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  • 1.
    Adell, Gunnar
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Zhang, Hong
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Jansson, Agneta
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer2001In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 50, no 3, p. 659-663Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival.

    PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.

    MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990.

    RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.

    CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.

  • 2.
    Daşu, Alexandru
    et al.
    Umeå University.
    Denekamp, Juliana
    Umeå University.
    Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction1999In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 43, no 5, p. 1083-1094Article in journal (Refereed)
    Abstract [en]

    PURPOSE: A dose "window of opportunity" has been identified in an earlier modeling study (1) if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays.

    METHODS AND MATERIALS: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction.

    RESULTS: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy. It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells.

    CONCLUSIONS: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy.

  • 3.
    Daşu, Alexandru
    et al.
    Umeå University.
    Toma-Daşu, Iuliana
    Stockholm University and Karolinska Institutet.
    In response to Dr. Karger et al.2008In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 70, no 5, p. 1614-1615Article in journal (Refereed)
    Abstract [en]

    n/a

  • 4.
    Daşu, Alexandru
    et al.
    Norrland University Hospital, Umeå.
    Toma-Daşu, Iuliana
    Stockholm University and Karolinska Institutet.
    What is the clinically relevant relative biologic effectiveness? A warning for fractionated treatments with high linear energy transfer radiation2008In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 70, no 3, p. 867-874Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To study the clinically relevant relative biologic effectiveness (RBE) of fractionated treatments with high linear energy transfer (LET) radiation and to identify the important factors that might influence the transfer of tolerance and curative levels from low LET radiation. These are important questions in the light of the growing interest for the therapeutic use of radiation with higher LET than electrons or photons.

    METHODS AND MATERIALS: The RBE of various fractionated schedules was analyzed with theoretical models for radiation effect, and the resulting predictions were compared with the published clinical and experimental data regarding fractionated irradiation with high LET radiation.

    RESULTS: The clinically relevant RBE increased for greater doses per fraction, in contrast to the predictions from single-dose experiments. Furthermore, the RBE for late-reacting tissues appeared to modify more quickly than that for early-reacting tissues. These aspects have quite important clinical implications, because the increased biologic effectiveness reported for this type of radiation would otherwise support the use of hypofractionation. Thus, the differential between acute and late-reacting tissues could put the late-reacting normal tissues at more risk from high LET irradiation; however, at the same time, it could increase the therapeutic window for slow-growing tumors.

    CONCLUSIONS: The modification of the RBE with the dose per fraction must be carefully taken into consideration when devising fractionated treatments with high LET radiation. Neglecting to do so might result in an avalanche of complications that could obscure the potential advantages of the therapeutic use of this type of radiation.

  • 5.
    Denekamp, Juliana
    et al.
    Umeå University.
    Daşu, Alexandru
    Umeå University.
    Waites, Anthony
    Umeå University.
    Littbrand, Bo
    Umeå University.
    Hyperfractionation as an effective way of overcoming radioresistance1998In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 42, no 4, p. 705-709Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To model the influence of hypoxic radioprotection in fractionated treatments over a range of fraction sizes. To determine whether there is a "therapeutic window" of dose per fraction where hypoxic radioresistance could be reduced, and if so, where it occurs in different cell lines.

    MATERIALS AND METHODS: A mathematical model has been used to simulate the response of cells to low doses of radiation, in the region of clinical interest. We have used the inducible repair variant of the linear quadratic (LQ) equation, with a hypersensitive region (alphaS) at low doses that gradually transforms to the accepted "resistance" in the shoulder region (alphaR). It contains two new parameters, the ratio alphaS/alphaR, and D(C). We have accepted that the "induction dose" D(C) is modified by anoxia to the same extent as the other parameters. We have initially modeled using theoretical parameters and then checked the conclusions with 14 sets of published experimental data for cell lines investigated for inducible repair.

    RESULTS: We have computed the clinical hypoxic protection (OER') as a function of dose per fraction in simulations of clinical fractionated schedules. We have identified a therapeutic window in terms of dose per fraction at about 0.5 Gy, where the OER' is minimized, regardless of the precise cell survival curve parameters. The minimum OER' varies from one cell line to another, falling to about 1.0 if alphaS/alphaR = 6-10 and even far below 1.0 if alphaS/alphaR > or = 20.

    DISCUSSION: Hyperfractionation using 0.5 Gy fractions may therefore be more effective than oxygen mimetic chemical sensitizers, since it could even make some tumor cells more sensitive than oxic normal tissues. The tumor lines that benefit most from this type of sensitization are those with the highest intrinsic oxic radioresistance, i.e. those with high SF2 values.

  • 6.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy2004In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 60, no 1, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.

  • 7.
    Kotti, Angeliki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist (Knutsen), Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients2014In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 88, no 5, p. 1196-1202Article in journal (Refereed)
    Abstract [en]

    Purpose

    The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.

    Methods and Materials

    The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.

    Results

    Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).

    Conclusions

    SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  • 8. Pachkoria, Ketevan
    et al.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jarlsfelt, Ingvar
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy2005In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 63, no 3, p. 739-744Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors. © 2005 Elsevier Inc.

  • 9.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy2006In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, no 4, p. 1143-1148Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers.

    Methods and Materials: p73 was immunohistochemically examined on biopsies (unirradiated, n = 102), distant (from the large bowel, n = 82), and adjacent (adjacent to primary tumor, n = 89) normal mucosa samples, primary tumors (n = 131), and lymph node metastasis (n = 32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT.

    Results: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p ≤ 0.0001). Nuclear (p = 0.02) and cytoplasmic (p = 0.003) p73 was higher in irradiated distant mucosa samples than in unirradiated ones, and nuclear p73 tended to be increased in irradiated primary tumors compared with unirradiated ones (p = 0.06). p73 was positively related to cyclooxygenase-2 expression in irradiated tumors (p = 0.03). p73-negative tumors tended to have a lower local recurrence after RT compared with unirradiated cases (p = 0.06).

    Conclusions: Normal epithelial cells seem more sensitive to RT than tumor cells regarding p73 expression. Patients with p73-negative rectal tumors may have a lower risk of local recurrence after RT.

  • 10.
    Söderlund Leifler, Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    ¨, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Skoog, Lambert
    Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
    Rutqvist, Lars Erik
    Department of Medicine/Huddinge, Karolinska Institute, Stockholm,Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Intact Mre11/Rad50/Nbs1 complex predicts good response to radiotherapy in early breast cancer2007In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 68, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Purpose: Post-operative radiotherapy is offered to a majority of breast cancer patients, since it significantly reduces the risk of local recurrence. However, some patients still develop recurrences. Owing to their vital roles in the repair of radiation-induced double-strand breaks, the Mre11/Rad50/Nbs1 (MRN) complex and the ATM protein might be implicated in tumour cell resistance to radiotherapy. The aim of this study was to investigate the expression and predictive role of these DNA repair proteins for the outcome of radiotherapy in breast cancer patients.

    Patients and Methods: The protein expression of ATM and the proteins in the MRN complex were investigated using immunohistochemistry in tumours from 224 women with early breast cancer, who were randomised to receive post-operative radiotherapy or adjuvant chemotherapy (CMF).

    Results: Compared to normal breast tissue, the staining intensity of Mre11, Rad50, Nbs1 and ATM was reduced in a majority of the tumours. Weak expression of the MRN complex was correlated to high histological grade and ER negativity (p=0.01 and p=0.0001). Radiotherapy significantly reduced the risk of local recurrence as compared to chemotherapy (p=0.04). The greatest benefit of radiotherapy was seen in patients with moderate/strong expression of the MRN complex (RR=0.27, 95% C.I. 0.098-0.72, p=0.009), whereas patients with negative/weak MRN had no benefit of radiotherapy compared to CMF. These results suggest that an intact MRN complex is important for the tumour cell eradicating effect of radiotherapy.

  • 11.
    Toma-Dasu, Iuliana
    et al.
    Stockholm University and Karolinska Institutet.
    Uhrdin, Johan
    RaySearch Laboratories AB.
    Lazzeroni, Marta
    Karolinska Institutet.
    Carvalho, Sara
    Maastricht University Medical Center, Maastricht, The Netherlands.
    van Elmpt, Wouter
    Maastricht University Medical Center, Maastricht, The Netherlands.
    Lambin, Philippe
    Maastricht University Medical Center, Maastricht, The Netherlands.
    Dasu, Alexandru
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Evaluating tumor response of non-small cell lung cancer patients with 18F-fludeoxyglucose positron emission tomography: potential for treatment individualization2015In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 91, no 2, p. 376-384Article in journal (Refereed)
    Abstract [en]

    Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive 18F-fludeoxyglucose positron emission tomography (FDG-PET) scans.

    Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, αeff, was determined at the voxel level. Correlations were sought between the average αeff or the fraction of negative αeff values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs).

    Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average αeff of 0.003 Gy-1 in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative αeff as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method.

    Conclusions: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative αeff could also be correlated with poor response. The proposed method, therefore, has potential to identify candidates for more aggressive strategies to increase the rate of local control and also avoid exposing to unnecessary aggressive therapies the majority of patients responding to standard treatment.

  • 12.
    Waldenström, Ann-Charlotte
    et al.
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Caroline
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Wilderäng, Ulrica
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Dunberger, Gail
    Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Lind, Helena
    Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Alevronta, Eleftheria
    Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    al-Abany, Massoud
    Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden / Department of Hospital Physics, Karolinska University Hospital, Stockholm, Sweden.
    Tucker, Susan
    Department of Bioinformatics and Computational Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
    Åvall-Lundqvist, Elisabeth
    Department of Gynecologic Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Johansson, Karl-Axel
    Department of Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Steineck, Gunnar
    Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden / Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Relative importance of hip and sacral pain among long-term gynecological cancer survivors treated with pelvic radiotherapy and their relationships to mean absorbed doses.2012In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 84, no 2, p. 428-436Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs.

    METHODS AND MATERIALS: We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2-15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors.

    RESULTS: Of the survivors, one in three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy.

    CONCLUSIONS: Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.

  • 13.
    Wallin, Åsa R.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy2006In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, no 2, p. 452-458Article in journal (Refereed)
    Abstract [en]

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients.

    Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT.

    Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes’ stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01).

    Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  • 14.
    Zeidan, Youssef H.
    et al.
    Amer Univ Beirut, Lebanon.
    Habib, Joyce G.
    Fouad Khoury and Makassed Gen Hosp, Lebanon; Univ Libre Bruxelles, Belgium.
    Ameye, Lieveke
    Universite´Libre de Bruxelles, Brussels, Belgium.
    Paesmans, Marianne
    Universite´Libre de Bruxelles, Brussels, Belgium.
    de Azambuja, Evandro
    Univ Libre Bruxelles, Belgium.
    Gelber, Richard D.
    Harvard Med Sch, MA USA; Frontier Sci and Technol Res Fdn Inc, MA USA.
    Campbell, Ian
    Univ Auckland, New Zealand.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Gutierez, Jorge
    Clin Los Condes, Chile.
    Anderson, Michael
    Copenhagen Univ Hosp, Denmark; Danish Breast Canc Cooperat Grp, Denmark.
    Lluch, Ana
    Univ Valencia, Spain.
    Gnant, Michael
    Med Univ Vienna, Austria; Austrian Breast and Colorectal Canc Study Grp, Austria.
    Goldhirsch, Aron
    European Inst Oncol, Italy; Int Breast Canc Study Grp, Switzerland.
    Di Leo, Angelo
    Hosp Prato, Italy.
    Joseph, David J.
    Univ Western Australia, Australia; Edith Cowan Univ, Australia; Breast Canc Trials Australia and New Zealand, Australia.
    Crown, John
    St Vincents Univ Hosp, Ireland.
    Piccart-Gebhart, Martine
    Univ Libre Bruxelles, Belgium.
    Francis, Prudence A.
    Int Breast Canc Study Grp, Switzerland; Peter MacCallum Canc Ctr, Australia; Univ Melbourne, Australia; Univ Newcastle, Australia.
    Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 101, no 2, p. 316-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To analyze the impact of postmastectomy radiation therapy (PMRT) for patients with T1-T2 tumors and 1 to 3 positive lymph nodes enrolled on the Breast International Group (BIG) 02-98 trial. Methods and Materials: The BIG 02-98 trial randomized patients to receive adjuvant anthracycline with or without taxane chemotherapy. Delivery of PMRT was nonrandomized and performed according to institutional preferences. The present analysis was performed on participants with T1-T2 breast cancer and 1 to 3 positive lymph nodes who had undergone mastectomy and axillary nodal dissection. The primary objective of the present study was to examine the effect of PMRT on risk of locoregional recurrence (LRR), breast cancer-specific survival, and overall survival. Results: We identified 684 patients who met the inclusion criteria and were included in the analysis, of whom 337 (49%) had received PMRT. At 10 years, LRR risk was 2.5% in the PMRT group and 6.5% in the no-PMRT group (hazard ratio 0.29, 95% confidence interval 0.12-0.73; P=.005). Lower LRR after PMRT was noted for patients randomized to receive adjuvant chemotherapy with no taxane (10-year LRR: 3.4% vs 9.1%; P=.02). No significant differences in breast cancer-specific survival (84.3% vs 83.9%) or overall survival (81.7% vs 78.3%) were observed according to receipt of PMRT. Conclusion: Our analysis of the BIG02-98 trial shows excellent outcomes in women with T1-T2 tumors and 1 to 3 positive lymph nodes found in axillary dissection. Although PMRT improved LRR in this cohort, the number of events remained low at 10 years. In all groups, 10-year rates of LRR were relatively low compared with historical studies. As such, the use of PMRT in women with 1 to 3 positive nodes should be tailored to individual patient risks. (C) 2018 Elsevier Inc. All rights reserved.

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