Erratum to: Tomotherapy PET-guided dose escalation--A dosimetric feasibility study for patients with malignant pleural mesothelioma.

Unfortunately, erroneous author affiliations were published in the article "Tomotherapy PET-guided dose escalation ­ A dosimetric feasibility study for patients with malignant pleural mesothelioma". The correct list of author affiliations reads as follows: Angelo Maggio 1, Claudia Cutaia 1, Amalia Di Dia 1, Sara Bresciani 1, Anna Miranti 1, Matteo Poli 1, Elena Delmastro 2, Elisabetta Garibaldi 2, Pietro Gabriele 2 and Michele Stasi 1. 1: Medical Physics Department, Candiolo Cancer Institute ­ FPO, IRCCS, Turin, Italy. 2: Radiotherapy Department, Candiolo Cancer Institute ­ FPO, IRCCS, Turin, Italy. We apologize for any inconveniences caused.

Chondrosarcoma of the nasal septum.

Chondrosarcomas are non-epithelial malignant, slow growing tumors that usually involve pelvis, ribs, and long bones of extremities, scapula and sternum. Median age at diagnosis for head and neck chondrosarcomas is in the fourth decade. The etiopathogenesis of chondrosarcomas remains unknown. Treatment of choice is surgical, with adjuvant therapy having a limited role. In fact, radiation therapy and chemotherapy are reserved for residual or recurrent disease and palliation. As for surgery, several surgical procedures have been described. Recently, endoscopic surgery has allowed for the successful and less invasive treatment of inverting papillomas and even nasopharyngeal angiofibromas, lesions previously requiring extended external approaches. The aim of this paper was to present a case of nasal septal chondrosarcoma that was successfully treated with endoscopic surgery and radiation adjuvant therapy.

Ankle Instability and Peroneal Disorders in Cavovarus Feet: Do I Need a Calcaneal Osteotomy?

In order to understand the relation among ankle instability, peroneal disorders, and cavovarus deformity, it is mandatory to clarify the different stages of those disorders and also to put them into relation to each other. Finally, we need to take the patients compliance and expectations into consideration to define the individually right way of treatment.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Third generation Dual Mobility Cups: could be the future in total hip arthroplasty? A five-year experience with dualis.

BACKGROUND: The concept of dual mobility (DM) is currently approved as a valid option for reducing the risk of dislocation, with an incidence ranging from 0% to 4.6%. The principle is to achieve a high joint stability through a large diameter polyethylene (PE) liner, and to reduce cutting forces due to a "low-friction" head-liner coupling mechanism. METHODS: From March 2015 to March 2020, 138 patients were treated with Dualis Cup (Gruppo Bioimpianti-Peschiera Borromeo, MI, Italy) for a total of 141 implants (three cases were bilateral). The average age at the time of the surgery was 77. Patients' clinical and X-ray follow-up was at 1, 3, 6, 12 months and then once a year. RESULTS: Seven patients (4.9%) had complications which required a second surgery, but only one case (0.7%) of intraprosthetic dislocation (which required cup revision), was directly ascribable to the DM cup. CONCLUSIONS: Improvements in design and materials of the third generation DM cups allowed both to reduce the rate of dislocations in high-risk patients (i.e., patients with neuro-muscular diseases and cognitive disorders, patients needing revisions, osteosynthesis failures, femoral neck fractures) and to achieve a survival rate similar to standard cups, ensuring a range of motion (ROM) very close to the physiological one. In our brief experience, Dualis Cups showed results comparable to those reported in the literature for Dual Mobility. If this data is confirmed by long-term studies, the use of DM cups could be extended even for young patients with high functional demands. (www.actabiomedica.it).

Hereditary paraganglioma syndrome associated with SDHD gene mutations: a patient with multicentric presentation treated with radiotherapy. Case report.

INTRODUCTION: Extra-adrenal paragangliomas are rare tumors arising from neuroendocrine cells. Sporadic and hereditary forms have been recognized. Among the latter, the PGL1 and PGL4 syndromes are associated with a high risk of multiple localizations. The treatment of choice for paragangliomas is surgical resection, but in some cases surgery can be difficult due to particular or multiple tumor sites or may result in severe neurological deficits. In such cases radiotherapy can be an effective alternative. In this paper we describe the case of a patient affected by hereditary paraganglioma syndrome with multicentric presentation who was treated at our center by external radiotherapy. CASE REPORT: A 55-year-old man presented in April 2008 with multiple paragangliomas: one in the left pontocerebellar angle, two in the middle neck, one mediastinal paraaortic mass, and an abdominal paraaortic lesion. The left pontocerebellar and mediastinal tumors were treated with three-dimensional conformal radiotherapy (3D-CRT) at total doses of 50.40 Gy and 55.80 Gy, respectively. The neck lesions were treated with intensity-modulated radiotherapy (IMRT) at a total dose of 55.80 Gy. The abdominal paraaortic lesion was surgically resected. RESULTS: No severe acute or late toxicity as evaluated with the EORTC-RTOG scale was observed. Fourteen months after the end of radiotherapy a whole body CT scan showed that the tumor lesions were stable in size and in their relations to contiguous structures. The arterial pressure was controlled by medical therapy and urine catecholamine levels were within the normal range. CONCLUSIONS: We believe that in patients affected by unresectable paragangliomas radiotherapy is a safe and effective alternative to surgery. The use of high-dose conformity techniques such as 3D-CRT and IMRT will allow higher local control rates with relatively few side effects thanks to the possibility of dose escalation and reduction of the amount of irradiated healthy tissues.

Orthopaedic patient workflow in CoViD-19 pandemic in Italy.

CoViD-19 epidemic started in China in late December 2019, and soon spread, turning into a pandemic. All medical specialties have soon been involved in the management of CoViD-19 patients; the daily Orthopaedic activity has been affected profoundly by this dramatic health emergency. The present paper aims to summarize all the measures and changes that had to be made in order to avoid the healthcare system collapse in the most affected areas, and provides an operative flowchart.

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth.

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer.

Radiotherapy after partial laryngectomy: an analysis of 36 cases and a proposal to optimize radiotherapy.

AIMS AND BACKGROUND: Laryngeal cancer treatment options include radical surgery, "organ preservation surgery", radiotherapy and chemotherapy. There is no proven evidence of a significant increase in late toxicity with adjuvant radiotherapy after conservative surgery. The aim of this retrospective study was to evaluate the toxicity, local-regional control and overall survival of adjuvant radiotherapy after conservative surgery. METHODS: A total of 36 patients was treated with radiotherapy after partial laryngectomy at the Radiotherapy Department of the Institute for Cancer Treatment and Research (IRCC) of Candiolo and of the Mauriziano Hospital in Turin, between 1994 and 2007. The postoperative treatment doses ranged from 45 to 70.2 Gy with conventional fractionation. The Kaplan-Meier method was applied for statistical analysis. The RTOG-EORTC scale was used to evaluate late and acute toxicity. RESULTS: Overall 5- and 10-year survival was 93% and 47%, respectively. Local control was 93.5% at 5 and was unchanged at 10 years. Grade 2 acute cutaneous and mucous toxicity was 41% and 62%, and grade 3, 6.9% and 3.5%, respectively. Only one patient required percutaneous endoscopic gastrostomy due to severe dysphagia and one patient required temporary tracheostomy for severe acute laryngeal edema (grade 3). Two patients experienced late toxicity greater than grade 3. The median dose to the residual larynx was 59.5 Gy (range, 45-70.2), and the median dose to the neck was 50.4 Gy (range, 39.6 -55.8). CONCLUSIONS: The results of our study showed a dose-dependent increase in the late toxicity trend at doses over and above 60 Gy, which is higher than the cutoff dose reported in the literature. There was no indication from our data that adjuvant postoperative radiotherapy means additional toxicity. The use of highly conformal techniques can further reduce toxicity of the radiotherapy.

Surgery and radiotherapy in the treatment of malignant parotid tumors: a retrospective multicenter study.

AIMS AND BACKGROUND: Major salivary gland cancers are rare, with many histologic types and subtypes. The low incidence and heterogeneity of primary parotid carcinomas makes their outcome difficult to evaluate. Treatment remains primarily surgical, but optimal therapeutic regimens have yet to be fully realized. The present study reviews the experience of three Italian institutions in the treatment of primary parotid carcinomas in order to describe the clinicopathological presentation and treatment options with emphasis on radiotherapy and to analyze the factors influencing survival. METHODS AND STUDY DESIGN: The records of 110 patients with primary parotid neoplastic lesions treated at three Italian institutions from 1993 to 2004 were retrospectively reviewed. Six patients were excluded from the study: 3 received surgery alone and 3 were not assessable, for a total of 104 assessable patients. Acute and late toxicity of radiotherapy was quantified following the recommendations of the RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit method. The influence of selected factors on 10-year disease-specific survival was analyzed. RESULTS: The 104 assessable patients were treated as follows: 11 patients received radiotherapy as their only treatment (3 with a palliative purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent neck dissection: neck lymph node metastases were found in all them. Their mean age was 60 years (range, 14-92). According to the UICC/2002 TNM Classification, 8 patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3 recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both local recurrence and distant metastases. No factors were observed that would negatively influence the prognosis. Actuarial 10-year disease-specific survival was 71% and actuarial 10-year local control 82%. CONCLUSIONS: The treatment of salivary gland malignancies remains primarily surgical. Our study confirms the results of the literature with surgery and adjunctive radiotherapy in patients with advanced-stage disease. No variables were observed to influence the prognosis.

Salvage radiation therapy after radical prostatectomy: survival analysis.

BACKGROUND: To evaluate the outcome of patients treated with salvage radiotherapy after radical prostatectomy and to investigate the effects of independent predictors on survival. METHODS: From January 2000 to December 2015, 234 patients with biochemical/clinical recurrences after radical prostatectomy were submitted to salvage radiotherapy (SRT). One hundred and fifty-seven patients (67%) received three-dimensional (3D) conformal radiotherapy while 77 patients (33%) were treated with intensity-modulated radiotherapy (IMRT) or IMRT/image-guided radiotherapy by tomotherapy. The median RT dose to prostate bed was 70.2 Gy (range: 66-79 Gy). The investigated endpoints were biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS). Different covariates were considered to investigate predictors of survival. RESULTS: With a median follow-up of 117 months the BRFS, CRFS, DMFS and PCSS at 10 years were 54%, 84%, 90%, and 94%, respectively. In multivariate analysis (MVA), the pathological Gleason Score (pGS) was the most important factor affecting BRFS, CRFS, DMFS and PCSS (P<0.007, HR>1.55); pathological stage (pT) was predictor of BRFS (P=0.007, HR=1.7) and PCSS (P=0.02, HR=4.2), and the last prostate-specific antigen during follow-up was an important survival predictor of CRFS (P=0.004, HR=1.26) and PCSS (P<0.0001, HR=1.04). The time between surgery and the start of SRT was correlated with BRFS (P<0.0001, HR=0.987) and CRFS (P=0.047, HR=0.989). In univariate analysis (UVA), positive surgical margins at the prostatectomy specimen improved BRFS (P=0.01, HR=0.54), CRFS (P=0.05, HR=0.46) and DMFS (P=0.005, HR=0.13) after SRT. CONCLUSIONS: At long-term follow-up, excellent outcome results of SRT on BRFS, CRFS, DMFS, and PCSS were obtained. Several prognostic factors such as pGS, pT and surgical margin status were found to be predictors of survival.

REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer.

PURPOSE: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. METHODS: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. RESULTS: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician- (47,025 forms) and patient- (54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade ≥2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). CONCLUSION: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. PATIENT SUMMARY: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short- and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity.

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

BACKGROUND: The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). METHODS: From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. RESULTS: The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. CONCLUSIONS: The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.

Are quality indicators for radiotherapy useful in the evaluation of service efficacy in a new based radiotherapy institution?

AIMS AND BACKGROUND: A number of documents assess the need for quality assurance in radiotherapy, which must be constantly monitored and possibly improved. In this regard, a system that confirms the quality of a department has been suggested and quality indicators have been used to improve the quality of the service. The National Health Service (Istituto Superiore di Sanità) approved a National Research Project to increase the quality of radiotherapy. The aim of the present study was to analyze the practical feasibility and efficacy of the quality indicators elaborated by the National Health Service study group in a radiotherapy unit. PATIENTS AND METHODS: The voluntary accredited program was carried out by the Radiotherapy Department of IRCC in Candiolo from June to August 2002. We analyzed 8 of the 13 indicators according to the National Health Service Project. For this purpose, 133 consecutive patients treated in our Unit were analyzed, and the results are reported according to the appropriate indicator (number of staff related to patients treated, waiting list, case history accuracy, multidisciplinary approach, number of treatment plans performed by CT, number of fields per fraction, number of portal imaging performed per overall treatment, and patient satisfaction). RESULTS: The number of professional staff related to the number of patients treated was easy to calculate and it could be the basis for further evaluation. The overall waiting time was 55.4 days, and it changed for different radiotherapy goals. We obtained 80% conformity in case-history accuracy. The number of multidisciplinary consultations performed ranged between 50% and 100%. The number of CT plans was about 1.6 +/- 0.9 plans per patient. The mean number of fields performed per day and per patient is 3.5 +/- 1.7 and was in agreement with the fact that more than 50% of treatments in our Center were performed with conformal radiotherapy. An average of 16.7 +/- 10.0 portal imaging per case was performed. The percentage of patient satisfaction with the staff obtained a very high compliance. CONCLUSIONS: The self evaluation promoted by the National Health Service Project allows the monitoring of the activities of the service in order to asses critical factors and it can be the starting point to improve the quality of the service and to compare national and international quality assurance results.

Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology).

PURPOSE: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care. MATERIAL AND METHODS: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1. Taking care and multidisciplinary approach, 2. Radiotherapy treatment and brachytherapy, 3. Follow-up. RESULTS: Nineteen centers treated gynecological malignancies and 12 of these had a multidisciplinary dedicated team. Radiotherapy option has been used in all clinical setting: definitive, adjuvant, and palliative. In general, 1978 patients were treated. There were 834 brachytherapy (BRT) treatments. The fusion between diagnostic imaging (magnetic resonance imaging - MRI, positron emission tomography - PET) and computed tomography (CT) simulation was used for contouring in all centers. Conformal RT and intensity modulated radiation therapy (IMRT) were the most frequent techniques. The image guided radiation therapy (IGRT) was used in 10/19 centers. There were 8 active BRT centers. Brachytherapy was performed both with radical intent and as boost, mostly by HDR (6/8 centers). The doses for exclusive BRT were between 20 to 30 Gy. The doses for BRT boost were between 10 and 20 Gy. Four centers used CT-MRI compatible applicators but only one used MRI for planning. The BRT plans on vaginal cuff were still performed on traditional radiographies in 2 centers. The plan sum was evaluated in only 1 center. Only 1 center performed in vivo dosimetry. CONCLUSIONS: In the last three years, multidisciplinary approach, contouring, treatment techniques, doses, and control systems were similar in Liguria-Piedmont and Valle d'Aosta. However, the technology implementation didn't translate in a real treatment innovation so far.

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally. METHODS: A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities. RESULTS: Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication. CONCLUSIONS: In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.

External beam radiotherapy with dose escalation in 1080 prostate cancer patients: definitive outcome and dose impact.

BACKGROUND: The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years. METHODS: From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months. RESULTS: For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%. CONCLUSIONS: The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.

Clinical and technical feasibility of ultra-boost irradiation in Dominant Intraprostatic Lesion by Tomotherapy: preliminary experience and revision of literature.

BACKGROUND: The aim of this paper was to present our experience of dominant intraprostatic lesions (DIL) irradiation up to an EQD2 of 93,2 Gy with helical tomotherapy. METHODS: Between March 2012 and December 2014, 15 staged II-III patients with intermediate-high risk prostate cancer were enrolled in our protocol of DIL dose escalation by Tomotherapy. All patients were submitted to a multiparametric MRI (including DCE and DWI series), in order to visualize DILs. Considering a mean α/ß ratio of 3 for prostate cancer the prescribed doses were: 83.2 Gy in 32 fractions of 2.6 per fraction (EQD2=93.2 Gy) on the DILs, 75.2 Gy in 32 fractions of 2.35 Gy per fraction (EQD2=80.5 Gy) on the prostate gland and 67.2 Gy in 32 fraction of 2.1 (EQD2=68.5 Gy) on the seminal vesicles. RESULTS: With a mean follow-up of 16 months (range 2-39), no overall severe acute toxicities >G3 were observed; one patient out of 15 (6.6%) had acute gastrointestinal (GI) toxicity equal to G2, while two cases (13.3%) had G2 acute genitourinary (GU) toxicity. No >G2 late toxicity was observed. At last follow-up, for all patients, the biochemical disease free survival was 100%. CONCLUSIONS: The irradiation of the whole prostate and seminal vesicles up to an EQD2 of 80.5 Gy and of DILs up to 93.2 Gy was clinically feasible and safe, without acute severe toxicity. Although with a short follow-up, late toxicities are currently absent and no patient relapsed.

Feasibility of intensity-modulated radiation therapy in the treatment of advanced cervical chordoma.

AIMS AND BACKGROUND: Postoperative radiation is often given in cases of cervical chordoma because of the high incidence of local recurrence. The tumor mass usually surrounds the spinal cord and infiltrates vertebral bone. A combined technique using protons or electrons to boost the initial photon fields is generally applied. We evaluated the use of dynamic intensity-modulated radiation therapy as an alternative technique for treating advanced cervical chordoma. METHODS AND STUDY DESIGN: A female patient with incomplete resection of a vertebral chordoma surrounding C2-C3 was irradiated with a total dose of 58 Gy (ICRU point) in 2 Gy daily fractions for 29 days between December 2001 and January 2002. Beam arrangement consisted of seven 6 MV non-opposed coplanar fields. Pretreatment quality assurance included checking of the absolute dose at reference points and 2D dose map analysis. Treatment was delivered with a 120-leaf collimator in sliding window mode. To verify the daily setup, portal images at 0 degrees and 90 degrees were compared with the simulation images before treatment delivery (manual matching) and after treatment delivery (automatic anatomy matching). RESULTS AND CONCLUSIONS: The mean dose to the planning target volume (PTV) was 57.6 +/- 2.1 Gy covering 95% of the PTV per 95% isodose. The minimum dose to the PTV (D99) was 53.6 Gy in the overlapping area between the PTV and the spinal cord planning organ at risk volume (PRV). The maximum dose to the spinal cord was 42.2 Gy and to the spinal cord PRV (8 mm margin) 53.7 Gy. The mean dose to the parotid glands was 37.4 Gy (homolateral gland) and 19.5 Gy (contralateral gland). Average deviation in setup was -1.1 +/- 2.5 mm (anterior-posterior), 2.4 +/- 1.3 mm (latero-lateral), 0.7 +/- 0.9 mm (craniocaudal) and -0.43 +/- 1 degree (rotation). CONCLUSIONS: In the treatment of chordomas surrounding the spinal cord, intensity-modulated radiotherapy can provide high dose homogeneity and PTV coverage. Frequent digital portal image-based setup control is able to reduce random positioning errors for head and neck cancer patients immobilized with conventional thermoplastic masks.