345 research outputs found
Benefits of a nationwide populationâbased skin cancer screening programme â still a controversial debate
Entwicklung von RF-Technologie fĂŒr die Ultrahochfeld-MRT: Optimierung und Anwendung einer Self-Grounded-Bow-Tie-Dipolantenne
Magnetic resonance imaging (MRI) is an important diagnostic imaging modality free of ionizing radiation. Sensitivity gain, signal-to-noise ratio (SNR) considerations, and changes in the tissue dependent MRI properties. Together with technical and scientific developments further research into increasing the magnetic field strength is justified, culminating in human applications at ultrahigh magnetic field (UHF, B0 â„ 7.0 T) MRI. Elevating the field strength results in an increased radiofrequency (RF) for signal transmission and reception in MRI (= Larmor frequency, f â 298 MHz at B0 = 7.0 T). The wavelength of this RF signal becomes sufficiently short when passing through tissue relative to the size of the target anatomy of the brain, upper torso, or abdomen. This phenomenon leads to constructive and deconstructive interference of the electromagnetic field (EMF) distribution, which results in a high susceptibility for non-uniformities in the magnetic RF transmission field (B1+). This detrimental excitation field distribution can cause shading, massive signal drop-off or even signal voids, and potentially offset the benefits of UHF-MRI due to compromised image quality.
UHF cardiovascular MR (CMR) benefits from SNR gains and changes in the tissue dependent MRI properties, but the B1+ distribution â in addition to the wavelength dependent non-uniformities â is further compromised by a dielectrically heterogeneous tissue environment. Research on UHF-CMR focuses on the improvement of the cardiac chamber morphology quantification, myocardial T1- and T2*-mapping, fat-water imaging, and vascular imaging (4D-flow). These applications benefit from a homogenous B1+ within the heart and the vascular structure. Several published reports on the development of RF antenna array technology tailored for UHF-CMR address this challenge with ideas and achievements to enable broad clinical UHF-CMR applications in the future. The primary objective of advancing this RF technology is to achieve a uniform B1+ distribution in the heart and the vascular structure with optimizing the magnetic field pattern. The second objective is the improvement of the RF antennaâs efficiency with the reduction of the specific absorption rate (SAR), which is achieved by an optimization of the electric field pattern. The control of the electric field is furthermore conceptually appealing beyond conventional MR imaging modalities and useful for localized and targeted RF induced thermal intervention. Combining MRI with a thermal intervention modality in an integrated Thermal MR system permits direct supervision of the treatment via MR-thermometry, as well as adapting and improving the focal point quality of the RF power deposition. The Thermal MR system is a platform for comprehensive investigation of the effects of temperature on molecular, biochemical, and physiological processes, ultimately yielding insights into temperature utilization for diagnosis and therapy in vivo.
EMF control of an RF antenna array depends on the radiation pattern of the antenna elements. Electrical dipoles are promising for UHF-MRI due to a linear polarized current pattern and an energy deposition perpendicular to the antenna. However, the channel count and therefore the degree of freedom for EMF shaping of previously reported antenna concepts is limited by the geometric extent and the coupling between the elements. The first section of this work addresses the design, implementation, and validation of a novel small-sized Self-Grounded Bow-Tie (SGBT) antenna, in combination with a dielectrically filled housing. The narrowband SGBT antenna variant is used in a 32-channel transmit/receive array configuration for UHF-CMR at 7.0 T. The second section focuses on the development of a modified broadband SGBT concept for the Thermal MR system. The broadband antenna increases the degree of freedom with an adaptation of the intervention frequency to improve the focal point quality (size, homogeneity, and specificity). The third section presents the implementation and validation of a signal generator in conjunction with the broadband SGBT variant introduced in section two. The device allows the generation of the intervention signal with a time dependent, channel-wise adaptation of amplitude, phase, and frequency. The work of this thesis offers a technical and conceptual framework for an increased degree of freedom for EMF shaping for a multitude of applications ranging from UHF-MRI to interventional MRI.Die Magnetresonanztomographie (MRI) ist ein wichtiges bildgebendes Diagnoseverfahren mit der Anwendung in vielen medizinischen Disziplinen. Die Forschung zu ultrahohen Magnetfeldern (UHF, B0 â„ 7.0 T) im humanen Bereich wird durch technische und wissenschaftliche Errungenschaften getrieben und basiert auf einer höheren SensitivitĂ€t, einem verbesserten Signal-Rausch-VerhĂ€ltnisses (SNR) sowie eine VerĂ€nderung der gewebsspezifischen MR Eigenschaften. Die höhere FeldstĂ€rke resultiert auch in einer erhöhten Radiofrequenz (RF) fĂŒr die MRI SignalĂŒbertragung (= Larmorfrequenz, f â 298 MHz bei B0 = 7.0 T). Die WellenlĂ€nge des RF Signals im Gewebe ist dabei bezogen zur Zielanatomie (e.g. SchĂ€del, Oberkörper und Abdomen) verkĂŒrzt was zu konstruktiven und destruktiven Interferenzen des elektromagnetischen Feldes (EMF) fĂŒhrt. Diese Interferenzen ergeben ein heterogenes RF Transmissionsfeld (B1+) mit Abschattungen, massiven SignalabfĂ€llen oder SignalausfĂ€llen welche die Vorteile der UHF-MRI durch eine beeintrĂ€chtigte BildqualitĂ€t schmĂ€lert.
Die UHF Herz MR (CMR) profitiert von einem SNR-Gewinn sowie von verĂ€nderten gewebsspezifischen MR Eigenschaften bei höheren FeldstĂ€rken. Jedoch wird die B1+ Verteilung, neben der gegebenen RF wellenlĂ€ngenabhĂ€ngigen HeterogenitĂ€t, durch dielektrische Gradienten im Bereich des Thorax zusĂ€tzlich beeintrĂ€chtigt. Die anwendungsbezogene Forschung und Entwicklung auf dem Gebiet der UHF-CMR konzentriert sich auf die Verbesserung der Quantifizierung der Herzkammermorphologie, des myokardialen T1- und T2*-Mappings, der Fett-Wasser-Bildgebung und der GefĂ€Ăbildgebung inklusive der Flussbildgebung (4D-Flow). Die Weiterentwicklung dieser Methoden streben eine breite klinische Anwendung an und profitieren von einer homogenen B1+ Verteilung im Herzen und in der GefĂ€Ăstruktur. Das primĂ€re Ziel der der Forschung und Entwicklung von RF Antennenarraytechnologie ist eine Optimierung der B1+ Verteilung. Das sekundĂ€re Ziel ist die Verbesserung der Effizienz durch die Verringerung der spezifischen Absorptionsrate (SAR) mittels einer elektrischen Feldoptimierung. Die Kontrolle des elektrischen Feldes kann aber auch ĂŒber die konventionelle MR Bildgebung hinaus genutzt werden und ermöglicht konzeptionell eine lokalisierte und gezielte RF induzierte thermische Intervention. Die Kombination von MRI und thermischen Interventionen in einem integrierten Thermal MR System ermöglicht die Anpassung und Verbesserung der lokalen Intervention durch eine Supervision der Behandlung mittels MR-Thermometrie. Das Thermal MR System stellt damit eine technologische Plattform dar, welche eine umfassende Untersuchung der Auswirkungen der Temperatur auf molekulare, biochemische und physiologische Prozesse erlaubt. Letztlich kann die Plattform Erkenntnisse darĂŒber liefern, wie die Temperatur fĂŒr Diagnosen und Therapien in vivo genutzt werden kann.
Die Kontrolle der EMF Verteilung durch ein RF Antennen Array ist abhĂ€ngig von den Abstrahlungseigenschaften der einzelnen Antennenelemente. Elektrische Dipole stellen durch eine linear polarisierte Stromverteilung und eine Abstrahlungsrichtung orthogonal zur Antenne eine vielversprechende Option dar. Allerdings ist die Kanalzahl und damit der Freiheitsgrad fĂŒr die EMF Optimierung bei bisher vorgestellten Antennenkonzepten durch die GröĂe und die Kopplung zwischen den Elementen begrenzt. Der erste Abschnitt dieser Arbeit befasst sich mit dem Entwurf, der Implementierung und der Validierung einer Self-Grounded Bow-Tie (SGBT) Antenne in Kombination mit einem dielektrisch gefĂŒllten GehĂ€use. Eine schmalbandige Antennenvariante wird in einer 32-Kanal Sende-/Empfangs-Array Konfiguration fĂŒr UHF-CMR bei 7,0 T vorgestellt. Der zweite Abschnitt befasst sich mit der Entwicklung eines modifizierten breitbandigen SGBT-Konzepts fĂŒr das Thermal MR System. Diese Antennenvariante erhöht die Freiheitsgrade fĂŒr die Optimierung der elektrischen Feldverteilung um die Interventionsfrequenz und erlaubt eine Verbesserung der lokalen ErwĂ€rmung (GröĂe, HomogenitĂ€t und SpezifitĂ€t). Im dritten Abschnitt dieser Arbeit wird die Implementierung und Validierung eines Signalgenerators in Verbindung mit der im zweiten Abschnitt vorgestellten Breitbandantennenvariante vorgestellt. Der Signalgenerator erzeugt einen Interventionssignal mit der zeitabhĂ€ngigen Anpassung von Amplitude, Phase und Frequenz fĂŒr jeden Kanal. Die Entwicklungen und Erkenntnisse dieser Arbeit bieten einen konzeptionellen Rahmen fĂŒr eine Vielzahl von realen Anwendungen, welche von der konventionellen MRI bis zu einem integrierten interventionellen Thermal MR System reichen.EC/H2020/743077/EU/Thermal Magnetic Resonance: A New Instrument to Define the Role of Temperature in Biological Systems and Disease for Diagnosis and Therapy/ThermalM
32âChannel selfâgrounded bowâtie transceiver array for cardiac MR at 7.0T
Purpose
Design, implementation, evaluation, and application of a 32âchannel SelfâGrounded BowâTie (SGBT) transceiver array for cardiac MR (CMR) at 7.0T.
Methods
The array consists of 32 compact SGBT building blocks. Transmission field (B1+) shimming and radiofrequency safety assessment were performed with numerical simulations and benchmarked against phantom experiments. In vivo B1+ efficiency mapping was conducted with actual flip angle imaging. The arrayâs applicability for accelerated high spatial resolution 2D FLASH CINE imaging of the heart was examined in a volunteer study (n = 7).
Results
B1+ shimming provided a uniform field distribution suitable for female and male subjects. Phantom studies demonstrated an excellent agreement between simulated and measured B1+ efficiency maps (7% mean difference). The SGBT array afforded a spatial resolution of (0.8 Ă 0.8 Ă 2.5) mm3 for 2D CINE FLASH which is by a factor of 12 superior to standardized cardiovascular MR (CMR) protocols. The density of the SGBT array supports 1D acceleration of up to R = 4 (mean signalâtoânoise ratio (whole heart) â„ 16.7, mean contrastâtoânoise ratio â„ 13.5) without impairing image quality significantly.
Conclusion
The compact SGBT building block facilitates a modular highâdensity array that supports accelerated and high spatial resolution CMR at 7.0T. The array provides a technological basis for future clinical assessment of parallel transmission techniques.EC/H2020/743077/EU/Thermal Magnetic Resonance: A New Instrument to Define the Role of Temperature in Biological Systems and Disease for Diagnosis and Therapy/ThermalMRBMBF, 01QE1815, Verbundprojekt: Seeing is Believing: Revolution der bildgebenden Diagnostik und Therapiekontrolle des Körperstammes durch superaufgelöste Hochfeld-Magnetresonanztomographie; Teilprojekt: Industrielle Forschung und Entwicklung lokaler Radiofrequenz-Antennen fĂŒr hochauflösende Hochfeld-MRT des Körperstamme
eHealth Literacy in German Skin Cancer Patients
The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patientsâ primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease
Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma
BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment
The price of tumor control
Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (nâ=â752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientĆ delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects
Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma
Background: Ipilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma. Patients and methods: We undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs),including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months. Results: 103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %,14 % and 27 %,respectively. Median OS was 6.8 months (95 % CI 5.3-9.9) for cutaneous, 9.6 months (95 % CI 1.6-11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %,17 % and 11 %,respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %),none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %),including 20 grade 3-4 events (19 %). No new and unexpected safety findings were noted. Conclusions: Ipilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines
Wideband SelfâGrounded BowâTie Antenna for Thermal MR
The objective of this study was the design, implementation, evaluation and application of a compact wideband selfâgrounded bowâtie (SGBT) radiofrequency (RF) antenna building block that supports anatomical proton (1H) MRI, fluorine (19F) MRI, MR thermometry and broadband thermal intervention integrated in a wholeâbody 7.0 T system.
Design considerations and optimizations were conducted with numerical electromagnetic field (EMF) simulations to facilitate a broadband thermal intervention frequency of the RF antenna building block. RF transmission (B1+) field efficiency and specific absorption rate (SAR) were obtained in a phantom, and the thigh of human voxel models (Ella, Duke) for 1H and 19F MRI at 7.0 T. B1+ efficiency simulations were validated with actual flipâangle imaging measurements. The feasibility of thermal intervention was examined by temperature simulations (f = 300, 400 and 500 MHz) in a phantom. The RF heating intervention (Pin = 100 W, t = 120 seconds) was validated experimentally using the proton resonance shift method and fiberoptic probes for temperature monitoring. The applicability of the SGBT RF antenna building block for in vivo 1H and 19F MRI was demonstrated for the thigh and forearm of a healthy volunteer.
The SGBT RF antenna building block facilitated 19F and 1H MRI at 7.0 T as well as broadband thermal intervention (234â561 MHz). For the thigh of the human voxel models, a B1+ efficiency â„11.8 ÎŒT/âkW was achieved at a depth of 50 mm. Temperature simulations and heating experiments in a phantom demonstrated a temperature increase ÎT >7 K at a depth of 10 mm.
The compact SGBT antenna building block provides technology for the design of integrated highâdensity RF applicators and for the study of the role of temperature in (pathoâ) physiological processes by adding a thermal intervention dimension to an MRI device (Thermal MR).BMBF, 13GW0102A, KMU-Innovativ - Verbundprojekt: Forschung fĂŒr Tumortherapie mit lokalisierter Hochfrequenz-Hyperthermie: Diagnostik, Therapiesteuerung und -kontrolle mit ultrahochfeld MRT (3-IN-1:THERAHEAT) - Teilvorhaben: Erforschung von Hochfrequenzantennen fĂŒr Tumortherapie mittels kontrollierter Hochfrequenz-HyperthermieEC/H2020/EU/743077/Thermal Magnetic Resonance: A New Instrument to Define the Role of Temperature in Biological Systems and Disease for Diagnosis and Therapy/ThermalM
Cancer immunotherapy is accompanied by distinct metabolic patterns in primary and secondary lymphoid organs observed by non-invasive in vivo18F-FDG-PET
Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4+ T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18F-FDG-PET/CT scans revealed enhanced 18F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point
The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network
Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientĆ delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects
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