Magnetic fields and apoptosis: a possible mechanism.

The potential therapeutic uses of electromagnetic fields (EMF), part of the nonionizing radiation spectrum, increase with time. Among them, those considering the potential antitumor effects exerted by the Magnetic Fields (MFs), part of the EMF entity, have gained more and more interest. A recent review on this subject reports the MFs' effect on apoptosis of tumor cells as one of the most important breakthroughs. Apoptosis is considered a key mechanism regulating the genetic stability of cells and as such is considered of fundamental importance in cancer initiation and development. According to an atomic/sub-atomic analysis, based on quantum physics, of the complexity of biological life and the role played by oxygen and its radicals in cancer biology, a possible biophysical mechanism is described. The mechanism considers the influence of MFs on apoptosis through an effect on electron spin that is able to increase reactive oxygen species (ROS) concentration. Impacting on the delicate balance between ROS production and ROS elimination in tumor cells is considered a promising cancer therapy, affecting different biological processes, such as apoptosis and metastasis. An analysis in the literature, which allows correlation between MFs exposure characteristics and their influence on apoptosis and ROS concentration, supports the validity of the mechanism.

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma.

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.

Palliative radiotherapy for painful bone metastases from solid tumors delivered with static ports of tomotherapy (TomoDirect): feasibility and clinical results.

PURPOSE: To evaluate the feasibility and response to palliative radiotherapy delivered with static ports of tomotherapy--TomoDirect (TD) in patients affected with painful bone metastases from solid tumors. METHODS: A prospective cohort of 130 patients (185 osseous lesions) was treated between 2010 and 2013 with TD. Three fractionation schedules were employed according to clinical decision-making (3 Gy × 10; 4 Gy × 5; 8 Gy × 1). Pain response was investigated at 2 weeks and 2 months (for evaluable patients). The Numeric Rating Scale (NRS-11) was used to assess pain. Response rates to radiotherapy were calculated following the criteria of the International Bone Metastases Consensus Group (IBMCG), accounting for the use of concomitant analgesics (response: complete or partial; non-response: stable pain, pain progression or "other"). Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). RESULTS: Most of the patients had 1-2 bone metastases (91); those with multiple lesions mostly had a metachronous presentation (60%). Synchronous lesions were mainly approached with multiple plans (63%). Most treatments employed 3-4 fields (77%). Treatment times ranged from 255 to 939 s depending on fractionation, fields, and target lesions number. At 2 weeks, the median self-reported worst pain decreased significantly as median oral morphine-equivalent dose regardless of fractionation used. The response rate according to the IBMCG-based response categories ranged from 45 to 55%. Pain relief duration seems (response at 2 months) slightly inferior with the single fraction approach, with a higher re-treatment rate. At 2 weeks, the median self-reported worst pain and OMED significantly decreased regardless of fractionation (response rate: 49-55%). Pain relief decreased at 2 months, especially for single fraction (higher re-treatment rate). CONCLUSION: TD is a valid option to deliver palliative radiotherapy for painful bone metastases from solid tumors.

Dosimetric characterization and use of GAFCHROMIC EBT3 film for IMRT dose verification.

Radiochromic film has become an important tool to verify dose distributions in highly conformal radiation therapy such as IMRT. Recently, a new generation of these films, EBT3, has become available. EBT3 has the same composition and thickness of the sensitive layer of the previous EBT2 films, but its symmetric layer configuration allows the user to eliminate side orientation dependence, which is reported for EBT2 films. The most important EBT3 characteristics have been investigated, such as response at high-dose levels, sensitivity to scanner orientation and postirradiation coloration, energy and dose rate dependence, and orientation dependence with respect to film side. Additionally, different IMRT fields were measured with both EBT3 and EBT2 films and evaluated using gamma index analysis. The results obtained show that most of the characteristics of EBT3 film are similar to the EBT2 film, but the orientation dependence with respect to film side is completely eliminated in EBT3 films. The study confirms that EBT3 film can be used for clinical practice in the same way as the previous EBT2 film.

Interventional radiology at a single institution over 9 years: a comprehensive evaluation of procedures and an estimation of collective effective dose.

PURPOSE: To investigate the exposure parameters, effective dose, frequency, and collective dose for interventional radiology (IR) procedures performed at a single institution during a 9-year period. MATERIALS AND METHODS: According to the anatomic region imaged, seven diagnostic and 16 therapeutic IR procedures performed between 2002 and 2010 were retrospectively investigated with regard to exposure setting parameters and frequency. Dose-area products (DAPs), cumulative doses (CDs), and irradiation time values were analyzed on a sample of 1,100 examinations. DAP distributions (median, mean, and percentiles) were adjunctively determined by using bootstrap resampling in PCXMC software to estimate patient effective dose. Data provided by the Radiological Information System allowed collective effective and per-capita doses to obtained. RESULTS: The exposure parameters showed widespread variability. The median DAP values for pelvic arteriography and pelvic arterial angioplasty/stent placement were 10,015 and 19,424 cGy·cm(2), respectively. For the 23 procedures studied, the estimated average per-procedure effective dose ranged from 0.34 to 104.9 mSv. The pelvis (37%) was the region most often imaged in diagnostic procedures, and angioplasty/stent treatment of vessels was the most frequently performed therapeutic procedure (44%). During the study period, IR procedures increased in frequency (+137%), with a consequent increase in the per-capita dose (0.172 to 0.461 mSv) and collective dose (21 to 58 man-Sv/y). CONCLUSIONS: A comprehensive Monte Carlo-aided analysis, which allowed evaluation of contributions in terms of per-procedure and collective doses to the population for the practice of IR, showed a significant growth rate during the study period.

Criteria and scheduling of quality control of B-mode and doppler ultrasonography equipment.

Periodic quality control (QC) for ultrasound scanners checks their overall performance, reducing the risk of inaccurate diagnoses. Data from routine annual QC activity were analyzed to optimize the scheduling and the criteria of further QC programs. Among all the ultrasound scanners (68 transducers) in use at the Regional Medical Department of the Aosta Valley, which are currently tested, 48.6% showed problems, mainly (35.3%) related to defects detectable by physical and mechanical inspection. Nearly two-thirds of these problems impacted QC parameters. Failures were significantly related to the workload and to the "technological level" of the equipment. QC scheduling should therefore include a daily/weekly physical inspection in addition to a more complete, objective and software algorithms-based test, the frequency of which should be tailored on the basis of the equipment characteristics. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012.

The use of a diode matrix in commissioning activities for electron energies > or = 9 MeV: a feasibility study.

The contribution of a commercially available diode matrix (MapCHECK, provided by Sun Nuclear, Melbourne, FL) for the commissioning procedures of the voxel based Monte Carlo (VMC++) algorithm for electron beams of MasterPlan treatment planning system was investigated. The attention is mainly focused on the calculation in homogeneous and heterogeneous phantoms. With this aim, following a data set similar to that proposed by Electron Collaborative Working Group (ECWG), the dose profiles and two-dimensional (2D) dose distributions measured by the diode matrix were compared with the calculated ones using the gamma analysis method with acceptance criteria for the dose difference and the distance to agreement equal to 4% and 4 mm, respectively. The average and standard deviation of the percentage of points satisfying the constraint gamma < or = 1 are 98.3 +/- 4.1% and 99.3 +/- 1.7% for the 9 and 12 MeV electron beam, respectively, showing that the accuracy of MasterPlan electron beam algorithm is good for simple two-dimensional geometries as well as for more complicated three-dimensional ones. The results are in agreement with those reported in literature by Cygler et al. ["Evaluation of the first commercial Monte Carlo dose calculation engine for electron beam treatment planning," Med. Phys. 31, 142-153 (2004)]. In addition, the authors have also analyzed the response of the 2D array in terms of dose profiles at different depths, comparing the results with those obtained in water phantom using an electron diode. The results show that in the low gradient regions there were no deviations larger than the criteria of acceptability set by Van Dyk et al. ["Commissioning and quality assurance of treatment planning computers," Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)]; in the high gradient region, the maximum deviations are less than 2 mm with most of the values less than 1 mm. The present article shows that MapCHECK can play a useful role in the commissioning of electron algorithms of treatment planning systems in the evaluation of the 2D dose distributions in homogeneous and heterogeneous phantoms. In fact, it provides accurate results with the merit of expediting the commissioning process by using measuring device that requires minimal setup time and data processing time.

Verification of Varian Enhanced Dynamic Wedge implementation in masterplan treatment planning system.

This paper investigates the accuracy of the two available calculation algorithms of the Oncentra MasterPlan three-dimensional treatment planning system (TPS)-- the pencil beam method and collapsed-cone convolution--in modeling the Varian enhanced dynamic wedge (EDW). Measurements were carried out for a dual high energy (6-15 MV) Varian DHX-S linear accelerator using ionization chambers for beam axis measurements (wedge factors and depth doses), film dosimetry for off-axis dose profiles measurements, and a diode matrix detector for two dimensional absolute dose distributions. Using both calculation algorithms, different configuration of symmetric and asymmetric fields varying the wedge's angle were tested. Accuracy of the treatment planning system was evaluated in terms of percentage differences between measured and calculated values for wedge factors, depth doses, and profiles. As far as the absolute dose distribution was concerned, the gamma index method (Low et al.) was used with 3% and 3 mm as acceptance criteria for dose difference and distance-to-agreement, respectively. Wedge factors and percentage depth doses were within 1% deviation between calculated and measured values. The comparison of measured and calculated dose profiles shows that the Van Dyk's acceptance criteria (Van Dyk et al.) are generally met; a disagreement can be noted for large wedge angles and field size limited to the low dose-low gradient region only. The 2D absolute dose distribution analysis confirms the good accuracy of the two calculation algorithms in modeling the enhanced dynamic wedge.

Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice.

In an 18-month carcinogenicity study, Pim1 transgenic mice were exposed to pulsed 900 MHz (pulse width: 0.577 ms; pulse repetition rate: 217 Hz) radiofrequency (RF) radiation at a whole-body specific absorption rate (SAR) of 0.5, 1.4 or 4.0 W/kg [uncertainty (k = 2): 2.6 dB; lifetime variation (k = 1): 1.2 dB]. A total of 500 mice, 50 per sex per group, were exposed, sham-exposed or used as cage controls. The experiment was an extension of a previously published study in female Pim1 transgenic mice conducted by Repacholi et al. (Radiat. Res. 147, 631-640, 1997) that reported a significant increase in lymphomas after exposure to the same 900 MHz RF signal. Animals were exposed for 1 h/day, 7 days/week in plastic tubes similar to those used in inhalation studies to obtain well-defined uniform exposure. The study was conducted blind. The highest exposure level (4 W/kg) used in this study resulted in organ-averaged SARs that are above the peak spatial SAR limits allowed by the ICNIRP (International Commission on Non-ionizing Radiation Protection) standard for environmental exposures. The whole-body average was about three times greater than the highest average SAR reported in the earlier study by Repacholi et al. The results of this study do not suggest any effect of 217 Hz-pulsed RF-radiation exposure (pulse width: 0.577 ms) on the incidence of tumors at any site, and thus the findings of Repacholi et al. were not confirmed. Overall, the study shows no effect of RF radiation under the conditions used on the incidence of any neoplastic or non-neoplastic lesion, and thus the study does not provide evidence that RF radiation possesses carcinogenic potential.

Transmission, penumbra and leaf positional accuracy in commissioning and quality assurance program of a multileaf collimator for step-and-shoot IMRT treatments.

AIMS AND BACKGROUND: The performance characteristics of a commercial multileaf collimator (MLC) for intensity modulated radiation therapy (IMRT) and a comprehensive quality assurance program (QA) to be performed during the commissioning of the MLC were investigated. MATERIALS AND METHODS: The midleaf transmission and interleaf leakage, the in-plane penumbra and its in-plane/cross-plane variation, the cross-plane penumbra and its in-plane/cross-plane variation, and the leaf positional accuracy of a high-energy photon (6 MV) Sli Precise Elekta linear accelerator were measured. Kodak EDR2 Ready Pack film was used for MLC transmission measurement; for the other characterization measurements we used Kodak X-Omat XV2 Ready Pack film placed at 5 cm depth in a solid RW3 phantom. Each film was digitized with a laser scanning photodensitometer VXR-12 Plus using the Omni Pro-Accept 6.OA film dosimetry system and converted to dose by means of H&D curves. The dose calibration measurements were performed with a Farmer ionization chamber according to the guidelines of the IAEA Technical Report No. 277. RESULTS: The average midleaf transmission and interleaf leakage were 1.8% +/- 0.1% and 2.1% +/- 0.2%, respectively. The average value of the cross-plane penumbra was 5.4 mm +/- 0.3 mm with maximum variation less than 0.4 mm and 1.0 mm in the in-plane and cross-plane direction, respectively. The average value of the in-plane penumbra was 3.2 mm +/- 0.2 mm and 3.5 mm +/- 0.2 mm for the step side and groove side of the leaves, respectively. A dose profile perpendicular to the direction of the leaf travel passing through the central axis shows a tongue-and-groove effect of about 33%. The positional accuracy of the leaves was investigated according to AAPM Report No. 72 TG50; the deviation of the net optical density along all the match lines was less than +/- 20%. Moreover, the results obtained with a step field technique showed a positional accuracy of less than 1 mm. CONCLUSIONS: The results suggest the necessity of extensive knowledge of the MLC dosimetric characteristics for IMRT applications in order to allow physicists to study their influence on treatment delivery and to perform a comprehensive routine QA program of the investigated parameters.

The contribution of interventional cardiology procedures to the population radiation dose in a 'health-care level I' representative region.

This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002-11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm(2) were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05-0.27 mSv y(-1)) and the collective dose (5.8-35 man Sv y(-1)). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors' institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10% of the total dose by medical ionising radiation examination categories.

Hypofractionated whole-breast radiotherapy and concomitant boost after breast conservation in elderly patients.

AIMS: To report the 5- and 10-year results of accelerated hypofractionated whole-breast radiotherapy (WBRT) with concomitant boost to the tumor bed in 83 consecutive patients with early breast cancer aged >70 years. METHODS: All patients were treated with breast conservation and hypofractionated WBRT. The prescription dose to the whole breast was 45 Gy (2.25 Gy/20 fractions) with an additional daily concomitant boost of 0.25 Gy to the surgical cavity (2.5 Gy/20 fractions up to 50 Gy). The maximum detected toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. We considered as skin toxicity: erythema, edema, desquamation, ulceration, hemorrhage, necrosis, telangiectasia, fibrosis-induration, hyperpigmentation, retraction and atrophy. Cosmetic results were assessed as set by the Harvard criteria. RESULTS: With a median follow-up of 60 months (range 36-88), no local recurrence was observed. The maximum detected acute skin toxicity was G0 in 57% of patients, G1 in 40% and G2 in 3%. Late skin and subcutaneous toxicity was generally mild with no ≥G3 events. The cosmetic results were excellent in 69% of patients, good in 22%, fair in 5%, and poor in 4%. CONCLUSIONS: The present results support the use of hypofractionation employing a concomitant boost to the lumpectomy cavity in women aged >70 years. This is a convenient treatment option for both this type of population and health-care providers.

Dosimetric evaluation of a commercial 3D treatment planning system using the AAPM Task Group 23 test package.

The accuracy of the dose calculation algorithm is one of the most critical steps in assessing the radiotherapy treatment to achieve the 5% accuracy in dose delivery, which represents the suggested limit to increase the complication-free local control of tumor. We have used the AAPM Task Group 23 (TG-23) test package for clinical photon external beam therapy to evaluate the accuracy of the new version of the PLATO TPS algorithm. The comparison between tabulated values and calculated ones has been performed for 266 and 297 dose values for the 4 and 18 MV photon beams, respectively. Dose deviations less than 2% were found in the 98.5%- and 90.6% analyzed dose points for the two considered energies, respectively. Larger deviations were obtained for both energies, in large dose gradients, such as the build-up region or near the field edges and blocks. As far as the radiological field width is concerned, 64 points were analyzed for both the energies: 53 points (83%) and 64 points (100%) were within +/-2 millimeters for the 4 and 18 MV photon beams, respectively. The results show the good accuracy of the algorithm either in simple geometry beam conditions or in complex ones, in homogeneous medium, and in the presence of inhomogeneities, for low and high energy beams. Our results fit well the data reported by several authors related to the calculation accuracy of different treatment planning systems (TPSs) (within a mean value of 0.7% and 1.2% for 4 and 18 MV respectively). The TG-23 test package can be considered a powerful instrument to evaluate dose calculation accuracy, and as such may play an important role in a quality assurance program related to the commissioning of a new TPS.

Electromagnetic energy as a bridge between atomic and cellular levels in the genetics approach to cancer treatment.

Literature on magnetic fields (MF) and gene expression, as well as on DNA damage, supports the hypothesis that electromagnetic energy may act at atomic level influencing genetic stability. According to quantum physics, MF act on the interconversion of singlet and triplet spin states, and therefore on genetic instability, activating oxidative processes connected to biological free radicals formation, particularly ROS. In the above frame, the results of in vitro and in vivo laboratory trials have been analyzed. The use of a static MF amplitude modulated by 50 Hz MF, with a time average total intensity of 5.5 mT, has been shown to influence tumor cell functions such as cell proliferation, apoptosis, p53 expression, inhibition of tumor growth and prolongation of survival in animals, evidence that MF can be more effective than chemotherapy (cyclophosphamide) in inhibiting metastatic spread and growth, having synergistic activity with chemotherapy (Cis-platin), and no observable side effects or toxicity in animals or in humans. The beneficial biological/clinical effects observed, without any adverse effects, have been confirmed by various authors and augur well for the potentiality of this new approach to treat genetically based diseases like cancer. Further studies are needed to develop a quantum physics approach to biology, allowing a stable bridge to be built between atomic and cellular levels, therefore developing quantum biology.

Image-guided Intensity-modulated Radiotherapy for Prostate Cancer Employing Hypofractionation and Simultaneous Integrated Boost: Results of a Consecutive Case Series with Focus on Erectile Function.

AIM: To report on clinical outcomes of prostate cancer patients treated with hypofractionated radiotherapy employing a simultaneous integrated boost strategy. PATIENTS AND METHODS: A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vesicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. RESULTS: After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2% of grade 3 events. Erectile function was partially affected by radiation in men potent at baseline. CONCLUSION: Hypofractionation delivered with intensity-modulated radiotherapy and a simultaneous integrated boost approach proved to be a safe and effective treatment option for patients with prostate cancer. Patients with a preserved baseline erectile function experience a decrease in functionality correlated with the mean dose received by penile bulb.

Bilateral breast radiation delivered with static angle tomotherapy (TomoDirect): clinical feasibility and dosimetric results of a single patient.

We herein report on a case of synchronous bilateral breast cancer patient undergoing adjuvant intensity-modulated whole breast with static angle tomotherapy (TomoDirect). The patient was treated with a hypofractionated schedule employing a simultaneous integrated boost approach. Radiotherapy schedule was 45 Gy/20 fractions (2.25 Gy daily) to the bilateral whole breast and 50 Gy/20 fractions (2.5 Gy daily) to the 2 lumpectomy cavities. Treatment was delivered over 4 weeks. Dosimetric results were robust with consistent target coverage and adequate normal tissue avoidance. Treatment was generally well-tolerated and acute toxicity profile was mild. The present report highlights the promising clinical feasibility of TomoDirect for bilateral breast irradiation.

Penile metastasis from prostate cancer: a case report.

Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic primary tumors, mainly bladder and prostate. We present a case of prostatic mucinous adenocarcinoma with penile metastasis symptomatic for pain, which was treated with external-beam radiation (35 Gy/14 fractions; 2.5 Gy daily) combined with androgen deprivation, resulting in complete pain relief and objective response after treatment.

Minimizing a tricky situation in breast irradiation with helical tomotherapy.

We report on a patient with breast cancer undergoing adjuvant intensity-modulated whole breast and lymph node irradiation with static angle tomotherapy (TomoDirect), who experienced a traumatic ipsilateral humeral fracture and was able to continue radiotherapy with helical tomotherapy and daily dosimetric monitoring by means of the Planned Adaptive module.

Intensity-modulated and hypofractionated simultaneous integrated boost adjuvant breast radiation employing statics ports of tomotherapy (TomoDirect): a prospective phase II trial.

PURPOSE: To report the 1-year outcomes of a prospective phase II study on hypofractionated whole-breast intensity-modulated radiotherapy (IM-WBRT) with a simultaneous integrated boost (SIB) to the tumor bed delivered with static ports of tomotherapy (TomoDirect) (TD). METHODS: A prospective cohort of 82 patients was enrolled between 2011 and 2012. Treatment schedule consisted of 45 Gy/20 fractions to the whole breast and 50 Gy/20 fractions to the surgical bed delivered concomitantly with TD over 4 weeks. A one-armed optimal two-stage Simon's design was selected to test the hypothesis that treatment modality under investigation would decrease acute skin toxicity over historical data using conventional fractionation and sequential boost. Primary endpoint was acute skin toxicity. Secondary endpoints included late toxicity, cosmesis, quality of life and local control. RESULTS: Median follow-up was 12 months (range 6-18). Maximum detected acute skin toxicity was G0 41 %; G1 53 %; G2 6 %; G3 <1 %. With two G2-G3 acute skin toxicity events in the first stage and four in the second, the study fulfilled the requirements for the definition of the treatment approach under investigation as promising. Late skin toxicity was mild with no >G2 events. Cosmesis was good/excellent in 91 % of patients and fair/poor in 9 %. Quality of life was preserved over time, with the exception of fatigue, which was transiently increased. CONCLUSIONS: Hypofractionated IM-WBRT with a SIB to the tumor bed delivered with TD provides consistent clinical results and it is able to reduce acute skin toxicity rate over conventionally fractionated and sequential boost tomotherapy-based IM-WBRT.

Hypofractionation and concomitant boost to deliver adjuvant whole-breast radiation in ductal carcinoma in situ (DCIS): a subgroup analysis of a prospective case series.

To report the four-year outcomes of accelerated hypofractionated whole-breast radiotherapy (WBRT) with a concomitant boost (CB) to the tumor bed in ductal carcinoma in situ (DCIS), we performed a subgroup analysis of 103 patients affected with DCIS within a cohort of 960 early breast cancer patients treated with breast conservation and hypofractionated WBRT. Prescription dose to the whole breast was 45 Gy (2.25 Gy/20 fractions) with an additional daily CB of 0.25 Gy to the surgical cavity (2.5 Gy/20 fractions up to 50 Gy). With a median follow-up of 48 months (range 12-91), no local recurrence was observed. Maximum detected acute skin toxicity was as follows: G0 in 35 % of patients, G1 in 54 %, G2 in 9 % and G3 in 2 %. Late skin and subcutaneous toxicity were generally mild with only 1 % of patients experiencing ≥G3 events (telangiectasia). No major lung and heart toxicity were detected. Cosmetic results were excellent in 50 % of patients, good in 37 %, fair in 9 % and poor in 4 %. Quality of life had a generally favorable profile both within the functioning and symptoms domains. The present result supports the hypothesis that DCIS patients could be safely treated with a hypofractionated schedule employing a CB to the lumpectomy cavity.