| 1. |
- Kovács, Anikó, 1961, et al.
(författare)
-
Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes : A Long-Term Follow-Up of the SweBCG91RT Randomized Trial
- 2019
-
Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:14, s. 1179-87
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1,178 patients with breast cancer stage I and II were randomly assigned to breast-conserving surgery plus postoperative RT or breast-conserving surgery only and followed for a median of 15.2 years. Tumor blocks were retrieved from 1,003 patients. Stromal TILs were assessed on whole-section hematoxylin-eosin-stained slides using a dichotomized cutoff of 10%. Subtypes were scored using immunohistochemistry on tissue microarray. In total, 936 patients were evaluated. RESULTS: Altogether, 670 (71%) of patients had TILs less than 10%. In a multivariable regression analysis with IBTR as dependent variable and RT, TILs, subtype, age, and grade as independent variables, RT (hazard ratio [HR], 0.42; 95% CI, 0.29 to 0.61; P < .001), high TILs (HR, 0.61; 95% CI, 0.39 to 0.96, P = .033) grade (3 v 1; HR, 2.17; 95% CI, 1.08 to 4.34; P = .029), and age (≥ 50 v < 50 years; HR, 0.55; 95% CI, 0.38 to 0.80; P = .002) were predictive of IBTR. RT was significantly beneficial in the low TILs group (HR, 0.37; 95% CI, 0.24 to 0.58; P < .001) but not in the high TILs group (HR, 0.58; 95% CI, 0.28 to 1.19; P = .138). The test for interaction between RT and TILs was not statistically significant (P = .317). CONCLUSION: This study shows that high values of TILs in the primary tumor independently seem to reduce the risk for an IBTR. Our findings further suggest that patients with breast cancer with low TILs may derive a larger benefit from RT regarding the risk of IBTR.
|
|
| 2. |
- Sjöström, Martin, et al.
(författare)
-
Response to Radiotherapy After Breast-Conserving Surgery in Different Breast Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial.
- 2017
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 35:28, s. 3222-3229
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A-like tumors (19% v 9%; P = .001), luminal B-like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2-positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence of an overall difference in RT effect between subtypes was weak ( P = .21). RT reduced the rate of death from breast cancer (BCD) for triple-negative tumors (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause was not improved by RT in any subtype. A hypothesized clinical low-risk group did not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or death from any cause. Conclusion Subtype was not predictive of response to RT, although, in our study, human epidermal growth factor receptor 2-positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on BCD. The effect of RT in the presumed low-risk luminal A-like tumors was excellent.
|
|
| 3. |
- Adra, Jamila, et al.
(författare)
-
Distribution of locoregional breast cancer recurrence in relation to postoperative radiation fields and biological subtypes.
- 2019
-
Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 105:2, s. 285-295
-
Tidskriftsartikel (refereegranskat)abstract
- and purpose: To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiotherapy (LRRT) for primary breast cancer. LRR-position in relation to applied radiotherapy and the primary tumours biological subtype were analysed with the aim to evaluate current target guidelines and RT techniques in relation to tumour biology.Medical records were reviewed for all patients who received postoperative LRRT for primary BC in southwestern Sweden from 2004-2008 (N=923). Patients with LRR as a first event were identified (N=57, distant failure and death were considered competing risks). CT images identifying LRR were used to compare LRR locations to postoperative LRRT fields. LRR risk and distribution were then related to the primary BC biological subtype and to current target guidelines.Cumulative LRR incidence after 10 years was 7.1% (95%CI 5.5-9.1). Fifty-seven of the 923 patients in the cohort developed LRR (30 local recurrences (LR), 30 regional recurrences (RR), of which 3 cases of simultaneous LR/RR). Most cases of LRR developed fully (56%) or partially (26%) within postoperatively irradiated areas. The most common location for out-of-field RR was cranial to RT fields in the supraclavicular fossa. Patients with an ER- (HR 4.6, p<0.001, 95%CI 2.5-8.4) or HER2+ (HR 2.4, p=0.007, 95%CI 1.3-4.7) primary BC presented higher risks of LRR compared to those with ER+ tumours. ER-/HER2+ tumours more frequently recurred in-field (68%) rather than marginal/out-of-field (32%). In addition, 75% of in-field recurrences derived from an ER-/HER+ tumour, compared to 45% of marginal/out-of-field recurrences. A complete pathological response in the axilla after neoadjuvant treatment was associated with a lower degree of LRR risk (p=0.022).Incidence and locations of LRR seems to be related to the primary BC biological subtype. Individualized LRRT according to tumour biology may be applied to improve outcomes.
|
|
| 4. |
- Alkner, Sara, et al.
(författare)
-
Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
-
Ingår i: BMJ open. - 2044-6055. ; 13:9
-
Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
|
|
| 5. |
- Alsadius, David, 1975, et al.
(författare)
-
Mean Absorbed Dose to the Anal-Sphincter Region and Fecal Leakage among Irradiated Prostate Cancer Survivors.
- 2012
-
Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 84:2
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To supplement previous findings that the absorbed dose of ionizing radiation to the anal sphincter or lower rectum affects the occurrence of fecal leakage among irradiated prostate-cancer survivors. We also wanted to determine whether anatomically defining the anal-sphincter region as the organ at risk could increase the degree of evidence underlying clinical guidelines for restriction doses to eliminate this excess risk. METHODS AND MATERIALS: We identified 985 men irradiated for prostate cancer between 1993 and 2006. In 2008, we assessed long-term gastrointestinal symptoms among these men using a study-specific questionnaire. We restrict the analysis to the 414 men who had been treated with external beam radiation therapy only (no brachytherapy) to a total dose of 70 Gy in 2-Gy daily fractions to the prostate or postoperative prostatic region. On reconstructed original radiation therapy dose plans, we delineated the anal-sphincter region as an organ at risk. RESULTS: We found that the prevalence of long-term fecal leakage at least once per month was strongly correlated with the mean dose to the anal-sphincter region. Examining different dose intervals, we found a large increase at 40 Gy; ≥40 Gy compared with <40 Gy gave a prevalence ratio of 3.8 (95% confidence interval 1.6-8.6). CONCLUSIONS: This long-term study shows that mean absorbed dose to the anal-sphincter region is associated with the occurrence of long-term fecal leakage among irradiated prostate-cancer survivors; delineating the anal-sphincter region separately from the rectum and applying a restriction of a mean dose <40 Gy will, according to our data, reduce the risk considerably.
|
|
| 6. |
- Alsadius, David, 1975, et al.
(författare)
-
Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer.
- 2011
-
Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 1879-0887.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer. METHODS: We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months. RESULTS: We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7). CONCLUSION: Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.
|
|
| 7. |
- Appelgren, M., et al.
(författare)
-
Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial
- 2022
-
Ingår i: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 63, s. 16-23
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
|
|
| 8. |
- de Boniface, J., et al.
(författare)
-
The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer
- 2020
-
Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 180:1, s. 167-176
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose None of the key randomised trials on the omission of axillary lymph node dissection (ALND) in sentinel lymph-positive breast cancer have reported external validity, even though results indicate selection bias. Our aim was to assess the external validity of the ongoing randomised SENOMAC trial by comparing characteristics of Swedish SENOMAC trial participants with non-included eligible patients registered in the Swedish National Breast Cancer Register (NKBC). Methods In the ongoing non-inferiority European SENOMAC trial, clinically node-negative cT1-T3 breast cancer patients with up to two sentinel lymph node macrometastases are randomised to undergo completion ALND or not. Both breast-conserving surgery and mastectomy are eligible interventions. Data from NKBC were extracted for the years 2016 and 2017, and patient and tumour characteristics compared with Swedish trial participants from the same years. Results Overall, 306 NKBC cases from non-participating and 847 NKBC cases from participating sites (excluding SENOMAC participants) were compared with 463 SENOMAC trial participants. Patients belonging to the middle age groups (p = 0.015), with smaller tumours (p = 0.013) treated by breast-conserving therapy (50.3 versus 47.1 versus 65.2%, p < 0.001) and less nodal tumour burden (only 1 macrometastasis in 78.8 versus 79.9 versus 87.3%, p = 0.001) were over-represented in the trial population. Time trends indicated, however, that differences may be mitigated over time. Conclusions This interim external validity analysis specifically addresses selection mechanisms during an ongoing trial, potentially increasing generalisability by the time full accrual is reached. Similar validity checks should be an integral part of prospective clinical trials. Trial registration: NCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015
|
|
| 9. |
- Karlsson, Per, 1963, et al.
(författare)
-
Radiotherapy for metastatic lesions
- 2017
-
Ingår i: Breast Cancer. Veronesi U., Goldhirsch A., Veronesi P., Gentilini O., Leonardi M. (eds).. - Cham : Springer. - 9783319488486 ; , s. 685-693
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Modern imaging and the development of new precise techniques in radiotherapy has changed the possibilities to detect and treat metastatic lesions. Metastatic breast cancer includes a wide range of clinical scenarios, and the use of radiotherapy must be adjusted to the patient need, all the way from symptom control with a single fraction late in life to potentially curative extensive radiotherapy in oligometastatic disease. The role of palliative radiotherapy in various metastatic sites and the evidence behind different fractionation schedules are reviewed. Treatments of metastatic spinal cord compression and radiotherapy in locally recurrent disease are discussed. The possibilities of stereotactic radiotherapy for brain metastases as well as stereotactic body radiotherapy for oligometastatic disease are presented and summarized. The integration of the systemic treatment with the radiotherapy and the importance of listening to the patient need and to put the radiotherapy decision within the context of a multidisciplinary team are emphasized. © Springer International Publishing AG 2017.
|
|
| 10. |
- Killander, F., et al.
(författare)
-
No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial, SweBCG 91 RT
- 2016
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 67, s. 57-65
-
Tidskriftsartikel (refereegranskat)abstract
- Background Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients. Patients and methods A total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program. Results After 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P < 0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P = 0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P = 0.68, nor was breast cancer–specific mortality significantly higher. Conclusions RT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.
|
|
