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Abstract Background Survey data are traditionally collected using pen-and-paper, with double data entry, comparison of entries and reconciliation of discrepancies before data cleaning can commence. We used Personal Digital Assistants (PDAs) for data entry at the point of collection, to save time and enhance the quality of data in a survey of over 21,000 scattered rural households in southern Tanzania. Methods Pendragon Forms 4.0 software was used to develop a modular questionnaire designed to record information on household residents, birth histories, child health and health-seeking behaviour. The questionnaire was loaded onto Palm m130 PDAs with 8 Mb RAM. One hundred and twenty interviewers, the vast majority with no more than four years of secondary education and very few with any prior computer experience, were trained to interview using the PDAs. The 13 survey teams, each with a supervisor, laptop and a four-wheel drive vehicle, were supported by two back-up vehicles during the two months of field activities. PDAs and laptop computers were charged using solar and in-car chargers. Logical checks were performed and skip patterns taken care of at the time of data entry. Data records could not be edited after leaving each household, to ensure the integrity of the data from each interview. Data were downloaded to the laptop computers and daily summary reports produced to evaluate the completeness of data collection. Data were backed up at three levels: (i) at the end of every module, data were backed up onto storage cards in the PDA; (ii) at the end of every day, data were downloaded to laptop computers; and (iii) a compact disc (CD) was made of each team's data each day. A small group of interviewees from the community, as well as supervisors and interviewers, were asked about their attitudes to the use of PDAs. Results Following two weeks of training and piloting, data were collected from 21,600 households (83,346 individuals) over a seven-week period in July-August 2004. No PDA-related problems or data loss were encountered. Fieldwork ended on 26 August 2004, the full dataset was available on a CD within 24 hours and the results of initial analyses were presented to district authorities on 28 August. Data completeness was over 99%. The PDAs were well accepted by both interviewees and interviewers. Conclusion The use of PDAs eliminated the usual time-consuming and error-prone process of data entry and validation. PDAs are a promising tool for field research in Africa.

Abstract Background Intermittent preventive treatment (IPT) is a promising intervention for malaria control, although there are concerns about its impact on drug resistance. Methods The key model inputs are age-specific values for a) baseline anti-malarial dosing rate, b) parasite prevalence, and c) proportion of those treated with anti-malarials (outside IPT) who are infected. These are used to estimate the immediate effect of IPT on the genetic coefficient of selection (s). The scenarios modelled were year round IPT to infants in rural southern Tanzania, and three doses at monthly intervals of seasonal IPT in Senegal. Results In the simulated Tanzanian setting, the model suggests a high selection pressure for drug resistance, but that IPTi would only increase this by a small amount (4.4%). The percent change in s is larger if parasites are more concentrated in infants, or if baseline drug dosing is less common or less specific. If children aged up to five years are included in the Tanzanian scenario then the predicted increase in s rises to 31%. The Senegalese seasonal IPT scenario, in children up to five years, results in a predicted increase in s of 16%. Conclusion There is a risk that the useful life of drugs will be shortened if IPT is implemented over a wide childhood age range. On the other hand, IPT delivered only to infants is unlikely to appreciably shorten the useful life of the drug used.

Background: Although antenatal care coverage in Tanzania is high, worrying gaps exist in terms of its quality and ability to prevent, diagnose or treat complications. Moreover, much less is known about the utilisation of postnatal care, by which we mean the care of mother and baby that begins one hour after the delivery until six weeks after childbirth. We describe the perspectives and experiences of women and health care providers on the use of antenatal and postnatal services.Methods: From March 2007 to January 2008, we conducted in-depth interviews with health care providers and village based informants in 8 villages of Lindi Rural and Tandahimba districts in southern Tanzania. Eight focus group discussions were also conducted with women who had babies younger than one year and pregnant women. The discussion guide included information about timing of antenatal and postnatal services, perceptions of the rationale and importance of antenatal and postnatal care, barriers to utilisation and suggestions for improvement.Results: Women were generally positive about both antenatal and postnatal care. Among common reasons mentioned for late initiation of antenatal care was to avoid having to make several visits to the clinic. Other concerns included fear of encountering wild animals on the way to the clinic as well as lack of money. Fear of caesarean section was reported as a factor hindering intrapartum care-seeking from hospitals. Despite the perceived benefits of postnatal care for children, there was a total lack of postnatal care for the mothers. Shortages of staff, equipment and supplies were common complaints in the community.Conclusion: Efforts to improve antenatal and postnatal care should focus on addressing geographical and economic access while striving to make services more culturally sensitive. Antenatal and postnatal care can offer important opportunities for linking the health system and the community by encouraging women to deliver with a skilled attendant. Addressing staff shortages through expanding training opportunities and incentives to health care providers and developing postnatal care guidelines are key steps to improve maternal and newborn health. [ABSTRACT FROM AUTHOR]

Background: Achieving the Millennium Development Goals for health requires a massive scaling-up of interventions in Sub Saharan Africa. Intermittent Preventive Treatment in infants (IPTi) is a promising new tool for malaria control. Although efficacy information is available for many interventions, there is a dearth of data on the resources required for scaling up of health interventions.Method: We worked in partnership with the Ministry of Health and Social Welfare (MoHSW) to develop an IPTi strategy that could be implemented and managed by routine health services. We tracked health system and other costs of (1) developing the strategy and (2) maintaining routine implementation of the strategy in five districts in southern Tanzania. Financial costs were extracted and summarized from a costing template and semi-structured interviews were conducted with key informants to record time and resources spent on IPTi activities.Results: The estimated financial cost to start-up and run IPTi in the whole of Tanzania in 2005 was US$1,486,284. Start-up costs of US$36,363 were incurred at the national level, mainly on the development of Behaviour Change Communication (BCC) materials, stakeholders' meetings and other consultations. The annual running cost at national level for intervention management and monitoring and drug purchase was estimated at US$459,096. Start-up costs at the district level were US$7,885 per district, mainly expenditure on training. Annual running costs were US$170 per district, mainly for printing of BCC materials. There was no incremental financial expenditure needed to deliver the intervention in health facilities as supplies were delivered alongside routine vaccinations and available health workers performed the activities without working overtime. The economic cost was estimated at 23 US cents per IPTi dose delivered.Conclusion: The costs presented here show the order of magnitude of expenditures needed to initiate and to implement IPTi at national scale in settings with high Expanded Programme on Immunization (EPI) coverage. The IPTi intervention appears to be affordable even within the budget constraints of Ministries of Health of most sub-Saharan African countries. [ABSTRACT FROM AUTHOR]

To describe and evaluate the use of handheld computers for the management of Health Management Information System data. Electronic data capture took place in 11 sentinel health centres in rural southern Tanzania. Information from children attending the outpatient department (OPD) and the Expanded Program on Immunization vaccination clinic was captured by trained local school-leavers, supported by monthly supervision visits. Clinical data included malaria blood slides and haemoglobin colour scale results. Quality of captured data was assessed using double data entry. Malaria blood slide results from health centre laboratories were compared to those from the study's quality control laboratory. The system took 5 months to implement, and few staffings or logistical problems were encountered. Over the following 12 months (April 2006-March 2007), 7056 attendances were recorded in 9880 infants aged 2-11 months, 50% with clinical malaria. Monthly supervision visits highlighted incomplete recording of information between OPD and laboratory records, where on average 40% of laboratory visits were missing the record of their corresponding OPD visit. Quality of microscopy from health facility laboratories was lower overall than that from the quality assurance laboratory. Electronic capture of HMIS data was rapidly and successfully implemented in this resource-poor setting. Electronic capture alone did not resolve issues of data completeness, accuracy and reliability, which are essential for management, monitoring and evaluation; suggestions to monitor and improve data quality are made. [ABSTRACT FROM AUTHOR]

Background: A study was undertaken to assess the interactions between prenatal exposures, early life infections, atopic predisposition, and allergen exposures in the development of wheezing up to the age of 4 years in a tropical region of Africa.Methods: The study subjects comprised children born at the district hospital in Ifakara, Tanzania during a 1 year period who were participating in a trial of iron supplementation and malaria chemoprophylaxis during the first year of life and followed for up to 4 years. From this group of subjects, 658 (79%) participated in the interview at 18 months and 528 (64%) in a second interview at 4 years. Wheezing was measured with the ISAAC questionnaire. A hospital based inpatient and outpatient surveillance system was set up to document all attendance by study children for any cause, including episodes of clinical malaria and lower respiratory tract infections. Total IgE levels and malaria parasites were measured in maternal and cord blood. Total IgE was also measured at 18 months of age. Indoor environmental levels of Der p I and Fel d I were determined using an enzyme linked immunosorbent assay at the same time as the interview at the age of 18 months.Results: The prevalence of wheezing at 4 years is common in Ifakara (14%, range 13-15%). The presence of malaria parasites in cord blood (odds ratio, OR = 6.84, 95% CI 1.84 to 24.0) and maternal asthma (OR = 8.47, 95% CI 2.72 to 26.2) were positively associated with wheezing at the age of 4 years, and cord blood total IgE was negatively associated (OR = 0.24, 95% CI 0.07 to 0.85) (all p<0.05). Parasitaemia at birth was not related to total IgE levels in cord blood (p=0.6). Clinical episodes of malaria during infancy were not associated with wheezing, and nor were levels of indoor aeroallergens.Conclusion: These findings suggest that events occurring during pregnancy may play a role in the future appearance of wheezing, although the results must be interpreted with caution because of the small numbers studied. [ABSTRACT FROM AUTHOR]

Background: Atopy is consistently associated with asthma, except in a study in Africa. We assessed the association between atopy and asthma in women from a semirural area of Tanzania (East Africa). Methods: All pregnant women delivering at the district hospital during a 1-year period were recruited (n=658, 60.6% of those selected). Asthma was investigated by a standard questionnaire and atopy by specific IgE (immunoglobulin E) antibodies to Dermatophagoides pteronyssinus (Der p 1) and cockroach. Results: The prevalence of wheezing chest was 10.7%; of asthma, 3.5%. Levels of specific IgE of >0.35 kU/l (73%) and high levels of total IgE (62% higher than 1000 kU/l) were highly prevalent. Specific IgE antibody levels in sera were not associated with asthma (3.8% of women with negative specific IgE to any antigen had asthma in comparison to 4.0% of women with positive specific IgE; odds ratio [OR]=1.06, 0.35–3.22). Total IgE was not different between women with asthma and women without asthma (P=0.36). Conclusions: In tropical regions, the association between allergy and asthma is complex, and specific IgE reactivity to environmental allergens may not be related to asthma. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): After the publication of the landmark SABR-COMET trial, concerns were raised over toxicity of SABR for oligometastases. This population-based study was designed as a bridge from phase II to phase III trials, while assessing the toxicity profile of SABR in a larger cohort from a provincial cancer program.Materials/methods: From November 2016 to July 2020, 399 patients were enrolled in this single arm, phase II trial of SABR in patients with oligometastatic or oligo-progressive disease. During this period, patients were only eligible for SABR in these settings on trial within our province, and therefore this analysis is population-based, with resultant minimal selection bias in comparison to previously published SABR series. The primary endpoint was toxicity and we hypothesized grade 4 toxicity < 5%. Grade 2 or higher toxicities were prospectively collected, and were rated as unrelated, unlikely, possibly, probably, or definitely related to SABR. Toxicities rated as possibly, probably, or definitely related to SABR were analyzed in this study. The radiotherapy details are previously published in the protocol; because of previously published high grade toxicity in this setting, all cases underwent individual peer review and organs at risk were prioritized over the planning target volumes.Results: The mean age was 68 years (SD 10.9, range 30-97). The participants were mostly male (69%). The most common histologies were prostate cancer (33%), colorectal cancer (14%), breast cancer (11%), and lung cancer (9%). The number of SABR treated sites were one (69%), two (22%), and three or more (9%). The most common sites of SABR were lung (33%), non-spine bone (28%), spine (14%), lymph nodes (13%), liver (5%) and adrenal (3%). Grade 2, 3, and 4 toxicity cumulative incidences were 11.4%, 4.6%, and 0.5%, respectively. There were no grade 5 toxicities. Grade 2 or higher specific toxicity included 4.8% pain, 1.3% pneumonitis, and 0.8% neuropathy. There were no reported gastrointestinal fistula, perforation, or hemorrhage. Cumulative incidence and prevalence of toxicity at 1 & 3 years will be updated and presented.Conclusion: The incidence of grade 2+ SABR toxicity on this population-based study was 16.5%, which is lower than that reported on SABR-COMET (29%). Importantly, there were no grade 5 toxicities attributed to SABR in this study to date. Severe (grade 3 or higher) toxicities were uncommon (5.0%). These results are encouraging that, in a population-based program with rigorous peer review quality assurance, SABR treatment for oligometastases has acceptable rates of toxicity. This supports further enrollment in randomized phase III trials. [ABSTRACT FROM AUTHOR]

Purpose: The optimal SABR treatment delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade ≥2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day versus daily with weekends and consecutive daily without weekends., Methods and Materials: Between January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as every other day, daily with weekends, or consecutive daily without weekends. Toxicity events were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan-Meier method was used to compute OS and LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modeling was used to assess for variables associated with OS and LF, respectively., Results: Of 404 patients meeting study criteria, 190, 111, and 103 received SABR every other day, daily with weekends, and consecutive daily without weekends, respectively. More patients receiving SABR daily with weekends were medically inoperable and more patients receiving SABR consecutive daily without weekends had tumors abutting the chest wall. Median follow-up time was 29.5 months (IQR, 19.2-38.4 months). Overall toxicity was low, with crude rates of acute and late grade ≥2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% CI, 3.7-11.3), 9.5% (95% CI, 3.9-15.1), and 11.0% (95% CI, 4.9-17.2) for the every other day, daily with weekends, and consecutive daily without weekends groups, respectively (P = .60). Schedules of daily with weekends and consecutive daily without weekends were not associated with LF. Similarly, no significant differences in median OS were found among the every other day, daily with weekends, and consecutive daily without weekends groups at 47.5 months (95% CI, 39.26-55.74), 52.7 months (95% CI, 34.7-70.7), and 49.0 months (95% CI, 31.6-66.4), respectively. Schedules of daily with weekends and consecutive daily without weekends were not associated with OS., Conclusions: This population-based study demonstrated no statistically significant differences in grade ≥2 toxicity rates, LF, and OS for patients with stage I NSCLC treated with lung SABR using 48 Gy in 4 fractions delivered every other day, daily with weekends, and consecutive daily without weekends. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule., Competing Interests: Disclosures Sarah Baker has received honoraria from AstraZeneca unrelated to this work. Devin Schellenberg has received honoraria for multidisciplinary presentations and discussions from AstraZeneca, Pfizer, and BMS unrelated to this work; has participated in advisory boards for AstraZeneca unrelated to this work; and is employed in a leadership position as Provincial Director of Radiation Oncology at BC Cancer. Benjamin Mou has received honoraria from Amgen, AstraZeneca, and Bristol Myers Squibb unrelated to this work. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of SABR to standard of care (SOC) systemic therapy., Methods and Materials: We enrolled patients with 1 to 5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs noncytotoxic), randomized 1:2 between continued SOC treatment versus SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all nonhematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events, and duration of systemic therapy postrandomization., Results: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. The median age was 67 years, and 39 (43%) were women. The most common primary sites were lung (44%), genitourinary (23%), and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. The median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs 4.3 months in the SOC arm, but curves cross and 2-year PFS was 9% vs 24%, respectively; P = .91). The median OS was 31.2 months versus 27.4 months, respectively (P = .22). Lesional control was superior with SABR (70% vs 38%, respectively; P = .0015). There were 2 (3.4%) grade 3 and no grade 4/5 adverse events attributable to SABR., Conclusions: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns. Regular routine assessment of protective efficacy of chemoprevention is key. Here, we apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings., Methods and Findings: We developed a model of genotype-specific drug protection, which accounts for underlying risk of infection and circulating genotypes. Using a Bayesian framework, we fitted the model to multiple simulated scenarios to explore variations in study design, setting, and participant characteristics. We find that a placebo or control group with no drug protection is valuable but not always feasible. An alternative approach is a single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug protection wanes, as long as transmission is relatively constant. We show that the currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period. However, in settings of unstable transmission, protective efficacy in a single-arm trial was overestimated by 24.3% if recruitment occurred during increasing transmission and underestimated by 15.8% when recruitment occurred during declining transmission. Protective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common., Conclusions: These findings have important implications for the current guidelines on chemoprevention efficacy studies and will be valuable for informing where these studies should be optimally placed. The results underscore the need for a comparator group in seasonal settings and provide evidence that the extension of follow-up in single-arm trials improves the accuracy of measures of protective efficacy in settings with more stable transmission. Extension of follow-up may pose logistical challenges to trial feasibility and associated costs. However, these studies may not need to be repeated multiple times, as the estimates of drug protection against different genotypes can be applied to different settings by adjusting for transmission intensity and frequency of resistance., Competing Interests: LCO has received a research grant from Merck pharmaceutical. RG is funded through a Unitaid grant that funds the Plus Project for his work at the London School of Hygiene and Tropical Medicine and works as an independent consultant paid by USAID, Population Services International and Bill and Melinda Gates Foundation., (Copyright: © 2024 Mousa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments., Methods: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level., Results: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium)., Conclusions: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Background: The RTS,S/AS01 E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use., Methods: In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission., Findings: By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury)., Interpretation: In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S., Funding: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid., Competing Interests: Declaration of interests KPA, AO, MJH, NW, PN, DA, SK, TM, DS, LO, PB, TA, and AMS previously participated in RTS,S malaria vaccine clinical trials as principal investigators or co-investigators before or following WHO's RTS,S malaria pilot implementation programme. The authors were not involved in the RTS,S vaccine delivery programme. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial., Methods and Materials: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity., Results: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001)., Conclusions: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention. We aimed to provide guidance for the early prioritisation of new and alternative SMC drugs and their target product profiles., Methods: In this modelling study, we combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic and pharmacodynamic models. We modelled SMC drug attributes for several possible modes of action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum parasite killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions., Findings: Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When children younger than 5 years receive four SMC cycles with high levels of coverage (ie, 69% of children receiving all cycles), drug candidates require a duration of protection half-life higher than 23 days (elimination half-life >10 days) to achieve reductions higher than 75% in clinical incidence and severe disease (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is crucial to achieve these targets, requiring more than 60% of children to receive all SMC cycles and more than 90% of children to receive at least one cycle regardless of the protection duration of the drug., Interpretation: Although efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determining cycle timing. Explicitly designing or selecting drug properties to increase community uptake is paramount., Funding: Bill & Melinda Gates Foundation and the Swiss National Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases., Materials and Methods: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3)., Results: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months., Conclusions: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL., (Copyright © 2023. Published by Elsevier Ltd.)

Aims: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline., Materials and Methods: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline., Results: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance., Conclusions: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose. Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery. Methods. CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments. Results. Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm 2 (controls) and 149-766 mm 2 (HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm 2 (controls) and 83-393 mm 2 (HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF). Conclusion. This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery., (Creative Commons Attribution license.)

Against a backdrop of stalled progress in malaria control, it is surprising that the various forms of malaria chemoprevention are not more widely used. The World Health Organization (WHO) has recommended several malaria chemoprevention strategies, some of them for over a decade, and each with documented efficacy and cost effectiveness. In 2022, the WHO updated and augmented its malaria chemoprevention guidelines to facilitate their wider use. This paper considers new insights into the empirical evidence that supports the broader application of chemoprevention and encourages its application as a default strategy for young children living in moderate to high transmission settings given their high risk of severe disease and death. Chemoprevention is an effective medium-term strategy with potential benefits far outweighing costs. There is a strong argument for urgently increasing malaria chemoprevention in endemic countries., (© 2024. The Author(s).)

Background: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience., Methods: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival., Discussion: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone., Trial Registration: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023., (© 2024. The Author(s).)

The WHO recommends that all affected countries work toward the elimination of malaria, even those still experiencing a high burden of disease. However, malaria programs in the final phase of elimination or those working to prevent re-establishment of transmission after elimination could benefit from specific evidence-based recommendations for these settings as part of comprehensive and quality-controlled malaria guidelines. The WHO convened an external guideline development group to formulate recommendations for interventions to reduce or prevent malaria transmission in areas with very low- to low-transmission levels and those that have eliminated malaria. In addition, several interventions that could be deployed in higher burden areas to accelerate elimination, such as mass drug administration, were reviewed. Systematic reviews were conducted that synthesized and evaluated evidence for the benefits and harms of public health interventions and summarized critical contextual factors from a health systems perspective. A total of 12 recommendations were developed, with five related to mass interventions that could be deployed at higher transmission levels and seven that would be most appropriate for programs in areas close to elimination or those working to prevent re-establishment of transmission. Four chemoprevention, two active case detection, and one vector control interventions were positively recommended, whereas two chemoprevention and three active case detection interventions were not recommended by the WHO. None of the recommendations were classified as strong given the limited and low-quality evidence base. Approaches to conducting higher quality research in very low- to low-transmission settings to improve the strength of WHO recommendations are discussed.

Objectives: Thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) are commonly used in the management of extensive-stage small-cell lung cancer (ES-SCLC); however, Phase III trials of first-line immunotherapy often excluded these options. Guidance is needed regarding appropriate use of TRT, PCI, and magnetic resonance imaging (MRI) surveillance while new data are awaited., Materials and Methods: In two web-based meetings, a pan-Canadian expert working group of five radiation oncologists and four medical oncologists addressed eight clinical questions regarding use of radiation therapy (RT) and MRI surveillance among patients with ES-SCLC receiving immunotherapy. A targeted literature review was conducted using PubMed and conference proceedings to identify recent (January 2019-April 2022) publications in this setting. Fifteen recommendations were developed; online voting was conducted to gauge agreement with each recommendation., Results: After considering recently available evidence across lung cancer populations and clinical experience, the experts recommended that all patients with a response to chemo-immunotherapy, good performance status (PS), and limited metastases be considered for consolidation TRT (e.g., 30 Gy in 10 fractions). When considered appropriate after multidisciplinary team discussion, TRT can be initiated during maintenance immunotherapy. All patients who respond to concurrent chemo-immunotherapy should undergo restaging with brain MRI to guide decision-making regarding PCI versus MRI surveillance alone. MRI surveillance should be conducted for two years after response to initial therapy. PCI (e.g., 25 Gy in 10 fractions or 20 Gy in 5 fractions) can be considered for patients without central nervous system involvement who have a response to chemo-immunotherapy and good PS. Concurrent treatment with PCI and immunotherapy or with TRT, PCI, and immunotherapy is appropriate after completion of initial therapy. All recommendations were agreed upon unanimously., Conclusions: These consensus recommendations provide practical guidance regarding appropriate use of RT and immunotherapy in ES-SCLC while awaiting new clinical trial data., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A. Sun has received honoraria from and participated in advisory boards with AstraZeneca. B. Abdulkarim has no conflicts to disclose. N. Blais reports receiving consulting fees from AstraZeneca. J. Greenland has received honoraria from AstraZeneca for attendance at advisory boards. A.V. Louie reports receiving honoraria from AstraZeneca for a speakers bureau and an advisory board. B. Melosky has received honoraria from AstraZeneca, BMS, Merck, and Roche. D. Schellenberg reports receiving institutional grants from Varian Medical Systems and payments from AstraZeneca, Merck, and Pfizer for presentations/educational events and advisory board participation. He also reports participation in Linear Accelerator selection for BC Cancer and receipt of a class action lawsuit payment from Medtronic. S. Snow reports research/trial funding paid to her institution by AstraZeneca, BMS, Merck, Novartis, Sanofi, and Takeda and receiving consulting fees from Novartis and Roche. She has also received honoraria for lectures and presentations at educational events from Amgen, AstraZeneca, Bayer, BMS, Elvium Life Sciences, Jazz Pharmaceuticals, Pfizer, and Taiho. S. Snow has also participated in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, EMD Serono, Janssen, Jazz Pharmaceuticals, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda, and Taiho, and was the President of Lung Cancer Canada and on its Board of Directors at the time of publication. G. Liu has received institutional research grants from NCI (US), CIHR (Canada), CCSRI (Canada), Amgen, AstraZeneca, Boehringer Ingelheim, and Takeda. He has received payment or honoraria from AstraZeneca, EMD Serono, Jazz Pharmaceuticals, Novartis, Pfizer, and Takeda, and has participated in data safety monitoring boards or advisory boards with AbbVie, AstraZeneca, BMS, EMD Serono, Jazz Pharmaceuticals, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Stereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS)., Methods: This single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated., Results: 549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86-0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93-0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69-0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and 'other' (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS., Conclusion: PTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Introduction: Stereotactic Ablative Radiation Therapy (SABR) is a therapeutic option for patients with inoperable oligometastatic colorectal carcinoma (CRC). Given the scarcity of prospective data on outcomes of SABR for metastatic CRC, this study aims to review SABR outcomes and determine predictive factors of local control (LC) and survival in patients with liver metastases from CRC., Materials and Methods: A retrospective review of SABR for CRC liver metastases between 2011 and 2019 was undertaken. Endpoints included LC, overall survival (OS), progression-free survival (PFS) and time to restarting systemic therapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify predictive factors., Results: Forty-eight patients were identified. The total number of tumors treated was 58. Median follow-up was 26.6 months. LC at 1, 2 and 3 years was 92.7%, 80.0%, and 61.2% respectively. Median time to local failure was 40.0 months (95% CI 31.8-76.1 months). Median OS was 31.9 months (95% CI 20.6-40.0 months). OS at 1, 2, and 3 years was 79.2%, 61.7%, and 44.9% respectively. Thirty-three patients (69%) restarted systemic therapy after completion of SABR. Median time to restarting chemotherapy was 11.0 months (95% CI 7.1-17.6 months). Systemic therapy free survival at 1, 2, and 3 years was 45.7%, 29.6%, and 22.6% respectively. On MVA, inferior LC was influenced by GTV volume ≥40 cm 3 (HR: 3.805, 95% CI 1.376-10.521, P = .01) and PTV D100% BED <100 Gy 10 (HR 2.971, 95% CI 1.110-7.953; P = .03). Inferior OS was associated with PTV volume ≥200 cm 3 (HR 5.679, 95% CI 2.339-13.755; P < .001)., Conclusion: SABR is an effective therapeutic option for selected patients with CRC liver metastases providing acceptable LC within the first 2 years. In many cases, it provides meaningful chemotherapy-free intervals. Higher biological effective doses are required to enhance LC., Competing Interests: Disclosure None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme., Methods and Materials: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling., Results: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS., Conclusions: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: A subset of patients with oligometastatic cancer experience early widespread cancer dissemination and do not benefit from metastasis-directed therapy such as SABR. This study aimed to identify factors associated with early polymetastatic relapse (PMR)., Methods and Materials: The SABR-5 trial was a single arm phase 2 study conducted at all 6 regional cancer centers across British Columbia (BC), Canada. SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastatic lesions (total, progressing, or induced) received SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2 and life expectancy ≥6 months. This secondary analysis evaluated factors associated with early PMR, defined as disease recurrence within 6 months of SABR, which is not amenable to further local treatment. Univariable and multivariable analyses were performed using binary logistic regression. The Kaplan-Meier method and log-rank tests assessed PMR-free survival and differences between risk groups, respectively., Results: Between November 2016 and July 2020, 381 patients underwent treatment on SABR-5. A total of 16% of patients experienced PMR. Worse performance status (Eastern Cooperative Oncology Group 1-2 vs 0; hazard ratio [HR] = 2.01, P = .018), nonprostate/breast histology (HR = 3.64, P <.001), and oligoprogression (HR = 3.84, P <.001) were independent predictors for early PMR. Risk groups were identified with median PMR-free survival ranging from 5 months to not yet reached at the time of analysis. Rates of 3-year overall survival were 0%, 53% (95% confidence interval [CI], 48-58), 77% (95% CI, 73-81), and 93% (95% CI, 90-96) in groups 1 to 4, respectively (P <.001)., Conclusions: Four distinct risk groups for early PMR are identified, which differ significantly in PMR-free survival and overall survival. The group with all 3 risk factors had a median PMR-free survival of 5 months and may not benefit from local ablative therapy alone. This model should be externally validated with data from other prospective trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial., Methods and Materials: The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here., Results: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P = .003), 4 or more metastases at SABR (HR, 1.48; P = .048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P = .008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P = .002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC., Conclusions: In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Long-term randomized data assessing the effect of ablative therapies in patients with oligometastases are lacking. The Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) randomized phase 2 trial was originally designed with 5 years of follow-up, but the trial was amended in 2016 to extend follow-up to 10 years. Herein we report oncologic outcomes beyond 5 years., Methods and Materials: Patients were eligible if they had a controlled primary tumor and 1 to 5 metastases, with all metastases amenable to SABR. Patients were randomized in a 1:2 ratio between palliative standard-of-care treatment (control arm) versus SABR to all metastases plus standard of care (SABR arm). The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), toxicity, quality of life (using the Functional Assessment of Cancer Therapy: General [FACT-G]), and time to new metastases., Results: Ninety-nine patients were randomized between 2012 and 2016 (n = 33 in arm 1 vs n = 66 in arm 2). Primary tumor sites included lung (n = 18), breast (n = 18), colon (n = 18), prostate (n = 16), and other (n = 29). Eight-year OS was 27.2% in the SABR arm versus 13.6% in the control arm (hazard ratio, 0.50; 95% confidence interval, 0.30-0.84; P = .008). Eight-year PFS estimates were 21.3% versus 0.0%, respectively (hazard ratio, 0.45; 95% confidence interval, 0.28-0.72; P < .001). Rates of grade ≥ 2 acute or late toxic effects were 30.3% versus 9.1% (P = .019), with no new grade 3 to 5 toxic effects. FACT-G quality of life scores declined over time in both arms, but there were no differences in quality of life scores between arms. The use of systemic therapy overall was similar between arms, but patients in the SABR arm were less likely to require cytotoxic chemotherapy (33.3% vs 54.6%, respectively, P = .043)., Conclusions: SABR achieved durable improvements in OS and PFS, with no new major toxicity signals with extended follow-up. A minority of patients randomized to the SABR arm (21.3%) achieved > 5 years of survival without recurrence., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Drugs have been used to prevent malaria for centuries, but only recently have they been used on a large scale to prevent malaria in the resident population of malaria endemic areas in sub-Saharan Africa. This paper discusses some of the reasons for the hesitancy in adoption of chemopreventive strategies in sub-Saharan Africa, reasons why this hesitancy has been overcome in recent years and the range of target groups now identified by the World Health Organization as those who can benefit most from chemoprevention. Adoption of carefully targeted chemopreventive strategies could help reverse the recent stagnation in the decline in malaria in sub-Saharan Africa that had been taking place during the previous two decades.