Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival.

PURPOSE: Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes. METHODS: We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival. RESULTS: A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors. CONCLUSION: The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.

Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

BACKGROUND: The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. METHODS: This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. RESULTS: Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. CONCLUSIONS: Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society.

Family Perspectives on Aggressive Cancer Care Near the End of Life.

IMPORTANCE: Patients with advanced-stage cancer are receiving increasingly aggressive medical care near death, despite growing concerns that this reflects poor-quality care. OBJECTIVE: To assess the association of aggressive end-of-life care with bereaved family members' perceptions of the quality of end-of-life care and patients' goal attainment. DESIGN, SETTING, AND PARTICIPANTS: Interviews with 1146 family members of Medicare patients with advanced-stage lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance study (a multiregional, prospective, observational study) who died by the end of 2011 (median, 144.5 days after death; interquartile range, 85.0-551.0 days). EXPOSURES: Claims-based quality measures of aggressive end-of-life care (ie, intensive care unit [ICU] admission or repeated hospitalizations or emergency department visits during the last month of life; chemotherapy ≤2 weeks of death; no hospice or ≤3 days of hospice services; and deaths occurring in the hospital). MAIN OUTCOMES AND MEASURES: Family member-reported quality rating of "excellent" for end-of-life care. Secondary outcomes included patients' goal attainment (ie, end-of-life care congruent with patients' wishes and location of death occurred in preferred place). RESULTS: Of 1146 patients with cancer (median age, 76.0 years [interquartile range, 65.0-87.0 years]; 55.8% male), bereaved family members reported excellent end-of-life care for 51.3%. Family members reported excellent end-of-life care more often for patients who received hospice care for longer than 3 days (58.8% [352/599]) than those who did not receive hospice care or received 3 or fewer days (43.1% [236/547]) (adjusted difference, 16.5 percentage points [95% CI, 10.7 to 22.4 percentage points]). In contrast, family members of patients admitted to an ICU within 30 days of death reported excellent end-of-life care less often (45.0% [68/151]) than those who were not admitted to an ICU within 30 days of death (52.3% [520/995]) (adjusted difference, -9.4 percentage points [95% CI, -18.2 to -0.6 percentage points]). Similarly, family members of patients who died in the hospital reported excellent end-of-life care less often (42.2% [194/460]) than those who did not die in the hospital (57.4% [394/686]) (adjusted difference, -17.0 percentage points [95% CI, -22.9 to -11.1 percentage points]). Family members of patients who did not receive hospice care or received 3 or fewer days were less likely to report that patients died in their preferred location (40.0% [152/380]) than those who received hospice care for longer than 3 days (72.8% [287/394]) (adjusted difference, -34.4 percentage points [95% CI, -41.7 to -27.0 percentage points]). CONCLUSIONS AND RELEVANCE: Among family members of older patients with fee-for service Medicare who died of lung or colorectal cancer, earlier hospice enrollment, avoidance of ICU admissions within 30 days of death, and death occurring outside the hospital were associated with perceptions of better end-of-life care. These findings are supportive of advance care planning consistent with the preferences of patients.

Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer.

PURPOSE: A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice. PATIENTS AND METHODS: Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score-matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias. RESULTS: Use of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of IP/IV chemotherapy varied by institution from 4% to 67% (P < .001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score-matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47). CONCLUSION: Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes.

Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors.

PURPOSE: To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors. PATIENTS AND METHODS: Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer-specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. RESULTS: In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer-specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor-positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A-like and luminal B-like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2-type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. CONCLUSION: Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor-positive tumors.

The role of families in decisions regarding cancer treatments.

BACKGROUND: Shared decision-making is an important component of patient-centered care and is associated with improved outcomes. To the authors' knowledge, little is known concerning the extent and predictors of the involvement of a patient's family in decisions regarding cancer treatments. METHODS: The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium is a large, multiregional, prospective cohort study of the cancer care and outcomes of patients with lung and colorectal cancer. Participants reported the roles of their families in decision-making regarding treatment. Multinomial logistic regression was used to assess patient factors associated with family roles in decisions. RESULTS: Among 5284 patients, 80 (1.5%) reported family-controlled decisions, with the highest adjusted rates (12.8%) noted among non-English-speaking Asians. Among the 5204 remaining patients, 49.4% reported equally sharing decisions with family, 22.1% reported some family input, and 28.5% reported little family input. In adjusted analyses, patients who were married, female, older, and insured more often reported equally shared decisions with family (all P <.001). Adjusted family involvement varied by race/ethnicity and language, with Chinese-speaking Asian (59.8%) and Spanish-speaking Hispanic (54.8%) patients equally sharing decisions with family more often than white individuals (47.6%). Veterans Affairs patients were least likely to report sharing decisions with family, even after adjustment for marital status and social support (P <.001). CONCLUSIONS: The majority of patients with newly diagnosed lung or colorectal cancer involve family members in treatment decisions. Non-English-speaking Asians and Hispanics rely significantly on family. Further studies are needed to determine the impact of family involvement in treatment decisions on outcomes; until then, physicians should consider eliciting patients' preferences for family involvement.

Catalog and comparison of societal preferences (utilities) for lung cancer health states: results from the Cancer Care Outcomes Research and Surveillance (CanCORS) study.

BACKGROUND: The EQ-5D and SF-6D are 2 health-related quality-of-life indexes that provide preference-weighted measures for use in cost-effectiveness analyses. METHODS: The National Cancer Institute's Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium included the EQ-5D and SF-12v2 in their survey of newly diagnosed lung cancer patients. Utilities were calculated from patient-provided scores for each domain of the EQ-5D or the SF-6D. Utilities were calculated for categories of cancer type, stage, and treatment. RESULTS: There were 5015 enrolled lung cancer patients with a baseline survey in CanCORS; 2396 (47.8%) completed the EQ-5D, and 2344 (46.7%) also completed the SF-12v2. The mean (standard deviation) utility from the EQ-5D was 0.78 (0.18), and from the SF-6D (derived from SF-12v2) was 0.68 (0.14). The EQ-5D demonstrated a ceiling effect, with 20% of patients reporting perfect scores, translating to a utility of 1.0. No substantial SF-6D floor effects were noted. Utilities increased with age and decreased with stage and comorbidities. Patient-reported (EQ-5D) visual analog scale scores for health status had a moderate (r = 0.48, p < 0.0001) positive correlation with utilities. A subset (n = 1474) completed follow-up EQ-5D questionnaires 11-13 months after diagnosis. Among these patients, there was a nonsignificant decrease in mean utility for stage IV and an increase in mean utility for stages I, II, and III. CONCLUSION: This study generated a catalog of community-weighted utilities applicable to societal-perspective cost-effectiveness analyses of lung cancer interventions and compared utilities based on the EQ-5D and SF-6D. Potential users of these scores should be aware of the limitations and think carefully about their use in specific studies.

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

PURPOSE: Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). PATIENTS AND METHODS: We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. RESULTS: Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. CONCLUSION: In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.

Symptom prevalence in lung and colorectal cancer patients.

CONTEXT: Relatively few data are available about symptoms among cancer patients. OBJECTIVES: To describe the prevalence and severity of symptoms among a large, representative cohort of newly diagnosed cancer patients. METHODS: We collected survey data about symptoms (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, and diarrhea) from 5422 patients with incident lung and colorectal cancer from the diverse, nationally representative Cancer Care Outcomes Research and Surveillance Consortium cohort. We described the prevalence of any symptoms and moderate/severe symptoms approximately four to six months after diagnosis. We used logistic regression to identify patient and clinical characteristics associated with symptoms, and calculated adjusted proportions of patients with symptoms. RESULTS: In total, 5067 (93.5%) patients reported at least one symptom in the four weeks before their survey, with 51% reporting at least one moderate/severe symptom. Lung cancer patients reported more symptoms than colorectal cancer patients. Patients who received treatment or had more comorbidities were more likely to report symptoms. For example, after adjustment, patients who received chemotherapy during the six weeks before the survey were more likely than others to report at least one symptom (97.3% vs. 90.8%, P<0.001), and at least one moderate/severe symptom (56.8% vs. 46.2%, P<0.001). After adjustment, early- vs. late-stage patients did not differ in reports of at least one symptom (93.6% vs. 93.4%, P=0.853) and differed only slightly in reports of at least one moderate/severe symptom (53.3% vs. 49.6%, P=0.009). CONCLUSION: Most recently diagnosed lung and colorectal cancer patients have cancer-related symptoms regardless of stage, and more than half have at least one moderate/severe symptom.

Inflammatory breast cancer management in the national comprehensive cancer network: the disease, recurrence pattern, and outcome.

BACKGROUND: Inflammatory breast cancer (IBC) is an uncommon clinicopathologic entity characterized by rapid progression and aggressive behavior. We used the National Comprehensive Cancer Network (NCCN) Outcomes Database to characterize recurrence patterns and outcomes. METHODS: Patients with newly diagnosed IBC treated between 1999 and 2009 at 12 NCCN institutions were identified, and baseline characteristics were obtained. Patients had multimodality therapy if they received 2 of 3 treatments: surgery, perioperative (neoadjuvant or adjuvant) chemotherapy, or perioperative radiation. The first site of recurrence/metastatic diagnosis was identified. Overall survival was calculated on the basis of stage at diagnosis and receipt of multimodality therapy. RESULTS: We identified 673 patients, of whom 195 (29%) had metastatic disease at presentation. Median follow-up was 29 months. Of patients in stage III, 82% received > 1 treatment modality. Among 203 patients in stage III with recurrence, the most frequent sites of first recurrence were bone (28%), central nervous system (CNS), lung, and liver (all 21%). Human epidermal growth factor receptor 2 positive and triple negative subtypes had higher rates of CNS recurrence (P = .001). Median survival was 66 months (95% confidence interval [CI], 54-107) for stage III and 26 months (95% CI, 22-33) for stage IV. Among 82% of patients in stage III receiving multimodality therapy, the median survival was 107 months (95% CI, 71 to not reached). CONCLUSIONS: This large, retrospective, multi-institutional study confirms the aggressive clinical features, unique recurrence patterns, and adverse prognosis of IBC. The high rate of CNS recurrence among high-risk subtypes, despite the inflammatory nature of the breast cancer, suggests that new strategies are needed for earlier detection or prevention of brain metastases to improve long-term prognosis.

Invasive procedures in the elderly after stage IV cancer diagnosis.

BACKGROUND: Invasive procedures are resource intense and may be associated with substantial morbidity. These harms must be carefully balanced with the benefits gained in life expectancy and quality of life. Prior research has demonstrated an increasing aggressiveness of care in cancer patients at the end-of-life. To better characterize surgical care in this setting, we sought to examine trends in the use of invasive procedures in patients diagnosed with metastatic cancer on presentation. MATERIALS AND METHODS: Using Surveillance Epidemiology and End Results -Medicare data, we identified invasive procedure claims from 1994-2009 for patients diagnosed with incident stage IV breast, colorectal, lung, and prostate cancer patients in 1995-2006. We grouped procedures into surgically relevant categories, using an adaptation of the Clinical Classifications Software, and measured utilization and relative changes over time. RESULTS: Of stage IV patients diagnosed in 2002-2006, 96% underwent a procedure during the course of their cancer care including 63% after the diagnostic period, and 25% in the last month of life. Between 1996 and 2006, minimal change was observed in utilization during the diagnostic period (+1.5%). However, there were significant increases during continuing care (+20.7%) and the last month of life (+21.5%). Procedures consistent with primary tumor resection decreased, whereas those with probable palliative intent and those unrelated to cancer increased. CONCLUSIONS: Nearly all patients who present with metastatic cancer undergo invasive procedures. Although overall utilization is increasing, the specific procedure types indicate that it may be appropriate, enhancing the quality of life in this vulnerable population.

Did changes in drug reimbursement after the medicare modernization act affect chemotherapy prescribing?

PURPOSE: The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs). PATIENTS AND METHODS: We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA. RESULTS: The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA. CONCLUSION: Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns.

The relationship between quality, spending and outcomes among women with breast cancer.

BACKGROUND: Substantial shortcomings in the quality of breast cancer (BC) care have been identified. While breast cancer is responsible for the largest share of cancer care spending, little is known about the value of care provided to US women with BC. METHODS: For women aged 65 to 70 years diagnosed July 1997 through December 2005 with stage 0-III BC who were continuously enrolled in fee-for-service Medicare, we evaluated performance relative to 20 measures recommending for proven therapies and seven measures recommending against unnecessary therapies. Using health care service area as the unit of analysis, we characterized quality for recommended and unnecessary therapies, median per-patient cost in the year after diagnosis for Medicare parts A and B, and five-year overall survival. We analyzed the relationships between quality, cost, and survival. All statistical tests were two-sided. RESULTS: We assessed the care provided to 15357 women and compiled quality, cost, and outcomes data for 99 regions. The median number of patients/region was 85 (interquartile range = 47-158); the five-year overall survival was 87.5%. Part B expenditure correlated positively with measures of recommended therapy (P = .027) and negatively with measures of unnecessary therapy (P = .004). Survival did not correlate with quality or cost. Regions demonstrating lower quality for both recommended and unnecessary therapy measures exhibited higher part A expenditure. CONCLUSIONS: BC patients experience wide variation in quality, cost, and survival. Process measures that assess recommended and unnecessary therapies did not correlate with survival, but did shed light on spending for related and unrelated services. Additional efforts to identify factors that impact the relationships between quality, cost, and outcomes are needed.

Impact of guideline changes on use or omission of radiation in the elderly with early breast cancer: practice patterns at National Comprehensive Cancer Network institutions.

BACKGROUND: Breast radiation therapy (RT) is a care standard after breast-conservation surgery that improves local control and survival in women. In 2004, a phase III trial demonstrated radiation after breast-conservation surgery provided no survival and limited local control benefit to women aged 70 years and older with stage I, estrogen receptor-positive cancers who receive endocrine therapy. This led to breast-conservation surgery and endocrine therapy alone being incorporated as a category I option in the National Comprehensive Cancer Network (NCCN) Guidelines for older women in 2004. We examined factors associated with change in radiation use in elderly patients at 13 NCCN centers. STUDY DESIGN: We identified women treated at NCCN centers meeting age and stage criteria during 2000 to 2009. Factors considered a priori potentially associated with RT use were evaluated in univariate and multivariable models, including year of diagnosis, tumor and patient characteristics, axillary surgery, and treating institution. Date of diagnosis was classified as 2000 to 2004 vs 2005 to 2009, reflecting when guidelines changed. RESULTS: Among 1,292 eligible cases, 78% received RT. In multivariable analysis, diagnosis after 2004 (p = 0.0003), older age (p < 0.0001), higher comorbidity score (p = 0.0006), smaller tumors (p = 0.0146), and omission of axillary surgery (p < 0.0001) predicted RT omission. Ninety-four percent of women aged 70 to 74 years received RT in 2000, compared with 88% in 2009. For the same times and age 80 years and older, RT use was 80% vs 41%. Finally, RT use was associated with treating institution (p < 0.0001). CONCLUSIONS: After guideline changes for RT use in older women, NCCN centers demonstrated wide variation in implementing change. This suggests other factors are also influencing guideline uptake.

Interinstitutional variation in management decisions for treatment of 4 common types of cancer: A multi-institutional cohort study.

BACKGROUND: When clinical practice is governed by evidence-based guidelines and there is consensus about their validity, practice variation should be minimal. For areas in which evidence gaps exist, greater variation is expected. OBJECTIVE: To systematically assess interinstitutional variation in management decisions for 4 common types of cancer. DESIGN: Multi-institutional, observational cohort study of patients with cancer diagnosed between July 2006 through May 2011 and observed through 31 December 2011. SETTING: 18 cancer centers participating in the formulation of treatment guidelines and systematic outcomes assessment through the National Comprehensive Cancer Network. PATIENTS: 25 589 patients with incident breast cancer, colorectal cancer, lung cancer, or non-Hodgkin lymphoma. MEASUREMENTS: Interinstitutional variation for 171 binary management decisions with varying levels of supporting evidence. For each decision, variation was characterized by the median absolute deviation of the center-specific proportions. RESULTS: Interinstitutional variation was high (median absolute deviation >10%) for 35 of 171 (20%) oncology management decisions, including 9 of 22 (41%) decisions for non-Hodgkin lymphoma, 16 of 76 (21%) for breast cancer, 7 of 47 (15%) for lung cancer, and 3 of 26 (12%) for colorectal cancer. Forty-six percent of high-variance decisions involved imaging or diagnostic procedures and 37% involved choice of chemotherapy regimen. The evidence grade underpinning the 35 high-variance decisions was category 1 for 0%, 2A for 49%, and 2B/other for 51%. LIMITATION: Physician identifiers were unavailable, and results may not generalize outside of major cancer centers. CONCLUSION: The substantial variation in institutional practice manifest among cancer centers reveals a lack of consensus about optimal management for common clinical scenarios. For clinicians, awareness of management decisions with high variation should prompt attention to patient preferences. For health systems, high variation can be used to prioritize comparative effectiveness research, patient-provider education, or pathway development. PRIMARY FUNDING SOURCE: National Cancer Institute and National Comprehensive Cancer Network.

Outcomes by tumor subtype and treatment pattern in women with small, node-negative breast cancer: a multi-institutional study.

PURPOSE: Treatment decisions for patients with T1a,bN0M0 breast cancer are challenging. We studied the time trends in use of adjuvant chemotherapy and survival outcomes among these patients. PATIENTS AND METHODS: This was a prospective cohort study within the National Comprehensive Cancer Network Database that included 4,113 women with T1a,bN0M0 breast cancer treated between 2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. RESULTS: Median follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2-negative tumors were treated with chemotherapy. Fifty-two percent of those with HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy, with an increase over the last decade. Survival outcomes diverged by subtype and size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in any subgroup. The 5-year DRFS for patients with T1a tumors untreated with chemotherapy ranged from 93% to 98% (n = 49 to 972), and for patients with T1b tumors, it ranged from 90% to 96% (n = 17 to 2,005). Patients with HR-positive/HER2-negative disease had the best DRFS estimates, and patients with HR-negative/HER2-negative tumors had the lowest. In this observational, nonrandomized cohort study, the 5-year DRFS for treated patients with T1a tumors was 100% for all subgroups (n = 12 to 33), and for patients with T1b tumors, it ranged from 94% to 96% (n = 88 to 241). CONCLUSION: Women with T1a,b tumors have an excellent prognosis without chemotherapy. Size and tumor subtype may identify patients in whom the rate of recurrence justifies consideration of chemotherapy. These patients represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.

Characterization and treatment of local recurrence following breast conservation for ductal carcinoma in situ.

PURPOSE: The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences. METHODS: We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182). RESULTS: Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09). CONCLUSION: We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.

Advanced imaging among health maintenance organization enrollees with cancer.

PURPOSE: Fee-for-service (FFS) Medicare expenditures for advanced imaging studies (defined as computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] scans, and nuclear medicine studies [NM]) rapidly increased in the past two decades for patients with cancer. Imaging rates are unknown for patients with cancer, whether under or over age 65 years, in health maintenance organizations (HMOs), where incentives may differ. MATERIALS AND METHODS: Incident cases of breast, colorectal, lung, prostate, leukemia, and non-Hodgkin lymphoma (NHL) cancers diagnosed in 2003 and 2006 from four HMOs in the Cancer Research Network were used to determine 2-year overall mean imaging counts and average total imaging costs per HMO enrollee by cancer type for those under and over age 65. RESULTS: There were 44,446 incident cancer patient cases, with a median age of 75 (interquartile range, 71-81), and 454,029 imaging procedures were performed. The mean number of images per patient increased from 7.4 in 2003 to 12.9 in 2006. Rates of imaging were similar across age groups, with the exception of greater use of echocardiograms and NM studies in younger patients with breast cancer and greater use of PET among younger patients with lung cancer. Advanced imaging accounted for approximately 41% of all imaging, or approximately 85% of the $8.7 million in imaging expenditures. Costs were nearly $2,000 per HMO enrollee; costs for younger patients with NHL, leukemia, and lung cancer were nearly $1,000 more in 2003. CONCLUSION: Rates of advanced imaging appear comparable among FFS and HMO participants of any age with these six cancers.

Physicians' propensity to discuss prognosis is associated with patients' awareness of prognosis for metastatic cancers.

BACKGROUND: Prognosis discussion is an essential component of informed decision-making. However, many terminally ill patients have a limited awareness of their prognosis and the causes are unclear. OBJECTIVE: To explore the impact of physicians' propensity to discuss prognosis on advanced cancer patients' prognosis awareness. DESIGN: Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study, a prospective cohort study with patient and physician surveys. SETTING/SUBJECTS: We investigated 686 patients with metastatic lung or colorectal cancer at diagnosis who participated in the CanCORS study and reported about their life expectancy. Data were linked to the physician survey from 486 physicians who were identified by these patients as filling important roles in their cancer care. RESULTS: Few patients with metastatic cancers (16.5%) reported an accurate awareness of their prognosis, defined as reporting a life expectancy of less than 2 years for lung cancer or less than 5 years for colorectal cancer. Patients whose most-important-doctor (in helping patient make decisions) reported discussing prognosis with terminally ill patients earlier were more likely than those whose doctors deferred these discussions to have an accurate prognosis awareness (adjusted proportion, 18.5% versus 7.6%; odds ratio, 3.23; 95% confidence interval, 1.39-7.52; p=0.006). CONCLUSIONS: Few patients with advanced cancer could articulate an accurate prognosis estimate, despite most having received chemotherapy and many physicians reported they would discuss prognosis early. Physicians' propensity to discuss prognosis earlier was associated with more accurate patient reports of prognosis. Enhancing the communication skills of providers with important roles in cancer care may help to improve cancer patients' understanding of their prognosis.

Associations between palliative chemotherapy and adult cancer patients' end of life care and place of death: prospective cohort study.

OBJECTIVES: To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients' subsequent intensive medical care and place of death. DESIGN: Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer. SETTING: Eight outpatient oncology clinics in the United States. PARTICIPANTS: 386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died. PRIMARY OUTCOMES: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients' place of death (for example, intensive care unit). SECONDARY OUTCOMES: survival, late hospice referrals (≤ 1 week before death), and dying in preferred place of death. RESULTS: 216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% v 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% v 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% v 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% v 66%; -10.8%, -1.0% to -20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% v 80%; adjusted risk difference -9.4%, -0.8% to -18.1%). CONCLUSIONS: The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients' attainment of their goals.