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Background:In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested.Methods:The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations.Results:Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively).Conclusion:A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies. [ABSTRACT FROM AUTHOR]

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Improvement of EFS of children older than 3 years with high risk medulloblastoma. Methods: Between 1993 and 1999, 115 patients (3–18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy (‘8in1’ and etoposide/carboplatin) before and after craniospinal radiotherapy. Results: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9–119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. Conclusion: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment. [Copyright &y& Elsevier]

In order to assess the role of genetic predispositionin the induction of radiation-induced tumors, we performed statistical analysis on data from the literature and from our own Institute with regard to theage at onset and the latency period of osteosarcoma as the second primarytumor for retinoblastoma with or without subsequent radiotherapy. In retinoblastomasurvivors who subsequently developed osteosarcoma, the age at onset of retinoblastomawas young (average of 12 months) in both unilateral and bilateral forms. Thissuggests that all or almost all of the patients were genetically predisposedby a mutation of one allele of the RB1 gene. For retinoblastoma patients, osteosarcomas occurred 1.2 years earlier inside than outside the radiationfield. The latency period between radiotherapy and osteosarcoma onset was1.3 years shorter inside than outside the radiation field. Interestingly,a bimodal distribution of latency periods was observed for osteosarcomasarising inside, but not outside the radiation field: 40% occurred after ashort latency, while the latency of the remaining 60% was comparable to thatof osteosarcoma occurring outside the radiation field. This suggests thatdifferent mechanisms may be involved in radiocarcinogenesis. A radiation-inducedmutation of the second RB1 allele may be the cause of osteosarcomas occurring after a short delay, while other genes may be affected in those occurringafter a longer delay. [ABSTRACT FROM AUTHOR]

Currently head and neck squamous cell-carcinomas are staged clinically, though this is not ideal. We did a multivariate prospective study of 234 patients with head and neck squamous-cell carcinoma and showed that high serum concentrations of sIL-2Ralpha at diagnosis were highly correlated with a shorter survival (p<0.0001). In addition, patients who had low serum sIL-2Ralpha concentrations at diagnosis were less likely to develop distant metastasis during the 36 months follow up compared with the group with high serum sIL-2Ralpha concentrations (p<0.001). These findings suggest that serum sIL-2Ralpha could be considered as an independent serum biomarker in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Purpose Due to the extensive initial distant tumour spread in metastatic rhabdomyosarcoma, the importance of local treatment is sometimes underestimated. A retrospective study was conducted to identify the prognostic value of aggressive local treatment in paediatric metastatic rhabdomyosarcoma. Patients Patients with metastatic rhabdomyosarcoma aged 1–21 years treated in France from 1998 to 2011 according to European protocols MMT-4-89, 4-91, 98 and recent national guidelines were selected. Survival comparison were performed between patients with ‘aggressive local treatment’ (surgery and radiotherapy) and exclusive surgery or radiotherapy, after exclusion of patients with early progression. End-points were event-free and overall survival (OS). Results A total of 101 children, median age 9 years, with majority of primaries in unfavourable sites (73 patients, pts), T2 tumours (66 pts), alveolar subtypes (65 pts) and large tumours (>5 cm, 83 pts) received various chemotherapy regimens. On univariate and multivariate analyses, OS was better after ‘aggressive local treatment’ (49 pts; 44.3 ± 8%), than after exclusive surgery (10 pts; 18.8% ± 15.5%) or exclusive radiotherapy (29 pts; 16.1 ± 7.2%, P < 0.006). Moreover, OS was better in the case of surgery with complete resection (41.1 ± 10.2%) or microscopic residue (56.4 ± 14.9%) than macroscopic residue (20.0 ± 12.6%; P < 0.03). Conclusions In this large retrospective analysis, OS appeared to be better for patients receiving ‘aggressive local treatment’ even after adjustment for the initial patient and tumour characteristics. Isolated debulking surgery is associated with a very poor outcome and should be avoided. Aggressive local treatment in patients with rhabdomyosarcoma, even with metastasis, should be seriously considered. [ABSTRACT FROM AUTHOR]

Preclinical studies have demonstrated that triple-negative breast cancer (TNBC) cells are sensitive to PARP inhibitors when used as radiosensitizers. Combining PARP-inhibitors with radiotherapy in TNBC patients may consequently enhance the biological effectiveness of the irradiation ultimately leading to improved locoregional control. We aimed to establish the appropriate dosing and safety profile of Olaparib used as a radiosensitizer in combination with radiotherapy in TNBC patients with residual disease after neoadjuvant chemotherapy. RADIOPARP (NCT03109080) was a prospective phase I dose-escalation trial establishing the tolerance profile of Olaparib combined with breast radiotherapy in high-risk early TNBC patients. Inclusion criteria were resected TNBC with non-complete pathological response after neoadjuvant chemotherapy, or unresectable TNBC despite prior neoadjuvant chemotherapy. Olaparib was started seven days before irradiation and continued during radiotherapy. A time-to-event continual reassessment method was used to increase Olaparib through four increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day) with a 25% maximum probability rate of dose-limiting toxicities (DLT). Radiotherapy delivered 50 Gy to the breast or the chest wall, with or without lymph node irradiation. Toxicities were graded according to CTCAE (version 4.03). Homologous recombination (HR) proficiency status was genetically determined based on shallow whole genome sequencing. Twenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without DLT and the MTD was not reached. With a median follow-up of 34 months, no late treatment-related grade ≥ 3 toxicity was observed, and the maximum observed treatment-related toxicities were limited to grade 2 breast pain (n=2), fibrosis (n=2), deformity (n=1) and telangiectasia (n=1). Three-year OS and EFS were 83% [95% CI: 70%-100%] and 68% [51%-91%], respectively. HR proficiency status was not associated with OS and EFS. Olaparib used as a radiosensitizer in combination with breast radiotherapy in TNBC patients was well-tolerated. The MTD was not reached, and no significant late toxicity was reported. For future trials evaluating the anti-tumor efficacy of this combination, an Olaparib dose of 200 mg twice a day should be considered. [ABSTRACT FROM AUTHOR]

Introduction Le traitement des rhabdomyosarcomes orbitaires (RMSO) comporte de la chimiothérapie associée au traitement local, basé sur la chirurgie ou principalement la radiothérapie. Ces derniers peuvent induire des effets tardifs notables peu décrits. Cette analyse rétrospective monocentrique a pour but de décrire les séquelles pour guider les décisions de décroissance thérapeutique pour cette tumeur de bon pronostic. Population 95 patients atteints de RMSO localisés, paraméningés (26%) ou non, ont été traités à l’Institut Curie entre 1975 et 2010, et 82 ont survécu avec suivi médian de 8,5 ans [0,6–24 ans]. Résultats L’âge médian au diagnostic était de 6 ans [0,7–19 ans]. Le taux de conservation oculaire à 5 ans est de 90% avec une atteinte ophtalmologique séquellaire chez 79%, principalement, cataracte (42%) et lésions cornéennes (40%). L’acuité visuelle résiduelle médiane est 4/10 [< 2/10–10/10]. Des séquelles orbito-faciales sont présentent chez 40% à type d’asymétrie (36%) et d’hypoplasie osseuse (35%) post radiques ou à la chirurgie mutilante (énucléation/exentération, 19%). Conclusions Ces données suggèrent que les séquelles locales tardives sont fréquentes et nécessitent un suivi ophtalmologique prolongé. L’irradiation engendre une morbidité iatrogène notable. [ABSTRACT FROM AUTHOR]

Objective: To assess the visualisation of the left anterior descending (LAD) coronary artery on CT images used for breast radiation treatment planning. Methods: Delineation of the LAD artery was achieved for 25 breast patients by 1 radiologist and 1 radiation oncologist independently on two sets of images for each patient: one pre-operative CT scan using intravenous (IV) contrast media to determine the primary gross tumour volume (GTV) and one post-operative CT scan used for treatment planning. A Student's paired t-test was used to compare the number of CT slices in which the LAD was visible for each patient in the two series. Interpolations and extrapolations of the LAD volume were performed for the left-sided cases using a published heart atlas in order to report doses to the LAD structure. Results: There was a non-significant difference between the results with and without IV contrast media (p=0.34 for the radiologist; p=0.90 for the radiation oncologist). The visible LAD artery corresponded to a 30% portion (range 12-47%) of the interpolated structure. The maximum dose to the left artery varied widely, from 2.7 to 41.7Gy, in the group of patients with left breast tumours. The largest values (>25Gy) corresponded to those patients in whom the LAD artery distal extremity lay inside the breast fields. Conclusions: With the current planning CT protocol, only one-third of the LAD artery could be objectively visualised. Contrast-enhanced imaging used for GTV delineation before the breast surgery did not improve the visualisation of the artery. Advances in Knowledge: This study has revealed the lack of consistency that may be encountered when contouring heart vessels, thereby questioning the reliability of dose reporting. [ABSTRACT FROM AUTHOR]

Background: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse.Methods: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials.Results: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival.Conclusion: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Preclinical studies have found that triple-negative breast cancer (TNBC) cells were sensitive to PARP1 inhibitors. The phase I dose-escalation RADIOPARP trial evaluated in TNBC patients the combination of breast radiotherapy and Olaparib, which was escalated to the target dose of 200 mg twice a day without dose-limiting toxicities. We report the one-year toxicity of this trial.Materials/methods: RADIOPARP is a monocentric prospective open-label phase I dose escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50mg, 100mg, 150mg or 200mg twice a day); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. One-year treatment-related toxicity was graded according to the CTCAE (version 4.03).Results: Twenty-four TNBC patients were enrolled between 09/2017 and 11/2019. Olaparib was escalated to 200 mg twice a day without dose-limiting toxicities. At one-year follow-up, no treatment-related grade ≥3 toxicity was observed (Table 1). Three patients had persistent grade 2 adverse events (breast pain, fibrosis and deformity); there were no cardiac, pulmonary or digestive toxicity.Conclusion: The one-year follow-up of the RADIOPARP phase I trial, evaluating breast radiotherapy with Olaparib in TNBC patients, demonstrated an acceptable toxicity profile of this combination with few low-grade adverse events. [ABSTRACT FROM AUTHOR]

Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (P<0.0001), and in patients of less than 12 months at diagnosis (P<0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (log-rank test; P<0.0001), but also in the subgroup of patients with localised disease (log-rank test, P=0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations. [ABSTRACT FROM AUTHOR]

The size of randomised phase III trials has greatly increased over the last two decades. Several national or multi-national trials, including thousands of patients, are now ongoing, as it is the case in the field of adjuvant therapy for breast cancer patients. We analyse the different parameters conditioning the size of the trial: type I (alpha) and type II (beta) error rates, the expected response (survival rate, recurrence rate...) in the control arm, and the difference in treatment responses between the two arms where detection needs to be considered just as important. In addition we shall discuss the limitations of such very large trials, and the possible alternatives for today and for the future. Very large trials could be considered as a consequence of slow progress compared to what we expect from anti-cancer strategies today. [ABSTRACT FROM AUTHOR]

This study is an analysis of the criteria considered when prescribing concomitant chemotherapy and radiotherapy, as a routine treatment for patients with anal canal cancer, and related complications. Between 1990 and 1996, 67 patients were treated at Institut Curie for invasive, nonmetastatic cancer of the anal canal. Median age was 65 years (range, 35-90 years). TNM stage distribution was as follows: seven T1, 17 T2, 27 T3, 16 T4, and 22 N+ patients. A total of 29 patients (i.e., five T1/T2, and 24 T3/T4) received concurrent chemotherapy and radiotherapy. Radiotherapy volumes and dose and prescribed dose for chemotherapy were not statistically different from one group of patients to another. Only 55% of T3/T4 patients underwent standard chemoradiation treatment for anal canal cancer. Age was the one of main factor in determining if the patient would undergo concomitant chemotherapy or not. For the T3/T4 patients, concomitant chemotherapy was prescribed to 69% of patients <55 years, 90% of patients between 56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients over 75 years (P<0.02).Overall survival at 4 years was 66%. The 4 years overall survival rate of T3/T4 patients, who underwent concomitant chemotherapy, was 72%, and that of T3/T4 patient who did not, was 34% (P<0.04). The patients who did not undergo chemotherapy were significantly older. The difference in cause-specific survival rates (72 vs 48%) was not significant. Relapse-free interval without local recurrence at 4 years was 70%. Relapse-free interval of T3/T4 patients was 78% with chemotherapy and 60% without chemotherapy (p=NS). Rates of treatment discontinuation and early toxicity were not statistically different. Late complications occurred in 33 patients, eight of whom had grade 2/3 tumours. At 2 years, complications occurred in 39% of patients who had undergone concomitant chemotherapy, and in 20% of patients who had not (p<0.02). Differences in grade 2/3 complications were not significant. In conclusion, although radiotherapy with concomitant chemotherapy is considered the current ‘gold-standard’ treatment for anal canal cancer, in our daily experience, only 55% of our T3/T4 patients have undergone this treatment. The remainder did not undergo chemotherapy mainly because they were deemed too old. In this series, no increase in local control and cause-specific survival was observed in patients who received concomitant chemotherapy; this may be due to the small number of patients included in the series. The increased rate of late complications observed in patients who received the combined treatment, however, provides evidence that this treatment should be restricted to younger patients without comorbidity and therefore justifies our position. Perhaps reduction of doses of chemotherapy must be discussed for older patients.British Journal of Cancer (2003) 89, 2057-2061. doi:10.1038/sj.bjc.6601378 www.bjcancer.com [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the efficacy of low-dose chemotherapy in infants with localised and unresectable neuroblastoma (NB). All consecutive infants with localised NB and no N-myc amplification were eligible in the SFOP-NBL 94 study. Primary tumour was deemed as unresectable according to imaging data showing any risk of immediate resection. Diagnostic procedures and staging were conducted according to INSS recommendations. For children, provided that they had no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit), chemotherapy consisted in low-dose cyclophosphamide (5 mg(-1)kg day(-1) x 5 days) and vincristine (0.05 mg kg(-1) at day 1)-CV and repeated one to three times every 2 weeks until surgical excision can be safely performed. No postoperative treatment was given. Between January 1995 and December 1999, 134 consecutive infants with localised NB were registered in the study, of whom 39 had an unresectable NB without N-myc amplification. Among them 28 had no threatening symptom and received CV according to the protocol. Objective response was observed in 14 (50%) and the other 14 were given second-line chemotherapy because of no response. Surgery was attempted in 38 patients including 14 after CV alone, leading to complete resection in 23. Relapses occurred in four patients all local. Survival and event-free survival were 100 and 90+/-5% with a median follow-up of 55 months (range 33-93). In conclusion primary low-dose chemotherapy without anthracyclines is efficient in about half of the infants presenting with an unresectable NB and no N-myc amplification, allowing excellent survival rates without jeopardising their long-term outcome even for nonresponding patients who received standard regimen. [ABSTRACT FROM AUTHOR]

Childhood malignant brain stem tumours have a very poor prognosis with a median survival of 9 months despite radiotherapy. No chemotherapy has improved survival. However, carboplatin has been reported to have activity in glial tumours as well as antitumour synergy with radiation. Our aims were to test the response rate of these tumours to carboplatin alone and to evaluate the efficacy on survival of carboplatin alone followed by concurrent carboplatin and radiotherapy. Patients younger than 16 years with typical clinical and radiological presentation of infiltrating brain stem tumour, as well as histologically-documented cases in the atypical forms, were eligible. Two courses of carboplatin (1050 mg/m2 over 3 days) were administered initially. This treatment was followed by a chemoradiotherapy phase including five weekly carboplatin courses (200 mg/m2) and conventional radiotherapy. 38 eligible patients were included. No tumour response was observed after the initial phase. This schedule of first-line carboplatin followed by concurrent carboplatin and radiotherapy did not improve survival. [Copyright &y& Elsevier]

Background: The production of the cytokine interferon gamma (IFN gamma) by activated peripheral blood mononuclear cells may be reduced in patients with invasive cervical carcinoma. This study was designed to assess the prognostic value of intratumoral IFN gamma messenger RNA (mRNA) levels in such patients.Methods: Biopsy specimens of primary cervical lesions were obtained from 27 patients with invasive squamous cell carcinoma before they received any therapy. Two prognostic groups were considered: 1) a group of 14 patients who had no apparent disease recurrence and who were alive 2 years after diagnosis (good-prognosis group) and 2) a group of 13 patients who had disease recurrence or died during the 2-year follow-up (poor-prognosis group). A competitive reverse transcription-polymerase chain reaction assay was used to measure levels of IFN gamma and beta actin mRNA. The expression of human leukocyte antigen (HLA) class II proteins (which is stimulated by IFN gamma) in tumor cells was studied by immunostaining.Results: Tumor specimens from all 14 patients in the good-prognosis group contained more than 10(3) IFN gamma mRNA copies per 5 x 10(5) beta actin mRNA copies, whereas tumor specimens from only six of the 13 patients in the poor-prognosis group contained this level of IFN gamma mRNA (two-sided P = .006). No clear relationship was observed between levels of IFN gamma mRNA and T-cell or natural killer cell infiltration in tumors; however, a statistically significant association was observed between HLA class II expression on tumor cells and IFN gamma mRNA levels (two-sided P = .01).Conclusions: A subgroup of poor-prognosis cervical carcinoma patients who have low levels of intratumoral IFN gamma mRNA was identified. [ABSTRACT FROM AUTHOR]

Objectifs: Le neuroblastome (NB) est un cancer pédiatrique avec une grande hétérogénéité clinique. Des nombreuses altérations génétiques récurrentes ont été décrites : une amplification de MYCN associée à un pronostic pauvre, ainsi que des variations de la ploïdie ou des altérations chromosomiques segmentaires (délétions du chromosome 1p, 3p, 4p, 11q ; gain du chromosome 2p, 17q) dont l’importance pronostique reste à être déterminée. Afin d’étudier l’association de ces altérations génétiques entre elles et leur impact pronostique, nous avons entrepris une analyse en CGH-array d’une grande série de NB. Méthodes: 389 échantillons de NB ont été analysés en hybridation génomique comparative (CGH), sur une puce d’ADN à BAC/PAC avec une résolution moyenne de 1Mb. Résultats: L’analyse du profil génomique permet de distinguer 2 différents types d’instabilité génétique : une instabilité numérique et une instabilité segmentaire. L’instabilité numérique est caractérisée par une variation en nombre de chromosomes entiers sans altérations segmentaires (n = 162). Elle est associée à une survie sans progression et une survie globale excellente. L’instabilité segmentaire se caractérise par des translocations chromosomiques déséquilibrées. Elle a été observée dans des tumeurs sans (n = 45) ou avec (n = 97) variations numériques, ou en association avec une amplification de MYCN (n = 67). Ce type génomique est associé à un risque élevé de rechute (p < 0.0001, log-rank test), quel que soit le type de l’altération segmentaire. En analyse multivariée, après prise en compte du type génomique, des altérations génétiques individuelles et des caractéristiques cliniques, un profil génomique de type segmentaire est le marqueur pronostique le plus fort (p < 0.0002). Les autres marqueurs retenus sont l’age (p = 0.022) et le stade (p = 0.06). Conclusion: Dans le NB, un profil génomique de type segmentaire est le marqueur pronostique le plus fort. Ceci souligne l’importance du mécanisme à l’origine des translocations déséquilibrées dans l’oncogenèse du NB. Le typage génomique devra donc être pris en compte pour l’attribution à un groupe de risque et la stratification thérapeutique. Le NB est le premier modèle de l’utilité d’une classification génomique pour une meilleure prise en charge thérapeutique. [Copyright &y& Elsevier]

Abstract: Introduction: Malignant sacrococcygeal (SC) germ cell tumours (GCT) may be diagnosed as primary pelvic tumour or malignant recurrence of foetal SC teratoma (FSCT) operated during the neonatal period. In order to evaluate the difference between these two populations, the authors report their experience with SC-GCT registered in the French TGM 95 protocol. Population and methods: The protocol comprised risk-adapted-chemotherapy (CT) followed by surgery. Standard risk (SR: localized tumour completely resected) had no adjuvant therapy. Intermediate-Risk (IR: localized tumour, incomplete or no initial surgery with αFP<15,000 ng/ml) received Vinblastine–Bleomycin–Cisplatin regimen; while High-Risk (HR: αFP > 15,000 ng/ml and/or metastases) received Etoposide–Ifosfamide–Cisplatin. Results: Fifty-seven patients with SC-GCT, aged 0–80 months (median 16), were registered between 1995 and 2005. Nineteen patients had secondary SC-GCT after FSCT. All patients received CT: 17 IR and 1 SR after reevolution; 39 HR (25 with metastases). 51 patients underwent delayed surgery, which was incomplete in 8 patients. Evolution: Seventy-two percent of the secondary SC-GCT had systematic biological follow-up. αFP increasing was the first presenting sign in 80% of the cases. Patients with secondary SC-GCT had a lower median αFP level at diagnosis, were less frequently classified as HR and received less CT. The two groups with secondary vs. primary SC-GCT had a statistically similar favourable outcome (Overall Survival: 93.8% vs. 86.2%; Event-Free Survival: 89.2 vs. 78.2%; p > 0.34 and >0.32), respectively, but with less burden of therapy. Conclusions: SC-GCT has a good overall prognosis provided complete surgery is achieved and CT is administered to IR and HR patients. SC-GCT in patients followed by αFP after treatment for FSCT had less tumour extension than newly-diagnosed patients, probably because of earlier detection of the disease. [Copyright &y& Elsevier]