Hans Christian Rischke

Salvage Lymph Node Dissection with Adjuvant Radiotherapy for Nodal Recurrence of Prostate Cancer

PURPOSE We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I–III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Detection of local recurrent prostate cancer after radical prostatectomy in terms of salvage radiotherapy using dynamic contrast enhanced-MRI without endorectal coil.

PurposeTo evaluate the value of dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) without endorectal coil (EC) in the detection of local recurrent prostate cancer (PC) after radical prostatectomy (RP).Material and methodsThirty-three patients with recurrent PC underwent DCE-MRI without EC before salvage radiotherapy (RT). At median 15 (mean 16±4.9, range 12–27) months after completion of RT all patients showed complete biochemical response. Additional follow up post RT DCE-MRI scans were available. Prostate specific antigen (PSA) levels at the time of imaging were correlated to the imaging findings.ResultsIn 22/33 patients (67%) early contrast enhancing nodules were detected in the post-prostatectomy fossa on pre-RT DCE-MRI images. The average pre-RT PSA level of the 22 patients with positive pre-RT DCE-MRI findings was significantly higher (mean, 0.74±0.64 ng/mL) compared to the pre-RT PSA level of the 11 patients with negative pre-RT DCE-MRI (mean, 0.24±0.13 ng/mL) (p<0.001). All post-RT DCE-MRI images showed complete resolution of initial suspicious lesions. A pre-RT PSA cut-off value of ≥0.54 ng/ml readily predicted a positive DCE-MRI finding.ConclusionsThis is the first study that shows that DCE-MRI without EC can detect local recurrent PC with an estimated accuracy of 83% at low PSA levels. All false negative DCE-MRI scans were detected using a PSA cut-off of ≥0.54 ng/mL.

3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions in patients with Prostate Cancer – an interobserver variability study

PurposeTo evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers.Material and methods90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties).ResultsGTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation.ConclusionsUsing T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application.

Correlation of the Genotype of Paragangliomas and Pheochromocytomas with Their Metabolic Phenotype on 3,4-Dihydroxy-6-18F-Fluoro-l-Phenylalanin PET

Paragangliomas and pheochromocytomas are genetically heterogeneous diseases. The purpose of this study was to determine the sensitivity and specificity of PET with 3,4-dihydroxy-6-18F-fluoro-L-phenylalanin (18F-DOPA) for the detection and staging of pheochromocytomas/paragangliomas. Furthermore, we assessed whether the genotypes of pheochromocytomas and paragangliomas correlate with the uptake of 18F-DOPA. Methods: We retrospectively analyzed 101 consecutive patients who underwent 18F-DOPA PET or 18F-DOPA PET/CT for known or suspected pheochromocytomas or paragangliomas. Maximum 18F-DOPA tumor uptake was quantified relative to uptake in the liver. Results: Histopathology, cross-sectional imaging, and follow-up indicated the presence of paragangliomas and pheochromocytomas in 68 patients and the absence of a tumor in 33 patients. The average 18F-DOPA uptake by paragangliomas and pheochromocytomas, expressed as a tumor-to-liver ratio, was 5.9 ± 5.2. There was no significant difference in uptake among patients with von Hippel Lindau syndrome (VHL; n = 19), succinate dehydrogenase B–D mutation (n = 21), neurofibromatosis type 1 (n = 1), RET (n = 1), no germline mutation (n = 20), or unknown mutation status (n = 6) (P = 0.84). All 8 patients with an SDHD mutation were true-positive on 18F-DOPA PET. There were 2 cases of false-negative results each in the group with SDHB (2/12) and VHL mutations (2/19) and 1 false-negative result in the subgroup of patients with unknown mutation status (1/6). Overall, 18F-DOPA PET yielded a sensitivity of 93% and a specificity of 88% for the detection of paragangliomas and pheochromocytomas on a patient basis (positive and negative predictive value, 94% and 85%, respectively). Conclusion: 18F-DOPA PET is a sensitive and specific imaging modality for the detection and staging of pheochromocytomas and paragangliomas in different genotypes, including VHL-, SDHB-, and SDHD-mutation carriers, and in patients with no germline mutation.

Comparison of (68)Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology.

Purpose: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. Methodology: Seven patients with histopathologically proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. Results: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). Conclusion: In a slice by slice analysis with histopathology, 68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.

Improved inter-observer agreement of an expert review panel in an oncology treatment trial – Insights from a structured interventional process

PURPOSE Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro-deoxyglucose (FDG)-positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG-PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (IDMC) triggered an interventional harmonisation process, which overall involved 11 experts uttering 6855 blinded diagnostic statements. After assessing the baseline inter-observer agreement (IOA) of a blinded re-review (phase 1), a discussion process led to improved reading criteria (phase 2). Those underwent a validation study (phase 3) and were then implemented into the study routine. After 2 months (phase 4) and 1 year (phase 5), the IOA was reassessed. RESULTS The initial overall IOA was moderate (kappa 0.52 CT; 0.53 PET). After improvement of reading criteria, the kappa values improved substantially (kappa 0.61 CT; 0.66 PET), which was retained until the late reassessment (kappa 0.71 CT; 0.67 PET). Subjective uncertainty was highly predictive for low IOA. CONCLUSION The IOA of an expert panel was significantly improved by a structured interventional harmonisation process which could be a model for future clinical trials. Furthermore, the low IOA in reporting nodal involvement in NSCLC may bear consequences for individual patient care.

Does Radiation Prevent 5-Fluorouracil-Induced Colitis in the Early Phase of Radiochemotherapy?

Case Report:A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary.Discussion:It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors’ knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis.Conclusion:This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU-based chemotherapy due to pulmonary relapse, and again, severe diarrhea occurred.Fallbericht:Ein 43-jähriger Mann mit histologisch gesichertem Adenokarzinom des unteren Rektumdrittels, Stadium cT3 cN2 M0, wurde einer präoperativen Radiochemotherapie (RCT) unterzogen. Parallel zu einer konformalen Strahlentherapie des Beckens in einer täglichen Fraktionierung von 1,8 Gy erhielt der Patient 5-Fluorouracil (5-FU, 350 mg/m2 über 24 h i.v., Tage 1–5 und 8–12), Leukovorin (200 mg/m2 als 1-h-Infusion, Tage 1–5 und 8–12) und Mitomycin C (12 mg/m2 als 1-h-Infusion, Tage 5 und 12). Am 10. Therapietag entwickelte der Patient starke abdominelle Schmerzen und profuse Diarrhöen. Die Abklärung mittels einer Computertomographie des Abdomens, Labor, Stuhlproben, Gastroskopie und Koloskopie mit Probeexzisionen aus den betroffenen Kolonabschnitten ergab eine nichtinfektiöse Kolitis, als deren wahrscheinlichste Ursache sich eine Reaktion auf 5-FU herausstellte. Als der Patient wegen im weiteren Verlauf aufgetretener pulmonaler Metastasen mit einer Kombination aus 5-FU, Oxaliplatin und Leukovorin behandelt wurde, litt er erneut unter starken Durchfällen, so dass zur besseren Verträglichkeit die Dosis reduziert werden musste.Diskussion:Da sich die Entzündung nur auf die nicht im Bestrahlungsvolumen gelegenen Kolonabschnitte beschränkte, wird vermutet, dass die gleichzeitig applizierte Bestrahlung aufgrund ihrer bei niedrigen bis moderaten Dosen erwiesenen antiinflammatorischen Eigenschaften das Auftreten der Entzündungsreaktion im distalen Sigma und Rektum in der Frühphase der RCT verhindert haben könnte. Nach Wissen der Autoren wurde eine solche Beobachtung noch nie veröffentlicht. Unter Berücksichtigung der relevanten Literatur und der eigenen Beobachtung wird diskutiert, dass sowohl eine erhöhte Leukozyten-/Endothelzelladhäsion als auch eine Modulation der Freisetzung reaktiver Sauerstoffspezies (ROS) und/oder die induzierbare Stickoxidsynthase (iNOS) eine Rolle bei der 5-FU-induzierten Kolitis spielen könnte.Schlussfolgerung:Diese Beobachtungen führten zu der Hypothese, dass der antientzündliche Effekt einer niedrigdosierten Bestrahlung, wie er zu Beginn der RCT noch anzunehmen ist, die Entstehung einer 5-FU-induzierten Kolitis verzögern könnte. Nebenwirkungen der RCT sollten in radiogene und chemotherapeutisch induzierte Effekte eingeteilt werden, wofür eine detaillierte diagnostische Abklärung erforderlich ist. Diese Erkenntnis hat einen wichtigen Einfluss auf die individuelle Therapieplanung. Da im beschriebenen Fall offenbar keine erhöhte Strahlenempfindlichkeit, sondern nur eine erhöhte Empfindlichkeit auf 5-FU bestand, konnte die Radiatio planmäßig fortgesetzt werden. Die Annahme einer erhöhten Empfindlichkeit auf 5-FU bestätigte sich, als der Patient wegen im Verlauf aufgetretener Lungenmetastasen eine palliative 5-FU-basierte Chemotherapie erhielt, wobei erneut schwere Diarrhöen auftraten.

PET/CT and MRI directed extended salvage radiotherapy in recurrent prostate cancer with lymph node metastases

PURPOSE PET/CT directed extended salvage radiotherapy (esRT) of involved lymph-node (LN) regions may be a salvage strategy for patients with nodal recurrent prostate cancer (PCa) after primary therapy or after previous prostate fossa salvage RT. The aim of the study was to determine the time until prostate-specific antigen (PSA) progression, pattern of failure and toxicity after esRT. MATERIAL AND METHODS 25 patients with nodal or nodal+local recurrent PCa confirmed by Choline-PET/CT and Magnetic Resonance Imaging (MRI) were treated with esRT at the sites of recurrence. Acute and late toxicity was recorded. In case of subsequent PSA progression, imaging was performed to confirm next relapse. Mean follow-up was 2.9 years. RESULTS According to Choline-PET/CT and MRI findings, 84% (21/25) of esRT were treatment of pelvic only, 12% (3/25) of retroperitoneal only and 4% (1/25) of both pelvic and retroperitoneal regions. 40% (10/25) received concomitant irradiation of the prostatic fossa (after primary radical prostatectomy). Median time to PSA progression of the whole cohort was 19.6 months. Median time to PSA progression for patients with 1-2 PET-positive LN (n=15) was 34.9 months versus median 12.7 months for patients with PET-positive LN≥3 (n=10), p-value: 0.0476. Acute and late toxicity was mild to moderate, no grade-3 adverse events were observed. CONCLUSION PET/CT and MRI directed esRT of nodal recurrent PCa with or without local recurrence is feasible with low acute and late toxicity. Patients with only one or two PET-positive LN treated by esRT achieved prolonged complete biochemical remission.

Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review.

Case Report:A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary.Discussion:It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors’ knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis.Conclusion:This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU-based chemotherapy due to pulmonary relapse, and again, severe diarrhea occurred.Fallbericht:Ein 43-jähriger Mann mit histologisch gesichertem Adenokarzinom des unteren Rektumdrittels, Stadium cT3 cN2 M0, wurde einer präoperativen Radiochemotherapie (RCT) unterzogen. Parallel zu einer konformalen Strahlentherapie des Beckens in einer täglichen Fraktionierung von 1,8 Gy erhielt der Patient 5-Fluorouracil (5-FU, 350 mg/m2 über 24 h i.v., Tage 1–5 und 8–12), Leukovorin (200 mg/m2 als 1-h-Infusion, Tage 1–5 und 8–12) und Mitomycin C (12 mg/m2 als 1-h-Infusion, Tage 5 und 12). Am 10. Therapietag entwickelte der Patient starke abdominelle Schmerzen und profuse Diarrhöen. Die Abklärung mittels einer Computertomographie des Abdomens, Labor, Stuhlproben, Gastroskopie und Koloskopie mit Probeexzisionen aus den betroffenen Kolonabschnitten ergab eine nichtinfektiöse Kolitis, als deren wahrscheinlichste Ursache sich eine Reaktion auf 5-FU herausstellte. Als der Patient wegen im weiteren Verlauf aufgetretener pulmonaler Metastasen mit einer Kombination aus 5-FU, Oxaliplatin und Leukovorin behandelt wurde, litt er erneut unter starken Durchfällen, so dass zur besseren Verträglichkeit die Dosis reduziert werden musste.Diskussion:Da sich die Entzündung nur auf die nicht im Bestrahlungsvolumen gelegenen Kolonabschnitte beschränkte, wird vermutet, dass die gleichzeitig applizierte Bestrahlung aufgrund ihrer bei niedrigen bis moderaten Dosen erwiesenen antiinflammatorischen Eigenschaften das Auftreten der Entzündungsreaktion im distalen Sigma und Rektum in der Frühphase der RCT verhindert haben könnte. Nach Wissen der Autoren wurde eine solche Beobachtung noch nie veröffentlicht. Unter Berücksichtigung der relevanten Literatur und der eigenen Beobachtung wird diskutiert, dass sowohl eine erhöhte Leukozyten-/Endothelzelladhäsion als auch eine Modulation der Freisetzung reaktiver Sauerstoffspezies (ROS) und/oder die induzierbare Stickoxidsynthase (iNOS) eine Rolle bei der 5-FU-induzierten Kolitis spielen könnte.Schlussfolgerung:Diese Beobachtungen führten zu der Hypothese, dass der antientzündliche Effekt einer niedrigdosierten Bestrahlung, wie er zu Beginn der RCT noch anzunehmen ist, die Entstehung einer 5-FU-induzierten Kolitis verzögern könnte. Nebenwirkungen der RCT sollten in radiogene und chemotherapeutisch induzierte Effekte eingeteilt werden, wofür eine detaillierte diagnostische Abklärung erforderlich ist. Diese Erkenntnis hat einen wichtigen Einfluss auf die individuelle Therapieplanung. Da im beschriebenen Fall offenbar keine erhöhte Strahlenempfindlichkeit, sondern nur eine erhöhte Empfindlichkeit auf 5-FU bestand, konnte die Radiatio planmäßig fortgesetzt werden. Die Annahme einer erhöhten Empfindlichkeit auf 5-FU bestätigte sich, als der Patient wegen im Verlauf aufgetretener Lungenmetastasen eine palliative 5-FU-basierte Chemotherapie erhielt, wobei erneut schwere Diarrhöen auftraten.