Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

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)

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

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.

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.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

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.

Deep inspiration breath hold versus free breathing technique in mediastinal radiotherapy for lymphoma.

OBJECTIVE: Radiotherapy plays an important role in the management of lymphoma and many patients with lymphoma are cured with treatment. Risk of secondary malignancy and long-term cardiac and pulmonary toxicity from mediastinal radiotherapy exists. Delivery of radiotherapy using a deep inspiration breath-hold (DIBH) technique increases lung volume and has the potential to reduce dose to heart and lungs. We undertook a prospective study to assess the dosimetric differences in DIBH and free breathing (FB) plans in patients requiring mediastinal radiotherapy in clinical practice. METHODS: We performed both FB and DIBH planning scans on 35 consecutive patients with mediastinal lymphoma needing radiotherapy. Contours and plans were generated for both data sets and dosimetric data were compared. All patients were planned using volumetric modulated arc therapy (VMAT). Data were compared for FB and DIBH plans with each patient acting as their own control using the related-samples Wilcoxon signed rank test. RESULTS: DIBH significantly reduced lung doses (mean 10.6 vs 11.4Gy, p < 0.0005; V20 16.8 vs 18.3%, p = 0.001) and spinal cord maximum dose (20.6 vs 22.8Gy, p = 0.001). DIBH increased breast V4 (38.5% vs 31.8%, p = 0.006) and mean right breast dose (4.2 vs 3.6Gy, p = 0.010). There was no significant difference in heart doses when the entire study cohort was considered, however, mean heart dose tended to be lower with DIBH for upper mediastinal (UM) tumours (4.3 vs 4.9Gy, p = 0.05). CONCLUSION: Our study describes the potential benefit of DIBH in a population reflective of clinical practice. DIBH can decrease radiation dose to lungs, heart and spinal cord, however, may increase dose to breasts. DIBH is not always superior to FB, and the clinical significance of differences in dose to organs at risk in addition to the time required to treat patients with DIBH must be considered when deciding the most appropriate radiotherapy technique for each patient. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest study comparing DIBH and FB planning for patients with lymphoma receiving mediastinal radiotherapy in clinical practice. It demonstrates the impact of an increasingly common radiotherapy technique on dose to organs at risk and the subsequent potential for long-term radiotherapy side-effects.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome. METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms. RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093). CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

Modifiable risk factors for acute skin toxicity in adjuvant breast radiotherapy: Dosimetric analysis and review of the literature.

Acute skin toxicity in adjuvant breast radiation can be reduced with modern radiotherapy (RT) techniques. However, having reviewed the literature, we found no dosimetric constraint for acute skin toxicity that would be applicable to modern RT planning. This study aimed to identify dosimetric factors that are associated with higher rates of acute skin toxicity. A retrospective review was carried out including women who received adjuvant forward-planned intensity-modulated radiotherapy (IMRT) after breast-conserving surgery. Acute skin toxicity grade was prospectively recorded. A total of 131 patients were analyzed. On multivariate analysis, the V105% > 30 cc (p = 0.013) and the use of conventional fractionation (CF) (p = 0.001) were statistically significant for acute skin toxicity. On literature review, current quantitative dosimetric parameters that have shown statistical significance include a V107% > 3 cc in hypofractionation (HF), V107% > 9 cc in CF, treated volume 110% > 5.13%, and V107% > 28.6%. There is little evidence on the predictive value of clinically applicable dosimetric factors in acute skin toxicity. Given the recent improvements in RT planning, we would consider a V107% or a V110% too high a dosimetric value to be useful for the majority of patients. We have shown that a V105% of greater than 30 cc is significantly associated with acute skin toxicity, controlling for other variables. We suggest that this is currently the most useful modifiable parameter available to reduce skin toxicity and is applicable to modern RT planning. We also suggest that consideration be given to hypofractionated schedules to further reduce acute skin toxicity.

An atlas to aid delineation of para-aortic lymph node region in cervical cancer: Design and validation of contouring guidelines.

INTRODUCTION: Previous studies have investigated the anatomical distribution of para-aortic lymph nodes (PAN) in patients with cervical cancer. However, an atlas for accurate clinical target volume (CTV) delineation has yet to be defined. The purpose of this study was to design and verify a computerized tomography (CT) atlas to provide guidance for contouring the PAN CTV in patients with cervical cancer. MATERIALS AND METHODS: This prospective study included 21 cervical cancer patients (design cohort) with 39 pathological PAN identified on (18)F-FDG PET-CT. PAN [left lateral para-aortic (LLPA), aorto-caval (AC), right para-caval (RPC) nodes] were delineated on CT simulation scans. Measurements were taken from the volumetric centre of the nodes to the edge of aorta and inferior vena-cava (IVC). Initially the aorta and IVC were expanded by the mean distance to the lymph node centre to create a CTV. Expansion margins were then increased asymmetrically until the CTV resulted in a clinically acceptable number of PAN included. The CTV was validated on a further 10 patients (validation cohort) with 29 PAN. A detailed contouring guide and accompanying visual atlas for elective PAN CTV delineation was created based on the validated margins. RESULTS: For the design cohort (n = 21 patients, 39 PAN), the mean distance from the centre of the node to the aorta was 8 mm (range 4-17) for both LLPA (range 4-17) and AC (range 4-15) regions. Mean distance from the IVC to the centre of the nodes was 5 mm (range 4-6) in the RPC region and 6 mm (range 3-15) in the AC region. No PAN was superior to the T12-L1 interspace or the left renal vein or inferior to the L5-S1 interspace. For validation cohort (n = 10 patients, 29 PAN), mean distance from centre of the node to the aorta was 9 mm (range 5-15) in the LLPA region, 7 mm (range 6.5-14) in the AC region. Mean distance from the ICV to the centre of the nodes was 3 mm (range 2.5-4) in the RPC region and 5 mm (range 3-10) in the AC region. A CTV expansion from the aorta of 10 mm circumferentially and 15 mm laterally, and from the IVC of 8 mm anteromedially and 6 mm posterolaterally resulted in coverage of 97% (38/39) of PAN in the design cohort. On prospective validation, the described CTV included 97% (28/29) of PAN in the validation cohort. CONCLUSION: We propose the following PAN CTV; expansion from aorta of 10 mm circumferentially except 15 mm laterally, expansion from the IVC of 8 mm anteromedial and 6 mm posterolaterally. The suggested CTV includes 97% (28/29) PAN in a validated patient cohort. A detailed guide and accompanying visual atlas is provided to aid delineation of the PAN CTV in patients with cervical cancer.

A cardiac contouring atlas for radiotherapy.

BACKGROUND AND PURPOSE: The heart is a complex anatomical organ and contouring the cardiac substructures is challenging. This study presents a reproducible method for contouring left ventricular and coronary arterial segments on radiotherapy CT-planning scans. MATERIAL AND METHODS: Segments were defined from cardiology models and agreed by two cardiologists. Reference atlas contours were delineated and written guidelines prepared. Six radiation oncologists tested the atlas. Spatial variation was assessed using the DICE similarity coefficient (DSC) and the directed Hausdorff average distance (d→H,avg). The effect of spatial variation on doses was assessed using six different breast cancer regimens. RESULTS: The atlas enabled contouring of 15 cardiac segments. Inter-observer contour overlap (mean DSC) was 0.60-0.73 for five left ventricular segments and 0.10-0.53 for ten coronary arterial segments. Inter-observer contour separation (mean d→H,avg) was 1.5-2.2mm for left ventricular segments and 1.3-5.1mm for coronary artery segments. This spatial variation resulted in <1Gy dose variation for most regimens and segments, but 1.2-21.8Gy variation for segments close to a field edge. CONCLUSIONS: This cardiac atlas enables reproducible contouring of segments of the left ventricle and main coronary arteries to facilitate future studies relating cardiac radiation doses to clinical outcomes.

Assessment of older patients with cancer: Edmonton Frail Scale (EFS) as a predictor of adverse outcomes in older patients undergoing radiotherapy.

OBJECTIVE: In this study we evaluate the usefulness of the Edmonton Frail Scale (EFS) in predicting which older patients are at risk of developing serious toxicities during radiotherapy. MATERIALS AND METHODS: This prospective study was carried out over an 18month period. Our primary aim was to examine the Edmonton Frail Scale (EFS) as a predictor of toxicity in patients over 70years undergoing radical radiotherapy for any malignant diagnosis. RESULTS: 63 patients were recruited: 29% experienced grade 3 or greater toxicities, with very few having multiple grade 3 or greater toxicities. The majority of patients experienced multiple grade 1 or 2 toxicities. Patients were often admitted: either electively due to geographical reasons, or due to toxicities. All patients completed their courses of radiotherapy. All grade 3 or 4 toxicities occurred within five radiotherapy sites; upper GI, gynaecological, lung, prostate and head & neck. There was no statistical correlation between EFS score and the presence of grade 3 or 4 toxicities. CONCLUSION: This study showed that neither EFS score, age nor ECOG performance status were predictive of radiotherapy toxicity, breaks in treatment or hospital admissions. Patients with oesophageal cancer, gynaecological cancers and lung cancer had a high rate of toxicity and hospital admission, which may highlight the need for additional patient support in these groups. Whilst comprehensive geriatric assessment is recommended, further research is needed to conclude if the frail elderly patient is at greater risk of toxicities from radiotherapy, and which geriatric assessment tool may be the most helpful.

Variation in treatment and outcome in the early stage oral cavity squamous cell carcinoma.

This study aims to determine the survival impact of patient characteristics and treatment options associated with the early stage oral cavity squamous cell carcinoma, OCSCC. The methods are analysis of Irish cancer database examining T1/2, N0, and M0 cases of OCSCC from 1997 to 2007 inclusive. In total, 397 cases were identified. Anterolateral tongue accounted for 52.9 % of cases. Increased age at diagnosis and smoking are independent prognostic survival indicators associated with poorer outcomes. Surgery as the initial intervention was associated with significantly better survival outcomes, while surgery and adjuvant radiotherapy significantly worse outcomes. Surgical intervention is recommended as the first-line treatment in the early stage OCSCC in combination with elective neck dissection.

Review of high-risk features of cutaneous squamous cell carcinoma and discrepancies between the American Joint Committee on Cancer and NCCN Clinical Practice Guidelines In Oncology.

Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network® (NCCN® ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017.

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study.

PURPOSE: Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort. PATIENTS AND METHODS: From twelve centres 731 patients, treated with definitive EBRT±concurrent chemotherapy followed by IGBT, were analysed. Kaplan-Meier estimates at 3/5years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3-4 late toxicity (CTCAEv3.0) was reported. RESULTS: Median follow up was 43months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA-IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46±2.5Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87±15Gy (EQD210), mean D2cc was: bladder 81±22Gy, rectum 64±9Gy, sigmoid 66±10Gy and bowel 64±9Gy (all EQD23). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3-G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. CONCLUSION: IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.

Impact of delineation uncertainties on dose to organs at risk in CT-guided intracavitary brachytherapy.

PURPOSE: This study quantifies the inter- and intraobserver variations in contouring the organs at risk (OARs) in CT-guided brachytherapy (BT) for the treatment of cervical carcinoma. The dosimetric consequences are reported in accordance with the current Gynecological Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology guidelines. METHODS AND MATERIALS: A CT planning study of 8 consecutive patients undergoing image-guided BT was conducted. The bladder, rectum, and sigmoid were contoured by five blinded observers on two identical anonymized scans of each patient. This provided 80 data sets for analysis. Dosimetric parameters analyzed were D0.1 cc, D1 cc, and D2 cc. The mean volume of each OAR was calculated. These endpoints were compared between and within the observers. The CT image sets from all patients were evaluated qualitatively. RESULTS: The interobserver coefficient of variation for reported D2 cc was 13.2% for the bladder, 9% for the rectum, and 19.9% for the sigmoid colon. Unlike the variation seen in bladder and rectal contours, which differed largely in localization of the organ walls on individual slices, sigmoid colon contours demonstrated large differences in anatomic interpretation. CONCLUSIONS: Variation in recorded D2 cc to the bladder and rectum is comparable with the previous published results. Inter- and intraphysician variations in reported D2 cc is high for the sigmoid colon, reflecting varying interpretation of sigmoid colon anatomy. Variation in delineation of the OARs may influence treatment optimization and is a potential source of uncertainty in the image-guided BT planning and delivery process.