Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial.

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.

Global Access to Radiotherapy in Low- and Middle-income Countries.

Over the last 60 years, the International Atomic Energy Agency (IAEA) has been working to introduce, expand and improve radiotherapy services, working with partners such as the World Health Organization (WHO) to improve cancer diagnosis, treatment, care and control through collective action in low- and middle-income countries (LMICs). The Lancet Oncology Commission on radiotherapy published a report that defined five calls for action to expand global access to radiotherapy, drawing on the previous work of the Global Taskforce on Radiotherapy for Cancer Control. The IAEA supports LMICs in the development of the required national infrastructure and regulatory authority for radiation and nuclear safety and in the training of human resources necessary for the provision of high-quality effective and safe radiation medicine services for the diagnosis, treatment and palliative care of cancer patients, helping in this way to address the different priorities outlined in the Lancet Commission report.

Need for radiotherapy in low and middle income countries ­ the silent crisis continues.

About 57% of the total number of cancer cases occur in low and middle income countries. Radiotherapy is one of the main components of cancer treatment and requires substantial initial investment in infrastructure and training. Many departments continue to have basic facilities and to use simple techniques, while modern technologies have only been installed in big cities in upper-middle income countries. More than 50% of cancer patients requiring radiotherapy in low and middle income countries lack access to treatment. The situation is dramatic in low income countries, where the proportion is higher than 90%. The overall number of additional teletherapy units needed corresponds to about twice the installed capacity in Europe. The figures for different income level groups clearly show the correlation between gross national income per capita and the availability of services. The range of radiotherapy needs currently covered varies from 0% and 3-4% in low income countries in Latin America and Africa up to 59-79% in upper-middle income countries in Europe and Central Asia. The number of additional radiation oncologists, medical physicist, dosimetrists and radiation therapists (RTTs) required to operate additional radiotherapy departments needed is 43 200 professionals. Training and education programmes are not available in every developing country and in many cases the only option is sending trainees abroad, which is not a cost-effective solution. The implementation of adequate local training should be the following step after establishing the first radiotherapy facility in any country. Joint efforts should be made to establish at least one radiotherapy facility in countries where they do not exist, in order to create radiotherapy communities that could be the base for future expansion.

Residual tumour volumes and grey zones after external beam radiotherapy (with or without chemotherapy) in cervical cancer patients. A low-field MRI study.

BACKGROUND: Grey zones, which are defined as tissue with intermediate signal intensity in the area of primary hyperintense tumour extension, can be seen during radiation with or without chemotherapy on the T2-weighted MRI in patients with cervical cancer. The purpose of this study was to systematically measure the tumour volume at the time of diagnosis and the residual tumour volume at the time of brachytherapy without and with consideration of the grey zones and to estimate tumour regression during external beam radiotherapy (EBRT). MATERIAL AND METHODS: T2-weighted MRI datasets of 175 patients with locally advanced cervical cancer (FIGO stage IB-IVA), who underwent combined external beam radiotherapy and brachytherapy with or without concomitant chemotherapy were available for this study. The gross tumour volume at the time of diagnosis (GTV(init)) and at the time of first brachytherapy without (GTV(res)) and with (GTV(res)+ GZ) consideration of grey zones were measured for each patient. A descriptive statistical analysis was performed and tumour regression rates without (R) and with consideration of grey zones (R(GZ)) were calculated. Further, the role of prognostic factors on GTV(init), GTV(res), GTV(res)+ GZ and tumour regression rates was investigated. RESULTS: The median GTV(init), GTV(res), GTV(res)+ GZ in all patients were 44.4 cm(3), 8.2 cm(3), 20.3 cm(3), respectively. The median R was 78.5% and the median R(GZ) was 50.1%. The histology and FIGO staging showed a significant impact on GTV(init), GTV(res) and GTV(res)+ GZ. CONCLUSION: Grey zones represent a substantial proportion of the residual tumour volume at the time of brachytherapy. Differentiation of high signal intensity mass and surrounding intermediate signal intensity grey zones may be reasonable.

Radiation-induced morphological changes in the vagina.

BACKGROUND AND PURPOSE: Treatment-induced chronic vaginal changes after definitive radio(chemo)therapy for locally advanced cervical cancer patients are reported as one of the most distressing consequences of treatment, with major impact on quality of life. Although these vaginal changes are regularly documented during gynecological follow-up examinations, the classic radiation morbidity grading scales are not concise in their reporting. The aim of the study was therefore to identify and qualitatively describe, on the basis of vaginoscopies, morphological changes in the vagina after definitive radio(chemo)therapy and to establish a classification system for their detailed and reproducible documentation. PATIENTS AND METHODS: Vaginoscopy with photodocumentation was performed prospectively in 22 patients with locally advanced cervical cancer after definitive radio(chemo)therapy at 3-24 months after end of treatment. All patients were in complete remission and without severe grade 3/4 morbidity outside the vagina. RESULTS: Five morphological parameters, which occurred consistently after treatment, were identified: mucosal pallor, telangiectasia, fragility of the vaginal wall, ulceration, and adhesions/occlusion. The symptoms in general were observed at different time points in individual patients; their quality was independent of the time of assessment. Based on the morphological findings, a comprehensive descriptive and semiquantitative scoring system was developed, which allows for classification of vaginal changes. A photographic atlas to illustrate the morphology of the alterations is presented. CONCLUSION: Vaginoscopy is an easily applicable, informative, and well-tolerated procedure for the objective assessment of morphological vaginal changes after radio(chemo)therapy and provides comprehensive and detailed information. This allows for precise classification of the severity of individual changes.

Image-guided adaptive brachytherapy for cervix carcinoma.

Sectional imaging has played an important role in the management of cervical cancer, in particular for staging, and is now considered for image-guided treatment planning, in particular for brachytherapy. Image-based three-dimensional brachytherapy is a relatively new approach that is increasingly replacing the traditional two-dimensional X-ray-based method. This overview focuses on the potential and some practicalities of this approach. The pros and cons of computed tomography- and magnetic resonance imaging-based brachytherapy are considered and an overview of the current state of research is given. The first encouraging clinical results are presented and future perspectives are discussed.