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- Ascierto, Paolo A, et al.
(författare)
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Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial.
- 2019
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Ingår i: JAMA oncology. - : American Medical Association (AMA). - 2374-2445 .- 2374-2437. ; 5:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- This analysis provides long-term follow-up in patients with BRAF wild-type advanced melanoma receiving first-line therapy based on anti-programmed cell death 1 receptor inhibitors.To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without a BRAF mutation.Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m2 every 3 weeks plus nivolumab-matched placebo every 2 weeks).Overall survival.At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months-not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59; P<.001). Complete and partial responses, respectively, were reported for 19.0% (40 of 210) and 23.8% (50 of 210) of patients in the nivolumab group compared with 1.4% (3 of 208) and 13.0% (27 of 208) of patients in the dacarbazine group. Additional analyses were performed on outcomes with subsequent therapies. Treatment-related grade 3/4 adverse events occurred in 15.0% (31 of 206) of nivolumab-treated patients and in 17.6% (36 of 205) of dacarbazine-treated patients. There were no deaths due to study drug toxic effects.Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreated BRAF wild-type advanced melanoma.ClinicalTrials.gov identifier: NCT01721772.
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- Fitzmauric, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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- Landgren, Ola, et al.
(författare)
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Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants: This prospective cross-sectional cohort study included 77469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures: Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results: Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P <.001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P <.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P <.001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS. Conclusions and Relevance: The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.
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- Yu, Nancy Y., et al.
(författare)
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Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer
- 2019
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Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 5:9, s. 1304-1309
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Tidskriftsartikel (refereegranskat)abstract
- Key PointsQuestionWhat is the long-term survival associated with tamoxifen therapy for postmenopausal patients with luminal A or luminal B subtype tumors? FindingsThis secondary analysis of the Stockholm Tamoxifen (STO-3) trial of 462 postmenopausal patients with lymph node-negative breast cancer found that patients with luminal A or luminal B tumor subtypes had a long-term risk of distant metastatic breast cancer and benefited from tamoxifen therapy for 15 years and 5 years after diagnosis, respectively. MeaningPatients with luminal A tumor subtype appeared to have a long-term benefit from tamoxifen therapy, and patients with luminal B subtype appeared to have an early benefit from therapy, when the risk of distant metastatic disease was high. This secondary analysis of the Stockholm Tamoxifen (STO-3) clinical trial, which was conducted from 1976 to 1990, assessed the long-term survival associated with tamoxifen therapy in postmenopausal patients with luminal A or B breast cancer tumor subtypes. ImportancePatients with estrogen receptor (ER)-positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood. ObjectiveTo compare the long-term survival from tamoxifen therapy for patients with luminal A or luminal B tumor subtype. Design, Setting, and ParticipantsSecondary analysis of patients from the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, which randomized postmenopausal patients with lymph node-negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. Tumor tissue sections were assessed in 2014 using immunohistochemistry and Agilent microarrays. Only patients with luminal A or B subtype tumors were evaluated. Complete long-term follow-up data up to the end of the STO-3 trial on December 31, 2012, were obtained from the Swedish National registers. Data analysis for the secondary analysis was conducted in 2017 and 2018. InterventionsPatients were randomized to receive at least 2 years of tamoxifen therapy or no endocrine therapy; patients without recurrence who reconsented were further randomized to 3 additional years of tamoxifen therapy or no endocrine therapy. Main Outcomes and MeasuresDistant recurrence-free interval (DRFI) by luminal A and luminal B subtype and trial arm was assessed by Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs) that were adjusted for patient and tumor characteristics. ResultsIn the STO-3 treated trial arm, 183 patients had luminal A tumors and 64 patients had luminal B tumors. In the untreated arm, 153 patients had luminal A tumors and 62 had luminal B tumors. Age at diagnosis ranged from 45 to 73 years. A statistically significant difference in DRFI by trial arm was observed (log rank, Pamp;lt;.001 [luminal A subtype, n=336], P=.04 [luminal B subtype, n=126]): the 25-year DRFI for luminal A vs luminal B subtypes was 87% (95% CI, 82%-93%) vs 67% (95% CI, 56%-82%) for treated patients, and 70% (95% CI, 62%-79%) vs 54% (95% CI, 42%-70%) for untreated patients, respectively. Patients with luminal A tumors significantly benefited from tamoxifen therapy for 15 years after diagnosis (HR, 0.57; 95% CI, 0.35-0.94), and those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR, 0.38; 95% CI, 0.24-0.59). Conclusions and RelevancePatients with luminal A subtype tumors had a long-term risk of distant metastatic disease, which was reduced by tamoxifen treatment, whereas patients with luminal B tumors had an early risk of distant metastatic disease, and tamoxifen benefit attenuated over time.
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- Mukama, Trasias, et al.
(författare)
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Risk-Adapted Starting Age of Screening for Relatives of Patients with Breast Cancer
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Breast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines. Objective: To identify the risk-adapted starting age of breast cancer screening on the basis of a woman's detailed family history. Design, Setting, and Participants: This nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (N = 5099172). Data from January 1, 1958, to December 31, 2015, were collected. Data were analyzed from October 1, 2017, to March 31, 2019. Exposures: Family history of breast cancer in FDRs and second-degree relatives (SDRs). Main Outcomes and Measures: Primary invasive breast cancer diagnosis and the age at which women with different constellations of family history attained the risk level at which breast screening is usually recommended. Results: Of the 5099172 women included in the study, 118953 (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102751 women (86.4%; mean [SD] age at diagnosis, 55.9 [11.1] years) did not have family history of breast cancer in FDRs and SDRs at the time of their diagnosis. Risk-adapted starting age of breast cancer screening varied by number of FDRs and SDRs with breast cancer diagnosis and the age at diagnosis of the FDRs. For example, for screening recommendation at age 50 years for the general population (2.2% 10-year cumulative risk), women with multiple affected FDRs, with the youngest affected relative receiving a diagnosis before age 50 years, reached the benchmark risk level at age 27 years. When the youngest relative received a diagnosis after age 50 years, however, this risk level was attained at age 36 years. Conclusions and Relevance: This study identifies possible risk-based starting ages for breast cancer screening based on population-based registers. These results may serve as high-quality evidence to supplement current screening guidelines for relatives of patients with breast cancer.
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