Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Functional development of preterm children born from singleton and multiple pregnancies: Preliminary study.

BACKGROUND: In recent years an increasing number of multiple pregnancies have been observed, which is a result of advancements made in reproductive technologies for infertility treatments as well as a tendency for women to delay childbearing until later in life. The risk of preterm birth in the case of a twin pregnancy is five to seven times higher than that of a singleton pregnancy, and in the case of triplet pregnancy, the risk is even 10 times higher. The objective of the study was to assess and compare the functional development of children aged between 2 and 2.5 who were prematurely born from singleton, twin and triplet pregnancies. MATERIAL AND METHODS: The study was carried out in a group of 43 children aged between 2 and 2.5 who were born prematurely (between the 32nd and 36th week of pregnancy) in 2017 and 2018. Group I was made up of 10 children born from singleton pregnancies, group II included 12 children born from six twin pregnancies and group III consisted of 21 children born from seven triplet pregnancies. The evaluation of functional development was conducted using the Munich Functional Developmental Diagnostics. RESULTS: There were no statistically significant differences in functional development between the studied singletons, twins and triplets. In the examined groups of singletons, twins and triplets, the calculated quotient medians for the 50th percentile approximated 1, which means that development was typical and did not differ from the development of the general population. In turn, for the 95th percentile, the median scores usually approximated 0.8, which also indicated that there was no significant delay in development. Had scores been higher than 1, this might have indicated a delay. CONCLUSIONS: On the basis of the study group, no relationship was found between the multiplicity of pregnancies and the functional development of premature babies born between the 32nd and 36th weeks of gestation.

The role of metastasectomy in renal cell carcinoma.

Despite significant advances in the systemic treatment of metastatic renal cell carcinoma, long-term survival remains low. A potential way to improve outcomes in selected cases is the use of metastasectomy, which is part of the multimodal treatment of this disease. Although the evidence supporting this approach is limited, we believe it is a reasonable option for certain patients. This review summarizes the evidence supporting this approach.

Effect of patient socioeconomic status on access to early-phase cancer trials.

PURPOSE: Little is known about the influence of socioeconomic factors on patient access to cancer trials. Differences should be considered to ensure generalizability of trial results and equality of access. METHODS: Phase I trials unit referrals at our center over 5 years, from 2007 to 2012, were reviewed. Socioeconomic status was defined by the Index of Multiple Deprivation (IMD; 1, least deprived; 5, most deprived). Multivariate analysis was performed comparing incident cancer cases with referred patients and those ultimately enrolled onto a trial. RESULTS: Four hundred thirty patients were referred (median age, 62 years). Compared with 10,784 incident cases, referral was less likely for patients in the more-deprived quintiles compared with the least deprived (IMD 5: odds ratio [OR], 0.53; 95% CI, 0.38 to 0.74). Once reviewed in the unit, enrollment onto a trial was not affected (IMD 5: OR, 0.81; 95% CI, 0.40 to 1.63). Ethnicity analysis showed the nonwhite population was less likely to be recruited (OR, 0.48; 95% CI, 0.26 to 0.88). This relationship was lost with adjustment for age, sex, cancer type, and deprivation index. CONCLUSION: We show for the first time to our knowledge that socioeconomic status affects early-phase cancer trial referrals. The least-deprived patients are almost twice as likely to be referred compared with the most deprived. This may be because more-deprived patients are less suitable for a trial-as a result of comorbidities, for example-or because of inequalities that could be addressed by patient or referrer education. Once reviewed at the unit, enrollment onto a trial is not affected by deprivation.