Characteristics and dosimetric impact of intrafraction motion during peripheral lung cancer stereotactic radiotherapy: is a second midpoint cone beam computed tomography of added value?

Background: In our department, during lung stereotactic body radiation therapy (SBRT), all patients receive an intra-fractional midpoint cone beam computed tomography (CBCT). This study aimed to quantify the benefit of adding a second midpoint CBCT over a course of peripheral lung SBRT. Materials and methods: Six-hundred-sixty-four CBCTs from 166 patients were retrospectively analyzed. Treatments were based on the internal target volume (ITV) approach. An isotropic 0.5 cm margin was used to create the planning target volume (PTV) around the ITV. The prescribed dose was 48 Gy in 4 fractions to the PTV. Patients were divided into two groups: patients for whom the 3D-intra-fractional-variation (IFV) was < 0.5 cm (105 patients, low risk group) and patients with at least one 3D-IFV ≥ 0.5 cm (61 patients, high-risk group). Plans simulating the dosimetric impact of the IFV were created as follows: the original 2 arcs (ARC ) were copied into a new plan consisting of 4 times ARC 1 and 4 times ARC 2. The delivery of ARC 1 was always assumed to have occurred with the isocenter initially coordinated, whereas the positions of ARC 2 were modified for each arc by the measured the 3D-IFV. Results: For the PTV, we obtained: D99% (Gy) = 45.2 vs. 48.2 Gy (p < 0.0001); Dmean = 53 vs. 54 Gy (p < .0001) for the reconstructed vs. planned dose values, respectively. For the ITV, the changes are less pronounced: D99% (Gy) = 52.2 vs. 53.6 Gy (p = 0.0007); Dmean = 56 vs. 56.8 Gy (p = 0.0144). The V48 Gy(%)-ITV coverage did not statistically change between the delivered vs. planned dose (p = 0.1803). Regarding the organs at risk for both groups, dose-volume-histograms were near-identical. Conclusion: We demonstrated that a single CBCT is sufficient and reliable to manage the IFV during peripheral lung SBRT.

Long term outcome after 48 Gy stereotactic ablative body radiotherapy for peripheral stage I non-small cell lung cancer.

BACKGROUND: To evaluate the outcome of patients treated with stereotactic ablative body radiotherapy (SABR) with curative intent for stage I non-small cell lung cancer (NSCLC) with regard to local, regional and distant tumor control, disease-free survival (DFS), overall survival (OS) and toxicity. METHODS: Data of 300 patients treated with SABR for NSCLC cancer for the period of November 2007 to June 2016 were retrospectively analyzed. Of which, 189 patients had single primary lung lesion and were included in the study. The prescribed dose for the tumor was 48 Gy, given in 12 Gy × 4 fractions for all patients. In 2010, an improved protocol was established in advanced technology for the planning CT, dose calculation and imaging. Cumulative incidence function (CIF) of local, regional, distant or any recurrences were computed using competing risk analysis with death as a competing event. Survivals (DFS and OS) were estimated using the Kaplan-Meier method and Cox proportional regression was used for comparisons. Toxicities were graded according to the common terminology criteria for adverse events version 4.0 (CTCAE v.4). RESULTS: Diagnosis was histologically confirmed in 42% of the patients (N = 80). At 1, 2 and 4 years, the cumulative incidence function (CIF) of local relapses were 8% [4-13%], 15% [10-21%] and 18% [12-25%], the CIF of regional relapses were 4% [2-8%], 10% [6-16%] and 12% [8-19%], the CIF of distant relapses were 9% [5-14%], 15% [11-22%] and 20% [15-28%] and the CIF of any relapses were 14% [10-20%], 28% [22-36%], 34% [27-43%], respectively. After 1, 2 and 4 years, the OS rates were 83% [95% CI: 78-89%] (N = 128), 65% [95% CI: 57-73%] (N = 78) and 37% [95% CI: 29-47%] (N = 53), respectively. The median survival time was 37 months. The DFS after 1, 2 and 4 years reached 75% [95% CI: 68-81%] (N = 114), 49% [95% CI: 42-58%] (N = 60) and 31% [95% CI: 24-41%] (N = 41), respectively. No grade 4 or 5 toxicity was observed. CONCLUSIONS: We observed a long-term local control and survival after SABR for peripheral stage I NSCLC in this large series of patients with the expected low toxicity.

An individualized radiation dose escalation trial in non-small cell lung cancer based on FDG-PET imaging.

AIM: The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity. PATIENTS AND METHODS: A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTVPET) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method. RESULTS: The average dose to PTVPET reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis. CONCLUSION: These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.

Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial.

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.

Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy.

BACKGROUND: After breast-conserving radiation therapy most patients experience acute skin toxicity to some degree. This may impair patients' quality of life, cause pain and discomfort. In this study, we investigated treatment and patient-related factors, including genetic polymorphisms, that can modify the risk for severe radiation-induced skin toxicity in breast cancer patients. METHODS: We studied 377 patients treated at Ghent University Hospital and at ST.-Elisabeth Clinic and Maternity in Namur, with adjuvant intensity modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer. Women were treated in a prone or supine position with normofractionated (25 × 2 Gy) or hypofractionated (15 × 2.67 Gy) IMRT alone or in combination with other adjuvant therapies. Patient- and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system. Desquamation was scored separately on a 3-point scale (0-none, 1-dry, 2-moist). RESULTS: Two-hundred and twenty patients (58%) developed G2+ dermatitis whereas moist desquamation occurred in 56 patients (15%). Normofractionation (both p < 0.001), high body mass index (BMI) (p = 0.003 and p < 0.001), bra cup size ≥ D (p = 0.001 and p = 0.043) and concurrent hormone therapy (p = 0.001 and p = 0.037) were significantly associated with occurrence of acute dermatitis and moist desquamation, respectively. Additional factors associated with an increased risk of acute dermatitis were the genetic variation in MLH1 rs1800734 (p=0.008), smoking during RT (p = 0.010) and supine IMRT (p = 0.004). Patients receiving trastuzumab showed decreased risk of acute dermatitis (p < 0.001). CONCLUSIONS: The normofractionation schedule, supine IMRT, concomitant hormone treatment and patient related factors (high BMI, large breast, smoking during treatment and the genetic variation in MLH1 rs1800734) were associated with increased acute skin toxicity in patients receiving radiation therapy after breast-conserving surgery. Trastuzumab seemed to be protective.

Coverage with evidence development program on stereotactic body radiotherapy in Belgium (2013-2019): a nationwide registry-based prospective study.

Background: Although stereotactic body radiotherapy (SBRT) was progressively adopted in clinical practice in Belgium, a reimbursement request in 2011 was not granted because of remaining clinical and economic uncertainty. A coverage with evidence development (CED) program on SBRT started in 2013, with the aim to assess clinical and technical patterns-of-care in Belgium and monitor survival per indication, in view of supporting inclusion in the reimbursement system. Methods: The Belgian National Institute for Health and Disability Insurance (NIHDI) initiated this prospective observational registry. Participating departments, using SBRT in clinical practice, signed the 'NIHDI convention'. Eligible patients had a primary tumour (PT) or oligometastatic disease (OMD). Patient, tumour, and treatment characteristics were collected through an online module of the Belgian Cancer Registry, prerequisite for financing. Five-year overall survival (5YOS) and 30- and 90-days mortality were primary outcomes, derived from vital status information. Findings: Between 10/2013 and 12/2019, 20 of the 24 accredited radiotherapy departments participated, 6 were academic. Registered cases per department ranged from 21 to 867. Of 5675 registrations analysed, the majority had good performance status and limited number of lesions. Enrolment of PTs remained stable over time, OMDs almost doubled. Peripheral lung lesions dominated in PTs as in OMDs. Other metastases were (para)spinal, 'non-standard' and hepatic. Thirty- and 90-days mortalities remained below 0.5% [95% CI 0.3%-0.8%] respectively 2.1% [95% CI 1.6%-2.7%]. 5YOS varied by indication, primary prostate patients performing best (85%, 95% CI [76%, 96%]), those with liver metastases worst (19%, 95% CI [15%, 24%]). Better OS was observed in academic departments, department size did not significantly impact survival. OMD survival was better in 2018-19. Interpretation: CED can be used to define patterns-of-care and real-life outcome of innovative radiotherapy. As the observed survival for different indications was in line with outcome in emerging literature, SBRT was included in the Belgian reimbursement system as of January 2020. Funding: NIHDI financed participating departments per registered case.

Radiotherapy-specific quality indicators at national level: How to make it happen.

PURPOSE /OBJECTIVE: To promote best practice and quality of care, the Belgian College of Physicians for Radiotherapy Centers established a set of radiotherapy specific quality indicators for benchmarking on a national level. This paper describes the development, the collected QIs, the observed trends and the departments' evaluation of this initiative. MATERIAL AND METHODS: The Donabedian approach was used, focussing on structural, process and outcome QIs. The criteria for QI selection were availability, required for low-threshold regular collection, and applicability to guidelines and good practice. The QIs were collected yearly and individualized reports were sent out to all RT departments. In 2021, a national survey was held to evaluate the ease of data collection and submission, and the perceived importance and validity of the collected QIs. RESULTS: 18 structural QI and 37 process and outcome parameters (n = 25 patients/pathology/department) were collected. The participation rate amounted to 95 % overall. The analysis gave a national overview of RT activity, resources, clinical practice and reported acute toxicities. The individualized reports allowed departments to benchmark their performance. The 2021 survey indicated that the QIs were overall easy to collect, relevant and reliable. The collection of acute recorded toxicities was deemed a weak point due to inter-observer variabilities and lack of follow-up time. CONCLUSION: QI collection on a national level is a valuable process in steering quality improvement initiatives. The feasibility and relevance was demonstrated with a high level of participation. The national initiative will continue to evolve as a quality monitoring and improvement tool.

Treatment and Prognosis of Patients with Lung Cancer and Combined Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians. METHODS: In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD (n = 29, 7%) were compared to those without ILD (n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes. RESULTS: Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant (p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03). CONCLUSIONS: Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

ProCaLung - Peer review in stage III, mediastinal node-positive, non-small-cell lung cancer: How to benchmark clinical practice of nodal target volume definition and delineation in Belgium☆.

BACKGROUND AND PURPOSE: The Quality Assurance project for stage III non-small cell lung cancer radiotherapy ProCaLung performed a multicentric two-step exercise evaluating mediastinal nodal Target Volume Definition and Delineation (TVD) variability and the opportunity for standardization. The TVD variability before and after providing detailed guidelines and the value of qualitative contour reviewing before applying quantitative measures were investigated. MATERIALS AND METHODS: The case of a patient with stage III NSCLC and involved mediastinal lymph nodes was used as a basis for this study. Twenty-two radiation oncologists from nineteen centers in Belgium and Luxembourg participated in at least one of two phases of the project (before and after introduction of ProCaLung contouring guidelines). The resulting thirty-three mediastinal nodal GTV and CTV contours were then evaluated using a qualitative-before-quantitative (QBQ) approach. First, a qualitative analysis was performed, evaluating adherence to most recent guidelines. From this, a list of observed deviations was created and these were used to evaluate contour conformity. The second analysis was quantitative, using overlap and surface distance measures to compare contours within qualitative groups and between phases. A 'most robust' reference volume for these analyses was created using the STAPLE-algorithm and an averaging method. RESULTS: Five GTV and seven CTV qualitative groups were identified. Second step contours were more often in higher-conformity groups (p = 0.012 for GTV and p = 0.024 for CTV). Median Residual Mean Square Distances improved from 2.34 mm to 1.36 mm for GTV (p = 0.01) and from 4.53 mm to 1.58 mm for CTV (p < 0.0001). Median Dice coefficients increased from 0.81 to 0.84 for GTV (p = 0.07) and from 0.82 to 0.89 for CTV (p ≤ 0.001). Using HC-contours only to generate references translated in more robust quantitative evaluations. CONCLUSION: Variability of mediastinal nodal TVD was reduced after providing the ProCaLung consensus guidelines. A qualitative review was essential for providing meaningful quantitative measures.

Delineation guidelines for the lymphatic target volumes in 'prone crawl' radiotherapy treatment position for breast cancer patients.

Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP. Nine volunteers were MRI scanned in both SP and PCP. Lymph node regions were delineated in SP using the existing ESTRO and PROCAB guidelines and were then translated to PCP, based on the observed changes in reference structure position. Nine PCP patient CT scans were used to verify if the new reference structures were consistently identified and easily applicable on different patient CT scans. Based on these data, a team of specialists in anatomy, CT- and MRI radiology and radiation oncology postulated the final guidelines. By taking the ESTRO and PROCAB guidelines for SP into account and by using a relatively big number of datasets, these new PCP specific guidelines incorporate anatomical variability between patients. The guidelines are easily and consistently applicable, even for people with limited previous experience with delineations in PCP.

A qualitative and a quantitative analysis of an auto-segmentation module for prostate cancer.

PURPOSE: This work describes the clinical validation of an automatic segmentation algorithm in CT-based radiotherapy planning for prostate cancer patients. MATERIAL AND METHODS: The validated auto-segmentation algorithm (Smart Segmentation, version 1.0.05) is a rule-based algorithm using anatomical reference points and organ-specific segmentation methods, developed by Varian Medical Systems (Varian Medical Systems iLab, Baden, Switzerland). For the qualitative analysis, 39 prostate patients are analysed by six clinicians. Clinicians are asked to rate the auto-segmented organs (prostate, bladder, rectum and femoral heads) and to indicate the number of slices to correct. For the quantitative analysis, seven radiation oncologists are asked to contour seven prostate patients. The individual clinician contour variations are compared to the automatic contours by means of surface and volume statistics, calculating the relative volume errors and both the volume and slice-by-slice degree of support, a statistical metric developed for the purposes of this validation. RESULTS: The mean time needed for the automatic module to contour the four structures is about one minute on a standard computer. The qualitative evaluation using a score with four levels ("not acceptable", "acceptable", "good" and "excellent") shows that the mean score for the automatically contoured prostate is "good"; the bladder scores between "excellent" and "good"; the rectum scores between "acceptable" and "not acceptable". Using the concept of surface and volume degree of support, the degree of support given to the automatic module is comparable to the relative agreement among the clinicians for prostate and bladder. The slice-by-slice analysis of the surface degree of support pinpointed the areas of disagreement among the clinicians as well as between the clinicians and the automatic module. CONCLUSION: The efficiency and the limits of the automatic module are investigated with both a qualitative and a quantitative analysis. In general, with efficient correction tools at hand, the use of this auto-segmentation module will lead to a time gain for the prostate and the bladder; with the present version of the algorithm, modelling of the rectum still needs improvement. For the quantitative validation, the concept of relative volume error and degree of support proved very useful.

Complete tumor response of a locally advanced lung large-cell neuroendocrine carcinoma after palliative thoracic radiotherapy and immunotherapy with nivolumab.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

Compliance and Outcome of Elderly Patients Treated in the Concurrent Once-Daily Versus Twice-Daily Radiotherapy (CONVERT) Trial.

INTRODUCTION: There is a lack of data on the efficacy and safety of concurrent chemoradiotherapy in elderly, limited-stage, patients with SCLC. METHODS: We compared outcomes of patients 70 years of age or older versus younger patients within the Concurrent Once-daily Versus twice-daily RadioTherapy (CONVERT) trial. Patients were randomized to receive 45 Gy/30 twice-daily fractions/19 days or 66 Gy/33 once-daily fractions/45 days concurrently with platinum-based chemotherapy. Overall survival and progression-free survival were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression. RESULTS: Of 547 patients randomized between April 2008 and November 2013, 57 did not receive protocol treatment and were excluded. Of the 490 patients included, 67 (14%) were 70 years of age or older (median age: 73 years; range: 70-82). Fewer older patients received the optimal number of radiotherapy fractions (73% versus 85%; p = 0.03); however, chemotherapy compliance was similar in both groups (p = 0.24). Neutropenia grade 3/4 occurred more frequently in the elderly (84% versus 70%; p = 0.02) but rates of neutropenic sepsis (4% versus 7%; p = 0.07) and death (3% versus 1.4%; p = 0.67) were similar in both groups. With a median follow-up of 46 months; median survival in the elderly versus younger groups was 29 (95% confidence interval [CI]: 21-39) versus 30 months (95% CI: 26-35), respectively; (hazard ratio: 1.15, 95% CI: 0.84-1.59; p = 0.38). Median time to progression in the elderly versus younger groups was 18 months (95% CI: 13-31) versus 16 months (95% CI: 14-19), respectively (hazard ratio: 1.04, 95% CI: 0.76-1.41; p = 0.81). CONCLUSIONS: Concurrent chemoradiotherapy with modern radiotherapy techniques should be a treatment option for fit, older patients.

The use of magnetic sensors to monitor moderate deep inspiration breath hold during breast irradiation with dynamic MLC compensators.

BACKGROUND AND PURPOSE: To reduce the dose to the heart during left breast irradiation, a moderate deep breath hold technique (MDIBH) was introduced. Originally, verification of the MDIBH was performed with portal images acquired in movie loop during the treatment delivery. However, this verification method is not compatible with the use of dynamic MLC compensation, recently introduced because of its often superior dose distribution. Magnetic sensors were evaluated as an additional/alternative method to monitor the breath hold. MATERIAL AND METHODS: In a first phase, the reproducibility of MDIBH for breast patients was evaluated by investigating for 19 patients the set-up errors derived from portal images in cine loop acquisition during MDIBH. In a second phase, for 10 patients, the breathing curves recorded by magnetic sensors were used to monitor beam-on and beam-off while portal images were simultaneously recorded in movie loop. In a third phase, breast patients treated with dynamic MLC compensation were trained for MDIBH and monitored with magnetic sensors. RESULTS: The interfraction reproducibility of MDIBH for the initial 19 patients was recorded: the mean set-up error, the systematic and the random deviations are all smaller than 4mm in the anterior-posterior direction and in the cranio-caudal direction and smaller than 2 degrees along the rotation axis. Magnetic sensors provided a reproducible breathing curve: while the mean amplitude recorded for 10 patients varied substantially between patients, the individual standard deviation of the amplitude for each session was smaller than 3mm. For these 10 patients, the intrafraction set-up variation between the first portal image of two consecutive breath holds and the intra-breath hold set-up variation between the first and last portal image of each breath hold is smaller than 2mm in the anterior-posterior direction, smaller than 3mm in the cranio-caudal direction and smaller than 1.5 degrees along the rotation axis. CONCLUSION: Using magnetic sensors to record the breathing curve of left breast patients in MDIBH, a verification method was developed, suitable for combining MDIBH with dynamic MLC compensation.

Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial.

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.

Guidelines for primary radiotherapy of patients with prostate cancer.

BACKGROUND AND PURPOSES: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing radiotherapy for prostate cancer requires a standardisation of target delineation as well as clinical quality assurance procedures. PATIENTS AND METHODS: Pathological and imaging studies provide valuable information on tumour extension. In addition, clinical investigations on patient positioning and immobilisation as well as treatment verification data offer an abundance of information. RESULTS: Target volume definitions for different risk groups of prostate cancer patients based on pathological and imaging studies are provided. Available imaging modalities, patient positioning and treatment preparation studies as well as verification procedures are collected from literature studies. These studies are summarised and recommendations are given where appropriate. CONCLUSIONS: On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group this article presents a common set of recommendations for external beam radiotherapy of patients with prostate cancer.

Vessel based delineation guidelines for the elective lymph node regions in breast cancer radiation therapy - PROCAB guidelines.

OBJECTIVE: A national project to improve the quality of breast radiation therapy was started, named PROCAB (PROject on CAncer of the Breast). One of the objectives was to reach a national consensus guideline for the delineation of the regional lymph node areas in breast radiation therapy. METHODS: The realization of the new guidelines was a step by step process that started with multiple expert meetings where the existing guidelines were analyzed and the delineations of the lymph node regions were performed together with a surgeon, specialized in the anatomy of the drainage of the breast. RESULTS: The delineation guidelines are vessel-based. Since the occurrence of pathological lymph nodes is typically around the veins, the cranial and caudal borders of all different nodal regions are based on a 5mm margin around the veins, except for the parasternal lymph node area. Compared to the existing guidelines there are some major changes. CONCLUSION: With this project a national as well as a European (ESTRO) consensus guideline for the delineation of the regional lymph node areas in breast RT is reached. The new delineation atlas is vessel-based and no longer field-based.

Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation.

BACKGROUND AND PURPOSE: Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI). MATERIALS AND METHODS: Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy. RESULTS: DIBH was able to reduce (p<0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH (p<0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH. CONCLUSIONS: This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI.

Reproducibility of deep inspiration breath hold for prone left-sided whole breast irradiation.

BACKGROUND: Investigating reproducibility and instability of deep inspiration breath hold (DIBH) in the prone position to reduce heart dose for left-sided whole breast irradiation. METHODS: Thirty patients were included and underwent 2 prone DIBH CT-scans during simulation. Overlap indices were calculated for the ipsilateral breast, heart and lungs to evaluate the anatomical reproducibility of the DIBH maneuver. The breathing motion of 21 patients treated with prone DIBH were registered using magnetic probes. These breathing curves were investigated to gain data on intra-fraction reproducibility and instability of the different DIBH cycles during treatment. RESULTS: Overlap index was 0.98 for the ipsilateral breast and 0.96 for heart and both lungs between the 2 prone DIBH-scans. The magnetic sensors reported population amplitudes of 2.8 ± 1.3 mm for shallow breathing and 11.7 ± 4.7 mm for DIBH, an intra-fraction standard deviation of 1.0 ± 0.4 mm for DIBH, an intra-breath hold instability of 1.0 ± 0.6 mm and a treatment time of 300 ± 69 s. CONCLUSION: Prone DIBH can be accurately clinically implemented with acceptable reproducibility and instability.

ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer.

BACKGROUND AND PURPOSE: Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. MATERIAL AND METHODS: During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. RESULTS: Borders of the CTV encompassing a 5mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. CONCLUSION: The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency.