Immunotherapy disparities in metastatic melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9525-9525 ◽  
Author(s):  
Thomas Oliver ◽  
Todd A. Pezzi ◽  
Ashley E. Pezzi ◽  
Amanda Shreders ◽  
Henry Dao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Therapy Response ◽  
Subsequent Development ◽  
The United States ◽  
Community Practice ◽  
Term Survival ◽  
Dismal Prognosis

9525 Background: Historically, patients with advanced malignant melanoma had a dismal prognosis with an estimated median overall survival of nine months. Therapy response rates and long-term survival have significantly improved with the advent of immunotherapies and targeted chemotherapies. First approved in 2011, there has been subsequent development of more advanced immunotherapeutic agents and targeted chemotherapies, with continued improvement in median overall survival. We examined patterns in the use of immunotherapy and other systemic therapies for metastatic melanoma, as well as the demographic and socioeconomic predictors for the use of these therapies, in order to identify and understand potential barriers to access in the United States. Methods: We used the NCDB for all patients aged 18-years and older who were diagnosed with metastatic melanoma of cutaneous origin from 2004-2014. Patients were included if they had distant metastases or American Joint Committee on Cancer (AJCC) Stage IV. Sociodemographic data, including race, age, insurance status, facility providing care, Charlson/Deyo comorbidity score11, and education by patient’s zip code, were collected. Results: In patients under age 65 with a Charlson-Deyo score of zero, immunotherapy utilization ranged between 8.5–13.4% during 2004 to 2010. In 2011, the usage increased to 16.5% and rose every subsequent year to 29.6% in 2014. Patients were less likely to receive immunotherapy if they had no insurance, were of older age, or received care at a community practice rather than an academic center. Those who received immunotherapy had greater overall survival compared with those who did not. Conclusions: Immunotherapy and targeted agents have become standard of care in those with metastatic melanoma. Adoption of immunotherapy use for metastatic melanoma has been relatively slow despite evidence showing an overall survival benefit; our analysis suggests this is explained in part by socioeconomic barriers.

Adrenalectomy for Metastatic Melanoma: Current Role in the Age of Nonsurgical Treatments

2015 ◽  
Vol 81 (10) ◽  
pp. 1005-1009 ◽  
Author(s):  
Devin C. Flaherty ◽  
Gary B. Deutsch ◽  
Daniel D. Kirchoff ◽  
Jihey Lee ◽  
Kelly T. Huynh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Surgical Resection ◽  
Stage Iv ◽  
Nonoperative Treatment ◽  
Unknown Primary ◽  
Adrenal Metastases ◽  
Term Survival ◽  
Relative Value ◽  
Resection Of Metastases

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: Data from the Italian cohort of ipilimumab expanded access programme (EAP).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9035-9035 ◽  
Author(s):  
Paolo Antonio Ascierto ◽  
Ester Simeone ◽  
Vanna Chiarion-Sileni ◽  
Paola Queirolo ◽  
Michele Del Vecchio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Disease Progression ◽  
Median Overall Survival ◽  
Therapeutic Option ◽  
Braf Inhibitor ◽  
Stage Iv ◽  
Sequential Treatment ◽  
Braf Inhibitors ◽  
A Prospective Study

9035 Background: Ipilimumab and vemurafenib have recently been approved as single agents for the treatment of unresectable or metastatic melanoma. Currently, limited data exist on the sequential treatment with these agents in patients (pts) with the BRAF mutation; here we evaluate the efficacy outcomes of pts enrolled in the EAP in Italy who sequentially received a BRAF-inhibitor and ipilimumab, or vice versa. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Patients were considered for this analysis if they tested positive for the BRAF mutation and had received a BRAF-inhibitor before or after ipilimumab treatment. Results: In total, 855 Italian pts participated in the EAP from June 2010 to January 2012 across 55 centres. Out of 173 BRAF positive pts, 93 (53.7%) were treated sequentially with both treatments: 48 pts received a BRAF inhibitor upon disease progression with ipilimumab and 45 pts received ipilimumab upon disease progression with a BRAF inhibitor. As of December 2012, median overall survival was 14.5 months (11.1-17.9) and 9.7 months (4.6-14.9) for the two groups, respectively (p=0.01). Among the 45 BRAF inhibitors pretreated pts, 18 (40%) had rapid disease progression (median overall survival: 5.8 months) and were unable to complete all four induction doses of ipilimumab, while the remaining 27 (60%) pts had slower disease progression (median overall survival: 19.3 months) and were able to complete the therapy with ipilimumab. Conclusions: These preliminary results suggest that, in BRAF-mutated pts, to start the sequential treatment with ipilimumab can provide a better survival than the reverse sequence. These findings deserve confirmation in a prospective study.

scholarly journals Butterfly Glioblastoma - the Impact of Tumor Volumes and Treatment Strategies on Clinical Outcome

2021 ◽  
Author(s):  
Line Sagerup Bjorland ◽  
Kathinka Dæhli Kurz ◽  
Fluge Øystein Fluge ◽  
Bjørnar Gilje ◽  
Rupavathana Mahesparan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Multimodal Treatment ◽  
Median Overall Survival ◽  
Treatment Strategies ◽  
Cox Proportional Hazards ◽  
Comprehensive Treatment ◽  
Term Survival ◽  
Dismal Prognosis ◽  
The Impact

Abstract PurposeButterfly glioblastoma is a rare subgroup of glioblastoma with a bihemispheric tumor crossing the corpus callosum, and is associated with a dismal prognosis. Prognostic factors are previously sparsely described and optimal treatment approaches remain uncertain. We aimed to analyse prognostic factors in butterfly glioblastoma, and to evaluate treatment strategies and outcome in a real-world setting.MethodsWe conducted a retrospective population-based cohort study of patients diagnosed with butterfly glioblastoma in Western Norway between 01/01/2007 and 31/12/2014. Clinical data were extracted from electronic medical records. Molecular and MRI volumetric analyses were retrospectively performed. Survival analyses were performed using Kaplan-Meier method and Cox proportional hazards regression models.ResultsAmong 381 patients diagnosed with glioblastoma, 33 patients (8.7%) met the criteria for butterfly glioblastoma. Median overall survival was 5.5 months (95% CI 3.1-7.9) and three-year survival was 9.1%. Older age and mainly deep-seated tumour location were associated with poor outcome, with adjusted hazard ratio (HR) 1.06 (95% CI 1.03-1.10), p<0.001, and adjusted HR 4.58 (95% CI 1.15-18.20), p=0.03. Best supportive care was associated with poorer survival compared to multimodal treatment (adjusted HR 5.11 (95% CI 1.09-23.89), p=0.04).ConclusionOutcome from butterfly glioblastoma was dismal, with a median overall survival of less than six months. However, long-term survival was comparable to that observed in glioblastoma in general, and multimodal treatment was associated with longer survival. This suggests that patients with butterfly glioblastoma may benefit from a more comprehensive treatment approach despite the overall poor prognosis.

scholarly journals Gastric Cancer Treatments and Survival Trends in the United States

2020 ◽  
Vol 28 (1) ◽  
pp. 138-151
Author(s):  
Kelly A. Stahl ◽  
Elizabeth J. Olecki ◽  
Matthew E. Dixon ◽  
June S. Peng ◽  
Madeline B. Torres ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Stage Iv ◽  
The United States ◽  
Current Treatment ◽  
Stage I ◽  
Stage Ii ◽  
Chi Square ◽  
Specific Guideline ◽  
Kaplan Meier

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

scholarly journals Long-Term Survival and Value of 18F-FDG PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with Second Peptide Receptor Radionuclide Therapy Course with 177Lu-DOTATATE

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 198
Author(s):  
Margarida Rodrigues ◽  
Kevin-Klaus Winkler ◽  
Hanna Svirydenka ◽  
Bernhard Nilica ◽  
Christian Uprimny ◽  
...  
Keyword(s):  
Overall Survival ◽  
Fdg Pet ◽  
Median Overall Survival ◽  
Peptide Receptor Radionuclide Therapy ◽  
Term Survival ◽  
Peptide Receptor ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to evaluate the long-term survival and efficacy of a second PRRT course with 177Lu-DOTATE in patients with advanced gastroenteropancreatic (GEP) NETs. Furthermore, the value of 18F-FDG PET/CT in these patients was evaluated. 40 patients with GEP NETs who underwent two PRRT courses with 177Lu-DOTATATE and combined examinations with 68Ga-DOTA-TOC and 18F-FDG PET/CT were evaluated. After the second PRRT course, two patients (5.0%) were in partial remission, 21 patients (52.5%) in stable disease and 17 patients (42.5%) had progressive disease. The median overall survival was 122.10 months. After the second PRRT course, the median overall survival was significantly higher (p = 0.033) in the 18F-FDG-negative group compared to the 18F-FDG-positive group (145.50 versus 95.06 months, respectively). The median time to progression was 19.37 months. In conclusion, a second PRRT course with 177Lu-DOTATE is an effective treatment approach for GEP NET patients with disease progression. A change in 18F-FDG status after PRRT may predict the disease course and survival. Patients who are 18F-FDG-negative have a significantly longer overall survival than those who are 18F-FDG-positive.

scholarly journals The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive Value for Neoadjuvant Chemotherapy

2018 ◽  
Vol 28 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Parvin Tajik ◽  
Roelien van de Vrie ◽  
Mohammad H. Zafarmand ◽  
Corneel Coens ◽  
Marrije R. Buist ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Value ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Figo Stage ◽  
Figo Staging ◽  
Stage Ivb

ObjectiveThe revised version of the International Federation of Gynaecology and Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a number of changes. One of these is the division of stage IV into 2 subgroups. Data on the prognostic and predictive significance of this classification are scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) in relation to the subclassification of FIGO stage IV is also unknown.MethodsWe used data of the EORTC 55971 trial, in which 670 patients with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO staging and presence of pleural effusion with positive cytology were used to classify tumors as either stage IVA or IVB. We tested the association between stage IVA/IVB and survival to evaluate the prognostic value and interactions between stage, treatment, and survival to evaluate the predictive performance.ResultsAmong the 160 participants with previous stage IV disease, 103 (64%) were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P = 0.044). Stage IVB patients treated with NACT had 9 months longer median overall survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA patients, no significant difference was observed (24 vs 26 months, P = 0.48).ConclusionsThe reclassification of FIGO stage IV into stage IVA or IVB was not prognostic as expected. Compared with stage IVA patients, stage IVB patients have a better overall survival and may benefit more from NACT.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Myeloid-derived suppressor cell quantity prior to treatment with ipilimumab at 10mg/kg to predict for overall survival in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2518-2518 ◽  
Author(s):  
Shigehisa Kitano ◽  
Michael Andrew Postow ◽  
Czrina Cortez ◽  
Teresa Rasalan ◽  
Humilidad F. Gallardo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Clinical Benefit ◽  
Stage Iv ◽  
T Cell Proliferation ◽  
Pre Treatment

2518 Background: Ipilimumab, an antibody that blocks the function of the immune inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4), significantly prolongs survival in patients with metastatic melanoma. Approximately 30% of patients derive clinical benefit from therapy. Defining biomarkers of response to ipilimumab therapy would enable selection of patients more likely to respond and is relevant for both practicing clinicians and for clinical trial design. We performed a pilot correlative study evaluating myeloid derived suppressor cells (MDSC), a population of immune suppressive monocytic cells, as a biomarker of clinical outcome. Methods: Peripheral blood from 26 patients with stage IV melanoma treated with ipilimumab 10mg/kg every 3 weeks for 4 doses at our center, as part of an expanded access program (BMS CA184-045) was assessed for MDSC quantity (%CD14+,HLA-DRlow/- cells) pre-treatment, at week 7, week 12, and week 24 by flow cytometry. MDSC ability to inhibit T cell proliferation was tested using an in vitro suppression assay. Results: We found that lower MDSC quantity pre-treatment predicted for improved overall survival (Hazard ratio 1.07 (1.03, 1.11) p=0.002) and trended toward associating with clinical benefit measured at week 24 imaging (p=0.09). This effect was independent of pre-treatment or week 7 absolute lymphocyte counts (ALC) and pre-treatment LDH when evaluated in a multivariate model with ALC and MDSC quantity HR 1.10; 95% CI 1.04, 1.17 p=0.0006 and LDH and MDSC quantity HR 1.06; 95% CI 1.01, 1.11 p = 0.013. Furthermore, a general trend of increasing MDSC number by week 24 from the pre-treatment baseline was associated with patients that did not achieve clinical benefit. MDSC suppressed peripheral blood T cell proliferation as measured by CFSE dilution in response to anti-CD3 antibody stimulation. Conclusions: Pre-treatment MDSC quantity may predict clinical response following ipilimumab therapy. Further studies evaluating MDSC as a biomarker of ipilimumab therapy are warranted both retrospectively and prospectively in a broader group of patients.

Estimated life years saved with trastuzumab in first-line HER2+ metastatic breast cancer from 1999 to 2013.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 625-625
Author(s):  
Mark Danese ◽  
Deepa Lalla ◽  
Melissa Brammer ◽  
Eduardo Santos ◽  
Abraham Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Median Overall Survival ◽  
Metastatic Breast ◽  
The United States ◽  
Sensitivity Analyses ◽  
Base Case ◽  
First Line ◽  
Life Years

625 Background: Trastuzumab was approved in the United States (US) in September 1998 for the treatment of HER2+ metastatic breast cancer (MBC). This model estimates the total number of life years saved (LYS) in US women treated with trastuzumab over a 15-year period (1999-2013). Methods: Using US population estimates and cancer registry-based incidence data, we estimated the number of women with recurrent stage I-III or de novo stage IV HER2+ MBC by year, age, hormone receptor, and nodal status. Trastuzumab utilization was based on published studies of HER2 testing rates, true positive rates in the community, and treatment initiation rates. Survival was estimated by extrapolating survival data pooled across 5 trials and 2 observational studies separately for women treated with trastuzumab and with chemotherapy alone. Few studies reported survival in women with HER2+ MBC without trastuzumab (N=3). Sensitivity analyses were conducted by estimating overall survival from the initial phase 3 trial (67% of placebo patients crossed over to trastuzumab after progression; HR=0.80), and assuming a higher risk reduction to account for crossover effects in clinical trials (HR=0.60). Results: In the base case, approximately 83,462 women with HER2+ MBC were estimated to receive 1st line trastuzumab over a 15-year period. The pooled median overall survival across studies without and with trastuzumab was 21.2 and 35.5 months, respectively. Patients were projected to live a total of 216,290 life years if trastuzumab had not been available and if they received chemotherapy only. These same patients were estimated to live a total of 294,877 life years with first-line trastuzumab, for an incremental benefit of 78,587 LYS. In sensitivity analysis, total LYS ranged from 48,334-96,360. Conclusions: Real-world evidence supports a median overall survival of approximately 36 months in women with HER2+ MBC receiving 1st line trastuzumab. Using a population-based, conservative model, we found that trastuzumab use has resulted in > 75,000 life years over 15 years in women with HER2+ MBC. Future research is warranted to examine the characteristics, experiences, and outcomes among women living longer with HER2+ MBC.

Impact of care at Memorial Sloan Kettering Cancer Center (MSKCC): A comprehensive cancer center on overall survival (OS) in patients (pts) with AJCC stage IV pancreas adenocarcinoma (PDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18128-e18128
Author(s):  
Fiona Boland ◽  
Ahmad Cheema ◽  
Maeve Aine Lowery ◽  
Kenneth H. Yu ◽  
Anna M. Varghese ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Stage Iv ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Contributing Factors ◽  
Term Survival ◽  
Entire Cohort ◽  
Line Therapy ◽  
Centralized Care

e18128 Background: PDAC has a rising incidence and relatively static mortality rates. Current cytotoxic regimens confer median survivals of 8.5- 11 months (Von Hoff, Conroy, et al. NEJM 2013, 2011). National Cancer Institute-designated Comprehensive Cancer Centers potentially allow greater access to multidisciplinary consultation for complex cancer care. Although the widespread benefits of NCICCCs are acknowledged, there is limited data demonstrating superior outcomes for patients treated at these centers. Methods: Patients with stage IV PDAC, diagnosed between 01/01/13 and 12/31/14, were identified and followed until death or 12/31/2016. These patients had care centralized to MSKCC and the analysis was conducted to evaluate key patient (pt) and disease characteristics, systemic therapies and outcomes.Survival times were calculated from the date of diagnosis. Results: N=391 pts identified, 210 males (54%), 181 females (46%). Median age 66 years (range 27-91). Table 1 outlines key points. For entire cohort, median overall survival (mOS): 11.4 + 9 months, 1-year (yr) and 2-yr survival rates (SR) of 48% and 15.1% respectively. N= 165 (42%) received mFOLFIRINOX-based regimen as 1st-line therapy with mOS 13.2 + 8.9 months, 1-yr and 2-yr SR of 59.4.% and 20% respectively. N= 118 (30.1%) received gemcitabine + nab-paclitaxel- based regimen as 1st line therapy had a mOS of 11.6 + 9 months with 1-yr and 2-yr SR of 49.1% and 16.2% respectively. Conclusions: At MSKCC, a major referral center for PDAC, outcomes for stage IV disease compare favorably to contemporary trial outcomes with notable 2-yr survivorship (long-term survival analysis of MPACT trial showed 1-yr and 2-yr SR of 35% and 10% respectively). Contributing factors likely reflect multidisciplinary expertize, patient selection and biases. Centralized care for complex illnesses may improve outcomes. [Table: see text]

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