De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy:nationwide registry study (BOOG 2013-07)

Background: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. Methods: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. Results: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. Conclusion:In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.</p

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy:nationwide registry study (BOOG 2013-07)

Background: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. Methods: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. Results: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. Conclusion:In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.</p

Ten-year conditional recurrence risks and overall and relative survival for breast cancer patients in the Netherlands: Taking account of event-free years

Background: Survival estimates from diagnosis are of limited importance for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analysed the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups. Second, we investigated 10-year conditional overall survival (OS) and relative survival (RS), adjusted for confounding. Patients and methods: All women diagnosed in 2005 with operated T1-2N0-1 breast cancer were selected from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated from diagnosis, and for patients without an event (local [LR], regional recurrence [RR], distant metastasis [DM] or death) every year following diagnosis. Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population. Results: We included 7969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates changed from 2.3% to 0.2%, and DM rates changed from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates changed from 6.2% to 0.8%, 5.2%–0.4% and 19.6%–1.5%, respectively. For the luminal A subtype, LR, RR and DM rates changed from 3.9% to 0.4%, 1.7%–0.5% and 7.3%–1.1%, while for triple negative, these rates changed from 5.6% to 0.7%, 4.9%–0.2% and 16.7%–0%, respectively. Differences between subgroups attenuated over time, and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed declining risk differences between subgroups over time. Conclusion: Differences in recurrence rates, OS and RS between prognostic subgroups declined as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients’ prognosis over time

Different statistical techniques dealing with confounding in observational research: measuring the effect of breast-conserving therapy and mastectomy on survival

Purpose: Propensity trimming, hierarchical modelling and instrumental variable (IV) analysis are statistical techniques dealing with confounding, cluster-related variation or confounding by severity. This study aimed to explain (dis)advantages of these techniques in estimating the effect of breast-conserving therapy (BCT) and mastectomy on 10-year distant metastasis-free survival (DMFS). Methods: All women diagnosed in 2005 with primary T1-2N0-1 breast cancer treated with BCT or mastectomy were selected from the Netherlands Cancer Registry. We used multivariable Cox regression to correct for confounding. Propensity trimming was used to create a more homogeneous population for which the treatment choice was not self-evident. Hospital of surgery was used as hierarchical level to handle hospital-related variation, and as IV to deal with unmeasured confounding. Results: Multivariable Cox regression showed higher 10-year DMFS for BCT than mastectomy [HR 0.70 (95% CI 0.60–82)]. Propensity trimming on the 10–90th and the 20–80th percentile of the propensity score distribution and hierarchical modelling showed similar HRs. IV analysis showed no significant difference between BCT and mastectomy. Conclusion: Unmeasured confounding is very difficult to eliminate in observational research. We cannot conclude that BCT or mastectomy has a causal relationship with 10-year DMFS. It is crucial to critically evaluate all model’s assumptions, and to be careful in drawing firm conclusions

Overall and disease-specific survival of Hodgkin lymphoma survivors who subsequently developed gastrointestinal cancer

BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased risk of gastrointestinal (GI) cancer. This study aims to evaluate whether survival of patients who survived HL and developed GI cancer differs from survival of first primary GI cancer patients. METHODS: Overall and cause-specific survival of GI cancer patients in a HL survivor cohort (GI-HL, N = 104, including esophageal, gastric, small intestinal, and colorectal cancer) was compared with survival of a first primary GI cancer patient cohort (GI-1, N = 1025, generated by case matching based on tumor site, gender, age, and year of diagnosis). Cox proportional hazards regression was used for survival analyses. Multivariable analyses were adjusted for GI cancer stage, grade of differentiation, surgery, radiotherapy, and chemotherapy. RESULTS: GI-HL cancers were diagnosed at a median age of 54 years (interquartile range 45-60). No differences in tumor stage or frequency of surgery were found. GI-HL patients less often received radiotherapy (8% vs 23% in GI-1 patients, P < 0.001) and chemotherapy (28% vs 41%, P = 0.01) for their GI tumor. Compared with GI-1 patients, overall and disease-specific survival of GI-HL patients was worse (univariable hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.03-1.65, P = 0.03; and HR 1.29, 95% CI 1.00-1.67, P = 0.049, respectively; multivariable HR 1.33, 95% CI 1.05-1.68, P = 0.02; and HR 1.33, 95% CI 1.03-1.72, P = 0.03, respectively). CONCLUSIONS: Long-term overall and disease-specific survival of GI cancer in HL survivors is worse compared with first primary GI cancer patients. Differences in tumor stage, grade of differentiation, or treatment could not explain this worse survival