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Oxaliplatin in der perioperativen, multimodalen Behandlung (präoperative Chemoradiotherapie, TME-Chirurgie und postoperative Chemotherapie) des Rektumkarzinoms – eine monozentrische Analyse –

dc.contributor.advisorLiersch, Torsten Prof. Dr.
dc.contributor.authorMichels, Beate
dc.date.accessioned2021-02-10T10:22:24Z
dc.date.available2021-02-18T23:50:02Z
dc.date.issued2021-02-10
dc.identifier.urihttp://hdl.handle.net/21.11130/00-1735-0000-0005-1568-F
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-8414
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-8414
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc610de
dc.titleOxaliplatin in der perioperativen, multimodalen Behandlung (präoperative Chemoradiotherapie, TME-Chirurgie und postoperative Chemotherapie) des Rektumkarzinoms – eine monozentrische Analyse –de
dc.typedoctoralThesisde
dc.title.translatedOxaliplatin in the perioperative, multimodal treatment (preoperative chemoradiotherapy, TME surgery and postoperative chemotherapy) of rectal cancer - a monocentric analysis -de
dc.contributor.refereeBraulke, Friederike PD Dr.
dc.date.examination2021-02-11
dc.description.abstractengDue to conflicting study results, the use of oxaliplatin (OX) in perioperative multimodal treatment (MMT) for locally advanced adenocarcinoma of the rectum (LARC; clinically staged as cUICC stages II or III) is not recommended in national S3 guidelines "ColoRectal Carcinoma" (2019). Preoperative chemoradiotherapy (CRT: RT with 50.4 Gray combined with 5-fluorouracil (5-FU)), total mesorectal excision (TME) and adjuvant chemotherapy (CTx) with 5-FU continues to be considered as standard. Between 07/2006 to 06/2016, a total of 177 LARC patients (55 w, 122 m; median age: 63 years) was treated at the university medical center of Göttingen (UMG) according to clinical trial protocols. Feasibility, toxicity (NCI-CTCAE criteria, version 4.03), and compliance to MMT (+/- OX) were investigated as well as treatment efficacy. Patients with cUICC stages II (4%), III (91%) and IV (5%), all localized < 12 cm above anal verge, were divided into cohort A (n=64, control: CRT + TME + adCTx (5-FU), B (n=63, intensified MMT: CRT+OX + TME + adCTx (FOLFOX) and C (n=50, total neoadjuvant treatment, TNT: CRT+OX + 3 applications of FOLFOX + TME). In 98% RT and 95% CTx, the planned preoperative CRT could be administered (5% dose reduction). The amount of toxicity ≥ CTC-grade 3 was < 5%. For patients of cohorts A and B, postoperative adCTx was associated with low rates of toxicity (≥ CTC-grade 3: < 8%) and resulted in patient`s compliance of 77% (23% dose reduction). After surgery pathological control of specimen revealed optimal, moderate or poor quality of TME in 79%, 18% and 3% (according to MERCURY criteria), respectively. Sphincter-saving low anterior resections were performed in 71%. R0- and negative CRM-status (≥ 2 mm resection margin without cancer cells) as well as MMT-induced shrinkage in tumor extent (ypTE: ≤ 25 mm) were achieved in 96%, 92% and > 50%, respectively. Postsurgical staging revealed stages ypUICC-0 to -IV in 14.5%, 23.1%, 27.7%, 24.9% and 9.6%, respectively. During median follow-up of 73 months, distant metastases were diagnosed in 31.3% and local recurrences in 5.4% of patients. Univariate analyses showed differences in DFS for MMT-induced tumor regression (p = 0.001), ypCRM (p = 0.002) and ypTE (p = 0.023) status as well as in ypUICC stages (p < 0.0009). In multivariate CSS analysis (forest plot), ≤ ypUICC stages II had longer CSS (p = 0.007; HR: 0.31; 95% CI: 0.14-0.73). The use of OX in perioperative MMT is safe, easy to apply and leads to strong early tumor regression, good compliance and promising survival, especially in TNT (cohort C).de
dc.contributor.coRefereeMeyer, Thomas Prof. Dr.
dc.subject.gerRektumkarzinom, Oxaliplatin, Multimodaltherapie, totale neoadjuvante Therapie, Überlebenszeiten (DFS und CSS)de
dc.subject.engRectal cancer, oxaliplatin, multimodal therapy, total neoadjuvant therapy, survival times (DFS and CSS)de
dc.identifier.urnurn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1568-F-8
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullChirurgie - Allgemein- und Gesamtdarstellungen (PPN619875968)de
dc.description.embargoed2021-02-18
dc.identifier.ppn1748057588
dc.creator.birthnameSkubichde


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