Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine - a case-control study.

OBJECTIVE: Evaluation of MRI-derived cerebral 23Na concentrations in patients with migraine in comparison with healthy controls. MATERIALS AND METHODS: In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years) were enrolled after evaluation of standardized questionnaires. Half (n = 12) of the cohort suffered from migraine, the other half was impaired by both migraine and tension-type headaches (TTH). The combined patient cohort was matched to 12 healthy female controls (mean age, 34 ± 11 years). All participants underwent a cerebral 23Na-magnetic resonance imaging examination at 3.0 T, which included a T1w MP-RAGE sequence and a 3D density-adapted, radial gradient echo sequence for 23Na imaging. Circular regions of interests were placed in predetermined anatomic regions: cerebrospinal fluid (CSF), gray and white matter, brain stem, and cerebellum. External 23Na reference phantoms were used to calculate the total 23Na tissue concentrations. Pearson's correlation, Kendall Tau, and Wilcoxon rank sum test were used for statistical analysis. RESULTS: 23Na concentrations of all patients in the CSF were significantly higher than in healthy controls (p < 0.001). The CSF of both the migraine and mixed migraine/TTH group showed significantly increased sodium concentrations compared to the control group (p = 0.007 and p < 0.001). Within the patient cohort, a positive correlation between pain level and TSC in the CSF (r = 0.62) could be observed. CONCLUSION: MRI-derived cerebral 23Na concentrations in the CSF of migraine patients were found to be statistically significantly higher than in healthy controls. KEY POINTS: • Cerebral sodium MRI supports the theory of ionic imbalances and may aid in the challenging pathophysiologic understanding of migraine. • Case-control study shows significantly higher sodium concentrations in cerebrospinal fluid of migraineurs. • Cerebral sodium MRI may become a non-invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level, and influence patient management.

Oncological outcome of primary non-metastatic soft tissue sarcoma treated by neoadjuvant isolated limb perfusion and tumor resection.

BACKGROUND: Isolated limb perfusion (ILP) is an effective limb salvage strategy in patients with advanced soft tissue sarcoma (STS) where surgery alone would result in significant functional morbidity or mandate an amputation. Most previous reports of patients undergoing ILP focus on limb salvage rates rather than local and distant relapse rates. Here, we report the oncological outcome of sarcoma patients treated by ILP and surgery. METHODS: Data were retrieved from prospective ILP databases from two ILP centers following similar ILP techniques and surgical approaches. Only patients with primary, intermediate, or high grade non-metastatic STS were included. RESULTS: The cohort comprised 90 patients. Median follow-up was 39 months (range 3-165 months). Median tumor size was 11 cm (range 5-34). Twenty of 90 (22%) patients underwent prior debulking surgery outside the centers. Twenty-nine of 90 (32%) had postoperative irradiation. Four of 90 underwent amputation either related to local recurrence or irresectability, 4 of 90 underwent amputation for treatment-related complications. Fifteen of 83 (18%) patients had local recurrences after ILP and limb sparing surgery, 39 of 90 (43%) developed metastatic disease. Twenty-two of 90 (24%) died of disease. CONCLUSION: Preoperative ILP and tumor resection resulted in good local control in a cohort of high-risk STS patients.

Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting.

BACKGROUND: The use of human acellular dermis (hAD) to close open abdomen in the treatment process of severe peritonitis might be an alternative to standard care. This paper describes an investigation of the effects of fluids simulating an open abdomen environment on the biomechanical properties of Epiflex® a cell-free human dermis transplant. METHODS: hAD was incubated in Ringers solution, blood, urine, upper gastrointestinal (upper GI) secretion and a peritonitis-like bacterial solution in-vitro for 3 weeks. At day 0, 7, 14 and 21 breaking strength was measured, tensile strength was calculated and standard fluorescence microscopy was performed. RESULTS: hAD incubated in all five of the five fluids showed a decrease in mean breaking strength at day 21 when compared to day 0. However, upper GI secretion was the only incubation fluid that significantly reduced the mechanical strength of Epiflex after 21 days of incubation when compared to incubation in Ringer's solution. CONCLUSION: hAD may be a suitable material for closure of the open abdomen in the absence of upper GI leakage and pancreatic fistulae.

Steady state vascular imaging with extracellular gadobutrol: evaluation of the additional diagnostic benefit in patients who have undergone a peripheral magnetic resonance angiography protocol.

BACKGROUND: To evaluate the feasibility and additional diagnostic benefit of a high-resolution steady state 3D-volume interpolated breath-hold exam (VIBE) sequence between a continuous table movement (CTM) MR angiography of the entire runoff vasculature and a time-resolved (TWIST) MRA of the calves. METHODS: In this retrospective IRB approved study 224 patients (72 women, 152 men, mean age 67.29 ± 13.9) were included who had undergone a low-dose MR angiographic protocol at 3T (Siemens TimTrio) after injection of 0.1 mmol/kg gadobutrol including a CTM MRA, a time-resolved MRA of the calf station and a steady state 3D VIBE sequence prior to the time-resolved MRA. One board-certified radiologist rated the image quality of the steady state VIBE sequences on an ordinal three point scale (excellent, good, poor) and analyzed the images for additional diagnostic findings of and beyond the vascular system in comparison to the CTM MRA and the time-resolved MRA. Descriptive statistics and demographic patient data were used for further evaluation. RESULTS: The image quality of the steady state imaging of the pelvis, upper and lower leg was excellent in up to 88%, 84% and 47%, respectively, while poor image quality was only detected in the upper (2%) and lower leg (6%). An additional diagnostic benefit was found in 44% of the patients overall. The most common relevant pathologies included inflammatory processes of the soft tissues (26%), thrombi (14%), abscesses (13%) and tumors (11%). In subgroups of patients above the age of 60, 65, 70, 75 and 80 years an additional pathology was found in 50% 33%, 44%, 65% and 58%, respectively. There was no significant difference in terms of additional findings between men and women (46% and 39%, p > 0.05) and inpatients and outpatients (42% and 45%, p > 0.05). CONCLUSION: Steady state imaging is also feasible with extracellular contrast agents with good image quality yielding additional diagnostic findings in up to 44% and above in patients older than 60 years of age irrespective of gender or patient status. Given the short acquisition time of 4 minutes this sequence could be added to all peripheral MRA exams.

Characteristics, treatment and prognostic factors of patients with gynaecological malignancies treated in a palliative care unit at a university hospital.

BACKGROUND: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors. METHODS: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated. RESULTS: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%. The median overall survival (OS) was 59 days. 53% of the patients died at the palliative care unit. In the Cox proportional hazards model, 8 parameters indicated an unfavourable outcome: anorexia/nausea, disordered mental status, elevated lactate dehydrogenase, γ-glutamyltransferase, leukocyte count, hypoalbuminaemia, anaemia and hypercalcaemia. Based on these parameters 3 risk groups were defined: low risk (0-2 factors), intermediate risk (3-5 factors), and high risk (6-8 factors). Median survival for high-risk group was 13 days, for intermediate group 61 days, and for low-risk patients 554 days (p < 0.0001). CONCLUSION: Weakness/fatigue, pain and anorexia were the main symptoms leading to the hospitalisation of patients with gynaecological malignancies. Symptom and pain control was accomplished in 80% of cases. 8 parameters were identified as indicating a poor outcome, and patients showing at least 6 or more of these factors had a very limited prognosis. Although studied retrospectively, these results may be helpful for individual treatment decisions in patients with advanced gynaecological malignancies. Prospective data and the introduction of documentation systems could help to gain more powerful knowledge about the quality of palliative care.

Predicting malignancy in mediastinal lymph nodes by endobronchial ultrasound: a new ultrasound scoring system.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound (EBUS) is now widely used in patients with resectable non-small-cell lung cancer to sample mediastinal lymph nodes (LN) for preoperative staging. The aim of this study was to investigate prospectively the utility of six ultrasound criteria to predict malignancy in mediastinal LN. METHODS: EBUS was performed in patients with mediastinal lymphadenopathy irrespective of the underlying disease. The following criteria were expected to predict malignancy: short axis >1 cm, heterogeneous pattern, round shape, distinct margin, absence of a central hilar structure and high blood flow in a LN. A sum score prediction model for malignancy was built. If more than two criteria were present, LN was classified as high risk for malignancy. Moreover, interrater variability of two blinded investigators was evaluated. RESULTS: Two hundred eighty-one LN in 145 patients were analysed. Forty-four percent of LN were found malignant, 10% revealed sarcoidosis, and 10% revealed tuberculosis. Interobserver agreement was very good. Positive predictive value was best for heterogeneity (73%), with a negative predictive value of more than 80%. The sum score resulted in an odds ratio of 15.5 if more than two criteria were positive (P < 0.00001). CONCLUSIONS: The assessment of ultrasound criteria during routine EBUS examinations is feasible and reproducible with very good interrater agreement. If less than three of the described criteria are present, a LN has a very low chance of being malignant. The best single criterion to predict malignancy is heterogeneity. The introduction of the sum score of ultrasound criteria could potentially increase diagnostic accuracy.

Implication of FDG-PET/CT in patients with potentially operable colorectal lung metastases.

OBJECTIVES: This prospective study assessed the role of F-18-FDG-PET/CT in clinical staging for patients with colorectal cancer planned for pulmonary metastasectomy by thoracotomy or video-assisted surgery. PATIENTS AND METHODS: In addition to conventional imaging, we performed 86 F-18-FDG-PET/CT studies in 76 patients with potentially resectable metastatic colorectal lung metastases. We then investigated the effect that PET/CT had on further clinical management. Based on the results from the 47 thoracotomies performed, we compared the number of pulmonary metastases discovered after histologic examination with the number predicted by the conventional computed tomography (CT) as an independent part of the F-18-FDG-PET/CT examination and by the F-18-FDG-PET component. RESULTS: F-18-FDG-PET/CT led to changes in treatment regime and diagnostic planning in many patients. In five patients PET/CT revealed previously undetected local recurrence of the primary colorectal cancer, in four patients hepatic metastases, in three patients bone metastases, in two patients soft-tissue metastases, and in three patients histologically preoperatively proven N2 or N3 station lymph node involvement. These all constituted exclusion criteria, and consequently the previously planned pulmonary metastasectomy was not performed. The sensitivity and positive predictive value (PPV) for detection of pulmonary metastases were 84.2% and 36.4% for CT and 75.0% and 61.6% for F-18-FDG-PET study. The calculated sensitivity, specificity, PPV, and NPV of F-18-FDG-PET/CT for detecting thoracic lymph node involvement were 85.7%, 93.0%, 66.7%, and 97.5%, respectively. Furthermore, we found that F-18-FDG-PET/CT may predict thoracic lymph node involvement based on the SUV of pulmonary nodules. CONCLUSIONS: F-18-FDG-PET/CT has a clear role in the diagnostic workup for pulmonary metastatic colorectal cancer and may save patients from futile surgery. It cannot, however, be relied on to detect all possible pulmonary and nodal metastases, which surgeons must always consider when making treatment decisions.

Presentation, treatment, and analysis of prognostic factors of terminally ill patients with gastrointestinal tumors.

BACKGROUND: Few data have been published about terminally ill patients with gastrointestinal tumors treated in palliative care units. PATIENTS AND METHODS: We analyzed the data of 737 admissions of 435 patients that were treated in a palliative care unit, and tried to identify prognostic factors for survival. RESULTS: Most frequent diagnoses at admission were colorectal, gastric, esophageal, and pancreatic cancer. Major clinical symptoms were pain (66.9%), anorexia (60.8%), weight loss (39.2%), and nausea/vomiting (36.6%). In 71.6% of the patients, morphine derivatives were administered. In 33.0% of cases, red blood cell transfusions were applied, parenteral nutrition was given in 31.3%. Median survival, calculated from the day of first hospitalization, was 35 days. On univariate analysis, several clinical and laboratory parameters were identified as prognostically important factors. In the multivariate Cox regression analysis, 5 parameters were significant: ascites and anorexia, elevated leukocyte count and lactate dehydrogenase activity, as well as decreased albumine levels. Using these parameters, patients were divided into 3 risk groups: low-risk (presence of 0-1 factors), intermediate risk (2-3 factors), and poor-risk patients (4-5 factors). Median survival for poor-risk patients was 18 days, intermediate- and low-risk patients survived 43 and 136 days, respectively (p < 0.0001). CONCLUSION: In multivariate analysis, 5 prognostic factors were identified, and 3 patient groups were defined. After multicenter validation, these factors may help to guide treatment decisions in terminally ill patients with gastrointestinal tumors.

Association between the novel classification of lung adenocarcinoma subtypes and EGFR/KRAS mutation status: A systematic literature review and pooled-data analysis.

OBJECTIVES: This study aims to determine the association of EGFR/KRAS mutation status with histological subtypes of lung adenocarcinoma (LAC) based on the IASLC/ATS/ERS classification. METHODS: Pubmed and Cochrane databases were searched from January 2011 to June 2018 for studies that included patients with LAC who underwent surgical resection were classified according to the new IASLC/ATS/ERS classification. EGFR/KRAS status assessment was requireded. The primary outcome was determined by the odds ratio (OR) of the incidence of mutation status of certain of each histological subtype. The reference group consisted of EGFR/KRAS mutation negative patients. RESULTS: Twenty-seven eligible studies involving 9022 patients with mutation gene detection were included for analysis. Among them, 6717 (74.5%) patients were from the Asian region and, 2305 (25.5%) patients were from Non-Asian regions. The most prevalent subtype was acinar (34.7%), followed by papillary (22.9%), lepidic (18.9%), solid (13.6%), micropapillary (6.3%), and invasive mucinous adenocarcinoma (3.5%). EGFR mutations were more common in patients with resected lepidic predominant adenocarcinoma (OR,1.76; 95%CI, 1.38-2.24;p < 0.01) and were rarely found in solid predominant adenocarcinoma (OR,0.28; 95%CI, 0.23-0.34;p < 0.01) or IMA (OR,0.10; 95%CI, 0.06-0.14;p < 0.01). Conversely, KRAS mutations were characterized by IMA (OR,7.01; 95%CI, 5.11-9.62;p < 0.01), and were less frequently identified in lepidic (OR,0.58; 95%CI, 0.45-0.75;p < 0.01) and acinar (OR,0.65; 95%CI, 0.55-0.78;p < 0.01) predominant subtypes. Further analyses were performed in Asian and Non-Asian groups and the results were consistent. CONCLUSIONS: The current study confirms that the IASLC/ATS/ERS classification is associated with driver gene alterations in resected LAC.

[Data documentation and data management with guidelines, experiences, caveats, and recommendations]. / Datenerhebung und Datenmanagement mit Richtlinien, Erfahrungen, Warnungen und Empfehlungen.

Reliable and correct data capture and safe data management are an inevitable prerequisite to gain valid data in clinical studies. The biostatistical analysis is the basis from which medical consequences about efficacy and safety of the treatment can be driven. The functional role of data capture and data management in relation to the study protocol, development of report forms, data flux between the involved institutions, and the data capture systems will be investigated. Main points of the data capture are the rationale of the study, the protocol, and the statistical analysis plan. Modularity, uniqueness, and reduction on the needs of the study protocol designate a good documentation form. Practical considerations will be given. Prompt and efficient communication between all involved participants is the organizational prerequisite for valid data, independent from the data capture system. Online data capture will displace the classical paper documentation form, however, accurate and careful documentation will remain. Data capture and data management are a crucial and cost-intensive chapter of a clinical study, formed by the technical ability and the team play of clinical principal investigators, biostatisticians, computer scientists, monitors, and the organizers of the study.

Regional chemotherapy by isolated limb perfusion prior to surgery compared with surgery and post-operative radiotherapy for primary, locally advanced extremity sarcoma: a comparison of matched cohorts.

BACKGROUND: Induction chemotherapy by isolated limb perfusion (ILP) with melphalan and tumour necrosis factor-α is an effective strategy to facilitate limb-conserving surgery in locally advanced extremity sarcoma. In a comparison of cohorts matched for grade, size and surgical resectability, we compared the outcome of patients undergoing induction ILP prior to limb-conserving surgery and selective post-operative radiotherapy with patients undergoing limb-conserving surgery and routine post-operative radiotherapy. METHODS: Patients with primary, grade 2/3 sarcomas of the lower limbs over 10 cm in size were identified from prospectively maintained databases at 3 centres. Patients treated at a UK centre underwent limb-conserving surgery and post-operative radiotherapy (Standard cohort). Patients at two German centres underwent induction ILP, limb-conserving surgery and selective post-operative radiotherapy (ILP cohort). RESULTS: The Standard cohort comprised 80 patients and the ILP cohort 44 patients. Both cohorts were closely matched in terms of tumour size, grade, histological subtype and surgical resectability. The median age was greater in the Standard vs the ILP cohort (60.5 years vs 56 years, p = 0.033). The median size was 13 cm in both cohorts. 5-year local-recurrence (ILP 12.2%, Standard 20.1%, p = 0.375) and distant metastases-free survival rates (ILP 49.6%, Standard 46.0% p = 0.821) did not differ significantly between cohorts. Fewer patients received post-operative radiotherapy in the ILP cohort compared with the Standard cohort (27% vs 82%, p < 0.001). CONCLUSION: In comparative cohorts, the outcomes of patients undergoing induction ILP prior to surgery did not differ from those undergoing standard management, although induction ILP was associated with a reduced need for adjuvant radiation.

Community-based lung cancer screening with low-dose CT in China: Results of the baseline screening.

OBJECTIVES: To investigate whether low-dose computed tomography (LDCT) screening is capable of enhancing the detection rate of early-stage lung cancer in high-risk population of China with both smoking and non-smoking related factors. METHODS: From 2013-2014, eligible participants with high-risk factors of lung cancer were randomly assigned to a screening group or a control group with questionnaire inquiries. Any non-calcified nodules or masses with longest diameters of ≥4 mm identified on LDCT images were considered as positive. RESULTS: A total of 6717 eligible participants were randomly enrolled to a study group (3550 to LDCT screening and 3167 to standard care). 3512 participants (98.9%) underwent LDCT screening, and 3145 participants (99.3%) received questionnaire inquiries. A positive screening result was observed in 804 participants (22.9%). In the two-year follow-up period, lung cancer was detected in 51 participants (1.5%) in the LDCT group versus 10 (0.3%) in the control group (stage I: 48 vs 2; stage II to IV or limited stage: 3 vs 8), respectively. Early-stage lung cancer was found in 94.1% vs 20%, respectively. CONCLUSIONS: Compared to usual care, LDCT led to a 74.1% increase in detecting early-stage lung cancer. This study provides insights about the non-smoking related risk factors of lung cancer in the Chinese population.

Coronary artery calcium in breast cancer survivors after radiation therapy.

The purpose of the current study is to investigate whether breast cancer survivors after radiation therapy have a higher burden of coronary artery calcium as a potential surrogate of radiation-induced accelerated coronary artery disease. 333 patients were included. 54 patients underwent chest CT ≥ 6 months after the start of radiation therapy (radiation therapy group), while 279 patients had a CT scan either prior to or without undergoing radiation therapy (RT). Coronary artery calcium was quantified from CT by applying a threshold-based automated algorithm. Mean age at diagnosis was similar (p = 0.771) between RT (57.4 ± 13.1 years) and NoRT (58.0 ± 11.9 years). Median time between radiation therapy and CT was 2 years. The groups showed no significant differences in race, smoking history, cancer laterality, or cancer stage. 39 (72.2%) of RT patients had a coronary artery calcium score of 0, compared to 201 (72.0%) in patients without radiation therapy. Median coronary artery calcium burden for both groups was not significantly different (p = 0.982), nor when comparing patients who underwent left- versus right-sided radiation therapy (p = 0.453). When adjusting for the time between diagnosis and CT, radiation therapy patients had a significantly lower risk of a positive coronary artery calcium score. In conclusion, breast cancer survivors after radiation therapy are not more likely to show coronary artery calcium on follow-up CT imaging. Our results thus do not support radiation-induced accelerated coronary artery disease as an explanation for higher rates of heart disease in this group.

mMRI at 3.0 T as an Evaluation Tool of Therapeutic Response to Neoadjuvant CRT in Patients with Advanced-stage Rectal Cancer.

AIM: To assess whether multiparametric MRI (mMRI) can serve as a tool for evaluating response to chemoradiation therapy (CRT) in advanced-stage rectal cancer. PATIENTS AND METHODS: Twenty-one patients underwent a mMRI protocol at 3T before and after CRT. Two experienced radiologists evaluated the MRI measurements and inter-reader correlation was assessed. Changes in functional parameters in relation to regression, as well as pT stage were analyzed. The perfusion parameters plasma flow (PF) and mean transit time (MTT) were calculated offline using the established UMM Perfusion tool. RESULTS: Apparent diffusion coefficient values were significantly different among the different tumor RGs before CRT (p=0.041). Changes of dynamic contrast enhanced (DCE) MRI values did not reflect treatment response (PF: p=0.5; MTT: p=0.74). CONCLUSION: The results of our study population indicate that a high initial apparent diffusion coefficient value may be predictive of response to therapy following CRT.

Preoperative therapy with pazopanib in high-risk soft tissue sarcoma: a phase II window-of-opportunity study by the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS).

INTRODUCTION: For resectable soft tissue sarcoma (STS), radical surgery, usually combined with radiotherapy, is the mainstay of treatment and the only potentially curative modality. Since surgery is often complicated by large tumour size and extensive tumour vasculature, preoperative treatment strategies with the aim of devitalising the tumour are being explored. One option is treatment with antiangiogenic drugs. The multikinase inhibitor pazopanib, which possesses pronounced antiangiogenic effects, has shown activity in metastatic and unresectable STS, but has so far not been tested in the preoperative setting. METHODS AND ANALYSIS: This open-label, multicentre phase II window-of-opportunity trial assesses pazopanib as preoperative treatment of resectable STS. Participants receive a 21-day course of pazopanib 800 mg daily during wait time for surgery. Major eligibility criteria are resectable, high-risk adult STS of any location, or metachronous solitary STS metastasis for which resection is planned, and adequate organ function and performance status. The trial uses an exact single-stage design. The primary end point is metabolic response rate (MRR), that is, the proportion of patients with >50% reduction of the mean standardised uptake value (SUVmean) in post-treatment compared to pre-treatment fluorodeoxyglucose positron emission tomography CT. The MRR below which the treatment is considered ineffective is 0.2. The MRR above which the treatment warrants further exploration is 0.4. With a type I error of 5% and a power of 80%, the sample size is 35 evaluable patients, with 12 or more responders as threshold. Main secondary end points are histopathological and MRI response, resectability, toxicity, recurrence-free and overall survival. In a translational substudy, endothelial progenitor cells and vascular epithelial growth factor receptor are analysed as potential prognostic and predictive markers. ETHICS AND DISSEMINATION: Approval by the ethics committee II, University of Heidelberg, Germany (2012-019F-MA), German Federal Institute for Drugs and Medical Devices (61-3910-4038155) and German Federal Institute for Radiation Protection (Z5-22463/2-2012-007). TRIAL REGISTRATION NUMBER: NCT01543802, EudraCT: 2011-003745-18; Pre-results.

Dynamic volume perfusion computed tomography parameters versus RECIST for the prediction of outcome in lung cancer patients treated with conventional chemotherapy.

INTRODUCTION: To compare dynamic volume perfusion computed tomography (dVPCT) parameters with Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for prediction of therapy response and overall survival (OS) in non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients treated with conventional chemotherapy. METHODS: A total of 173 lung cancer patients (131 men; 61 ± 10 years) undergoing dVPCT before (T1) and after chemotherapy (T2) and follow-up were prospectively included. dVPCT-derived blood flow, blood volume, mean transit time, and permeability (PERM) were assessed, compared between NSCLC and SCLC and patients' response to therapy was determined according to RECIST 1.1. RESULTS: One hundred of one hundred and seventy-three patients underwent dVPCT at T1 and T2 within a median of 44 (range, 31-108) days. dVPCT values were differing in NSCLC and SCLC, but were not significantly differing between patients with partial response, stable, or progressive disease. Eighty-five patients (NSCLC = 72 and SCLC = 13) with a follow-up for greater than or equal to 6 months were analyzed for OS. Fifty-six of eighty-five patients died during follow-up. Receiver operating characteristic analysis determined T1/T2 with highest predictive values regarding OS for blood flow, blood volume, mean transit time, and permeability (area under the curve: 0.53, 0.61, 0.54, and 0.53, respectively, all p > 0.05). Kaplan-Meier statistics revealed OS of patient groups assigned according to dVPCT T1/T2 cutoff values was not differing for neither dVPCT parameter, whereas RECIST groups significantly differed in OS (p = 0.02). Cox proportional hazards regression determined progressive disease status to independently predict OS (p = 0.004), while none of the dVPCT parameters did so. CONCLUSIONS: dVPCT values, differ between NSCLC and SCLC, are not related to RECIST 1.1 classification and do not improve OS prediction in lung cancer patients treated with conventional chemotherapy.

Multiplex profiling of tumor-associated proteolytic activity in serum of colorectal cancer patients.

PURPOSE: The monitoring of tumor-associated protease activity in blood specimens has recently been proposed as new diagnostic tool in cancer research. In this paper, we describe the screening of a peptide library for identification of reporter peptides (RPs) that are selectively cleaved in serum specimens from colorectal cancer patients and investigate the benefits of RP multiplexing. EXPERIMENTAL DESIGN: A library of 144 RPs was constructed that contained amino acid sequences of abundant plasma proteins. Proteolytic cleavage of RPs was monitored with MS. Five RPs that were selectively cleaved in serum specimens from tumor patients were selected for further validation in serum specimens of colorectal tumor patients (n = 30) and nonmalignant controls (n = 60). RESULTS: RP spiking and subsequent quantification of proteolytic fragments with LC-MS showed good reproducibility with CVs always below 26%. The linear discriminant analysis and PCA revealed that a combination of RPs for diagnostic classification is superior to single markers. Classification accuracy reached 88% (79/90) when all five markers were combined. CONCLUSIONS AND CLINICAL RELEVANCE: Functional protease profiling with RPs might improve the laboratory-based diagnosis, monitoring and prognosis of malignant disease, and has to be evaluated thoroughly in future studies.

Positron emission tomography as a surrogate marker for evaluation of treatment response in patients with desmoid tumors under therapy with imatinib.

We used 2-deoxy-2-[(18)F] fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate patients with desmoid tumors undergoing therapy with imatinib. The study included 22 patients with progressive disease (PD) of a biopsy proven desmoid tumor treated orally with imatinib 800 mg daily. Patients were examined using PET prior to onset of therapy and during treatment. Restaging was performed in parallel using computed tomography (CT) and/or magnetic resonance imaging (MRI). Outcome of 22 evaluable patients was as follows: five patients with partial response (PR); twelve patients with stable disease (SD) accounting for 77% with non-progressive disease; five patients showed PD. A 30% decrease of the mean average standardized uptake value (SUV) of sequential PET examinations could be demonstrated; no patient demonstrated a substantial increase in SUV. Patients with PR/SD were matched to a group of nonprogressive disease and tested versus PD. The initial average SUV and SUVmax seem to be candidates for a response prediction with an approximate P-value of 0.06553 and 0.07785, respectively. This is the first larger series of desmoid patients monitored using PET showing that early SUV changes may help to discriminate responders from nonresponders and, thus, to decide whether imatinib therapy should be continued.