•Application of consensus guidelines results in increased consistency in high-dose CTV1.•A 3-year local control is not influenced by GTV-CTV1 margin.•Half of analysable radiology-verified local ...recurrences are in primary GTV.•76 % of radiology-verified local recurrences are inside CTV1 using 5 mm margin consensus.
Treatment planning using a five-millimetre geometrical margin from GTV to high-dose CTV (CTV1) has been used in DAHANCA treatment centres since 2013. We aimed to evaluate changes in CTV1 volumes, local control (LC), and recurrence pattern after the implementation of five-millimetre geometrical margins nationally.
1,948 patients with pharyngeal, and laryngeal squamous cell carcinomas completed definitive IMRT-based treatment in 2010–2012 and 2013–2015 in three centres. The patient-specific margin was calculated as median surface distance from primary tumour GTV (GTV-T) to CTV1. Radiologically verified local recurrences were analysed using a centre of mass (COM) of the delineated recurrence volume, measuring the shortest distance between COM to GTV-T and CTV1 boundaries.
Median GTV-CTV1 was 0.9 (0.0–0.97) and 0.47 cm (0.4–0.5) for 2010–2012 and 2013–2015, respectively. Median CTV1 changed in three centres from 76, 28, 42 cm3 to 61, 53, 62 cm3 for 2010–2012 and 2013–2015, respectively. Local failures occurred at 247 patients during first three years after radiotherapy. The 3-year LC rate for 2010–2012 and 2013–2015 was 0.84 and 0.87 (p = 0.06).
Out of 146 radiology-verified analysable local recurrences, 102 (69.9%) were inside the CTV1. In 74.6% and 91% of cases, the LRs were covered by 95% isodose in 2010–2012 and 2013–2015, respectively.
DAHANCA radiotherapy guidelines based on a geometrically generated isotropic CTV1 margin led to less variation in treatment volumes and between centres than previous guidelines. The transition towards consensus GTV-CTV1 margins did not influence local tumour control. The majority of local recurrences were inside CTV1 and covered by the prescription dose.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Head and neck cancer patients at risk of distant metastases (DM) are difficult to identify.•We investigated the influence of initial tumor volume (cm3) on the risk of DM.•Gross tumor volumes (GTV) ...were extracted from treatment planning systems.•We found that GTV is an independent factor strongly associated with the risk of DM.•This may improve the selection of patients for intervention trials.
Distant metastases (DM) in head and neck squamous cell carcinomas (HNSCC) are in most circumstances non-curable. The TNM staging system is insufficient to predict the risk of DM. This study investigates if the DM risk can be predicted using a multivariate model including pre-treatment total tumor volume for both p16-positive oropharyngeal squamous cell carcinoma (OPSCC) and all other sites (other HNSCC).
The study includes patients with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017 from three head and neck cancer centers. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database. Total (nodal and primary) tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems. The GTV was grouped by volume (cm3) in four intervals and included in a multivariate Cox proportional hazard regression controlled for pre-selected clinical values incl. stage.
The study includes 2,865 patients, of which 321 (11 %) had DM post-treatment. The risk of DM was assessed in a multivariate model based on 2,751 patients (p16-positive OPSCC: 1,032; and other HNSCC: 1,719). There was a significant association between GTV and the risk of DM, and in tumor volumes ≥ 50 cm3 hazard ratios of 7.6 (2.5–23.4) for p16-positive OPSCC and 4.1 (2.3–7.2) in other HNSCC were observed.
Tumor volume is an independent risk factor for DM. The addition of total tumor volume to a predictive model is important to identify subgroups of HNSCC patients at high risk of DM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme.•Mentor-mentee couples were formed after online or onsite speed dating.•The programme was ...evaluated after one year and was scored a 9 out of 10 by both mentors and mentees.•All of the mentors indicated that they wanted to participate again as mentors.•Building upon the initial pilot's success, the mentoring programme's has become a yearly programme.
The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme. At evaluation after one year, both mentors and mentees scored the programme with a median score of 9 on a scale of 10. All of the mentors indicated that they wanted to participate again as mentors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•The majority (80 %) of loco-regional failures in HNSCC arise within high-dose volume.•Treatment failure in HNSCC is in most cases due to tumor radioresistance.•Most failure sites in both ...p16-positive and negative SCC were high-dose failures.
Patients with failure after primary radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. This study investigates pattern of failure after primary curatively intended IMRT in a randomized controlled trial in relation to HPV/p16 status.
Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Of 608 patients, 151 had loco-regional failure within five years, from whom 130 pairs of scans (planning-CT and diagnostic failure scan) were collected and deformably co-registered. Point of origin-based pattern of failure analysis was conducted, including distance to CTV1 and GTV, and estimated dose coverage of the point of origin.
Of 130 patients with pairs of scans, 104 (80 %) had at least one local or regional failure site covered by 95 % of prescribed dose and 87 (67 %) of the failures had point of origin within the high-dose CTV (CTV1). Of failures from primary p16 + OPSCC, the majority of both mucosal (84 %) and nodal (61 %) failures were covered by curative doses. For p16− tumors (oral cavity, OPSCC p16neg, hypopharynx and larynx), 75 % of mucosal and 66 % of nodal failures were high-dose failures.
Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Head and neck magnetic resonance imaging and computed tomography co-registration.•Validation of planning and recurrence scan co-registration separated in time.•Mean distances to agreement for ...regions of interest/normal tissue were tolerable.
MRI (magnetic resonance imaging) scans are frequently used in follow-up after radiotherapy for head and neck cancer. With the overall aim of enabling MRI-based pattern of failure analysis, this study evaluated the accuracy of recurrence MRI (rMRI) deformable co-registration with planning CT (computed tomography)-scans (pCT). Uncertainty of anatomical changes between pCT and rMRI was assessed by similarity metric analyses of co-registered image structures from 19 patients. Average mean distance to agreement and Dice similarity coefficient performed adequately. Our findings provide proof of concept for reliable co-registration of pCT and rMRI months to years apart for MRI-based pattern of failure analysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
INTRODUCTIONThe prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in ...HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19.MATERIALS AND METHODSWe included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel.RESULTSHPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected.Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7).CONCLUSIONIn the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•Tumor volume, SLC3A2 and CD44 are prognostic for high-dose failure in HNSCC.•SLC3A2 is a biomarker for high-dose failure in (C-)RT for p16 + oropharyngeal SCC.•Tumor volume is the main driver for ...high-dose failure in p16- HNSCC.•Tumor hypoxia was not prognostic in patients treated with concomitant nimorazole.
Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint.
Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx).
Higher risk of HDF was seen for patients with larger primary and nodal volume (>25 cm3, Hazard Ratio (HR): 3.00 95 % CI: 1.73–5.18), high SLC3A2 (HR: 2.99 1.28–6.99), CD44 (>30 % positive, HR: 2.29 1.05–5.00), and p16- tumors (HR: 2.53 1.05–6.11). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 1.79–6.04) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 1.58–24.23) for p16 + OPSCC (n = 162).
Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Variations in symptom development among breast cancer (BC) survivors are understudied. We examined: (Q1) Symptom trajectories of pain, fatigue, insomnia, breast, and arm symptoms in BC survivors, ...(Q2) possible patterns or cluster-like associations between trajectory classification of different symptoms, and (Q3) characteristics of survivors assigned to high-burden symptom trajectories.
Participants were 968 women (mean age = 59.6 years) treated for early-stage BC and followed across a three-year postoperative period. As part of routine follow-up procedures, patients reported symptom burden and functioning levels at each hospital visit using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the BC-specific module (QLQ-BR-23). Growth mixture modeling (GMM) analysis was used to differentiate potential subgroups of individuals with similar longitudinal symptom patterns, i.e., symptom trajectories (Q1). With this approach, groups experiencing persistent, highly distressing cancer- and treatment-related late effects (LEs) may be identified. Latent class analysis (LCA) was used for Q2 and logistic regression analysis for Q3.
GMM identified two relatively parallel trajectories across the tested symptoms: The majority of the sample exhibited a low-burden symptom trajectory (74.4-89.2%) and a minority by a high-burden symptom trajectory (10.8-25.6%). LCA revealed that approximately one in five women (18.8%) were likely to be members of the high-burden symptom trajectory across all tested symptoms. In addition to a high probability of being burdened over time across multiple symptoms, these women were also characterized by poorer self-reported physical and social functioning.
A substantial minority followed a high-burden symptom trajectory for several years following BC treatment. Associations were found in trajectory classification across symptoms, indicating that cancer-related LEs appear in clusters of multiple concurrent symptoms.
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Survival rates for breast cancer (BC) are increasing, leading to growing interest in treatment-related late-effects. The aim of the present study was to explore late effects using Patient-Reported ...Outcome Measures in postmenopausal BC survivors in standard follow-up care. The results were compared to age- and gender-matched data from the general Danish population.
Postmenopausal BC survivors in routine follow-up care between April 2016 and February 2018 at the Department of Oncology, Aarhus University Hospital, Denmark were asked to complete the EORTC QLQ-C30 and BR23 questionnaires together with three items on neuropathy, myalgia, and arthralgia from the PRO-CTCAE. Patients were at different time intervals from primary treatment, enabling a cross-sectional study of reported late effects at different time points after primary treatment. The time intervals used in the analysis were year ≤1, 1-2, 2-3, 3-4, 4-5 and 5+. The QLQ-C30 results were compared with reference data from the general Danish female population. Between-group differences are presented as effect sizes (ESs) (Cohen's d).
A total of 1089 BC survivors participated. Compared with the reference group, BC survivors reported better global health status 2-3 and 4-5 years after surgery (d = 0.26) and physical functioning 2-3 years after (0.21). Poorer outcomes in BC survivors compared with the reference group were found for cognitive functioning (0-4 and 5+ years), fatigue (0-2 years), insomnia (1-3 years), emotional functioning (3-4 years), and social functioning (≤1 year after surgery) with ESs ranging from 0.20 to 0.41. For the remaining outcomes, no ESs exceeded 0.20.
Only small to medium ESs were found for better global health and physical functioning and poorer outcomes for cognitive functioning, fatigue, insomnia, emotional functioning, and social functioning in postmenopausal BC survivors, who otherwise reported similar overall health-related quality of life compared with the general Danish female population.
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