Impact of Using Unedited CT-Based DIR-Propagated Autocontours on Online ART for Pancreatic SBRT

PURPOSE: To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking. MATERIALS AND METHODS: The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints. RESULTS: Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans. CONCLUSION: For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC

Technical feasibility of online adaptive stereotactic treatments in the abdomen on a robotic radiosurgery system

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) has been proven to be beneficial for several disease sites in the (lower) abdomen. However, the quality of the treatment plan, based on a single planning computed tomography (CT), can be compromised due to large inter-fraction motion of the target and organs at risk (OARs) in this anatomical region. The aim of this study was to investigate the feasibility of online adaptive SBRT treatments on a robotic radiosurgery system and to record estimated total treatment times. MATERIALS AND METHODS: For two disease sites, locally advanced pancreatic cancer (LAPC) and oligometastatic lymph nodes, four patients with repeat CTs were included in the feasibility study. Quick treatment plan templates were generated based on the planning CT and validated by running them on the plan and fraction CTs. For two cases a dummy run was performed and the individual steps were timed. Dose delivery was the largest contributor to the total treatment time, followed by contour adaptation. RESULTS: Running the quick plan templates resulted in plans similar to unrestricted plans, obeying the OAR constraints. The dummy runs showed that online adaptive treatments were completed in 64 to 83 min respectively for oligometastases and LAPC, comparable to other clinically available solutions. CONCLUSIONS: This study showed the feasibility of online re-planning for two challenging disease sites within a clinically acceptable time frame on a robotic radiosurgery system, making use of commercially available elements that are not integrated by the vendor

Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

markdownabstract__Introduction:__ The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence following SABR for early stage non-small cell lung cancer (NSCLC). __Methods:__ Patients who underwent surgical salvage for a local recurrence following SABR for NSCLC were identified from two Dutch institutional databases. Complications were scored using the Dindo-Clavien-classification. __Results:__ Nine patients who underwent surgery for a local recurrence were identified. Median time to local recurrence was 22 months. Recurrences were diagnosed with CT- and/or 18FDG-PET-imaging, with four patients also having a pre-surgical pathological diagnosis. Extensive adhesions were observed during two resections, requiring conversion from a thoracoscopic procedure to thoracotomy during one of these procedures. Three patients experienced complications post-surgery; grade 2 (N = 2) and grade 3a (N = 1), respectively. All resection specimens showed viable tumor cells. Median length of hospital stay was 8 days (range 5-15 days) and 30-day mortality was 0 %. Lymph node dissection revealed mediastinal metastases in 3 patients, all of whom received adjuvant therapy. __Conclusions:__ Our experience with nine surgical procedures for local recurrences post-SABR revealed two grade IIIa complications, and a 30-day mortality of 0 %, suggesting that salvage surgery can be safely performed after SABR

Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy

AimTo investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity.Materials and methodsA cohort of consecutive patients with colorectal liver metastases treated with stereotactic body radiation therapy (SBRT) between December 2002 and December 2013 were eligible for this study. Inclusion criteria were a Karnofsky performance status ≥80% and, according to the multidisciplinary tumor board, ineligibility for surgery or radiofrequency ablation. Exclusion criteria were a lesion size >6[[ce:hsp sp="0.25"/]]cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5[[ce:hsp sp="0.25"/]]Gy or 16.75[[ce:hsp sp="0.25"/]]Gy prescribed at the 65–67% isodose. To analyze local control, CT or MRI scans were acquired during follow-up. Toxicity was scored using the Common Toxicity Criteria Adverse Events v4.0.ResultsA total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5[[ce:hsp sp="0.25"/]]Gy to 32 lesions, and 50.25[[ce:hsp sp="0.25"/]]Gy to 23 lesions. Median follow-up was 26 and 25 months for these two groups. Local control at 2 and 3 years was 74 and 66% in the low dose group while 90 and 81% was reached in the high dose group. No significant difference in local control between the two dose fractionation schemes could be found. Grade 3 toxicity was limited and was not increased in the high dose group.ConclusionsSBRT for colorectal liver metastases offers a high chance of local control at long term. High irradiation doses may contribute to enhance this effect without increasing toxicity

Proton and photon radiotherapy in stage III NSCLC:Effects on hematological toxicity and adjuvant immune therapy

Background and purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. Materials and methods: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. Results: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0–4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9–12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16–0.79, P = 0.01). Conclusion: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.</p

Distributed learning on 20 000+ lung cancer patients - The Personal Health Train

Background and purpose Access to healthcare data is indispensable for scientific progress and innovation. Sharing healthcare data is time-consuming and notoriously difficult due to privacy and regulatory concerns. The Personal Health Train (PHT) provides a privacy-by-design infrastructure connecting FAIR (Findable, Accessible, Interoperable, Reusable) data sources and allows distributed data analysis and machine learning. Patient data never leaves a healthcare institute. Materials and methods Lung cancer patient-specific databases (tumor staging and post-treatment survival information) of oncology departments were translated according to a FAIR data model and stored locally in a graph database. Software was installed locally to enable deployment of distributed machine learning algorithms via a central server. Algorithms (MATLAB, code and documentation publicly available) are patient privacy-preserving as only summary statistics and regression coefficients are exchanged with the central server. A logistic regression model to predict post-treatment two-year survival was trained and evaluated by receiver operating characteristic curves (ROC), root mean square prediction error (RMSE) and calibration plots. Results In 4 months, we connected databases with 23 203 patient cases across 8 healthcare institutes in 5 countries (Amsterdam, Cardiff, Maastricht, Manchester, Nijmegen, Rome, Rotterdam, Shanghai) using the PHT. Summary statistics were computed across databases. A distributed logistic regression model predicting post-treatment two-year survival was trained on 14 810 patients treated between 1978 and 2011 and validated on 8 393 patients treated between 2012 and 2015. Conclusion The PHT infrastructure demonstrably overcomes patient privacy barriers to healthcare data sharing and enables fast data analyses across multiple institutes from different countries with different regulatory regimens. This infrastructure promotes global evidence-based medicine while prioritizing patient privacy

Endovascular coils as lung tumour markers in real-time tumour tracking stereotactic radiotherapy: preliminary results

To evaluate the use of endovascular coils as markers for respiratory motion correction during high-dose stereotactic radiotherapy with the CyberKnife, an image-guided linear accelerator mounted on a robotic arm. Endovascular platinum embolisation coils were used to mark intrapulmonary lesions. The coils were placed in subsegmental pulmonary artery branches in close proximity to the target tumour. This procedure was attempted in 25 patients who were considered unsuitable candidates for standard transthoracic percutaneous insertion. Vascular coils (n = 87) were succesfully inserted in 23 of 25 patients. Only minor complications were observed: haemoptysis during the procedure (one patient), development of pleural pain and fever on the day of procedure (one patient), and development of small infiltrative changes distal to the vascular coil (five patients). Fifty-seven coils (66% of total inserted number) could be used as tumour markers for delivery of biologically highly effective radiation doses with automated tracking during CyberKnife radiotherapy. Endovascular markers are safe and allow high-dose radiotherapy of lung tumours with CyberKnife, also in patients who are unsuitable candidates for standard transthoracic percutaneous marker insertion

Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery

Contains fulltext : 96401.pdf (publisher's version ) (Open Access

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care