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Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy. Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu). Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value. Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value. Trial registry: ClinicalTrials.gov identifier: NCT03426657. [ABSTRACT FROM AUTHOR]

Background: A combined modality treatment employing radiation and chemotherapy plays a central role in the management of solid tumors. In our study, we examined the cytotoxic and radiosensitive effect of the microtubule stabilizer epothilone B on two human epithelial tumor cell lines in vitro and its influence on the microtubule assembly.Methods: Cancer cells were treated with epothilone B in proliferation assays and in combination with radiation in colony-forming assays. For the analysis of ionizing radiation-induced DNA damage and the influence of the drug on its repair a γH2AX foci assay was used. To determine the effect of epothilone B on the microtubule assembly in cells and on purified tubulin, immunofluorescence staining and tubulin polymerization assay, respectively, were conducted.Results: Epothilone B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC(50) values in the low nanomolar range. Colony forming assays showed a synergistic radiosensitive effect on both cell lines which was dependent on incubation time and applied concentration of epothilone B. The γH2AX assays demonstrated that ionizing radiation combined with the drug resulted in a concentration-dependent increase in the number of double-strand breaks and suggested a reduction in DNA repair capacity. Epothilone B produced enhanced microtubule bundling and abnormal spindle formation as revealed by immunofluorescence microscopy and caused microtubule formation from purified tubulin.Conclusion: The results of this study showed that epothilone B displays cytotoxic antitumor activity at low nanomolar concentrations and also enhances the radiation response in the tumor cells tested; this may be induced by a reduced DNA repair capacity triggered by epothilone B. It was also demonstrated that epothilone B in fact targets microtubules in a more effective manner than paclitaxel. [ABSTRACT FROM AUTHOR]

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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.)

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4 + 5.4) Gy. Concurrently, irinotecan 40 mg m(-2) once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m(-2) twice daily were administered. Surgery was performed 4-6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand-foot syndrome at the 825 mg m(-2) dose level. The maximum tolerated dose of capecitabine was 750 mg m(-2). Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Early gastric cancer (EGC) can present an indication for local resection procedures under pertain circumstances. Especially endoscopic mucosal resections (EMRs) and laparoscopic resections or those combined with endoscopy have been made possible in recent years.Methods: From 1996 to 2004, of a total of 425 patients with gastric cancer, 58 patients with EGC (13.6%) were prospectively analyzed and observed. Of these, 35 patients had preoperatively diagnosed submucosal infiltration and subsequently underwent gastrectomy and standard lymphnodectomy. Of the 23 patients with intramucosal EGC, 22 underwent local resection. One patient displayed lymph node and liver metastasis at the time of diagnosis and received chemotherapy following staging laparoscopy.Results: Among the 23 patients with intramucosal EGC, 13 were female and 10 male. The average age of the patients was 77.4 years (range: 69-86). The rate of lymph node metastasis was 12.5% (n = 35) for submucosal EGC and 4.3% (n = 23) for intramucosal EGC. Twenty-two patients with intramucosal EGC underwent local resection (four EMR, six laparoscopic intragastric resection, 12 laparoscopic wedge resection). The average tumor size was 1.2 cm (range 0.3-2.3). The definitive histological findings yielded in all patients tumor-free resection margins without venous or lymphangic infiltration. In 10 of 18 patients undergoing laparoscopic resection a simultaneous sentinel lymph node sampling (4 +/- 3 LN) was performed. There were no metastases detected. Method-specific complications did not occur. The morbidity of this patient group was 13.6% (three of 22). Mortality was zero. The average postoperative hospital stay was 6.5 days (range 2-12). In the median follow-up of 30.3 months (range 1-86) no recurrences have yet been diagnosed. Four patients died within the observation period of non-cancer-related causes.Conclusions: Minimally invasive local resection of intramucosal EGC represents a favorable option when strict determination of indication has taken place. [ABSTRACT FROM AUTHOR]

Zielsetzung der adjuvanten/neoadjuvanten Therapie des Rektumkarzinoms ist die Reduktion der lokalen Rezidivrate und der Fernmetastasierungsrate im Vergleich zur alleinigen Operation. Bis vor kurzem war die postoperative Radiochemotherapie die Standardbehandlung im UICC-Stadium II und III. Aufgrund randomisierter Studien findet derzeit ein Paradigmenwechsel hin zur neoadjuvanten Behandlung statt. Schwedische und niederländische Studien zeigten, dass durch eine präoperative Bestrahlung mit 5 × 5 Gy eine Reduktion der lokalen Rezidivrate im Vergleich zur alleinigen Operation erreicht wird. Die kürzlich publizierte deutsche Studie der AIO/CAO/ARO ergab, dass durch eine neoadjuvante Radiochemotherapie im Vergleich zur postoperativen Behandlung eine signifikante Verbesserung der lokalen Rezidivrate sowie eine Senkung der akuten und chronischen Toxizität der Behandlung erreicht werden kann. Im Vergleich zur präoperativen Behandlung mit 5 × 5 Gy, kann die neoadjuvante Radiochemotheraopie bei tief sitzenden Tumoren eine Sphinkter erhaltende Therapie ermöglichen. Unbefriedigend ist derzeit noch die hohe Rate an Fernmetastasen mit 30-40%. Eine Intensivierung der präoperativen Radiochemotherapie mit Oxaliplatin oder CPT-11 verdoppelt im Vergleich zu allein 5-FU-basierten Schemata die pathologische komplette Remissionsrate. Ob dies auch in Kombination mit einer intensivierten postoperativen Chemotherapie zu einer Reduktion der Fernmetastasierungsrate führt, soll in geplanten randomisierten Studien abgeklärt werden. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy intensified with irinotecan in patients with locally advanced rectal cancer. Eligible patients had nonmetastatic disease at a locally advanced stage that made R0 resection and sphincter preservation uncertain. They received preoperative radiation over 6 weeks to 45 Gy and boost of 5.4 Gy and concurrent continuous infusion 5-fluorouracil 250 mg m(-2) day(-1) and weekly irinotecan 40 mg m(-2). In all, 37 patients entered the study. T stage at baseline as determined by ultrasound was T2/T3/T4 in 2/19/16 patients; 31 patients had lymph node involvement. The predominant toxicity was diarrhoea (grade 3/4 in 10/2 patients). Haematologic toxicity and surgical complications were moderate. Among 36 patients undergoing surgery, 32 (89%) had R0 resection and 23 (64%) sphincter preservation. Pathologic complete response (pCR) was achieved in eight (22%) of 36 patients, and 10 patients (28%) had only microscopic residual disease. At 4 years, overall survival was 66%, disease-free survival 73%, local relapse rate 7%, and distant failure rate 24%. Extent of resection and postoperative nodal status were significant predictors of overall and disease-free survival. Intensified neoadjuvant chemoradiotherapy with irinotecan can be safely administered and results in a high pCR rate. [ABSTRACT FROM AUTHOR]

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Copyright of Fresenius' Zeitschrift für Analytische Chemie 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.)

A response by the authors to a comment by Dr S. Papagrigoriadis on their article "Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study," published in Vol. 94 of this journal is presented.