| 1. |
- Daşu, Alexandru, et al.
(författare)
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Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction
- 1999
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 43:5, s. 1083-1094
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
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| 3. |
- Denekamp, Juliana, et al.
(författare)
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Hyperfractionation as an effective way of overcoming radioresistance
- 1998
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 42:4, s. 705-709
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Rojas, Ana Maria, et al.
(författare)
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Carbogen and nicotinamide as radiosensitisers in a murine mammary carcinoma using conventional and accelerated radiotherapy
- 1996
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016 .- 1879-355X. ; 34:2, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare the radiosensitivity of mouse tumors treated in air with conventional and accelerated radiotherapy with that of tumors treated in carbogen alone or carbogen combined with nicotinamide. METHODS AND MATERIALS: CaNT mammary tumors were irradiated with either 30 x-ray fractions in 6 weeks or 40 fractions in 26 days in air, carbogen alone, or carbogen combined with 120 mg/kg of nicotinamide (NAM), the latter given intraperitonealy 30 min before each fraction. The response to treatment was assessed using local control, weight loss, and metastasis-free survival. RESULTS: Both carbogen and carbogen plus nicotinamide significantly increased tumor radiosensitivity; enhancement ratios (ERs) in the 6-week regimen were similar to those seen in the accelerated schedule. The majority of the effect was achieved by carbogen alone but the addition of NAM further enhanced tumor radiosensitization (ERs of 1.5 and 1.4 for carbogen in the conventional and accelerated schedule, respectively, were significantly lower than ERs of 1.7 and 1.6 obtained with carbogen plus nicotinamide; p < or = 0.005). Treatment protraction significantly increased radioresistance, especially when tumors were treated under air. An extra 1.5 Gy per day was required in air to counterbalance proliferation; in carbogen alone and carbogen plus nicotinamide a dose loss of 0.9 and 0.6 Gy per day was observed, respectively. Compared with treatments in air alone delivered in 6 weeks, acceleration of treatment combined with carbogen and nicotinamide gave the greatest increase in tumor radiosensitization (ER = 1.9). No toxic side effects and no detrimental changes in body weight were encountered when the sensitizers were administered 30 times (one fraction per day) or 40 times (two fractions per day). In both regimens, the incidence of metastases in mice treated with carbogen or carbogen plus nicotinamide was similar to that seen in animals treated in air. There was, however, a nonsignificant trend of a higher proportion of mice with metastasis in the accelerated schedule compared with the 6-week schedule. CONCLUSIONS: In both conventional and accelerated experimental radiotherapy, carbogen alone or combined with a small clinically relevant dose of NAM were well tolerated, achieved large and significant increases in radiosensitization, and did not affect the incidence of metastases. The sparing of damage, resulting from extending the overall treatment time, was less when the sensitizers were administered than when irradiations were performed in air. The study suggests that clinical radiotherapy regimens, which aim to reduce hypoxic and/or tumor clonogen proliferation, would benefit from the use of carbogen, especially if the gas is combined with nicotinamide and treatment acceleration.
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| 6. |
- Cheng, Chee-Wai, et al.
(författare)
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Dosimetric comparison of treatment planning systems in irradiation of breast with tangential fields
- 1997
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016. ; 38:4, s. 835-842
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The objectives of this study are: (1) to investigate the dosimetric differences of the different treatment planning systems (TPS) in breast irradiation with tangential fields, and (2) to study the effect of beam characteristics on dose distributions in tangential breast irradiation with 6 MV linear accelerators from different manufacturers. METHODS AND MATERIALS: Nine commercial and two university-based TPS are evaluated in this study. The computed tomographic scan of three representative patients, labeled as "small", "medium" and "large" based on their respective chest wall separations in the central axis plane (CAX) were used. For each patient, the tangential fields were set up in each TPS. The CAX distribution was optimized separately with lung correction, for each TPS based on the same set of optimization conditions. The isodose distributions in two other off-axis planes, one 6 cm cephalic and the other 6 cm caudal to the CAX plane were also computed. To investigate the effect of beam characteristics on dose distributions, a three-dimensional TPS was used to calculate the isodose distributions for three different linear accelerators, the Varian Clinac 6/100, the Siemens MD2 and the Philips SL/7 for the three patients. In addition, dose distributions obtained with 6 MV X-rays from two different accelerators, the Varian Clinac 6/100 and the Varian 2100C, were compared. RESULTS: For all TPS, the dose distributions in all three planes agreed qualitatively to within +/- 5% for the "small" and the "medium" patients. For the "large" patient, all TPS agreed to within +/- 4% on the CAX plane. The isodose distributions in the caudal plane differed by +/- 5% among all TPS. In the cephalic plane in which the patient separation is much larger than that in the CAX plane, six TPS correctly calculated the dose distribution showing a cold spot in the center of the breast contour. The other five TPS showed that the center of the breast received adequate dose. Isodose distributions for 6 MV X-rays from three different accelerators differed by about +/- 3% for the "small" patient and more than +/- 5% for the "large" patient. For two different 6 MV machines of the same manufacturer, the isodose distribution agreed to within +/- 2% for all three planes for the "large" patient. CONCLUSION: The differences observed among the various TPS in this study were within +/- 5% for both the "small" and the "medium" patients while doses at the hot spot exhibit a larger variation. The large discrepancy observed in the off-axis plane for the "large" patient is largely due to the inability of most TPS to incorporate the collimator angles in the dose calculation. Only six systems involved agreed to within +/- 5% for all three patients in all calculation planes. The difference in dose distributions obtained with three accelerators from different manufacturers is probably due to the difference in beam profiles. On the other hand, the 6 MV X-rays from two different models of linear accelerators from the same manufacturer have similar beam characteristics and the dose distributions are within +/- 2% of each other throughout the breast volume. In general, multi-institutional breast treatment data can be compared within a +/- 5% accuracy.
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| 7. |
- Gustavsson, Anita, et al.
(författare)
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No serious late cardiac effects after adjuvant radiotherapy following mastectomy in premenopausal women with early breast cancer
- 1999
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016. ; 43:4, s. 745-754
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess cardiac mortality, coronary artery disease, myocardial dysfunction, and valvular heart disease in women younger than 65 years of age, at least 10 years after adjuvant radiotherapy following mastectomy in early breast cancer. METHODS AND MATERIALS: Ninety women (45-64 years old) with Stage II breast cancer without relapse, included in the South Sweden Breast Cancer Trial (premenopausal arm), with or without adjuvant postoperative radiotherapy +/- cyclophosphamide were examined with myocardial scintigraphy and echocardiography/Doppler, 10-17 years after radiotherapy. Thirty-four patients had been irradiated for left-sided tumors, 33 for right-sided tumors, and 23 patients had not been treated with radiotherapy. The radiotherapy (conventional roentgen, electron beams, and high-energy photon beams combined, in each patient) included the chest wall and the regional lymph nodes, with a specified target dose of 38-48 Gy, administered in daily fractions of 1.9-2.4 Gy, 5 days/week. RESULTS: No cardiac deaths were found among the original 275 patients randomized to adjuvant therapy. In the 90 patients examined, abnormal findings were recorded for ECG (14 patients), exercise test (5 patients), myocardial scintigraphy (6 patients), thickening of valve cusps (14 patients), and mild valvular regurgitation (20 patients). All patients had normal systolic function. Diastolic dysfunction was observed in 6 patients (abnormal relaxation in 4 patients and restrictive filling abnormality in 2 patients). Although no significant differences were found between the 3 study groups, there was a tendency to more abnormal findings after radiotherapy. CONCLUSION: Women younger than 50 years of age at the time of adjuvant radiotherapy following mastectomy in early breast cancer, had no serious cardiac sequelae 13 years (median) later, despite partly old-fashioned radiation techniques.
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| 8. |
- Knöös, Tommy, et al.
(författare)
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Volumetric and dosimetric evaluation of radiation treatment plans: radiation conformity index
- 1998
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - 0360-3016. ; 42:5, s. 1169-1176
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The use of conformal radiation therapy has grown substantially during the last years since three-dimensional (3D) treatment planning systems with beams-eye-view planning has become commercially available. We studied the degree of conformity reached in clinical routines for some common diagnoses treated at our department by calculating a radiation conformity index (RCI). METHODS AND MATERIALS: The radiation conformity index, determined as the ratio between the target volume (PTV) and the irradiated volume, has been evaluated for 57 patients treated with 3D treatment plans. RESULTS AND CONCLUSION: The RCI was found to vary from 0.3 to 0.6 (average 0.4), a surprisingly low figure. The higher RCI is typical for pelvic treatments (e.g., prostate) and stereotactic treatments. The lower RCI is found for extended tumors, such as mammary carcinomas where the adjacent nodes are included. The latter is also valid for most lung cancer patients studied. The RCI gives a consistent method for quantifying the degree of conformity based on isodose surfaces and volumes. Care during interpretation of RCI must always be taken, since small changes in the minimum dose can dramatically change the treated volume.
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| 9. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The immunohistochemical expression of DNA-PKCS and Ku (p70/p80) in head and neck cancers: relationships with radiosensitivity
- 1999
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 45:4, s. 1005-10
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The DNA-PK complex is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. This study evaluated the relationship between the immunohistochemical expression of the individual components of DNA-PK and cellular radiosensitivity in head and neck cancers. METHODS AND MATERIALS: Biopsies from patients with previously untreated squamous cell carcinomas of the head and neck were assessed for inherent tumor radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft agar clonogenic assay. Paraffin-embedded tumor material from 64 successfully grown specimens was immunohistochemically stained for expression of DNA-PKcs and Ku (p70/p80). The same tumor material was previously analyzed for the immunohistochemical expression of p53. RESULTS: A significant correlation was found between the degree of expression of DNA-PKcs and Ku (p70/p80) (r = 0.55, p<0.001). There were no overall significant differences in the levels of expression of DNA-PKcs and Ku (p70/p80) in tumors from patients of either sex, different sites, histologies, and stages. No relationship was found between SF2 and the expression of either DNA-PKcs (r = 0.22, p = 0.081) or Ku (p70/p80) (r = 0.064, p = 0.62). Comparison with previous immunohistochemical characterization showed no significant correlations between the expression levels of p53 and either DNA-PKcs (r = 0.093, p = 0.46) or Ku (p70/p80) (r = -0.17, p = 0.17). CONCLUSIONS: This study suggests that determining the immunohistochemical expression of DNA-PK in head and neck cancers from multiple sites does not have a role as a predictive assay of tumor in vitro radiosensitivity.
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