Automated radiation treatment planning for cervical cancer

CITATION: Rhee, D. J. et al. 2020. Automated radiation treatment planning for cervical cancer. Seminars in Radiation Oncology, 30(4):340-347, doi:10.1016/j.semradonc.2020.05.006.The original publication is available at https://www.sciencedirect.comThe radiation treatment-planning process includes contouring, planning, and reviewing the final plan, and each component requires substantial time and effort from multiple experts. Automation of treatment planning can save time and reduce the cost of radiation treatment, and potentially provides more consistent and better quality plans. With the recent breakthroughs in computer hardware and artificial intelligence technology, automation methods for radiation treatment planning have achieved a clinically acceptable level of performance in general. At the same time, the automation process should be developed and evaluated independently for different disease sites and treatment techniques as they are unique from each other. In this article, we will discuss the current status of automated radiation treatment planning for cervical cancer for simple and complex plans and corresponding automated quality assurance methods. Furthermore, we will introduce Radiation Planning Assistant, a web-based system designed to fully automate treatment planning for cervical cancer and other treatment sites.Publisher's versio

Artificial Intelligence-Based Radiotherapy Contouring and Planning to Improve Global Access to Cancer Care.

PURPOSE: Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world. METHODS: The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale. RESULTS: For cervical cancer, RPA plans using bony landmarks were scored as usable as-is in 81% (with minor edits 93%); using soft tissue contours, plans were scored as usable as-is in 79% (with minor edits 96%). For postmastectomy breast cancer, RPA plans were scored as usable as-is in 44% (with minor edits 91%). For whole-brain treatment, RPA plans were scored as usable as-is in 67% (with minor edits 99%). For head/neck cancer, the normal tissue autocontours were acceptable as-is in 89% (with minor edits 97%). The clinical target volumes (CTVs) were acceptable as-is in 40% (with minor edits 93%). The volumetric-modulated arc therapy (VMAT) plans were acceptable as-is in 87% (with minor edits 96%). For cervical cancer, the normal tissue autocontours were acceptable as-is in 92% (with minor edits 99%). The CTVs for cervical cancer were scored as acceptable as-is in 83% (with minor edits 92%). The VMAT plans for cervical cancer were acceptable as-is in 99% (with minor edits 100%). CONCLUSION: The RPA, a web-based tool designed to improve access to high-quality RT in low-resource settings, has high rates of clinical acceptability by practicing clinicians around the world. It has significant potential for successful implementation in low-resource clinics

Customizable landmark-based field aperture design for automated whole-brain radiotherapy treatment planning.

PURPOSE: To develop and evaluate an automated whole-brain radiotherapy (WBRT) treatment planning pipeline with a deep learning-based auto-contouring and customizable landmark-based field aperture design. METHODS: The pipeline consisted of the following steps: (1) Auto-contour normal structures on computed tomography scans and digitally reconstructed radiographs using deep learning techniques, (2) locate the landmark structures using the beam's-eye-view, (3) generate field apertures based on eight different landmark rules addressing different clinical purposes and physician preferences. Two parallel approaches for generating field apertures were developed for quality control. The performance of the generated field shapes and dose distributions were compared with the original clinical plans. The clinical acceptability of the plans was assessed by five radiation oncologists from four hospitals. RESULTS: The performance of the generated field apertures was evaluated by the Hausdorff distance (HD) and mean surface distance (MSD) from 182 patients' field apertures used in the clinic. The average HD and MSD for the generated field apertures were 16 ± 7 and 7 ± 3 mm for the first approach, respectively, and 17 ± 7 and 7 ± 3 mm, respectively, for the second approach. The differences regarding HD and MSD between the first and the second approaches were 1 ± 2 and 1 ± 3 mm, respectively. A clinical review of the field aperture design, conducted using 30 patients, achieved a 100% acceptance rate for both the first and second approaches, and the plan review achieved a 100% acceptance rate for the first approach and a 93% acceptance rate for the second approach. The average acceptance rate for meeting lens dosimetric recommendations was 80% (left lens) and 77% (right lens) for the first approach, and 70% (both left and right lenses) for the second approach, compared with 50% (left lens) and 53% (right lens) for the clinical plans. CONCLUSION: This study provided an automated pipeline with two field aperture generation approaches to automatically generate WBRT treatment plans. Both quantitative and qualitative evaluations demonstrated that our novel pipeline was comparable with the original clinical plans

A risk assessment of automated treatment planning and recommendations for clinical deployment

CITATION: Kisling, K. et al. 2019. A risk assessment of automated treatment planning and recommendations for clinical deployment. Medical Physics, 46(6): 2567-2574. doi:10.1002/mp.13552The original publication is available at https://aapm.onlinelibrary.wiley.com/journal/24734209Purpose: To assess the risk of failure of a recently developed automated treatment planning tool, the radiation planning assistant (RPA), and to determine the reduction in these risks with implementation of a quality assurance (QA) program specifically designed for the RPA. Methods: We used failure mode and effects analysis (FMEA) to assess the risk of the RPA. The steps involved in the workflow of planning a four-field box treatment of cervical cancer with the RPA were identified. Then, the potential failure modes at each step and their causes were identified and scored according to their likelihood of occurrence, severity, and likelihood of going undetected. Additionally, the impact of the components of the QA program on the detectability of the failure modes was assessed. The QA program was designed to supplement a clinic's standard QA processes and consisted of three components: (a) automatic, independent verification of the results of automated planning; (b) automatic comparison of treatment parameters to expected values; and (c) guided manual checks of the treatment plan. A risk priority number (RPN) was calculated for each potential failure mode with and without use of the QA program. Results: In the RPA automated treatment planning workflow, we identified 68 potential failure modes with 113 causes. The average RPN was 91 without the QA program and 68 with the QA program (maximum RPNs were 504 and 315, respectively). The reduction in RPN was due to an improvement in the likelihood of detecting failures, resulting in lower detectability scores. The top-ranked failure modes included incorrect identification of the marked isocenter, inappropriate beam aperture definition, incorrect entry of the prescription into the RPA plan directive, and lack of a comprehensive plan review by the physician. Conclusions: Using FMEA, we assessed the risks in the clinical deployment of an automated treatment planning workflow and showed that a specialized QA program for the RPA, which included automatic QA techniques, improved the detectability of failures, reducing this risk. However, some residual risks persisted, which were similar to those found in manual treatment planning, and human error remained a major cause of potential failures. Through the risk analysis process, we identified three key aspects of safe deployment of automated planning: (a) user training on potential failure modes; (b) comprehensive manual plan review by physicians and physicists; and (c) automated QA of the treatment plan.https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.13552Publisher’s versio

ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol.

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs. ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners

A retrospective analysis of the effect of planning tumour volume on survival in cervical carcinoma

CITATION: Fourie, I. & Simonds, H. M. 2018. A retrospective analysis of the effect of planning tumour volume on survival in cervical carcinoma. Southern African Journal of Gynaecological Oncology, 10(2):25-29, doi:10.1080/20742835.2018.1531469.The original publication is available at https://www.tandfonline.comIntroduction: Locally advanced stages of invasive cervical cancer (ICC) are associated with poor outcomes; factors influencing survival include increased tumour volume. In resource-constrained settings access to diagnostic imaging with CT and MRI is limited. Alternative methods of establishing tumour volume can be defined with use of the planning target volume (PTV) delineated prior to radiotherapy. The aim of this study is to determine whether increased PTV size impacted on overall survival in a cohort of cervical cancer patients with Stage IIB/IIIB disease who completed radical radiotherapy. Materials and methods: A retrospective analysis was undertaken of patients with histologically confirmed Stage IIB/IIIB ICC treated with radical radiotherapy. Exclusion criteria included patients who did not complete prescribed radiotherapy and brachytherapy. Demographic and treatment details were collected. Planning target volumes were retrieved. Kaplan–Meier analysis was used to calculate the overall survival rate. A multivariate Cox proportional hazard model was derived to assess associations with all-cause mortality. Results: A total of 71 patients met the inclusion/exclusion criteria. The median PTV was 653 cc. On univariate analysis factors significantly associated with a lower overall survival included HIV positivity and the presence of hydronephrosis. Increased PTV size paradoxically showed a trend to improved overall survival. On multivariant analysis HIV status, advanced stage, hydronephrosis and a smaller PTV were significantly related to higher all-cause mortality. Conclusion: It is concluded that, when using planning target volumes, the hypothesis that larger volumes impact on overall survival was disproved. A larger cohort and more accurate methods of determining tumour volume, including PET/CT, will be considered in future prospective studies.https://www.tandfonline.com/doi/full/10.1080/20742835.2018.1531469Publisher's versio

Long-term complications of pelvic radiotherapy

CITATION: Simonds, H. 2010. Long-term complications of pelvic radiotherapy. Southern African Journal of Gynaecological Oncology, 2(2):62-65.The original publication is available at http://www.sajgo.co.zaComplications following pelvic radiation are frequently under-reported and inadequately addressed. This overview examines the nature and the intensity of complications encountered by cancer survivors; it focuses specifically on gastrointestinal and vaginal complications, and the problems surrounding the methods of recording and assessing toxicities.http://www.sajgo.co.za/index.php/sajgo/article/view/43Publisher's versio

The impact of HIV status on staging, treatment and outcomes in locally advanced cervical carcinoma

Thesis (PhD)--Stellenbosch University, 2019.ENGLISH ABSTRACT: Cervical carcinoma is one of the most frequently diagnosed malignancies in women in many countries in sub-Saharan Africa, including South Africa. In sub-Saharan Africa, among women without HIV the age-standardised cervical cancer incidence rate is greater than 40 per 100 000. However, women infected with both the human-immunodeficiency virus (HIV) and the human papilloma virus (HPV) have a higher risk of developing cervical carcinoma than women infected with HPV alone. Published studies of the ideal staging methods, treatment algorithms, and outcomes for women with comorbid locally advanced cervical carcinoma and HIV are scarce. The aim of this body of work is to fill some of these gaps. We conducted four cohort studies of patients with locally advanced cervical carcinoma with or without HIV, recording demographic data, staging information and treatment delivered. Additional information gathered for individual studies included treatment response and survival outcomes. We evaluated the statistical significance of differences between HIV-positive and negative patients. Logistic regression models were utilised to evaluate risk for toxicity, treatment response, and survival outcomes. In the first of three retrospective cohort studies, among 383 patients, early response to chemoradiation was found to be related to advanced stage [OR 2.39, 95% CI 1.45-3.96] and completion of brachytherapy [OR 3.14; 95% CI 1.24-7.94] but not HIV status. In the second retrospective study, among 213 patients undergoing radical radiotherapy, acute Grade 3 / 4 toxicity was associated with receiving chemotherapy [OR4.41; 95%CI 1.76- 11.1; p 0.023] and having HIV [OR 2.16; 95% CI0.98-4.8; p 0.05]. In a prospective study of 492 patients, OS at 5 years was 49.5% (95%CI; 44.6% - 54.4%) among HIV-negative patients but only 35.9% (95% CI; 23.9% - 48.0%) among HIV-positive patients (p=0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, hydronephrosis, and delivery of concurrent chemotherapy. In the fourth cohort study, among 273 patients with locally advanced cervical carcinoma who underwent a radiotherapy planning PET-CT scan, overall 235 (84.5%) were upstaged. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Following the PET-CT scan, among the 263 patients who attended for radiotherapy treatment, intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). This body of work demonstrated that in HIV-positive patients, integration of PET-CT into staging algorithms for cervical carcinoma is a viable option. During treatment HIV-positive patients experienced increased toxicity, but most were able to complete treatment, and their 5-year overall survival was nearly 40%. Among women with locally advanced cervical cancer, those with HIV infection should be treated with the best standard of care. Future research should focus on factors that improve outcomes for these women.AFRIKAANSE OPSOMMING: Servikale karsinoom is een van die mees gediagnoseerde kwaadaardige gewasse in vroue in baie lande in sub-Sahara Afrika, insluitende Suid-Afrika. Die voorkoms van servikale kanker is meer as 40 per 100 000 (ouderdom-gestandaardiseerde koers) in sub- Sahara Afrika, selfs onder vroue sonder menslike immuniteitsgebrek virus (MIV). Vroue met beide MIV en menslike papilloom virus (MPV) infeksies het 'n hoër risiko vir die ontwikkeling van servikale karsinoom as vroue wat slegs MPV infeksie het. Daar is 'n tekort aan gepubliseerde werk oor die ideale stadiërings ondersoeke, behandeling algoritmes en uitkomste vir vroue met lokaal gevorderde servikale karsinoom en MIV infeksie. Verder dit is onduidelik wat die impak van MIV-positiwiteit mag hê op hierdie parameters. Die doel van hierdie navorsing is om sommige van hierdie vrae te antwoord. Pasiënte, met of sonder MIV en lokaal gevorderde servikale karsinoom is in vier kohort studies bestudeer. In al die studies is inligting versamel oor demografie, stadiëring en die behandeling ontvang. Bykomende inligting vir individuele studies het respons op behandeling en oorlewing-uitkomste ingesluit. Die statistiese betekenisvolheid van verskille tussen MIV-positiewe en negatiewe pasiënte is bereken. Logistiese regressie modelle is gebruik om die risiko vir newe-effekte, behandelingsuitkoms en oorlewing te evalueer. In die eerste van die drie terugskouende kohort studies op 383 pasiënte, is bevind dat vroeë reaksie op chemo- bestraling betekenisvol verband hou met gevorderde stadium van karsinoom [KV 2.39, 95% VI 1.45- 3.96] en voltooiing van bragiterapie [KV 3.14; 95% VI 1.24-7.94] maar nie met MIV status nie. In die tweede terugskouende studie, wat 213 pasiënte ingesluit het wat radikale radioterapie ondergaan het, was akute graad 3 / 4 toksisiteit betekenisvol geassosieer met byvoeging van chemoterapie [KV4.41; 95% VI 1.76-11.1; p 0.023] en MIV positiwiteit [KV 2.16; 95% VI 0.98-4.8; p 0.05]. Vyf jaar algehele oorlewing is in 'n prospektiewe studie van 492 pasiënte geëvalueer. Die algehele oorlewing van MIV-negatiewe pasiënte was 49.5% (95% VI 44.6% – 54.4%) teen 5 jaar. Die algehele oorlewing van MIV-positiewe pasiënte was aansienlik laer, 35.9% (95% VI 23.9% – 48.0%) teen 5 jaar (p = 0.002). In die Cox modelle was die faktore wat uitkoms beïnvloed het, MIV-infeksie, stadium IIIB siekte, die teenwoordigheid van hidronefrose en toediening van gelyktydige chemoterapie. In die vierde kohort studie van 273 pasiënte met lokaal gevorderde servikale karsinoom, het pasiënte vir radioterapie beplanning 'n Pet-RT (rekenaar tomografie) skandering ontvang. In totaal is 235 pasiënte (84.5%) se stadiëring verhoog weens die bykomende inligting verkry van Pet-RT skandering. Verhoging in stadium het nie verband gehou met MIV-status nie (MIV-negatiewe 83.9% teenoor MIV-positiewe 87.2%; p = 0.47). Van die 263 pasiënte wat wel radioterapie behandeling ontvang het, is die plan verander vir 124 pasiënte as gevolg van die Pet-RT skandering (46.3%), 53.6% van MIV-positiewe pasiënte en 42.9% van MIV-negatiewe pasiënte (p = 0.11). Hierdie navorsing het getoon dat integrasie van Pet-RT in stadiëring algoritmes vir servikale karsinoom 'n redelike opsie is vir MIV-positiewe pasiënte. Verder is aangetoon MIV-positiewe pasiënte meer newe-effekte ervaar tydens behandeling, maar in staat is om behandeling in die meerderheid van gevalle te voltooi met 'n 5-jaar algehele oorlewing van bykans 40%. In vroue met lokaal gevorderde servikale kanker moet diegene met MIV-infeksie met die beste standaard van sorg behandel word. Toekomstige navorsing moet fokus op faktore wat uitkomste verbeter vir hierdie vroue.Doctora