Financial Performance of Accountable Care Organizations: A 5-Year National Empirical Analysis.

GOALS: Of 513 accountable care organizations (ACOs) participating in the Medicare Shared Savings Program (MSSP) in 2020, 67% generated a positive shared savings of approximately $2.3 billion. This research aimed to examine their financial performance trends and drivers over time. METHODS: The unit of analysis was the ACO in each year of the study period from 2016 to 2020. The dependent variable was the ACOs' total shared savings earned annually per beneficiary. The independent variables included ACO age, risk model, clinician staffing type, and provider type (hybrid, hospital-led, or physician-led). Covariates were the average risk score among beneficiaries, payer type, and calendar year. The Centers for Medicare & Medicaid Services (CMS) public use files (PUFs) and a commercial healthcare data aggregator were the data sources. RESULTS: ACOs' earned shared savings grew annually by 35%, while the proportions of ACOs with positive shared savings grew by 21%. For 1-year increase in ACO age, an additional $0.57 of shared savings per beneficiary was observed. ACOs with two-sided risk contracting were associated with an average marginal increase of $109 in shared savings per beneficiary compared to ACOs with one-sided risk contracting. Primary care physicians were associated with the greatest increase in earned shared savings per beneficiary. In contrast, nurse practitioners/physician assistants/clinical nurse specialists were associated with a reduction in earned shared savings. Under a one-sided risk model, hospital-led ACOs were associated with $18 higher average shared savings earning per beneficiary compared to hybrid ACOs, while physician-led ACOs were associated with lower average saved shared earnings per beneficiary at -$2 compared to hybrid ACOs. Provider-type results were not statistically significant at the 5% nominal level. No statistically significant differences were observed between provider types under a two-sided risk model. PRACTICAL APPLICATIONS: For all ACO provider types, building broader primary care provider networks was correlated with positive financial results. Future research should examine whether ACOs are conducting specific preventive screenings for cancer or monitoring conditions such as diabetes, hypertension, heart disease, obesity, mental disorders, and joint disorders. Such studies may answer health policy and strategy questions about the effects of incentives for improved ACO performance in serving a healthier population.

Significant Incidental Findings in the National Lung Screening Trial.

Importance: Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described. Objective: To describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology's white papers on incidental findings. Design, Setting, and Participants: This was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers. Main Outcomes and Measures: Significant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm. Results: Of 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer. Conclusions and Relevance: This case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.

The potential impact of proxy reports for symptom experience and care quality and experience in advanced cancer.

OBJECTIVES: As the US tests models of care for the seriously ill, patient perceptions of the quality of care are important. Proxies are often needed for this group. We sought to understand the potential impact of proxy reports for the assessment of care quality and experience in cancer. METHODS: Secondary data analysis of a deidentified prospective study that included surveys of perceived care quality, including symptom management, from patients with advanced cancer receiving chemotherapy and their caregivers. Surveys were administered at diagnosis (time 1) and treatment (time 2), with top-box scoring used for analysis. Overall concordance was assessed using metrics including Gwet's AC1. The proportion of the highest scores by respondent type within 2 subgroups were examined: (1) symptom burden and (2) practice setting. RESULTS: Data from 83 dyads were analyzed. Proxies and patients frequently reported the highest scores for quality (time 1: proxies: 77% and patients: 80%). At time 1, 14% of proxies and 10% of patients reported an unmet need for symptom palliation. Most patients reporting an unmet need gave the top score for quality (75%), but fewer proxies did so (45%). Proxy and patient reports were similar within practice settings. Concordance was at least moderate (nearly all outcomes >0.5 and some >0.8) by Gwet's AC1. SIGNIFICANCE OF RESULTS: Findings of at least moderate concordance and similar experience outcomes within subgroups suggest the use of proxies may not change estimates substantially. However, consideration should be taken when evaluating symptom management, particularly if such evaluations inform assessment of provider performance.

Association of Patient-Reported Physician Awareness of Complementary Medicine, Medical Care Experience and Care Quality.

The aim was to examine the association of patient-reported physician awareness of biological CAM use and patient perceptions of care experience and quality with a population-based study of patients with incident lung and colorectal cancer. This was a secondary data analysis using regression models. Outcomes of interest were patient reports of medical care experience and quality ratings. Among 716 patients who reported biological CAM use, 69% reported their physicians were aware of this. Patients who reported physician awareness of biological CAM use had higher adjusted scores for medical care experience ( + 5.4, 95%CI:2.3,8.6) and care quality ( + 3.6, 95%CI:-0.3, + 7.5). These associations suggest that physicians should be encouraged to inquire about biological CAM use.

Does Knowledge of Treatment Assignment Affect Patient Report of Symptoms, Function, and Health Status? An Evaluation Using Multiple Myeloma Trials.

OBJECTIVES: Unblinded trials are common in oncology, but patient knowledge of treatment assignment may bias response to questionnaires. We sought to ascertain the extent of possible bias arising from patient knowledge of treatment assignment. METHODS: This is a retrospective analysis of data from 2 randomized trials in multiple myeloma, 1 double-blind and 1 open label. We compared changes in patient reports of symptoms, function, and health status from prerandomization (screening) to baseline (pretreatment but postrandomization) across control and investigational arms in the 2 trials. Changes from prerandomization scores at ~2 and 6 months on treatment were evaluated only across control arms to avoid comparisons between 2 different experimental drugs. All scores were on 0- to 100-point scales. Inverse probability weighting, entropy balancing, and multiple imputation using propensity score splines were used to compare score changes across similar groups of patients. RESULTS: Minimal changes from screening were seen at baseline in all arms. In the control arm, mean changes of <7 points were seen for all domains at 2 and 6 months. The effect of unblinding at 6 months in social function was a decline of less than 6 points (weighting: -3.09; 95% confidence interval -8.41 to 2.23; balancing: -4.55; 95% confidence interval -9.86 to 0.76; imputation: -5.34; 95% confidence interval -10.64 to -0.04). CONCLUSION: In this analysis, we did not find evidence to suggest that there was a meaningful differential effect on how patients reported their symptoms, function or health status after knowing their treatment assignment.

Patient and proxy reports regarding the experience of treatment decision-making in cancer care.

OBJECTIVE: Shared decision-making, including the elicitation of patient preferences regarding treatment decisions, is considered part of high-quality cancer care. However, patients may not be able to self-report due to illness, and therefore proxy reports may be used. We sought to determine the difference between proxy and patient reports about patient decisions and preferences among patients who received or were scheduled for chemotherapy using data from a large, population-based survey of patients with incident lung or colorectal cancer. METHODS: Of 3573 patients who received or were scheduled for chemotherapy, 3108 self-reported and 465 had proxies reporting on their behalf about preferred and actual decision roles regarding this treatment. Preferred and actual decision roles were assessed using the Control Preferences Scale, and categorized as shared, patient-controlled, or doctor-controlled. Multivariable logistic regression models were used to assess the association between patient and proxy responses and whether preferences were met. The models adjusted for sociodemographic and clinical variables and patient/proxy-reported health status. RESULTS: Sixty-three percent of all respondents reported actual roles in decisions that matched their preferred roles (role attainment). Proxies and patients were similarly likely to report role attainment (65% vs 63%). In adjusted analyses, proxies were more likely report role attainment (OR = 1.27, 95%CI = 1.02-1.59), but this difference was smaller if health variables were excluded from the model (OR = 1.14, 95%CI = 0.92-1.41). CONCLUSION: Most patients' preferences for treatment participation were met. Surveys from proxies appear to yield small differences on the reports of attainment of preferred treatment decision-making roles in cancer care vs surveys from patients.

Analyzing patient-reported outcome data when completion differs between arms in open-label trials: an application of principal stratification.

PURPOSE: Cancer trials are often open-label and include patient-reported outcomes (PROs). Previous work has demonstrated that patients may complete PRO assessments less frequently in the control arm compared with the experimental arm in open-label trials. Such differential completion may affect PRO results. This paper sought to explore principal stratification methodology to address potential bias caused by the posttreatment intermediate variable of questionnaire completion. METHODS: We evaluated six randomized trials (five open-label and one double-blind) of anticancer therapies with varying levels of PRO completion submitted to the Food and Drug Administration (FDA). We applied complete case analysis (CCA), multiple imputation (MI), and principal stratification to evaluate PRO results for quality of life (QOL) and the domains of physical, role, and emotional function (PF, RF, and EF). Assignment to potential principal strata was by the expectation maximization algorithm using patient baseline characteristics. RESULTS: Completion rates in the experimental arm ranged from 66% to 94% and 51% to 95% in the control arm. Four trials had negligible completion differences between arms (1%-2%), and two had large differences favoring the experimental arm (15%-17%). For trials with negligible completion differences, principal stratification results were similar to CCA and MI results for all domains. Notable differences in point estimates may be observed in trials with large differences in completion rates. However, in the examined trials, the confidence intervals for the principal stratification estimates overlapped with the ones obtained using CCA. CONCLUSIONS: The principal stratification estimand may be a useful additional analysis, especially if PRO completion differs between arms.

The Association of Proxy Care Engagement with Proxy Reports of Patient Experience and Quality of Life.

OBJECTIVE: To assess the association of proxy-specific covariates with proxy-reported patient cancer care experience, quality rating, and quality of life. DATA SOURCES/STUDY SETTING: Secondary analysis of data from the Cancer Care Outcomes Research and Surveillance (CanCORS) study. STUDY DESIGN: Cross-sectional observational study. The respondents were proxies for patients with incident colorectal or lung cancer. DATA COLLECTION/EXTRACTION METHODS: Analyses used linear regression models and adjusted for patient sociodemographic and clinical characteristics. Outcomes included patients' experiences with medical care, nursing care, and care coordination, overall quality ratings, and physical and mental health, all scored on 0-100 scales (0 = worst, 100 = best). Independent variables included the proxy's relationship with the patient and engagement in patient care. PRINCIPAL FINDINGS: Of 1,011 proxies, most were the patient's spouse (50 percent) or child (36 percent). Although most proxies (66 percent) always attended medical visits, 3 percent reported never attending. After adjustment, on average children reported worse experiences and poorer quality care than spouses (4-9 points lower across outcomes). Proxies who never attended medical visits reported significantly worse medical care (-11 points, 95 percent CI = -18 to -3) and care coordination (-13 points, 95 percent CI = -20 to -6). CONCLUSIONS: Collecting data on proxy engagement in care is warranted if proxy responses are used.

Proxy and patient reports of health-related quality of life in a national cancer survey.

BACKGROUND: Proxy respondents are frequently used in surveys, including those assessing health-related quality of life (HRQOL). In cancer, most research involving proxies has been undertaken with paired proxy-patient populations, where proxy responses are compared to patient responses for the same individual. In these populations, proxy-patient differences are small and suggest proxy underestimation of patient HRQOL. In practice, however, proxy responses will only be used when patient responses are not available. The difference between proxy and patient reports of patient HRQOL where patients are not able to report for themselves in cancer is not known. The objective of this study was to evaluate the difference between patient and proxy reports of patient HRQOL in a large national cancer survey, and determine if this difference could be mitigated by adjusting for clinical and sociodemographic information about patients. METHODS: Data were from the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Patients or their proxies were recruited within 3-6 months of diagnosis with lung or colorectal cancer. HRQOL was measured using the SF-12 mental and physical composite scales. Differences of ½ SD (=5 points) were considered clinically significant. The primary independent variable was proxy status. Linear regression models were used to adjust for patient sociodemographic and clinical covariates, including cancer stage, patient age and education, and patient co-morbidities. RESULTS: Of 6471 respondents, 1011 (16%) were proxies. Before adjustment, average proxy-reported scores were lower for both physical (-6.7 points, 95% CI -7.4 to -5.9) and mental (-6 points, 95% CI -6.7 to -5.2) health. Proxy-reported scores remained lower after adjustment (physical: -5.8 points, -6.6 to -5; mental: -5.8 points, -6.6 to 5). Proxy-patient score differences remained clinically and statistically significant, even after adjustment for sociodemographic and clinical variables. CONCLUSIONS: Proxy-reported outcome scores for both physical and mental health were clinically and significantly lower than patient-reported scores for these outcomes. The size of the proxy-patient score differences was not affected by the health domain, and adjustment for sociodemographic and clinical variables had minimal impact.

Differences between Proxy and Patient Assessments of Cancer Care Experiences and Quality Ratings.

OBJECTIVE: To assess the impact of proxy survey responses on cancer care experience reports and quality ratings. DATA SOURCES/STUDY SETTING: Secondary analysis of data from Cancer Care Outcomes Research and Surveillance (CanCORS). Recruitment occurred from 2003 to 2005. STUDY DESIGN: The study was a cross-sectional observational study. The respondents were patients with incident colorectal or lung cancer or their proxies. DATA COLLECTION/EXTRACTION METHODS: Analyses used linear regression models with an independent variable for proxy versus patient responses as well as study site and clinical covariates. The outcomes were experiences with medical care, nursing care, care coordination, and care quality rating. Multiple imputation was used for missing data. PRINCIPAL FINDINGS: Among 6,471 respondents, 1,011 (16 percent) were proxies. The proportion of proxy respondents varied from 6 percent to 28 percent across study sites. Adjusted proxy scores were modestly higher for medical care experiences (+1.28 points [95 percent CI:+ 0.05 to +2.51]), but lower for nursing care (-2.81 [95 percent CI: -4.11 to -1.50]) and care coordination experiences (-2.98 [95 percent CI: -4.15 to -1.81]). There were no significant differences between adjusted patient and proxy ratings of quality. CONCLUSIONS: Proxy responses have small but statistically significant differences from patient responses. However, if ratings of care are used for financial incentives, such differences could be exaggerated across practices or areas if proxy use varies.

Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia.

Comparative data on immunochemotherapy regimens for Waldenström macroglobulinaemia/lymphoplasmacytic lymphoma (WM/LPL) are lacking. We analysed overall survival (OS), risk of hospitalizations, transfusions and plasmapheresis in a population-based cohort of patients ≥65 years old initiating WM/LPL therapy in 1999-2013. To minimize bias, we applied a propensity score-based causal inference method. We conducted three analyses of: patients treated with or without rituximab, patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators. Among 1310 patients, 78·5% received rituximab. Patients who received rituximab had significantly better OS [hazard ratio (HR) 0·62, 95% confidence interval (CI) 0·55-0·71] and lower risk of transfusions (risk difference -3·3%, 95% CI -6·3 to -0·3) than those who did not, without a significant difference in hospitalizations or plasmapheresis. We observed no significant difference in OS (HR 0·91, 95% CI 0·79-1·04) between rituximab monotherapy and combination immunochemotherapy, but toxicity outcomes were lower with rituximab alone. Neither survival (HR 1·10, 95%CI 0·92-1·32) nor toxicity outcomes differed significantly between regimens based on purine analogues or alkylators. The survival advantage strongly supports rituximab as part of upfront therapy for WM/LPL, whereas regimens with either purine analogues or alkylating agents result in similar outcomes.

Different analyses estimate different parameters of the effect of erythropoietin stimulating agents on survival in end stage renal disease: a comparison of payment policy analysis, instrumental variables, and multiple imputation of potential outcomes.

OBJECTIVE: To compare the assumptions and estimands across three approaches to estimate the effect of erythropoietin-stimulating agents (ESAs) on mortality. STUDY DESIGN AND SETTING: Using data from the Renal Management Information System, we conducted two analyses using a change to bundled payment that, we hypothesized, mimicked random assignment to ESA (pre-post, difference-in-difference, and instrumental variable analyses). A third analysis was based on multiply imputing potential outcomes using propensity scores. RESULTS: There were 311,087 recipients of ESAs and 13,095 non-recipients. In the pre-post comparison, we identified no clear relationship between bundled payment (measured by calendar time) and the incidence of death within 6 months (risk difference -1.5%; 95% confidence interval [CI] -7.0%, 4.0%). In the instrumental variable analysis, the risk of mortality was similar among ESA recipients (risk difference -0.9%; 95% CI -2.1, 0.3). In the multiple imputation analysis, we observed a 4.2% (95% CI 3.4%, 4.9%) absolute reduction in mortality risk with the use of ESAs, but closer to the null for patients with baseline hematocrit level >36%. CONCLUSION: Methods emanating from different disciplines often rely on different assumptions but can be informative about a similar causal contrast. The implications of these distinct approaches are discussed.

Monitoring methods in the surgical arena: assumptions and potential pitfalls.

Utilization of statistical graphical methods to detect deterioration and to compare performance of health providers (e.g., surgeons, surgical departments, centers, etc.) has been rapidly increasing. These methods rely heavily on assumptions that may not be applicable in all surgical scenarios. The results produced by those methods could have major potential impact on funding, court rulings, insurance rates, etc. Thus, if one wants to use these graphical methods, it is imperative that the methods produce highly reliable results, even when some of the assumptions that underlie such methods are violated. In this manuscript, we discuss some of the assumptions that underlie such methods. We examine the performance of these methods when some assumptions are violated by using simulations based on analyses of plausible data. Our results show that using current graphical methods to compare two or more health providers when the assumptions are not met could result in misleading conclusions. Hence, researchers should apply these types of graphical methods with appropriate care, and only after making sure that the underlying assumptions are valid or the methods are robust enough to those violations.

All-trans retinoic acid modifies the expression of clock and disease marker genes.

Restricted feeding (RF), a regimen that restricts the duration of food availability with no calorie restriction, entrains the circadian clock in peripheral tissues. Restricted feeding leads to high-amplitude circadian rhythms, which have been shown to promote wellness and reduce disease and inflammatory markers. Retinoids, such as all-trans retinoic acid (ATRA), act as anti-inflammatory agents. Thus far, the effect of ATRA combined with RF on the ability to delay the occurrence of age-associated changes, such as cancer and inflammation, is not known. We measured circadian expression of clock genes, disease marker genes and inflammatory markers in the serum, liver and jejunum in mice fed ad libitum (AL) or RF supplemented with 15 or 250 µg/kg body/day ATRA for 16 weeks. Our results show that ATRA supplementation led to phase shifts and reduced amplitudes in clock genes. Under AL, ATRA reduced the average daily messenger RNA (mRNA) levels of some disease markers, such as liver Afp and jejunum Afp, Alt and Gadd45ß and aspartate transaminase (AST) protein in the serum, but increased the expression level of liver Crp mRNA. Under RF, ATRA reduced the average daily levels of jejunum Alt and Gadd45ß and AST protein in the serum, but increased liver Afp, Alt, Gadd45ß and Arginase mRNA. Altogether, our findings suggest that ATRA strongly affects circadian oscillation and disease marker levels. Moreover, its impact is different depending on the feeding regimen (AL or RF).

Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers.

The circadian clock in peripheral tissues can be entrained by restricted feeding (RF), a regimen that restricts the duration of food availability with no calorie restriction (CR). However, it is not known whether RF can delay the occurrence of age-associated changes similar to CR. We measured circadian expression of clock genes, disease marker genes, metabolic factors and inflammatory and allergy markers in mouse serum, liver, jejunum and white adipose tissue (WAT) after long-term RF of 4 months. We found that circadian rhythmicity is more robust and is phase advanced in most of the genes and proteins tested under RF. In addition, average daily levels of some disease and inflammatory markers were reduced under RF, including liver Il-6 mRNA, tumour necrosis factor (TNF)-α and nuclear factor κB (NF-κB) protein; jejunum Arginase, Afp, Gadd45ß, Il-1α and Il-1ß mRNA, and interleukin (IL)-6 and TNF-α protein and WAT Il-6, Il-1ß, Tnfα and Nfκb mRNA. In contrast, the anti-inflammatory cytokine Il-10 mRNA increased in the liver and jejunum. Our results suggest that RF may share some benefits with those of CR. As RF is a less harsh regimen to follow than CR, the data suggest it could be proposed for individuals seeking to improve their health.

"Gloves-and-socks" melanoma: does histology make a difference?

BACKGROUND: Acral lentiginous melanoma (ALM) is associated with low survival. OBJECTIVE: The aim of the study was to compare the clinical course of ALM, non-ALM hand and foot melanoma, and melanoma of the extremities in nonacral locations. METHODS: Data on 168 patients operated on for cutaneous melanoma of the extremities from 1993 to 2005 were examined. Twenty-nine had ALM, 16 non-ALM, and 123 other-extremity melanoma. All known melanoma prognosticators were analyzed for their impact on survival at a median of 53 months' follow-up. RESULTS: The ALM group was significantly older (p=.015). No differences between the ALM and non-ALM groups were noted in tumor characteristics, lymph node status, and survival. However, the other-extremity melanoma group presented with significantly thinner lesions, fewer positive sentinel lymph nodes, and lower tumor stage and, consequently, had significantly better disease-specific and disease-free survival (p=.006, p=.0001). The acral lesions were nearly free of peritumoral lymphocytic infiltration. Multivariate analysis identified only tumor thickness (p=.0127), stage (p=.00001), and patient age (p=.012) as independent prognosticators of disease-specific survival. CONCLUSION: Cutaneous melanomas in acral sites, regardless of histology, tend to be diagnosed at an advanced stage probably owing to older patient age, difficult-to-see sites, and biologic factors, leading to reduced patient survival.

Two strategies for coping with food shortage in desert golden spiny mice.

Desert rodents face periods of food shortage and use different strategies for coping with it, including changes in activity level. Golden spiny mice (Acomys russatus) inhabit rock crevasses and do not dig burrows nor store food. When kept under 50% food restriction most, but not all, golden spiny mice defend their body mass by physiological means. We tested the hypothesis that these rodents use two different behavioral strategies, i.e., increasing activity level and searching for food or decreasing activity level and conserving energy to cope with food shortage. Twelve golden spiny mice were fed ad libitum for 14 days, followed by 40 days of 50% food restriction, and 14 days of refeeding. Body mass, food consumption and general activity were monitored. Seven mice significantly reduced activity level, concentrating their activity around feeding time, lowering energy expenditure and thus keeping their body mass constant ("resistant"), while five ("non-resistant") significantly increased activity level (possibly searching for food) and thus energy expenditure, thereby losing mass rapidly (more than 25% of body mass). The non-resistant golden spiny mice were active throughout many hours of the day, with high variability both between and among individuals. The use of two strategies to cope with food shortage as found in the golden spiny mice may be of evolutionary advantage, since it allows a more flexible reaction to food restriction at the population level.

Breast cancer in octogenarians.

BACKGROUND: The number of older cancer patients has increased in recent years. Guidelines for their care are often lacking. Data on the natural course of breast cancer and outcome of therapy in this population are needed. METHODS: The authors undertook a retrospective chart review with complete follow-up of 135 women diagnosed with localized breast cancer at age 80 years or older, who received standard or less than standard local treatment in 2 tertiary centers in Israel between 1991 and 2001. RESULTS: Median age at diagnosis was 83 years. In 60 (44%) patients, initial local treatment consisted of modified radical mastectomy or lumpectomy and axillary dissection followed by radiation therapy [standard local treatment (SLT)]; 75 (56%) patients received less than SLT. Tumors were stage T1-T2 in 90% of cases, 76% of the tumors were hormone-sensitive. Infiltrating duct carcinoma predominated (90 cases), mostly (80 of 90) Grade 2-3. Lymph node metastases were detected in 32 of 73 (44%) patients who underwent axillary lymph node dissection. At a median of 70 months after diagnosis, 18 (13%) patients had disease recurrence, and 34 (25%) had died. Axillary failures were detected only in the less-than-SLT group. This did not indicate worse overall or disease-specific survival. CONCLUSION: Most breast cancer octogenarians in this series lived > 6 years after diagnosis. These data do not support the assumption that breast tumors are histologically more indolent in elderly patients. Less than SLT can be applied to this patient group with somewhat increased axillary failure rates that may be addressed upfront by the sentinel node technique.

Patterns of failure in patients with malignant melanoma treated with high-dose interferon-alpha2b in the adjuvant setting.

The aim of this prospective study was to record the pattern of failure associated with high-dose interferon-alpha2b (IFN) adjuvant therapy after surgery. It included 55 consecutive patients with stage IIB and III melanoma (median age 50 years) rendered disease-free by surgery but considered at high risk for relapse from a tertiary referral, university-affiliated medical centre. Intervention consisted of IFN 20 mU/m(2) per day intravenously, 5 days a week for 4 weeks, followed by subcutaneous IFN 10 mU/m(2) per day three times a week for 48 weeks. Treatment was stopped at completion of protocol, at disease progression or due to unacceptable toxicity. Dose modification followed treatment-related toxicity. Twenty-six of the 55 patients (47%) relapsed: 14 during treatment and 12 after completion of the protocol. Eighteen of these 26 patients (69%) relapsed initially in a single organ, most commonly in soft tissue or the CNS. A single metastasis was noted in 12 of the 18 patients, and multiple metastases confined to a single organ were detected in the other six. No statistically significant survival advantage could be demonstrated in association with any of the patterns of relapse. Patients treated for stage IIB disease fared better than those treated for stage III disease, regardless of whether the regional metastases were microscopic or palpable. IFN seems to be more commonly associated with a single-organ/single-metastasis pattern of failure, and more soft tissue and CNS relapses. This pattern did not translate into a survival advantage in this series. Larger databases should be explored to validate these trends.