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Introduction In 2010, the seventh Tumour-Node-Metastasis (TNM) cancer staging system of the International Union for Cancer Control (UICC) and the American Joint Committee of Cancer (AJCC) introduced a subdivision of M1 in the TNM classification of colorectal carcinomas. For the eighth TNM edition which will be released in the autumn of 2016 and will become effective in January 2017 new proposals are appreciated. The aim of our study was to define a new and better proposal for M1 subclassification. Methods In a total of 814 patients with stage IV colorectal carcinoma treated between 1995 and 2013 prognostic factors were analysed in univariate and multivariate analyses. Results Advanced age, treatment in the earlier period 1995–2003, involvement of multiple metastatic sites, and non-curative resection were found to be independent prognostic factors. In patients with only one metastatic site, survival was good in patients with liver or lung metastasis, moderate in patients with metastasis of the peritoneum or non-regional lymph nodes and poor in patients with other rarely metastatic involved organs. The new proposal defines M1a, Metastasis confined to one organ: liver or lung (2-year survival 51.6%); M1b, Metastasis confined to one organ: peritoneum or non-regional lymph nodes, or Metastasis confined to liver plus lung (2-year survival 39.4%); and M1c, Metastasis confined to one organ: all other sites, or Metastasis in more than one organ, except liver plus lung (2-year survival 21.6%). Conclusion The new proposal can identify three prognostic groups in stage IV colorectal carcinomas with significant differences in survival. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists.Materials and Methods: We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme.Results: Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature.Conclusion: When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel approaches are needed to selectively target mutant forms of EGFR. • Design of a homemade virtual library starting from flavone skeleton. • Three-track virtual screening identified mutant-selective hits. • Synthesis and testing of selected hits in an activity-based enzyme assay. • Nitroflavone scaffold shows selectivity for the EGFR mutants over the wild type one. The inhibition of the Epidermal Growth Factor (EGFR) represents one of the most promising strategies in non-small cell lung cancer (NSCLC) therapy. The recently identified C797S mutation causes resistance of EGFRL858R/T790M against osimertinib, the latest approved third generation EGFR inhibitor. The identification of small molecules capable of selectively inhibiting the T790M mutations also in the late-onset C797S mutation is a desirable strategy and novel chemical structures might provide new insight in the overcoming resistance mechanisms. Here we report the identification of a novel mutant-selective privileged molecular core; guided by a structure-based drug design, a flavone skeleton has been rationally modified, and a virtual library generated. Reversible EGFR inhibitors targeting both L858R/T790M and L858R/T790M/C797S mutations with a higher affinity with respect to the wild type one are discovered via a three-track virtual screening. Selected hits were synthesized and tested in an activity-based enzyme assay against wild-type EGFR, L858R/T790M, as well as L858R/T790M/C797S. The results showed that a nitroflavone-based compound inhibits the phosphorylation of EGFR mutants at low-micromolar concentration showing selectivity over the wild type ones. Structurally similar flavone analogues have been synthesized and the following inhibition assays underlied the importance of both the presence and position of the nitrophenoxy moiety. [ABSTRACT FROM AUTHOR]

Objective The treatment of trigeminal neuralgia is challenging with respect to a sufficient outcome. Medication still represents the basic therapy. If a neurovascular compression syndrome is diagnosed with high resolution MRI more than 80% of the patients undergoing surgery based on microvascular decompression are free of pain in a ten year period as shown in one of our previous follow-up studies. In addition to that, percutaneous treatment options such as thermo-coagulation of the Gasserian ganglion can be effective but are affected with a higher recurrence rate and cannot be used in all cases. Therefore, we started selecting patients with intractable, therapy-resistant trigeminal neuralgia for stereotactic radiosurgery of the trigeminal nerve. Preliminary results of this approach are presented in this study. Methods From 2012 to 2014 eight patients suffering from intractable trigeminal neuralgia underwent linear accelerator-based stereotactic radiosurgery with a Novalis system after fixing a stereotactic frame to the patient’s head under local anesthesia. For the treatment, doses ranging from 60 Gy to 70 Gy were used in a target located at the pontine trigeminal root entry zone of the trigeminal nerve. 80% of the dosage was calculated at a 4mm iso-center. We treated 4 male and 4 female patients (average age 68 years). 4 patients suffered from left-sided and 4 patients from right-sided trigeminal neuralgia. V2 and V3 were the most affected branches. All patients had a history of facial pain for several years with two patients suffering from multiple sclerosis-related trigeminal neuralgia. In all cases, two, three or even four different drugs were used with increasing side effects. For none of the patients, neurovascular compression syndrome was found with MRI. One patient, however, underwent surgery with microvascular decompression. Three patients underwent thermo-coagulation of the Gasserian ganglion once or twice without a lasting effect on facial pain. Four patients had to take a permanent anticoagulation because of pre-existing conditions so that no invasive treatment option could be used. Results Taking into account the follow-up time between 2 years and 1 month, all eight patients had benefit from stereotactic radiosurgery treatment: two patients are completely free of pain without any medication, two patients are free of pain with substantially reduced medication and four patients showed relevant improvement of facial pain including their usual medication or even with reduced medication. In consequence, all patients reported considerably reduced side effects of medication and a relevant improvement in their quality of life. Concerning the side effects of radiosurgery, only one patient developed a facial hypoesthesia. Presumably, this was related to a previous prophylactic brain radiation due to lung cancer. General symptoms such as headache or dizziness were mild and lasted for a short time only. Conclusions The use of linear accelerator-based stereotactic radiosurgery is a safe and effective therapeutic option even for the treatment of intractable and so far therapy-resistant trigeminal neuralgia. It significantly reduces the use of medication and improves the quality of life. In order to prove the adequate long-term control of facial pain further follow-up examinations are necessary with a higher number of patients. However, our preliminary results are encouraging and demonstrate effectiveness in cases where all other treatment options failed. [ABSTRACT FROM AUTHOR]