Calculation and spectroscopy of the Landau band structure at a thin and atomically precise tunneling barrier

Two laterally adjacent quantum Hall systems separated by an extended barrier of a thickness on the order of the magnetic length possess a complex Landau band structure in the vicinity of the line junction. The energy dispersion is obtained from an exact quantum-mechanical calculation of the single electron eigenstates for the coupled system by representing the wave functions as a superposition of parabolic cylinder functions. For orbit centers approaching the barrier, the separation of two subsequent Landau levels is reduced from the cyclotron energy to gaps which are much smaller. The position of the anticrossings increases on the scale of the cyclotron energy as the magnetic field is raised. In order to experimentally investigate a particular gap at different field strengths but under constant filling factor, a GaAs/AlGaAs heterostructure with a 52 Angstrom thick tunneling barrier and a gate electrode for inducing the two-dimensional electron systems was fabricated by the cleaved edge overgrowth method. The shift of the gaps is observed as a displacement of the conductance peaks on the scale of the filling factor. Besides this effect, which is explained within the picture of Landau level mixing for an ideal barrier, we report on signatures of quantum interferences at imperfections of the barrier which act as tunneling centers. The main features of the recent experiment of Yang, Kang et al. are reproduced and discussed for different gate voltages. Quasiperiodic oscillations, similar to the Aharonov Bohm effect at the quenched peak, are revealed for low magnetic fields before the onset of the regular conductance peaks.Comment: 8 pages, 10 figures, 1 tabl

Intraoperative electron radiation therapy (IOERT) in patients with locally recurrent renal cell carcinoma

Background: To analyze our experience with intraoperative electron radiation therapy (IOERT) followed by moderate doses of external beam radiation therapy (EBRT) in patients with locally recurrent renal cell carcinoma. Methods: From 1992 to 2010, 17 patients with histologically proven, locally recurrent renal cell carcinoma (median tumor size 7 cm) were treated by surgery and IOERT with a median dose of 15 Gy. All patients met the premise of curative intent including 7 patients with oligometastases at the time of recurrent surgery, which were resected and/or irradiated. The median time interval from primary surgery to local recurrence was 26 months. Eleven patients received additional 3D-conformal EBRT with a median dose of 40 Gy. Results: Surgery resulted in free but close margins in 6 patients (R0), while 9 patients suffered from microscopic (R1) and 2 patients from macroscopic (R2) residual disease. After a median follow-up of 18 months, two local recurrences were observed, resulting in an actuarial 2-year local control rate of 91%. Eight patients developed distant failures, predominantly to liver and bone, resulting in an actuarial 2-year progression free survival of 32%. An improved PFS rate was found in patients with a larger time interval between initial surgery and recurrence (> 26 months). The actuarial 2-year overall survival rate was 73%. Lower histological grading (G1/2) was the only factor associated with improved overall survival. Perioperative complications were found in 4 patients. No IOERT specific late toxicities were observed. Conclusions: Combination of surgery, IOERT and EBRT resulted in high local control rates with low toxicity in patients with locally recurrent renal cell cancer despite an unfavorable surgical outcome in the majority of patients. However, progression-free and overall survival were still limited due to a high distant failure rate, indicating the need for intensified systemic treatment especially in patients with high tumor grading and short interval to recurrence

PSMA-PET based radiotherapy: a review of initial experiences, survey on current practice and future perspectives

Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy. This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist’s point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here

Rotational IMRT techniques compared to fixed gantry IMRT and Tomotherapy: multi-institutional planning study for head-and-neck cases

<p>Abstract</p> <p>Background</p> <p>Recent developments enable to deliver rotational IMRT with standard C-arm gantry based linear accelerators. This upcoming treatment technique was benchmarked in a multi-center treatment planning study against static gantry IMRT and rotational IMRT based on a ring gantry for a complex parotid gland sparing head-and-neck technique.</p> <p>Methods</p> <p>Treatment plans were created for 10 patients with head-and-neck tumours (oropharynx, hypopharynx, larynx) using the following treatment planning systems (TPS) for rotational IMRT: Monaco (ELEKTA VMAT solution), Eclipse (Varian RapidArc solution) and HiArt for the helical tomotherapy (Tomotherapy). Planning of static gantry IMRT was performed with KonRad, Pinnacle and Panther DAO based on step&shoot IMRT delivery and Eclipse for sliding window IMRT. The prescribed doses for the high dose PTVs were 65.1Gy or 60.9Gy and for the low dose PTVs 55.8Gy or 52.5Gy dependend on resection status. Plan evaluation was based on target coverage, conformity and homogeneity, DVHs of OARs and the volume of normal tissue receiving more than 5Gy (V_5Gy). Additionally, the cumulative monitor units (MUs) and treatment times of the different technologies were compared. All evaluation parameters were averaged over all 10 patients for each technique and planning modality.</p> <p>Results</p> <p>Depending on IMRT technique and TPS, the mean CI values of all patients ranged from 1.17 to 2.82; and mean HI values varied from 0.05 to 0.10. The mean values of the median doses of the spared parotid were 26.5Gy for RapidArc and 23Gy for VMAT, 14.1Gy for Tomo. For fixed gantry techniques 21Gy was achieved for step&shoot+KonRad, 17.0Gy for step&shoot+Panther DAO, 23.3Gy for step&shoot+Pinnacle and 18.6Gy for sliding window.</p> <p>V_5Gyvalues were lowest for the sliding window IMRT technique (3499 ccm) and largest for RapidArc (5480 ccm). The lowest mean MU value of 408 was achieved by Panther DAO, compared to 1140 for sliding window IMRT.</p> <p>Conclusions</p> <p>All IMRT delivery technologies with their associated TPS provide plans with satisfying target coverage while at the same time respecting the defined OAR criteria. Sliding window IMRT, RapidArc and Tomo techniques resulted in better target dose homogeneity compared to VMAT and step&shoot IMRT. Rotational IMRT based on C-arm linacs and Tomotherapy seem to be advantageous with respect to OAR sparing and treatment delivery efficiency, at the cost of higher dose delivered to normal tissues. The overall treatment plan quality using Tomo seems to be better than the other TPS technology combinations.</p

Heat Shock Protein 70 (Hsp70) Peptide Activated Natural Killer (NK) Cells for the Treatment of Patients with Non-Small Cell Lung Cancer (NSCLC) after Radiochemotherapy (RCTx) – From Preclinical Studies to a Clinical Phase II Trial

Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose IL-2 (TKD/IL-2). Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and non-small cell lung cancer (NSCLC) in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2014. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum-based radiochemotherapy (RCTx) with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with RCTx alone. As secondary endpoints overall survival, toxicity, quality-of-life, and biological responses will be determined in both study groups

Berechnung und Tunnelspektroskopie der Landau-Bandstruktur zweier lateral gekoppelter Quanten-Hall-Systeme mit variablem Fermi-Niveau

Die quasifreien Ladungsträger eines zweidimensionalen Elektronensystems kondensieren im senkrechten Magnetfeld in den äquidistanten und vielfach entarteten Landau-Niveaus. Variationen des elektrostatischen Potentials führen zur lokalen Aufhebung der Entartung und somit zur Entstehung von Landau-Bändern. Im Bereich einer Tunnelbarriere, die zwei lateral benachbarte Elektronensysteme voneinander trennt, liegt eine komplexe Landau-Bandstruktur vor. Im Falle schwacher Kopplung läßt sich diese näherungsweise als Überlagerung der zueinander spiegelverkehrten Dispersionen beider Teilsysteme darstellen, wobei an den Kreuzungspunkten zur Aufhebung der Entartung Landau-Bandlücken existieren. Der Tunnelstrom durch die Barriere nimmt ein Maximum an, wenn das Fermi-Niveau mit einer der Antikreuzungen übereinstimmt. Im ersten Teil der vorliegenden Arbeit wird eine Methode zur Berechnung der Landau-Bandstruktur eines Quanten-Hall-Systems mit einer unidirektionalen und stückweise konstanten Potentialmodulation vorgestellt. Die Kenntnis der Energieeigenzustände ermöglicht im zweiten Teil der Dissertation die Auswertung der magnetfeldabhängigen Leitwertkurven für zwei lateral gekoppelte Elektronensysteme. Im Rahmen der Effektive-Masse-Näherung wird die Schrödinger-Gleichung für ein 2D-Elektron gelöst, das sich im parabolischen magnetischen Einschlußpotential und im abschnittsweise konstanten Leitungsbandverlauf einer intrinsischen Halbleiter-Heterostruktur befindet. Die exakte Lösung des Problems ist durch einen Ansatz mit Parabolischen Zylinderfunktionen möglich. Nach der Diskussion der allgemeinen Eigenschaften des Energiespektrums und der zugehörigen Wellenfunktionen wird ein dedizierter Algorithmus zur Lösung der Stetigkeitsbedingungen in einem System mit drei Bereichen konstanten Potentials vorgestellt. Das Verfahren, das universell für einen harmonischen Oszillator mit überlagertem, zweistufigen Potential anwendbar ist, erlaubt die Berechnung der Landau-Bandstruktur im Bereich einer Tunnelbarriere (mit oder ohne Vorspannung) oder eines rechteckförmigen Potentialtopfs (Quantendraht). Zwei lateral benachbarte Elektronensysteme wurden im Rahmen dieser Arbeit mit Hilfe der Methode des Überwachsens von Spaltflächen im GaAs/AlGaAs-Materialsystem bei Verwendung einer 52 Angström dicken Barriere realisiert. Im Vergleich zu Experimenten mit modulationsdotierten Elektronensystemen (Kang et al., Nature 403, 59 (2000)) zeichnet sich das Probendesign durch eine Steuerelektrode aus, die es ermöglicht, eine bestimmte Landau-Bandlücke unter Variation des Fermi-Niveaus bei verschiedenen Magnetfeldern zu spektroskopieren. Anstatt für eine Betrachtung derselben Antikreuzung bei verschiedenen Barrierendicken mehrere Proben zu präparieren, kann die effektive Barrierenform (in Einheiten der magnetischen Länge und der Zyklotron-Energie) als Funktion der magnetischen Flußdichte variiert werden. Für eine zunehmende Amplitude des Magnetfelds ergeben Bandstrukturrechnungen einen Anstieg der Landau-Bandlücken auf der Skala der Zyklotron-Energie. Dieser Effekt zeigt sich im Experiment in Form einer Verschiebung der Leitwertspitzen auf der Skala des Füllfaktors in Richtung größerer Werte. Bei hohen Steuerspannungen baut sich aufgrund von Leckströmen eine interne Vorspannung auf. Die entsprechende Verzerrung der Bandstruktur bewirkt eine Verschiebung der Leitwertspitzen in Richtung kleinerer Füllfaktoren. Der Tunnelstrom ist nicht nur durch die Bandstruktur und die Lage des Fermi-Niveaus, sondern auch maßgeblich durch zufällig innerhalb der Barriere verteilte Defekte mit lokal erhöhter Tunnelwahrscheinlichkeit bestimmt. Wenn das unterste Landau-Band vollständig gefüllt ist, treten aufgrund dieser Tunnelzentren zwischen gegenüberliegenden Randkanälen Aharonov-Bohm-Oszillationen auf. Unter Verwendung der Energieeigenfunktionen der interferierenden Randzustände wird aus der Periode dieser Leitwertoszillationen der Abstand der beteiligten Tunnelzentren bestimmt. Gleichzeitig mit den Aharonov-Bohm-Oszillationen treten langperiodische und irreguläre Strukturen im Bereich der Leitwertspitze mit dem kleinsten Füllfaktor auf. Sie sind eine Folge des Unordnungspotentials, das in der realen Probe dazu führt, daß die Lage der Randkanäle keine glatte Funktion der magnetischen Flußdichte ist. Bei kleinen Magnetfeldern werden Leitwertfluktuationen beobachtet, die nicht das Ergebnis interferierender Randkanäle sind, sondern die in dem Mehrfachspalt-Interferometer der gekoppelten Elektronensysteme aufgrund der im Bereich der Barriere reduzierten Zahl an transversalen Moden auftreten

Aggressive local treatment containing intraoperative radiation therapy (IORT) for patients with isolated local recurrences of pancreatic cancer: a retrospective analysis

Abstract Background To evaluate the use of intraoperative radiation therapy (IORT) in the multimodality treatment of patients with isolated local recurrences of pancreatic cancer. Methods We retrospectively analyzed 36 patients with isolated local recurrences of pancreatic cancer who have been treated with a combination of surgery, IORT and EBRT. Median time from initial treatment to recurrence was 20 months. All patients were surgically explored. In 18 patients a gross total resection was achieved, whereas the other half received only debulking or no resection at all. All patients received IORT with a median dose of 15 Gy. Additional EBRT was applied to 31 patients with a median dose of 45 Gy, combined with concurrent, mainly gemcitabine-based chemotherapy. Results Median follow-up in surviving patients was 23 months. Local progression was found in 6 patients after a median time of 17 months, resulting in estimated 1- and 2-year local control rates of 91% and 67%, respectively. Distant failure was observed in 23 patients, mainly in liver or peritoneal space. The median estimated progression-free survival was 9 months with 1- and 2-year rates of 40% and 26%, respectively. We found an encouraging estimated median overall survival of 19 months, transferring into 1- and 2-year rates of 66% and 45%. Notably 6 of 36 patients (17%) lived for more than 3 years. Severe postoperative complications were found in 3 and chemoradiation-related grade III toxicity in 6 patients. No severe IORT related toxicity was observed. Conclusion Combination of surgery, IORT and EBRT in patients with isolated local recurrences of pancreatic cancer resulted in encouraging local control and overall survival in our cohort with acceptable toxicity. Our approach seems to be superior to palliative chemotherapy or chemoradiation alone and should be further investigated in a prospective setting specifically addressing isolated local recurrences of pancreatic cancer.</p

Oligometastases from prostate cancer: local treatment with stereotactic body radiotherapy (SBRT)

Abstract Background The impact of local tumor ablative therapy in oligometastasized prostate cancer (PC) is still under debate. To gain data for this approach, we evaluated oligometastasized PC patients receiving stereotactic body radiotherapy (SBRT) to bone metastases. Methods In this retrospective study, 15 oligometastasized PC patients with a total of 20 bone metastases were evaluated regarding biochemical progression-free survival (PSA-PFS), time to initiation of ADT, and local control rate (LCR). Three patients received concomitant androgen deprivation therapy (ADT). Results The median follow-up after RT was 22.5 months (range 7.0–53.7 months). The median PSA-PFS was 6.9 months (range 1.1–28.4 months). All patients showing a decrease of PSA level after RT of at least factor 10 reveal a PSA-PFS of >12 months. Median PSA-PFS of this sub-group was 23.1 months (range 12.1–28.4 months). Local PFS (LPFS) after 2 years was 100%. One patient developed a local failure after 28.4 months. Median distant PFS (DPFS) was 7.36 months (range 1.74–54.34 months). The time to initiation of ADT in patients treated without ADT was 9.3 months (range 2.6–36.1 months). In all patients, the time to intensification of systemic therapy or the time to initiation of ADT increased from 9.3 to 12.3 months (range 2.6–36.1 months). Gleason-Score, ADT or the localization of metastasis had no impact on PFS or time to intensification of systemic therapy. No SBRT related acute or late toxicities were observed. Conclusion Our study shows that SBRT of bone metastases is a highly effective therapy with an excellent risk-benefit profile. However, PFS was limited due to a high distant failure rate implying the difficulty for patient selection for this oligometastatic concept. SBRT offers high local cancer control rates in bone oligometastases of PC and should be evaluated with the aim of curation or to delay modification of systemic treatment