Background. Although treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion. Methods. A population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (B 30, 31-60, 61-90, 91-120, 121-365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology. Results. Among 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05-1.10; P \ 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9-96.1%) versus 94.9% (95% CI 94.6-95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11-1.15; P \ 0.001). Conclusions. Despite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised. Ductal carcinoma in situ (DCIS) is a premalignant lesion composed of malignant mammary ductal epithelial cells that have not yet invaded the basement membrane, whose standard interventions have included lumpectomy and radiotherapy or total mastectomy alone, followed by endocrine therapy. 1-5 Defined as American Joint Commission of Cancer (AJCC) Stage 0, patient outcomes following standard treatment are excellent, with 5-year survival typically [ 95%. 2,6-8 Recently, therapies for DCIS have been scrutinized, as current data suggest that \ 50% of afflicted patients will develop invasive cancer without treatment. 1,2,8 Additionally, although DCIS detection has increased over recent decades secondary to mammographic improvements, advanced stage distributions have not correspondingly declined, suggesting that screening may detect some DCIS that would remain subclinical. 2,4,9-13 Many have Dr. Ward is a military service member. This work was prepared as part of his official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.
SBRT for pancreatic cancer results in LC rates of 60% to 83% and clinically significant toxicity of <7%. Increasing BED10 beyond 70 Gy was not associated with increased rates of 1-year LC or acute toxicity. Increasing BED3 beyond 100 Gy was not associated with increased rates of late toxicity.
Background and Objectives The paradoxical rise in overall and cancer-specific mortality despite increased detection and treatment of Renal Cell Carcinoma (RCC) is termed “treatment disconnect.” We reassess this phenomenon by evaluating impact of missing data and rising incidence on mortality trends. Research Design, Subjects, and Measures Using Surveillance, Epidemiology, and End Results (SEER) data, we identified patients with RCC diagnosis from 1973–2011. We estimated mortality rates by tumor size after accounting for lags from diagnosis to death using multiple imputations for missing data from 1983. Mortality rates were estimated irrespective of tumor size after adjustment for prior cumulative incidence using ridge regression. Results 78,891 patients met inclusion criteria. Of 70,212 patients diagnosed since 1983, 10.4% had missing data. Significant attenuation in cancer-specific mortality was noted from 1983–2011 when comparing observed to imputed rates: Δobs0.05 versus Δimp0.10 (p=0.001, <2cm tumors); Δobs0.29 versus Δimp0.18 (p=0.005, 2–4cm tumors); Δobs0.46 versus Δimp-0.20 (p<0.001, 4–7cm tumors); Δobs0.93 versus Δimp-0.15 (p<0.001, >7 cm tumors). Holding incidence of RCC constant to 2011 rates, temporal increase in overall mortality for all patients was attenuated (p<0.001) when comparing observed estimates (3.9 to 6.8) to 2011 adjusted estimates (5.9 to 7.1), suggesting that rapidly rising incidence may influence reported overall mortality trends. These findings were supported by assessment of mortality to incidence ratio trends. Conclusions Missing data and rising incidence may contribute substantially to the “treatment disconnect” phenomenon when examining mortality rates in RCC using tumor registry data. Caution is advised when basing clinical and policy decisions on these data.
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