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The evidence for adjuvant therapy in locally advanced rectal cancer after TME surgery is sparse. The aim of this study was to identify predicting factors of overall survival (OS) in these patients and combine them into a nomogram for individualized treatment. 1798 patients with pathologically staged II/III rectal adenocarcinoma treated by radical TME surgery from a single center's database were reviewed. The nomogram was derived by Cox proportional hazards regression. Its performance was assessed by concordance index and calibration curve in internal validation with bootstrapping. Pooled Cox model analysis identified age, sex, grade of histology, pathological T and N stage, residual tumor, concurrent radiochemotherapy (RTCT), adjuvant chemotherapy cycles (CT), radiotherapy (RT) unexpected interruption days and intensity-modulated radiation therapy (IMRT) as significant covariates for 5-year OS (P<0.05). Postoperative RTCT, CT and IMRT all improved OS. The proposed model can predict 5-year OS with a C-index of 0.7105. IMRT significantly benefited OS in multivariate analysis (p=0.0441).In conclusion, our nomogram can predict 5-year OS after TME surgery for locally advanced rectal cancer with simple and effective advantage. This model may provide not only baseline OS estimate but also a tool for candidates selecting of adjuvant treatment in prospective studies., Competing Interests: The authors have declared no conflicts of interest.

To validate autocontouring software (AS) in a clinical practice including a two steps delineation quality assurance (QA) procedure.The existing delineation agreement among experts for rectal cancer and the overlap and time criteria that have to be verified to allow the use of AS were defined.Median Dice Similarity Coefficient (MDSC), Mean slicewise Hausdorff Distances (MSHD) and Total-Time saving (TT) were analyzed.Two expert Radiation Oncologists reviewed CT-scans of 44 patients and agreed the reference-CTV: the first 14 consecutive cases were used to populate the software Atlas and 30 were used as Test.Each expert performed a manual (group A) and an automatic delineation (group B) of 15 Test patients.The delineations were compared with the reference contours.The overlap between the manual and automatic delineations with MDSC and MSHD and the TT were analyzed.Three acceptance criteria were set: MDSC ≥ 0.75, MSHD ≤1mm and TT sparing ≥ 50%.At least 2 criteria had to be met, one of which had to be TT saving, to validate the system.The MDSC was 0.75, MSHD 2.00 mm and the TT saving 55.5% between group A and group B. MDSC among experts was 0.84.Autosegmentation systems in rectal cancer partially met acceptability criteria with the present version., Competing Interests: The authors report no conflicts of interest. The authors are alone responsible for the content and writing of the paper.

Background: The hypopharynx is the site with the worst prognosis among head and neck squamous cell carcinomas (SCCs). The purpose of this study was to evaluate the oncologic outcomes of hypopharyngeal SCCs to identify the major clinical predictive factors and to compare the different primary therapeutic modalities., Methods: The medical records of 123 consecutive patients diagnosed with primary resectable hypopharyngeal SCC were reviewed. The correlations of oncologic endpoints with tumor parameters and primary treatment were evaluated., Results: The overall survival (OS) rate was 76% and the disease-specific survival (DSS) rate was 80% at 3 years in the entire group. Sex and T and N classifications significantly influenced survival in both univariate and multivariate analyses. Seventy-four percent of our patients underwent both surgery and radiotherapy (RT), and the temporal sequence of the 2 modalities did not affect prognosis., Conclusion: The primary treatment modality in patients with resectable hypopharyngeal SCC did not affect prognosis in univariate and multivariate analyses for any stage considered., (© 2015 Wiley Periodicals, Inc.)

Objectives/hypothesis: Squamous cell carcinoma arising from the nasal vestibule is a rare condition accounting for about 1% of head and neck malignancies with several peculiarities concerning both staging and treatment. The aim of this study was to compare the oncological and functional results of two different treatment modalities for the primary site: surgery and brachytherapy., Study Design: A case series with the comparison of two different treatment modalities., Methods: We evaluate clinical and survival data of 12 untreated patients, enrolled by a multidisciplinary tumor board, comparing oncological, functional, and esthetic results after surgery or after interstitial brachytherapy as exclusive treatments for the primary site. The functional and esthetic outcome was subjectively rated by the patients using a five-point scale., Results: Locoregional control and survival are not significantly different between patients primarily treated by surgery and by brachytherapy. The functional and esthetic outcome, as assessed by the degree of satisfaction of the patients, is significantly better after primary brachytherapy than after primary surgery (P = .014)., Conclusions: In our experience brachytherapy, accomplished in close cooperation between surgeons and radiation oncologists, achieves oncological results that are not different from surgery, but with a higher degree of patient satisfaction, mainly due to the esthetic outcome., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

The advances in diagnostic and treatment technology are responsible for a remarkable transformation in the internal medicine concept with the establishment of a new idea of personalized medicine. Inter- and intra-patient tumor heterogeneity and the clinical outcome and/or treatment's toxicity's complexity, justify the effort to develop predictive models from decision support systems. However, the number of evaluated variables coming from multiple disciplines: oncology, computer science, bioinformatics, statistics, genomics, imaging, among others could be very large thus making traditional statistical analysis difficult to exploit. Automated data-mining processes and machine learning approaches can be a solution to organize the massive amount of data, trying to unravel important interaction. The purpose of this paper is to describe the strategy to collect and analyze data properly for decision support and introduce the concept of an 'umbrella protocol' within the framework of 'rapid learning healthcare'.

Decision Support Systems (DSSs) are increasingly exploited in the area of prognostic evaluations. For predicting the effect of therapies on patients, the trend is now to use image features, i.e. information that can be automatically computed by considering images resulting by analysis. The DSSs application as predictive tools is particularly suitable for cancer treatment, given the peculiarities of the disease -which is highly localised and lead to significant social costs- and the large number of images that are available for each patient. At the state of the art, there exists tools that allow to handle image features for prognostic evaluations, but they are not designed for medical experts. They require either a strong engineering or computer science background since they do not integrate all the required functions, such as image retrieval and storage. In this paper we fill this gap by proposing Moddicom, a user-friendly complete library specifically designed to be exploited by physicians. A preliminary experimental analysis, performed by a medical expert that used the tool, demonstrates the efficiency and the effectiveness of Moddicom.

Background: Antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, are effective in loco-regional advanced squamous cell carcinoma of the head and neck (SCCHN) in association with radiotherapy. Cutaneous reactions are well known as adverse events during treatment with EGFR inhibitors., Objective: To identify a multidisciplinary approach for mucous-cutaneous toxicity during cetuximab-radiotherapy treatment in order to reduce the risk of an early radio-chemotherapy interruption., Methods: The data of 38 patients with SCCHN receiving cetuximab and radiotherapy were retrospectively analyzed. The control group (n = 15) received the standardized treatments according to the severity of skin reactions with dermatologic visits only for high degrees of toxicity. The experimental group (n = 23) was monitored and daily treated by dermatologists since grade 1 of cutaneous toxicity. The primary end-point of our study was the mean days of antitumor therapy interruption., Results: The mean number of days of antitumor therapy suspension was 12.6 (7.6) in the standard treatment group and 5.0 (6.6) in the experimental group (p = 0.002). This difference was observed for each grade of toxicity., Conclusion: The early interruption of radio-chemotherapy has a negative impact on survival in patients with SCCHN. In our study, a closer dermatological examination and treatment for all degrees of toxicity reduced early interruptions of chemo-radiotherapy.

Purpose: To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer., Materials and Methods: Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients., Results: A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05)., Conclusions: Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Purpose: Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients., Methods and Materials: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated by immunohistochemistry in FPPE specimens., Results: Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461)., Conclusion: Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Predictive models allow treating physicians to deliver tailored treatment moving from prescription by consensus to prescription by numbers. The main features of an umbrella protocol for standardizing data and procedures to create a consistent dataset useful to obtain a trustful analysis for a Decision Support System for rectal cancer are reported., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate in two different settings - clinical practice and education/training - the reliability, time efficiency and the ideal sequence of an atlas-based auto-segmentation system in pelvic delineation of locally advanced rectal cancer., Methods: Fourteen consecutive patients were selected between October and December 2011. The images of four were used as an atlas and 10 used for validation. Two independent operators participated: a Delineator to contour and a Reviewer to perform an independent check (IC). The CTV, pelvic subsites and organs at risk were contoured in four different sequences. These included A: manual; B: auto-segmentation; C: auto-segmentation + manual revision; and D: manual + auto-segmentation + manual revision. Contouring was performed by the Delineator using the same planning CT. All of them underwent an IC by a Reviewer. The time required for all the contours were recorded and overlapping evaluation was assessed using a Dice coefficient., Results: In the clinical practice setting there have been 13 minutes time saved between sequences A versus sequences B (from 38 to 25 minutes, p = 0.002), a mean Dice coefficient in favor of sequences A for CTV and all subsites (p = 0.0195). In the educational/training setting there have been 35.2 minutes time saved between sequences C and D 8 (from 73.1 min to 37.9 min, p = 0.002)., Conclusion: The preliminary data suggest that the use of an atlas-based auto-contouring system may help improve efficiencies in contouring in the clinical practice setting and could have a tutorial role in the educational/training setting.

Purpose: Measuring parotid density changes in patients treated with IMRT for head-neck cancer (HNC) and assessing correlation with treatment-related parameters., Patients and Materials: Data of 84 patients treated with IMRT for different HNC were pooled from three institutions. Parotid deformation and average Hounsfield number changes (ΔHU) were evaluated through MVCT (with Helical Tomotherapy) or diagnostic kVCT images taken at the treatment start/end. Parotids were delineated in the first image and propagated to the last using a previously validated algorithm based on elastic registration. The correlation between ΔHU and several treatment-related parameters was tested; then, logistic uni- and multi-variate analyses taking "large" ΔHU as end-point were carried out. Due to the better image quality, analyses were repeated considering only kVCT data., Results: ΔHU was negative in 116/168 parotids (69%; for kVCT patients: 72/92, 78%). The average ΔHU was significantly different from zero (-7.3, 0.20-0.25 HU/fraction, p<0.001). Individual ΔHU was highly correlated with parotid deformation both in terms of volume change and mean value of the Jacobian of the deformation field (Jac&#95;mean), and with neck thickness variation; these correlations were much stronger for kVCT data. Logistic analyses considering ΔHU<-11 (quartile value) as the end-point showed a two-variable model including large deformation (Jac&#95;mean<0.68) and initial neck thickness to be the most predictive variables (p<0.0005, AUC=0.683; AUC=0.776 for kVCT); the odd ratio of large vs moderate/small parotid deformation was 3.8 and 8.0 for the whole and the kVCT population respectively., Conclusions: Parotid density reduced in most patients during IMRT and this phenomenon was highly correlated with parotid deformation. The individual assessment of density changes was highly reliable just with diagnostic KvCT. Density changes should be considered as an additional objective measurement of early parotid radiation-induced modifications; further research is warranted., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Treatment for laryngeal squamous cell carcinoma (SCC) has been predominantly surgical for decades, but in the last 20 years nonsurgical modalities (radiotherapy), with the aim of organ preservation, also became predominant among advanced stages. Retrospectively evaluating our series of stage III and stage IV laryngeal SCCs, we compared the 2 main therapeutic modalities., Methods: Medical records of 65 consecutive patients with advanced laryngeal SCC, from November 2005 to January 2009, were reviewed., Results: Among irradiated patients 2-year organ preservation was 86% for cT2, 43% for cT3, and 17% for cT4a (p = .037, Wilcoxon test). With respect to survival, the only significant differences between surgery and radiotherapy were detected among cT4a SCCs (p = .03, Wilcoxon test), in favor of surgery., Conclusions: The present results confirm the surgical recommendation for cT4a laryngeal SCCs. On the other hand, for T < 4, our results confirm that radiochemotherapy warrants a survival similar to that of total laryngectomy, thus allowing us to preserve the larynx in a relevant number of cases., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: To evaluate the prognostic value of "early" and "late" Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with radio-chemotherapy (RTCT)., Materials and Methods: Twenty-six patients treated with RTCT for HNSCC were included. All patients underwent (18)F-FDG PET-CT at baseline ("staging" PET-CT), after 2 weeks of treatment ("early" PET-CT) and 8-12 weeks after treatment ("late" PET-CT). Changes in FDG uptake in the primary tumor (T) and lymph nodes (N) were correlated with local and regional control, respectively; overall metabolic response was correlated with relapse free survival (RFS) and disease specific survival (DSS)., Results: After a median follow-up of 29.2 months, 19/26 patients were living and 17/19 had no evidence of disease. When comparing "staging", "early" and "late" PET results, a significant decrease of FDG SUV(max) in T and N was documented. When correlating changes in FDG uptake in T and N with local and regional control, a statistically significant correlation only with the "late" reduction was found. Statistical analysis failed to demonstrate any correlation between the "early" metabolic response and the patient clinical outcome while the "late" metabolic response revealed a strong correlation with RFS (p = 0.01) and DSS (p = 0.009)., Conclusions: In patients with HNSCC, PET-CT performed after RTCT predicts the clinical outcome, since it strongly correlates with RFS and DSS. On the other hand, the predictive role of "early" metabolic response was not confirmed by this study., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Medulloblastoma (MB) occurs infrequently in adult patients and standard treatment is still controversial. We report our long-term, single-institution experience of adult MB and a review of the literature. We analysed adult patients with histologically proved MB treated by postoperative radiotherapy. Primary endpoints were local control (LC), disease-free survival (DFS), and overall survival (OS). Acute toxicity was reported according to CTC-NCI score vers. 3.0 and specific neuropsychological assessment analysis was performed to define late brain toxicity. From 1990-2008, 13 patients were treated by craniospinal (CSI, 12/13) or cranial irradiation (1/13, because of bad clinical conditions). Median follow up was 101 months (64-218). Complete radiological response was observed in 12/13 patients and a partial response in 1/13. Ten-year LC, OS, and DFS were 91, 76, and 84%, respectively. Two patients died because of local and spinal progression after 13 and 62 months. Acute G3 haematological toxicity (RTOG score) was observed for one patient only. The neuropsychological analysis did not reveal late toxicity related to brain radiotherapy. This experience confirms the efficacy and safety of radiotherapy in adult MB patients, resulting in very interesting 10-year LC and OS.

Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT)., Methods and Materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score≥7 and/or prostate-specific antigen level≥20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT)., Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p=NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p=.03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p=NS)., Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes., Methods: Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival., Results: Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40)., Conclusion: Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

Background and Purpose: To compare oncological outcome and voice quality among a uniform and well-defined subset of patients with T1 glottic carcinoma., Patients and Methods: Patients, affected by laryngeal glottic carcinoma, treated by laser CO2 surgery or radiotherapy, have been analyzed. Overall survival and disease-free survival were calculated. In order to verify differences in functional outcomes and voice quality, all patients were interviewed during their last follow-up visit during 2009 using the VHI (Voice Handicap Index) questionnaire. The data were analyzed using the MedCalc software., Results: A total of 143 patients were analyzed: 73 underwent surgery and 70 underwent radiotherapy. No statistically significant differences were found between the two groups in terms of overall survival and disease-free survival; dividing patients into stages T1a and T1b also made no difference. In order to evaluate the differences in outcomes for surgery and radiotherapy, patients were interviewed using the VHI questionnaire. Better scores for each category in the VHI were found for patients receiving radiotherapy compared to surgery (physical: p = 0.0023; functional: p < 0.0001; environmental: p < 0.001). The median VHI score for radiotherapy patients was 4, while for surgical patients it was 18 (p < 0.0001)., Conclusion: This study confirms the well-known knowledge that results from radiotherapy and surgery in early glottic cancer treatment are equivalent. Furthermore, the role of patient preference in the treatment modality choice and the value of a multidisciplinary approach for a detailed and multi-oriented discussion with the patient are outlined.

Purpose: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs)., Patients and Methods: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis., Results: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months., Conclusion: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Background and Purpose: In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors., Methods and Materials: Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT., Results: Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed., Conclusion: In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC)., Materials: Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (DeltaV) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between DeltaVcc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a DeltaVcc/% larger than the median value. Linear models of DeltaV (continuous variable) based on the most predictive variables found at the MVA were developed., Results: Median DeltaVcc/% were 6.95 cc and 26%, respectively. The most predictive independent variables of DeltaVcc at MVA were the initial parotid volume (IPV, OR: 1.100; p=0.0002) and Dmean (OR: 1.059; p=0.038). The main independent predictors of DeltaV% at MVA were age (OR: 0.968; p=0.041) and V40 (OR: 1.0338; p=0.013). DeltaVcc and DeltaV% may be well described by the equations: DeltaVcc=-2.44+0.076 Dmean (Gy)+0.279 IPV (cc) and DeltaV%=34.23+0.192 V40 (%)-0.2203 age (year). The predictive power of the DeltaVcc model is higher than that of the DeltaV% model., Conclusions: IPV/age and Dmean/V40 are the major dosimetric and clinical/anatomic predictors of DeltaVcc and DeltaV%. DeltaVcc and DeltaV% may be well described by bi-linear models including the above-mentioned variables., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer., Methods: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score., Results: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT=17) and 1.31 (95% CI: 1.04-1.66; NNT=13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found., Conclusion: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.

Aims and Background: The aim of the study was to analyze the feasibility of a setting up of a radiotherapy department using videoconferencing technology., Material and Methods: A videoconferencing network was started to link an academic center of radiotherapy to a peripheral center of research at the start of its activity. Two years of data of involved professionals, subjects of links, audio, video link problems and running costs were recorded., Results: A total of 418 links was established for an overall duration of 458 hours. The participants included all departmental staff. Videoconferencing involved teaching, ward organization, medical care and scientific subjects. In the second year ofexperience, the number of videoconferencing links was higher than the first (232 vs 186). Link times were reasonable for both skilled and unskilled operators. Overall, the cost per minute of link was 0.2 Euro, and the mean cost per link was 13 Euros. Videoconferencing was integrated with fax and computer networks to enhance sharing paper and electronic documents. Audio-video technical problems progressively decreased: the link was definitively interrupted or its activation unfeasible in only 1.0% of cases., Conclusions: Our experience suggests that the establishment of a link between radiotherapy departments addressed to these aims is feasible by a videoconferencing network.

Radiotherapy still plays a major role in the treatment of brain lesions. Its end-points are not only better survival but especially better disease control that positively impacts on better quality of life. However radiotherapy is not free of both acute and late side-effects. Data on late toxicity are disappointing, for inadequate follow-up time and the absence of cards for collecting information shared by the scientific community in an attempt to acheive a common, universal language. While these treatments should be considered for palliation, the main goal is always the patient with his/her quality of life, and their toxicity should be monitored to optimize therapeutic outcomes and lower the incidence of complications. The monitoring system of late toxicity used by the authors is presented.

The radiation-induced cardiovascular pathology represents a major cause of morbidity and mortality in patients undergoing therapeutic chest irradiation. There is a broad range of clinical manifestations probably associated with dose, volume and technique of irradiation. From the assumption that prevention is the best way to manage radiation-induced cardiotoxicity, based on the pathophysiogenesis of heart structures, a number of reports of the literature are reviewed. They consider the incidence of cardiovascular disease in patients affected by Hodgkin's lymphoma and breast cancer. The dosimetric prevention is takled in terms of therapeutic procedures and doses (IMRT, 3DCRT) with particular reference to the impact on cardiotoxicity of parameters as maximum heart distance (MHD), mean lung dose (MLD), normal tissue complication probability (NTCP) and V30. The different evaluation criteria of cardiotoxicity are reported, based on the review of the major scoring scales of acute and late complications, which have been worked out in the course of time (LENT-SOMA, RTOG, CTC v.2.0 and CTC v.3.0). The monitoring system of late toxicity used by the authors is presented.

Unplanned gaps in radiotherapy can impact on its clinical effect, especially in tumors with accelerated repopulation. In the literature, several technical solutions have been proposed. According to the situation, compensation for the effect on the tumor to the detriment of normal tissue tolerance can be achieved. An approach, modulated according to the gap duration and timing is proposed aimed at constant tumor control with no significant increased risk of side-effects. The decisional algorithm and calculation formulae are used in our center in teaching addressed to residents to make them familiar with the possible clinical applications of radiobiological knowledge.

Background and Purpose: Three-dimensional conformal radiotherapy and intensity modulated radiotherapy allow accurate dose delivery on target volumes. Due to the different background among specialists involved in target volume definition, the contouring emerges as one of the most questionable steps in treatment planning procedures. A software tool devoted to contouring training, named tutorial for image guided external radiotherapy ('TIGER'), based on the Visible Human Project images data-set, is described., Materials and Methods: TIGER is addressed to facilitate the learning of axial anatomical images, to promote the training and reproducibility in contouring process, to allow the availability of a tool to enhance the 'drill and practice' approach in training programs. TIGER includes three different environments: Anatomic tutorial devoted to facilitate a self-learning approach to axial body sections; Contouring tutorial addressed to practice contouring process of anatomical structures and to undergo a test program prepared by tutors; Teacher's tools to offer to tutors the opportunity to insert new outlines in TIGER-database, according to local needs or conventions, and to use them in tutorial programs. TIGER-database is grouped in six main anatomical sections: head and neck, male thorax, female thorax, abdomen, male pelvis, and female pelvis. Overall 432 corresponding CT-VH images and 1189 contours of 134 different anatomical structures and lymphatic drainage areas are available. The access to the TIGER software is allowed by ESTRO web site (http://www.estro.be)., Conclusions: TIGER provides an interactive human anatomy cross-sectional oriented source to facilitate the interpretation of CT scan images usually contoured in daily practice. It offers a drill tool to facilitate the learning of a reproducible contouring procedure.

Despite the low local recurrence rate that can be achieved by adequate surgery (total mesorectal excision--TME), radiation therapy was shown to play a significant role in reducing this risk. The widespread use of TME in many European Centers has introduced a new terminology and the need to identify the area at major risk for local failure using this surgical procedure. In the surgical series where extended extra-mesorectal surgery was performed, the role of lymphatic spread was evidenced, especially for low rectal cancer, through the pelvic parietal fascia and lateral pelvic spaces. The aim of this study was to better define some anatomic concepts and the main risk factors which impact on CTV contouring and field conformation in rectal cancer treatment. This information helps formulating guidelines for CTV contouring in daily radiotherapy practice, in order to define the best therapy, according to the tumor stage and location.

Elderly age is one of the main risk factors to be associated with the onset of different tumors. The tumor in the elderly almost always appears at a late, advanced stage for the lack of an accurate attention to symptoms-signs, as well as for the absence of involvement in mass screening campaigns. In the choice of a radiotherapy treatment in the elderly, the healthy tissues adjacent to the tumor may show a different ability for repair; this should be kept in mind in the definition of the target volume together with the possible presence of comorbidities specific to the elderly age.

In the last two decades there was a radical change in radiotherapy setup. The growing availability of CT equipment and console for computer-aided treatment planning setup enabled the use of advanced technologies as conformal 3D radiation therapy in most centers. In particular in 1987 virtual simulation was proposed for setup. During its use a number of application modalities appeared. Virtual simulation in some centers is applied alone while in others it is associated with conventional simulation. However, from numerous reports published in last years it seems that virtual simulation significantly improves treatment quality independently of radical or palliative intent and of the size of treated volumes (high doses to small volumes or wide shaped fields). Some studies stressed that virtual simulation could significantly shorten treatment planning times with consequent cost reduction. The use of virtual simulation evidenced associated problems and in particular setup limitations due to the CT gantry size, the need to up-date the conventional modalities of setup verification according to the new technologies and more generally to up-date quality assurance procedures in an advanced technological setting. Finally there was the self-evident need of a better knowledge of the anatomy on axial sections, of tumor spread routes in particular.

Purpose: Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease., Methods and Materials: The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies., Results: With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume., Conclusion: The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor.