Bystander effects and radiotherapy

Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.     

Condensed-history Monte-Carlo simulation for charged particles: what can it do for us?

Condensed-history (CH) Monte-Carlo (MC) groups together the vast number of individual charged-particle collisions using multiple scattering theory for elastic angular changes and stopping power for energy losses. CH codes such as EGS4 have been enormously successful in simulating the transport of electrons, for example, in radiotherapy. MC-derived values of the water-to-air stopping-power ratio, s _w/air, are used in all modern codes of practice for absolute dose determination in radiotherapy clinics. MC can also directly yield the dose ratio D _med/D _det for a dosimeter in a medium, and Correlated Sampling has been exploited to increase the efficiency, e. g., the central electrode in an ion chamber (aluminium vs. graphite). The extremely low density of the gas in an ion chamber poses problems for CH codes. However, multiple scattering can now be combined with single scattering and is expected to finally resolve important chamber perturbation effects. An exciting application of CH MC in radiotherapy is the computation of dose distributions in patients. Currently one can achieve an uncertainty around 1% (1 SD) in mm-sized voxels in several minutes for an electron beam and in around an hour for a photon treatment plan on hardware costing less than $20,000, and thus avoid all the various approximations conventionally used to account for inhomogeneities. In the microdosimetry/track structure field, CH codes have shown that the fluence (dΦ/dE) per unit dose at low electron energies is virtually independent of incident particle energy or depth, which simply explains the negligible RBE variation. Received: 1 April 1999 / Accepted in revised form: 1 July 1999     

Total skin electron beam therapy for primary cutaneous T-cell lymphomas: clinical characteristics and outcomes in a Mexican reference center

AimThe aim of this study was to assess treatment modalities, treatment response, toxicity profile, disease progression and outcomes in 14 patients with a confirmed diagnosis of primary cutaneous T-cell lymphoma (PCTCL) treated with total skin electron beam therapy (TSEBT).BackgroundPrimary cutaneous lymphomas (PCLs) are extranodal non-Hodgkin lymphomas originating in the skin without evidence of extracutaneous disease at diagnosis. Despite advances in systemic and local therapy options, the management of advanced stages remains mostly palliative.Materials and MethodsThis is a retrospective study of patients with PCTCL, diagnosed and treated in a reference center in Mexico City, analyzing treatment modalities, response to treatment, long-term outcome, and mortality.ResultsEight males (57%) and 6 (43%) females were identified. Most patients were stage IVA (n = 5, 36%) followed by stage IB and IIB (28.5% and 21.4%, respectively). Eleven patients received the low-dose RT scheme (12 Gy), 1 patient, the intermediate-dose RT scheme (24 Gy), and 2 patients, the conventional-dose RT scheme (36 Gy). Mean follow-up time was 4.6 years. At first follow-up examination, 6–8 weeks after radiotherapy, the overall response rate (ORR) for the cohort was 85%. The median PFS for the whole cohort was 6 months.ConclusionThis study reinforces the role of TSEBT when compared with other treatment modalities and novel agents. Low-dose TSEBT is now widely used because of the opportunity for retreatment.     

Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature

Treatment delays in completing radiotherapy (RT) for many neoplasms are a major problem affecting treatment outcome, as increasingly shown in the literature. Overall treatment time (OTT) could be a critical predictor of local tumor control and/or survival. In an attempt to establish a protocol for managing delays during RT, especially for heavily overloaded units, we have extensively reviewed the available literature on head and neck cancer. We confirmed a large deleterious effect of prolonged OTT on both local control and survival of these patients.     

SBRT and extreme hypofractionation: A new era in prostate cancer treatments?

AimRadiation therapy (RT) is a standard therapeutic option for prostate cancer (PC). In the last decades, several innovative technology applications have been introduced. 3-Dimensional conformal RT, volumetric/rotational intensity modulated RT associated or not with image-guided RT, are becoming largely diffused in the treatment of PC.BackgroundConsidering that PC could have a low α/β ratio, similar to late-reacting normal tissues, it could also be highly responsive to fraction size. Thus, the reduction of the number of fractions and the increase of the dose/fraction seem to be reasonable choices in the treatment of this cancer. This review reported the technology evolution, the radiobiological and the clinical data about the role of extreme hypofractionated RT in the treatment approach of PC patients.Materials and methodsMedline search and analysis of published studies containing key words: prostate cancer, radiotherapy, stereotactic radiotherapy.ResultsRecent technological developments, combined with an improved knowledge of the radiobiological models in favor of a high sensitivity of PC to larger fraction sizes are opening a new scenario in its treatment, reporting favorable efficacy and acceptable toxicity, despite short follow-up.ConclusionThus, thanks to technological improvement and the recent radiobiological data, “extreme hypofractionated RT” has been strongly introduced in the last years as a potential solid treatment option for PC.     

Curcumin induces radiosensitivity of in vitro and in vivo cancer models by modulating pre-mRNA processing factor 4 (Prp4)

Radiation therapy plays a central role in adjuvant strategies for the treatment of both pre- and post-operative human cancers. However, radiation therapy has low efficacy against cancer cells displaying radio-resistant phenotypes. Ionizing radiation has been shown to enhance ROS generation, which mediates apoptotic cell death. Further, concomitant use of sensitizers with radiation improves the efficiency of radiotherapy against a variety of human cancers. Here, the radio-sensitizing effect of curcumin (a derivative of turmeric) was investigated against growth of HCT-15 cells and tumor induction in C57BL/6J mice. Ionizing radiation induced apoptosis through ROS generation and down-regulation of Prp4K, which was further potentiated by curcumin treatment. Flow cytometry revealed a dose-dependent response for radiation-induced cell death, which was remarkably reversed by transfection of cells with Prp4K clone. Over-expression of Prp4K resulted in a significant decrease in ROS production possibly through activation of an anti-oxidant enzyme system. To elucidate an integrated mechanism, Prp4K knockdown by siRNA ultimately restored radiation-induced ROS generation. Furthermore, B16F10 xenografts in C57BL/6J mice were established in order to investigate the radio-sensitizing effect of curcumin in vivo. Curcumin significantly enhanced the efficacy of radiation therapy and reduced tumor growth as compared to control or radiation alone. Collectively, these results suggest a novel mechanism for curcumin-mediated radio-sensitization of cancer based on ROS generation and down-regulation of Prp4K.     

Tumores hipofisarios no funcionantes: actualización 2012

Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes > 4 cm³. Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long–term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ.