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Papers by savino cilla

Plenary sessions, 2019

patients experience persisting substantial symptoms. LAPERS/ median prevalence ratios close to 1 ... more patients experience persisting substantial symptoms. LAPERS/ median prevalence ratios close to 1 indicate that the proportion of patients experiencing substantial symptoms displayed in the prevalence over time are the same individual patients with persisting symptoms. Conclusions LAPERS method provides complementary information to prevalence and incidence rates. LAPERS provides a more appropriate tool for a valid assessment of patients' burden of substantial toxicity.

Journal of Pain Research, 2018

Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is... more Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000-December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%-91.5%), with high heterogeneity (Q 2 test: P<0.001; I 2 =83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%-18.0% and 6.0%-8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.

Radiotherapy and Oncology, 2016

________________________________________________________________________________ gantry speed GS)... more ________________________________________________________________________________ gantry speed GS) and T3 (variation of MLC Speed MLCS) were updated. Even so, we decided to redraw completely T2 and T3, in the respect of the effective main concept. A family of new plans was generated to guarantee flexibility in the QA procedure and to support the user in a possible troubleshooting.

Radiotherapy and Oncology, 2016

The phantom study showed that phantom position was linearly correlated with the exit detector mea... more The phantom study showed that phantom position was linearly correlated with the exit detector measurements resulting in an r > 0.99. The standard deviation in the measured breast surface position, σ, was 2.28 mm for the 453 analyzed detector fluences (σmin = 1.39 mm, σmax = 4.33 mm). The uncertainty in the detector measurements was estimated to be under one detector channel's width. Conclusion: The σ results of this study should be an indicator of the overall positioning uncertainty in our IGRT process for these treatments, i.e. kVCT-MVCT image registration, patient movement, and respiratory motion. Even if only one projection of the treatment data was used in the estimation, our results compare very well with similar studies' (von Tienhoven et al (1991), Smith et al (2005), Wang et al (2013)) findings on breast displacement due to respiratory motion. Furthermore, the novelty of this study is its evaluation of the breast position was performed on exit detector fluence of intensity-modulated fields, which we believe to be a first.

Radiotherapy and Oncology, 2016

Purpose or Objective: Retrospective review of results of radiotherapy for stage T1 glottic carcin... more Purpose or Objective: Retrospective review of results of radiotherapy for stage T1 glottic carcinoma. Material and Methods: A retrospective review was done of all patients with squamous cell carcinoma of the glottis stage T1 treated with radiotherapy between 1960 and 2012 inclusive. There were 995 patients identified. All patients were treated with wedged lateral or angled anterior oblique technique. The main site of relapse was local and hence the main end point for anaysis was local control at 5 years. Survival curves were calculated using Kaplan Meier method and log rank test used to comparer differences. Results: Overall the 5 year freedom from relapse was 88%. The only factor which influenced outcome was time period of radiotherapy with those between 1960 and 1980 had a 84% relapse free rate, significantly worse than the latter time period. Other factors examined included sex, age, substage T1a and T1b, grade, radiation dose, radiation field size and duration of radiation, and none of those factors had a significant effect on outcome. There were 121 relapses, most in the primary alone and most within the first two years. Conclusion: The overall 5 year freedom from relapse was 88%. EP-1037 Dysphagia and irradiation of constrictor pharyngeal muscles: a clinical-dosimetric correlation

Radiotherapy and Oncology, 2016

Purpose or Objective: to analyze possible clinical value of lymph flow visualization as the guide... more Purpose or Objective: to analyze possible clinical value of lymph flow visualization as the guide for irradiation of IMLN. Material and Methods: On the first stage of the study we combined data of 8 published studies that analyzed lymph flow from primary BC (4541 patients) after intra-peritumoral injection of nanosized 99mTc-colloids. Using this data we determined probability of lymph flow from BC of internal/central or lateral localization to IMLN. In 7 studies (4359 women) axillary staging was accompanied by biopsy of sentinel lymph nodes localized in internal mammary region. This data made it possible to estimate probability of IMLN metastatic invasion in relation with the status of axillary LN. At the final stage of the study we calculated probability of IMLN invasion by BC in 4 randomized and 2 observation studies that analyzed effect of IMLN irradiation on overall survival. Additionally, we tried to calculated possible additional gain in survival if patients from this 6 (4+2) trials would be treated according to lymph flow guided irradiation of IMLN. Results: According to results of 8 published studies lymphflow from lateral BC to IMLN was detected in 16% (727/4541), from internal/central lesions-in 35% (1589/4541).Evaluation of 7 studies (4359 women) showed that in patients with noninvolved axillary LN metastases in IMLN were revealed in 7.8%, in patients with positive axillary nodes-in 38.1% cases. In all 6 studies that evaluated clinical value of IMLN irradiation, calculated probabilities of IMLN metastatic invasion in "high risk patients" didn't exceed 10%. If IMLN irradiation would be performed only in patients with lymph flow to IMLN about 72.1%-76.8% of "high risk patients" would escape RT to IM region. In remained 23.2%-28.9% patients with visualized internal mammary sentinel lymph nodes their irradiation would improve overall survival from 1.6%-3.3% to 6.9%-14.2%. Conclusion: visualization of lymph flow from breast cancer after intratumoral injection of 99mTc-nanocolloids make decision about irradiation of IMLN more precise and efficient. Irradiation of visualized IMLN can significantly (6.9%-14.2%) improved overall survival in this group of patients with BC.

Radiotherapy and Oncology, 2016

Purpose or Objective: Many patients with advanced cancer develop bone metastases, with pain as a ... more Purpose or Objective: Many patients with advanced cancer develop bone metastases, with pain as a common, devastating consequence. Adequate treatment is important to maintain quality of life. Radiotherapy is the standard treatment for patients with painful bone metastases. Metaanalyses of radiotherapy trials have consistently shown a pain response rate of approximately 60% implying that many patients are treated insufficiently. It would be worthwhile to identify patients who will not respond to radiotherapy as these patients might be candidates for other treatments. Furthermore, better understanding and identification of the patients who do not respond to radiation, might help in the development of innovative treatments as alternative or addition to standard (radiation) treatment options. We studied the relationship between patient and treatment characteristics and pain response in patients with metastatic bone disease, with the aim to construct a prediction model to guide individualized treatment decision-making. Material and Methods: We analyzed all prospectively collected data on pain response from a palliative radiotherapy clinic in an academic hospital. Patients were considered responders if they reported a decrease in pain score of at least 2 points with stable analgesic use within 3 months after treatment. A multivariable logistic regression model was developed with age, gender, primary tumor, Karnofsky performance status (KPS), painful localization, presence of visceral metastases, previous systemic treatment, analgesic use at baseline, and baseline pain score. For variable selection, we started with the full model and applied backward stepwise selection with a selection criterion of p < 0.20. Performance of the model was quantified using the c-statistic and corrected for optimism. A worst case scenario (assuming no response in patients who were lost to follow up) was added as sensitivity analysis. Results: A total of 1018 patients treated between January 1999 and November 2007 were included. Outcome was recorded in 588 (58%) patients, of which 394 (67%) reported a response. Primary tumor, KPS, baseline pain score, and analgesic use were predictive for response with a corrected c-statistic of 0.59 (Table). Assuming non-response in the 430 patients without follow up (worst case scenario), there was still an association between response and primary tumor, KPS, and baseline pain score.

Radiotherapy and Oncology, 2016

ESTRO 35 2016 ___________________________________________________________________________________... more ESTRO 35 2016 _____________________________________________________________________________________________________ progression of a baseline VCF. Each metastatic spinal segment was also evaluated according to the six Spinal Instability Neoplastic Score (SINS) criteria (location, pain, bone lesion type, spinal alignment, posterolateral element involvement, bone lesion type, presence of a baseline fracture) to evaluate the predictive significance. Results: The median spine RT total dose, dose per fraction, and number of fractions was 30 Gy (range, 8-60 Gy), 3 Gy (range, 1.2-18 Gy), and 10 fraction (range, 1-25), respectively. The median follow-up for the entire cohort was 10 months. Nine percent (23/267) had been previously irradiated, 8% (20/267) had a baseline VCF, and 47% (83/176) were lytic tumor. In all spinal segments, 33 VCF (33/267, 12%) were observed following RT, including 21 de novo fractures and 11 progressive fractures, and the median time to VCF was 4 months. The 1-year fracture free probability (FFP) was 85%. Multivariate analysis identified sex (p = 0.005), metastatic involvement (p = 0.012), prior RT (p = 0.006), and baseline VCF (p < 0.001) as predictors of VCF. Among 176 metastatic spinal segments, we observed 32 fractures (32/176, 18%) with 1-year FFP of 78.1%. Multivariate analysis showed that the risk of VCF in metastatic spine segments was statistically significant in patients with SINS class II/III with or without pre-existing baseline VCF (p < 0.001) and prior RT(p < 0.001). Conclusion: The risk of VCF is higher in women patients with a baseline VCF and prior RT. Additionally, in metastatic spine segments, the risk of VCF is significant in patients with SINS class II/III with or without pre-existing baseline VCF and prior RT. SINS criteria can be used as an option for predicting VCF risk before performing RT specific to spinal metastases from CRC. EP-1428 Routine Whole Body MRI of bone metastases may reduce the incidence of spinal cord compression

Radiotherapy and Oncology, 2016

To analyze feasibility and toxicity of radical hypofractionated RT schedules in elderly patients ... more To analyze feasibility and toxicity of radical hypofractionated RT schedules in elderly patients with NSCLC Material and Methods: Material and methods: Elderly patients (≥70 years old) affected by stage III inoperable NSCLC were treated in our institution with radical IMRT (VMAT RA) according to moderately hypofractionated schedules: 56 Gy/20 fractions or 55 Gy/22 fractions or 50 Gy/20 fractions depending on dose constraints of adjacent organs at risk. Patients underwent simulation CT in supine position, immobilized with a thermoplastic mask. PET CT was performed for simulation and coregistered with CT. Primary end point of this analysis were acute and late toxixcities, secondary end points were local control and overall survival. Results: Results: 41 patients, treated between January 2013 and April 2015, were included in this analysis. Mean age was 78.59 years (range 70-86). 22 patients were staged IIIA, 19 patients IIIB. All but one patients had pathological nodal involvement (N1:5, N2: 24, N3: 11). Most of patients were unsuitable for chemotherapy for comorbidities and poor general conditions. 15 patients received chemotherapy before RT, concomitant RT-CHT was not allowed. Acute G1-2 toxicity was recorded in 25 patients(61), mostly esophagitis, dyspnea and dry cough. Late toxicity was recorded in 13 patients, the most reported side effects were pneumonitis and dyspnea. No G3 or G4 acute or late toxicity were recorded. A complete response was obtained in two patients, 26 showed a partial response, while progressive disease was recorded in 2 cases. At time of analysis, with a mean follow up of 9.89 months (range 1.08-25.43), 17 patients died for disease progression, one patient died for other causes, 8 patients were alive with distant metastases and 15 were alive without distant progression. Actuarial OS at 1 and 2 years were 51.3% and 35.1% respectively. Mean estimated OS was 15.12 months (range 12.02-18.22). Actuarial local control at 1 and 2 years were 72%. 10 patients experienced local progression. Mean estimated LC was 12.4 months (range 9.6-15.1). Conclusion: Conclusion: Radical hypofractionated IMRT (VMAT RA) is a valid treatment for locally advanced inoperable NSCLC in elderly frail patients. Our study shows that this approach is safe and feasible also in a fragile elder population. Survival data are satisfactory.

Radiotherapy and Oncology, 2016

Purpose or Objective: Neoadjuvant chemoradiotherapy (CRT) is considered a standard approach for l... more Purpose or Objective: Neoadjuvant chemoradiotherapy (CRT) is considered a standard approach for locally invasive rectal cancer. Several phase 3 studies have shown an improvement in local control with combined radiotherapy and capecitabine / 5-fluorouracil. There is good evidence that increased dose of radiotherapy is associated with both better pathological response and survival in many malignancies, although the data in rectal cancer is less convincing. In this study we assessed the impact of doseescalated radiotherapy on pathological outcome. Material and Methods: We evaluated all patients who received chemo-radiotherapy for rectal cancer and subsequently had an anterior resection/ abdominoperineal resection with a total mesorectal excision (TME) between February 2012 and December 2014. Patients received 50.4Gy 1.8Gy fractions, and more recently those who have T3/4 disease with a threatened circumferential margin had a simultaneous integrated boost of the primary tumour to a total dose of 53.2Gy, with concurrent capecitabine chemotherapy (825mg/m2 BD) daily throughout treatment. Treatment was initially using 3-D conformal radiotherapy but more recently has been using a VMAT technique with cone beam CT used during treatment. Surgery was performed 8-12 weeks after completion of CRT.The primary end point was pathological response (Dworak score 0-4) of the operative specimen. Scores of 0-2 were considered to be nonpathological responders and scores of 3-4 were considered to be pathological responders. Results: A total of 73 patients received neoadjuvant chemoradiotherapy. 61 patients weretreated with a standard radiotherapy fractionation of 50.4Gy in 28 fractions (Group A) and 12 patients were treated with a dose escalated fractionation to the primary tumour of 53.2Gy in 28 fractions (Group B). The rate of pathological response was 39.3% in Group A and 86.7% with Group B (t=3.55, p<0.001). Conclusion: This study demonstrates the beneficial effects of dose-escalated radiotherapy and wetherefore recommend this regime be considered for inclusion in future phase 2 studies. EP-1287 Radiation-induced rectal toxicity in prostate cancer: a proctoscopy evaluation

Radiotherapy and Oncology, 2016

Purpose or Objective: Pediatric cancer treatment, including radiotherapy (RT) achieves high cure ... more Purpose or Objective: Pediatric cancer treatment, including radiotherapy (RT) achieves high cure rates, but can cause late health problems. We aim to describe temporal trends of pediatric RT use in the Netherlands based on treatment experience in the DCOG-LATER cohort of five-yr childhood cancer survivors (CCS). Material and Methods: The Dutch Childhood Oncology Group-Late effects after childhood cancer (DCOG-LATER) is a collaborative effort of all 7 academic paediatric oncology/hematology centres in the Netherlands for optimal patient care and research. The DCOG-LATER cohort includes 6168 five-yr CCS diagnosed 1963-2001 prior to age 18 yrs. Most children were treated according to (inter) national study protocols. Trained data-managers obtained individual medical file information on prior cancer diagnosis and treatment including prescribed RT dose, field(s), fractionation schedule, machine and RT technique from data were coded and stored in a web-based database using study coding manuals. Here we summarize trends in RT use by calendar period (1963-1979 vs 1980-2001) and diagnosis group. Results: In all, 2426 (39%) CCS received external beam RT (EBRT) for a primary tumor or recurrence, most often photons, or, <1989, Cobalt-60. Use of orthovoltage and electrons was limited. Brachytherapy (2%) and radio isotopes (2%) were given, mainly during 1990-2001. RT use decreased substantially for all cancer types; most dramatic changes were seen among CCS of acute lymphoblastic leukemia, Non-Hodgkin lymphoma, neuroblastoma, and nephroblastoma, for whom RT-use declined from 92%, 79%, 59% and 76% (1963-1979), to 15%, 8%, 8%, and 27% (1990-2001), respectively, but also for bone tumors (75%-32%), retinoblastoma (57%-16%), and CNS tumors (82%-47%). Modest declines were seen for CCS of Hodgkin lymphoma (74%-50%), soft tissue sarcomas (57%-36%), and germ-cell tumors (43%-26%). Among 2094 leukemia survivors, 773 had any RT, directed to the cranium (56%), total body (22%), cranio-spinal axis (12%), and testes (4%). Formal trend analyses by childhood cancer type, body compartment, and RT dose will be presented.

Radiotherapy and Oncology, 2013

S420 2nd ESTRO Forum 2013 pulmonary complications in according to the Radiation Therapy Oncology ... more S420 2nd ESTRO Forum 2013 pulmonary complications in according to the Radiation Therapy Oncology Group toxicity criteria. Conclusions: Our preliminary data suggested that radical treatment with SBRT is safe, feasible and provides a chance for long-term survival by offering favourable local control. 4D CT/PET planning and daily MV-CD evaluation are effective in target repositional accuracy for lung SBRT.

Radiotherapy and Oncology, 2015

S788 3rd ESTRO Forum 2015 below 1 cm 3. Some TPS shows differences in volume calculation between ... more S788 3rd ESTRO Forum 2015 below 1 cm 3. Some TPS shows differences in volume calculation between contour and calculation modules (iPlan, Oncentra, Monaco) and Elekta Oncentra have the highest differences compared with the others TPSs. Monaco losses some very small structure (<0.3 cm 3) when importing contours. In figure 1b it is shown minimum, maximum and mean differences of every TPS versus mean reference volume for all structure studied. Conclusions: It is necessary to study and QA volume reconstruction algorithm of TPSs before starting an SRS/SBRT program. Specific tests for small volumes below 1 cm 3 have to be made and developed. EP-1456 On the dosimetric impact of virtual material assignment to the ArcCHECK phantom for quality control with Acuros XB

Technology in Cancer Research & Treatment, 2016

This work reports the extension of a semiempirical method based on the correlation ratios to conv... more This work reports the extension of a semiempirical method based on the correlation ratios to convert electronic portal imaging devices transit signals into in vivo doses for the step-and-shoot intensity-modulated radiotherapy Siemens beams. The dose reconstructed at the isocenter point D iso , compared to the planned dose, D iso,TPS , and a g-analysis between 2-dimensional electronic portal imaging device images obtained day to day, seems to supply a practical method to verify the beam delivery reproducibility. Method: The electronic portal imaging device images were obtained by the superposition of many segment fields, and the algorithm for the D iso reconstruction for intensity-modulated radiotherapy step and shoot was formulated using a set of simulated intensitymodulated radiotherapy beams. Moreover, the in vivo dose-dedicated software was integrated with the record and verify system of the centers. Results: Three radiotherapy centers applied the in vivo dose procedure at 30 clinical intensity-modulated radiotherapy treatments, each one obtained with 5 or 7 beams, and planned for patients undergoing radiotherapy for prostatic tumors. Each treatment beam was checked 5 times, obtaining 900 tests of the ratios R ¼ D iso /D iso,TPS. The average R value was equal to 1.002 + 0.056 (2 standard deviation), while the mean R value for each patient was well within 5%, once the causes of errors were removed. The g-analysis of the electronic portal imaging device images, with 3% 3 mm acceptance criteria, showed 90% of the tests with P g < 1 ! 95% and g mean 0.5. The off-tolerance tests were found due to incorrect setup or presence of morphological changes. This preliminary experience shows the great utility of obtaining the in vivo dose results in quasi real time and close to the linac, where the radiotherapy staff may immediately spot possible causes of errors. The in vivo dose procedure presented here is one of the objectives of a project, for the development of practical in vivo dose procedures, financially supported by the Istituto Nazionale di Fisica Nucleare.

IFMBE Proceedings, 2009

The paper reports a feasibility study to carry out the adaptive radiotherapy of the lung tumors, ... more The paper reports a feasibility study to carry out the adaptive radiotherapy of the lung tumors, guided by an in-vivo dosimetry method. At the moment the image guided radiotherapy (IGRT) is used for this aim, but it requires many periodic radiological images during the treatment that increase the workload and patient dose. The in-vivo dosimetry method reported here can reduce

Radiotherapy and Oncology, 2013

S292 2nd ESTRO Forum 2013 Conclusions: TG119 structures and plans were found to be easily adaptab... more S292 2nd ESTRO Forum 2013 Conclusions: TG119 structures and plans were found to be easily adaptable to Delta4 phantom CT enabling a rigorous evaluation procedure for IMRT plans verification. Preliminary results on VMAT plans showed that TG119 could be a practical commissioning procedure for modulated arc therapy too. Delta4 allows a fast on-line 3D dose distributions analysis substituting more traditional dosimeters suggested in TG119, but this solution is more expensive than the one proposed inside this report and it is not available in every department for intercomparison purposes.

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2015

Portal imaging by amorphous silicon (aSi) photodiode is currently the most applied technology for... more Portal imaging by amorphous silicon (aSi) photodiode is currently the most applied technology for invivo dosimetry (IVD) of static and dynamic radiotherapy beams. The strategy, adopted in this work to perform the IVD procedure by aSi EPID, is based on: in patient reconstruction of the isocenter dose and day to day comparison between 2D-portal images to verify the reproducibility of treatment delivery. About 20.000 tests have been carried out in this last 3 years in 8 radiotherapy centers using the SOFTDISO program. The IVD results show that: (i) the procedure can be implemented for linacs of different manufacturer, (ii) the IVD analysis can be obtained on a computer screen, in quasi real time (about 2 min after the treatment delivery) and (iii) once the causes of the discrepancies were eliminated, all the global IVD tests for single patient were within the acceptance criteria defined by: 7 5% for the isocenter dose, and P γ o 1 Z 90% of the checked points for the 2D portal image γ-analysis. This work is the result of a project supported by the

Oncology letters, 2013

The aim of this study was to report early clinical experience in stereotactic body radiosurgery (... more The aim of this study was to report early clinical experience in stereotactic body radiosurgery (SBRS) delivered using volumetric intensity modulated arc therapy (VMAT) in patients with primary or metastatic tumors in various extra-cranial body sites. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, metastatic), and sequentially assigned to a particular dose level. Technical feasibility and dosimetric results were investigated. The acute toxicity, tumor response and early local control were also studied. In total, 25 lesions in 20 consecutive patients (male/female, 11/9; median age, 67 years; age range, 47-86 years) were treated. Of these 25 lesions, 4 were primary or metastatic lung tumors, 6 were liver metastases, 8 were bone metastases and 7 were nodal metastases. The dose-volume constraints for organs at risk (OARs) were observed in 19 patients using a single-arc technique. Only in one pati...

Calorimetry in Particle Physics, 2005

Abstract: An approach to verify the intensity modulated radiation therapy (IMRT) using an anthrop... more Abstract: An approach to verify the intensity modulated radiation therapy (IMRT) using an anthropomorphic phantom is reported. Step and shoot IMRT was delivered to a Rando phantom and the portal dose computed by a treatment planning system (TPS) was verified ...

Plenary sessions, 2019

Journal of Pain Research, 2018

Radiotherapy and Oncology, 2016

Radiotherapy and Oncology, 2013

Radiotherapy and Oncology, 2015

Technology in Cancer Research & Treatment, 2016

IFMBE Proceedings, 2009

Radiotherapy and Oncology, 2013

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2015

Oncology letters, 2013

Calorimetry in Particle Physics, 2005