P. Mangili

LETHAL PULMONARY COMPLICATIONS SIGNIFICANTLY CORRELATE WITH INDIVIDUALLY ASSESSED MEAN LUNG DOSE IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES TREATED WITH TOTAL BODY IRRADIATION

PURPOSE To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT). METHODS The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP). RESULTS Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role. CONCLUSION The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.

PHASE I-II STUDY OF HYPOFRACTIONATED SIMULTANEOUS INTEGRATED BOOST WITH TOMOTHERAPY FOR PROSTATE CANCER

PURPOSE To report planning and acute toxicity data of the first 60 patients treated within a Phase I-II study with moderate hypofractionation by image-guided helical tomotherapy. METHODS AND MATERIALS Various clinical target volumes (CTVs) were defined: CTV1-pelvic nodes; CTV2-upper portion of seminal vesicles; CTV3-lower portion of SV; CTV4-prostate; overlap between planning target volume (PTV) 4 and rectum. Different doses to each PTV were simultaneously delivered in 28 fractions. For 31 low-risk patients: 56.0, 61.6, and 71.4 Gy for PTV2-4, respectively; for 20 intermediate-risk patients: 51.8, 61.6, 65.5, and 74.2 Gy for PTV1-4, respectively; for 9 high-risk patients: 51.8 and 65.5 Gy for PTV1-2 and 74.2 Gy for PTV3-4. For all patients, the dose to overlap was 65.5 Gy. RESULTS The mean fraction of rectum receiving more than 65 Gy (V65) and rectal Dmax were 10% and 70.8 Gy respectively. In cases of pelvic node irradiation, the intestinal cavity (outside PTV) receiving > 45 and 50 Gy was 86 and 12 cc, respectively. A homogeneous dose distribution within each PTV was guaranteed. Acute genitourinary toxicity according to RTOG scoring system was as follows: 21/60 (35%) Grade 1, 12/60 (20%) Grade 2, 2/60 (3%) Grade 3. Acute rectal toxicities were: 18/60 (30%) Grade 1. Twelve (20%) patients showed Grade 1 upper intestinal toxicity (uGI). No patients experienced > or = Grade 2 acute rectal or uGI side effects. CONCLUSIONS This study shows excellent results with regard to acute toxicity. Further research is necessary to assess definitive late toxicity and tumor control outcome.

Detection of systematic errors in external radiotherapy before treatment delivery

The execution of an independent control of monitor units (MU) and dose distribution calculation, together with a check of the data reported in the treatment chart is an effective tool in strongly reducing the occurrence of systematic errors before treatment delivery. In this paper we report the results of the analysis of 6272 controls (about 5000 patients) registered over more than 5 years; 70 serious errors (producing a deviation larger than 5% from the prescribed daily dose) and 147 minor errors were detected and corrected before the start of the treatment. The error rate was found to be strongly operator-dependent (serious error rate ranging from 0.3 to 2.5% when considering different operators). A time-trend analysis showed a significant reduction of serious errors, i.e. 1.5% in the period from September 1991 to April 1994 compared to 0.9% in the period from April 1994 to November 1996. However, even if the double check was highly effective in revealing human errors, three serious systematic errors (errors occurring during the calculation/planning/transcription phases) escaped the control and were detected by diode in vivo dosimetry during the period October 1994 to November 1996 (in 650 patients controlled).

Sparing the penile bulb in the radical irradiation of clinically localised prostate carcinoma: A comparison between MRI and CT prostatic apex definition in 3DCRT, Linac-IMRT and Helical Tomotherapy

BACKGROUND AND PURPOSE To assess the impact of using MRI and Helical Tomotherapy (HT) compared to 3DCRT and dynamic IMRT on the dose to the penile bulb (PB). MATERIALS AND METHODS Eight patients diagnosed with prostate cancer entered a treatment protocol including CT and MRI simulation. The prostate apex was defined on both MRI and CT. Treatment plans (HT, Linac-IMRT, 3DCRT and conventional technique), were elaborated on both MRI and CT images. A dose of 71.4Gy (2.55Gy/fraction) was prescribed; it was requested that PTVs be covered by 95% isodose line. The mean dose and V50 of PB were evaluated. RESULTS PTV-MRI plans reduced PB mean dose and V50 compared to PTV-CT plans. This improvement, deriving also from the treatment modality, was 89% for 3DCRT, 99% for Linac-IMRT and 97% for HT (p<0.01), considering V50. Conventional plans resulted in a significantly higher mean PB dose/V50 compared to 3DCRT-PTV-CT (+27%/+38%), Linac-IMRT-PTV-CT (+42%/+57%) and HT-PTV-CT (+32%/+48%) (p<0.01). The comparison between conventional and PTV-MRI techniques showed a still larger increase: +73%/+93% 3DCRT; +86%/+99% Linac-IMRT; +56%/+99% HT (p<0.01). The PB mean dose reduction with Linac-IMRT compared to 3DCRT was 24% (p=0.034) and 40% (p=0.027) for PTV-CT and PTV-MRI, respectively. This gain remained significant even when comparing Linac-IMRT to HT: 21% (p=0.07) PTV-CT and 68% (p=0.00002) PTV-MRI. HT was superior to 3DCRT with respect to PTV-CT (average gain 4%, p=0.044), whereas it resulted to be detrimental considering PTV-MRI (26Gy vs 16.5Gy), possibly due to the helical delivery of HT; however, in a patient where the distance bulb-PTV <1cm, HT provided better PB sparing than 3DCRT (29.5Gy vs 45.2Gy). CONCLUSIONS MRI allowed efficient sparing of PB irrespective of the treatment modality. Linac-IMRT was shown to further reduce the dose to the bulb compared to 3DCRT and HT.

In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience

BACKGROUND AND PURPOSE In-vivo dosimetry is vital to assure an accurate delivery of total body irradiation (TBI). In-vivo lung dosimetry is strongly recommended because of the risk of radiation-induced interstitial pneumonia (IP). Here we report on our 5-year experience with in-vivo dosimetry using diodes in combination with portal films and assessing the effectiveness of in-vivo dosimetry in improving the accuracy of the treatment. Moreover, we wished to investigate in detail the possibility of in-vivo portal dosimetry to yield individual information on the lung dose and to evaluate the impact of CT planning on the correspondence between stated and in-vivo measured doses. MATERIALS AND METHODS From March 1994 to March 1999, 229 supine-positioned patients were treated at our Institute with TBI, using a 6 MV X-rays opposed lateral beam technique. 146 patients received 10 Gy given in three fractions, once a day (FTBI), shielding the lungs by the arms; 70 received 12-13.2 Gy, given in 6-11 fractions, 2-3 fractions per day (HFTBI): in this case about 2/3 of the lungs were shielded by moulded blocks (mean shielded lung dose equal to 9 or 9.5 Gy). Thirteen patients received 8 Gy given in a single fraction (SFTBI, lung dose: 7 Gy). For all HFTBI and FTBI patients, midline in-vivo dosimetry was performed at the first fraction by positioning two diodes pairs (one at entrance and one at the exit side) at the waist (umbilicus) and at the pelvis (ankles). If at least one of the two diodes doses (waist-pelvis) was outside +/-5% from the prescribed dose, actions could be initiated, together with possible checks on the following fractions. Transit dosimetry by portal films was performed for most patients; for 165 of them (117 and 48, respectively for FTBI and HFTBI) the midline in-vivo dose distribution of the chest region was derived and mean lung dose assessed. As a CT plan was performed for all HFTBI patients, for these patients, the lung dose measured by portal in-vivo dosimetry was compared with the expected value. RESULTS Concerning all diodes data, 528 measurements were available: when excluding the data of the first fraction(s) of the patients undergoing corrections (n = 392), mean and SD were respectively 0.0% and 4.5% (FTBI: -0.3 +/- 4.8%; HFTBI: 0.4 +/- 3.9%). In total 105/229 patients had a change after the first fraction and 66/229 were controlled by in-vivo dosimetry for more than one fraction. Since January 1998 a CT plan is performed for FTBI patients too: when comparing the diodes data before and after this date, a significant improvement was found (i.e. rate of deviations larger than 5% respectively equal to 30.7% and 13.1%, P = 0.007). When considering only the patients with a CT plan, the global SD reduced to 3.5%. Concerning transit dosimetry data, for FTBI, the mean (midline) lung dose was found to vary significantly from patient to patient (Average 9.13 +/- 0.81 Gy; range 7.4-11.4 Gy); for the HFTBI patients the mean deviation between measured and expected lung dose was 0.0% (1 SD = 3.8%). CONCLUSIONS In vivo dosimetry is an effective tool to improve the accuracy of TBI. The impact of CT planning for FTBI significantly improved the accuracy of the treatment delivery. Transit dosimetry data revealed a significant inter-patient variation of the mean lung dose among patients undergoing the same irradiation technique. For patients with partial lung shielding (HFTBI), an excellent agreement between measured and expected lung dose was verified.

Physics aspects of prostate tomotherapy : Planning optimization and image-guidance issues

Purpose. To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). Methods and materials. Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4–74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. Results. At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation ≥3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts ≥3 mm. Conclusions. HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema.

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. PACS number: 87.55.Qr

Variations of tumor control and rectum complication probabilities due to random set-up errors during conformal radiation therapy of prostate cancer

BACKGROUND AND PURPOSE The effect of random set-up errors on tumor control probability (TCP) and rectum complication probability (NTCP) on 3D conformal treatment planning of prostate cancer has been investigated by applying the convolution method originally proposed by Leong (Leong, J. Implementation of random positioning error in computerized radiation treatment planning systems as a result of fractionation. Phys. Med. Biol. 32: 327-334, 1987). MATERIALS AND METHODS The combined influence of the standard deviation of the random shifts probability distribution (sigma) of the dose and of the Beams-eye-view margin (M) between the clinical target volume (CTV) and the edge of the blocks have been investigated in two patients. RESULTS AND CONCLUSIONS Random set-up error has been found to decrease TCP (for a typical 70 Gy CTV mean dose) by up to 6% for a 1 cm margin (sigma = 7 mm). When M is equal to or larger than 1.5 cm, no relevant effects on TCP are obtained. Maximum acceptable TCP values (corresponding to a rectum NTCP equal to 5%) have been derived and the dependence on sigma and M has been investigated.

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.

Dosimetric evaluation of a commercial 3-D treatment planning system using Report 55 by AAPM Task Group 23

BACKGROUND AND PURPOSE A relevant part of radiotherapy treatment planning system QA concerns dose calculation verification. Report 55 by AAPM TG-23 is an instrument for performing dosimetric evaluation of treatment planning systems in case of external photon beams. It was employed by different groups in three radiotherapy departments for controlling performances of RTPS CadPlan Varian-Dosetek, versions 2.7.9, 3.0.6 and 3.1.1. MATERIALS AND METHODS Once the basic data of the AAPM 4 MV and 18 MV X-ray units had been converted into the CadPlan format and the AAPM units configured, the whole set of TG23 tests were carried out on three different systems. According to Report 55, comparisons between values measured by TG-23 and calculated by RTPS were made in terms of dose at selected points and radiological field width at different depths. RESULTS As far as dose is concerned, 266 data were compared for 4 MV and 297 for 18 MV. Ninety-five-point-nine percent of dose deviations for 4 MV and 92.6% for 18 MV are less than 2%. Most of the relevant discrepancies for both energies occur in a test case where dose has to be calculated under a long narrow block centred on the beam axis. Deviations as much as 6.1% for 4 MV and -7.5% for 18 MV were observed in points at 1 cm depth under the block. Poor results were also observed in the rectangular field 25 x 5, in points outside the field edges under collimators. As regards radiological field width, 58 out of 64 comparisons for 4 MV occurred in the range +/- 2 mm. For 18 MV the biggest deviation was -2.2 mm. CONCLUSIONS The TG-23 tests demonstrated that the accuracy of the RTPS in dose calculation is good in most of the typical radiotherapy applications. Our results are better than those recently published for other RTPS. The TG-23 package turned out to be an effective instrument for QA and calculation verification, as well as being a powerful method for training purpose in configuring and using a RTPS.