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PURPOSE Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up. METHODS Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS. RESULTS Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months). CONCLUSIONS This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach.

Stereotactic ablative radiation therapy (SABR) is used in non-oncologic indications, recently even for cardiac arrhythmias. Thus, aim of this analysis is to review preclinical, early clinical evidences and future direction of the latter new treatment approach. A collection of available data regarding SABR and cardiac arrhythmias was made, by Pubmed research and 2 independent researchers, including preclinical and clinical data. A review of ongoing trials was conducted on ClinicalTrials.gov. Preclinical research conducted in animal models showed that a safe and effective noninvasive treatment approach for cardiac arrhythmias could be represented by SABR with a median time of response around 2–3 months. The treatment dose plays a crucial role: the atrioventricular node would seem more radiosensitive than the other cardiac electric zones. Clinical data, such as published case series, case reports and early prospective studies, have already suggested the feasibility, efficacy and safety of SABR (25 Gy in one session) for refractory ventricular arrhythmias. Considering the ongoing trials of SABR and new technological improvements in radiotherapy (e.g. hybrid magnetic resonance) and in arrhythmias noninvasive mapping systems, the future analyses will improve the reliability of those preliminary results.

Pancreatic neuroendocrine tumours (PNETs) are a rare and heterogeneous group of tumours with various clinical manifestations and biological behaviours. They represent approximately 2-4% of all pancreatic tumours, with an incidence of 2-3 cases per million people. PNETs are classified clinically as non-functional or functional, and pancreatic resection is recommended for lesions greater than 2 cm. The surgical approach can involve "typical" and "atypical" resections depending on the number, size and location of the tumour. Typical resections include pancreaticoduodenectomy, distal pancreatectomy enucleation and, rarely, total pancreatectomy. Atypical resections comprise central pancreatectomies or enucleations. Minimally invasive pancreatic resection has been proven to be technically feasible and safe in high-volume and specialized centres with highly skilled laparoscopic surgeons, with consolidated benefits for patients in the postoperative course. However, open and minimally invasive pancreatic surgery remains to have a high rate of complications; there is no specific technical contraindication to minimally invasive pancreatic surgery, but an appropriate patient selection is crucial to obtain satisfactory clinical and oncological outcomes.

The aim of this study was to analyze the feasibility and clinical results of linear accelerator (linac-)based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) with flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) in elderly patients affected by brain metastases (BMs). Patients selected for the present analysis were ≥65 years old with a life expectancy of >3 months, a controlled or synchronous primary tumor, and

The difficulty in conducting meaningful clinical research is a multifactorial issue, involving political, financial and cultural problems, which can lead to unexpected negative long-term consequences, in terms of knowledge advancement and impact on patient care. The aims of the present review were to evaluate the publications of Italian radiotherapy (RT) groups during a 20-year period and to verify whether research is still appealing to young radiation oncologists (ROs) in Italy. PubMed database was searched for English-language articles published by Italian groups from January 1985 to December 2005. Analyzed variables were: publication/year, kind of study, geographical area and age of the first author. The systematic review identified 3291 articles: 1207 papers fulfilled the inclusion criteria. The number of Italian published papers increased during the examined period. Retrospective analyses, prospective phase I–II trials and literature reviews were 44, 20 and 14.5% of all published manuscripts, respectively. Randomized trials showed a mild increase from 2000 to 2005, but their absolute number remained low respect to other types of studies (4%). Northern Italy produced the very most of Italian research papers (58.7%). The age of the first/second author was evaluated on 716 papers: In more than 50% of cases, the first author was younger than 40. Despite a general gradual improvement, RT clinical research suffers in Italy (as elsewhere) from insufficient funding, with a negative impact on evidence production. It is worth noting that clinical research is still appealing and accessible to junior Italian RO.

A multicenter phase II study for assessing the efficacy and the toxicity of hypofractionated radiotherapy with SIB plus temozolomide in patients with glioblastoma was carried out by the Brain Study Group of the Italian Association of Radiation Oncology. Twenty-four patients with newly diagnosed glioblastoma belonging to Recursive Partitioning Analysis classes III and IV were enrolled. The prescribed dose was 52.5 Gy in 15 fractions of 3.5 Gy and 67.5 in 15 fractions of 4.5 Gy to the SIB volume. Dose constraints for the hypofractionated schedule were provided. Radiotherapy was associated with concomitant and sequential temozolomide. Median overall survival (OS) was 15.1 months, while median progression-free survival (PFS) was 8.6 months. Actuarial OS at 12 months was 65.6% ± 0.09, whereas actuarial PFS at 12 months was 41.2% ± 0.10. Status of methylation of MGMT promoter resulted to be a significant prognostic factor for OS. Radiotherapy-related acute toxicity was not relevant. Three patients (12.5%) had G3 myelotoxicity that required temozolomide temporary interruption or dose reduction during the chemotherapy. However, chemotherapy was not definitely discontinued for toxicity in any case. One patient out of 24 (4.2%) developed radionecrosis that required surgical resection with no evidence of disease in the surgical specimen. This trial confirms that hypofractionated radiotherapy with SIB and association with temozolomide may be a reasonable and feasible option for good prognosis patients with GBM.

To analyze the impact of 18F-fluorodeoxyglucose-PET/CT (PET/CT) in the radiotherapy (RT) planning strategy in HNC, correlating CT-scan and PET/CT performances. Inclusion criteria were: age >18 years old, histologically proven head and neck cancer (HNC), patients candidate to definitive RT ± chemotherapy, stage of disease by means of PET/TC and CT-scan performed at our Cancer Care Center. Sixty patients were analyzed. The following primary tumor sites were investigated: nasopharynx (13%), oropharynx (42%), oral cavity (32%) and larynx non-glottic (13%). Globally, PET/CT findings caused changes on nodal radiation treatment volumes in 10% of all the population of study. Specifically, in 5 cases out of 19 oral cavity tumors (26%), PET/CT detected neck-nodes positive (not detected at CT-scan). These findings have allowed to change the patients management, including PET/CT neck-nodes positive in the high-risk RT volumes. In the RT planning strategy, the present findings support the use of PET/CT to improve upfront regional staging of HNC disease, particularly for oral cavity tumors. Further investigations are advocated to evaluate if this strategy could impact on long-term outcomes in terms of local control and overall survival.

In the last few years, the major change has occurred in the expansion of indications for radiosurgery (SRS) to include patients with more than four brain metastases (BM). To address the expanding indications for SRS in the treatment of multiple BMs, HyperArcTM (Varian Medical System, Palo Alto, CA, U.S.) was recently introduced in order to automate and simplify sophisticated treatments such as SRS/FSRT for multiple lesions (up to 20 BM). In this editorial some consideration about HyperArc cost-effectiveness were discussed in terms of reduction of treatment delivery time (multiple intracranial targets can be treated in a few minutes), the reduction of overall treatment time (treatment course of SRS of multiple BMs in a single session, rather than having to irradiate lesion per lesion during separate sessions on different days); reduction of costs for health systems. In summary HyperArc™ system is a promising, safe and accurate solution for SRS/SFRT to treat multiple BMs in a single or few sessions. This has the potential to impact direct and indirect costs of SRS/SFRT delivery.

Cancer cachexia is a syndrome characterized by weight loss (WL) and sarcopenia. Aim of the study was to assess the impact of cachexia on head and neck changes during definitive cisplatin and image-guided volumetric-modulated arc radiation therapy in a series of locally advanced oropharyngeal cancer.Volume variations of sternocleidomastoid muscle (SCM) were considered as surrogate of muscle changes related to sarcopenia. Two head and neck diameters, encompassing the cranial limits of II and III nodal levels (defined as 'head diameter' and 'neck diameter', respectively), were measured. All parameters were defined retrospectively by means of on-board cone beam computed tomography images at 1-8th to 15-22th and at last fraction (fx) of radiotherapy (RT). Cachexia was defined as WL5% during treatment. Analysis was conducted correlating the parameter changes with three WL ranges:5, 5-9 and10%.Thirty patients were evaluated. One hundred and fifty contoured SCMs and three hundred diameters were collected. Median WL was 6.5% (range, 0-16%). The most significant SCM shrinkage was recorded at 15th fx (mean 1.6 cc) related to WL 5-9% and WL10% (P 0.001). For 'head diameter', the peak reduction was recorded at the 15th fx (mean 8 mm), statistically correlated to WL10% (P 0.001). The peak reduction in 'neck diameter' was registered at the 22th fx (mean 6 mm), with a gradual reduction until the end of treatment for WL5%.In a homogeneous cohort of patients, present study quantified the impact of cachexia on head and neck changes. Present data could provide adaptive RT implications for further investigations.

To estimate and reduce uncertainties of a self-consistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT). Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (α) and the repair (β) radio-sensitivities were estimated together with the doubling time (T d) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (T k) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results. The best estimate and the 95 % confidence intervals (95 % CIs) were: α = 0.24 Gy−1 (0.23–0.26), β = 0.023 Gy−2 (0.021–0.025), α/β = 10.6 Gy (8.4–12.6), T d = 3.5 days (3.1–3.9), T k = 19.2 days (15.1–23.3), N = 7 × 107 (4 × 107–1 × 108). From these data, the dose required to offset repopulation occurring in 1 day (D prolif) and starting after T k was also estimated as 0.69 Gy/day (0.52–0.86). The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC.

Background and purpose. The aim of this study was to estimate a radiobiological set of parameters from the available clinical data on glioblastoma (GB).Patients and methods. A number of clinical trial outcomes from patients affected by GB and treated with surgery and adjuvant radiochemotherapy were analyzed to estimate a set of radiobiological parameters for a tumor control probability (TCP) model. The analytical/graphical method employed to fit the clinical data allowed us to estimate the intrinsic tumor radiosensitivity (alpha), repair capability (b), and repopulation doubling time (T-d) in a first phase, and subsequently the number of clonogens (N) and kick-off time for accelerated proliferation (T-k). The results were used to formulate a hypothesis for a scheduleexpected to significantly improve local control. The 95 % confidence intervals (CI95 %) of all parameters are also discussed.Results. The pooled analysis employed to estimate the parameters summarizes the data of 559 patients, while the studies selected to verify the results summarize data of 104 patients. The best estimates and the CI95 % are alpha = 0.12 Gy(-1) (0.10-0.14), b = 0.015 Gy(-2) (0.013-0.020), alpha/b = 8 Gy (5.0-10.8), T-d = 15.4 days (13.2-19.5), N = 1.10(4) (1.2.10(3)-1.10(5)), and T-k = 37 days (29-46). The dose required to offset the repopulation occurring after 1 day (D-prolif ) and starting after T-k was estimated as 0.30 Gy/day (0.22-0.39).Conclusion. The analysis confirms a high value for the alpha/b ratio. Moreover, a high intrinsic radiosensitivity together with a long kick-off time for accelerated repopulation and moderate repopulation kinetics were found. The results indicate a substantial independence of the duration of the overall treatment and an improvement in the treatment effectiveness by increasing the total dose without increasing the dose fraction.

To evaluate radiotherapy treatment planning accuracy by varying computed tomography (CT) slice thickness and tumor size. CT datasets from patients with primary brain disease and metastatic brain disease were selected. Tumor volumes ranging from about 2.5 to 100 cc and CT scan at different slice thicknesses (1, 2, 4, 6 and 10 mm) were used to perform treatment planning (1-, 2-, 4-, 6- and 10-CT, respectively). For any slice thickness, a conformity index (CI) referring to 100, 98, 95 and 90 % isodoses and tumor size was computed. All the CI and volumes obtained were compared to evaluate the impact of CT slice thickness on treatment plans. The smallest volumes reduce significantly if defined on 1-CT with respect to 4- and 6-CT, while the CT slice thickness does not affect target definition for the largest volumes. The mean CI for all the considered isodoses and CT slice thickness shows no statistical differences when 1-CT is compared to 2-CT. Comparing the mean CI of 1- with 4-CT and 1- with 6-CT, statistical differences appear only for the smallest volumes with respect to 100, 98 and 95 % isodoses—the CI for 90 % isodose being not statistically significant for all the considered PTVs. The accuracy of radiotherapy tumor volume definition depends on CT slice thickness. To achieve a better tumor definition and dose coverage, 1- and 2-CT would be suitable for small targets, while 4- and 6-CT are suitable for the other volumes.

To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM).From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for 5 days every 28 days.Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens.Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule.

The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID was used in cine mode acquisition: acquired images were used to the aim. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

La radiochemioterapia (RTCHT) e il trattamento standard nei pazienti affetti da glioblastoma (GBM), ma a causa della mancanza di evidenze nei pazienti anziani, la radioterapia e la chemioterapia possono essere utilizzate singolarmente o integrate. Il nostro studio retrospettivo valuta la tossicita acuta e l’outcome della RTCHT con temozolomide (TMZ) nei pazienti anziani affetti da GBM. Sono stati valutati pazienti con eta superiore a 65anni affetti da GBM sottoposti a chirurgia o biopsia e RTCHT. I pazienti sono stati suddivisi secondo le classi prognostiche del radiation Therapy Oncology Group (RTOG)- recursive partitioning analysis (RPA). La tossicita acuta durante RTCHT e stata valutata secondo la scala National Cancer Institute-Common Toxicity Criteria (NCICTC) vers.3. Da aprile 2005 a gennaio 2011, 35 pazienti (18 donne e 17 uomini) sono stati trattati presso la nostra divisione. Solo 11 pazienti (31,43%) sono stati sottoposti a resezione completa. La sopravvivenza libera da progressione e la sopravvivenza mediane sono state di 8 e 13 mesi, rispettivamente. All’analisi univariata e multivariata solo la classe RPA ha mostrato influenzare la sopravvivenza (p=0,01; p=0,03). La tossicita acuta, durante RTCHT, e stata accettabile (11,43% di trombocitopenia G3–4; 8,57% di tossicita neurologica G3–4). I nostri dati suggeriscono che nei pazienti anziani l’associazione di radioterapia e temozolomide sembra essere efficace e sicura.

To evaluate the dosimetric changes of parotid glands (PG) during a course of intensity-modulated radiotherapy (IMRT) in head and neck (H&N) cancer patients. Ten patients with H&N cancer treated by IMRT were analyzed. The original treatment plan (CTplan) was transferred to cone-beam computed tomography (CBCT) acquired at the 15th and 20th treatment day (CBCTplan I and II, respectively). The PG mean dose (D mean), the dose to 50 % of the volume, and the percent of volume receiving 30 and 50 Gy were measured by the dose volume histogram. 30 IMRT plans were evaluated (3 plans/patient). All dosimetric end points increased significantly for both PG only when CTplan was compared to CBCTplan I. The D mean increased significantly only for ipsilateral PG (p = 0.02) at week 3. During a course of IMRT, CBCT is a feasible method to check the PG dosimetric variations. Perhaps, the 3rd week of radiotherapy could be considered as the time-check-point.

This study evaluated the biochemical diseasefree survival (bDFS) rate, overall survival rate (OS) and toxicity after low-dose rate I125 permanent-implant prostate brachytherapy (LDR-BRT) in elderly patients affected by prostate cancer. Patients aged ≥65 years with a diagnosis of prostate cancer and treated at our institution were retrospectively evaluated. All patients received LDR-BRT as monotherapy; the prescribed dose was 145 Gy to the prostate. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) recurrence risk groups. Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria. The Radiation Therapy Oncology Group (RTOG) scale was used for toxicity. The bDFS was calculated from implant date to biochemical recurrence. Between June 2003 and December 2008, 80 elderly patients with a median age of 75 (range, 65–86) years were treated with LDR-BRT: 51 low risk (64%), and 29 intermediate risk (36%). Over a median follow-up period of 53 (range, 28–94) months, the global actuarial 5-year bDFS rate was 91.3% and the 5-year OS was 95%. Toxicity was mild: late grade-3 genitourinary toxicity was observed in only four patients (5%). Our data suggest that LDR-BRT is effective and safe as monotherapy in elderly patients.

Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers. One hundred sixty-five consecutive patients with newly diagnosed (77 patients) or recurrent (88 patients) glioblastoma were studied. Forty-seven patients underwent surgery + Gliadel. The impact of age (≥65 vs.

To assess the role of comorbidity on outcome in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant Temozolomide, patients over 65 years with glioblastoma, who underwent surgical resection or biopsy and radiochemotherapy, were evaluated. The Adjusted-Age Charlson Comorbidity Index and the Adult Comorbidity Evaluation-27 were used to assess comorbidity. From April 2005 to January 2011, 35 patients (median age 72 years) were treated in our Institution. Thirteen patients had a Charlson score more than 3, while, according to the Adult Comorbidity Evaluation-27, 21 patients had mild or severe comorbid conditions. Patients with low Charlson comorbidity score experienced a longer survival time than those with higher score (22 vs. 10 months, respectively). The Adjusted-Age Charlson Comorbidity Index influenced survival at univariate and multivariate analysis (p = 0.004, p = 0.001, respectively). No comorbidity index was a predictor for progression-free survival. Our data suggested that the association of radiotherapy with TMZ was safe and effective. Perhaps, the comorbidity assessment could be an appropriate tool in the treatment decision for elderly patients with glioblastoma.

A modification of the Talairach stereotactic system is described which is able to incorporate CT data and provides both co-ordinate calculations, directly from the CT console screen and by a fiducial reference system. The device maintains the original base plate, thus allowing its interfacing with all the accessories of the early apparatus and its direct use in the stereotactic operating room. The instrument has shown great reliability in the localisation of brain lesions and considerable flexibility in many stereotactic operations such as biopsy procedures, brachytherapy, radiosurgery and stereotactically assisted resections.