National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis.

BACKGROUND: In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. METHODS: In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. FINDINGS: 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (ß=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (ß=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. INTERPRETATION: Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. FUNDING: None.

Impact of HPV vaccination and cervical screening on cervical cancer elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries.

BACKGROUND: The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. FINDINGS: Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4-19·8) to 2·1 (2·0-2·6) cases per 100 000 women-years over the next century (89·4% [86·2-90·1] reduction), and to avert 61·0 million (60·5-63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6-1·6) cases per 100 000 women-years (96·7% [91·3-96·7] reduction) and averted an extra 12·1 million (9·5-13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58-65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89-100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37-99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71-100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11-31 years. Long-term vaccine protection was required for elimination. INTERPRETATION: Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Québec-Santé, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

Mortality impact of achieving WHO cervical cancer elimination targets: a comparative modelling analysis in 78 low-income and lower-middle-income countries.

BACKGROUND: WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. FINDINGS: In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120. INTERPRETATION: These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.

How to reduce the impact of cervical cancer worldwide: Gaps and priority areas identified through the essential cancer and primary care packages: An analysis of effective interventions.

BACKGROUND: Cervical cancer is a preventable cancer; therefore, countries should provide strategic, evidence-based health services to reduce its incidence and impact on their populations. Two packages of health services that group together all the services related to cervical cancer, the Essential Cancer Package (9 interventions) and the Primary Care Package (5 interventions), are defined in this article with the aim of assessing the global status of the availability of health services and their coverage in 194 countries worldwide. METHODS: The study was based on the 2017 World Health Organization (WHO) Noncommunicable Disease Country Capacity Survey. Although the survey covered multiple noncommunicable diseases, this report examined only those results pertaining to cervical cancer in the 194 WHO member states divided by WHO region and World Bank income. RESULTS: Only 21% of the countries reported providing all 9 interventions of the Essential Cancer Package, with the highest proportions being found in Europe (45.3%) and among high-income countries (HICs; 54.3%). As for the Primary Care Package, only 19.1% of countries provided all 5 interventions, with the highest proportions being found in Europe (39.6%) and among HICs (45.5%). CONCLUSIONS: The complete development and appropriate coverage of each service listed in both the Essential Cancer Package and the Primary Care Package are essential to reduce the impact of cervical cancer worldwide, and they should be integrated into all cancer control planning efforts.

Outcome of treatment of recurrent glioblastoma multiforme in elderly and/or frail patients.

Optimal treatment of recurrent glioblastoma multiforme (rGBM) in elderly and/or frail patients remains virtually unexplored, the best supportive care (BSC) only is routinely administered due to the fatal prognosis. We evaluated the impact of different treatment methods on post-progression survival (PPS) and overall survival (OS) of such patients. Data from 98 elderly and/or frail rGBM patients, treated initially with 1-week or 3-week radiotherapy (RT) within the phase III IAEA study (2010-2013), were analyzed. KPS at relapse and salvage treatment methods were recorded. Kaplan-Meier method was used to estimate PPS and OS for different treatment modalities. Eighty-four patients experienced recurrence: 47 (56%) received BSC, 21 (25%)-chemotherapy (CHT), 8 (9.5%)-surgery, 3 (3.5%)-RT, for 5 (6%) the data was unavailable. Median OS from randomization for all 84 patients was 35 weeks: 55 versus 30 weeks for any treatment versus BSC, p < 0.0001. Median PPS was 15 weeks: 23 weeks with any treatment versus 9 weeks with BSC, p < 0.0001. For local treatment (surgery and/or RT) median PPS was 51 versus 21 weeks for CHT, p = 0.36. In patients with poor KPS (≤60) at relapse median PPS was 9 weeks with BSC versus 21 weeks with any treatment, p = 0.014. In poor KPS patients median PPS for local treatment was 14 weeks versus 21 weeks with CHT, p = 0.88. An active therapeutic approach may be beneficial for selected elderly and/or frail rGBM patients. Poor KPS patients may also benefit from active treatment, but there is no benefit of local treatment over CHT.

Magnetic resonance imaging for assessment of parametrial tumour spread and regression patterns in adaptive cervix cancer radiotherapy.

PURPOSE: To investigate the impact of magnetic resonance imaging (MRI)-morphologic differences in parametrial infiltration on tumour response during primary radiochemotherapy in cervical cancer. MATERIAL AND METHODS: Eighty-five consecutive cervical cancer patients with FIGO stages IIB (n = 59) and IIIB (n = 26), treated by external beam radiotherapy (± chemotherapy) and image-guided adaptive brachytherapy, underwent T2-weighted MRI at the time of diagnosis and at the time of brachytherapy. MRI patterns of parametrial tumour infiltration at the time of diagnosis were assessed with regard to predominant morphology and maximum extent of parametrial tumour infiltration and were stratified into five tumour groups (TG): 1) expansive with spiculae; 2) expansive with spiculae and infiltrating parts; 3) infiltrative into the inner third of the parametrial space (PM); 4) infiltrative into the middle third of the PM; and 5) infiltrative into the outer third of the PM. MRI at the time of brachytherapy was used for identifying presence (residual vs. no residual disease) and signal intensity (high vs. intermediate) of residual disease within the PM. Left and right PM of each patient were evaluated separately at both time points. The impact of the TG on tumour remission status within the PM was analysed using χ(2)-test and logistic regression analysis. RESULTS: In total, 170 PM were analysed. The TG 1, 2, 3, 4, 5 were present in 12%, 11%, 35%, 25% and 12% of the cases, respectively. Five percent of the PM were tumour-free. Residual tumour in the PM was identified in 19%, 68%, 88%, 90% and 85% of the PM for the TG 1, 2, 3, 4, and 5, respectively. The TG 3-5 had significantly higher rates of residual tumour in the PM in comparison to TG 1 + 2 (88% vs. 43%, p < 0.01). CONCLUSION: MRI-morphologic features of PM infiltration appear to allow for prediction of tumour response during external beam radiotherapy and chemotherapy. A predominantly infiltrative tumour spread at the time of diagnosis resulted in a significantly higher rate of residual tumour in the PM at the time of brachytherapy in comparison to a predominantly expansive tumour spread.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

Cervical Cancer-Associated Suffering: Estimating the Palliative Care Needs of a Highly Vulnerable Population.

PURPOSE: To enable design of optimum palliative care for women with cervical cancer, we studied the most common types of suffering and their severity, prevalence, and duration. METHODS: We first reviewed the literature on the major types, severity, prevalence, and duration of suffering associated with cervical cancer. We then conducted a modified Delphi process with experts in cervical cancer care to supplement the literature. For each type of suffering, we distinguished between decedents (those who die from cervical cancer in a given year) and nondecedents (those who have cervical cancer in a given year but do not die). By applying the suffering prevalence and duration estimates to the number of decedents, nondecedents, and family caregivers in 2017, we were able to estimate their palliative care needs and the intensity of palliative care needed to respond adequately to this suffering. RESULTS: There is a high prevalence among decedents of moderate or severe pain (84%), vaginal discharge (66%), vaginal bleeding (61%), and loss of faith (31%). Among both decedents and nondecedents, there is a high prevalence of clinically significant anxiety (63% and 50%, respectively), depressed mood (52% and 38%, respectively), and sexual dysfunction (87% and 83%, respectively). Moderate or severe financial distress is prevalent among decedents, nondecedents, and family caregivers (84%, 74%, and 66%, respectively). More than 40% of decedents and nondecedents are abandoned by their intimate partners. Most patients experience some combination of moderate or severe physical, psychological, social, and spiritual suffering. In total, 258,649 decedents and 2,558,857 nondecedents needed palliative care in 2017, approximately 85% of whom were in low- and middle-income countries where palliative care is rarely accessible. CONCLUSION: Among women with advanced cervical cancer, suffering is highly prevalent and often severe and multifaceted.

Essential Package of Palliative Care for Women With Cervical Cancer: Responding to the Suffering of a Highly Vulnerable Population.

Women with cervical cancer, especially those with advanced disease, appear to experience suffering that is more prevalent, complex, and severe than that caused by other cancers and serious illnesses, and approximately 85% live in low- and middle-income countries where palliative care is rarely accessible. To respond to the highly prevalent and extreme suffering in this vulnerable population, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an essential package of palliative care for cervical cancer (EPPCCC). The EPPCCC consists of a set of interventions, medicines, simple equipment, social supports, and human resources, and is designed to be safe and effective for preventing and relieving all types of suffering associated with cervical cancer. It includes only inexpensive and readily available medicines and equipment, and its use requires only basic training. Thus, the EPPCCC can and should be made accessible everywhere, including for the rural poor. We provide guidance for integrating the EPPCCC into gynecologic and oncologic care at all levels of health care systems, and into primary care, in countries of all income levels.

Augmented Package of Palliative Care for Women With Cervical Cancer: Responding to Refractory Suffering.

The essential package of palliative care for cervical cancer (EPPCCC), described elsewhere, is designed to be safe and effective for preventing and relieving most suffering associated with cervical cancer and universally accessible. However, it appears that women with cervical cancer, more frequently than patients with other cancers, experience various types of suffering that are refractory to basic palliative care such as what can be provided with the EPPCCC. In particular, relief of refractory pain, vomiting because of bowel obstruction, bleeding, and psychosocial suffering may require additional expertise, medicines, or equipment. Therefore, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an augmented package of palliative care for cervical cancer with which even suffering refractory to the EPPCCC often can be relieved. The package consists of medicines, radiotherapy, surgical procedures, and psycho-oncologic therapies that require advanced or specialized training. Each item in this package should be made accessible whenever the necessary resources and expertise are available.

Examining policy cohesion for cervical cancer worldwide: analysis of WHO country reports.

INTRODUCTION: Cervical cancer is controllable through appropriate interventions such as vaccination, screening, treatment, early diagnosis and palliative care. The greatest burden of cervical cancer lies in low-income countries (LIC) where most of these services are missing or developed asymmetrically. Indeed, it is important to have not just an expansion, but a symmetric and concordant development of each service. Therefore, policies of countries should be aligned to provide concordant services and achieve the best outcomes with available resources. This is called 'policy cohesion' and for the first time in literature we will analyse cervical cancer policy coherence in all the 194 WHO member states. METHODS: The study is based on the 2017 WHO Non-Communicable Disease Country Capacity Surveys (NCD CCS). Although the survey covers multiple non-communicable diseases, in this report we will only discuss those results pertaining to cervical cancer, analysing the cervical cancer policy cohesion of 194 WHO member states, divided by WHO region and World Bank income group. RESULTS: Human papilloma virus vaccination exists in 53% of countries. 76% of countries offer cervical screening: among these countries, treatment, early diagnosis guidelines and palliative care are missing in 13%, 13% and 40%, respectively. In the African region, this discord is even more profound: 32%, 17% and 60%, respectively. CONCLUSION: Especially in those settings where resources are limited, early detection guidelines, treatment and palliative care should be implemented along with secondary prevention strategies. Symmetric development of concordant cervical cancer services maximises cervical cancer control efficacy.

Microdistribution of targeted, fluorescently labeled anti-carcinoembryonic antigen antibody in metastatic colorectal cancer: implications for radioimmunotherapy.

PURPOSE: Most radioimmunotherapy studies on radiolabeled antibody distribution are based on autoradiographic and radioluminographic data, which provide a lack of detailed information due to low resolution. We used fluorescently labeled anti-carcinoembryonic antigen (CEA) antibody (A5B7) to investigate quantitatively the kinetics and microdistribution of antibody in a clinically relevant orthotopic colorectal cancer model (LS174T) using high-resolution digital microscopy. EXPERIMENTAL DESIGN: Nude mice bearing LS174T liver orthotopic tumors received a single i.v. injection of fluorescently labeled A5B7 and were sacrificed at 10 minutes, 1 hour, or 24 hours postinjection. Before sacrifice, mice were injected with the perfusion marker Hoechst 33342. An anti-CD31 antibody was used to detect blood vessel distribution. Cryostat sections were processed with immunofluorescence procedures and analyzed with fluorescence microscopy and image analysis techniques. The fluorescence images were related to morphologic images of the same or adjacent tumor sections. RESULTS: Fluorescently labeled antibody showed rapid, selective uptake into tumor deposits, with a strong negative correlation with tumor size at 10 minutes and 1 hour (P < or = 0.01). By 24 hours, the correlation was no longer significant. The study showed movement of antibody across the tumor with time and a tendency to localize more uniformly by later time points (24 hours). The rate of antibody motility was similar in small and large tumor metastases, but small deposits showed more rapid antibody localization. Intratumoral vessels were positively related to tumor size (P < or = 0.001). CONCLUSION: The obtained data suggest that radioimmunotherapy can be highly efficient in an adjuvant or minimal residual disease setting.

Present status and future of high-precision image guided adaptive brachytherapy for cervix carcinoma.

INTRODUCTION: Image guided adaptive brachytherapy (IGABT) for cervical cancer, using mainly MRI, is an evolving method, increasingly replacing the 2D approach based on conventional radiography. During the complex 4D chain of this procedure image-assistance is provided for disease assessment, provisional treatment planning ("pre-planning"), applicator placement and reconstruction, as well as for contouring, definitive treatment planning and quality control of dose delivery. With IGABT changes of topography adjacent to the applicator, caused by tumour regression, oedema, organ changes and dilation are identified. Thus, the CTV for IGABT is primarily based on the tumour volume at the time of BT and takes into account both time and spatial domains. IGABT requires systematic concepts for target, OAR, biological modelling, DVH analysis, and dose-volume-adaptation. METHODS AND RESULTS: This report focuses on the advantages and uncertainties, dose-effect relations and clinical results of the IGABT procedure addressing the current status and future perspectives. Uncertainties during the 4D chain of IGABT are mainly related to target contouring, applicator reconstruction, as well as to inter-fraction, intra-fraction and inter-application variability, as caused by tumour response and organ changes. Different from EBRT where set-up uncertainties are compensated by adding a margin to the CTV, no margins to the lateral and anterior-posterior directions can be used for IGABT. DISCUSSION: By 3D treatment planning for IGABT significant improvement of the DVH parameters is achieved compared to 2D library plans. In small tumours the benefit is primarily obtained by a decrease of dose to nearby OAR while in large tumours the use of supplementary interstitial techniques and optimization may double the target volume that can be treated at a therapeutic dose level. The clinical impact of IGABT could recently be demonstrated by the establishment of some correlations between target- and organ-related DVH parameters versus disease control and side effects, which need further clarification. Overall, a very high local control rate can be achieved with minor treatment related morbidity. This favourable therapeutic ratio seems to be now reproducible under different conditions at various treatment centres. These results have to be validated within the upcoming multi-centre prospective IntErnational study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE).

Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail patients with glioblastoma.

BACKGROUND AND PURPOSE: Short-course radiotherapy (25 Gy in five fractions) was recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15 fractions in elderly and/or frail patients with glioblastoma multiforme. This study compared the cost-effectiveness of the two regimens. MATERIAL AND METHODS: The direct unit costs of imaging, radiotherapy (RT), and dexamethasone were collected from the five primary contributing countries to the trial, constituting the data of 88% of all patients. Effectiveness was measured by the restricted mean overall survival (RMOS) and progression free survival (RMPFS). The incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were also estimated for comparison. RESULTS: The median OSs for the short-course and commonly used RTs were 8.2 (95% confidence interval [CI] 6.1-10.3) and 7.7 (95% CI 5.5-9.9) months, respectively (log rank p = 0.340). Median PFSs were also not different (p = 0.686). The differences in the RMOS and the ICER, however, were +0.11 life-years and -$3062 United States dollars (USD) per life-year gained, respectively. The differences in the RMPFS and the ICER were +0.02 PFS and -$17,693 USD, respectively. CONCLUSION: The ICER of -$3062 per life-year gained and -$17,693 per PFS gained indicates that the short-course RT is less costly compared to the longer RT regimen.

Radiotherapy utilization in developing countries: An IAEA study.

BACKGROUND: The planning of national radiotherapy (RT) services requires a thorough knowledge of the country's cancer epidemiology profile, the radiotherapy utilization (RTU) rates and a future projection of these data. Previous studies have established RTU rates in high-income countries. METHODS: Optimal RTU (oRTU) rates were determined for nine middle-income countries, following the epidemiological evidence-based method. The actual RTU (aRTU) rates were calculated dividing the total number of new notifiable cancer patients treated with radiotherapy in 2012 by the total number of cancer patients diagnosed in the same year in each country. An analysis of the characteristics of patients and treatments in a series of 300 consecutive radiotherapy patients shed light on the particular patient and treatments profile in the participating countries. RESULTS: The median oRTU rate for the group of nine countries was 52% (47-56%). The median aRTU rate for the nine countries was 28% (9-46%). These results show that the real proportion of cancer patients receiving RT is lower than the optimal RTU with a rate difference between 10-42.7%. The median percent-unmet need was 47% (18-82.3%). CONCLUSIONS: The optimal RTU rate in middle-income countries did not differ significantly from that previously found in high-income countries. The actual RTU rates were consistently lower than the optimal, in particular in countries with limited resources and a large population.

Quality of radiotherapy services in post-Soviet countries: An IAEA survey.

BACKGROUND: The quality of radiotherapy services in post-Soviet countries has not yet been studied following a formal methodology. The IAEA conducted a survey using two sets of validated radiation oncology quality indicators (ROIs). METHODS: Eleven post-Soviet countries were assessed. A coordinator was designated for each country and acted as the liaison between the country and the IAEA. The methodology was a one-time cross-sectional survey using a 58-question tool in Russian. The questionnaire was based on two validated sets of ROIs: for radiotherapy centres, the indicators proposed by Cionini et al., and for data at the country level, the Australasian ROIs. RESULTS: The overall response ratio was 66.3%, but for the Russian Federation, it was 24%. Data were updated on radiotherapy infrastructure and equipment. 256 radiotherapy centres are operating 275 linear accelerators and 337 Cobalt-60 units. 61% of teletherapy machines are older than ten years. Analysis of ROIs revealed significant differences between these countries and radiotherapy practices in the West. Naming, task profile and education programmes of radiotherapy professionals are different than in the West. CONCLUSIONS: Most countries need modernization of their radiotherapy infrastructure coupled with adequate staffing numbers and updated education programmes focusing on evidence-based medicine, quality, and safety.

Survival Outcomes With Short-Course Radiation Therapy in Elderly Patients With Glioblastoma: Data From a Randomized Phase 3 Trial.

PURPOSE: To perform a subset analysis of survival outcomes in elderly patients with glioblastoma from a randomized phase 3 trial comparing 2 short-course radiation therapy (RT) regimens in elderly and/or frail patients. METHODS AND MATERIALS: The original trial population included elderly and/or frail patients with a diagnosis of glioblastoma. Patients joined the phase 3, randomized, multicenter, prospective, noninferiority trial; were assigned to 1 of 2 groups in a 1:1 ratio, either short-course RT (25 Gy in 5 fractions, arm 1) or commonly used RT (40 Gy in 15 fractions, arm 2); and were stratified by age (<65 years and ≥65 years), Karnofsky Performance Status (KPS), and extent of surgery. For the subset analysis in this study, only patients aged ≥65 years were evaluated (elderly and frail patients were defined as patients aged ≥65 years with KPS of 50%-70%; elderly and non-frail patients were defined as patients aged ≥65 years with KPS of 80%-100%); 61 of the 98 initial patients comprised the patient population, with 26 patients randomized to arm 1 and 35 to arm 2. RESULTS: In this unplanned analysis, the short-course RT results were not statistically significantly different from the results of commonly used RT in elderly patients. The median overall survival time was 6.8 months (95% confidence interval [CI], 4.5-9.1 months) in arm 1 and 6.2 months (95% CI, 4.7-7.7 months) in arm 2 (P=.936). The median progression-free survival time was 4.3 months (95% CI, 2.6-5.9 months) in arm 1 and 3.2 months (95% CI, 0.1-6.3 months) in arm 2 (P=.706). CONCLUSIONS: A short-course RT regimen of 25 Gy in 5 fractions is an acceptable treatment option for patients aged ≥65 years, mainly those with a poor performance status or contraindication to chemotherapy, which would be indicated in cases of methylated O6 methylguanine-DNA-methyltransferase promoter tumors.

American Brachytherapy Society: Brachytherapy treatment recommendations for locally advanced cervix cancer for low-income and middle-income countries.

PURPOSE: Most cervix cancer cases occur in low-income and middle-income countries (LMIC), and outcomes are suboptimal, even for early stage disease. Brachytherapy plays a central role in the treatment paradigm, improving both local control and overall survival. The American Brachytherapy Society (ABS) aims to provide guidelines for brachytherapy delivery in resource-limited settings. METHODS AND MATERIALS: A panel of clinicians and physicists with expertise in brachytherapy administration in LMIC was convened. A survey was developed to identify practice patterns at the authors' institutions and was also extended to participants of the Cervix Cancer Research Network. The scientific literature was reviewed to identify consensus papers or review articles with a focus on treatment of locally advanced, unresected cervical cancer in LMIC. RESULTS: Of the 40 participants invited to respond to the survey, 32 responded (response rate 80%). Participants were practicing in 14 different countries including both high-income (China, Singapore, Taiwan, United Kingdom, and United States) and low-income or middle-income countries (Bangladesh, Botswana, Brazil, India, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). Recommendations for modifications to existing ABS guidelines were reviewed by the panel members and are highlighted in this article. CONCLUSIONS: Recommendations for treatment of locally advanced, unresectable cervical cancer in LMIC are presented. The guidelines comment on staging, external beam radiotherapy, use of concurrent chemotherapy, overall treatment duration, use of anesthesia, applicator choice and placement verification, brachytherapy treatment planning including dose and prescription point, recommended reporting and documentation, physics support, and follow-up.