[Show abstract][Hide abstract] ABSTRACT: Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication. We describe our initial results for re-irradiation in heavily pre-treated ACC patients.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate HPV-DNA and p16INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer.Methods
From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.ResultsMedian follow-up was 48.6 months (range 2.8–169.1 months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p = 0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p < 0.001] and improved local control [81.0% vs. 55.9%, p = 0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p = 0.015] and PFS [p = 0.002] for cHPPAC.Conclusion
The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.
Radiotherapy and Oncology 11/2014; · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Protons and carbon ions currently are the most used charged-particle therapies in the cancer treatment of humans. This review summarizes the physical and biological differences and their impact on clinical use. Furthermore, published data in the treatment of several tumor entities and the use of protons and carbon ions are collected and discussed.
The Cancer Journal 11/2014; 20(6):433-9. · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is compared with step-and-shoot IMRT (SSIMRT) of the prostate gland by measuring the dose distribution within patients' lymphocytes. In this prospective study, blood was taken from 20 patients before and 10 min after their first irradiation fraction for each technique. The isolated leukocytes were fixed 2 h after radiation. DNA double-stranded breaks in lymphocyte nuclei were stained immunocytochemically using anti-gamma-H2AX antibodies. Gamma-H2AX foci distribution in lymphocytes was determined for each patient. Using a calibration line, dose distributions in patients' lymphocytes were determined by studying the gamma-H2AX foci distribution, and these data were used to generate a cumulative dose-lymphocyte histogram (DLH). Measured in vivo (DLH), significantly fewer lymphocytes indicated low-dose exposure (<40% of the applied dose) during TOMO compared with SSIMRT. The dose exposure range, between 45 and 100%, was equal with both radiation techniques. The mean number of gamma-H2AX foci per lymphocyte was significantly lower in the TOMO group compared with the SSIMRT group. In radiotherapy of the prostate gland, TOMO generates a smaller fraction of patients' lymphocytes with low-dose exposure relative to the whole body compared with SSIMRT. Differences in the constructional buildup of the different linear accelerator systems, e.g. the flattening filter, may be the cause thereof. The influence of these methods on the incidence of secondary malignancy should be investigated in further studies.
Journal of Radiation Research 10/2014; · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed.
Methods and Materials
From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy.
Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged.
Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.
International journal of radiation oncology, biology, physics 09/2014; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors.
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: OriginalbeitragTjessem KH, Johansen S, Malinen E et al (2013) Long-term cardiac mortality after hypofractionated radiation therapy in breast cancer. Int J Radiat Oncol Biol Phys 87:337–343Ziel der ArbeitWährend der letzten Jahre gewinnt die hypofraktionierte Radiotherapie beim Mammakarzinom zunehmend an Bedeutung. Tjessem und Kollegen aus Norwegen führten daher eine retrospektive Analyse der kardial bedingten Letalität innerhalb von 20 Jahren nach lokoregionaler Bestrahlung bei Patientinnen mit Mammakarzinom in Bezug auf den Grad der Hypofraktionierung und weiterer Behandlungsvariablen durch.Patienten und MethodeDie Fall-Kontroll-Studie umfasste 1566 norwegische Mammakarzinompatientinnen aus den Jahren 1975 bis 1991. Zwei hypofraktionierte Bestrahlungsregime kamen zum Einsatz: entweder 4,3 Gy 2-mal/Woche bis zu einer Gesamtdosis von 43,0 Gy (n = 1107) oder 2,5 Gy 4-mal/Woche bis zu einer Gesamtdosis von 50,0 Gy (n = 459). Um die kardiale Dosis retrospektiv abschätzen zu können, wurden ...
Strahlentherapie und Onkologie 08/2014; 190(8):774-775. · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current study was conducted to evaluate the long-term results of irradiation with carbon ions in a raster scanning technique in patients with skull base chordomas.
[Show abstract][Hide abstract] ABSTRACT: Scalp angiosarcoma represents a therapeutic challenge to all disciplines. This case report demonstrates the potential usefulness of helical tomotherapy (HT) as a new radiotherapeutic treatment option. A 71-year-old woman presented with a superficial angiosarcoma of the scalp, forehead, and left pre- and postauricular areas, with several nodular ulcerating and bleeding lesions. Irradiation of the gross tumor was performed with a total dose of 70 Gy in 2-Gy fractions and of the left cervical lymph nodes with 56 Gy in 1.6-Gy fractions. Good target coverage was achieved without compromising organs at risk, notably the brain. Treatment was very fast (661 seconds per fraction) and was administered with minimal acute toxicity (National Cancer Institute Common Toxicity Criteria: grade 2 erythema and grade 2 dysphagia). During treatment, tumor nodules dissolved into hyperkeratosis. We conclude that with HT, irradiation of the scalp and cervical lymph nodes can be conducted with minimal acute toxicity and without junction problems.
[Show abstract][Hide abstract] ABSTRACT: BackgroundConcurrent chemotherapy and radiation therapy is the preferred standard of care for patients with anal cancer. Several studies have suggested a benefit of intensity-modulated radiation therapy (IMRT) compared with 3D-conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our institution.MethodsA cohort of 105 anal cancer patients was treated with chemoradiation or radiation alone (16.2%) between January 2000 and December 2011. 37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up exams were performed every 3 to 6 months for a minimum of 3 years and then annually.ResultsMedian follow-up was 41.4 months (2.8 – 158.4). Overall survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT group without statistically significant difference. 3-year Colostomy-free survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3) acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT compared to IMRT/Tomotherapy.ConclusionThe use of IMRT can reduce acute severe side effects of the skin and gastrointestinal tract but did not demonstrate improved results regarding OS, PFS, LC and CFS.
[Show abstract][Hide abstract] ABSTRACT: Purpose
Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy.
Methods and Materials
Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporal correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V95) and 107% (V107) of the planned doses.
4D dose reconstruction based on daily measured data is possible in a clinical setting. V95 and V107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V95 > 87%, SD < 3%) and overdose (mean V107 < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients.
A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.
International journal of radiation oncology, biology, physics 05/2014; 89(1):175–181. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chordomas are relatively rare lesions of the bones. About 30% occur in the sacrococcygeal region. Surgical resection is still the standard treatment. Due to the size, proximity to neurovascular structures and the complex anatomy of the pelvis, a complete resection with adequate safety margin is difficult to perform. A radical resection with safety margins often leads to the loss of bladder and rectal function as well as motoric/sensoric dysfunction. The recurrence rate after surgery alone is comparatively high, such that adjuvant radiation therapy is very important for improving local control rates. Proton therapy is still the international standard in the treatment of chordomas. High-LET beams such as carbon ions theoretically offer biologic advantages in slow-growing tumors. Data of a Japanese study of patients with unresectable sacral chordoma showed comparable high control rates after hypofractionated carbon ion therapy only.Methods and design: This clinical study is a prospective randomized, monocentric phase II trial. Patients with histologically confirmed sacrococcygeal chordoma will be randomized to either proton or carbon ion radiation therapy stratified regarding the clinical target volume. Target volume delineation will be carried out based on CT and MRI data. In each arm the PTV will receive 64 GyE in 16 fractions. The primary objective of this trial is safety and feasibility of hypofractionated irradiation in patients with sacrococygeal chordoma using protons or carbon ions in raster scan technique for primary or additive treatment after R2 resection. The evaluation is therefore based on the proportion of treatments without Grade 3-5 toxicity (CTCAE, version 4.0) up to 12 months after treatment and/or discontinuation of the treatment for any reason as primary endpoint. Local-progression free survival, overall survival and quality of life will be analyzed as secondary end points.
The aim of this study is to confirm the toxicity results of the Japanese data in raster scan technique and to compare it with the toxicity analysis of proton therapy given in the same fractionation. Using this data, a further randomized phase III trial is planned, comparing hypofractionated proton and carbon ion irradiation.Trial registration: ClinicalTrials.gov Identifier: NCT01811394.
[Show abstract][Hide abstract] ABSTRACT: Radiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial.
Fifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of78Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).
Of the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months.
The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety and efficacy of reirradiation with carbon ions in patients with relapse of skull base chordoma and chondrosarcoma.
Reirradiation with carbon ions was performed on 25 patients with locally recurrent skull base chordoma (n = 20) or chondrosarcoma (n = 5). The median time between the last radiation exposure and the reirradiation with carbon ions was 7 years. In the past, 23 patients had been irradiated once, two patients twice. Reirradiation was delivered using the active raster scanning method. The total median dose was 51.0 GyE carbon ions in a weekly regimen of five to six fractions of 3 GyE. Local progression-free survival (LPFS) was evaluated using the Kaplan-Meier method; toxicity was evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE v.4.03).
The treatment could be finished in all patients without interruption. In 80 % of patients, symptom control was achieved after therapy. The 2-year-LPFS probability was 79.3 %. A PTV volume of < 100 ml or a total dose of > 51 GyE was associated with a superior local control rate. The therapy was associated with low acute toxicity. One patient developed grade 2 mucositis during therapy. Furthermore, 12 % of patients had tympanic effusion with mild hypacusis (grade 2), while 20 % developed an asymptomatic temporal lobe reaction after treatment (grade 1). Only one patient showed a grade 3 osteoradionecrosis.
Reirradiation with carbon ions is a safe and effective method in patients with relapsed chordoma and chondrosarcoma of the skull base.
Strahlentherapie und Onkologie 03/2014; · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the alpha/beta value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (alpha/beta = 4.0) and rectum (alpha/beta = 3.9).
The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL).
This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation.Trial registration: Clinical Trial Identifier: NCT01641185 (clinicaltrials.gov).
BMC Cancer 03/2014; 14(1):202. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adjuvant and salvage radiotherapy of the prostate bed are established treatment options for prostate cancer. While the benefit of an additional radiotherapy of the pelvic lymph nodes is still under debate, the PLATIN 3 prospective phase II clinical trial was initiated to substantiate toxicity data on postoperative IMRT of the pelvic lymph nodes and the prostate bed.
From 2009 to 2011, 40 patients with high-risk prostate cancer after prostatectomy with pT3 R0/1 M0 or pT2 R1 M0 or a PSA recurrence and either > 20% risk of lymph node involvement and inadequate lymphadenectomy or pN + were enrolled. Patients received two months of antihormonal treatment (AT) before radiotherapy. AT continuation was mandatory during radiotherapy and was recommended for another two years. IMRT of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated boost to the prostate bed (68.0 Gy) was performed in 34 fractions. PSA level, prostate-related symptoms and quality of life were assessed at regular intervals for 24 months.
Of the 40 patients enrolled, 39 finished treatment as planned. Overall acute toxicity rates were low and no acute grade 3/4 toxicity occurred. Only 22.5% of patients experienced acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. During follow-up, 10.0% late grade 2 GI and 5.0% late grade 2 GU toxicity occurred, and one patient developed late grade 3 proctitis and enteritis. After a median observation time of 24 months the PLATIN 3 trial has shown in 97.5% of all patients sufficient safety and thus met its prospectively defined aims. After a median of 24 months, 34/38 patients were free of a PSA recurrence.
Postoperative whole-pelvis IMRT with an integrated boost to the prostate bed can be performed safely and without excessive toxicity.Trial registration: Trial Numbers: ARO 2009--05, ClinicalTrials.gov: NCT01903408.
BMC Cancer 01/2014; 14(1):20. · 3.32 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Purpose/Objective(s): Prediction of dose heterogeneities caused by interplay effects in scanned ion beam therapy is challenging, due to the irregular patient motion and temporal variations of the beam delivery. Verification of the delivered dose, however, is desirable. We have investigated retrospective time-resolved (4D) treatment dose reconstruction based on online motion and beam monitoring for patients with mobile liver tumors.
Materials/Methods: The six selected patients with mobile hepatocellular carcinoma received treatment with scanned carbon ion beams in four fractions. Tumor motion amplitudes were 2-13 mm and 0-7 mm in the superior-inferior and anterior-posterior directions, respectively. Either abdominal compression (5 patients) or gating (1 patient) was used for motion mitigation. External monitoring of the patient motion was facilitated with a commercial system using a pressure sensor attached to a waist belt. The temporal structure of the beam delivery sequence (BDS) was acquired via the treatment records of the control system. Post-treatment 4D dose reconstruction was performed using our 4DTPS. Simulation of the 4D dose delivery in each fraction was based on the pre-treatment 4D computed tomography (4DCT) of the patient, the deformation maps obtained from deformable image registration of the 4DCT, the clinical treatment plan, and the temporally aligned motion monitoring and BDS data. For two patients, the total treatment dose was calculated by direct summation of the fractional dose distributions. The fractional and total dose to the clinical target volume (CTV) was assessed using the volume fractions receiving at least 95% and 107% of the prescribed dose (V95 and V107), respectively, and the volume receiving less than 95% of the prescribed dose (V<95).
Results: A total of 17 fractional dose distributions were reconstructed. V95 and V107 values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. For two patients, all fractional dose distributions exhibited V95 values larger than 95%. Four of the patients had V<95 volumes above 10 mL. The total treatment dose to the CTV exhibited improved dose coverage (V95 >95%) and over dose (V107 <10%) w.r.t. the single fraction dose for the two analyzed patients. V<95 volumes were reduced to below 2 mL.
Conclusions: A considerable impact of interplay effects on the single fraction CTV dose was found for the majority of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. The 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose verification.
American Society for Radiation Oncology 55th Annual Meeting, Atlanta, GA (USA); 10/2013
[Show abstract][Hide abstract] ABSTRACT: Whenever treating a patient with percutaneous radiotherapy, a certain amount of dose is inevitably delivered to healthy tissue. This is mainly due to beam's entry and exit in the region of the target volume. In regions distant from the target volume, dose is delivered by leakage from the MLC and head scatter from the accelerator head and phantom scatter from the target volume (peripheral dose). Helical tomotherapy is a form of radiation therapy with a uniquely designed machine and delivery pattern which influence the peripheral dose. The goal of this work was to investigate peripheral dose in helical tomotherapy. The experiments were used to establish a complex characterization of the peripheral dose.
A 30*30*60cm(3) slab phantom and TLD-100 (Lithium fluoride) were used for the experiments. Treatment procedures were generated with the tomotherapy planning system (TPS). Additionally, procedures were created on the Operator Station of the tomotherapy system without a calculation of the dose distribution. The peripheral dose which was produced by a typical tomotherapy treatment plan was measured. Furthermore, these procedures were used to differentiate the parts of the peripheral dose in phantom scatter dose and head scatter and leakage dose. Additionally, the relation between peripheral dose and treatment time and between peripheral dose and delivered dose was investigated. Additionally, the peripheral dose was measured in an Alderson phantom.
Distances of 30cm or more resulted in a decrease of the peripheral dose to less than 0.1% of the target dose. The measured doses have an offset of approximately 1cGy in comparison to the calculated doses from the TPS. The separated head scatter and leakage dose was measured in the range of 1cGy for typical treatments. Furthermore, the investigations show a linear correlation between head scatter leakage dose and treatment time and between scatter dose parts and delivered dose. A peripheral dose of 0.28% of the target dose was measured in the Alderson phantom at a distance of 17.5cm from the edge of the target volume.
The peripheral dose delivered by a tomotherapy treatment is clinically unobjectionable. The measurements confirmed a linear correlation between head scatter and leakage and treatment time and between scatter dose and delivered dose.
Zeitschrift für Medizinische Physik 07/2013; · 1.81 Impact Factor