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To evaluate the local control (LC), progression free survival (PFS), out-field PFS, overall survival (OS), toxicity and failure predictors of SRT in a series of various sites oligometastatic CRC patients. Patients with oligometastatic CRC disease were analyzed retrospectively. The SRT prescribed dose was dependent on the lesion volume and its location. 102 consecutive oligometastatic CRC patients (150 lesions) were included. They underwent SRT between 2012 and 2015. Median prescription dose was 45 Gy (median dose/fraction was 15 Gy/3 fractions biological equivalent dose (BED10) 112.5 Gy). Median follow-up was 11.4 months. No patients experienced G3 and G4 toxicity. No progression was found in 82% (radiological response at 3 months) and 85% (best radiological response) out of 150 evaluable lesions. At 1 and 2 years: LC was 70% and 55%; OS was 90% and 90%; PFS was 37% and 27%; out-field PFS was 37% and 23% respectively. Progressive disease was correlated with BED10 (better LC when BED10 was ≥ 75 Gy (p < 0.0001)). In multivariate analysis, LC was higher in lesions with a Plpnning target volume (PTV) volume < 42 cm3 and BED10 ≥ 75 Gy. Patients with Karnofsky performance status < 90 showed higher out-field progression. SRT is an effective treatment for patients with oligometastases from CRC. Its low treatment-associated morbidity and acceptable LC make of SRT an option not only in selected cases. Further studies should be focused to clarify which patient subgroup will benefit most from this treatment modality and to define the optimal dose to improve LC while maintaining low toxicity profile. [ABSTRACT FROM AUTHOR]

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Background: Radiotherapy can cause adverse skin reactions over the course of their treatment. Currently, management is based on several tropical products although there is no gold-standard approach to prevention and management of radiation toxicity. Method: We report our experience of vitamin E acetate in the treatment of radiation dermatitis in breast cancer patients who experienced grade 4 side effects (according to Radiation Therapy Oncology Group criteria). Results: Clinical management consisted of oral antibiotics and local application of vitamin E acetate and local escarectomy. All of the patients achieved complete re-epithelialization within 40 days. Conclusion: Skin ulceration and necrosis post-radiation may interrupt oncological treatment in breast cancer patients. In acute radiodermatitis with skin necrosis, we propose the use of oral antibiotics together with escarectomy and the application of vitamin E acetate to facilitate the healing process in order to minimize the interruption to the oncological treatment. [ABSTRACT FROM AUTHOR]

Background: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. Methods: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. Results: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. Conclusions: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that after breast-conserving surgery for breast cancer, radiotherapy may be applied to the portion of the breast where the primary tumour was removed (partial breast irradiation (PBI), avoiding the irradiation of the whole breast. We developed a procedure of PBI consisting of a single high dose of radiotherapy of 21 Gy with electrons equivalent to 58-60 Gy in fractionated doses, delivered during the surgical session by a mobile linear accelerator, positioned close to the operating table. Patients and methods: From July 1999 to December 2006, 1246 patients with primary carcinoma of less than 2.5-cm maximum diameter, mostly over 48 years, were treated with electron intra-operative radiotherapy (ELIOT) at a single dose of 21 Gy. Results: After a follow-up from 0.3 to 94.7 months (median 26), 24 (1.9%) patients showed a local recurrence and 22 developed distant metastases. Sixteen patients died, seven from breast carcinoma and nine from others causes. The five-year crude survival was 96.5%. Six (0.5%) developed severe breast fibrosis, which resolved in 2-3 years. An additional 40 patients suffered for mild fibrosis. Cosmetic results were good. Conclusions: Electron intra-operative radiotherapy is a safe method for treating conservatively operated breasts and avoids the long period of post-operative radiotherapy, greatly improving the quality of life and reduces the cost of radiotherapy. ELIOT markedly reduces the radiation to normal surrounding tissues and deep organs. Results on short- and medium-term toxicity are good. Data on local control are encouraging. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic relevance of Ki-67 labeling index (LI) in patients with Ductal Intraepithelial Neoplasia (DIN) of the breast. Patients and Methods: From January 1997 to December 2007, histological samples and clinical data of 1,171 consecutive patients operated for DIN in a single institution were collected. The study was performed in accordance with the REMARK criteria. The independent prognostic role of Ki-67 LI was evaluated with a multivariable Cox regression model. A restricted cubic splines model was used to evaluate the prognostic role of Ki-67 LI as a continuous variable. Results: Overall, median age was 52 years (range 23-88), median Ki-67 LI 15% (range 1-80) and median follow-up 86 months (range 1-192). Overall, 549 (46.9%) women were premenopausal at the time of diagnosis. A total of 872 (74.5%) patients underwent breast conservative surgery (BCS). Whole breast radiotherapy (RT) was administered to 356 patients, and 506 patients received low dose tamoxifen (HT) (20mg/week or 5 mg/day). Histologically, most of the cases had a prevalent solid or cribriform pattern (75%), were DIN1c and DIN2 (80%), ER+ (80%), and showed a high (≥ 14%) Ki-67 LI (54%). The prevalence of the immunohistochemically defined subtypes was 39.5% for Luminal (Lum) A, 22.8% for LumB/Her-2-, 18.2% for LumB/Her2+, 15.8% for Her-2+, and 3.7% for Triple Negative. Overall, the rate of invasive and in situ recurrences (5-year cumulative incidence) was 10.7%. Firstly, we analyzed the role of RT according to Ki-67 LI as a continuous variable in DIN2/DIN3 patients after BCS. The curve and interaction model was adjusted for menopause, BMI, Her-2 and ER status, histological grade, presence of necrosis and microcalcifications, and HT. RT was protective in subjects with DIN with Ki-67 LI ≥ 14%, while no evidence of effect was seen for Ki-67 LI <14%. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-value for the interaction between RT and Ki-67 LI <0.01). Accordingly, RT was effective in all DIN subtypes with the exception of LumA. The adjusted HRRT vs No RT for LumB/Her2-, LumB/Her2+, and Her2 subtypes was 0.20 (95 % CI, 0.08-0.48), 0.44 (95 % CI, 0.16-1.20), and 0.15 (95 % CI, 0.04-0.50), respectively. The HRRT vs No RT for Triple Negative subtype was 0.40 (95 % CI, 0.07-2.41) and was not adjusted because of the sparse number of events. Finally, we focused the analysis on DIN2 patients stratified by Ki-67 LI. Again, after adjustment for menopause, surgical margins, presence of necrosis, microcalcifications, and HT, RT was not effective in DIN2 patients with Ki-67 LI <14% [HRRT vs No RT: 1.15 (95 % CI 0.47-2.80)]. On the contrary, DIN2 patients with a Ki-67 LI ≥ 14% mostly benefit of RT in terms of ipsilateral recurrence[HRRT vs No RT: 0.18 (95% CI 0.07-0.46)]. Low dose tamoxifen was effective in either LumA [adjusted HRHT vs No HT: 0.56 (95 % CI 0.33-0.97)] and LumB/HER2- DIN [HRHT vs No HT: 0.51 (95 % CI 0.27-0.95)], but not in LumB/Her2+ [HRHT vs No HT: 1.06 (95 % CI 0.56-2.05). Conclusion: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. [ABSTRACT FROM AUTHOR]

The "Assisi Think Tank Meeting" (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices., Methods: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units., Results: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart D mean , 16.7 % for ipsilateral lung D mean , and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D 0.03cc , D 5% and D mean , respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability., Conclusion: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (1) All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. (2) This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. (3) Stefania Zara is employees of the company “Tecnologie Avanzate TA Srl” that distributes the software RayStation in Italy; this company supports the group in terms of collecting data. Data were analyzed objectively and independently from the vendor; (4) Remaining authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessio Sarti reports financial support was provided by S.I.T. Sordina IORT Technologies S.p.A. Vincenzo Patera reports financial support was provided by S.I.T. Sordina IORT Technologies S.p.A. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Risk factors for local recurrence after mastectomy in ductal carcinoma in situ (DCIS) emerged as a grey area during the second "Assisi Think Tank Meeting" (ATTM) on Breast Cancer., Aim: To review practice patterns of post-mastectomy radiation therapy (PMRT) in DCIS, identify risk factors for recurrence and select suitable candidates for PMRT., Methods: A questionnaire concerning DCIS management, focusing on PMRT, was distributed online via SurveyMonkey., Results: 142 responses were received from 15 countries. The majority worked in academic institutions, had 5-20 years work-experience and irradiated <5 DCIS patients/year. PMRT was more given if: surgical margins <1 mm, high-grade, multicentricity, young age, tumour size >5 cm, skin- or nipple- sparing mastectomy. Moderate hypofractionation was the most common schedule, except after immediate breast reconstruction (57% conventional fractionation)., Conclusions: The present survey highlighted risk factors for PMRT administration, which should be further evaluated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The aim of this study is to evaluate the dose delivered and the image quality of pre-treatment MVCT images with Hi-Art TomoTherapy system, varying acquisition and reconstruction parameters., Materials and Methods: Catphan 500 MVCT images were acquired with all acquisition pitch and reconstruction intervals; image quality was evaluated in terms of noise, uniformity, contrast linearity, contrast-to-noise ratio (CNR) and spatial resolution with the Modulation Transfer Function (MTF). Dose was evaluated as Multi Slice Average Dose (MSAD w ) and measurements were performed with the Standard TomoTherapy® Quality Assurance Kit composed by the TomoTherapy Phantom, the Exradin A1SL ion chamber and TomoElectrometer. For each pitch-reconstruction interval, acquisitions were repeated 5 times., Results: Differences in noise and uniformity, though statistically significant in some cases, were very small: noise ranged from 2.3% for Coarse - 3 mm to 2.4% for Coarse - 6 mm, while uniformity passed from 99.5% for Coarse - 6 mm to 99.8% for Normal - 4 mm. No differences at all were found for CNR for high and low density inserts, while MTF was higher for pitch Coarse, even if no differences in spatial resolution were observed visually (spatial resolution was up to 4 lp/cm for all combinations of pitch and reconstruction interval). Dose was dependent on pitch, being 1.0 cGy for Coarse, 1.5 cGy for Normal and 2.85 cGy for Fine., Conclusions: We observed negligible differences in image quality among different pitch and reconstruction interval, thus, considerations regarding pre-treatment imaging modalities should be based only on dose delivered and on the desired resolution along the cranio-caudal axis for image-guided radiotherapy and adaptive radiotherapy purposes., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Local recurrences after breast-conserving surgery occur mostly in the quadrant harbouring primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area while irradiation of the whole breast may be avoided. We have developed a new technique of intraoperative radiotherapy of a breast quadrant after the removal of the primary carcinoma (ELIOT). A mobile linear accelerator with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Different dose levels were tested from 10 to 21 Gy without important side effects. A randomized trial is currently ongoing in order to compare conventional irradiation and ELIOT. More than 400 patients have been enrolled. In addition a new approach for nipple and areola complex conservation, including ELIOT, is under investigation.

Aims and Background: To report the technique of 3D-conformal radiation therapy (3D-CRT) currently used at our Institute for the treatment of prostate cancer with a curative intent. A critical review of the technical aspects of the technique is provided., Methods and Study Design: Between December 1995 and October 2000, 334 patients with biopsy-proven adenocarcinoma of the prostate were treated with 3D-CRT. All patients were treated in a prone position with 15 MV X-ray beams and a 6-field technique for all but 20 patients, who were treated with a 3-field technique. Patients were simulated with the rectum and bladder empty. To ensure reproducible positioning, custom-made polyurethane foam or thermoplastic casts were produced for each patient. Subsequently, consecutive CT scan slices were obtained. The clinical target volume and critical organs (rectum and bladder) were identified on each CT slice. The beam's eye view technique was used to spatially display these structures, and the treatment portals were manually shaped based on the images obtained. The beam apertures were initially realized by conventional Cerrobend blocks (48 patients), which were replaced in October 1997 by a computer-driven multi-leaf collimator. The total target dose prescribed at the ICRU point is 76 Gy, delivered in 38 fractions and 54 days. The seminal vesicles are excluded at 70 Gy. Dose-volume histograms were obtained for all patients. If more than 30% of the bladder and/or more than 20% of the rectum receive >95% of the prescribed total dose, the treatment plan is judged as unsatisfactory and is adjusted. The dose-volume histogram can be improved by changing the beam's arrangement and/or weights or by introducing or modifying the wedge filters., Conclusions: 3D-CRT in prostate cancer patients is a highly sophisticated and time-consuming method of dose delivery. Important technical issues remain to be clarified.

Aims and Background: To define the role of radiotherapy in the treatment of small-cell lung cancer (SCLC) on the basis of clinical data reported in the medical literature., Methods: Published reports are critically reviewed, with particular attention to randomized trials., Results: Thoracic radiotherapy has an important role in improving local control and 3-year survival in limited-stage SCLC; radiation should be delivered early in the course of the chemotherapy program, avoiding large volumes and total doses exceeding 40-50 Gy. Thoracic radiotherapy probably has no role in resected patients treated with adjuvant chemotherapy and may even be detrimental in patients with extensive SCLC. Prophylactic cranial irradiation has been shown to reduce the risk of brain relapse, but it is not associated with a consistent increase in survival or cure rate: its use in clinical practice is therefore not advised., Conclusions: Survival rates approaching 50% at 2 years are now possible in limited SCLC with the integrated effort of the surgeon, the medical oncologist and the radiation oncologist; their strict cooperation appears to be of the utmost importance in the earliest phase of treatment planning.

In this work we first analyzed the reliability of materials supplied by the main firms, which must be considered when defining the lesion and planning target volume. The coordinates of specific target landmarks, i.e., bone, calcium deposition or catheters, on baseline CT scans were compared with those measured on control scans. Since the PLATO-SRS system yields 3 coordinates for each target, the final error is calculated by the evaluation of the shift of the different coordinates. The mean error reported for the first material (ORFIT) was 5 mm (13/23 patients). This margin of error is too high and was considered unacceptable; a second material was then tested. The latter, which is not recyclable and softens at higher temperatures, exhibited a mean error of 2.5 mm (10/23 patients), which allows daily repositioning of greater reliability. Treatment was repeated in 4/20 arcs in all, which number depended mainly on fraction size. Correct lesion location and patient positioning were allowed by laser landmarks on the mask made directly on the treatment couch. The laser too was checked before each treatment session, i.e., preferentially at the end of an ordinary working day.