PubMed1994

The expression pattern of contractile and intermediate filament proteins in developing skeletal muscle and rhabdomyosarcoma of childhood: diagnostic and prognostic utility.

In order to investigate whether rhabdomyosarcoma (RMS) can be related to equivalent stages of skeletal muscle development, muscle tissue of 21 human foetuses and 112 primary RMSs were characterized immunohistochemically using antibodies directed against vimentin, desmin, muscle-specific actin (HHF35), sarcomeric actin (sr-actin), smooth muscle actin (sm-actin), and troponin-T. During fetal skeletal muscle development, all myotubes/fibres of the first and second generations expressed desmin, HHF35, and sr-actin. Vimentin was almost exclusively present in immature primary and secondary myotubes/fibres. Troponin-T was expressed in immature myotubes/fibres of the first and second generations as well as mature fibres of the second generation. Sm-actin was never expressed. Vimentin was expressed in 96 per cent of primary and 98 per cent of relapsed RMS; HHF35 in 96 and 98 per cent, respectively; desmin in 95 and 100 per cent; troponin-T in 82 and 75 per cent; sr-actin in 71 and 86 per cent; and sm-actin in 13 and 17 per cent. The proportion of RMS cells reacting with vimentin, HHF35, and desmin was consistently higher than those expressing sr-actin and troponin-T. Neither the shape nor size of neoplastic RMS cells nor the histopathological types were related to the expression pattern of the investigated markers. RMS with aberrant expression of two or more markers predicted a worse prognosis than RMS in which at most one marker was aberrantly expressed (25 per cent and 54 per cent 10-year survival, P = 0.01). These results demonstrate that HHF35, desmin, sr-actin, and troponin-T have the potential to confirm the commitment of the tumours to the myogenic pathway which supports the diagnosis of RMS. However, it was impossible to relate RMS to equivalent stages of skeletal muscle development. Aberrant marker expression by RMS cells correlated significantly with patients' survival.

Actins↗
PubMed1994

Histopathological classification of childhood rhabdomyosarcomas: relationship with clinical parameters and prognosis.

To define a useful and prognostically relevant classification system for rhabdomyosarcomas (RMSs), tissue sections of 113 well-documented, protocol-treated cases were retrieved from the files of the Emma Kinderziekenhuis Amsterdam, the Netherlands, and reclassified by a panel of pediatric pathologists. The following subtypes were recognized: embryonal RMS (n = 66), alveolar RMS (including the solid variant) (n = 16), botryoid RMS (n = 11), embryonal sarcoma (n = 6), and spindle cell RMS (n = 5). Nine cases were classified as RMS not otherwise specified (NOS). The above-mentioned histopathological subtypes correlated significantly with survival (P = .005) in patients with nonparameningeal tumors. Indeed, the best prognosis was observed in patients with spindle cell RMS, embryonal sarcoma, and botryoid RMS (10-year survival rates of 80% to 86%). Patients with embryonal RMS had an intermediate prognosis (10-year survival rate of 55%) and patients with alveolar RMS fared poorly (10-year survival rate of 9%). Survival rate was poor in patients with a localized parameningeal tumor, irrespective of histopathological subtype (10-year survival rate of 33%). Furthermore, this study confirmed the known impact on prognosis of localization (P = .008) and tumor node metastasis (TNM) stage (P = .0005). Classification of RMS subtypes proved to be fairly well reproducible (kappa ranging from 0.47 to 0.85 and percentage of concordance ranging from 50% to 85%). The best agreement was noted in botryoid RMS and the worst in embryonal sarcoma. However, improvement of agreement was noted for the latter subtype during the consecutive classification sessions. In summary, this study shows the strong prognostic value of histopathological subtypes and parameningeal tumor localization.

Child↗
PubMed1994

Histopathological features and grading in rhabdomyosarcomas of childhood.

Rhabdomyosarcoma represents a large group of soft tissue sarcomas displaying heterogeneous histopathological features. In addition to their histopathological classification, the variable expression of a number of histopathological features may contribute to the heterogeneity and may be related to prognosis. Tissue sections of 113 well-documented, protocol-treated patients with long term follow-up (mean 6 years) were analysed by a panel of four paediatric pathologists. The following features were assessed: presence of rhabdomyoblasts, degree of maturation of rhabdomyoblasts, heterogeneous maturation patterns, mitotic activity, tumour necrosis, myxoid component, and septa. A scoring system was allocated to each index. High degree of maturation (amount of cytoplasm greater than surface area of the nucleus), absence of tumour necrosis (< 10% of tumour surface), and absence of septa (< 10% of tumour surface) significantly correlated with a favourable clinical course. Reproducibility in the assessment of these three features was good: mean kappa varying from 0.53 to 0.64. A rhabdomyosarcoma score function for survival was defined by: (-0.27 x degree of maturation score) + (0.007 x percentage septated area) + (0.031 x percentage tumour necrosis). Based on the score a two-grade system was elaborated, i.e. grade I (score < -0.20) v. grade II (score > or = -0.20). Rhabdomyosarcoma grade appeared to be the best factor in predicting patients survival: 69% long-term survival in patients with grade I v. 33% in patients with grade II (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Expression of developmentally regulated muscle proteins in rhabdomyosarcomas.

Human skeletal muscle differentiation and maturation follows a precise sequence of events. To investigate whether and to what extent rhabdomyosarcoma (RMS) cells follow a comparable sequence, 29 fresh frozen specimens of RMS (14 primary and 15 relapses) were immunostained with antibodies directed against developmentally regulated myosin heavy chains (MHC), ie, fetal, fast, and slow MHC, in addition to desmin and vimentin. Four distinct patterns of expression were observed: I) RMS cells expressing exclusively vimentin and desmin (n = 7), II) in addition to expression of vimentin and desmin, a minority of neoplastic cells were immunoreactive with fetal MHC (n = 6), III) in addition to pattern II, fast MHC was expressed (n = 7), and IV) RMS cells simultaneously expressing vimentin, desmin, fetal, fast, and slow MHC (n = 9). Accordingly, the proportion of the MHC immunoreactive RMS cells increased gradually along with the four patterns of expression evolving from less than 25% up to 75% for fetal MHC, from less than 25% up to 50% for fast MHC, and up to 25% for slow MHC in the last category. Vimentin and desmin were coexpressed by almost all RMS cells. Double immunostaining revealed that comparable with the myogenic cells in the developing fetal skeletal muscle, expression of fetal MHC could be demonstrated in the same neoplastic cells either in conjunction with fast or slow MHC. In contrast, only in RMS, slow MHC expression in conjunction with fast MHC could be observed in the neoplastic cells. Neither the shape or size of neoplastic RMS cells, nor the histopathological types, nor tumor localization were related to the expression pattern of developmentally regulated MHC (fetal, fast, and slow MHC). These results confirm the commitment of the RMS cells to the myogenic pathway and demonstrate a restricted and aberrant differentiation pattern of the neoplastic cells in RMS compared with normal myogenesis, independent of histopathological types of RMS.

Adolescent↗
PubMed1993

Excess of multifocal tumors in nephroblastoma: implications for mechanisms of tumor development and genetic counseling.

Referring to the mutational theory of carcinogenesis in embryonal tumors, it is commonly accepted that patients with multifocal tumors are hereditary cases. This is based on the implicit assumption that each tumor results from a single mutational event occurring in a cell that has already inherited a mutation, and that these tumors are independent. We studied the distribution of tumors in 1,868 cases where the focality was known (SIOP 1, 2, 5 and 6). Using all the supposed gene carriers (bilateral and unilateral multifocal cases), and assuming a Poisson distribution of tumors, we estimated the mean number m of tumors in each kidney to be 0.37. Comparing the observed distribution of cases to the expected one, we found a very bad fit to this hypothesis (P < 10(-9)). This is due to an excess of multifocal tumors, particularly in unilateral cases. These findings have important implications in genetic counseling, since the usual practice of considering multifocal tumor patients as hereditary cases may result in a large overestimate of the recurrence risk in such cases. The implications for the mechanisms of tumor development are also discussed.

Chi-Square Distribution↗
PubMed1993

Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes.

We analyzed the management of regional lymph nodes in 110 patients with squamous cell carcinoma of the penis treated at the Netherlands Cancer Institute between 1956 and 1989 with curative intent. Of 66 patients who presented with unsuspected nodes 57 were placed on a surveillance program, while lymph node dissection was performed in 5 (with adjuvant external radiation therapy in 1) and 4 were treated with external radiation therapy only. The management of 40 patients with clinically suspected nodes included surveillance in 5, lymph node dissection in 27 (with adjuvant radiotherapy in 11), biopsy in 4 and external radiation therapy in 4. Postoperative radiotherapy had been given if more than 2 nodes were involved or when extracapsular growth was observed. Overall, 25 patients had a regional recurrence, 5 of whom could be cured subsequently. All regional recurrences developed within 2 years after primary treatment. Analysis showed 100% survival in histologically proved node negative patients (stage pN0). The success of lymph node dissection was related to the extent of the metastatic spread and to the number of involved nodes. Patients with 1 positive node and unilateral inguinal involvement showed a statistically significant survival advantage compared to patients with more extensive spread. Considering the indications for node dissection we found a clear relationship among T category, grade and the probability of lymph node invasion. Patients with stage T1 tumors and stage T2, grades 1 and 2 tumors presented significantly less often with lymphatic invasion than those with other categories of disease and were less likely to have a regional recurrence after treatment of the primary tumor only. In these categories we recommend surveillance of the regional lymph nodes in patients who present with unsuspected nodes. However, patients with stage T2 grade 3, stage T3 and operable stage T4 tumors should undergo an immediate inguinal node dissection because of the high probability of clinically occult lymph node invasion (in our material more than 50%). With respect to the extent of the node dissection, we found that the likelihood of spread to the contralateral and/or pelvic regions was related to the number of invaded nodes in the inguinal region. We recommend contralateral node dissection and unilateral pelvic node dissection when 2 or more positive nodes are found in the dissected groin specimen. Primary pelvic node dissection should be performed in patients who present initially with cytologically or biopsy proved positive inguinal nodes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Prognostic importance of DNA flow cytometric variables in rhabdomyosarcomas.

AIM: To determine whether DNA ploidy patterns and S phase fraction offer prognostic information in patients with rhabdomyosarcoma (RMS). METHODS: DNA flow cytometry was performed on formalin fixed, paraffin wax embedded samples from primary tumours, and metastatic deposits or recurrences in 70 patients. DNA histogram analysis was done using a semi-automated cell cycle analysis program. RESULTS: Of the 70 primary tumours, 23 were DNA diploid, 32 DNA aneuploid, eight DNA multiploid, and seven DNA tetraploid. The prognosis for DNA aneuploid patterns was favourable, intermediate within the group of DNA tetraploid tumours and poor among patients with DNA diploid and DNA multiploid tumours (p = 0.009). In multivariate analysis (Cox regression model) DNA ploidy was an important independent prognostic factor, along with TNM stage, localisation, and histopathological classification. Ten out of 32 patients with a high S phase fraction (> 15%) with primary RMS achieved long term survival in contrast to 20 out of 29 patients with a low S phase fraction (< or = 15%) (p = 0.008). In 24 cases the DNA ploidy of cases of relapse was analysed. Of the 15 cases, in which stem line changes had occurred, 13 died of disease. No stem line changes were noted in nine cases and in this group four patients died of disease (p = 0.02). CONCLUSIONS: Assessment of DNA ploidy and S phase fraction in primary RMS and evaluation of stem line changes in cases of relapse are important variables in predicting prognosis.

Adolescent↗
PubMed1993

Second cancer risk following testicular cancer: a follow-up study of 1,909 patients.

PURPOSE: Improved survival in testicular cancer has been accompanied by concern about long-term side effects of therapy. We assessed the evolution of second cancer (SC) risk over a prolonged follow-up period, which has been rarely studied in large patient series. PATIENTS AND METHODS: We estimated the risk of SCs in 1,909 patients with testicular cancer diagnosed in the Netherlands from 1971 to 1985. Complete medical information was obtained up to at least January 1988 for 92% of patients. Median follow-up was 7.7 years. For 89% of second tumors the diagnosis was confirmed through review of histologic slides; for an additional 8%, the diagnosis was verified by pathology reports only. RESULTS: Seventy-eight patients developed a SC 1 year or more after start of treatment, as compared with 47.6 expected on the basis of incidence rates in the general population (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.1). The mean 15-year actuarial risk of all SCs was 9.8% (95% CI, 7.5% to 12.8%). Significantly increased RRs were observed for all gastrointestinal cancers combined (RR, 2.6; 95% CI, 1.7 to 3.9), stomach cancer (RR, 3.7; 95% CI, 1.8 to 6.8), contralateral testicular cancer (CLTC) (RR, 35.7; 95% CI, 21.8 to 55.2), and leukemia (RR, 5.1; 95% CI, 1.4 to 13.0). Patients who had received irradiation to the paraaortic lymph nodes and who survived testicular cancer for more than 5 years were at particularly high risk of developing stomach cancer (RR, 6.9; 95% CI, 3.3 to 12.7). The median interval between the diagnosis of testicular cancer and stomach cancer was 12.4 years. Patients treated with chemotherapy (CT) did not experience an increase in SCs in general. Indeed, CT-treated patients, as compared with those who received radiotherapy (RT), or surgery alone, had significantly reduced risk of CLTC. This finding might be attributed to an eradicating effect of CT on carcinoma in situ or subclinical CLTC. The excess risk of leukemia was not found to be clearly related to CT. CONCLUSION: Testicular cancer patients who receive RT experience elevated risk of gastrointestinal tumors. CT does not seem to increase SC risk and may even decrease the risk of a CLTC. Following testicular cancer, the 15-year actuarial risk of all SCs is only about half the risk experienced by patients with Hodgkin's disease.

Adult↗
PubMed1993

Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor.

PURPOSE: The Sixth International Society of Pediatric Oncology study (SIOP6) concerned Wilms' tumor with favorable histology, preoperatively treated to obtain a high rate of stage I patients, and sought to reduce treatment for patients with stage I and stage II negative nodes (IIN0) tumors and to find better therapy to prevent relapses in stage II positive nodes (IIN1) and stage III patients. PATIENTS AND METHODS: Eligible patients (N = 509) had received four weekly doses of vincristine (VCR) and two courses of dactinomycin (AMD) preoperatively and were assigned after surgery, according to stage and lymph node involvement, to three different prognostic groups, which were to be randomized. Stage I patients (n = 303) received VCR and AMD either for 17 weeks (S) or 38 weeks (L). Stage IIN0 patients (n = 123) received either 20 Gy irradiation (R+) or no irradiation (R-) and received VCR and AMD for 38 weeks. Stage IIN1 and III patients (n = 83) received intensified VCR and AMD (INTVCR) versus VCR, AMD, and Adriamycin (ADRIA; Doxorubicin Farmitalia Carbo Erba, Rueil, Malmaison, France; doxorubicin). Assessment criteria were 2-year disease-free survival (DFS) and 5-year survival (SURV) percentages. A stopping rule was added that took into account abdominal recurrences for the stage IIN0 trial. RESULT: A 52% rate of stage I tumors was obtained, with a low rate of ruptures (7%). The 2-year DFS and 5-year SURV rates according to the different therapeutic groups were stage I, 92% versus 88% (equivalent) and 95% versus 92% for S and L, respectively; stage IIN0, 72% versus 78% (stage equivalent) and 88% versus 85% for R+ and R-, respectively; and stage IIN1 and stage III, 49% versus 74% (P < .029) and 77% versus 80% for INTVCR and ADRIA, respectively, which results in an 82% DFS and 89% SURV rate for the entire trial population. However, six abdominal metastases observed during the first year of follow-up (FU) in the R- group versus none in the R+ group resulted in discontinuation of the stage IIN0 trial. CONCLUSION: Risk-adapted therapy to limit risk of sequelae is possible. More intensive chemotherapy is necessary to prevent abdominal recurrences in nonirradiated stage IIN0 patients treated preoperatively. A three-drug protocol is necessary in stage IIN1 and stage III patients.

Adolescent↗