| 1. |
- Caspers, Irene A., et al.
(författare)
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The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer : Results from the randomized CRITICS trial
- 2024
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Ingår i: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 129:4, s. 734-744
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectiveThis study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).MethodsA post-hoc analysis of the CRITICS-trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy-related toxicity and compliance were compared.ResultsData from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor-positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.ConclusionsPositive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.
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| 2. |
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| 3. |
- Ekerman, Petrus, 1697-1783
(författare)
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Dissertationis gradualis, de usu auctorum classicorum in stilo Latino perpoliendo, pars posterior, quam, ex consensu ampl. facult. philosoph. in regia academia Upsaliensi, præside ... mag. Petro Ekerman ... publico defert examini alumnus regius, Samuel Petrus Lind, Calmariensis, in aud. Carol. maj. ad d. VII. Martii, anni MDCCLXIV. H. A. M. C.
- 1764
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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| 4. |
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| 5. |
- Goldman, Ulla Blom, et al.
(författare)
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Long-term functional and radiological pulmonary changes after radiation therapy for breast cancer
- 2014
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:10, s. 1373-1379
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Tidskriftsartikel (refereegranskat)abstract
- Background. We assessed late functional and radiological pulmonary changes in breast cancer patients after a median of 11 years following radiotherapy (RT). Material and methods. Seventy women who received adjuvant loco-regional RT for breast cancer during November 1994-May 1998 accepted to participate in this follow-up study. Pulmonary function tests (PFTs) (n = 56) were compared to pre-RT examinations and diagnostic computer tomography (CT) of the lungs (n = 70) were performed and compared to four months post-RT examinations. Result. The median-matched vital capacity (VC), forced expiratory volume in one second (FEV1), and total lung capacity (TLC) were reduced 15%, 9%, and 7%, respectively, at the long-term follow-up (p < 0.001). We could not, however, detect a correlation between ipsilateral V-20 and VC-changes. Diffusion capacity (DLCO) appeared to improve compared with the pre-RT baseline level probably due to transient chemotherapy-induced toxicity. The median-matched percentage of the predicted DLCO 11 years after RT was, however, only 86%, indicating a chronic therapy-induced reduction also of this metric. According to the Arriagada classification, ipsilateral V-20 and long-term CT-changes showed a significant correlation (r(s) : 0. 57; p<0.001) in a small subset of the women. Conclusion. A chronic clinically significant reduction of PFTs compared to pre-RT values and CT-changes four months after RT were still detectable after a median follow-up of 11 years. There was a statistical correlation between V-20 and abnormalities on CT but no statistical correlation between V-20 and VC-changes.
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| 6. |
- 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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| 7. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study
- 2010
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 95:3, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer. Material and methods: Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000 mg/m(2) bid d1-14 + oxaliplatin 130 mg/m(2) d1, q3w) were followed by XELOX-RT (radiotherapy (50.4 Gy), combined with capecitabine 750-675 mg/m(2) bid every radiotherapy day and oxaliplatin 40-30 mg/m(2) once weekly). Primary end-points were tolerance (phase I) and objective response (phase II). Results: The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30 mg/m(2) and 675 mg/m(2), respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting. Conclusions: XELOX-RT (30 mg/m(2) oxaliplatin/675 mg/m(2) capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer. (C) 2010 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 95 (2010) 292-297
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| 8. |
- Hultman, Bo, et al.
(författare)
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Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
- 2013
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:4, s. 824-830
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.Material and methodsEighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.ResultsAt the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.DiscussionNeoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.
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| 9. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 10. |
- Kumagai, K., et al.
(författare)
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Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer : A direct and adjusted indirect comparison meta-analysis
- 2015
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:3, s. 282-294
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Forskningsöversikt (refereegranskat)abstract
- Several phase I/II studies of chemoradiotherapy for gastric cancer have reported promising results, but the significance of preoperative radiotherapy in addition to chemotherapy has not been proven. In this study, a systematic literature search was performed to capture survival and postoperative morbidity and mortality data in randomised clinical studies comparing preoperative (chemo)radiotherapy or chemotherapy versus surgery alone, or preoperative chemoradiotherapy versus chemotherapy for gastric and/or gastro-oesophageal junction (GOJ) cancer. Hazard ratios (HRs) for overall mortality were extracted from the original studies, individual patient data provided from the principal investigators of eligible studies or the earlier published meta-analysis. The incidences of postoperative morbidities and mortalities were also analysed. In total 18 studies were eligible and data were available from 14 of these. The meta-analysis on overall survival yielded HRs of 0.75 (95% CI 0.65-0.86, P < 0.001) for preoperative (chemo)radiotherapy and 0.83 (95% CI 0.67-1.01, P = 0.065) for preoperative chemotherapy when compared to surgery alone. Direct comparison between preoperative chemoradiotherapy and chemotherapy resulted in an HR of 0.71 (95% CI 0.45-1.12, P = 0.146). Combination of direct and adjusted indirect comparisons yielded an HR of 0.86 (95% CI 0.69-1.07, P = 0.171). No statistically significant differences were seen in the risk for postoperative morbidity or mortality between preoperative treatments and surgery alone, or preoperative (chemo)radiotherapy and chemotherapy. Preoperative (chemo)radiotherapy for gastric and GOJ cancer showed significant survival benefit over surgery alone. In comparisons between preoperative chemotherapy and (chemo)radiotherapy, there is a trend towards improved survival when adding radiotherapy, without increased postoperative morbidity or mortality.
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| 11. |
- Lind, Pehr
(författare)
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Short-term pulmonary side-effects following radiation therapy in breast cancer
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this dissertation was to study the short-term pulmonary side-effects following adjuvant radiotherapy for breast cancer in terms of clinical pulmonary complications, loss of pulmonary function and radiological abnormalities, and the association to irradiated lung volume and dose. Furthermore, we wanted to estimate the influence of covariates, e.g. age, sequential chemotherapy, concurrent tamoxifen treatment, smoking habits, pretreatment functional level and premorbidity, on the early radiation-induced response of lung. Severe pulmonary complications, i.e. managed with corticosteroids, were diagnosed among 10 % of the patients who were treated with loco-regional radiotherapy including the internal mammary nodes (IMN). Age and reduced pre-treatment functional level were independently associated with pulmonary complications. The mean irradiated ipsilateral lung volume receiving more than 20 Gy was larger among the patients diagnosed with both clinical and radiological pneumonitis than in patients experiencing neither of the two side-effects. Severe pulmonary complications were very rare (<1%) among patients who were treated with local radiotherapy. A mean reduction in pulmonary function, i.e. vital capacity, was observed among patients treated with loco-regional radiotherapy including the IMN compared both to patients in whom the IMN were excluded from the target volume and to patients who were treated with local radiotherapy. The mean reduction in vital capacity among patients who were diagnosed with severe pulmonary complications was clinically significant and equivalent to the loss of 3/4 of a lung lobe. Furthermore, postirradiatory reduction in vital capacity was independently associated to only irradiated lung volume. The patients who were pre-treated with chemotherapy had lower mean diffusion capacity than expected, i.e. 78 % of predicted, at baseline and this was probably caused by drug-induced toxicity. Radiological abnormalities were most often seen among patients in whom large lung volumes had been included within the fields of irradiation. Postirradiatory radiological abnormalities were more frequently seen in older patients and were associated with both pulmonary complications and loss of vital capacity. Computerised tomography was found to be a more sensitive technique for diagnosing postirradiatory radiological abnormalities and was more strongly associated to functional end-points than chest radiography. In conclusion, loco-regional radiotherapy in breast cancer is associated with clinically significant short-term pulmonary side-effects. The results of this work also suggest that a more individualised treatment planning aimed at reducing the irradiated lung volume receiving more than 20 Gy may reduce the incidence of pulmonary side-effects in this group of patients.
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| 12. |
- 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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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
- 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. ; 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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| 17. |
- Mondlane, Gracinda, et al.
(författare)
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Evaluation of the risk for radiation-induced liver disease following photon- or proton-beam radiosurgery of liver metastases
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Radiotherapy of liver metastases is being performed with photon-beam stereotactic body radiation therapy (SBRT). However, the high risk for radiation-induced liver disease (RILD) is the treatment limiting factor. The use of proton beams in these treatments could improve the sparing of the healthy part of the liver. The aim of this study was to evaluate the use of 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 radiosurgery, were retrospectively planned with IMPT. A CTV-based robust optimisation (accounting for setup and range uncertainties) combined with 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. Mean liver doses larger than the threshold value of 32 Gy led to values of NTCP for RILD exceeding 5 % (7 patients for SBRT and 3 patients for IMPT). ΔNTCP values (RILD) ranging between -98% and -17 % (7 patients) and between 0 % and 2 % (3 patients) were estimated. Conclusions: In this study, liver metastases patients that could benefit from being treated with IMPT, based on the NTCP reductions, could be identified. The clinical implementation of such model-based approach to select liver metastases patients to proton therapy needs to be made with caution and considering the uncertainties involved in the NTCP estimations.
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| 18. |
- Nearchou, Andreas, et al.
(författare)
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Acquired Hypothyroidism as a Predictive Marker of Outcome in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors : A Literature-Based Meta-Analysis
- 2015
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Ingår i: Clinical Genitourinary Cancer. - : Elsevier BV. - 1558-7673 .- 1938-0682. ; 13:4, s. 280-286
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Forskningsöversikt (refereegranskat)abstract
- Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution.
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| 19. |
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| 20. |
- Neoptolemos, John P., et al.
(författare)
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Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4) : a multicentre, open-label, randomised, phase 3 trial
- 2017
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10073, s. 1011-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.Methods: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1: 1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.Findings: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28.0 months (95% CI 23.5-31.5) compared with 25.5 months (22.7-27.9) in the gemcitabine group (hazard ratio 0.82 [95% CI 0.68-0.98], p=0.032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group.Interpretation: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.
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| 21. |
- Valachis, Antonis, et al.
(författare)
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Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer : A Systematic Review and Meta-Analysis
- 2013
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 18:4, s. 353-361
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Forskningsöversikt (refereegranskat)abstract
- Background. The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer. Materials and Methods. We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70-1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio[OR], 0.94; 95% CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%. Conclusion. Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.
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| 22. |
- Valachis, Antonis, et al.
(författare)
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Cardiac toxicity in breast cancer patients treated with dual HER2 blockade
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:9, s. 2245-2252
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Tidskriftsartikel (refereegranskat)abstract
- Although dual HER2 blockade shows promising results in patients with HER2-positive breast cancer it is unclear whether this treatment strategy increases the risk for cardiac adverse events. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. We searched Medline, the Cochrane library, as well as the electronic abstract databases of the major international congresses' proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) therapy in breast cancer. The trials were considered eligible if the only systematic difference between the study arms was the type of anti-HER2 therapy used. Study outcomes were the congestive heart failure (CHF) grade 3 and left ventricular ejection fraction (LVEF) decline <50% or more than 10% from baseline. Six trials were considered eligible. Overall incidence results for CHF in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 0.88% (95% CI: 0.47-1.64%) and 1.49% (95% CI: 0.98-2.23%). The incidence of LVEF decline was 3.1% (95% CI: 2.2-4.4%) and 2.9% (95% CI: 2.1-4.1%), respectively. The OR of CHF between anti-HER2 combination and monotherapy was 0.58 (95% CI: 0.26-1.27, p-value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53-1.48, p-value= 0.64). This meta-analysis provides evidence supporting comparable cardiac toxicity between anti-HER2 combination therapy and anti-HER2 monotherapy. What's new? Breast cancers caused by HER2 overexpression generally have poor prognosis. Drugs targeting the HER2 receptor can thwart the cancer, but also increase the risk of heart problems. New treatments are coming along which combine two anti-HER2 agents for an even greater anticancer effect, but will these dual therapies cause worse cardiac effects? In this report, the authors collected data from trials comparing dual anti-HER2 therapy with anti-HER2 monotherapy, and specifically looked at risk of cardiac side effects. They conclude that doubling up on anti-HER2 drugs did not increase the cardiac toxicity compared with the use of anti-HER2 drugs individually.
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| 23. |
- Valachis, Antonis, et al.
(författare)
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Lapatinib, trastuzumab or the combination added to preoperative chemotherapy for breast cancer : a meta-analysis of randomized evidence
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 135:3, s. 655-662
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Forskningsöversikt (refereegranskat)abstract
- We compared the efficacy and safety of the addition of lapatinib versus trastuzumab or their combination to neoadjuvant chemotherapy in HER2-positive breast cancer. Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, and toxicity. Pooled risk ratios (RR) were estimated for each endpoint with fixed or random effects models, depending on between studies heterogeneity. Six trials were identified with 1,494 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm versus lapatinib plus chemotherapy (RR 1.25, 95 % confidence interval [CI] 1.08-1.43; p = 0.003) (6 trials; 1,494 patients). Probability to pCR was significantly higher in the group receiving lapatinib and trastuzumab than in the group with trastuzumab alone (RR 1.39, 95 % CI 1.20-1.63; p < 0.001) (4 trials; 779 patients). Grade III-IV diarrhea and dermatologic toxicities were statistically more frequent in patients receiving lapatinib. No differences were observed regarding cardiac adverse events among patients receiving trastuzumab, lapatinib, or their combination. These data supports the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer in the neoadjuvant setting. The direct comparison of trastuzumab and lapatinib showed that lapatinib is inferior in terms of pCR and associated with a higher risk for toxicity.
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| 24. |
- Valachis, Antonis, et al.
(författare)
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Surgical management of breast cancer in BRCA-mutation carriers : a systematic review and meta-analysis
- 2014
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 144:3, s. 443-455
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Forskningsöversikt (refereegranskat)abstract
- This meta-analysis investigates the oncological safety of breast-conserving therapy BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral breast recurrence (IBR) or CBC and grades these factors based on the level of evidence. A PubMed search was conducted through April 2013 to identify studies that described the risk for IBR and CBC after BCT in BRCA-mutation carriers versus non-carriers as well as studies that investigated risk factors for IBR and CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when sufficient studies were available. Ten studies investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR 1.45, 95 % CI 0.98-2.14). However, a significant higher risk for IBR in BRCA-mutation carriers was observed in studies with a median follow-up a parts per thousand yen7 years (RR 1.51, 95 % CI 1.15-1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95 % CI 2.50-5.08). Use of adjuvant chemotherapy and oophorectomy were associated with a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use of tamoxifen, and age at first breast cancer. Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk for IBR. However, several aspects should be taken into account before the final decision-making.
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| 25. |
- von Dobeln, Gabriella Alexandersson, et al.
(författare)
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Pulmonary function and cardiac stress test after multimodality treatment of esophageal cancer
- 2016
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Ingår i: Practical Radiation Oncology. - : Elsevier BV. - 1879-8500 .- 1879-8519. ; 6:3, s. E53-E59
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Curative treatment of esophageal cancer is accompanied by frequent and sometimes severe side effects. However, prospectively collected data on side effects are scarce. The aim of this study was to evaluate if pulmonary function and exercise capacity were affected in the acute setting after neoadjuvant treatment and if there were long-lasting effects after neoadjuvant treatment and surgery. We also aimed to investigate whether the addition of radiation therapy to chemotherapy would aggravate side effects. Methods and materials: A cohort of 97 patients enrolled in the randomized NeoRes trial was used for the present analysis. The patients had been randomized to receive 3 cycles of cisplatin and fluorouracil with or without concurrent radiation therapy to 40 Gy. A cardiac stress test on a stationary bicycle and a spirometry were performed before and after neoadjuvant treatment and 1 to 2 years later after surgery provided that the cancer had not recurred. Results: We found impairment in pulmonary function measured as vital capacity and forced expiratory volume in 1 second and a decrease in exercise capacity after neoadjuvant treatment and 1 to 2 years later after surgery. We did not detect any differences between patients treated with chemoradiation therapy and those treated with chemotherapy alone. Conclusions: Multimodality treatment of esophageal cancer caused short-term and lasting impairments in pulmonary function and exercise capacity. The reductions were not aggravated by the addition of radiation therapy to neoadjuvant chemotherapy.
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