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Purpose: We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients.Patients and methods: We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy.Results: OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had longer OS than those who did not, in all 215 patients and in the NA and NoNA groups (P = 0.000). In several multivariate analyses, completing radiotherapy was a universally favorable prognostic factor, while neoadjuvant therapy was never identified as a negative prognostic factor.Conclusion: In our series of unresected patients receiving neoadjuvant treatment, in spite of the delay in starting radiotherapy, OS was not inferior to that of a similar group of patients with no delay in starting radiotherapy. [ABSTRACT FROM AUTHOR]

Resumen Objetivo Estudiar el impacto clínico en el manejo de los pacientes de la 18 F-fluorocolina ( 18 F-COL) en la recurrencia de neoplasias cerebrales primarias. Material y métodos Se estudió prospectivamente a 21 pacientes con sospecha de recidiva de neoplasia cerebral primaria mediante PET/TC cerebral con 18 F-COL en uso compasivo. La distribución por patología de los pacientes estudiados fue: 3 astrocitomas grado ii , 3 astrocitomas grado iii , un oligodendroglioma grado ii , 3 oligodendrogliomas grado iii , un oligoastrocitoma grado iii , 4 glioblastomas multiformes, una gliomatosis cerebri y 5 meningiomas. Se consideraron positivos los estudios en los que había una captación visualmente significativa respecto al fondo del parénquima cerebral. Resultados Diecisiete de los pacientes fueron positivos, comprobándose dicho resultado por histología (10 de ellos) o seguimiento clínico y por neuroimagen, sin hallarse falsos positivos o negativos. El índice target to backgroud ratio medio para los positivos fue de 8,02 y para los negativos de 0,94, lo que representa una diferencia significativa (p = 0,003). Conclusión La PET/TC con 18 F-COL presenta resultados alentadores en la valoración de pacientes con sospecha de recidiva. Aim To study the usefulness of 18 F-fluorocholine (FCH) in detecting the recurrence of primary brain tumours. Material and methods A prospective study was conducted on brain PET/CT with FCH for compassionate use in 21 patients with suspected recurrence of a primary brain tumour. The distribution by pathology was: three grade ii astrocytomas, three grade iii astrocytomas, one grade ii oligodendroglioma, three grade iii oligodendrogliomas, one grade iii oligoastrocytoma, four glioblastoma multiform, one gliomatosis cerebri, and five meningiomas. Studies in which there was a visually significant uptake in the brain parenchyma were classified as positive. Results A total of 17 patients were classified as positive, with the results being confirmed by histology (10 cases) or clinical follow-up and imaging, with no false positives or negatives. The mean SUVmax for positive patients was 8.02 and 0.94 for the negative ones, which was significantly different ( P =.003) Conclusion PET/CT with FCH shows encouraging results in the evaluation of patients with suspected recurrence of primary brain neoplasms. [ABSTRACT FROM AUTHOR]

Purpose: Over the past years, radiotherapy techniques have changed significantly. The impact of these changes in the management of nasopharyngeal carcinoma (NPC) has not been fully evaluated. Methods/patients: Between 1984 and 2014, 223 NPC were diagnosed in our hospital. Prior to 2000, patients were treated with 2D treatment plan (RT2D) that evolved to 3D schemes thereafter (RT3D). Results: Tumors in the RT3D period showed significantly lower stages than those in the RT2D period. 5-year cause-specific survival improved from 55.7% (95% CI: 46.7-64.7%) in the RT2D period to 78.7% (95% CI: 68.7-88.7%) in the RT3D period ( P = 0.006). This difference was greater for non-keratinizing NPC, where specific survival went from 63.2% (95% CI: 52.2-74.2%) to 84.4% (95% CI: 74.4-94.4%) ( P = 0.014). Conclusion: Recent changes in treatment strategies including concurrent chemoradiation and 3D radiotherapy may have impacted in better survival for NPC. Improved imaging techniques may have contributed by earlier detection and better treatment planning. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ. Patients and methods: Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks. Results: Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44 %) had gross total resection. O-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9 % (95 % CI 9.3-40.0 %). The median PFS and overall survival (OS) were 4.2 months (95 % CI 3.6-5.4 months) and 7.3 months (95 % CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19 %; 95 % CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50 % events) of 9.5 months (95 % CI 7.9-23.6) and 15.4 (95 % CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed. Conclusions: This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy. [ABSTRACT FROM AUTHOR]

Standard treatment for glioblastoma multiforme is surgery followed by radiotherapy and chemotherapy, generally with temozolomide. However, disease recurs in almost all patients. Diagnosis of progression is complex given the possibility of pseudoprogression. The Response Assessment in Neuro-Oncology criteria increase the sensitivity for detecting progression. Most patients will not be candidates for new surgery or re-irradiation, and anticancer drugs are the most common approach for second-line treatment, if the patient's condition allows. Antiangiogenics, inhibitors of the epidermal growth factor receptor, nitrosoureas, and re-treatment with temozolomide have been studied in the second line, but a standard therapy has not yet been established. This review considers currently available medical treatment options for patients with glioblastoma recurrence. [ABSTRACT FROM AUTHOR]

Background This phase I trial assessed safety, pharmacokinetics (PK), dose limiting toxicity (DLT), maximum tolerated dose and recommended dose (RD) of the combination of sorafenib plus ifosfamide in patients with advanced sarcoma. Methods Twelve sarcoma patients (9 soft-tissue, 3 bone sarcoma) were treated with sorafenib plus ifosfamide (starting doses 200 mg bid and 6 g/m respectively). A 3 + 3 dose escalation design with cohorts of 3-6 patients was used. A study to assess the in vitro efficacy of the combination was also conducted. Results Three DLTs were observed: fatigue grade 4 with sorafenib 400 mg bid plus ifosfamide 6 g/m and encephalopathy and emesis grade 3 with sorafenib 400 mg bid plus ifosfamide 7.5 g/m. Other toxicities included diarrhea, hand-foot syndrome, mucositis, neutropenia, skin rash and thrombocytopenia. There were no relevant effects on PK of sorafenib but an increase in ifosfamide active metabolite 4-hydroxy-ifosfamide was observed. Eight patients achieved stable disease lasting more than 12 weeks. An additive effect was observed in vitro. Conclusions RD was sorafenib 400 mg bid plus ifosfamide 6 g/m, allowing administration of active doses of both agents. Limited preliminary antitumor activity was also observed. A phase II study is currently ongoing. [ABSTRACT FROM AUTHOR]

This multicenter phase II study conducted by the Spanish Neuro-Oncology Group evaluated the activity of an extended, dose-dense temozolomide regimen in patients with temozolomide-refractory malignant glioma. Adult patients (at least 18 years of age) with WHO grade III or IV glioma and a Karnofsky Performance Status of 60 or higher were treated with temozolomide (85 mg/m2/day) for 21 consecutive days every 28-day cycle until disease progression or unacceptable toxicity. All patients had developed progressive disease either during or less than 3 months after completing previous temozolomide treatment. Forty-seven patients were treated with a median of 2 (range, 1–13) cycles of temozolomide. Before study entry, patients had received a median of 6 cycles of temozolomide: 39 (83%) as part of initial therapy and 23 (49%) as second-line therapy. Three patients (6.4%) had a partial response with durations of 8.0, 3.5, and 3.2 months; 15 patients (31.9%) had stable disease with a median duration of 2.1 months, including 2 patients with stable disease (SD) for greater than 6 months (14 and 16 months). Median time to progression was 2 months, and median overall survival from study entry was 5.1 months. The 6-month progression-free survival rate was 16.7%. The most common hematologic toxicities were lymphopenia, thrombocytopenia, and leukopenia. Lymphopenia occurred in 83% of patients and was grade 3 in 28%, but no opportunistic infections occurred. In conclusion, this extended dose-dense schedule of temozolomide appears to have modest activity in patients refractory to previous treatment with temozolomide and is associated with manageable toxicity. [ABSTRACT FROM AUTHOR]

The metabolism of all- trans- and 9- cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations. [ABSTRACT FROM AUTHOR]

Metastatic tumors to the gastrointestinal tract are rare; the stomach and small bowel are the most common organs involved. Lung cancer, renal cell carcinoma, breast carcinoma, and malignant melanoma are the most common primary tumors metastatic to the duodenum. We report a metastasis to the duodenum from an adenocarcinoma of the cecum presenting as a duodenal obstruction 4.5 yr after the surgical resection of the primary tumor. The condition of the patient was temporarily controlled with the implantation of an endoduodenal metallic prosthesis as a palliative measure. [ABSTRACT FROM AUTHOR]