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Introduction: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe., Methods: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy., Results: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality., Conclusion: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy., Objective: The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up., Design, Setting, and Participants: Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III "boost no boost" trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years., Interventions: No further treatment or 16-Gy boost, after BCS and 50-Gy WBI., Main Outcomes and Measures: Time to ipsilateral breast tumor recurrence (IBTR) as first event., Results: The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P < .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P < .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high-risk patients (≤50 years with DCIS present)., Conclusions and Relevance: The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately., Trial Registration: clinicaltrials.gov Identifier: NCT02295033.

Background: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results., Methods: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033., Findings: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001)., Interpretation: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years., Funding: Fonds Cancer, Belgium., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Advances in the field of radiation oncology in the last decade resulted in an increasing number of opportunities to optimize therapy. Increased accuracy to deliver the dose to tumors while sparing normal tissues demands more precise delineation of the tumors. When considering to deliver a boost to more aggressive parts of tumors, intratumoral heterogeneity needs to be assessed accurately. Adaptive radiotherapy demands evaluation of response during the course of radiotherapy, in terms of both volumetric and functional changes. Molecular imaging with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has found its way into clinical practice for various indications in head and neck cancer and new applications are under investigation. In this review, an overview is provided of the current status and developments of the use of FDG-PET/CT in radiation oncology, describing the current status in radiation treatment planning, adaptation of therapy and the position compared to other imaging techniques.

Aim: Integration of positron emission tomography (PET) information into computer tomography (CT)- based intensity modulated external beam radiation therapy (IMRT) allows adaptation of the target volume to functional parameters, but only when the image registration procedure is reliable. The aim of this study was to select the optimal method for software fusion of dedicated PET and CT, and to validate the procedure for IMRT head-neck area., Method: Fifteen patients with head and neck squamous cell carcinoma underwent separate CT and F-18-fluorodeoxyglucose positron emission tomography(FDG-PET), both in a custom-moulded rigid mask fitted with 4 multimodality fiducial markers. Five image registration methods were applied . PET emission and CT were registered manually (ME) and using the landmarks (LM). PET transmission and CT were registered manually (MT) using a mutual information-based method (MI) and an iterative closest point method (ICP). The error in image registration of each method was determined by evaluating the markers., Results: LM showed an average registration error of 1.4 mm at the location of the markers, and 0.3mm in the planning area. However, this method proved to be laborious. Apart from LM, the best method was ICP, with registration errors of 3 and 2mm, respectively. The respective errors were 4.7 and 3.5 mm with ME, 3.6 and 2.7 mm with MT, and 5.3 and 4.1mm with MI., Conclusion: Image fusion of dedicated PET and CT of the head-neck area can be performed reliably using the operator-independent ICP method with no need for laborious markers. The achieved accuracy permits implementation of dedicated PET images in external beam radiation therapy.

In two women, aged 86 and 56 years, respectively, who suffered from back pain and loss of strength, and in a 55-year-old man who lost sensation and strength in his left leg, spinal-cord compression in connection with vertebral destruction was seen on radiological examination. When spinal-cord compression is the result of a local malignant tumour, the therapy often entails emergency radiotherapy. In the first two patients, histological examination revealed a solitary plasmocytoma and curative high-dose radiotherapy was applied. The third patient also had a lung tumour and received low-dose palliative radiotherapy to the vertebrae, as a metastasis was suspected. Later, however, histopathologic examination of the vertebral lesion revealed osteomyelitis due to Listeria monocytogenes and the lung tumour was diagnosed as a pT2N0M0 broncho-alveolar carcinoma which was surgically removed. When a patient is referred with a nontraumatic spinal-cord injury, it is important to complete the radiological and histological examinations before starting emergency radiotherapy in order to prevent an inadequate or even incorrect treatment.