Application of failure mode and effects analysis (FMEA) to pretreatment phases in tomotherapy.

The aim of this paper was the application of the failure mode and effects analysis (FMEA) approach to assess the risks for patients undergoing radiotherapy treatments performed by means of a helical tomotherapy unit. FMEA was applied to the preplanning imaging, volume determination, and treatment planning stages of the tomotherapy process and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system; and 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. A total of 74 failure modes were identified: 38 in the stage of preplanning imaging and volume determination, and 36 in the stage of planning. The threshold of 125 for RPN was exceeded in four cases: one case only in the phase of preplanning imaging and volume determination, and three cases in the stage of planning. The most critical failures appeared related to (i) the wrong or missing definition and contouring of the overlapping regions, (ii) the wrong assignment of the overlap priority to each anatomical structure, (iii) the wrong choice of the computed tomography calibration curve for dose calculation, and (iv) the wrong (or not performed) choice of the number of fractions in the planning station. On the basis of these findings, in addition to the safety strategies already adopted in the clinical practice, novel solutions have been proposed for mitigating the risk of these failures and to increase patient safety.

Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy.

Purpose: To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. Methods: Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D0.03) and selected clinical variables. Results: Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%). Conclusion: In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

AIM: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients. MATERIALS AND METHODS: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost. Median age was 62 (IQR:51.1-70.5) years. Chemotherapy was prescribed for 28% of patients, hormonal therapy for 80.3%, monoclonal antibodies for 8.2%. RESULTS: Median follow-up was 72.4 (IQR: 44.6-104.1) months. Acute RTOG toxicity was: 69.8% Grade (G) 1, 14.3% G2 and 1.7% G3. Late SOMA-LENT toxicities were: edema-hyperpigmentation (E-H): G1 28.67%, G2 4.41%, G3 0.15%; fibrosis-atrophy-telangiectasia-pain (F-A-T-P): G1 14.6%, G2 3.2%, G3 0.8%, G4 0.1%. Median time to first occurrence was 6 and 18 months, respectively. Aesthetic result after surgery was excellent in 28.7%, good in 41.5%, acceptable in 20.3% and poor in 9.5% of patients. Change in breast appearance after radiotherapy was mild in 6.9%, moderate in 2.3% and marked in 1.3% of patients. Concomitant chemotherapy, obesity, smoking, use of bolus and planning target volume (PTV) were associated with higher acute toxicity. Patients ≥55 years old were less likely to experience acute toxicity. PTV and acute G2 toxicity were associated with ≥G2 E-H. PTV, concomitant chemotherapy, hypertension and ≥G2 acute toxicity were associated with increased risk of F-A-T-P. CONCLUSION: Hypofractionated whole-breast radiotherapy without boost demonstrated mild acute and late toxicity in a large cohort of consecutive patients. Moderate and marked changes in breast appearance were registered for 3.6% of patients and occurred between 18 to 42 months.

Replacing Manual Planning of Whole Breast Irradiation With Knowledge-Based Automatic Optimization by Virtual Tangential-Fields Arc Therapy.

PURPOSE: To implement Knowledge Based (KB) automatic planning for right and left-sided whole breast treatment through a new volumetric technique (ViTAT, Virtual Tangential-fields Arc Therapy) mimicking conventional tangential fields (TF) irradiation. MATERIALS AND METHOD: A total of 193 clinical plans delivering TF with wedged or field-in-field beams were selected to train two KB-models for right(R) and left(L) sided breast cancer patients using the RapidPlan (RP) tool implemented in the Varian Eclipse system. Then, a template for ViTAT optimization, incorporating individual KB-optimized constraints, was interactively fine-tuned. ViTAT plans consisted of four arcs (6 MV) with start/stop angles consistent with the TF geometry variability within our population; the delivery was completely blocked along the arcs, apart from the first and last 20° of rotation for each arc. Optimized fine-tuned KB templates for automatic plan optimization were generated. Validation tests were performed on 60 new patients equally divided in R and L breast treatment: KB automatic ViTAT-plans (KB-ViTAT) were compared against the original TF plans in terms of OARs/PTVs dose-volume parameters. Wilcoxon-tests were used to assess the statistically significant differences. RESULTS: KB models were successfully generated for both L and R sides. Overall, 1(3%) and 7(23%) out of 30 automatic KB-ViTAT plans were unacceptable compared to TF for R and L side, respectively. After the manual refinement of the start/stop angles, KB-ViTAT plans well fitted TF-performances for these patients as well. PTV coverage was comparable, while PTV D1% was improved with KB-ViTAT by R:0.4/L:0.2 Gy (p < 0.05); ipsilateral OARs Dmean were similar with a slight (i.e., few % volume) improvement/worsening in the 15-35 Gy/2-15 Gy range, respectively. KB-ViTAT better spared contralateral OARs: Dmean of contralateral OARs was 0.1 Gy lower (p < 0.05); integral dose was R:5%/L:8% lower (p < 0.05) than TF. The overall time for the automatic plan optimization and final dose calculation was 12 ± 2 minutes. CONCLUSIONS: Fully automatic KB-optimization of ViTAT can efficiently replace manually optimized TF planning for whole breast irradiation. This approach was clinically implemented in our institute and may be suggested as a large-scale strategy for efficiently replacing manual planning with large sparing of time, elimination of inter-planner variability and of, seldomly occurring, sub-optimal manual plans.

Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized?

AIM: We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. METHODS AND MATERIALS: From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14-70.53) years. HISTOLOGY: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (-), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. RESULTS: Median follow up was 72.43 (IQR: 44.63-104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. CONCLUSION: While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription.

Results of a two-year quality control program for a helical tomotherapy unit.

BACKGROUND AND PURPOSE: Image-guided helical tomotherapy (HT) is a new modality for delivering intensity modulated radiation therapy (IMRT) with helical irradiation: the slip ring continuously rotates while the couch moves into the bore. The radiation source (Linac, 6 MV) is collimated into a fan beam and modulated by means of a binary multileaf collimator (MLC). A xenon detector array, opposite the radiation source, allows a megavoltage-CT (MVCT) acquisition of patient images for set-up verification. The aim of this paper is to report the results of a two-year quality control (QC) program for the physical and dosimetric characterization of an HT unit installed at our Institute and clinically activated in November 2004, in order to monitor and verify the stability and the reliability of this promising radiation treatment unit. MATERIALS AND METHODS: Conventional Linac acceptance protocols (ATP) and QC protocols were adapted to HT with the addition of specific items reflecting important differences between the two irradiation modalities. QC tests can be summarized as: (a) mechanical and geometrical characterization of the system's components: evaluation of alignment among radiation source-gantry rotation plan-jaws-MLC-MVCT; (b) treatment beam configuration in static condition: depth dose curves (PDD) and profiles, output factors, output reproducibility and linearity; (c) dynamic component characterization: accuracy and reproducibility of MLC positioning; rotational output reproducibility and linearity, leaf latency, couch movement constancy; (d) gantry-couch and MLC-gantry synchronization; and (e) MVCT image quality. Peculiar periodicity specific tolerance and action levels were defined. Ionization chambers (Exradin A1SL 0.056 cc), films (XOmat-V/EDR2), water and solid water phantoms were used to perform quality assurance measurements. RESULTS: Over a two-year period the final average output variation after possible beam output adjustment was -0.2+/-1% for the static condition and equal to 0+/-1% for the rotational condition: around 98% of the collected output data was within the action level compared to 94% if no beam output adjustment was considered. An average energy variation of -0.4+/-0.4% was found. The daily absolute dose verification of IMRT plans showed a dose reproducibility of -0.5+/-1.2% and -0.4+/-2.2%, for low and high dose gradient regions, respectively. Source-jaws-MLC and MVCT alignment results and jaw and leaf positioning accuracy were +/-1mm. Couch-gantry-MLC synchrony tests showed good stability level (

Agreement criteria between expected and measured field fluences in IMRT of head and neck cancer: the importance and use of the gamma histograms statistical analysis.

BACKGROUND AND PURPOSE: The aim of this study was to analyse our pre-treatment QA data in order to establish uniquely defined agreement criteria between planned and delivered dose distribution for clinical QA practice in IMRT of head and neck (HN) patients. MATERIALS AND METHODS: Pre-treatment QA dosimetry using films in combination with ionisation chambers is routinely evaluated for each patient. This evaluation is performed by comparing planned and measured dose distributions in terms of absolute point dose measurements, planar dose verification and gamma function analysis using 4%/3mm values as acceptance criteria. In the current investigation, gamma histograms, calculated on dose levels higher than 10% of the prescription dose (1.8Gy/fraction), were further analysed by considering mean values, gamma values corresponding to Delta=mean+1.5 SD (named as gamma(Delta)) and the % of points with gamma<1, gamma<1.5 and gamma>2. When considering the patient population, the average values of all these parameters and their confidence limits (mean value+1.5 SD) were calculated. The results here presented refer to 57 HN patients treated in the period September 04-April 06. RESULTS: Better results were found for treatments performed with our newly installed linac (e.g. average gamma(Delta): 0.8 vs. 1.1 for the preexisting one, p<0.001), due to a more accurate dosimetric configuration. Also, confidence limits for the percentage of points with gamma<1, gamma<1.5 and gamma>2 were found to be quite different for the two linacs (95.3%, 98.9% and 0.4% for the newly installed unit, 87.6%, 95.2% and 2.0% for the preexisting one). CONCLUSIONS: Statistical analyses of gamma evaluation of QA pre-treatment dosimetry are useful to properly define confidence limits of the agreement between expected and measured fluences based on our institutional experience. Our results confirm that the dosimetry configuration of the beam may significantly affect the agreement between planned and measured IMRT beam fluences.

Significant improvement in normal tissue sparing and target coverage for head and neck cancer by means of helical tomotherapy.

PURPOSE: In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed. MATERIALS AND METHODS: In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord Dmax similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (n=3), hypopharinx (n=1) and larynx (n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5 cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5 cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54 Gy in 30 fractions on PTV1 and 16.2 Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15 Gy were concomitantly delivered while delivering 16.2 Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose-volume histograms (DVH) and dose statistics on PTVs and OARs. RESULTS: When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96-97% for Tomotherapy plans. Dmax within PTV1 decreased from 60.3 Gy (IMRT) to 57.4 Gy (TOMO-a) and 58.7 Gy (TOMO-b). Spinal cord Dmax decreased from 31.6 Gy (IMRT) to 26.5 Gy (TOMO-a) and 24.6 Gy (TOMO-b). No attempts to further reduce spinal cord Dmax were done. Mean dose to the parotids decreased from 26.1 Gy (IMRT) to 25.1 Gy (TOMO-a) and 20.8 Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9 Gy (IMRT) to 34.0 Gy (TOMO-a) and 30.7 Gy (TOMO-b). When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3. CONCLUSIONS: Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.

Comparing 3DCRT and inversely optimized IMRT planning for head and neck cancer: equivalence between step-and-shoot and sliding window techniques.

BACKGROUND AND PURPOSE: To investigate the feasibility and the advantages of using Intensity-Modulated Radiotherapy (IMRT) for the treatment of head-and-neck cancer. Comparing different methods to deliver IMRT in this clinical setting. MATERIALS AND METHODS: Seven patients (four radical; three post-operative), treated on a 6MV Varian Linac (equipped with an 80 leaves MLC) in accordance with a routine 3DCRT plan, were replanned. Original treatment plans were computed to irradiate a primary Planning Target Volume (PTV1, 54 Gy) and then to perform a boost on a PTV2 (radical: 70.2 Gy; post-operative: 64.8 Gy). IMRT dose plans were inversely-optimized using appropriate constraints with the Helios tool on a Varian Eclipse system. Once the optimal fluences were calculated, different modalities to deliver IMRT were considered: Sliding Window (SW) and Step and Shoot (SS) techniques using a different number of intensity levels to approximate the optimal fluences (e.g. 5, 10 and 20). Mean dose, maximum dose and a number of dose-volume parameters regarding CTV1, CTV2, PTV1, PTV2, OARs (spinal and planning spinal cord, parotids, optical structures, brain and temporal mandibular joint) were considered to compare the five modalities (3DCRT, SW, SS5, SS10, SS20); the Conformity Index (CI), the Irradiated Volume (IV) and the Treated Volume (TV) were also considered in the comparison. RESULTS: A more uniform coverage of the PTV in the IMRT dose plans with respect to the 3DCRT plan was found (for PTV2: V90% = 94.3 for 3DCRT, 97.6 for SS5, 98 for SS10 and 98.1 for SW; V107% = 20.7 for 3DCRT, 5.9 for SS5, 2 for SS10 and 1.3 for SW). Concerning OARs, they all present a significant reduction of mean and/or maximum dose and dose-volume patterns assessed from DVHs: in particular the mean dose of parotids decrease on average of about 13.5Gy passing from 3DCRT to IMRT with an average reduction of NTCP ranging from about 20% to more than 40% for radically treated patients, depending on the chosen end-point. IV and TV are also slightly smaller with IMRT. The results obtained with SS techniques employing 10 or more intensity levels are comparable with those obtained with SW; no differences between SS10 and SW may be appreciated when considering the DVHs of PTV, CTV and OARs. On the other hand, in some cases SS5 may be slightly sub-effective with respect to SS10-SW when considering PTV coverage and Dmax of the spinal cord. CONCLUSIONS: With the Varian planning and delivery system, Step-and-shoot approximations of inversely optimised fluences in head-neck IMRT compare well with SW delivery, even with only five intensity levels. With a number of intensity level of 10 or more, no differences can be appreciated in PTV coverage/OAR sparing with respect to SW.

Dosimetric and clinical predictors of toxicity following combined chemotherapy and moderately hypofractionated rotational radiotherapy of locally advanced pancreatic adenocarcinoma.

BACKGROUND AND PURPOSE: Hypofractionated radiotherapy (RT) of pancreatic adenocarcinoma is limited by the tolerance of adjacent normal tissues. A better understanding of the influence of dosimetric variables on the rate of toxicity after RT must be considered an important goal. METHODS AND MATERIALS: Sixty-one patients with histologically proven locally advanced disease (LAPD) were analyzed. The therapeutic strategy consisted of induction chemotherapy (ChT) followed by concurrent chemoradiotherapy (CRT). In 39 out of 61 patients the target volume was based on a four-dimensional CT (4D-CT) procedure. Delivered dose was 44.25Gy in 15 fractions to PTV2, which consisted of pancreatic tumor and regional lymph nodes considered radiologically involved; 23 out of 61 patients received a simultaneous integrated boost (SIB) to a tumor sub-volume infiltrating the great abdominal vessels (PTV1) with dose in the range of 48-58Gy. RT was delivered with Helical Tomotherapy. Dose-volume histograms (DVHs) of target volumes and organs at risk (OARs) were collected for analysis. The predictive value of clinical/dosimetric parameters was tested by univariate/multivariate analyses. RESULTS: The crude incidence of acute gastrointestinal (GI) grade 2 toxicity was 33%. The 12-month actuarial rate of "anatomical" (gastro-duodenal mucosa damage) toxicity was 13% (95% CI: 4-22%). On univariate analysis, several stomach and duodenum DVH endpoints are predictive of toxicity after moderately hypofractionated radiotherapy. Multivariate analysis confirmed that baseline performance status and the stomach V20[%] were strong independent predictors of acute GI grade ⩾2 toxicity. The high-dose region of duodenum DVH (V45[%]; V40[%]) was strongly correlated with grade ⩾2 "anatomical" toxicity; the best V40[%] and V45[%] cut-off values were 16% and 2.6% respectively. CONCLUSION: Regarding dosimetric indices, stomach V20[%] correlates with a higher rate of acute toxicity; more severe acute and late anatomical toxicities are related to the high dose region of duodenum DVH.

Hypofractionated image-guided IMRT in advanced pancreatic cancer with simultaneous integrated boost to infiltrated vessels concomitant with capecitabine: a phase I study.

PURPOSE: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. METHODS AND MATERIALS: Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. RESULTS: From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. CONCLUSIONS: A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.

Anatomical and clinical predictors of acute bowel toxicity in whole pelvis irradiation for prostate cancer with Tomotherapy.

PURPOSE: Assessing predictors of acute bowel toxicity after whole-pelvis irradiation (WPRT) Image-guided Tomotherapy with simultaneous integrated boost on prostate/prostate bed. METHODS AND MATERIALS: In the period March 2005-April 2009, 178 patients were treated with radical or adjuvant/salvage intent with WPRT Tomotherapy. Median dose to the pelvic nodes was 51.8 Gy/28 fractions while concomitantly delivering 65.5-74.2 Gy to prostate/prostatic bed. The impact of many anatomical and clinical parameters on ≥ Grade 2 acute bowel toxicity was investigated by logistic analyses. RESULTS: Only 15/178 patients (8.4%) experienced Grade 2 toxicity (none Grade 3). Main predictors at univariate analysis were nodal CTV (CTVN ≥ 380 cc; OR: 3.7, p=0.017), treatment duration (< 40 days; OR: 6.2, p=0.006) and Grade 2 acute rectal toxicity (OR: 6.5, p=0.015). A multivariate analysis including only pre-treatment variables revealed an independent role of CTVN and age; if including treatment-related factors the best predictors were age, treatment duration and Grade 2 rectal toxicity. This last was correlated with the overlap between PTVN and loops (OVPN ≥ 51 cc; OR: 14.4, p=0.0003) that is representative of the volume of loops receiving the prescribed dose (51.8 Gy, 1.85 Gy/fr). CONCLUSIONS: Acute bowel toxicity after WPRT Tomotherapy is mild, relatively rare and associated to larger CTVN and older age. While efforts to further reduce it do not appear to be relevant, the pre-treatment assessment of "high-risk" patients may help physicians in better managing symptoms. A prospective validation would be very important in confirming these results and in better refining dose-volume bowel effects including symptoms milder that the ones here investigated and retrospectively assessed.

Internal target volume defined by contrast-enhanced 4D-CT scan in unresectable pancreatic tumour: evaluation and reproducibility.

We compared customized ITVs obtained with CE-4D-CT imaging (ITV(4D)) with a population-based (ITV(PBC)) in 29 patients (PTs) and evaluated the intra-observer ITV delineation reproducibility in 5 PTs with unresectable pancreatic ductal adenocarcinoma (PDA). The ITV(PBC) was quite different from the ITV(4D), with under/over estimation of volume. Intra-observer volume delineation variability on CE-4D-CT and on a single-phase CE-CT were similar (27.6% vs 24.9%).

Salvage brachytherapy for local recurrence after radical prostatectomy and subsequent external beam radiotherapy.

OBJECTIVES: To evaluate the technical feasibility, safety, and efficacy of seed implantation for local recurrence after radical prostatectomy and external beam radiotherapy. METHODS: Between October 1999 and March 2002, 10 patients with targeted, histologically proven local relapse after surgery and subsequent external beam radiotherapy (only in 8 patients), underwent permanent brachytherapy with palladium-103 and iodine-125 after complete restaging. In all patients, an intraoperative morphovolumetric ultrasound study of the target was performed, with a planning target volume ranging from 5 to 26.7 cm(3). The preimplant prostate-specific antigen values ranged from 1.1 to 6.31 ng/mL. RESULTS: Postplan dosimetry was performed to determine the percentage of the target volume that received a dose equal to, or greater than, the prescribed dose (range 84.5% to 95.9%) and the dose that was delivered to the 90% of the target volume (range 85.08% to 129.43%). The urinary scores, measured using the International Prostate Symptom Score, had normalized at 3 months. Only 1 patient had worsened incontinence during the first 2 months, with subsequent restoration of the previous situation. The other patients did not have any changes in their previous clinical condition. One patient experienced occasional gross hematuria that had been present after external beam radiotherapy. No rectal complications were reported. After a median follow-up of 20.6 months, 7 patients showed a decreasing or stable prostate-specific antigen level. CONCLUSIONS: This preliminary experience has demonstrated that seed implantation of a neoplastic local recurrence is technically feasible and safe and allows for accurate dosimetry when the area to be treated can be defined by ultrasonography. Longer follow-up, accurate patient selection, and larger series of patients could help to better define the oncologic outcome.