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Purpose: Combined modality therapy is a mainstay option for thoracic malignancies and head and neck cancers. The integration of different strategies is based on the multidisciplinary approach of modern clinical oncology. Radiation oncologists have to be educated, trained, and updated to provide state-of-the-art care to cancer patients and thus educational meetings are crucial. Methods: The Italian Association of Radiation Oncology Young Members Working Group (AIRO Giovani) organized its 8th national meeting, focused on combination therapy in lung, esophageal, and head and neck cancer (with a specific focus on larynx-preservation strategies for larynx/hypopharynx tumors), involving young professionals working in Italy. The meeting was addressed to young radiation oncologists, presenting state-of-the-art knowledge, based on the latest evidence in this field. We performed a review of the current literature based on the highlights of the Congress. Results: The multimodality approach of head and neck and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but also has to take into account new information and data coming from basic and translational research and including molecular biology, genetics, and immunology. All these aspects are crucial for the treatment of non-small-cell lung cancer and esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The integration of different treatments in the clinical decision-making process to combine therapies is crucial. Conclusions: Combination therapy has proved to be a consolidated approach in these specific oncologic settings, highlighting the importance of multimodality management in modern clinical oncology. Dedicated meetings on specific topics are helpful to improve knowledge and skills of young professionals in radiation oncology.

Background: Cervical cancer is associated with a high yearly mortality. The presence of persistent disease after radiotherapy is a significant predictor of patient survival. The aim of our study was to assess if tumor volume regression measured with MR imaging at the time of brachytherapy can discriminate between patients who eventually will achieve a complete response to radiotherapy from those who will not. The second objective was to evaluate whether tumor volume regression predicts overall treatment failure. Methods: MRI was evaluated quantitatively in 35 patients; by means of tumor volumetry on T2-weighted MR images before treatment, at the first BCT application, and at the final BCT. The MR images were independently analyzed by two investigators. As a reference standard histopathologic confirmation of residual tumor and/or clinical exam during follow-up > 1 year were used. Area under the curve were compared, P-values <0.05 were considered significant. Results: There was a good correlation between volume measurements made by the two observers. A residual tumor volume >9.4 cm3 at final BCT and tumor volume regression < 77 % of the pre-treatment volume were significantly associated with local residual tumor after completion of therapy (p < 0.02) (AUC, 0.98-1.00). A volume > 2.8 cm3 at final BCT was associated with overall treatment failure (p < 0.03 ). Conclusion: Our study shows that volume analysis during BCT is a predictive tool for local tumor response and overall treatment outcome. The potential of local response assessment to identify patients at high risk of overall treatment failure is promising.

The optimal approach to the diagnosis and treatment of locally advanced rectal cancer involves multidisciplinary, integrated management. In the past 30 years, survival and freedom from disease have increased, but the ideal multidisciplinary management remains to be determined. The preferred integrated treatment modality is preoperative radio(chemo)therapy followed by total mesorectal excision. Certain aspects of this standard are still debated, and the European and American approaches vary. The chief recommendations per international guidelines are summarized, and the next generation of integrated treatments for locally advanced rectal cancer is discussed.

To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small (≤400 mL), medium (400-700 mL), and large (≤700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volume of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V5Gy did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V5Gy, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size. © 2012.

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The aim of this study is to propose and validate an original new class of solutions for three-dimensional conformal radiation therapy (3DCRT) treatment planning for non-small cell lung cancer (NSCLC) according to the different patterns of disease presentation (on the basis of tumor location and volume) and to explore beams arrangement (planar or no-planar solutions) to respect dose constraints to the lung parenchyma. Benchmarks matched to validate the new approach are interuser reproducibility and saving on planning time. Tumor location was explored and specific categories created according to the tumor volume and location. Therefore, by applying planar and no-planar 3D plans, we searched for an optimization of the beams arrangement for each category. Dose-volume histograms (DVHs) were analyzed and a plan comparison performed. Results were then validated (class solution planning confirmation) by applying the same strategy to another group of patients. This has been realized at two dose levels (50.4 and 59.4 Gy). Fifty-nine patients were enrolled in this dosimetric study. In the first 27 patients ("exploratory sample") three main planning target volume location categories were identified according to the pattern of the disease presentation: (1) centrally located; (2) peripheral T and mediastinal N (P+N); and (3) superior sulcus. Original class solutions were proposed for each location category. On the next 32 patients ("validation sample"), the treatment planning started directly with the recommended approach. Mean V20Gy value was 18.8% (SD ± 7.25); mean V30Gy:12% (SD ± 4.05); and mean lung dose: 11.6Gy (SD ± 5.77). No differences between the two total dose level groups were observed. These results suggest a simple and reproducible tool for treatment planning in NSCLC, allowing interuser reproducibility and cutting down on planning time. © 2010 American Association of Medical Dosimetrists.

Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.

Introduction: We report the results of a phase II trial exploring the efficacy and the feasibility of combination of gemcitabine and cisplatin concurrent with radiotherapy followed by surgery in patients with stage III non-small cell lung cancer. Methods: Patients with histocytologically confirmed non-small cell lung cancer were treated with cisplatin 80 mg/sqm/wk of 1 and 4 or 20 mg/sqm/d of weeks 1 and 4 and weekly gemcitabine at 300 to 350 mg/m plus involved field radiotherapy. A 3D-conformal radiotherapy was delivered up to 50.4 Gy, with daily fractionation of 1.8 Gy. After clinical, radiologic, and pneumological reassessment, patients who reentered criteria for resectability were operated. Results: The stage at diagnosis was IIIA-N2 in 29 patients and IIIB-T4N0-2 for vascular direct infiltration for the remaining 21. Fifteen patients (30%) experienced acute grade 3 to 4 hemathological toxicity, whereas acute grade 3 esophageal toxicity was recorded in three patients (6%). One patient developed a grade 4 pulmonary toxicity (2%). Clinical response was 40 (80%) partial response, one (2%) stable disease, and nine (18%) progressive disease. Thirty-six patients (72%) underwent surgery. Final pathology showed a downstaging to stage 0 to I in 25 cases (50%). Median overall survival for all patients was 21.8 months, with a 3-year survival of 40.2%. CONCLUSIONS:: The results of this phase II trial confirm the feasibility and the efficacy of concurrent chemoradiotherapy followed by surgery. © 2009 by the International Association for the Study of Lung Cancer.

In this paper the cine acquisition mode of an electronic portal imaging device (EPID) has been calibrated and tested to determine the in vivo dose for dynamic conformal arc radiation therapy (DCAT). The EPID cine acquisition mode, that allows a frame acquisition rate of one image every 1.66 s, was studied with a monitor unit rate equal to 100 UM/min. In these conditions good signal stability, ±1% (2SD) evaluated during three months, signal reproducibility within ±0.8% (2SD) and linearity with dose and dose rate within ±1% (2SD) were obtained. The transit signal, St, (due to the transmitted beam below the phantom) measured by the EPID cine acquisition mode was used to determine, (i) a set of correlation functions, F(w,L), defined as the ratio between St and the dose at half thickness, Dm, measured in solid water phantoms of different thicknesses, w and with square fields of side L, (ii) a set of factors, f(d,L), that take into account the different X-ray scatter contribution from the phantom to the St signal as a function of the variation, d, of the air gap between the phantom and the EPID. The reconstruction of the isocenter dose, Diso, for DCAT was obtained convolving the transit signal values, obtained at different gantry angles, with the respective reconstruction factors determined by a house-made software. The method was tested with cylindrical and anthropomorphic phantoms and the results show that the reconstructed Diso values can be obtained with an accuracy within ±2.5% in cylindrical phantom and within ±3.4% for anthropomorphic phantom. In conclusion, the transit dosimetry by EPID was assessed to be adequate to perform DCAT in vivo dosimetry, that is not realizable with the other traditional techniques. Moreover, the method proposed here could be implemented to supply in vivo dose values in real time. © 2007 Elsevier B.V. All rights reserved.