on behalf of the Rare Tumors in Pediatric Age Group BACKGROUND: Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. METHODS: A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin. RESULTS: Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported. CONCLUSIONS: This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes.

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We confirm the activity of androgen deprivation therapy in androgen receptor-expressing recurrent/metastatic salivary gland cancers. The hypothesis that an androgen receptor increased gene copy number may represent a possible mechanism of primary resistance should be further investigated.

This study validates the risk grouping previously identified. Risk-driven clinical decision making and trial designs will help in better defining the most appropriate treatment in OPC patients.

Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas (DIPG). Findings on the role of EGFR signaling in the onset of childhood DIPG prompted the use of nimotuzumab, an anti-EGFR monoclonal antibody. Assuming a potential synergy with both radiotherapy and vinorelbine, a pilot phase 2 protocol was launched that combined nimotuzumab with concomitant radiation and vinorelbine. An amendment in July 2011 introduced re-irradiation at relapse. The primary endpoint for first-line treatment was objective response rate (CR + PR + SD) according to the RECIST. This report concerns the outcome of this strategy as a whole. Vinorelbine 20 mg/m(2) was administered weekly, with nimotuzumab 150 mg/m(2) in the first 12 weeks of treatment; radiotherapy was delivered from weeks 3 to 9, for a total dose of 54 Gy. Vinorelbine 25 mg/m(2) and nimotuzumab were given every other week thereafter until the tumor progressed or for up to 2 years. Re-irradiation consisted of 19.8 Gy, fractionated over 11 days. Baseline and latest MRIs were assessed blindly by an outside neuroradiologist. Twenty five children (mean age 7.4 years) were enrolled as of August 2009 (median follow-up 29 months). A response was observed in 24/25 patients (96 %). The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. Eleven of 16 locally-relapsing patients were re-irradiated. One-year PFS and OS rates were 30 ± 10 % and 76 ± 9 %, respectively; 2-year OS was 27 ± 9 %; the median PFS and OS were 8.5 and 15 months, respectively. This strategy generated interesting results and warrants further investigation.

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After successfully using cisplatin (30 mg/m(2)/day) and etoposide (150 mg/m(2)/day) in ten three-day courses for progressive low-grade gliomas, a subsequent protocol reduced the daily doses of cisplatin (to 25 mg) and etoposide (to 100 mg), with the objective of achieving the same response and three-year PFS rates with lower neurotoxicity and myelotoxicity. We treated 37 patients (median age 6 years); 23 had optochiasmatic tumours and nine were metastatic cases. Diagnoses were clinical in 13 cases and histological in 24, and comprised: pilocytic astrocytoma (17), ganglioglioma (3), pilomyxoid astrocytoma (2), and fibrillary astrocytoma (2). Treatment was prompted by radiological evidence of progression and/or clinical deterioration a median 18 months after the first diagnosis. After initial MRI staging, neurological and clinical examinations were performed before each chemotherapy cycle, with MRI after the first three courses and every three months thereafter. After a median 48 months, a volume reduction was appreciable in 24 cases (65%) and response was maximum 12 months after starting treatment. The three-year EFS and OS rates were 65 and 97%, respectively. Clinical, neurological, or functional improvements were seen in 26/37 cases. No children had a WBC nadir below 2,000/mm(3). Audiological toxicity caused damage in 4/34 cases. The previous protocol had achieved volume reductions in 70% of cases, causing audiological damage (data updated) in 11/31 (P = 0.023), with three-year PFS and OS rates of 70 and 100%, respectively. Lower doses of cisplatin/etoposide are still effective in progressive low-grade glioma, with less acute and persistent morbidity.

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