Genome Sequencing of Multiple Primary Lung Cancers Harbouring Mixed Histology and Spontaneously Regressing Small-Cell Lung Cancer.

Up to 15% of lung cancer patients present two or more anatomically separate primary lung lesions, known as multiple primary lung cancers (MPLCs). While surgical resection or stereotactic body radiation therapy (SBRT) is the standard of care for most early-stage lung cancer cases, this may not be an option for patients with widespread tumours, highlighting the need for the improved targeted management of MPLC patients, which remains challenging. Moreover, the spontaneous regression (SR) of small-cell lung cancer (SCLC) is rare, with only four cases accounted for between 1988 and 2018. We report a rare MPLC case harbouring the mixed histology of non-small-cell lung cancer adenocarcinoma (NSCLCa) and SCLC and the SR of SCLC without treatment. The patient was diagnosed in 2015 with MPLCs, identified as NSCLCa and SCLC. In 2016, a restaging PET/CT scan prior to the start of treatment showed SCLC SR. In 2018, a further tumour was detected in the patient's mandible, and a re-biopsy of the SCLC revealed histology consistent with NSCLCa. Whole-genome sequencing (WGS) analysis identified a high expression of programmed death ligand-1 (PDL-1) in the NSCLCa, which was treated with pembrolizumab. WGS revealed distinct genomic profiles and mutational mechanisms in MPLCs, suggesting the need for distinct targeted therapies to improve the management of MPLC patients and highlighting the importance of precision evaluation.

The role of radiotherapy in the management of nodal disease in breast cancer.

The management of nodal disease in breast cancer has evolved over the last two decades. With minimalist surgical approaches for early breast cancers becoming commonplace, the question of whether radiation can replace surgery to reduce morbidity is an important question in this population, as decision making has become more complex. In more advanced disease, and in patients with significant high-risk clinical and/or pathological features, the dilemma of who should receive regional nodal irradiation has been addressed in large studies but remains controversial. In this article, we summarise and discuss the recent trials which guide modern clinical practice, as well as some of the ongoing studies which aim to address outstanding questions within the field.

A National Cyberattack Affecting Radiation Therapy: The Irish Experience.

On Friday, May 14, 2021, the Health Service Executive, the organization providing public health services in the Republic of Ireland, was the victim of a significant cyberattack on its information technology systems. All systems were subsequently shut down to prevent further damage and to allow cybersecurity experts to investigate the attack. As a result, oncology services were severely disrupted, with the cessation of radiation therapy treatments in all public radiation therapy departments. Ireland has 5 large public and 6 smaller private radiation therapy centers in total. Because of the widespread adoption of electronic medical records in radiation therapy departments, it wasn't possible to retrieve patient details of those who were undergoing radiation therapy at the time of the cyberattack. In total, 513 patients nationally had their radiation therapy interrupted. A national radiation therapy cyberattack response team was formed immediately to oversee the response to the attack. The immediate concerns were radiation therapy emergencies and category 1 patients where gaps in treatment would have an adverse effect on outcome. Communication with patients and the public was also established as a priority and agreements were reached with the private sector for the treatment of patients affected by the cyberattack. The national media was used to alert patients of the need to communicate with their radiation therapy department. Dedicated phone lines were established. Locally, radiation therapy departments held daily crisis meetings with key staff members, including information technology personnel. Individual centers employed different technologies for treatment planning and data storage, so local solutions to the cyberattack to reestablish radiation therapy for patients were developed. In addition, national documentation on prioritization of patients to resume treatment was produced and a national approach was made to compensate for gaps in treatment caused by the attack. All 5 centers had reestablished radiation therapy by May 30, although there has been a long aftermath to the cyberattack. In this article, we provide an overview of the effects of the cyberattack on our national radiation therapy service and our strategy to resume patient treatment in a timely fashion.

Effect of the Cyberattack Targeting the Irish Health System in May 2021 on Radiation Treatment at St. Luke's Radiation Oncology Network.

On May 14, 2021, the Health Service Executive (HSE) of Ireland experienced a major ransomware cyberattack. The HSE initially took down all of its information technology systems to protect its core systems. All Internet connections within the HSE were unavailable from 7 am for approximetely three weeks which had a major effect on the radiation oncology service nationally within the public service. St. Luke's Radiation Oncology Network (SLRON) is a complex, 3-center radiation oncology service, and it is the largest in the country; with 14 linear accelerators, it is one of the largest radiation centers in Europe. This article details the response of SLRON to the outage resultant from the cyberattack. Although the outage affected all patient services, including laboratory, diagnostic imaging, and inpatient care, the article primarily focuses on our response to get the radiation oncology service restarted as quickly as possible and details the steps we took to reinstate our systems safely, how we prioritized patient treatments, and how we communicated with patients, staff, and the public without having access to standard communication pathways. All decisions were risk assessed and were made with the best resources available to us at the time to maximize the outcome for our patients and mitigate significant delays. The risk remains ongoing, and the onerous task of uploading backlogs and reconciling patient records is a continuing risk.

Anal squamous cell carcinoma: a retrospective case series.

BACKGROUND: Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000-2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. METHODS: Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. RESULTS: Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1-15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4-16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3-12.2 years). CONCLUSION: Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

Treatment of multiple intracranial metastases in radiation oncology: a contemporary review of available technologies.

The use of stereotactic radiosurgery to treat multiple intracranial metastases, frequently concurrently, has become increasingly common. The ability to accurately and safely deliver stereotactic radiosurgery treatment to multiple intracranial metastases (MIM) relies heavily on the technology available for targeting, planning, and delivering the dose. A number of platforms are currently marketed for such applications, each with intrinsic capabilities and limitations. These can be broadly categorised as cobalt-based, linac-based, and robotic. This review describes the most common representative technologies for each type along with their advantages and current limitations as they pertain to the treatment of multiple intracranial metastases. Each technology was used to plan five clinical cases selected to represent the clinical breadth of multiple metastases cases. The reviewers discuss the different strengths and limitations attributed to each technology in the case of MIM as well as the impact of disease-specific characteristics (such as total number of intracranial metastases, their size and relative proximity) on plan and treatment quality.

Determining normal tissue dose in intracranial stereotactic radiosurgery: A diameter-based predictive nomogram.

Purpose: A major factor in dose-fractionation selection for intracranial metastases in stereotactic radiosurgery (SRS) is the size of the target lesion and consequently the dose-volume to the surrounding normal brain tissue (NTV), as this has been correlated with brain radiation necrosis (RN). This study outlines the development and validation of a predictive model that can estimate the NTV for a range of dose-fractionation schemes based on target diameter from a patient's MRI. Methods: Data from a cohort of historical SRS clinical treatment plans were used to extract three key input parameters for the model - conformity index, gradient index, and a scaling factor which were then defined as a function of target volume. The relationship between the measured tumour diameter and the NTV was established by approximating the target to a spherical volume covered by the prescription dose. A scaling factor (λNTV) describes the non-linear fall-off of dose beyond the target. This was then used to provide a first-order approximation of the resulting NTV. The predictive model was retrospectively validated using linear regression against actual NTV values from 39 historical SRS plans which were independent to the derivation process. The model was validated for both three-dimensional (3D) target diameter and axial-only two-dimensional (2D) estimates of target diameter values. Results: The prediction model directly relates lesion diameter to NTV volume (cc) and thus RN risk for a given dose-fractionation. The predicted NTV (cc) for both 3D- and 2D-based volume estimates could statistically significantly predict the actual NTV (cc): R2=0.942 (p<.0005) for 3D-based estimate, and R2=0.911 (p=<.0005) for axial-only 2D-based estimate. Conclusion: This knowledge-based method for NTV prediction in intracranial SRS provides the clinician with a decision support tool to appropriately select dose-fractionation prior to treatment planning.

Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: Current challenges and future directions.

Patients with metastatic disease are routinely serially imaged to assess disease burden and response to systemic and local therapies, which places ever-expanding demands on our healthcare resources. Image interpretation following stereotactic body radiotherapy (SBRT) for spine metastases can be challenging; however, appropriate and accurate assessment is critical to ensure patients are managed correctly and resources are optimised. Here, we take a critical review of the merits and pitfalls of various imaging modalities, current response assessment guidelines, and explore novel imaging approaches and the potential for radiomics to add value in imaging assessment.

Glioblastoma Multiforme in the over 70's: "To treat or not to treat with radiotherapy?"

BACKGROUND: The incidence of Glioblastoma Multiforme (GBM) is increasing among the older population and is associated with poor prognosis. Management guidelines are lacking in this group. The purpose of this study was to analyze survival data and determine predictors of survival in patients aged ≥70 years treated with radiotherapy (RT) and/or Temozolomide. MATERIALS AND METHODS: A retrospective analysis of all GBM patients treated at our institution between January 2011 and January 2017 was carried out. RESULTS: One-hundred and four patients were eligible. Median age was 73.8 years (70-87). Thirty-three patients received radical RT and 71 palliative RT. Overall median survival (MS) was 6 months. The MS was 10.6 months for radical patients and 4.9 months for palliative patients (P < 0.0005). The MS was 6.9 months in patients aged 70-75 years and 5.2 months in those aged 76-80 years (P = 0.004). The debulked group had a statistically significantly longer survival (8.0 months) than the biopsy only group (4.9 months). Biopsy only (hazard ratio [HR] 2.4), ECOG performance status 3 vs 0 (HR 6.4), and increasing age (HR 1.06) were associated with statistically significant shorter survival after adjustment for the effects of concurrent chemo, delay in starting RT, and RT dose. CONCLUSION: The MS for radical patients was favorable and approaching current literature for the under 70 age group. Radical treatment should be considered for good performance patients aged 70-75 years. Increasing age was associated with shorter MS in patients aged ≥76 years. Debulking and good performance status were associated with improved survival.

Metastasis of papillary thyroid carcinoma to the thoracic spine.

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common form of well-differentiated thyroid carcinoma. Despite its well-differentiated microscopic features, PTC may be minimally or overtly invasive. We present the case of a patient in whom thoracic spinal cord compression was the first presentation of metastatic PTC. CASE REPORT: A 65-year-old woman presented with deteriorating mobility over a 2-month period. Her past history was significant for a right hemithyroidectomy 10 years prior. Examination revealed bilateral lower limb weakness, worse on the right side. Investigations showed a large extradural contrast-enhancing mass at the T7 spinal level. Laminectomy and debulking of this lesion was undertaken. Histopathological examination revealed PTC. The patient proceeded to further treatment with external beam radiotherapy. DISCUSSION: Spinal metastases are an unusual presentation of PTC. Further research into the outcomes for these patients is imperative to bettering our ability to care for these patients through a multi-modality approach.
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