This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian ...tube, or primary peritoneal cancer.
Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m(2) intravenously every 3 weeks) or PLD (50 mg/m(2) intravenously every 4 weeks).
A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm.
Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.
Retrospective studies on MRI-only radiotherapy have been presented. Widespread clinical implementations of MRI-only workflows are however limited by the absence of guidelines. The MR-PROTECT trial ...presents an MRI-only radiotherapy workflow for prostate cancer using a new single sequence strategy. The workflow incorporated the commercial synthetic CT (sCT) generation software MriPlanner™ (Spectronic Medical, Helsingborg, Sweden). Feasibility of the workflow and limits for acceptance criteria were investigated for the suggested workflow with the aim to facilitate future clinical implementations.
An MRI-only workflow including imaging, post imaging tasks, treatment plan creation, quality assurance and treatment delivery was created with questionnaires. All tasks were performed in a single MR-sequence geometry, eliminating image registrations. Prospective CT-quality assurance (QA) was performed prior treatment comparing the PTV mean dose between sCT and CT dose-distributions. Retrospective analysis of the MRI-only gold fiducial marker (GFM) identification, DVH- analysis, gamma evaluation and patient set-up verification using GFMs and cone beam CT were performed.
An MRI-only treatment was delivered to 39 out of 40 patients. The excluded patient was too large for the predefined imaging field-of-view. All tasks could successfully be performed for the treated patients. There was a maximum deviation of 1.2% in PTV mean dose was seen in the prospective CT-QA. Retrospective analysis showed a maximum deviation below 2% in the DVH-analysis after correction for rectal gas and gamma pass-rates above 98%. MRI-only patient set-up deviation was below 2 mm for all but one investigated case and a maximum of 2.2 mm deviation in the GFM-identification compared to CT.
The MR-PROTECT trial shows the feasibility of an MRI-only prostate radiotherapy workflow. A major advantage with the presented workflow is the incorporation of a sCT-generation method with multi-vendor capability. The presented single sequence approach are easily adapted by other clinics and the general implementation procedure can be replicated. The dose deviation and the gamma pass-rate acceptance criteria earlier suggested was achievable, and these limits can thereby be confirmed. GFM-identification acceptance criteria are depending on the choice of identification method and slice thickness. Patient positioning strategies needs further investigations to establish acceptance criteria.
Mycosis fungoides is a disease with manifestation of the skin that has traditionally been treated with electron therapy. In this paper, we present a method of treating the entire skin with ...megavoltage photons using helical tomotherapy (HT), verified through a phantom study and clinical dosimetric data from our first two treated patients. A whole body phantom was fitted with a wetsuit as bolus, and scanned with computer tomography. We accounted for variations in daily setup using virtual bolus in the treatment plan optimization. Positioning robustness was tested by moving the phantom, and recalculating the dose at different positions. Patient treatments were verified with in vivo film dosimetry and dose reconstruction from daily imaging. Reconstruction of the actual delivered dose to the patients showed similar target dose as the robustness test of the phantom shifted 10 mm in all directions, indicating an appropriate approximation of the anticipated setup variation. In vivo film measurements agreed well with the calculated dose confirming the choice of both virtual and physical bolus parameters. Despite the complexity of the treatment, HT was shown to be a robust and feasible technique for total skin irradiation. We believe that this technique can provide a viable option for Tomotherapy centers without electron beam capability.
•1 min time reduction for prostate patient setup using SGRT.•Accurate initial positioning for deep-seated target with surface imaging.•Improved workflow using intuitive color map for setup guidance.
...The aim of this study was to evaluate if surface guided radiotherapy (SGRT) can decrease patient positioning time for localized prostate cancer patients compared to the conventional 3-point localization setup method. The patient setup accuracy was also compared between the two setup methods.
A total of 40 localized prostate cancer patients were enrolled in this study, where 20 patients were positioned with surface imaging (SI) and 20 patients were positioned with 3-point localization. The setup time was obtained from the system log files of the linear accelerator and compared between the two methods. The patient setup was verified with daily orthogonal kV images which were matched based on the implanted gold fiducial markers. Resulting setup deviations between planned and online positions were compared between SI and 3-point localization.
Median setup time was 2:50 min and 3:28 min for SI and 3-point localization, respectively (p < 0.001). The median vector offset was 4.7 mm (range: 0–10.4 mm) for SI and 5.2 mm for 3-point localization (range: 0.41–17.3 mm) (p = 0.01). Median setup deviation in the individual translations for SI and 3-point localization respectively was: 1.1 mm and 1.9 mm in lateral direction (p = 0.02), 1.8 and 1.6 mm in the longitudinal direction (p = 0.41) and 2.2 mm and 2.6 mm in the vertical direction (p = 0.04).
Using SGRT for positioning of prostate cancer patients provided a faster and more accurate patient positioning compared to the conventional 3-point localization setup.
In magnetic resonance (MR) only radiotherapy, the target delineation needs to be performed without computed tomography (CT). We investigated in thirteen patients with prostate cancer, how the ...clinical target volume (CTV) was affected, when the target delineation procedure was changed from using both CT and MR images to using MR images only. The mean volume of the CTVCT/MR was 61.0 cm3 as compared to 49.9 cm3 from MR-only based target delineation, corresponding to an average decrease of 18%. Our results show that CTVMR-only was consistently smaller than CTVCT/MR, which has to be taken into consideration before clinical commissioning of MR-only radiotherapy.
Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or ...equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity.
Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea.
A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0–10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the “hottest” 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage.
On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions).
The purpose of this study was to evaluate the safety and efficacy of PET and MRI guided re-irradiation of recurrent high-grade glioma (HGG) and to assess the impact of radiotherapy dose, ...fractionation and irradiated volume.
Patients with localized, recurrent HGG (grades III-IV) and no other treatment options were eligible for a prospective phase I trial. Gross tumor volumes for radiotherapy were defined using T1-contrast enhanced MRI and 18F-fluoro-ethyl tyrosine PET. Radiotherapy was delivered using volumetric modulated arc therapy with a 2-mm margin. The dose prescription of four consecutive groups was (1) 35 Gy/10fr., (2) 42 Gy/10fr., (3) 29.5 Gy/5fr. and (4) 35 Gy/10fr. to larger tumor volumes (100–300 cm3), respectively.
Thirty-one patients were treated of which 81% had glioblastoma. The median progression-free survival was 2.8 months (95%CI: 2.1–3.5) and the median overall survival was 7.0 months (95%CI: 3.5–10.5). Early side effects were mild and included headache and fatigue. Seven patients were progression-free beyond 10 weeks and were evaluable for late toxicity. Among these patients, three (43%) suffered late adverse events which included radionecrosis and irreversible white matter changes.
Re-irradiation showed limited efficacy and 43% of patients achieving disease control suffered late toxicity that was manageable but not negligible.
We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus ...the current standard using MRI alone. Specifically, we investigated the influence of tumor grade, MR-defined tumor volume, and the extent of surgical resection on PET positivity.
Fifty-four consecutive high-grade glioma patients (World Health Organization grades III-IV) with confirmed histology were scanned using FET-PET/CT and T1 and T2/fluid attenuated inversion recovery MRI. Gross tumor volume and clinical target volumes (CTVs) were defined in a blinded fashion based on MRI and subsequently PET, and volumetric analysis was performed. The extent of the surgical resection was reviewed using postoperative MRI.
Overall, for ∼ 90% of the patients, the PET-positive volumes were encompassed by T1 MRI with contrast-defined tumor plus a 20-mm margin. The tumor volume defined by PET was larger for glioma grade IV (P < .001) and smaller for patients with more extensive surgical resection (P = .004). The margin required to be added to the MRI-defined tumor in order to fully encompass the FET-PET positive volume tended to be larger for grade IV tumors (P = .018).
With an unchanged CTV margin and by including FET-PET for gross tumor volume definition, the CTV will increase moderately for most patients, and quite substantially for a minority of patients. Patients with grade IV glioma were found to be the primary candidates for PET-guided radiation therapy planning.
Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient ...characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT.
Adult patients with grade 2-3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment.
Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p = .38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p = .016). The PT patients had a significantly better PFS and OS than the XRT patients (p = .025 and .035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p < .001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively.
Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.
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