Impact of concurrent (CON) and sequential (SEQ) radiotherapy (RT) with adjuvant aromatase inhibitors (AI) in early-stage breast cancer (EBC): NCIC CTG MA.27.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
Abdullah Khalaf Altwairgi ◽  
Wendy Parulekar ◽  
Judy-Anne W. Chapman ◽  
Lois E. Shepherd ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Annual Meeting ◽  
Aromatase Inhibitors ◽  
Early Stage ◽  
Hazard Ratio ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Event Free Survival ◽  
Free Survival

500 Notice of Retraction: "Impact of concurrent (CON) and sequential (SEQ) radiotherapy (RT) with adjuvant aromatase inhibitors (AI) in early-stage breast cancer (EBC): NCIC CTG MA.27." Abstract 500, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, has been retracted by Wendy Parulekar, MD, and Timothy J. Whelan, BM, BCh, MSc, on behalf of all authors of the abstract. The abstract concluded by suggesting that concurrent administration of an AI during the period of radiation may improve event-free survival as compared to commencing AI after completing radiation therapy. After submitting the abstract for the 2012 ASCO Annual Meeting, the authors identified issues associated with the statistical analysis of this research, which led them to reanalyze the data and in so doing, they reached different conclusions from those described in the abstract. As opposed to the abstract, which reports a hazard ratio (HR) of AI administration that is concurrent with RT vs. sequential to RT of 0.78 (p=0.001), they have determined that using a more appropriate analysis, the hazard ratio is 0.84 (p=0.13). Multiple sensitivity analyses have been performed and yield hazard ratios of 0.81-0.84 and p values of 0.07 to 0.13. In view of these findings, the conclusions reported in the abstract cannot be supported. Background: Optimal timing of administration of adjuvant (adj) RT and AI in EBC is unknown. Methods: MA.27 was a phase III RCT of exemestane to anastrozole in postmenopausal women with hormone receptor positive EBC (Goss et al. Cancer Res. 70(24, Suppl):75s, 2010). The final trial database was used for this retrospective analysis. Median follow-up was 4.1 years. MA.27 patients received CON-AI [any overlap with AI; 4233 (57%) patients], SEQ-AI [RT preceded AI, no overlap with AI; 1010 (14%) patients] and No RT [AI only; 2128 (29%) patients]. Outcome measures for this analysis were: event free survival (EFS; time to locoregional or distant disease recurrence, new primary BC, or death from any cause), locoregional recurrence (LRFS), distant recurrence (DDFS) and overall survival (OS). RT groups were compared univariately (uni) with stratified log-rank tests, and multivariately (multi) with step-wise stratified Cox regression adjusted by stratification factors: nodal status, adj chemotherapy (chemo), celecoxib, aspirin, and trastuzumab. Results: 7371 eligible women received AI; were included in the analysis; and 71% (5243) received adj RT. CON-AI and SEQ-AI groups were comparable by median age (63 v 63), proportion T1 tumours (75% v 75 %), and mastectomy rate (10% v 11%). The frequency of axillary dissection for CON-AI and SEQ-AI was 48% v 44%, proportion N0 was 73% v 69%, and proportion receiving adj chemo 29% v 41%. CON-AI had similar uni results to SEQ-AI: EFS, HR=0.86, p=0.20; LRFS, HR=0.82, p=0.51; DDFS, HR=0.92, p=0.59; and OS, HR=1.04, p=0.80. In multi analyses, CON-AI had better EFS than SEQ-AI patients [stratified HR of CON-AI to SEQ-AI 0.78 (0.66 – 0.91), p=0.001]; as well, age≥70 (p<0.0001), ECOG PS≥1 (p<0.0001), L-sided tumours (p=0.02), T2-T4 (p<0.0001), N2/N3 (p<0.0001), and no adj chemo (p=0.01) had significantly shorter EFS. There was no multi difference between CON-AI and SEQ-AI for LRFS (p=0.50), DDFS (p=0.72), or OS (p=0.85). Conclusions: Patients receiving CON-AI had significantly better EFS than SEQ-AI suggesting timing of administration of AI and RT may affect patient outcomes. Further research is necessary to confirm these findings.

scholarly journals Association between waiting time for radiotherapy after surgery for early-stage breast cancer and survival outcomes in Ontario: a population-based outcomes study

2019 ◽  
Vol 27 (2) ◽  
Author(s):  
M. J. Raphael ◽  
R. Saskin ◽  
S. Singh
Keyword(s):  
Breast Cancer ◽  
Waiting Time ◽  
Adjuvant Radiotherapy ◽  
Early Stage ◽  
Breast Conserving Surgery ◽  
Population Based ◽  
Early Stage Breast Cancer ◽  
Survival Outcomes ◽  
Event Free Survival ◽  
Free Survival

Background: Following surgery for early stage breast cancer, adjuvant radiotherapy decreases the risk of locoregional recurrence and death from breast cancer. It is unclear if delays to the initiation of adjuvant radiotherapy are associated with inferior survival outcomes. Methods: This population-based, prospective cohort study included a random sample of 25% of all women with stage I and II breast cancer treated with adjuvant radiotherapy in Ontario, Canada between September 1, 2001 and August 31, 2002, when due to capacity issues, wait times for radiation were abnormally long. Pathology reports were manually abstracted and deterministically-linked to population-level administrative databases to obtain information on recurrence and survival outcomes. Cox proportional hazard modeling was used to evaluate the association between waiting time and survival outcomes. A composite survival outcome was used to ensure that all possible measurable harms of delay would be captured. The composite outcome, event-free survival, included locoregional recurrence, development of metastatic disease or breast cancer-specific mortality. Results: We identified 1,028 women with Stage I and II breast cancer who were treated with breast-conserving surgery and adjuvant radiotherapy. Among 599 women who were treated with adjuvant radiation without intervening chemotherapy, waiting time ≥12 weeks from surgery to start of radiation appears to be associated with worse event-free survival after a median follow-up of 7.2 years (HR, composite outcome = 1.44, 95% CI: 0.98-2.11; p= 0.07). Among 429 women who received intervening adjuvant chemotherapy, waiting time ≥6 weeks from completion of chemotherapy to start of radiation was associated with worse event-free survival after a median follow-up of 7.4 years (HR 1.50, 95% CI: 1.00-2.22; p= 0.047). Conclusion: Delay to the initiation of adjuvant radiotherapy following breast-conserving surgery is associated with inferior breast cancer survival outcomes. The good prognosis for patients with early stage breast cancer limits the statistical power to detect an effect of delay to radiotherapy. Given that there is no plausible advantage to delay, we agree with Mackillop et al, that time to initiation of radiotherapy should be kept “as short as reasonably achievable.”

Impact on Survival of Time From Definitive Surgery to Initiation of Adjuvant Chemotherapy for Early-Stage Breast Cancer

2006 ◽  
Vol 24 (30) ◽  
pp. 4888-4894 ◽  
Author(s):  
Caroline Lohrisch ◽  
Charles Paltiel ◽  
Karen Gelmon ◽  
Caroline Speers ◽  
Suzanne Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Hazard Ratio ◽  
Early Stage Breast Cancer ◽  
Curative Surgery ◽  
Free Survival ◽  
Cancer Agency ◽  
Impact On Survival ◽  
Definitive Surgery

Purpose To determine if time to start of adjuvant chemotherapy after curative surgery influences survival in early-stage breast cancer. Patients and Methods A retrospective review was conducted of 2,594 patients receiving adjuvant chemotherapy for stage I and II breast cancer between 1989 and 1998 at the British Columbia Cancer Agency. Relapse-free survival (RFS) and overall survival (OS) were compared among patients grouped by time from definitive curative surgery to start of adjuvant chemotherapy (≤ 4 weeks, > 4 to 8 weeks, > 8 to 12 weeks, and >12 to 24 weeks). Results RFS and OS were similar for women starting chemotherapy up to 12 weeks after surgery. OS hazard ratio (univariate) for initiation of chemotherapy more than 12 weeks compared with 12 weeks or less after surgery was 1.5 (95% CI, 1.07 to 2.10; P = .017). Five-year OS rates were 84%, 85%, 89%, and 78%, (log-rank P = .013); RFS rates were 74%, 79%, 82%, and 69% (log-rank P = .004) for patients starting chemotherapy 4 weeks or fewer, more than 4 to 8 weeks, more than 8 to 12 weeks, and more than 12 to 24 weeks after surgery, respectively. In multivariate analysis, independent prognostic factors were grade, size, nodal status, estrogen receptor, age, and lymphatic and/or vascular invasion. Initiation of adjuvant chemotherapy more than 12 weeks from surgery remained significantly associated with inferior survival, with a hazard ratio of 1.6 (95% CI, 1.2 to 2.3; P = .005). Conclusion This retrospective analysis suggests that adjuvant chemotherapy is equally effective up to 12 weeks after definitive surgery but that RFS and OS appear to be compromised by delays of more than 12 weeks after definitive surgery.

Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE): An international, randomized, double-blind, placebo-controlled phase III clinical trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS670-TPS670
Author(s):  
Paul Edward Goss ◽  
Carlos H. Barrios ◽  
Richard Bell ◽  
Dianne M Finkelstein ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Stage ◽  
Human Monoclonal Antibody ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Free Survival ◽  
Oral Bisphosphonate ◽  
Her 2

TPS670 Background: Bone is a common site of distant recurrence in women with early-stage breast cancer, and represents approximately 40% of all first recurrences. Tumor cells in bone release growth factors and cytokines that stimulate osteoclast-mediated bone resorption through the RANK ligand (RANKL) pathway. In preclinical studies, RANKL inhibition significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is a fully human monoclonal antibody that binds to RANKL with high affinity and specificity. It is approved for the prevention of skeletal-related events in patients with established bone metastases from a variety of solid tumors. The purpose of the D-CARE trial is to evaluate the ability of denosumab to prolong bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. Methods: Approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination must be planned. Exclusion criteria include: a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization or any intravenous BP use. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. All patients receive vitamin D (≥ 400 IU) and calcium (≥ 500 mg) supplements. Primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Safety, quality of life assessments, breast density, and biomarkers are additional endpoints. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete in October 2016. Paul Goss and Dianne Finkelstein supported in part by the Avon Foundation New York.

Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer at high risk of disease recurrence (D-CARE): An international, placebo-controlled, randomized, double-blind phase III clinical trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS662-TPS662
Author(s):  
Paul E. Goss ◽  
Carlos H. Barrios ◽  
Arlene Chan ◽  
Dianne M. Finkelstein ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Bone Metastasis ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Patient Reported

TPS662 Background: In women with early-stage breast cancer, bone is a common site of distant recurrence and represents approximately 40% of all first recurrences. Preclinical studies demonstrated that inhibition of RANKL significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumors. The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints include safety, breast density, time to first on-study SRE (following the development of bone metastasis), patient reported outcomes, and biomarkers. Methods: In this international, randomized, double-blind, and placebo-controlled phase 3 trial, 4509 women with stage II or III breast cancer at high risk for recurrence and with known hormone and HERE2 receptor status were randomized. High risk was defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size > 5 cm (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, were not eligible. Patients were randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) were required. The trial, sponsored by Amgen Inc., began enrolling patients in June 2010 and completed enrollment in late 2012. Clinical trial information: NCT01077154.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Positron Emission Tomography–Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL): A Multicenter, Randomized Phase III Trial

2018 ◽  
Vol 36 (20) ◽  
pp. 2024-2034 ◽  
Author(s):  
Ulrich Dührsen ◽  
Stefan Müller ◽  
Bernd Hertenstein ◽  
Henrike Thomssen ◽  
Jörg Kotzerke ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Survival Rates ◽  
Hazard Ratio ◽  
Emission Tomography ◽  
Phase Iii ◽  
Event Free Survival ◽  
Free Survival ◽  
Interim Pet ◽  
Positron Emission ◽  
To Receive

Purpose Interim positron emission tomography (PET) using the tracer, [18F]fluorodeoxyglucose, may predict outcomes in patients with aggressive non-Hodgkin lymphomas. We assessed whether PET can guide therapy in patients who are treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patients and Methods Newly diagnosed patients received two cycles of CHOP—plus rituximab (R-CHOP) in CD20-positive lymphomas—followed by a PET scan that was evaluated using the ΔSUVmax method. PET-positive patients were randomly assigned to receive six additional cycles of R-CHOP or six blocks of an intensive Burkitt’s lymphoma protocol. PET-negative patients with CD20-positive lymphomas were randomly assigned or allocated to receive four additional cycles of R-CHOP or the same treatment with two additional doses rituximab. The primary end point was event-free survival time as assessed by log-rank test. Results Interim PET was positive in 108 (12.5%) and negative in 754 (87.5%) of 862 patients treated, with statistically significant differences in event-free survival and overall survival. Among PET-positive patients, 52 were randomly assigned to R-CHOP and 56 to the Burkitt protocol, with 2-year event-free survival rates of 42.0% (95% CI, 28.2% to 55.2%) and 31.6% (95% CI, 19.3% to 44.6%), respectively (hazard ratio, 1.501 [95% CI, 0.896 to 2.514]; P = .1229). The Burkitt protocol produced significantly more toxicity. Of 754 PET-negative patients, 255 underwent random assignment (129 to R-CHOP and 126 to R-CHOP with additional rituximab). Event-free survival rates were 76.4% (95% CI, 68.0% to 82.8%) and 73.5% (95% CI, 64.8% to 80.4%), respectively (hazard ratio, 1.048 [95% CI, 0.684 to 1.606]; P = .8305). Outcome prediction by PET was independent of the International Prognostic Index. Results in diffuse large B-cell lymphoma were similar to those in the total group. Conclusion Interim PET predicted survival in patients with aggressive lymphomas treated with R-CHOP. PET-based treatment intensification did not improve outcome.

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