Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience

Purpose

We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1–2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies.

Methods

Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan.

Results

Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32 % of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28?±?10 % and 0 %, respectively, for OS, they were 44?±?12 % and 22?±?10 % but no patient was cured. The median PFS after a first relapse was 7 months (range 1–29); the median OS was 7 months (range 4–44). No patients died due to treatment toxicity. Late recurrence (more than 1–2 years after diagnosis) and involvement of single sites were favorable prognostic factors.

Conclusions

Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.     

Evaluation of a PCR/DNA Probe Colorimetric Membrane Assay for Identification of Campylobacter spp. in Human Stool Specimens

DNA was extracted from 50 human stool specimens using the QIAamp DNA stool minikit. PCR amplification was followed by post-PCR hybridization to DNA probes specific for the Campylobacter genus, Campylobacter jejuni, and Campylobacter coli in a colorimetric membrane assay. Thirty-two of 38 culture-positive specimens were PCR/DNA probe positive for C. jejuni. The assay is rapid and simple and can be applied to stool specimens for the detection of Campylobacter.     

Treatment with 5-Fluorouracil/Folinic Acid, Oxaliplatin, and Irinotecan Enables Surgical Resection of Metastases in Patients With Initially Unresectable Metastatic Colorectal Cancer

Background The prognosis of unresectable metastatic colorectal cancer might be improved if a radical surgical resection of metastases could be performed after a response to chemotherapy. Methods We treated 74 patients with unresectable metastatic colorectal cancer (not selected for a neoadjuvant approach) with irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin (FOLFOXIRI and simplified FOLFOXIRI). Because of the high activity of these regimens (response rate, 72%), a secondary curative operation could be performed in 19 patients (26%). Results Four patients underwent an extended hepatectomy, nine patients underwent a right hepatectomy, three patients underwent a left hepatectomy, and three patients had a segmental resection. In five patients, surgical removal of extrahepatic disease was also performed. In seven patients, surgical resection was combined with intraoperative radiofrequency ablation. The median overall survival of the 19 patients who underwent operation is 36.8 months, and the 4-year survival rate is 37%. The median overall survival of the 34 patients who were responsive to chemotherapy, but who did not undergo operation, is 22.2 months (P = .0114). Conclusions The FOLFOXIRI regimens we studied have significant antitumor activity and allow a radical surgical resection of metastases in patients with initially unresectable metastatic colorectal cancer not selected for a neoadjuvant approach and also those with extrahepatic disease. The median survival of patients with resected disease is promising.     

Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: results from the asymptomatic carotid stenosis and risk of stroke study

The aim of this study was to determine the effect of image normalization on plaque classification and the risk of ipsilateral ischemic neurologic events in patients with asymptomatic carotid stenosis. The first 1,115 patients recruited to the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study with a follow-up of 6 to 84 months (mean 37.1 months) were included in this study. Duplex ultrasonography was used for grading the degree of internal carotid artery stenosis and for plaque characterization (types 1-5), which was performed before and after image normalization. One hundred sixteen ipsilateral ischemic hemispheric events occurred. Image normalization resulted in 60% of plaques being reclassified. Before image normalization, a high event rate was associated with all types of plaque. After image normalization, 109 (94%) of the events occurred in patients with plaque types 1 to 3. For patients with European Carotid Stenosis Trial (ECST) 70 to 99% diameter stenosis (equivalent to North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50-99%) with plaque types 1 to 3, the cumulative stroke rate was 14% at 7 years (2% per year), and for patients with plaque types 4 and 5, the cumulative stroke rate was 0.9% at 7 years (0.14% per year). The results suggest that asymptomatic patients with plaque types 4 and 5 classified as such after image normalization are at low risk irrespective of the degree of stenosis.     

Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia

Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.     

Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) often clinically present with metastases to regional lymph nodes. Fine-needle aspiration of neck masses is routinely used to establish the presence of metastatic carcinoma and in turn to initiate a subsequent workup to determine the site of tumor origin. Human papillomavirus (HPV) 16 is an important etiologic agent for HNSCCs that arise from the oropharynx but less so for tumors from non-oropharyngeal sites. HPV16 detection thus provides a strategy for localizing an important subset of HNSCCs, but this approach has not been applied to fine-needle aspiration specimens. EXPERIMENTAL DESIGN: We did in situ hybridization for HPV16 on 77 consecutive aspirated neck masses diagnosed as metastatic squamous cell carcinoma. P16 immunohistochemistry was also done because p16 overexpression may serve as a surrogate marker of HPV-associated HNSCC. RESULTS: HPV16 was detected in 13 of the 77 (17%) aspirates. By site of origin, HPV16 was detected in 10 of 19 metastases from the oropharynx but in none of 46 metastases from other sites (53% versus 0%; P < 0.0001). HPV16 was not detected in 2 branchial cleft cysts misdiagnosed as metastatic squamous cell carcinoma, but it was detected in 3 of 10 metastases from occult primary tumors. P16 expression was associated with the presence of HPV16: 12 of 13 HPV16-positive metastases exhibited p16 expression, whereas only 4 of 62 HPV16-negative metastases were p16 positive (92% versus 6%; P < 0.0001). P16 expression also correlated with site of tumor origin: 13 of 19 oropharyngeal metastases were p16 positive, whereas only 1 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001). CONCLUSIONS: HPV16 status can be determined in tumor cells aspirated from the necks of patients with metastatic HNSCC. Its presence is a reliable indicator of origin from the oropharynx.     

Primary thyroid carcinoma in children: A retrospective study of 20 patients

A total of 20 children (median age 11 years) were treated for primary thyroid carcinoma from 1976 to 1990. Papillary adenocarcinoma was diagnosed in 19 and follicular in one case. Nineteen of 20 patients were considered amenable to surgery, which consisted of total thyroidectomy in 14 and partial thyroidectomy in 5. Only one patient with extensive perithyroid soft tissue infiltration was treated with external beam radiotherapy. Monolateral or bilateral cervical nodal dissection was performed in eight and six children, respectively; in nine cases without clinical evidence of metastatic nodes. Pathological examination showed that tumor extent was greater than that clinically assessed: Multiple tumor foci within the thyroid were assessed in 8/19, unilateral positive nodes in 8, and bilateral in 6, and soft tissue infiltration in 7. Subsequently 10 patients received thyroid-stimulating hormone (TSH) suppressive hormonotherapy. Relapses occurred in 7/20 at 2–48 months (median 18) from primary treatment: Four in cervical nodes, two in cervical nodes and lungs, and one in lungs. These seven patients were salvaged with node dissection and radioiodine therapy for lung metastases. All the 20 children are alive and disease-free after a median follow-up of longer than 10 years. The incidence of relapse was greater in the group of patients not given TSH-suppressive hormonotherapy. Total thyroidectomy produced permanent hypoparathyroidism in 5/14 (36%). Thyroid carcinoma in children of this series frequently presented with multiple tumor foci within the thyroid and cervical node metastases. Prognosis was favourable even after relapse and was not related to the extent of surgical treatment. Limited surgery and suppressive hormonotherapy may be adequate therapy for thyroid carcinoma in children. © 1995 Wiley-Liss, Inc.