Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial.

BACKGROUND: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. METHODS: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. FINDINGS: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. INTERPRETATION: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. FUNDING: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.

The Impact of Kundalini Yoga on Cognitive Function and Memory: A Systematic Review of Randomized Controlled Trials.

Cognitive decline and dementia are significant public health challenges influenced by various modifiable and non-modifiable risk factors. Kundalini yoga (KY) has emerged as a promising non-pharmacological intervention to enhance cognitive function and memory in older adults at risk of cognitive decline. This systematic review aims to evaluate the effects of KY on cognitive function, memory impairment, and related neurobiological and psychological outcomes in older adults. A comprehensive literature search was conducted across PubMed, MEDLINE, Scopus, Web of Science, and the Cochrane Library, covering studies published from January 2000 to December 2023. Randomised controlled trials (RCTs) were included to compare KY with other cognitive enhancement strategies, such as memory enhancement training (MET) and psychoeducation. Five RCTs with 215 participants met the inclusion criteria. The studies varied in sample size (11 to 81 participants) and duration (12 to 24 weeks). The participants were older adults (≥55 years) with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). The interventions compared KY with MET or psychoeducation. KY consistently improved memory performance and executive function. Significant mood enhancements, increased hippocampal volume, and better neural connectivity were observed. KY also reduced pro-inflammatory cytokines and altered ageing-related gene expression, demonstrating both cognitive and neurobiological benefits. KY appears to be a promising intervention for enhancing cognitive function, mood, and neurobiological health in older adults at risk of cognitive decline and dementia. While further research with more extensive, well-designed RCTs is needed to confirm these findings and optimise intervention strategies, the existing evidence supports the integration of KY into cognitive health programmes. Practitioners should ensure proper training and gradual progression to maximise benefits and minimise risks.

Impact of prostate radiotherapy on survival outcomes in clinically node-positive prostate cancer: A multicentre retrospective analysis.

PURPOSE: To evaluate clinical outcomes for cN1M0 prostate cancer treated with varied modalities. MATERIALS AND METHODS: Men with radiological stage cN1M0 prostate cancer on conventional imaging, treated from 2011-2019 with various modalities across four centres in the UK were included. Demographics, tumour grade and stage, and treatment details were collected. Biochemical and radiological progression-free survival (bPFS, rPFS) and overall survival (OS) were estimated using Kaplan Meier analyses. Potential factors impacting survival were tested with univariable log-rank test and multivariable Cox-proportional hazards model. RESULTS: Total 337 men with cN1M0 prostate cancer were included, 47% having Gleason grade group 5 disease. Treatment modalities included androgen deprivation therapy (ADT) in 98.9% men, either alone (19%) or in combinations including prostate radiotherapy (70%), pelvic nodal radiotherapy (38%), docetaxel (22%), or surgery (7%). At median follow up of 50 months, 5-year bPFS, rPFS, and OS were 62.7%, 71.0%, and 75.8% respectively. Prostate radiotherapy was associated with significantly higher bPFS (74.1% vs 34.2%), rPFS (80.7% vs 44.3%) and OS (86.7% vs 56.2%) at five years (log rank p < 0.001 each). On multivariable analysis including age, Gleason grade group, tumour stage, ADT duration, docetaxel, and nodal radiotherapy, benefit of prostate radiotherapy persisted for bPFS [HR 0.33 (95% CI 0.18-0.62)], rPFS [HR 0.25 (0.12-0.51)], and OS [HR 0.27 (0.13-0.58)] (p < 0.001 each). Impact of nodal radiotherapy or docetaxel was not established due to small subgroups. CONCLUSION: Addition of prostate radiotherapy to ADT in cN1M0 prostate cancer yielded improved disease control and overall survival independent of other tumour and treatment factors.

Metastatic spinal cord compression: radiotherapy outcome and dose fractionation.

BACKGROUND AND PURPOSE: No standard dose fractionation has been defined for metastatic spinal cord compression. This retrospective analysis was undertaken to explore the impact of hypofractionated treatment compared to conventional multifraction treatment. MATERIALS AND METHODS: One hundred and two consecutive patients referred to Mount Vernon Cancer Centre with metastatic spinal canal compression confirmed on MR scan in 95% with median age 68 years (range 32-90) and main primary tumour types breast (28%), prostate (28%) and lung (20%); 51% of patients were fully ambulant at diagnosis, 41% ambulant but with paraparesis and 9% had complete paraplegia. Spinal radiotherapy was given delivering a single dose in 32% and 20 Gy in five fractions in 64%. RESULTS: The median survival was 3.5 months; survival was significantly related to primary site and motor function at presentation. Normal ambulation was achieved in 58% at 2 weeks and 71% up to 2 months after treatment. No patient who presented with paraplegia regained function. At presentation 59% of patients had severe pain, which fell to 8% at 2 weeks. Comparing those patients who received one or two dose treatments with those who received protracted fractionation, the two groups were matched for age, sex, primary site and site of compression. Relatively more patients treated with one or two doses had paraplegia; 19% vs. 3%. Despite this outcome in the two groups was equivalent for motor and sphincter function and pain control. CONCLUSIONS: Metastatic spinal canal compression carries a poor prognosis. Urgent treatment will maintain and improve motor function in patients presenting ambulant but those who have paraplegia at presentation do not improve and have a very short survival. In this series no difference in outcome was seen between patients treated with one or two radiation doses compared to multifraction treatment; a randomised trial comparing fractionation schedules would be justified.