Journal
Journal of Clinical Oncology
Patients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this ...setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.
The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS ...use in elderly patients with NSCLC.
Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases.
We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not.
The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.
Local Therapy and Survival in Breast Cancer Punglia, Rinaa S; Morrow, Monica; Winer, Eric P ...
The New England journal of medicine,
06/2007, Letnik:
356, Številka:
23
Journal Article
Recenzirano
Some investigators have viewed breast cancer as a local disease that then spreads; others have seen it as a systemic disease from the start. This review argues for another view, since the failure to ...achieve initial local control allows some tumors to disseminate later, reducing a patient's chance of long-term survival. Recent evidence supports a larger role for aggressive, local therapy for breast cancer.
This review argues that initial local control allows some tumors to disseminate later. Recent evidence supports a larger role for aggressive, local therapy for breast cancer.
The effect of local therapy on the survival of patients with breast cancer has been debated for decades. Three viewpoints have been proposed on the basis of various hypotheses concerning the biology of breast cancer. Is breast cancer a local disease that spreads predictably over time to develop distant metastases? Is it a systemic disease from the outset, with distant metastases present well before diagnosis? Or is the truth somewhere in between, with many cancers being localized at diagnosis and, if untreated or recurrent, acquiring the ability to metastasize and kill? These differing views have vastly different implications for the . . .
Purpose The Oncotype DX DCIS Score short form (DCIS Score) estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving ...surgery without adjuvant radiation therapy (RT). We determined the cost effectiveness of strategies using this test. Materials and Methods We developed a Markov model simulating 10-year outcomes for 60-year-old women eligible for the Eastern Cooperative Oncology Group E5194 study (cohort 1: low/intermediate-grade DCIS, ≤ 2.5 cm; cohort 2: high-grade DCIS, ≤ 1 cm) with each of five strategies: (1) no testing, no RT; (2) no testing, RT only for cohort 2; (3) no RT for low-grade DCIS, test for intermediate- and high-grade DCIS, RT for intermediate- or high-risk scores; (4) test all, RT for intermediate- or high-risk scores; and (5) no testing, RT for all. We used utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women needed to irradiate per IBE prevented. Results No strategy using the DCIS Score was cost effective. The most cost-effective strategy (RT for none or RT for all) was sensitive to small differences between the utilities of receiving or not receiving RT and remaining without recurrence. The numbers needed to irradiate per IBE prevented were 10.5, 9.1, 7.5, and 13.1 for strategies 2 to 5, respectively, relative to strategy 1. Conclusion Strategies using the DCIS Score lowered the proportion of women undergoing RT per IBE prevented. However, no strategy incorporating the DCIS Score was cost effective. The cost effectiveness of RT was exquisitely utility sensitive, highlighting the importance of engaging patient preferences in this decision. Physicians should discuss trade-offs associated with omitting or adding adjuvant RT with each patient to maximize quality-of-life outcomes.
The standard management of medically inoperable Stage I non-small-cell lung cancer (NSCLC) conventionally has been fractionated three-dimensional conformal radiation therapy (3D-CRT). The relatively ...poor local control rate and inconvenience associated with this therapy have prompted the development of stereotactic body radiotherapy (SBRT), a technique that delivers very high doses of irradiation typically over 3 to 5 sessions. Radiofrequency ablation (RFA) has also been investigated as a less costly, single-day therapy that thermally ablates small, peripheral tumors. The cost-effectiveness of these three techniques has never been compared.
We developed a Markov model to describe health states of 65-year-old men with medically inoperable NSCLC after treatment with 3D-CRT, SBRT, and RFA. Given their frail state, patients were assumed to receive supportive care after recurrence. Utility values, recurrence risks, and costs were adapted from the literature. Sensitivity analyses were performed to model uncertainty in these parameters.
The incremental cost-effectiveness ratio for SBRT over 3D-CRT was $6,000/quality-adjusted life-year, and the incremental cost-effectiveness ratio for SBRT over RFA was $14,100/quality-adjusted life-year. One-way sensitivity analysis showed that the results were robust across a range of tumor sizes, patient utility values, and costs. This result was confirmed with probabilistic sensitivity analyses that varied local control rates and utilities.
In comparison to 3D-CRT and RFA, SBRT was the most cost-effective treatment for medically inoperable NSCLC over a wide range of treatment and disease assumptions. On the basis of efficacy and cost, SBRT should be the primary treatment approach for this disease.
To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype.
Between 2000 and 2009, 5673 patients with stage I to III breast ...carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen ER/progesterone PR+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT.
With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively.
TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.
Traditionally, larger tumor size and increasing lymph node (LN) involvement have been considered independent predictors of increased breast cancer-specific mortality (BCSM). We sought to characterize ...the interaction between tumor size and LN involvement in determination of BCSM. In particular, we evaluated whether very small tumor size may predict for increased BCSM relative to larger tumors in patients with extensive LN involvement.
Using Surveillance, Epidemiology and End Results registry data, we identified 50,949 female patients diagnosed between 1990 and 2002 with nonmetastatic T1/T2 invasive breast cancer treated with surgery and axillary LN dissection. Primary study variables were tumor size, degree of LN involvement, and their corresponding interaction term. Kaplan-Meier methods, adjusted Cox proportional hazards models with interaction terms, and a linear trend test across nodal categories were performed.
Median follow-up was 99 months. In multivariable analysis, there was significant interaction between tumor size and LN involvement (P < .001). Using T1aN0 as reference, T1aN2+ conferred significantly higher BCSM compared with T1bN2+ (hazard ratio HR, 20.66 v 12.53; P = .02). A similar pattern was seen among estrogen receptor (ER) -negative patients with T1aN2+ compared with T1bN2+ (HR, 24.16 v 12.67; P = .03), but not ER-positive patients (P = .52). The effect of very small tumor size on BCSM was intermediate among N1 cancers, between that of N0 and N2+ cancers.
Very small tumors with four positive LNs may predict for higher BCSM compared with larger tumors. In extensive node-positive disease, very small tumor size may be a surrogate for biologically aggressive disease. These results should be validated in future database studies.
Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking.
To characterize the incidence proportions and median survivals of patients ...with breast cancer and brain metastases at the time of cancer diagnosis.
Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort.
Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer.
We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR-positive HER2-positive subtype displayed the longest median survival (21.0 months); patients with triple-negative subtype had the shortest median survival (6.0 months).
The findings of this study provides population-based estimates of the incidence and prognosis for patients with brain metastases at time of diagnosis of breast cancer. The findings lend support to consideration of screening imaging of the brain for patients with HER2-positive or triple-negative subtypes and extracranial metastases.
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