Dietary anthocyanins and health: data from FLORA and ATHENA EU projects.

Adherence to a 'Mediterranean diet' has been shown to be beneficial to human health. Fruit and vegetables represent some of the main components of the Mediterranean diet and their role has been increasingly considered in the process of preventing or reducing the risk of chronic degenerative diseases, such as cerebrovascular or coronary heart disorders, cancer and neurodegenerative diseases. To investigate the beneficial effect of these dietary compounds, two EU-funded projects were conducted during the last 10 years. Their results from experimental models suggest that dietary anthocyanin enrichment is beneficial against a number of ischemic and degenerative conditions. On the other hand, human studies demonstrated that anthocyanin supplementation can counteract the inflammatory response to stress conditions, such as a fatty meal. Moreover, an intervention trial in patients with breast cancer undergoing radiotherapy is presently testing the possible beneficial effect of the administration of a product enriched in anthocyanins on the inflammatory response to radiation and on its consequent skin toxicity, as well as on systemic low-grade inflammation reaction.

On the cutting edge of intensity modulated radiotherapy and simultaneous integrated boost (IMRT-SIB): The case of a patient with 8 brain metastases.

BACKGROUND: Patients with multiple brain metastases, especially those with more than 3 lesions, usually undergo to palliative whole brain (WB) radiotherapy (RT). METHODS: A breast cancer patient with 8 brain metastases was treated on the brain by a radical RT regimen. Prescription doses were according to the simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) technique with all lesions as well brain irradiated simultaneously in 20 daily fractions. Doses of 40.0 Gy (2.0 Gy/fraction) and 50.0 Gy (2.5 Gy/fraction) were prescribed to the whole brain and to eight individual metastases, respectively. RESULTS: Mean volume of the eight metastases was 8.1 cc (range: 3.8-10.1 cc). For all lesions, the volume receiving 95% of prescribed dose was 100% and dose homogeneity was within 3%. Moreover, maximum doses were less than 105% of prescribed dose, while average mean dose to lesions was 50.6 Gy (range: 49.7-51.5 Gy). Whole brain mean dose was 45.2 Gy. Maximum doses to brainstem and optic chiasma were limited to 44.5 Gy and 42.9 Gy, respectively, while maximum doses to eyes, lens and optic nerves were limited to 9.2 Gy, 4.9 Gy and 41.0 Gy, respectively. From a clinical point of view, subsequent MRI brain controls showed a complete clinical response. Forty months after treatment the patient is disease free and shows no late brain and skin toxicities. CONCLUSION: This case demonstrates the technical feasibility of a SIB-IMRT treatment in patients with more than 3 brain metastases.

Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

OBJECTIVE: This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS: A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When?

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.

Active Breathing Coordinator in adjuvant three-dimensional conformal radiotherapy of early stage breast cancer: a feasibility study.

AIMS: To investigate the technical feasibility of utilizing the Active Breathing Coordinator for planning of postoperative three-dimensional conformal radiation therapy in patients with early stage breast cancer undergoing breast conservation therapy. METHODS: Patients with early stage breast cancer for whom adjuvant radiotherapy after breast-conserving surgery was planned were consecutively enrolled. Five sessions of simulation with the Active Breathing Coordinator were planned for each patient. Computed tomography for simulation was not acquired until a good level of compliance with the procedure was achieved by the patient. Patients who did not show a satisfactory level of compliance after the planned fifth session were defined as noncompliant. Two simulation computed tomography scans were acquired: the first without the Active Breathing Coordinator during free breathing, the second with the Active Breathing Coordinator. Forward intensity-modulated treatment plans were calculated. Mean lung dose (MLDipsilateral) and V30 (V30lung) for the ipsilateral lung and V30 for the heart (V30heart), were evaluated. RESULTS: Twenty consecutive patients were enrolled (6 with left-sided breast cancer and 14 with right-sided breast cancer). Eighteen of the patients completed the simulation computed tomography with the Active Breathing Coordinator after 1-5 sessions (median, 3). In 16 of the 18 patients, a reduction of V301ung was observed with the Active Breathing Coordinator. In 15 of the 18 patients, a reduction of MLDipsiateral was also observed. In 5 of the 6 patients with left-sided breast cancer, a reduction of V30heart was noted. CONCLUSIONS: Routine application of the Active Breathing Coordinator in clinical practice is feasible, even though it requires an increased workload. Dosimetric results are encouraging in terms of a better sparing of the ipsilateral lung and the heart.

Intensity-modulated radiation therapy with simultaneous integrated boost in unresected left-sided pleural mesothelioma: a case report.

A 77-year-old male patient with unresected malignant pleural mesothelioma, clinical stage T3N0M0 according to the New International Staging System for Diffuse Malignant Pleural Mesothelioma, received intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) after 6 cycles of chemotherapy with cisplatin and pemetrexed. SIB-IMRT delivered 40.5 Gy (1.5 Gy/fraction) to the left pleura and 50 Gy (1.85 Gy/fraction) to the sites of macroscopic disease. Radiotherapy was well tolerated. Two months after the end of radiotherapy the patient showed grade 2 lung toxicity (febrile episodes accompanied by dry cough) that was successfully treated with steroid therapy. Local control lasted for 2 years after SIB-IMRT. Then the tumor recurred marginally to the radiation field and the patient underwent chemotherapy with pemetrexed. Three years from the diagnosis, the patient is alive and in good general condition. He only takes prednisone 5 mg/daily for exertional dyspnea. To the best of our knowledge this is the first reported use of SIB-IMRT in unresected malignant pleural mesothelioma. Considering the dosimetric advantages of SIB-IMRT and the clinical results observed in our patient, additional evaluation of this technique seems justified.

Phase I-II studies on accelerated IMRT in breast carcinoma: technical comparison and acute toxicity in 332 patients.

BACKGROUND AND PURPOSE: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. MATERIALS AND METHODS: Prescribed dose to the breast was 50.4Gy in the CG, 40Gy in MARA-1 (low risk of local recurrence), and 50Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4Gy (sequential 10Gy electron boost), 44Gy (concomitant 4Gy boost), and 60Gy (concomitant 10Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4weeks); 16 fractions for MARA-1 study (3.2weeks) and 25 fractions for MARA-2 study (5weeks). RESULTS: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed D(max) and V(107%) reduction (p<0.001) and D(min) improvement (p<0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p<0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. CONCLUSIONS: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6weeks; MARA-1, 3.2weeks; MARA-2, 5weeks) with acceptable short-term toxicity.

Integration between in vivo dosimetry and image guided radiotherapy for lung tumors.

The article reports a feasibility study about the potentiality of an in vivo dosimetry method for the adaptive radiotherapy of the lung tumors treated by 3D conformal radiotherapy techniques (3D CRTs). At the moment image guided radiotherapy (IGRT) has been used for this aim, but it requires taking many periodic radiological images during the treatment that increase workload and patient dose. In vivo dosimetry reported here can reduce the above efforts, alerting the medical staff for the commissioning of new radiological images for an eventual adaptive plan. The in vivo dosimetry method applied on 20 patients makes use of the transit signal St on the beam central axis measured by a small ion chamber positioned on an electronic portal imaging device (EPID) or by the EPID itself. The reconstructed in vivo dosimetry at the isocenter point Diso requires a convolution between the transit signal St and a dose reconstruction factor C that essentially depends on (i) tissue inhomogeneities along the beam central axis and (ii) the in-patient isocenter depth. The C factors, one for every gantry angle, are obtained by processing the patient's computed tomography scan. The method has been recently applied in some Italian centers to check the radiotherapy of pelvis, breast, head, and thorax treatments. In this work the dose reconstruction was carried out in five centers to check the Diso in the lung tumor during the 3D CRT, and the results have been used to detect the interfraction tumor anatomy variations that can require new CT imaging and an adaptive plan. In particular, in three centers a small ion chamber was positioned below the patient and used for the St measurement. In two centers, the St signal was obtained directly by 25 central pixels of an a-Si EPID, equipped with commercial software that enabled its use as a stable detector. A tolerance action level of +/- 6% for every checked beam was assumed. This means that when a difference greater than 6% between the predicted dose by the treatment planning system, Diso,TPS, and the Diso was observed, the clinical action started to detect possible errors. 60% of the patients examined presented morphological changes during the treatment that were checked by the in vivo dosimetry and successively confirmed by the new CT scans. In this work, a patient that showed for all beams Diso values outside the tolerance level, new CT scans were commissioned for an adaptive plan. The lung dose volume histograms (DVHs) for a Diso,TPs=2 Gy for fraction suggested the adaptive plan to reduce the dose in lung tissue. The results of this research show that the dose guided radiotherapy (DGRT) by the Diso reconstruction was feasible for daily or periodic investigation on morphological lung tumor changes. In other words, since during 3D CRT treatments the anatomical lung tumor changes occur frequently, the DGRT can be well integrated with the IGRT.

Complexity index (COMIX) and not type of treatment predicts undetected errors in radiotherapy planning and delivery.

BACKGROUND AND PURPOSE: Quality assurance procedures (QA) may reduce the risk of errors in radiotherapy. The aim of this study was to assess a QA program based on independent check (IC) procedures in patients undergoing 3D, intensity modulated (IMRT) and extracranial stereotactic (ESRT) radiotherapy. MATERIALS AND METHODS: IC for set-up (IC1) and for radiotherapy treatments (IC2) was tested on 622 patients over a year. Fifteen events/parameters and 17 parameters were verified by IC1 and IC2, respectively. A third evaluation check (IC3) was performed before treatment. Potential errors were classified based on their magnitude. Incidents involving only incorrect or incomplete documentation were segregated. Treatments were classified based on a complexity index (COMIX). RESULTS: With IC1, 75 documentation incidents and 31 potential errors were checked, and with IC2 111 documentation incidents and 6 potential errors were checked. During the study period 10 errors undetected by standard procedures (IC1, IC2) were detected by chance or by IC3. The incidence of errors and serious errors undetected by standard procedures was 1.6% and 0.6%, respectively. There was no higher incidence of errors undetected in patients undergoing IMRT or ESRT, while there was a higher incidence of errors undetected in more complex treatments (p < 0.001). CONCLUSIONS: Systematic QA procedures can reduce the risk of errors. The risk of errors undetected by standard procedures is not correlated with the treatment technological level (3D versus IMRT/ESRT).

Squamous cell carcinoma antigen in patients with locally advanced cervical carcinoma undergoing preoperative radiochemotherapy: association with pathological response to treatment and clinical outcome.

OBJECTIVE: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. METHODS: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. RESULTS: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. CONCLUSIONS: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome.

Real time transit dosimetry for the breath-hold radiotherapy technique: an initial experience.

INTRODUCTION: The breath-hold is one of the techniques to obtain the dose escalation for lung tumors. However, the change of the patient's breath pattern can influence the stability of the inhaled air volume, IAV, used in this work as a surrogate parameter to assure the tumor position reproducibility during dose delivery. MATERIALS AND METHOD: In this paper, an Elekta active breathing coordinator has been used for lung tumor irradiation. This device is not an absolute spirometer and the feasibility study here presented developed (i) the possibility to select a specific range epsilon of IAV values comfortable for the patient and (ii) the ability of a transit signal rate S(t), obtained by a small ion-chamber positioned on the portal image device, to supply in real time the in vivo isocenter dose reproducibility. Indeed, while the selection of the IAV range depends on the patient's ability to follow instructions for breath-hold, the S(t) monitoring can supply to the radiation therapist a surrogate of the tumor irradiation reproducibility. RESULTS: The detection of the S(t) in real time during breath-hold was used to determine the interfraction isocenter dose variations due to the reproducibility of the patient's breathing pattern. The agreement between the reconstructed and planned isocenter dose in breath-hold at the interfraction level was well within 1.5%, while in free breathing a disagreement up to 8% was observed. The standard deviation of the S(t) in breath-hold observed at the intrafraction level is a bit higher than the one obtained without the patient and this can be justified by the presence of a small residual tumor motion as heartbeat. CONCLUSION: The technique is simple and can be implemented for routine use in a busy clinic.

Videoconferencing to enhance the integration between clinical medicine and teaching: a feasibility study.

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.

Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: a Pareto front analysis for liver metastases.

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout.

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients.

AIM: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. METHODS: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. RESULTS: Median follow-up was 52 months (range: 3-115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38-3.34 and HR: 1.12, 95% CI: 1.07-1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08-1.20 and HR: 1.14, 95% CI: 1.01-1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61-3.41 and HR: 3.07, 95% CI: 1.11-8.53, respectively) compared to CG. CONCLUSION: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1-G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

Large discrepancies between planned and actually delivered dose in IMRT of head and neck cancer. A case report.

The case is reported of a patient with locally recurrent carcinoma of the tongue treated with intensity-modulated radiotherapy (IMRT) (simultaneous integrated boost) plus concurrent chemotherapy, who during the third week of radiotherapy developed grade 3 mucositis. Treatment was interrupted for 10 days until significant resolution of the symptoms. At the time of treatment resumption the patient showed 8% weight loss, and in vivo portal dose verification revealed large discrepancies between the computed and measured doses. A new CT scan showed marked tumor shrinkage and modifications to the critical structures. The comparison between the original plan and the hybrid IMRT showed a minimal dose increase in the new target volumes and a marked dose increase in the organs at risk. This case confirms the need for a robust quality assurance program when using IMRT, the feasibility and efficacy of in vivo dosimetry to detect significant discrepancies between planned and delivered dose, and the need to combine IMRT with 4-dimensional radiotherapy, at least for head and neck cancer.

Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma.

AIMS AND BACKGROUND: In recent years, preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol. The aim of the study was to evaluate definitive results in terms of toxicity, response and clinical outcome. MATERIAL AND METHODS: Twenty-eight patients with unresectable (cT4, 19 patients) or resectable (cT3, 9 patients) nonmetastatic pancreatic tumors received radiotherapy (39.6 Gy) plus 5-fluorouracil (continuous infusion, days 1-4 at 1000 mg/m(2)/day). After 4 weeks, patients were evaluated for surgical resection. In 9 resected patients, electron-beam intra-operative radiotherapy (10 Gy) was given before reconstruction. Thereafter, in resected patients, adjuvant chemotherapy was prescribed. RESULTS: During chemoradiation, 1 patient (3.6%) developed grade 3 acute gastrointestinal toxicity and 2 patients (7.1%) developed grade 3 hematological toxicity. Three of 19 patients with unresectable tumors had tumor downstaging (15.8%). Two patients showed partial response (response rate, 7.1%; 95% CI, 0.2-25.3) and 4 patients (14.3%) had minimal tumor response. Four patients (14.3%) showed progressive disease after chemoradiation. One postoperative death was recorded. The median survival time was 11.3 months (20.5 and 9.0 months in resected and unresected patients, respectively). Only one local failure was recorded in 8 patients resected with negative margins. CONCLUSIONS: Although the response rate is still low, our preliminary results suggest that preoperative 5-fluorouracil chemoradiation is well tolerated and may result in tumor downstaging. Delivery of intra-operative radiotherapy seems to be associated with a low rate of local recurrences.

Volumetric modulated arc therapy (VMAT) and simultaneous integrated boost in head-and-neck cancer: is there a place for critical swallowing structures dose sparing?

OBJECTIVE: To explore the potential of volumetric-modulated arc therapy (VMAT) to reduce the risk of swallowing problems after curative chemoradiotherapy. METHODS: 20 patients with head and neck cancer who previously underwent radiotherapy were selected. Radiotherapy was prescribed according to simultaneous integrated boost technique with all targets irradiated simultaneously over 30 daily fractions. Doses of 70.5 (67.5), 60.0 and 55.5 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Pharyngeal constrictor muscles (PCM) and glottic and supraglottic larynx (SGL) were considered organs at risk related to swallowing dysfunction (SW-OARs). Upper pharyngeal constrictor muscles (uPCM), middle pharyngeal constrictor muscles (mPCM) and lower pharyngeal constrictor muscles (lPCM) part of PCM were also outlined separately. Clinical standard plans (standard-VMAT) and plans aiming to spare SW-OARs (swallowing dysfunction-VMAT) were also created. Normal tissue complication probabilities (NTCP) for physician-rated swallowing dysfunction were calculated using a recently predictive model developed by Christianen et al. RESULTS: Planning with two strategies demonstrated comparable planning target volume coverage and no differences in sparing of parotid glands and other non-swallowing organs at risk. SW-VMAT plans provided mean dose reduction for uPCM and SGL by 3.9 and 4.5 Gy, respectively. NTCP values for Radiation Therapy Oncology Group grade 2-4 swallowing dysfunction was decreased by 9.2%. Dose reductions with SW-VMAT depended on tumour location and overlap with SW-OARs. CONCLUSION: VMAT plans aiming at sparing swallowing structures are feasible, providing a significant reduction in NTCP swallowing dysfunction with respect to conventional VMAT. ADVANCES IN KNOWLEDGE: Dysphagia is today considered one of the dose-limiting toxicities of chemoradiotherapy. The dose sparing of swallowing structures represents a major challenge in radiotherapy. VMAT is a complex new technology having the potential to significantly reduce the risk of dysphagia after curative chemoradiotherapy.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience.

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36min/Gy. The mean number of monitor units was 3162, i.e., 121.6MU/Gy. Pretreatment verification (3%-3mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.

Initial clinical experience with Epid-based in-vivo dosimetry for VMAT treatments of head-and-neck tumors.

We evaluated an EPID-based in-vivo dosimetry algorithm (IVD) for complex VMAT treatments in clinical routine. 19 consecutive patients with head-and-neck tumors and treated with Elekta VMAT technique using Simultaneous Integrated Boost strategy were enrolled. In-vivo tests were evaluated by means of (i) ratio R between daily in-vivo isocenter dose and planned dose and (ii) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ%) and mean γ-values (γmean), using a global 3%-3 mm criteria. Alert criteria of ±5% for R ratio, γ% < 90% and γmean > 0.67 were chosen. A total of 350 transit EPID images were acquired during the treatment fractions. The overall mean R ratio was equal to 1.002 ± 0.019 (1 SD), with 95.9% of tests within ±5%. The 2D portal images of γ-analysis showed an overall γmean of 0.42 ± 0.16 with 93.3% of tests within alert criteria, and a mean γ% equal to 92.9 ± 5.1% with 85.9% of tests within alert criteria. Relevant discrepancies were observed in three patients: a set-up error was detected for one patient and two patients showed major anatomical variations (weight loss/tumor shrinkage) in the second half of treatment. The results are supplied in quasi real-time, with IVD tests displayed after only 1 minute from the end of arc delivery. This procedure was able to detect when delivery was inconsistent with the original plans, allowing physics and medical staff to promptly act in case of major deviations between measured and planned dose.

Impact of dose and volume on rectal tolerance.

Based on the successful results achieved in survival and local control with radiotherapy of prostate cancer recent studies tried to establish some models to reliably predict late rectal toxicity. In fact, the rectum, due to its location, represents an organ at risk of acute and late toxicity with the onset of acute or chronic radiation proctitis. The concept of late consequential effect has gained ground. It implies that the late damage might be a direct consequence of the acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) led to the identification of parameters, based on dose-volume histograms (DVH), able to separate patients at low and high risk of toxicity. Precise predictive dosimetric factors play a major role in the definition of the onset of toxicity. The monitoring system of late toxicity used by the authors is presented.