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Purpose To evaluate the impact of endorectal balloon (ERB) on anorectal dose during postoperative VMAT of prostate cancer. Methods In ten patients referred for salvage radiotherapy CTs were obtained without ERB and with air-filled ERB of 50ml and 100ml. CTs were repeated weekly (4–6 control CTs) and registered to the respective planning CT. For each planning CT, a VMAT plan was made with defined anorectal dose constraints and propagated on the respective control CTs. The dose volumes V40Gy, V60Gy and V65Gy of the rectal and anal wall (Rwall and Awall, respectively) and the ERB position were obtained from each plan. Results In plans with ERB, the mean Rwall dose volumes V40Gy, V60Gy and V65Gy were higher by 8%, 5% and 2% (ERB 50ml) and 2%, 3% and 3% (ERB 100ml) in comparison to plans without ERB. The respective Awall dose volume differences were 2%, 0%, −1% (ERB 50ml), and −3%, −2%, −2% (ERB 100ml). The dose volume variability of the Rwall was comparable with and without ERB, but was slightly reduced by ERB for the Awall. The mean ERB position variability was >2mm in anterior–posterior and inferior–superior directions. Conclusion The use of ERB during post-operative VMAT has no advantages for anorectal dose.

To present an update of a prospective study evaluating an accelerated hypofractionated whole breast irradiation (WBI) schedule of the START A trial plus hypofractionated boost in breast cancer patients.One hundred and forty consecutive patients ≥55 years were included in this study. Patients received postoperative WBI with 13×3.2 Gy to 41.6 Gy plus a boost of 3.0 Gy/fraction to 9-12 Gy applied in3.5 weeks, depending on the resection margin. Prospectively planned follow-up (FU) visits, including objective and subjective assessment of treatment tolerance, were performed at 0 and 8 weeks, as well as one, two, four or more years following radiotherapy (RT).The 3-year rates of local control, nodal control, disease-free and overall survival were 99%, 100%, 96% and 91%, respectively. Cosmetic outcome was very good with 99% (n=110/111), 98% (n=99/101) and 100% (n=59/59) of the patients being satisfied or very satisfied one, two and four years after RT, respectively.Acceleration of the START A regime with 41.6 Gy WBI plus additional boost of 9-12 Gy remained effective and well-tolerated.

Purpose Prospective evaluation of accelerated hypofractionated radiotherapy (RT) in breast cancer patients treated with 41.6 Gy in 13 fractions plus boost delivered five times a week. Patients and methods Between 03/2009 and 10/2012 98 consecutive patients aged >55 years presenting with breast cancer (invasive cancer: n = 95, ductal carcinoma in situ (DCIS): n = 3) after breast conserving surgery were treated in our institution with the following schedule: 41.6 Gy in 13 fractions 4 times a week and 9 or 12 Gy boost in 3 or 4 fractions (on day 5 each week), cumulative dose: 50.6 Gy in 3.2 weeks or 53.6 Gy in 3.4 weeks, respectively depending on resection status. 56 patients had a T1 tumor, 39 a T2 tumor. N-status was as follows: N0: n = 71, N1: n = 25, N2/3: n = 2. 23 patients (24%) received chemotherapy before RT. A prospectively planned follow-up (FU) visit with objective and subjective assessment of treatment tolerance (questionnaires) was performed 0 and 8 weeks after RT completion, and one, two and four years later, respectively. Results Mean/median follow-up was 32/28 months (range: 12-56). After 2 years local control, loco-regional control and disease-free survival was 100%, 100%, and 98%, respectively. Overall survival was 96% at 2 years. Cosmetic outcome was very good with patients being satisfied or very satisfied in 99% (n = 86/87), 97% (n = 55/57) and 100% (n = 25/25) after one, two and four years after RT, respectively. No grade ≥ 2 pain was described in the 25 patients with a FU of at least 4 years. Fibrosis, telangiectasia and edema were found in 7-15%, 0-22% and 0-11% at one, two, and four years, respectively, and are comparable to other trials. Conclusion The applied hypofractionated RT regime with single doses of 3.2 Gy plus boost doses of 9-12 Gy in 3–4 fractions applied in 5 sessions a week was effective and well tolerated on intermediate term FU.

To evaluate the potential usage of flattening filter-free (FFF) photon beams in the treatment of prostate cancer.Volumetric-modulated arc therapy (VMAT) treatment planning was performed for 7 patients using TrueBeam(®) linear accelerator and photon beams with (X6, X10) and without (X6FFF, X10FFF) flattening filter. Prescribed dose was 19 × 3 Gy = 57 Gy. One or two 360° arcs with dose rate of 600 MU/min for flattened beams, and 1,200 MU/min for FFF beams were used.No difference was detected between the four beams in PTV coverage, conformity, and homogeneity. Mean body dose and body volume receiving 50% of the prescribed dose decreased with increasing mean energy (r(2) = 0.8275, p0.01). X6FFF delivered 3.6% more dose compared with the X6 (p0.01). X10FFF delivered 3.0% (p0.01), and the X10 5.8% (p 0.01) less mean body dose compared with X6. There was a significant increase in the mean dose to the rectum for the X10 compared with X6 (2.6%, p0.01). Mean dose to the bladder increased by 1.3% for X6FFF and decreased by 2.3% for X10FFF. Using a single arc and FFF, treatment time was reduced by 35% (2 SD = 10%).FFF beams resulted in dose distributions similar to flattened beams. X10FFF beam provided the best solution, sparing rectum and bladder and minimizing whole-body dose. FFF beams lead to a time efficient treatment delivery, particularly when combined with hypofractionated VMAT.

Purpose: : To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. Patients and Methods: : 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. Results: : The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG ≥3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. Conclusion: : As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated TBI at the low-dose rate that was generally used here. Conditioning for bone marrow transplantation without radiation is an attractive option, but is not sufficiently effective to completely replace TBI for the most common pediatric indications

Publisher Summary This chapter focuses on discovering oxygen sensing pathways by microscopy. Under normoxic conditions, O 2 sensing leads to an optimizing of cell function as exemplified by an enhanced phosphoenol pyruvate carboxykinase (PCK) expression in the periportal liver zone with high PO 2 levels and of enhanced glukokinase (GK) expression in the perivenous liver zone with low PO 2 levels. Under arterial hypoxia tissue, PO 2 frequency distribution is left shifted, leading to a hypoxic response of O 2 sensing for adaptation of cell function. In this chapter, three optical methods used to identify, locate, and image several putative members of the oxygen sensing pathway and their reaction to hypoxia are discussed. The three optical methods are based on light absorption photometry, the optical probe technique, and two-photon confocal laser microscopy. The described microscopic techniques are unique tools to reveal nature, regulation, and localization of critical members of the oxygen sensing pathway. Three-dimensional imaging of intracellular oxygen sensing and concepts related to two photon confocal laser-scanning microscopy and intracellular localization of prolyl hydroxylases are described.

The carotid body (CB) located at the carotid artery bifurcation informs the central nervous system about arterial p02 changes. The CB response to hypoxic stimuli includes augmented transmitter release and increased generation of action potentials in the carotid sinus nerve (CSN). Until now the molecular and cellular mechanisms of the oxygen sensing signal cascade are not clear. Cellular oxygen sensing processes are believed to be initiated by specialised cytochromes (Bunn and Poyton, 1996; Lopez-Barneo et al. 2001). In recent studies (Lahiri and Acker, 1999; Lahiri et. al 1999) simultaneous recordings of rat CB light absorption spectra and chemoreceptor discharge were used to characterize heme proteins as primary oxygen sensor. Redox spectra were deconvoluted by means of redox differential spectra of isolated non mitochondrial cytochrome b558 and mitochondrial cytochromes c550, b563 and the cytochrome c oxydase (CCO) peaking at 603 nm. Mathematically deconvolution fitted very closely to experimental spectra in the wavelength range between 520 and 570 nm confirming the contribution of cytochromes b558, c550 and b563 in the carotid body tissue. However, the wavelength range between 570 and 620 nm normally dominated by cytochrome aa3 of the CCO (absorbance peak at 603 nm) was fitted only partly indicating an additional component.

Light-absorption spectra and afferent chemoreceptor discharge were simultaneously recorded on superfused rat carotid bodies (CBs) under the influence of cytochrome a3-CuB ligands (O2, CN-, CO) in order to identify the primary mitochondrial cytochrome c oxidase (CCO) oxygen sensor. Spectra could be described on the basis of weighted light-absorption spectra of cytochrome b558 of the NAD(P)H oxidase and mitochondrial cytochromes b and c, CCO, cytochrome a3, and an unusual cytochrome a peaking at 592 nm. Discharge signals were deconvoluted into phasic and tonic activity for comparing different CB responses. The spectral weight of cytochrome a592 decreased significantly starting at high PO2 (100 mm Hg) and low sodium cyanide (CN-, 10 mM) accompanied by increasing phasic peak discharge. Combined CO-hypoxia or CO-CN- application inhibited photolysis of CO-stimulated chemoreceptor discharge, revealing photometrically cytochrome a592 as central in oxygen sensing. Control spectra in tissue from sympathetic and nodose ganglia did not show any cytochrome a592 contribution. According to these results, cytochrome a592 is assumed as a unique component of CB CCO, revealing in contrast to other cytochromes an apparent low PO2 and high CN- affinity, probably due to a shortcut of electron flow within CCO between CuA and cytochrome a3-CuB.