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.

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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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.

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.

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.

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.

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.

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.

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.

Stereotactic radiosurgery to surgical cavity post resection of brain metastases: Local recurrence and overall survival rates. A single-centre experience.

INTRODUCTION: We reviewed local control (LC) and overall survival (OS) post intracranial SRS to cavity post resection of brain metastases at one institution, and factors affecting LC. METHODS: A retrospective review was conducted of adjuvant SRS at one institution from 2013 to 2016. Patient records, treatment plans and diagnostic images were reviewed. Local failure was MRI defined. Categorical variables were analysed using chi-square and Fisher's exact tests. Continuous variables were analysed using Mann-Whitney tests. The Kaplan-Meier method was used to estimate survival times and the log-rank test was used to compare differences in survival. RESULTS: Forty-seven patients with 48 cavities were treated with SRS post operatively. LC rate was 69%, and the distant intracranial failure rate was 47% for entirety of the follow-up period. The 12-month freedom from local recurrence (FFLR) was 77% (63-91%). Median OS (95% CI) was 22.7 (14.6-30.8) months. Patients with a single metastasis had longer FFLR (30.1 vs 14.4 months; P = 0.014). Median interval from surgery to SRS was 6.3 weeks. Patients with interval >7 weeks had increased local recurrence (LR) (62%) than <7 weeks (37%), P = 0.025. Patients with a margin < 2 mm were more likely to experience LR (48%) than those with margin equal to 2 mm (20%); this approached statistical significance (P = 0.063). The median follow-up for all patients was 15.4 months (2-41). CONCLUSIONS: We determined LC and OS post adjuvant SRS at our institution. Based on the findings of this retrospective review SRS should be given promptly post operatively with a 2 mm PTV margin.

Treatment techniques for 3D conformal radiation to breast and chest wall including the internal mammary chain.

Breast, chest wall, and regional nodal irradiation have been associated with an improved outcome in high-risk breast cancer patients. Complex treatment planning is often utilized to ensure complete coverage of the target volume while minimizing the dose to surrounding normal tissues. The 2 techniques evaluated in this report are the partially wide tangent fields (PWTFs) and the 4-field photon/electron combination (the modified "Kuske Technique"). These 2 techniques were evaluated in 10 consecutive breast cancer patients. All patients had computerized tomographic (CT) scans for 3D planning supine on a breast board. The breast was defined clinically by the physician and confirmed radiographically with radiopaque bebes. The resulting dose-volume histograms (DVHs) of normal and target tissues were then compared. The deep tangent field with blocks resulted in optimal coverage of the target and the upper internal mammary chain (IMC) while sparing of critical and nontarget tissues. The wide tangent technique required less treatment planning and delivery time. We compared the 2 techniques and their resultant DVHs and feasibility in a busy clinic.

Twice-daily high-dose-rate brachytherapy for medically inoperable uterine cancer.

PURPOSE: Medically inoperable patients with uterine cancer pose a therapeutic challenge. We developed a twice-daily schedule of high-dose-rate brachytherapy (HDRB) after a single insertion procedure that required a hospitalization of 3 days. METHODS AND MATERIALS: Favorable patients were offered brachytherapy alone, and all other patients received HDRB after pelvic external beam radiation therapy (EBRT). The prescribed dose was 7Gyx5 fractions and 4-5Gyx4-5 fractions for those treated after EBRT. HDRB was delivered with a b.i.d. schedule (4-6-h interval). RESULTS: Twenty-two patients (21 Stage I, 1 Stage IIB) were deemed medically inoperable. Sixteen patients received EBRT followed by HDRB, and six received HDRB alone. There were no procedural complications or significant acute toxicity. No thromboembolic events occurred within 30 days of the implant. CONCLUSIONS: This technique allows patients to be treated using a single procedure for insertion, with brief hospitalization for twice-daily HDRB.

The curative management of synchronous rectal and prostate cancer.

OBJECTIVE: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. METHODS: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. RESULTS: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. CONCLUSION: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients.

Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults.

CONTEXT: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors. OBJECTIVE: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors. METHOD: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12-150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients. RESULTS: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient. CONCLUSION: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.

Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: results of a prospective study.

BACKGROUND AND PURPOSE: To determine whether treatment prone on a belly-board significantly reduces the volume of small bowel irradiated in women receiving adjuvant radiotherapy for gynecologic cancer, and to prospectively study acute small bowel toxicity using an accepted recording instrument. MATERIAL AND METHODS: Thirty-two gynecologic patients underwent simulation with CT scanning supine and prone. Small bowel was delineated on every CT slice, and treatment was prone on the belly-board using 3-5 fields-typically Anterior, Right and Left Lateral, plus or minus Lateral Boosts. Median prescribed dose was 50.4 Gy and all treatments were delivered in 1.8 Gy fractions. Concomitant Cisplatin was administered in 13 patients with cervical carcinoma. Comparison of small bowel dose-volumes was made between supine and prone, with each subject acting as their own matched pair. Acute small bowel toxicity was prospectively measured using the Common Toxicity Criteria: Version 2.0. RESULTS: Treatment prone on the belly-board significantly reduced the volume of small bowel receiving > or = 100; > or = 95; > or = 90; and > or = 80% of the prescribed dose, but not > or = 50%. This was found whether volume was defined in cubic centimeters or % of total small bowel volume. Of 29 evaluable subjects, 2 (7%) experienced 1 episode each of grade 3 diarrhoea. All other toxicity events were grade 2 or less and comprised diarrhoea (59%), abdominal pain or cramping (48%), nausea (38%), anorexia (17%), vomiting (10%). There were no Grade 4 events and no treatment days were lost due to toxicity. CONCLUSIONS: Treatment prone on a belly-board device results in significant small bowel sparing, during adjuvant radiotherapy for gynecologic cancer. The absence of Grade 4 events or Treatment Days Lost compares favorably with the published literature.

A single institutional experience with definitive radiotherapy for cervical cancer using both high- and low-dose-rate brachytherapy.

OBJECTIVE: To evaluate outcomes in cervical cancer patients treated with high-dose-rate (HDRB) or low-dose-rate (LDRB) brachytherapy. METHODS: A retrospective chart review compared control rates, survival, and complications in the two groups. RESULTS: All patients received pelvic EBRT (45 Gy/5 weeks). 106 patients receiving LDRB were compared to 107 treated with HDRB. The median point A LDRB and HDRB dose was 42 Gy and 25 Gy/5, respectively. Tumor size and stage (I(B) 23% LDRB, 30% HDRB, II(A) 22% LDRB, 11% HDRB, II(B) 44% LDRB, 48% HDRB, III(B) 11% LDRB and HDRB) were similar, but more HDRB patients received chemosensitization (44% versus 6%). After adjusting for lymph node status with cox regression, no difference in 5-year survival (53% HDRB and 61% LDRB P = 0.088) or 5-year DFS (54% both groups, P = 0.089) was found between the two groups. Local recurrences occurred in 19% of the LDRB and 5% of the HDRB cohort. The time to LR was significantly longer in the HDRB group, and this persisted after adjusting for the increased used of chemotherapy in these patients. There was no significant difference in grade III or IV toxicity (6.6% LDRB and 3.7% HDRB). CONCLUSIONS: This HDRB dose fractionation schedule yielded improved local control but similar survival compared to LDRB.

Preoperative chemoradiation for locally advanced carcinoma of the vulva.

OBJECTIVE: A twice daily (BID) radiation treatment schedule (interval of 4-6 h) delivered concurrent with chemotherapy for advanced or critically located carcinoma of the vulva was modeled on the schema developed by the Gynecology Oncology Group (GOG). Inguinal nodes were included in the treatment fields even if clinically negative. This review analyzed the outcomes using this approach. METHODS: A retrospective review was conducted of the records of 18 patients with vulvar cancer. Patients were treated with a modified GOG schema using 5-fluorouracil (5FU) and cisplatin with BID radiation treatments during the first and last weeks of treatment and seven daily radiation treatments in between. The regional nodes and primary tumor were prescribed 44.6 Gy. Resection of the primary tumor bed and inguinal dissection was planned at 4-6 weeks post-treatment. Clinical and pathological responses as well as locoregional control and toxicity were assessed. RESULTS: All patients responded. There were 13/18 complete clinical responses (cCR), of whom 12 remained NED at 25 months. Of the five partial clinical response (cPR) patients, two have suffered local recurrences, despite surgical resection in one and electron boost in the other. All patients developed a desquamative perineal skin reaction necessitating a mean treatment break of 15 days. No severe hematological toxicity was encountered, and only one patient had grade 3 small bowel toxicity. One patient required surgical debridement for groin wound breakdown. CONCLUSION: The use of BID chemoradiation resulted in complete or partial responses in all cases. Post-treatment groin dissection can be performed without significant post-operative complications.