[Radiological-nuclear medicine hybrid diagnostics with SPECT/CT for chronic foot and ankle diseases : A new and important diagnostic tool]. / Radiologisch-nuklearmedizinische Hybriddiagnostik mit SPECT/CT bei chronischen Fuß- und Sprunggelenkserkrankungen : Eine neue und wichtige Erweiterung des diagnostischen Spektrums.

BACKGROUND AND AIM: In contrast to standard methods (sonography, X­ray, CT (computed tomography), MRI (magnetic resonance imaging), numerous diseases of the foot or ankle can be diagnosed using SPECT/CT (single photon emission computed tomography/computed tomography) with regard to their clinical relevance with high accuracy (up to > 90%). The aim of this review is to provide an up-to-date overview of the importance of SPECT/CT in selected diseases of the foot and ankle. MATERIAL AND METHODS: A literature search was carried out in the Pubmed database using the following terms: SPECT/CT, SPECT, skeletal scintigraphy, CT, computed tomography, foot and ankle disease, OSG, tarsal root, foot pain. The publications were selected with regard to questions and diagnoses that frequently occur in foot and ankle diagnostics. Furthermore, papers that describe a more precise diagnosis, a change in therapy management or a reduction in symptoms due to the use of SPECT/CT were selected. RESULTS: Several studies have shown that a focally increased bone metabolism in osteoarthritis and osteochondral lesions correlates significantly with the development of pain. The presence of symptomatic ossicles such as the os naviculare accessorium type II and os trigonum can be clearly demonstrated with the help of SPECT/CT and cannot be assigned as the source of the symptoms as accurately with any other imaging method. Bony reactions in the area of coalitions, arthrodesis, osteosynthesis, occult fractures, prostheses and diabetic foot cannot be detected with comparable accuracy using any other imaging method, so that therapy concepts in unclear cases, based only on standard imaging are changed in up to 2/3 of cases by SPECT/CT information. DISCUSSION AND CONCLUSION: SPECT/CT is useful when there are clinical uncertainties despite standard imaging.

Impact of radiotherapy protocol adherence in NSCLC patients treated with concurrent chemoradiation: RTQA results of the PET-Plan trial.

INTRODUCTION: The success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial. METHODS: In the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed. RESULTS: Between 05/2009-11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8-4.4, p < 0.0001) and a higher risk of loco-regional progression (HR 5.7, 95% CI 2.7-11.1, p < 0.0001). These results were significant also in the subgroup of patients receiving ≥ 60 Gy. Patients with maD concerning normal tissue delineation and/or dose constraints had a worse OS (p = 0.006) although no higher incidence of grade ≥ 3 toxicities. CONCLUSIONS: Non-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA.

Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer-A Secondary Analysis of the PET Plan Trial.

(1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1-5, 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1-5, 29-33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician's discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.

Single fraction multimodal image guided focal salvage high-dose-rate brachytherapy for recurrent prostate cancer.

PURPOSE: We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging - transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. RESULTS: Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. CONCLUSIONS: Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials.

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.

MRI versus 68Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is widely used in radiation treatment planning of primary prostate cancer (PCA). Focal dose escalation to the dominant intraprostatic lesions (DIPL) may lead to improved PCA control. Prostate-specific membrane antigen (PSMA) is overexpressed in most PCAs. (68)Ga-labelled PSMA inhibitors have demonstrated promising results in detection of PCA with PET/CT. The aim of this study was to compare (68)Ga-PSMA PET/CT with MRI for gross tumour volume (GTV) definition in primary PCA. METHODS: This retrospective study included 22 patients with primary PCA analysed after (68)Ga-PSMA PET/CT and mpMRI. GTVs were delineated on MR images by two radiologists (GTV-MRIrad) and two radiation oncologists separately. Both volumes were merged leading to GTV-MRIint. GTVs based on PET/CT were delineated by two nuclear medicine physicians in consensus (GTV-PET). Laterality (left, right, and left and right prostate lobes) on mpMRI, PET/CT and pathological analysis after biopsy were assessed. RESULTS: Mean GTV-MRIrad, GTV-MRIint and GTV-PET were 5.92, 3.83 and 11.41 cm(3), respectively. GTV-PET was significant larger then GTV-MRIint (p = 0.003). The MRI GTVs GTV-MRIrad and GTV-MRIint showed, respectively, 40 % and 57 % overlap with GTV-PET. GTV-MRIrad and GTV-MRIint included the SUVmax of GTV-PET in 12 and 11 patients (54.6 % and 50 %), respectively. In nine patients (47 %), laterality on mpMRI, PET/CT and histopathology after biopsy was similar. CONCLUSION: Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % - 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. (68)Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.

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.

Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only.

BACKGROUND: Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. METHODS: A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. RESULTS: Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. CONCLUSION: ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse.

Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer.

BACKGROUND: In a previous study we demonstrated that, based on 11C/18 F-choline positron emission tomography-computerized-tomography as a diagnostic tool, salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer (PCa). However, the toxicity of this combined treatment strategy has not been systematically investigated before. The aim of the current study was to evaluate the acute and late toxicity and quality of life of ART after LND in pelvic/retroperitoneal nodal recurrent PCa. MATERIAL AND METHODS: 43 patients with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse events from the Common-Terminology-Criteria for Adverse Events Version 4.0-catalogue and by review of medical records. QLQ-C30 (EORTC quality of life assessment) and PR25 (prostate cancer module) questionnaires were used to investigate quality of life. Toxicity was evaluated before starting of ART, during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up (mean 3.2 years after end of ART) reflecting late toxicity. RESULTS: 71.7% (33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms representing toxicities were observed before ART, 107 during ART, 88 after end of ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea (19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The spectrum of late toxicities was almost equal to those before beginning of ART. No grade 3 adverse events or chronic lymphedema at extremities were observed. We observed no clear correlation between localisation of treated regions, technique of ART and frequency or severity of toxicities. Mean quality of life at final evaluation was 74%. CONCLUSION: ART after extended LND in PCa relapse is justifiable with respect to adverse effects and toxicity. The side effects were circumscribed and well tolerated. The spectrum of adverse events at latest follow up was almost equal to those before start of ART.

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

PURPOSE: To 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 METHODS: 90 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). RESULTS: GTV 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. CONCLUSIONS: Using 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.

Hybrid imaging of peripheral skeletal disease by SPECT/high-resolution flat-panel CT.

UNLABELLED: The aim of this study was to determine the impact of high-resolution cone-beam CT with flat-panel detectors on the interpretation of bone SPECT in diseases of the peripheral skeleton. METHODS: Forty-one consecutive patients with peripheral skeletal disease were examined with a SPECT/high-resolution CT system providing isotropic voxels of 0.33 × 0.33 × 0.33 mm. High-resolution images were retrospectively analyzed by 2 readers and compared with low-resolution images obtained by filtering the high-resolution images to a lower resolution. RESULTS: SPECT/high-resolution CT demonstrated higher diagnostic confidence scores (1.98 ± 0.27 vs. 1.3 ± 0.45, P < 0.01) and better interobserver agreement (κ = 0.5 vs. 0.2) than SPECT/low-resolution CT. The diagnosis made by SPECT/high-resolution CT was in agreement with the final clinical diagnosis in 95% (reader 1) and 90% (reader 2) of the cases, as compared with 59% (reader 1) and 60% (reader 2) of the cases for SPECT/low-resolution CT (P < 0.01). CONCLUSION: High-resolution flat-panel CT has the potential to significantly improve SPECT/CT imaging in diseases of the peripheral skeleton.

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

PURPOSE: To 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 METHODS: Thirty-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. RESULTS: In 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. CONCLUSIONS: This 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.

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.

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.

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.