Application of Fluorescence in Situ Hybridization to Detect MYCN Amplification on Paraffin-embedded Tissue Sections of Neuroblastoma - Single Institute Study.

BackgroundNeuroblastoma is the most common extracranial solid tumour in children. Amplification of the MYCN gene was observed in approximately 20-30% of tumours. It is strongly correlated with advanced stage of disease, rapid tumour progression, resistant to chemotherapy and poor outcome independent of patient age and stage of advanced disease. Amplification of the MYCN identify high-risk patients.MethodsTo assess neuroblastoma tumours with MYCN amplification we used paraffin-embedded tissue sections in 57 patients by fluorescent in situ hybridization (FISH). ResultsTwenty-eight (49,1%) of patients had localized neuroblastoma (1–3 stages), 5,3% stage 4S, and 45,6% stage 4 disease. Thirty-eight (66,7%) of patients had got abdominal/adrenal mass at diagnosis. Twenty-seven (47,4%) patients were <18 month of age, thirty (52,6%) patients were >18 month of age. MYCN amplification appeared in 12 (21%) tumour specimens. ConclusionsFluorescent in situ hybridization is a high-sensitive, useful technique for detecting MYCN amplification on paraffin- embedded tissue section of neuroblastoma tumours thus facilitating therapeutic decisions based on the presence or absence of this important biologic marker.

The natural history and treatment of non-functioning pituitary adenomas (non-functioning PitNETs)

Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism and manifestations attributed to mass effects on nearby structures. NFpitNETs follow generally an indolent course, but in 5–10% of cases they exhibit more aggressive behaviour, characterised by rapid growth, invasiveness and early recurrence. The initial size of the adenoma, the presence of symptoms and the histological subtype are related to the natural course of NFpitNETs. Active surveillance is usually the strategy of choice in the case of an asymptomatic NFpitNET, while surgical resection is recommended in case of visual and/or neurological abnormalities or rapid tumour growth. Based on previous and emerging data, approximately 50% of patients show tumour growth, while 20% of patients with NF-macroadenomas on active surveillance may require further intervention during a follow-up period of 7 years. Adjuvant radiotherapy is usually considered for large residual tumours or recurrent and/or aggressive adenomas, but there is evidence that medical therapy, especially with cabergoline, can occasionally be beneficial, whereas newer molecular agents are under investigation. Thus, while highly effective medical therapy is awaited, a move towards a more conservative approach seems appropriate, at least until we have better molecular markers of progressiveness.

Case of small bowel perforation secondary to nivolumab and ipilimumab related tumour regression

A 56-year-old man undergoing immunotherapy treatment for metastatic melanoma presented with sudden onset testicular pain radiating into his abdomen. On examination, the abdomen was generally tender with associated guarding. Imaging revealed a perforation of the small bowel at the site of a metastatic lesion. Histology revealed that this process was non-inflammatory in nature. A diagnosis of small bowel perforation secondary to immunotherapy driven rapid tumour regression was made. The patient was treated with a small bowel resection plus anastomosis and made a full recovery. This case highlights the rare potential side effect of immunotherapy in causing non-inflammatory bowel perforations secondary to rapid tumour regression.

A phase I/II study (TaxXel) on the treatment with docetaxel in combination with capecitabin in patients with metastatic esophageal cancer or cancer in the cardia region.

e14531 Background: This is an open label, non-randomized, multicenter phase I-II study with Docetaxel (Doc) given in combination with capecitabine (Cap) in patients (pts) with metastatic oesophageal cancer (mEC) or cancer in the cardia region (mCCR). Methods: In phase I, pts were treated with Cap day 1-14, 22-36 and Doc day 1, 8, 15, 22, 29. Cap was dose escalated from 1300 mg up to 1650mg/m2 per day according to modified Fibonacci design. The dose of Doc was fixed to 30mg/m2 in both Phase I-II. In Phase II 1650mg/m2 Cap was given. The primary objective in phase I was to define a dose of Cap recommended for the Phase II and to determine the feasibility and safety of this treatment. The primary objective in the phase II was to determine the response rate (RR), safety profile, quality of life and survival.The median age was 64.8 years, PS was 0 in 23 pts, I in 57 and II in 13 pts. The histology was as follows: 58 adenoca, 33 squamous cell ca and 2 poorly diff ca. Forty-three pts had previously been treated with chemotherapy, 41 with radiotherapy, 50 were chemotherapy-naive and 31 had underwent surgery. Results: From March 2006 to Oct 2010, 93 eligible pts with measurable disease were enrolled in the study. Fourteen were treated in phase I and 79 in phase II. Four pts (1 in ph I and 3 in ph II) did not receive any study treatment. Twenty-seven pts of 93 (29%) were not evaluable according to study protocol which included CT after 6 w of treatment due to rapid tumour progression and deterioration of general condition. RR was 29%, 2 CR and 25 PR, 15 pts (16%) had SD and 24 pts (26%) had PD. Median OS was 7.3 months (5.76-8.9) and median PFS was 4.2 months (2.3-4.7 months).Treatment related grad 3 or 4 toxicity was as follows: 60% of pts experienced any grade 3 or 4 toxicity, 30% related to infections, 24% had nausea, diarrhea, vomiting, mucositis, <10% had cardiac related symptoms, <1% had an allergic reaction to Doc. Conclusions: Cap together with Doc appears tolerable and has a RR of 29% in selected group of patients with mET and mCCR. Majority of treatment courses were given on out-patient bases. However, there is un urgent need to define an optimal therapy regime and further studies are warranted.

Efficacy of neoadjuvant therapy with cisplatin, fluorouracil, and cetuximab in locally advanced nonresectable epidermoid skin carcinoma

e17008 Background: No standard therapy is known for locally advanced unresectable cutaneous epidermoid carcinoma. Chemotherapy (platin ± fluorouracil) and radiotherapy are commonly used separately or in association (1) mostly as palliative treatments. We report six patients with locally advanced unresectable skin epidermoid carcinomas in whom the association of cisplatin, fluorouracil and cetuximab induced a tumor reduction allowing secondary complete surgical resection. Results: All 6 patients had voluminous tumours located on the face (nose, ear, cheek, forhead). For 5 patients, tumours were recurring after one or several surgical resections. One patient had a rapidly progressing non resectable inflammatory tumour on the nose when he was first diagnosed. All patients received 2 to 3 cycles of chemotherapy associating cisplatin 100 mg/m2 J1, fluorouracil 1,000 mg/m2 J1–5, cetuximab J1-J8-J15 (J1 = J21). Tolerance was manageable. A dramatic response with rapid tumour regression, allowing subsequent surgical resection was observed for all patients. Histology showed a complete sterilisation without any active tumoral residue in 2 patients and complete resection (R0) in the remaining patients. Conclusions: The association of cisplatin, fluorouracil and cetuximab is approved for treatment of metastatic head and neck carcinoma (2, 3) but has not been evaluated yet in cutaneous epidermoid carcinoma. The dramatic tumor responses observed in our 6 patients warrant evaluation of this association both in the neoadjuvant and in the metastatic settings for patients with non resectable skin squamous cell carcinomas. No significant financial relationships to disclose.