Effectiveness of fractionated stereotactic radiotherapy for uveal melanoma.

PURPOSE: To study the effectiveness and acute side effects of fractionated stereotactic radiation therapy (fSRT) for uveal melanoma. METHODS AND MATERIALS: Between 1999 and 2003, 38 patients (21 male, 17 female) were included in a prospective, nonrandomized clinical trial (mean follow-up of 25 months). A total dose of 50 Gy was given in 5 consecutive days. A blinking light and a camera (to monitor the position of the diseased eye) were fixed to a noninvasive relocatable stereotactic frame. Primary end points were local control, best corrected visual acuity, and toxicity at 3, 6, 12, and 24 months, respectively. RESULTS: After 3 months (38 patients), the local control was 100%; after 12 months (32 patients) and 24 months (15 patients), no recurrences were seen. The best corrected visual acuity declined from a mean of 0.21 at diagnosis to 0.06 2 years after therapy. The acute side effects after 3 months were as follows: conjunctival symptoms (10), loss of lashes or hair (6), visual symptoms (5), fatigue (5), dry eye (1), cataract (1), and pain (4). One eye was enucleated at 2 months after fSRT. CONCLUSIONS: Preliminary results demonstrate that fSRT is an effective and safe treatment modality for uveal melanoma with an excellent local control and mild acute side effects. The follow-up should be prolonged to study both long-term local control and late toxicity.

A modified relocatable stereotactic frame for irradiation of eye melanoma: design and evaluation of treatment accuracy.

PURPOSE: To describe a reliable, patient-friendly relocatable stereotactic frame for irradiation of eye melanoma and to evaluate the repositioning accuracy of the stereotactic treatment. METHODS AND MATERIALS: An extra construction with a blinking light and a camera is attached to a noninvasive relocatable Gill-Thomas-Cosman stereotactic frame. The position of the blinking light is in front of the unaffected eye and can be adjusted to achieve an optimal position for irradiation. The position of the diseased eye is monitored with a small camera. A planning CT scan is performed with the affected eye in treatment position and is matched with an MR scan to improve the accuracy of the delineation of the tumor. Both the translation and rotation of the affected eye are calculated by comparing the planning CT scan with a control CT scan, performed after the radiation therapy is completed. RESULTS: Nineteen irradiated eye melanoma patients were analyzed. All patients received 5 fractions of 10 Gy within 5 days. The depth-confirmation helmet measurements of the day-to-day treatment position of the skull within the Gill-Thomas-Cosman frame were analyzed in the anteroposterior, lateral, and vertical directions and were 0.1 +/- 0.3, 0.0 +/- 0.2, and 0.2 +/- 0.2 mm (mean +/- SD), respectively. The average translations of the eye on the planning and control CT scan were 0.1 +/- 0.3 mm, 0.1 +/- 0.4, and 0.1 +/- 0.5 mm, respectively. The median rotation of the diseased eye was 8.3 degrees. CONCLUSIONS: The described Rotterdam eye fixation system turned out to be a feasible, reliable, and patient-friendly system.

Dosimetric comparison between high-precision external beam radiotherapy and endovascular brachytherapy for coronary artery in-stent restenosis.

PURPOSE: Several drawbacks of endovascular brachytherapy for the treatment of coronary artery in-stent restenosis may be addressed by high-precision external beam radiotherapy (EBRT). The dosimetric characteristics of both treatment techniques were compared. METHODS AND MATERIALS: The traversed volume of 10 coronary artery stents during the cardiac cycle was determined by electrocardiographically gated multislice spiral CT in 10 patients. By use of this traversed volume, high-precision EBRT treatment plans were generated for stents in the left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA). The maximum dose to the nontargeted major coronary arteries was determined and compared to similar data calculated for endovascular brachytherapy. RESULTS: High-precision EBRT targeted at LCx stents contributed a mean maximum dose (D(max)) of 83.5% (range: 71.6-95.3%) and 16.3% to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 39.3% (range: 14.5-94.8%) and 5.2% (range: 0-13.4%) to the LCx and RCA, respectively. Targeted RCA stents contributed a mean D(max) of 6.2% (range: 0-12.4%) and 5.8% (range: 0-11.5%) to the LCx and LAD, respectively. Endovascular brachytherapy targeted at LCx stents contributed a mean D(max) of 1.7% (range: 0.7-2.7%) and 1.0% (range: 0.6-1.4%) to the LAD and RCA, respectively. Targeted LAD stents contributed a mean D(max) of 5.2% (range: 0.5-11.4%) and 0.7% (range: 0.4-1.1%) to the LCx and RCA, respectively; targeted RCA stents contributed a mean D(max) of 0.3% (range: 0.2-0.5%) and 0.2% (range: 0.1-0.3%) to the LCx and LAD, respectively. CONCLUSIONS: Although the doses distributed throughout the heart were higher for high-precision EBRT compared to endovascular brachytherapy, they are expected to be clinically irrelevant when nontargeted major coronary arteries are not closely situated to the targeted vessel segment. These encouraging results warrant further investigation of high-precision EBRT as a potential alternative to endovascular brachytherapy for the treatment of coronary artery in-stent restenosis.

High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Optimal source position for irradiation of coronary bifurcations in endovascular brachytherapy with catheter based beta or iridium-192 sources.

BACKGROUND AND PURPOSE: Intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) is usually performed with catheter-based treatment techniques in a straight vessel segment. There is a growing interest for treatment of bifurcations, which requires consecutive positioning of the source in main vessel and side branch. MATERIALS AND METHODS: In-house developed software (IC-BT doseplan) is used to explore the optimal positioning of the source in modelled bifurcations with different shape for the source types available in our hospital, i.e. (90)Sr/(90)Y, (32)P and (192)Ir. The results were summarised in look-up tables. The usefulness of these look-up tables was tested on various clinical examples. RESULTS: Tabulated results for the modelled bifurcations yield an estimation of the distance between the sources (gap width) in relation to the geometry and source type: (90)Sr/(90)Y gap range 3-8.5 mm, (32)P gap range 2-7 mm and (192)Ir gap range 3.5-8 mm. The average dose relative to 2 mm from the source axis is: (90)Sr/(90)Y, (mean+/-SD) 120+/-40%; (32)P, 125+/-50% and (192)Ir, 120+/-22%. The look-up tables also provide the coarse location and value of maximum and minimum dose: (90)Sr/(90)Y, 220-60%, (32)P, 230-55% and (192)Ir, 170-85%. It appeared that the look-up tables provide a good approximation of the optimal gap width in the clinical examples. CONCLUSIONS: Tabulated optimal gap widths are very useful for quick estimation of the required gap width for a given bifurcation and source type, in case the prescribed dose in both vessels is the same. In unfavourable geometries there is a risk of local underdosage. Individual treatment planning using a program such as IC-BT doseplan is then recommended.

Inaccuracy in manual multisegmental irradiation in coronary arteries.

PURPOSE: Retrospective evaluation of the accuracy of manual multisegmental irradiation with a source train for irradiation of long (re)stenotic lesions in coronary arteries, following percutaneous transluminal coronary angioplasty (PTCA). MATERIAL AND METHODS: Thirty-six patients were treated with intracoronary irradiation following PTCA with manual multisegmental irradiation. These patients were included in the multicenter, multinational 'European Surveillance Registry with the Novoste Beta-Cath system' (RENO). In all 36 patients the target length (i.e. PTCA length plus 5-mm margin at each side) was too long for the available source train lengths (30 and 40 mm). In 33 patients the radiation delivery catheter was manually positioned twice and in three patients three times in series, trying to avoid any gap or overlap. The total number of junctions was 39. Following a successful PTCA procedure the site of angioplasty was irradiated using the Novoste Beta-Cath afterloader with a 5-F non-centered catheter which accommodates the sealed beta-emitting (90)Sr/(90)Y source train or dummy source train. Radiation was delivered first to the distal part of the target length. Fluoroscopic images of this source position were stored in the computer memory. For irradiation of the proximal part of the target length, the delivery catheter had to be retracted over a distance equal to the source length used for the distal part. This was done by a continuous overlay video loop with ECG-gated replay of the image stored in the computer memory. The dummy source was used to position the delivery catheter so that the junction between both source positions was as precise as possible. Measurements of gap or overlap between the source positions were performed retrospectively on printed images. Doses were calculated, in accordance with the Novoste study protocol, at a distance of 2 mm from the source axis (=dose prescription distance) in several points along the irradiated length. RESULTS: Interventional or PTCA length varied between 33 and 95 mm. The lesion sites were in the left anterior descending artery, (n=6), right coronary artery (n=20), left circumflex artery (n=6) and one vein graft. The administered radiation dose was determined by the vessel diameter and the presence of a stent. This dose, prescribed at a distance of 2 mm from the source axis, varied between 16 and 22 Gy. No gap or overlap was seen between the two source trains in only two out of 39 cases. In 16 cases there was a gap ranging between 0.6 and 9.6 mm and 18 cases showed an overlap of 0.5-14.4 mm. In three patients the measurement was not possible. In case of a gap the minimal dose calculated at 2 mm from the source axis varies between 0 and 87% of the prescribed dose, depending on the distance between both sources. In case of overlap the maximal dose varies between 110 and 200% of the prescribed dose at 2 mm from the source axis. CONCLUSIONS: The results show the inaccuracy of manual multisegmental irradiation using a source train in coronary arteries, causing unacceptable dose inhomogeneities at a distance of 2 mm from the source axis at the junction between both source positions. Moreover, a perfect junction will never be possible due to movement of the non-centered radiation delivery catheter in the vessel lumen, as applied in this study. Manual multisegmental irradiation is therefore not recommended. Using longer line sources or source trains or preferably an automated stepping source is a more reliable and safer technique for treatment of long lesions.

Local control in advanced cancer of the nasopharynx: is a boost dose by endocavitary brachytherapy of prognostic significance?

PURPOSE: To analyze whether local tumor control in advanced nasopharyngeal cancer (NPC) can be optimized by boosting the primary dose by endocavitary brachytherapy (EBT). METHODS AND MATERIALS: To study the role of EBT, three data sets on NPC, that is, the "Vienna", "Rotterdam," and "Amsterdam" series, with a total number of 411 advanced NPC patients, were available. The Rotterdam series consisted of 72 patients (34 T1,2N+ and 38 T3,4N0,+) and were treated with neoadjuvant chemotherapy followed by external beam radiotherapy (dose 70/2Gy). After 70/2Gy, a boost was applied by EBT (in case of T1,2N+) or stereotactic radiation (in case of T3,4 tumors). The Amsterdam (Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute) series consisted of 76 patients (40 T1,2N+ and 36 T3,4N0,+) and were irradiated to a dose of 70/2Gy with concomitant chemotherapy. No second boost by EBT was applied. RESULTS: In the case of T1,2N+ tumors, the local relapse rate (LRR) was significantly smaller if a boost was applied, that is, 0% (0/34, EBT boost) vs. 14% (14/102, no EBT boost) (p=0.023). For the T3,4 tumors, an LRR of 10% (4/38, EBT or stereotactic radiation boost) vs. 15% (17/111, no boost) was found (p=0.463). CONCLUSIONS: In the case of advanced NPC (T1,2N+ vs. T3,4N+,0), for early T-stages (T1,2N+), an EBT boost seems an excellent way to deliver highly conformal high doses of radiation to the nasopharynx, with high local control rates. For advanced T-stages (T3,4N+,0), the reduction in LRR (10% vs. 15%) was not significant (p=0.463).

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results.

PURPOSE: To determine local control, late toxicity and metastatic free survival (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT) for uveal melanoma (UM). METHODS AND MATERIALS: Between 1999 and 2007, 102 UM patients were included in a prospective study of a single institution (median follow-up (FU) 32 months; median tumor thickness 6 mm); five fractions of 10 Gy were given. Primary endpoints were local tumor control and late toxicity (including visual outcome and eye preservation). Secondary endpoint was MFS. RESULTS: Local tumor control was achieved in 96% of the patients. Fifteen enucleations were performed, 2-85 months after radiation. Four eyes were enucleated because of local tumor progression. Nine patients developed grade 3 or 4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients suffered from keratitis sicca. Best corrected visual acuity (BCVA) decreased from a mean of 0.26 at diagnosis to 0.16, 3 months after radiation and it gradually declined to 0.03, 4 years after therapy. The 5-year actuarial MFS was 75% (95% CIs: 62-84%). CONCLUSIONS: fSRT is an effective treatment modality for uveal melanoma with a good local control. With that, fSRT is a serious eye sparing treatment modality. However, our FU is relatively short. Also, the number of secondary enucleations is substantial, mainly caused by NVG.

Lacrimal gland radiosensitivity in uveal melanoma patients.

PURPOSE: To find a dose-volume effect for inhomogeneous irradiated lacrimal glands. METHODS AND MATERIALS: Between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 Gy was given on 5 consecutive days. The mean of all Schirmer test results obtained > or =6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (DES) was related to the lacrimal gland dose distribution. RESULTS: Of the 72 patients, 17 developed a late Schirmer value <10 mm; 9 patients developed DES. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. reduced tear production (p = 0.000) and vs. the appearance of DES (p = 0.003), respectively. A median dose of 7 Gy/fraction to the lacrimal gland caused a 50% risk of low Schirmer results. A median dose of 10 Gy resulted in a 50% probability of DES. CONCLUSION: We found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of DES.