Lancet Oncology最新文献

Background: The number of new cancer cases in Commonwealth countries rose by 35% between 2008 and 2018, but progress in cancer control has been slow in many low-income and lower-middle-income member states. We aimed to examine cancer outcomes and priority areas in the Commonwealth to provide insight and guidance on prioritisation of efforts to improve cancer survival and make the best use of scarce resources.

Methods: We adapted a previously developed microsimulation model of global cancer survival for 11 cancer sites (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate). All 56 Commonwealth countries were included and classified based on the 2020 World Bank Income groups (low-income, lower-middle-income, upper-middle-income, and high-income countries) and Commonwealth geographical areas. We modelled the number of incident cancer cases in each Commonwealth country in 2020, based on age group-specific estimates of incidence rates from GLOBOCAN 2020. We simulated 5-year net survival for each patient, accounting for the stage at diagnosis (I-IV), availability of specific treatment and imaging modalities, and quality of care (based on residual differences in expected versus observed survival after accounting for the availability and effectiveness of treatment and imaging modalities). We also simulated counterfactual policy scenarios, in which we scaled up various aspects of cancer care to the mean level of high-income countries to estimate the comparative effectiveness of different policies.

Findings: Incident cancers in the Commonwealth accounted for an estimated 14·3% of global diagnosed cancer cases in 2020 among the 11 cancers modelled (1 610 000 Commonwealth cases [95% UI 1 556 000-1 674 000] of 11 227 000 global cases [11 069 000-11 406 000]) and are estimated to increase to 17·3% in 2050 due to population growth (3 330 000 [3 154 000-3 539 000] of 19 308 000 [18 706 000-19 911 000]). The 5-year net survival across 11 cancers combined in 2020 was 30·7% (95% UI 22·4-38·6) in Commonwealth countries, ranging from 4·1% (0·04-15·2) in low-income countries, 17·8% (3·7-30·9) in lower-middle-income countries, 33·1% (23·7-46·0) in upper-middle-income countries, to 59·0% (57·8-60·2) in high-income countries. Among single treatment policies, scaling up access to radiotherapy had the largest survival impact in low-income countries, surgery had the largest impact in lower-middle-income and upper-middle-income countries, and targeted therapy had the largest impact in high-income countries. By geographical area, improving radiotherapy availability was estimated to have the largest impact in Africa, surgery in Asia, targeted therapy in the Caribbean and the Americas and Europe, and quality of care in the Pacific Commonwealth countries. Comparing packages of scaling up the availability of all treatment modalities versus imaging modalities, expanding

Background: In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with resected stage III melanoma. Earlier results showed no effect of pembrolizumab on health-related quality of life (HRQOL). Little is known about HRQOL after completion of treatment with pembrolizumab, an important research area concerning patients who are likely to become long-term survivors. This study reports long-term HRQOL results.

Methods: This double-blind, randomised, controlled, phase 3 trial compared adjuvant pembrolizumab with placebo in patients aged 18 years or older with previously untreated stage IIIA, IIIB, or IIIC resected cutaneous melanoma and an Eastern Cooperative Oncology Group performance status score of 1 or 0, recruited from 123 academic centres and community hospitals in 23 countries. Patients were randomly assigned (1:1) with a minimisation technique stratified for stage and geographical region to receive 200 mg of intravenous pembrolizumab or placebo every 3 weeks for up to 18 doses. Investigators, patients, and those collecting or analysing data were masked to group assignment. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, measured with the EORTC Quality of Life Questionnaire-Core 30. All patients with a baseline HRQOL evaluation available who were alive 108 weeks from randomisation were included in this analysis of long-term HRQOL. Long-term HRQOL included assessments measured every 6 months between 108 weeks and 48 months after randomisation. The threshold of clinical relevance for all HRQOL scales used was an average change of 5 points. The trial is ongoing, recruitment is completed, and HRQOL data collection is finalised. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37.

Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were randomly assigned to pembrolizumab (n=514) or placebo (n=505). Completion of the HRQOL evaluation at baseline exceeded 90% (481 [94%] patients in the pembrolizumab group and 467 [92%] in the placebo group), and ranged between 60% and 90% for post-baseline timepoints. Among patients with a baseline HRQOL evaluation, 365 (39%) were female and 583 (61%) were male. The mean change from baseline to long-term HRQOL was -0·56 (95% CI -2·33 to 1·22) in the pembrolizumab group and 1·63 (-0·12 to 3·38) in the placebo group. The difference between the two groups was -2·19 (-4·65 to 0·27, p=0·081). Differences for all other scales were smaller than 5 and not statistically significant.

Interpretation: Adjuvant pembrolizumab did not have a significant impact on long-term HRQOL compared with placebo in patients with resected stage III melanoma. These findings, tog

Background: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial.

Methods: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m², methotrexate 50 mg/m², and fluorouracil 600 mg/m² every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat.

Findings: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43).

Interpretation: