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Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival.

ABSTRACT: Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients.We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female patients with early-stage breast cancer who received RT before (n?=?2554; 1.02%) or after (n?=?247,641; 98.98%) surgery. Disease-free survival, defined as time to diagnosis of a second primary tumor at any location, was calculated from automated patient identification matching of all SEER records.Partial and complete mastectomies were performed in 94.4% and 5.6% of patients, respectively. In the largest cohort of estrogen receptor-positive women who underwent partial mastectomy, the HR of developing a second primary tumor after neoadjuvant compared with adjuvant RT was 0.64 (95% CI 0.55-0.75; P?

SUBMITTER: Poleszczuk J

PROVIDER: S-EPMC5493088 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival.

Poleszczuk Jan J Luddy Kimberly K Chen Lu L Lee Jae K JK Harrison Louis B LB Czerniecki Brian J BJ Soliman Hatem H Enderling Heiko H

Breast cancer research : BCR 20170630 1

<h4>Background</h4>Compared with surgery alone, postoperative adjuvant radiotherapy (RT) improves relapse-free survival of patients with early-stage breast cancer. We evaluated the long-term overall and disease-free survival rates of neoadjuvant (presurgical) versus adjuvant RT in early-stage breast cancer patients.<h4>Methods</h4>We used the Surveillance, Epidemiology, and End Results (SEER) database provided by the National Institutes of Health to derive an analytic dataset of 250,195 female p ...[more]

PMID: 28666457

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Project description:Importance:Previous comparisons of surgery and stereotactic body radiotherapy (SBRT) for early-stage (ES) non-small cell lung cancer (NSCLC) did not account for the extent of regional lymph node examination (LNE) during surgery. Objective:To compare long-term overall survival (OS) of patients with ES NSCLC after surgery vs SBRT when the extent of regional LNE in patients undergoing surgery is thoroughly considered. Design, Setting, and Participants:Cohort study with survival comparisons using the multivariable Cox proportional hazards model and after propensity score matching. Data from the National Cancer Database were analyzed from October 28, 2018, through April 18, 2019. Patients with ES NSCLC diagnosed between January 1, 2004, and December 31, 2015, who underwent any curative-intent surgery or SBRT were included. Main Outcomes and Measures:Long-term OS. Results:Of 104?709 total patients, 91?330 underwent surgery (42?508 [46.5%] male; median [interquartile range] age, 68 [61-75] years) and 13?379 received SBRT (6065 [45.3%] male; median [interquartile range] age, 75 [68-81] years). Surgery, especially lobectomy (hazard ratio [HR], 0.53; 95% CI, 0.50-0.56), and regional LNE, especially when more than 10 lymph nodes were examined (HR, 0.73; 95% CI, 0.69-0.77), were associated with better long-term OS (P?<?.001). Pneumonectomy was not associated with reduced mortality risk when 0 nodes were examined (HR for stage T1, 1.43; 95% CI, 0.67-3.06; P?=?.35; HR for stage T2-T3, 0.62; 95% CI, 0.34-1.13; P?=?.12) or when more than 15 nodes were examined for stage T1 disease in patients younger than 80 years (HR, 0.77; 95% CI, 0.54-1.09; P?=?.14) or when patients aged 80 years or older received regional LNE of any extent (>15 nodes examined: HR for stage T1, 0.65; 95% CI, 0.16-2.64; P?=?.54; HR for stage T2-T3, 0.90; 95% CI, 0.50-1.60; P?=?.71). Less extensive surgery was not associated with improved OS when 0 nodes were examined in patients aged 80 years or older with stage T2 to T3 tumors (HR for lobectomy, 0.90; 95% CI, 0.65-1.25; P?=?.53) and in selected operable patients older than 75 years with stage T1 tumors (HR for lobectomy, 1.07; 95% CI, 0.57-2.00; P?=?.84). Conclusions and Relevance:This study found that, overall, surgery coupled with regional LNE of appropriate extent was associated with the best long-term OS in patients with ES NSCLC.

Project description:Importance:Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective:To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants:In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions:The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures:A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results:Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P?=?.052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P?=?.38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P?=?.98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P?=?.80). Conclusions and Relevance:These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration:ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.

Project description:Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time.Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length.The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The 'prognostic benefit' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1-0.4) at 6 months to 2.2 (95% CI 1.3-3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1-2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4-1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group.From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.

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Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival.

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Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival.

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