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To investigate therapeutic outcome of dose escalation ≥ 80 Gy in nonresected non-small cell lung cancer (NSCLC). 124 consecutive patients with histologically/cytologically proven NSCLC were enrolled. Tumor stage I, II, IIIA, and IIIB was diagnosed in 30, eight, 39, and 47 patients, respectively. 38 patients (31%) had weight loss > 5% during the 3 months before diagnosis. A median dose of 88.2 Gy (range 80.0–96.0 Gy), 69.3 Gy (63.0–88.0 Gy) and 56.7 Gy was applied to primary lesions, involved lymph nodes, and elective nodes (within a region of about 6 cm cranial to macroscopically involved nodes), respectively. Daily fractional ICRU doses of 2.0–2.2 Gy were delivered by the conformal target-splitting technique. 58 patients (47%) received induction chemotherapy, in median two cycles prior to radiotherapy. Median follow-up time of all patients was 19 months, of patients alive 72.4 months (69–121 months). The cumulative actual overall survival rate at 2 and 5 years amounts to 39% and 11.3%, respectively, resulting in a median overall survival time of 19.6 months. According to stages I, II, IIIA, and IIIB, the median overall survival times are 31.8, 31.4, 19.0, and 14.5 months, respectively. The locoregional tumor control rate at 2 years is 49%. Apart from one treatment-related death (pneumonitis), acute toxicity according to EORTC/RTOG scores was moderate: lung grade 2 (n = 7), grade 3 (n = 3); esophagus grade 1 (n = 11); heart grade 3 (n = 1, pericarditis). No late toxicity grade > 1 has been observed. Sequential, conventionally fractionated high-dose radiotherapy by conformal target splitting is well tolerated. The results for survival and locoregional tumor control seem to at least equalize the outcome of simultaneous chemoradiation approaches, which, at present, are considered “state of the art” for patients with nonresected NSCLC. A higher potential of radiation therapy might be reached by accelerated fractionation regimens.

Purpose Our purpose was to investigate the tolerability of accelerated, twice-daily, high-dose radiotherapy. The secondary endpoints were survival and locoregional tumor control. Methods and Materials Thirty consecutive patients with histologically/cytologically proven non–small-cell lung cancer were enrolled. Tumor Stage I, II, IIIA, and IIIB was found in 7, 3, 12, and 8 patients, respectively. We applied a median of 84.6 Gy (range, 75.6–90.0 Gy) to the primary tumors, 63.0 Gy (range, 59.4–72.0 Gy) to lymph nodes, and 45 Gy to nodes electively (within a region of about 6 cm cranial to macroscopically involved sites). Fractional doses of 1.8 Gy twice daily, with an interval of 11 hours, were given, resulting in a median treatment time of 35 days. In the majority of patients the conformal target-splitting technique was used. In 19 patients (63%) two cycles of induction chemotherapy were given. The median follow-up time of survivors is 72 months (range, 62–74 months). Results We found Grade 1, 2 and 3 acute esophageal toxicity in 11 patients (37%), 2 patients (7%), and 2 patients (7%), respectively. Grade 2 acute pneumonitis was seen in 2 patients (7%). No late toxicity greater than Grade 1 was observed. The actual overall survival rates at 2 and 5 years are 63% and 23%, respectively; the median overall survival, 27.7 months. In 9 patients a local failure occurred, 7 of them presenting initially with an atelectasis without availability of 18-fluorodeoxyglucose–positron emission tomography staging at that time. In 4 patients recurrence occurred regionally. Conclusions This Phase I/II trial with long-term follow-up shows low toxicity with promising results for survival and locoregional tumor control.

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Wave–particle duality is frequently the first topic students encounter in elementary quantum physics. Although this phenomenon has been demonstrated with photons, electrons, neutrons, and atoms, the dual quantum character of the famous double-slit experiment can be best explained with the largest and most classical objects, which are currently the fullerene molecules. The soccer-ball-shaped carbon cages C60 are large, massive, and appealing objects for which it is clear that they must behave like particles under ordinary circumstances. We present the results of a multislit diffraction experiment with such objects to demonstrate their wave nature. The experiment serves as the basis for a discussion of several quantum concepts such as coherence, randomness, complementarity, and wave–particle duality. In particular, the effect of longitudinal (spectral) coherence can be demonstrated by a direct comparison of interferograms obtained with a thermal beam and a velocity selected beam in close analogy to the usua...

We report on fullerene interference experiments using the two abundant fullerenes C60 and C70. Compared to previous experiments the detected molecular flux has been improved by about an order of magnitude. This now permits either a better collimation or a velocity selection. In both cases, demonstrated here, we see a good improvement of the interference contrast for both fullerene species. In the case of C60 the interference minima go down to the background level — indicating almost perfect coherence.

We discuss the experimental challenges in coherent matter wave optics with fullerenes. In particular, the properties of our matter wave source and the features of our efficient, molecule-selective detector with high spatial resolution are presented. Their development was crucial for the successful recording of the molecular quantum interference patterns of individual molecules.

The goal of this work was to evaluate toxicity and local control following hypofractionated stereotactic radiation treatment with special focus on changes in tumor volume and hearing capacity.In all, 29 patients with unilateral acoustic neuroma were treated between 2001 and 2007 within a prospective radiation protocol (7 × 4 Gy ICRU dose). Median tumor volume was 0.9 ml. Follow-up started at 6 months and was repeated annually with MRI volumetry and audiometry. Hearing preservation was defined as preservation of Class A/B hearing according to the guidelines of the American Academy of Otolaryngology (1995).No patient had any intervention after a median imaging follow-up of 89.5 months, one patient showed radiological progression. Transient increase of tumor volume developed in 17/29 patients, whereas 22/29 patients (75.9%) presented with a volume reduction at last follow-up. A total of 21 patients were eligible for hearing evaluation. Mean pure tone average (PTA) deteriorated from 39.3 to 65.9 dB and mean speech discrimination score (SDS) dropped from 74.3 to 38.1%. The 5-year actuarial Class A/B hearing preservation rate was 50.0 ± 14.4%.Radiation increases only minimally, if at all, the hearing deterioration which emerges by observation alone. Presbyacusis is not responsible for this deterioration. Transient tumor enlargement is common. Today radiation of small- and medium-sized acoustic neuroma can be performed with different highly conformal techniques as fractionated treatment or single low-dose radiosurgery with equal results regarding tumor control, hearing preservation, and side effects. Hypofractionation is more comfortable for the patient than conventional regimens and represents a serious alternative to frameless radiosurgery.

Background In this study we investigate the accuracy of industrial six axes robots employed for patient positioning at the Heidelberg Ion Beam Therapy Center. Methods In total 1018 patient setups were monitored with a laser tracker and subsequently analyzed. The measurements were performed in the two rooms with a fixed horizontal beam line. Both, the 3d translational errors and the rotational errors around the three table axes were determined. Results For the first room the 3d error was smaller than 0.72 mm in 95 percent of all setups. The standard deviation of the rotational errors was at most 0.026° for all axes. For the second room Siemens implemented an improved approach strategy to the final couch positions. The 95 percent quantile of the 3d error could in this room be reduced to 0.53 mm; the standard deviation of the rotational errors was also at most 0.026°. Conclusions Robots are very flexible tools for patient positioning in six degrees of freedom. This study proved that the robots are able to achieve clinically acceptable accuracy in real patient setups, too.

Purpose To investigate repositioning accuracy in particle radiotherapy in 6 degrees of freedom (DOF) and intensity-modulated radiotherapy (IMRT, 3 DOF) for two immobilization devices (Scotchcast masks vs thermoplastic head masks) currently in use at our institution for fractionated radiation therapy in head and neck cancer patients. Methods and materials Position verifications in patients treated with carbon ion therapy and IMRT for head and neck malignancies were evaluated. Most patients received combined treatment regimen (IMRT plus carbon ion boost), immobilization was achieved with either Scotchcast or thermoplastic head masks. Position corrections in robotic-based carbon ion therapy allowing 6 DOF were compared to IMRT allowing corrections in 3 DOF for two standard immobilization devices. In total, 838 set-up controls of 38 patients were analyzed. Results Robotic-based position correction including correction of rotations was well tolerated and without discomfort. Standard deviations of translational components were between 0.5 and 0.8 mm for Scotchcast and 0.7 and 1.3 mm for thermoplastic masks in 6 DOF and 1.2 - 1.4 mm and 1.0 - 1.1 mm in 3 DOF respectively. Mean overall displacement vectors were between 2.1 mm (Scotchcast) and 2.9 mm (thermoplastic masks) in 6 DOF and 3.9 - 3.0 mm in 3 DOF respectively. Displacement vectors were lower when correction in 6 DOF was allowed as opposed to 3 DOF only, which was maintained at the traditional action level of > 3 mm for position correction in the pre-on-board imaging era. Conclusion Setup accuracy for both systems was within the expected range. Smaller shifts were required when 6 DOF were available for correction as opposed to 3 DOF. Where highest possible positioning accuracy is required, frequent image guidance is mandatory to achieve best possible plan delivery and maintenance of sharp gradients and optimal normal tissue sparing inherent in carbon ion therapy.

Quantum superposition lies at the heart of quantum mechanics and gives rise to many of its paradoxes. Superposition of de Broglie matter waves1 has been observed for massive particles such as electrons2, atoms and dimers3, small van der Waals clusters4, and neutrons5. But matter wave interferometry with larger objects has remained experimentally challenging, despite the development of powerful atom interferometric techniques for experiments in fundamental quantum mechanics, metrology and lithography6. Here we report the observation of de Broglie wave interference of C60 molecules by diffraction at a material absorption grating. This molecule is the most massive and complex object in which wave behaviour has been observed. Of particular interest is the fact that C60 is almost a classical body, because of its many excited internal degrees of freedom and their possible couplings to the environment. Such couplings are essential for the appearance of decoherence7,8, suggesting that interference experiments with large molecules should facilitate detailed studies of this process.

In this study, a new method is introduced, which allows the overlay of three-dimensional structures, that have been delineated on transverse slices, onto the fluoroscopy from conventional simulators in real time. Setup deviations between volumetric imaging and simulation were visualized, measured and corrected for 701 patient isocenters. Comparing the accuracy to mere virtual simulation lacking additional X-ray imaging, a clear benefit of the new method could be shown. On average, virtual prostate simulations had to be corrected by 0.48 cm (standard deviation [SD] 0.38), and those of the breast by 0.67 cm (SD 0.66). The presented method provides an easy way to determine entity-specific safety margins related to patient setup errors upon registration of bony anatomy (prostate 0.9 cm for 90% of cases, breast 1.3 cm). The important role of planar X-ray imaging was clearly demonstrated. The innovation can also be applied to adaptive image-guided radiotherapy (IGRT) protocols.

For intraoperative radiotherapy (IORT) during breast-conserving treatment four different techniques have been addressed: interstitial brachytherapy, an inflatable balloon with a central high-dose-rate source (MammoSite), a miniature orthovolt system (Intrabeam), and linac-based electron radiotherapy (IOERT). The dosimetric properties of these methods are compared. Planning target volumes (PTVs) of the same size but of different shapes are assumed, corresponding to the technique’s specific situs. Dose distributions for the PTVs and for surrounding tissues are demonstrated by dose-volume histograms and a list of physical parameters. A dose inhomogeneity index (DII) is introduced to describe the deviation of a delivered from the prescribed dose, reaching its minimal value 0 in case of perfect homogeneity. In terms of DII, IOERT reaches the lowest value followed by the MammoSite, the Intrabeam and interstitial implants. The surrounding tissues receive the smallest average dose with IOERT, closely followed by the orthovolt system. When comparing simplified geometric figures, IOERT delivers the most homogeneous dose distributions. However, in clinical reality PTVs often present asymmetric shapes instead of ideal geometries. Due to a strictly centric dose fall-off, any system with a round central applicator will have technical limits. During IOERT margin-directed applicator guidance is possible and interstitial brachytherapy allows for polygonal dose shaping. These techniques seem to be superior for asymmetric PTV irradiation.

Aim of this study is to show that ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery can be reduced by proper surgery and modern radiotherapy techniques. Three hundred and seventy eight women with stage I or II breast cancer had breast conserving surgery and received 51–56.1 Gy of postoperative radiation to the whole breast in 1.7 Gy fractions, but patients received different boost strategies. Group 1 (n = 188) received electron boost radiation of 12 Gy subsequent to the irradiation to the whole breast, group 2 (n = 190) received intraoperative electron boost radiation of 9 Gy directly to the tumor bed, followed by whole breast irradiation. After a median follow up period of 81.0 months in group 1 and a median follow up period of 51.1 months in group 2, 12 IBTRs (6.4%) could be observed in group 1 and no IBTR could be observed in group 2 (0.0%). The 5-year actuarial rates of IBTR were 4.3% (95% CI, 1.9–8.3%) and 0.0% (95% CI, 0.0–1.9%), respectively (p = 0.0018). The 5-year actuarial rates of distant recurrence were 8.6% (95% CI, 4.9–13.5%) and 4.2% (95% CI, 1.8–8.2%), respectively (p = 0.08). The 5 year disease-free survival rates were 90.9% (95% CI, 85.8–94.7%) in group 1 and 95.8% (95% CI, 91.8–98.2%) in group 2 (p = 0.064). Immediate IORT-boost and whole breast irradiation yields excellent local control at 5 years, and was associated with a statistically significant decreased rate of IBTR compared with a similar cohort of patients treated with whole breast irradiation and conventional electron boost. © 2005 Wiley-Liss, Inc.

When thinking about quantum non-locality a modern physicist would probably think of two-particle entanglement first. And many beautiful experimental demonstrations have been published on quantum systems which violate Bell's inequalities [1].

We demonstrate that structures made of light can be used to coherently control the motion of complex molecules. In particular, we show diffraction of the fullerenes C60 and C70 at a thin grating based on a standing light wave. We prove experimentally that the principles of this effect, well known from atom optics, can be successfully extended to massive and large molecules which are internally in a thermodynamic mixed state and which do not exhibit narrow optical resonances. Our results will be important for the observation of quantum interference with even larger and more complex objects., Comment: 4 pages, 3 figures

The Heisenberg uncertainty principle for material objects is an essential corner stone of quantum mechanics and clearly visualizes the wave nature of matter. Here we report a demonstration of the Heisenberg uncertainty principle for the most massive, complex and hottest single object so far, the fullerene molecule C70 at a temperature of 900 K. We find a good quantitative agreement with the theoretical expectation: dx * dp = h, where dx is the width of the restricting slit, dp is the momentum transfer required to deflect the fullerene to the first interference minimum and h is Planck's quantum of action., Comment: 4 pages, 4 figures

Summary form only given, as follows. In a recent experiment we were able to demonstrate the de Broglie wave character of the fullerene molecule C/sub 60/ by diffraction at a free standing material grating. This proves that it is possible to preserve quantum coherence almost completely in the external degrees of freedom of a hot, massive and complex object over a long time and distance. This may seem astonishing in the light of the fact that the fullerenes were produced in a thermal source which was kept at about 900 K. At such a high temperature the de Broglie wavelength is about 400 times smaller than the size of the molecule (/spl lambda//sub dB//spl sim/25 pm), all internal degrees of freedom (174 different vibrational modes, and rotational modes up to J>100) are excited and the molecules may emit a few infrared photons (blackbody radiation and vibrational quanta) during their time of flight through the apparatus. Our published measurements so far have been essentially consistent with the absence of decoherence during the time of flight of the molecules. The interference contrast in all experiments has however so far been limited by the thermal velocity spread and the finite collimation of the fullerene beam.

While in the last decade atom interferometry[1] has become a rapidly expanding field, coherent de Broglie optics with large molecules has still remained completely unexplored. We propose that interesting new physics is to be expected in such experiments. In particular the mechanisms of decoherence in mesoscopic systems may be studied far beyond existing experiments[2]. New insights may also be expected for the possibilities of entanglement of large objects. New boundary effects should be observable in the scattering of large particles at small apertures. Finally, new experimental technologies like molecular nano-lithography and quantum physics of small biomolecules would be opened up. In order to successfully perform such experiments it is essential to find suitable beam sources, efficient detectors, and coherent optical elements for macromolecules. Some prospects shall be outlined below. Large molecules pose several experimental challenges since most of them cannot simply be thermally vaporized without fragmentation or structural changes nor can their de Broglie wavelengths be easily modified. We have chosen C60 for our first experiments because of its ready availability, its exceptionally high stability against thermal decomposition and its particularly high symmetry.

Using the complementary wave- and particle-like natures of photons, it is possible to make ``interaction-free'' measurements where the presence of an object can be determined with no photons being absorbed. We investigated several ``interaction-free'' imaging systems, i.e. systems that allow optical imaging of photosensitive objects with less than the classically expected amount of light being absorbed or scattered by the object. With the most promising system, we obtained high-resolution (10 \mu m), one-dimensional profiles of a variety of objects (human hair, glass and metal wires, cloth fibers), by raster scanning each object through the system. We discuss possible applications and the present and future limits for interaction-free imaging., Comment: 10 pages, 6 encapsulated Postscript figure files, accepted for publication in Physical Review A