Palliative radiotherapy: New prognostic factors for patients with bone metastasis.

PURPOSE: Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival. MATERIALS AND METHODS: Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used. RESULTS: Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy. CONCLUSION: Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer.

OBJECTIVE: For locally advanced cervical cancer patients, treated with External Beam Radiotherapy (EBRT), Quality of Life (QoL) questionnaires arefrequently used to evaluate treatment-related symptoms and functioning scales. Currently, it is unknown how those evolve during the radiation treatment course. In this prospective study we report on weekly-captured patient-reported QoL and symptoms during image-guided adaptive radiotherapy (IGART) of cervical cancer patients. MATERIAL AND METHODS: Between January 2012 and September 2016, all locally advanced cervical cancer patients treated with IGART and brachytherapy with or without chemotherapy or hyperthermia, were eligible. QoL was assessed at baseline; weekly during the first five weeks of treatment; 1week, 1 and 3months after treatment, using the EORTC QLQ-C30 and the QLQ-CX24 questionnaires. Comparisons were made with an age-matched norm population. RESULTS: Among the 138 (70%) responders, most symptoms showed a moderate-to-large increase, reaching a maximum at the end of treatment, or first week after treatment with return to baseline value at 3months after treatment. While most symptoms gradually increased during the first five weeks, diarrhea and bowel cramps already markedly increased within the first three weeks to reach a plateau at the 5th week of treatment. Global health and functioning were temporarily decreased and returned to a plateau at baseline level 3months after treatment, except for cognitive functioning. CONCLUSION: A profound impact on QoL was observed during the radiation treatment course, temporarily affecting functioning. The maximum impaired was reached at the end of EBRT.

Individualized nonadaptive and online-adaptive intensity-modulated radiotherapy treatment strategies for cervical cancer patients based on pretreatment acquired variable bladder filling computed tomography scans.

PURPOSE: To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients. METHODS AND MATERIALS: For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-range of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix-uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix-uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated. RESULTS: The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% ± 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and -1% to 9%; p < 0.004) and the CTV-to-PTV volume (4-96 ml). CONCLUSIONS: Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.

Set-up verification of cervix cancer patients treated with long treatment fields; implications of a non-rigid bony anatomy.

BACKGROUND AND PURPOSE: For cervix cancer patients, treatment fields may extend up to vertebra L1. In clinical practice, set-up verification is based on measured displacements of the pelvic rim as visible in the caudal part of the treatment fields. The implications of this procedure for the positions of bony structures in the cranial part of the fields were investigated. MATERIALS AND METHODS: Twelve patients had four repeat simulator sessions. Both during treatment simulation (the reference) and the repeat sessions, anterior radiographs were acquired covering the whole treatment field. The films were used to investigate differences between the cranial and the caudal parts of the treatment field in day-to-day bony anatomy displacements. RESULTS: Both in the transversal and the longitudinal directions, these differences were significant (3.5 mm, 1 SD). Indications were found that large differences in the cranio-caudal direction may be correlated with (non-rigid) internal pelvic rim rotations around a lateral axis. In the longitudinal direction, the position of L1 correlated much better with the position of vertebra S1 than with the position of the pelvic rim, which is usually used for set-up verification. CONCLUSIONS: Due to the non-rigid bony anatomy of the studied patients, the usual set-up verification and correction procedure can result in set-up errors of 10 mm and more for structures in the cranial part of the treatment field, even in the case of a perfect set-up of the pelvic rim. Possibly, other patient set-up and immobilization procedures may result in a better day-to-day reproducibility of the 3D bony anatomy shape. (Remaining) Differences in anatomy position changes between the caudal and cranial field ends may be accounted for by using non-uniform clinical target volume-to-planning target volume margins, or by an adapted patient set-up verification and correction protocol.

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Definition and validation of a reference target volume in early stage node-positive cervical carcinoma, based on lymphangiograms and CT-scans.

PURPOSE: To establish a reference planning target volume for postoperative radiotherapy in stage Ib and IIa N+ cervical carcinoma, based on 47 lymphangiograms and 15 CT-scans. METHODS: Radiation oncologists (n=17) from all radiotherapy institutes in The Netherlands were asked to define the clinical target volume (CTV) and planning target volume (PTV), and to delineate (on simulation films) the radiotherapy treatment portals following a radical hysterectomy with lymph node dissection for an early stage cervical carcinoma with positive iliac lymph nodes. A reference PTV was defined by using 47 normal lymphangiograms and CT-data of the pelvis from 15 patients who underwent surgery for cervical carcinoma. The simulation films were digitized and evaluated for adequacy in covering the PTV, previously individually determined by the radiation oncologists. Subsequently, the simulation films were also evaluated for adequacy in covering the reference PTV. RESULTS: Large variations were observed in the portals used and in treatment techniques. From the digitized films, it appeared that in 50% of the cases the defined PTV was not covered adequately. Furthermore, 71% of the treatment plans would not cover the lateral borders of the reference PTV sufficiently. CONCLUSIONS: There appears to be no consensus on the target volumes to be irradiated in postoperative radiotherapy of early stage cervical carcinoma. When a PTV defined on the basis of lymphangiograms and CT-data is taken as a reference, 71% of the treatment plans would not cover this PTV adequately. These findings indicate the need for a consensus in the design of standardized treatment volumes.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors.

PURPOSE: Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS: Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS: The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS: On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

Transit dosimetry with an electronic portal imaging device (EPID) for 115 prostate cancer patients.

PURPOSE: Comparison of predicted portal dose images (PDIs) with PDIs measured with an electronic portal imaging device (EPID) may be used to detect errors in the dose delivery to patients. However, these comparisons cannot reveal errors in the MU calculation of a beam, since the calculated number of MU is used both for treatment (and thus affects the PDI measurement) and for PDI prediction. In this paper a method is presented that enables "in vivo" verification of the MU calculation of the treatment beams. The method is based on comparison of the intended on-axis patient dose at 5 cm depth for each treatment beam, D5, with D5 as derived from the portal dose Dp measured with an EPID. The developed method has been evaluated clinically for a group of 115 prostate cancer patients. METHODS AND MATERIALS: The patient dose D5 was derived from the portal dose measured with a fluoroscopic EPID using (i) the predicted beam transmission (i.e., the ratio of the portal dose with and without the patient in the beam) calculated with the planning CT data of the patient, and (ii) an empirical relation between portal doses Dp and patient doses D5. For each beam separately, the derived patient dose D5 was compared with the intended dose as determined from the relative dose distribution as calculated by the treatment planning system and the prescribed isocenter dose (2 Gy). For interpretation of observed deviating patient doses D5, the corresponding on-axis measured portal doses Dp were also compared with predicted portal doses. RESULTS: For three beams, a total of 7828 images were analyzed. The mean difference between the predicted patient dose and the patient dose derived from the average measured portal dose was: 0.4+/-3.4% (1 SD) for the anterior-posterior (AP) beam and -1.5+/-2.4% (1 SD) for the lateral beams. For 7 patients the difference between the predicted portal dose and the average measured portal dose for the AP beam and the corresponding difference in patient dose were both greater than 5%. All these patients had relatively large gas pockets (3-3.5 cm in AP direction) in the rectum during acquisition of the planning CT, which were not present during (most) treatments. CONCLUSIONS: An accurate method for verification of the MU calculation of an x-ray beam using EPID measurements has been developed. The method allows the discrimination of errors that are due to changes in patient anatomy related to appearance or disappearance of gas pockets in the rectum and errors due to a deviating cGy/MU-value.

Three-dimensional treatment planning for postoperative radiotherapy in patients with node-positive cervical cancer. Comparison between a conventional and a conformal technique.

PURPOSE: Reduction of irradiated small bowel volume, using a conformal three-dimensional treatment planning technique in postoperative radiotherapy of cervical cancer patients. PATIENTS AND METHODS: Large gynecological treatment fields including the para-aortic nodes were analyzed in 15 patients. A conventional treatment plan with anterior and posterior (AP-PA) parallel opposed fields and a 3D 4-field conformal radiotherapy plan with a central blocking of small bowel were compared for each patient. Dose-volume histograms and dose parameters were established. Because of the tolerance constraints of the small bowel, the cumulative dose applied to the target was 48.6 Gy. RESULTS: The mean Tumor Control Probability (TCP) values for both the conventional and the conformal technique were 0.60 and 0.61, respectively, with ranges of 0.56 to 0.67 and 0.57 to 0.66, respectively. The mean volume receiving 95% or more of the prescribed dose (V95) of the small bowel was 47.6% (32.5 to 66.3%) in the AP-PA technique and 14.9% (7.0 to 22.5%) in the conformal technique (p < 0.001), indicating a significant reduction in irradiated volume of small bowel in the higher dose range. The mean Normal Tissue Complication Probability (NTCP) decreased from 0.11 to 0.03 with the conformal plan. In patients who received a pedicled omentoplasty during surgery, the mean V95 for small bowel could be reduced to 8.5% (7.0 to 9.9%). The mean median dose to the kidneys was only slightly elevated in the conformal treatment. Especially the mean dose to the right kidney in conventional vs conformal treatment was 3.3 vs 7.9 Gy. The mean near-minimum dose (D95) to the rectosigmoid decreased from 48.4 to 30.1 Gy in the conformal plan compared to the conventional plan. CONCLUSION: The small bowel dose can be significantly reduced with 3D treatment planning, particularly if a pedicled omentoplasty is performed. This allows dose escalation to the tumor region without unacceptable toxicity for the small bowel.

In vivo dosimetry for prostate cancer patients using an electronic portal imaging device (EPID); demonstration of internal organ motion.

PURPOSE: To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients. METHODS: For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient. RESULTS: For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion). CONCLUSIONS: The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

[Clinical course after surgery of aneurysms of the anterior communicating artery]. / Evolution, après chirurgie des anévrysmes de l'artère communicante antérieure.

The evolution and correlations between initial state and outcome (one year) are analysed in 81 patients with anterior cerebral artery aneurysm. The age and initial evaluations are seldomly correlated with late evaluations, Jennett and Holbook scales, frontal syndrome, amnesia. The evaluations at one month are very significantly correlated to the late evaluations.