| 1. |
- Giraud, Paul, et al.
(författare)
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Investigation of Relation of Radiation Therapy Quality With Toxicity and Survival in LAP07 Phase 3 Trial for Locally Advanced Pancreatic Carcinoma
- 2021
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 110:4, s. 993-1002
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The LAP07 multicenter randomized study assessed whether chemoradiation therapy increases overall survival versus continuation chemotherapy in patients whose locally advanced pancreatic cancer was controlled after 4 months of induction chemotherapy. This analysis investigated whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity. Methods and Materials: This is a planned analysis of secondary objectives in the framework of a randomized international phase 3 trial. The protocol included detailed written RT guidelines. All participating institutions undertook an initial benchmark case to check adherence to protocol guidelines. Centers with major deviation were not allowed to include patients until they achieved a significant improvement and rigorously followed the guidelines. On-trial RT quality assurance consisted of a central review of treatment plan with dose-volume histograms for each patient. Adherence to guidelines was graded as per protocol (PP), minor deviation (MiD), or major deviation (MaD). Results: Fifty-seven benchmark cases were evaluated, 26% were classified as PP, 60% were MiD, and 14% were MaD. Among the 442 included patients, 133 patients were randomized in the chemoradiation therapy arm, and 117 patients were assessable for RT quality analysis. RT quality was graded as PP in 38.5% of patients, MiD in 43.6% of patients, and MaD in 17.9% of patients. The most frequent protocol violations were dose distribution heterogeneities. Median overall survival was 17 months with PP and MiD versus 13.4 months with MaD (hazard ratio [HR], 1.63; 95% confidence interval [CI], 0.99-2.71; P = .055). There was no difference in terms of progression-free survival (HR, 1.09; 95% CI, 0.66-1.8; P = .72). Patients with MaD had more nausea than patients treated PP or with MiD (P = .0045). Conclusions: MaD was associated with a trend for worst survival. There was no difference in terms of progression-free survival. Because of the low rate of major deviations, their effects on the LAP07 trial results may be negligeable. (C) 2021 Elsevier Inc. All rights reserved.
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| 2. |
- Gubanski, Michael
(författare)
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Aspects of chemotherapy and photon and proton radiotherapy in patients with gastric cancer
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastric cancer remains a major health problem worldwide. The addition of chemotherapy alone or in combination with radiotherapy to surgery in local gastric cancer improves outcome. In more advanced stages, the optimal palliative chemotherapy remains unknown, as well as the effect of different regimens on the patients’ quality of life. The aim of this thesis was to explore a new concept in chemotherapy, i.e. the sequential approach, and a new modality in radiotherapy, i.e. proton therapy, in the treatment of patients with gastric cancer. Quality of life (QoL) in patients treated with chemotherapy, and target delineation in radiotherapy of gastric cancer, were also studied. In Paper I, we evaluated the efficacy of sequential chemotherapy in patients with locally advanced and/or metastatic gastric cancer, with alternating irinotecan and docetaxel in combination with infusion 5-Fu. Eighty-one patients were randomized. No differences favoring either arm were found with respect to response rate, overall survival (OS), or toxicity. The median OS of 11 months indicated that the sequential approach was effective and similar to triple combinations, with potentially less toxicity. In Paper II, we evaluated the effect of sequential chemotherapy on the QoL in the same cohort. It was measured before, during, and after treatment. There were no statistically significant differences in QoL scores between the two treatment arms and no changes in mean scores during treatment. During the last 8 weeks of treatment, a significantly larger portion of patients with radiological response reported sustained or better QoL scores than those with no radiological response. In Paper III, we investigated the effect of inter physician variation on the delineation of target volumes in gastric cancer patients treated with perioperative chemoradiotherapy (CRT). Despite the use of a delineation atlas, we found a large variation in CTV and PTV volumes. There was only a small variation in target coverage and doses to organs at risk (OARs) in the corresponding plans. In Paper IV, we compared proton therapy to modern photon radiotherapy with respect to doses to OARs in gastric cancer patients treated with perioperative CRT. Protons offered significantly lower doses to the left kidney, liver, and spinal cord, and statistically lower risks for all types and malignant secondary neoplasms compared to photons. In Paper V, we evaluated the importance of daily anatomical variations, i.e. intestinal gas filling, on the dose distribution of proton beam therapy. The effect of intestinal gas variations on the PTV/CTV coverage was large. The sparing effect of protons was, however, sustained or the dose to the OARs did not significantly exceed the dose delivered with photons. In conclusion, sequential chemotherapy and proton radiotherapy are attractive alternatives in the treatment of gastric cancer. Standardization of target definitions in CRT, e.g. by reducing the inter physician variation, is important and should also be further investigated.
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| 3. |
- Gubanski, Michael, et al.
(författare)
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Randomized phase II study of sequential docetaxel and irinotecan with 5-fluorouracil/folinic acid (leucovorin) in patients with advanced gastric cancer : the GATAC trial
- 2010
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Ingår i: Gastric Cancer. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 13:3, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- Background. The optimal chemotherapy in patients with advanced gastric carcinoma (GC) is yet to be determined. We compared sequential administration of docetaxel and irinotecan, both in combination with infused 5-fluorouracil/leucovorin (5-Fu/Lv), and randomly assigned patients to start with either of the two. Methods. Patients with previously untreated locally advanced or metastatic GC and with measurable lesions (response evaluation criteria in solid tumors; RECIST) were randomly assigned to start with docetaxel 45 m (arm T) or irinotecan 180 mg/m(2) (arm C) with bolus/44-h infusion of 5-Fu/Lv (day 1 every 2 weeks). After four courses, there was a pre-scheduled crossover to the alternative regimen for four additional courses. Results. Eighty-one patients were randomized and 78 started treatment. Complete and partial responses were seen in 31 (40%) patients after 8 weeks and in 32 (41%) after 16 weeks, with similar results in both study arms. The median overall survival (OS) was 11.5 and 10.6 months in arms T and C, respectively (P = 0.3). The two schedules were feasible and did not differ in the overall rate of severe adverse events (SAEs). Conclusion. This is the first randomized comparison of two of the newer cytostatic drugs in GC therapy. No differences favoring either arm T or arm C were found with respect to response rate, OS, or toxicity. The median OS of 11 months indicates that sequential administration of the two combinations is effective and is similar to triple combinations. Thus, comparable efficacy to platinum combinations appears to be obtained with newer, less toxic regimens when given sequentially.
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| 4. |
- Gubanski, Stanislaw, 1950, et al.
(författare)
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Polymer composition and electrical devices
- 2021
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Patent (övrigt vetenskapligt/konstnärligt)abstract
- The invention relates to a polymer composition comprising a polymer (a) and a nanoparticle filler (b), wherein the polymer composition comprises a volume percentage (vol. %) of the nanoparticle filler (b), which is Dvol vol. %, and has a center-to-center average distance, in nanometer (nm), in two dimensions (2D) and with a free radius, from one nanoparticle to its nearest nanoparticle neighbour, which is R1st nm, and wherein the polymer composition shows a dependency between said center-to-center average distance to nearest neighbour, R1st, and said volume percentage, Dvol vol. %, which is R1st=E/(Dvol+0.3)+F, wherein Dvol1≤Dvol≤Dvol2, E1≤E≤E2, F1≤F≤F2, and Dvol1 is 0.010 and Dvol2 is 4.4, E1 is 100 and E2 is 280, and F1 is 50 and F2 is 140; an electrical device, e.g. a power cable; and a process for producing an electrical device.
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| 5. |
- Mondlane, Gracinda, 1987-
(författare)
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Comparative study of Radiation Therapy of Targets in the Upper Abdomen with Photon- or Scanned Proton-beams
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recently, there has been an increase in the number of proton beam therapy (PBT) centers operating worldwide. For certain cases, proton beams have been shown to provide dosimetric and radiobiological advantages when used for cancer treatment, compared to the regular photon-beam based treatments. Under ideal circumstances, the dose given to the tissues surrounding a target can be reduced with PBT. The risk for side effects following treatment is then expected to decrease. Until present, mainly stationary targets, e.g. targets in the brain, have been treated with PBT. There is currently a growing interest to treat also target volumes in other parts of the body with PBT. However, there are sources of uncertainties, which must be more carefully considered when PBT is used, especially for PBT carried out with scanned proton beams. PBT is more sensitive to anatomical changes, e.g. organ motion or a variable gas content in the intestines, which requires that special precautions are taken prior to treating new tumour sites. In photon beam radiotherapy (RT) of moving targets, the main consequence of organ motion is the loss of sharpness of the dose gradients (dose smearing). When scanned proton beams are used, dose deformation caused by the fluctuations in the proton beam range, due to varying tissue heterogeneities (e.g., the ribs moving in and out of the beam path) and the so-called interplay effect, can be expected to impact the dose distributions in addition to the dose smearing. The dosimetric uncertainties, if not accounted for, may cause the planned and accurately calculated dose distribution to be distorted, compromising the main goal of RT of achieving the maximal local disease control while accepting certain risks for normal tissue complications.Currently there is a lack of clinical follow-up data regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumour sites in moving organs. On the other hand, the use of photon beams for this kind of cancer treatment is well-stablished. A treatment planning comparison between RT carried out with photons and with protons may provide guidelines for when PBT could be more suitable. New clinical applications of particle beams in cancer therapy can also be transferred from photon-beam treatments, for which there is a vast clinical experience. The evaluation of the different uncertainties influencing RT of different tumour sites carried out with photon- and with proton-beams, will hopefully create an understanding for the feasibility of treating cancers with scanned proton beams instead of photon beams. The comparison of two distinct RT modalities is normally performed by studying the dosimetric values obtained from the dose volume histograms (DVH). However, in dosimetric evaluations, the outcome of the treatments in terms of local disease control and healthy tissue toxicity are not estimated. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. In this thesis, different factors that should be taken into consideration in PBT, for treatments influenced by organ motion and density heterogeneities, were studied and their importance quantified.This thesis consists of three published articles (Articles I, II and III). In these reports, the dosimetric and biological evaluations of photon-beam and scanned proton-beam RT were performed and the results obtained were compared. The studies were made for two tumour sites influenced by organ motion and density changes, gastric cancer (GC) and liver metastases. For the GC cases, the impact of changes in tissue density, resulting from variable gas content (which can be observed inter-fractionally), was also studied. In this thesis, both conventional fractionations (implemented in the planning for GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. In this work, it was found that proton therapy provided the possibility to reduce the irradiations of the normal tissue located near the target volumes, compared to photon beam RT. However, the effects of density changes were found to be more pronounced in the plans for PBT. Furthermore, with proton beams, the reduction of the integral dose given to the OARs resulted in reduced risks of treatment-induced secondary malignancies.
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| 6. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases
- 2017
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Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 42, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe potential of proton therapy to improve the sparing of the healthy tissue has been demonstrated in several studies. However, even small doses delivered to the organs at risk (OAR) may induce long-term detriments after radiotherapy. In this study, we investigated the possibility to reduce the risk of radiation-induced secondary cancers with intensity modulated proton therapy (IMPT), when used for radiosurgery of liver metastases.Material and methodsTen patients, previously treated for liver metastases with photon-beam based stereotactic body radiation therapy (SBRT) were retrospectively planned for radiosurgery with IMPT. A treatment plan comparison was then performed in terms of calculated risk of radiation-induced secondary cancer. The risks were estimated using two distinct models (Dasu et al., 2005; Schneider et al., 2005, 2009). The plans were compared pairwise with a two-sided Wilcoxon signed-rank test with a significance level of 0.05.ResultsReduced risks for induction of fatal and other types of cancers were estimated for the IMPT plans (p < 0.05) with the Dasu et al. model. Using the Schneider et al. model, lower risks for carcinomainduction with IMPT were estimated for the skin, lungs, healthy part of the liver, esophagus and the remaining part of the body (p < 0.05). The risk of observing sarcomas in the bone was also reduced with IMPT (p < 0.05).ConclusionThe findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT.
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| 7. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Comparison of gastric-cancer radiotherapy performed with volumetric modulated arc therapy or single-field uniform-dose proton therapy
- 2017
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 56:6, s. 832-838
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton-beam therapy of large abdominal cancers has been questioned due to the large variations in tissue density in the abdomen. The aim of this study was to evaluate the importance of these variations for the dose distributions produced in adjuvant radiotherapy of gastric cancer (GC), implemented with photon-based volumetric modulated arc therapy (VMAT) or with proton-beam single-field uniform-dose (SFUD) method. Material and methods: Eight GC patients were included in this study. For each patient, a VMAT- and an SFUD-plan were created. The prescription dose was 45 Gy (IsoE) given in 25 fractions. The plans were prepared on the original CT studies and the doses were thereafter recalculated on two modified CT studies (one with extra water filling and the other with expanded abdominal air-cavity volumes). Results: Compared to the original VMAT plans, the SFUD plans resulted in reduced median values for the V18 of the left kidney (26%), the liver mean dose (14.8 Gy (IsoE)) and the maximum dose given to the spinal cord (26.6 Gy (IsoE)). However, the PTV coverage decreased when the SFUD plans were recalculated on CT sets with extra air- (86%) and water-filling (87%). The added water filling only led to minor dosimetric changes for the OARs, but the extra air caused significant increases of the median values of V18 for the right and left kidneys (10% and 12%, respectively) and of V10 for the liver (12%). The density changes influenced the dose distributions in the VMAT plans to a minor extent. Conclusions: SFUD was found to be superior to VMAT for the plans prepared on the original CT sets. However, SFUD was inferior to VMAT for the modified CT sets.
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| 8. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Dosimetric Comparison of Plans for Photon- or Proton-Beam Based Radiosurgery of Liver Metastases
- 2016
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Ingår i: International Journal of Particle Therapy. - 2331-5180. ; 3:2, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Radiosurgery treatment of liver metastases with photon beams has been an established method for more than a decade. One method commonly used is the stereotactic body radiation therapy (SBRT) technique. The aim of this study was to investigate the potential sparing of the organs at risk (OARs) that the use of intensity-modulated proton therapy (IMPT), instead of SBRT, could enable.Patients and Methods: A comparative treatment-planning study of photon-beam and proton-beam based liver-cancer radiosurgery was performed. Ten patients diagnosed with liver metastasis and previously treated with SBRT at the Karolinska University Hospital were included in the study. New IMPT plans were prepared for all patients, while the original plans were set as reference plans. The IMPT planning was performed with the objective of achieving the same target dose coverage as with the SBRT plans. Pairwise dosimetric comparisons of the treatment plans were then performed for the OARs. A 2-sided Wilcoxon signed-rank test with significance level of 5% was carried out.Results: Improved sparing of the OARs was made possible with the IMPT plans. There was a significant decrease of the mean doses delivered to the following risk organs: the nontargeted part of the liver (P = .002), the esophagus (P = .002), the right kidney (P = .008), the spinal cord (P = .004), and the lungs (P = .002). The volume of the liver receiving less than 15 Gy was significantly increased with the IMPT plans (P = .004).Conclusion: The IMPT-based radiosurgery plans provided similar target coverage and significant dose reductions for the OARs compared with the photon-beam based SBRT plans. Further studies including detailed information about varying tissue heterogeneities in the beam path, due to organ motion, are required to evaluate more accurately whether IMPT is preferable for the radiosurgical treatment of liver metastases.
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| 9. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Estimation of Risk of Normal-tissue Toxicity Following Gastric Cancer Radiotherapy with Photon- or Scanned Proton-beams
- 2018
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:5, s. 2619-2625
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Gastric cancer (GC) radiotherapy involves irradiation of large tumour volumes located in the proximities of critical structures. The advantageous dose distributions produced by scanned-proton beams could reduce the irradiated volumes of the organs at risk (OARs). However, treatment-induced side-effects may still appear. The aim of this study was to estimate the normal tissue complication probability (NTCP) following proton therapy of GC, compared to photon radiotherapy. Patients and Methods: Eight GC patients, previously treated with volumetric-modulated arc therapy (VMAT), were retrospectively planned with scanned proton beams carried out with the single-field uniform-dose (SFUD) method. A beam-specific planning target volume was used for spot positioning and a clinical target volume (CTV) based robust optimisation was performed considering setup- and range-uncertainties. The dosimetric and NTCP values obtained with the VMAT and SFUD plans were compared. Results: With SFUD, lower or similar dose-volume values were obtained for OARs, compared to VMAT. NTCP values of 0% were determined with the VMAT and SFUD plans for all OARs (p>0.05), except for the left kidney (p<0.05), for which lower toxicity was estimated with SFUD. Conclusion: The NTCP reduction, determined for the left kidney with SFUD, can be of clinical relevance for preserving renal function after radiotherapy of GC.
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| 10. |
- Mondlane, Gracinda, 1987-, et al.
(författare)
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Estimation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
- 2018
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Ingår i: Radiation Oncology. - : Springer Science and Business Media LLC. - 1748-717X .- 1748-717X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radiotherapy of liver metastases is commonly being performed with photon-beam based stereotactic body radiation therapy (SBRT). The high risk for radiation-induced liver disease (RILD) is a limiting factor in these treatments. The use of proton-beam based SBRT could potentially improve the sparing of the healthy part of the liver. The aim of this study was to use estimations of normal tissue complication probability (NTCP) to identify liver-metastases patients that could benefit from being treated with intensity-modulated proton therapy (IMPT), based on the reduction of the risk for RILD.Methods: Ten liver metastases patients, previously treated with photon-beam based SBRT, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties), combined with a PTV-based conventional optimisation, was performed. A robustness criterion was defined for the CTV (V95% > 98% for at least 10 of the 12 simulated scenarios). The NTCP was estimated for different endpoints using the Lyman-Kutcher-Burman model. The ΔNTCP (NTCPIMPT − NTCPSBRT) for RILD was registered for each patient. The patients for which the NTCP (RILD) < 5% were also identified. A generic relative biological effectiveness of 1.1 was assumed for the proton beams.Results: For all patients, the objectives set for the PTV and the robustness criterion set for the CTV were fulfilled with the IMPT plans. An improved sparing of the healthy part of the liver, right kidney, lungs, spinal cord and the skin was achieved with the IMPT plans, compared to the SBRT plans. Mean liver doses larger than the threshold value of 32 Gy led to NTCP values for RILD exceeding 5% (7 patients with SBRT and 3 patients with the IMPT plans). ΔNTCP values (RILD) ranging between − 98% and − 17% (7 patients) and between 0 and 2% (3 patients), were calculated.Conclusions: In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, were identified. The clinical implementation of such a model-based approach to select liver metastases patients to proton therapy needs to be made with caution while considering the uncertainties involved in the NTCP estimations.
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