Validation of a Quality Metric Score to Assess the Placement of Hydrogel Rectal Spacer in Patients Treated With Prostate Stereotactic Radiation Therapy.

Purpose: To evaluate the quality of the interspace between the prostate and rectum and assess the effect on the dose to the rectum by measuring the spacer quality score (SQS) before and after implanting a hydrogel rectal spacer. Methods and Materials: Thirty patients with prostate cancer were treated with stereotactic ablative body radiation therapy as part of the SPORT clinical trial. Each patient had a 10 mL polyethylene glycol hydrogel spacer inserted transperineally. Computed tomography scans were acquired before and after spacer insertion, 10MV flattening filter free (FFF) stereotactic ablative body radiation therapy (SABR) treatment plans were generated using each image set. To calculate the SQS, the prostate-rectal interspace (PRI) was measured in the anterior-posterior orientation, parallel to the anatomic midline at the prostate base, apex, and midgland on the prespacer and postspacer computed tomography. Measurements were taken in 3 transverse positions between the prostate and the rectum, and PRI scores of 0, 1, and 2 were assigned if the interspace between prostate and rectum was <0.3, 0.3 to 0.9, or ≥1 cm, respectively. The overall SQS was the lowest of the PRI scores. Differences between prespacer and postspacer PRIs and SQS were investigated by performing Fisher's exact test and differences between doses to the rectum were investigated by performing the paired samples Wilcoxon rank-sum test and Student t test. Results: Statistically significant differences between prespacer versus postspacer patients were found when grouping patients according to their overall SQS. The PRI summary score did not reach statistical significance between prespacer and postspacer at the base but was significantly higher for the prostate midline and apex. Statistically significant differences in some rectum dose-volume metrics were found when grouping patients according to their PRIs and SQS. Conclusions: SQS before and after the spacer insertion was evaluated and was found to be correlated with pre- and postspacer rectal dosimetry. Sources of improvement of the SQS scoring metric and limitations are discussed.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma

Background and purpose To predict treatment-related cardiovascular disease (CVD) and second cancer 30-yea. absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. Material and methods This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016–2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose–response relationships. Results Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4–6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2–23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. Conclusion For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects (AU)

A Randomized Feasibility Trial of Stereotactic Prostate Radiation Therapy With or Without Elective Nodal Irradiation in High-Risk Localized Prostate Cancer (SPORT Trial).

PURPOSE: The aim of this study was to establish the feasibility of a randomized clinical trial comparing SABR with prostate-only (P-SABR) or with prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavorable intermediate- or high-risk localized prostate cancer and to explore potential toxicity biomarkers. METHODS AND MATERIALS: Thirty adult men with at least 1 of the following features were randomized 1:1 to P-SABR or PPN-SABR: clinical magnetic resonance imaging stage T3a N0 M0, Gleason score ≥7 (4+3), and prostate-specific antigen >20 ng/mL. P-SABR patients received 36.25 Gy/5 fractions/29 days, and PPN-SABR patients received 25 Gy/5 fractions to pelvic nodes, with the final cohort receiving a boost to the dominant intraprostatic lesion of 45 to 50 Gy. Phosphorylated gamma-H2AX (γH2AX) foci numbers, citrulline levels, and circulating lymphocyte counts were quantified. Acute toxicity information (Common Terminology Criteria for Adverse Events, version 4.03) was collected weekly at each treatment and at 6 weeks and 3 months. Physician-reported late Radiation Therapy Oncology Group (RTOG) toxicity was recorded from 90 days to 36 months postcompletion of SABR. Patient-reported quality of life (Expanded Prostate Cancer Index Composite and International Prostate Symptom Score) scores were recorded with each toxicity time point. RESULTS: The target recruitment was achieved, and treatment was successfully delivered in all patients. A total of 0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity, respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade ≥2 GI and GU toxicity, respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and hematuria). No other grade ≥3 toxicity was observed. In addition, 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clinically important change in late Expanded Prostate Cancer Index Composite bowel and urinary summary scores, respectively. γH2AX foci numbers at 1 hour after the first fraction were significantly higher in the PPN-SABR arm compared with the P-SABR arm (P = .04). Patients with late grade ≥1 GI toxicity had significantly greater falls in circulating lymphocytes (12 weeks post-radiation therapy, P = .01) and a trend toward higher γH2AX foci numbers (P = .09) than patients with no late toxicity. Patients with late grade ≥1 bowel toxicity and late diarrhea experienced greater falls in citrulline levels (P = .05). CONCLUSIONS: A randomized trial comparing P-SABR with PPN-SABR is feasible with acceptable toxicity. Correlations of γH2AX foci, lymphocyte counts, and citrulline levels with irradiated volume and toxicity suggest potential as predictive biomarkers. This study has informed a multicenter, randomized, phase 3 clinical trial in the United Kingdom.

Maternal and perinatal outcomes following a diagnosis of Hodgkin lymphoma during or prior to pregnancy: A systematic review.

BACKGROUND: The initial peak incidence of Hodgkin lymphoma (HL) occurs during reproductive years. OBJECTIVES: Synthesise published literature on the relationship between HL and maternal and perinatal outcomes. SEARCH STRATEGY: Systematic search of PubMed/Medline, Cochrane Library, Scopus, Embase and Science Direct from inception to June 2022, supplemented by hand-searching reference lists. SELECTION CRITERIA: Two reviewers independently reviewed titles, abstracts and full-text articles. Published studies containing original data were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and appraised study quality. Outcomes for pregnant women with a previous/current diagnosis of HL were compared separately with women never diagnosed with HL. Where data permitted, meta-analyses of odds ratios and proportions were performed. Certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. MAIN RESULTS: Of the 5527 studies identified, 33 met the inclusion criteria. In the groups with HL before pregnancy and HL during pregnancy, adjusted odds ratios were not statistically significant for congenital malformation (aOR 1.7, 95% CI 0.9-3.1, and aOR 1.84, 95% CI 0.81-4.15, respectively), preterm birth (PTB) (aOR 0.99, 95% CI 0.65-1.51, and aOR 6.74, 95% CI 0.52-88.03, respectively) and miscarriage (aOR 0.78, 95% CI 0.55-1.10, and aOR 0.38, 95% CI 0.05-2.72, respectively). The aORs for all other outcomes were not statistically significant, except for blood transfusion (aOR 1.38, 95% CI 1.05-1.82) and venous thromboembolism (VTE) (aOR 7.93, 95% CI 2.97-21.22) in the group for HL during pregnancy. The proportion of anaemia was also increased in this group (69%, 95% CI 57%-80% vs 4%, 95% CI 4%-5%, respectively). The GRADE certainty of findings ranged from low to very low. CONCLUSIONS: Rates of most adverse pregnancy outcomes among women with a previous/current HL diagnosis are not increased significantly compared with the general pregnant population. Women with HL diagnosed during pregnancy may have a higher PTB rate and increased likelihood of VTE, anaemia and blood transfusion; however, small study numbers and the low to very low GRADE certainty of findings preclude firm conclusions.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.

Radiation oncology teaching provision and practice prior to and during the first wave of the COVID-19 pandemic in medical schools in the United Kingdom and the Republic of Ireland: a cross-sectional survey.

OBJECTIVES: Radiotherapy is a key cancer treatment modality but is poorly understood by doctors. We sought to evaluate radiation oncology (RO) teaching in medical schools within the United Kingdom (UK) and Republic of Ireland (RoI), as well as any impacts on RO teaching delivery from the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A bespoke online survey instrument was developed, piloted and distributed to oncology teaching leads at all UK and RoI medical schools. Questions were designed to capture information on the structure, format, content and faculty for RO teaching, as well as both the actual and the predicted short- and long-term impacts of COVID-19. RESULTS: Responses were received from 29/41 (71%) UK and 5/6 (83%) RoI medical schools. Pre-clinical and clinical oncology teaching was delivered over a median of 2 weeks (IQR 1-6), although only 9 (27%) of 34 responding medical schools had a standalone RO module. RO teaching was most commonly delivered in clinics or wards (n = 26 and 25 respectively). Few medical schools provided teaching on the biological basis for radiotherapy (n = 11) or the RO career pathway (n = 8), and few provide teaching delivered by non-medical RO multidisciplinary team members. There was evidence of short- and long-term disruption to RO teaching from COVID-19. CONCLUSIONS: RO teaching in the UK and RoI is limited with minimal coverage of relevant theoretical principles and little exposure to radiotherapy departments and their non-medical team members. The COVID-19 pandemic risks exacerbating trainee doctors' already constrained exposure to radiotherapy. ADVANCES IN KNOWLEDGE: This study provides the first analysis of radiotherapy-related teaching in the UK and RoI, and the first to explore the impact of the COVID-19 pandemic on radiationoncology teaching.

Anaplastic thyroid cancer: outcomes of trimodal therapy.

BACKROUND: The purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent. MATERIALS AND METHODS: Retrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes. RESULTS: Seven patients (4 female) were identified. Median age was 58 years (range 52-83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40-90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66 Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence. CONCLUSIONS: Despite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases.

A rare case of melanotic hyperpigmentation of the tongue secondary to radiotherapy.

Melanotic hyperpigmentation of the mucosa secondary to radiotherapy is a rare occurrence. It is a diagnosis of exclusion. Literature review has identified only two case reports published to date. We present a case of a patient treated at our institution. An 18-year-old male patient of Nigerian descent underwent radical radiotherapy (36 Gy in 18 daily fractions) to his right neck for paediatric type follicular lymphoma over a period of four weeks. He developed hyperpigmented tongue lesions during the third week of radiotherapy. There was no associated tongue discomfort, inflammation, infection, or pigmentation change elsewhere in the oral mucosa. Review of medications and past medical history did not demonstrate any potential contributing factors. Full blood count and biochemistry, morning cortisol levels and coagulation screen were all normal apart from mild neutropenia and lymphopenia. His oral cavity received a mean dose of 16.4 Gy, with the right side of his tongue receiving up to 37.5 Gy as this was within the planning target volume (PTV). He had an excellent response to radiotherapy and remains in remission. The tongue lesions resolved spontaneously 3 months post treatment.

Chemoradiotherapy for anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Anal cancer is a relatively rare cancer, making up approximately 0.4% of all new diagnoses of cancer.(1) The incidence of anal cancer, however, has increased in recent years.(2) The aim of this paper is to review current treatment of anal squamous cell carcinoma (SCC), the most common type of anal cancer. METHODS: This review article focuses on recent and ongoing trials studying the outcomes of various chemoradiotherapy (CRT) regimens in the treatment of anal SCC. PubMed was initially searched for relevant trials. This search was then supplemented by hand searches of reference lists and abstracts of relevant conferences. MAIN FINDINGS: CRT with mitomycin C (MMC) and 5-fluorouracil (5-FU) has been proven to have effective results in the treatment of anal SCC. Salvage surgery has a role in some patients in the treatment of persistent or recurrent disease beyond 26 weeks. The addition of induction or maintenance chemotherapy to CRT has not been shown to have any benefit. CONCLUSIONS: Primary CRT with MMC and 5-FU is the current standard treatment for anal SCC. There is currently no role for induction or maintenance chemotherapy.

The natural history of pregnancies with a diagnosis of trisomy 18 or trisomy 13; a retrospective case series.

BACKGROUND: Trisomy 18 (T18) and trisomy 13 (T13) are the second and third commonest autosomal aneuploidy syndromes respectively. While specific aspects of affected pregnancies have been documented in the literature, few studies document the overall natural history of the trisomies. This study aimed to examine the natural history (including diagnosis, pregnancy outcome, complications and survival) of T18 and T13 pregnancies in a setting where termination of pregnancy for fetal abnormality is not available. METHODS: Cases were identified using birth registers, labour ward records, annual reports, medical records, ultrasound reports and reports from prenatal genetic testing. All identified T18 and T13 pregnancies in the study region from 2001 to 2012 were included. Individual chart reviews were performed for each case. Data were analysed using SPSS Version 20. RESULTS: Forty-six T18 and twenty-four T13 pregnancies were identified. Most T18 cases (65%) were diagnosed prenatally, while only one third (33%) of T13 cases were prenatally diagnosed. Only three T18 pregnancies and one T13 pregnancy were electively terminated. A proportion of undiagnosed infants were delivered by emergency caesarean section. 48% (T18) and 46% (T13) infants survived following birth, for a median of 1.5 days (T18) and 7 days (T13). One T13 infant is currently alive over one year of age. CONCLUSIONS: This large series provides information for professionals and women regarding the natural histories of trisomies 18 and 13. These pregnancies can go undiagnosed antenatally without routine anomaly scanning. While many fetuses die in-utero, postnatal survival is possible.