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Recently, VOLO™ was introduced as a new optimizer for CyberKnife® planning. In this study, we investigated possibilities to improve treatment plans for MLC-based prostate SBRT with enhanced peripheral zone dose while sparing the urethra, and central lung tumors, compared to existing Sequential Optimization (SO). The primary focus was on reducing OAR doses. For 25 prostate and 25 lung patients treated with SO plans, replanning with VOLO™ was performed with the same planning constraints. For equal PTV coverage, almost all OAR plan parameters were improved with VOLO™. For prostate patients, mean rectum and bladder doses were reduced by 34.2% (P < 0.001) and 23.5% (P < 0.001), with reductions in D0.03cc of 3.9%, 11.0% and 3.1% for rectum, mucosa and bladder (all P ≤ 0.01). Urethra D5% and D10% were 3.8% and 3.0% lower (P ≤ 0.002). For lung patients, esophagus, main bronchus, trachea, and spinal cord D0.03cc was reduced by 18.9%, 11.1%, 16.1%, and 13.2%, respectively (all P ≤ 0.01). Apart from the dosimetric advantages of VOLO™ planning, average reductions in MU, numbers of beams and nodes for prostate/lung were 48.7/32.8%, 26.5/7.9% and 13.4/7.9%, respectively (P ≤ 0.003). VOLO™ also resulted in reduced delivery times with mean/max reductions of: 27/43% (prostate) and 15/41% (lung), P < 0.001. Planning times reduced from 6 h to 1.1 h and from 3 h to 1.7 h for prostate and lung, respectively. The new VOLO™ planning was highly superior to SO planning in terms of dosimetric plan quality, and planning and delivery times.

Background: Stereotactic body radiotherapy (SBRT) in ultra-central (UC) lung tumors, defined in the presence of planning target volume (PTV) overlap or direct tumor abutment to the central bronchial tree or esophagus, may be correlated to a higher incidence of severe adverse events. Outcome and toxicity in oligometastatic (≤3 metastases) non-small-cell lung cancer (NSCLC) patients receiving SBRT for UC tumors were evaluated. Methods: Oligometastatic NSCLC patients treated with SBRT for UC were retrospectively reviewed. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were calculated. Incidence and grade of toxicity were evaluated. Statistical analysis was performed to assess the impact of clinical and treatment-related variables on outcome and toxicity occurrence. Results: Seventy-two patients were treated to a median biologically effective dose (BED) of 105 (75–132) Gy10 . Two-year LC, DMFS, PFS, and OS were 83%, 46%, 43%, and 49%. BED>75 Gy10 was correlated to superior LC (p = 0.02), PFS (p = 0.036), and OS (p < 0.001). Grade ≥3 toxicity rate was 7%, including one fatal esophagitis. No variables were correlated to DMFS or to occurrence of overall and grade ≥3 toxicity. Conclusions: SBRT using dose-intensive schedules improves outcome in NSCLC patients. Overall toxicity is acceptable, although rare but potentially fatal toxicities may occur.

Objective: To evaluate the incidence of pulmonary metastases on chest computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC). Methods: All patients diagnosed with LAPC in a single tertiary center (Erasmus MC) between October 2011 and December 2017 were reviewed. The staging chest CT scan and follow-up chest CT scans were evaluated. Pulmonary nodules were divided into three categories: apparent benign, too small to characterize, and apparent malignant. Results: In 124 consecutive patients diagnosed with LAPC, 119 (96%) patients underwent a staging chest CT scan at the initial presentation. In 88 (74%) patients no pulmonary nodules were found; in 16 (13%) patients an apparent benign pulmonary nodule was found, and in 15 (13%) patients a pulmonary nodule too small to characterize was found. Follow-up chest CT scan(s) were performed in 111 (93%) patients. In one patient with either no pulmonary nodule or an apparent benign pulmonary nodule at initial staging, an apparent malignant pulmonary nodule was found on a follow-up chest CT scan. However, a biopsy of the nodule was inconclusive. Of 15 patients in whom a pulmonary nodule too small to characterize was found at staging, 12 (80%) patients underwent a follow-up CT scan; in 4 (33%) of these patients, an apparent malignant pulmonary nodule was found. Conclusion: In patients with LAPC in whom at diagnosis a chest CT scan revealed either no pulmonary nodules or apparent benign pulmonary nodules, routine follow-up chest CT scans is not recommended. Patients with pulmonary nodules too small to characterize are at risk to develop apparent malignant pulmonary nodules during follow-up.

Bone metastases are a frequent and important source of morbidity in cancer patients. Stereotactic body radiation therapy (SBRT) is an established treatment option for local control and pain relief of bone metastases, and it is increasingly used as upfront treatment, postoperative consolidation or salvage treatment after prior RT. However, heterogeneity of dose schedules described in literature represents a severe limitation in the definition of the role of SBRT as a standard of care. No consensus is available on the use of single versus multiple fraction SBRT for bone metastases. Advantages of single-fraction SBRT include shorter overall duration of treatment, absence of inter-fraction uncertainty, improved compliance, theoretical increased efficacy, and lower costs. However, caution has been advised due to reports of severe late toxicities, in particular, vertebral collapse fracture (VCF). The aim of this paper is to review dose fractionation and indications for the management of bone metastases using SBRT.

Background: We conducted a multicentre phase II trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer (LAPC), (LAPC-1 trial). Methods: Patients with biopsy-proven LAPC treated in four hospitals in the Netherlands between December 2014 and June 2017. Patients received 8 cycles of FOLFIRINOX followed by SBRT (5 fractions/8 Gy) if no tumour progression after the FOLFIRINOX treatment was observed. Primary outcome was 1-year overall survival (OS). Secondary outcomes were median OS, 1-year progression-free survival (PFS), treatment-related toxicity, and resection rate. The study is registered with ClinicalTrials.gov, NCT02292745, and is completed. Findings: Fifty patients were included. Nineteen (38%) patients did not receive all 8 cycles of FOLFIRINOX, due to toxicity (n = 12), disease progression (n = 6), or patients’ preference (n = 1). Thirty-nine (78%) patients received the SBRT treatment. The 1-year OS and PFS were 64% (95% CI: 50%-76%) and 34

Introduction: One-third of the patients with pancreatic cancer present with locally advanced unresectable pancreatic cancer (LAPC). Our aim was to determine survival outcomes and toxicity after FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) followed by radiotherapy (RT) in biopsy-proven patients with LAPC. Methods: We analysed a cohort of biopsy-proven patients with LAPC, who were eligible for induction FOLFIRINOX (eight cycles) and subsequent RT (30 fractions, 60 Gy). Eligible patients underwent a staging laparoscopy to detect occult metastasis before the treatment. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), treatment-related toxicity, and resection rate. Results: Forty-four patients were diagnosed with biopsy-proven LAPC. Twenty-five patients were eligible and all underwent staging laparoscopy before the treatment. In three (12%) patients occult metastases were found. Twenty-two patients started induction FOLFIRINOX, 17 (77%) completed all cycles. Seventeen (77%) patients were treated with subsequent RT, with 16 (94%) receiving the full dosage. Three (14%) patients underwent a radical resection after the treatment. Median OS was 15.4 months (95% confidence interval [CI], 10.0-20.7), median PFS was 11 months (95% CI, 7.7-14.4). Conclusions: Median OS after FOLFIRINOX and RT was 15 months in patients with LAPC. Toxicity remains severe, however, mos

The aim of our study was to assess the incidence of pain flare and the effectiveness of stereotactic body radiotherapy (SBRT) in pain management of patients with bone oligometastases. We evaluated 48 patients accounting for 54 treatments. The Edmonton Classification System for Cancer Pain (ECS-CP) was applied to identify indicators of treatment-resistant pain, in patients with active pain (NRS ≥ 2) at baseline. Statistical analysis was performed to identify predictors of pain flare and pain control. Pain flare occurred in 38% of treated patients (n = 18/48): No correlation was found between pain flare and patient- or treatment-related variables. In the subset of patients with active pain at baseline (n = 23), pain control was obtained in 62% of patients at 1 year; median time to pain progression after SBRT was 29 months (CI95% 6–52 months). Presence of ≥2ECS-CP features was correlated with earlier pain progression (4 vs. 30 months, p = 0.012). Pain flare occurred in 38% of cases irrespectively of steroid premedication and dose regimen. In patient with baseline active pain, durable pain control was obtained. Presence of ≥2 complexity indicators at the ECS-CP assessment was correlated with impaired pain control and may deserve future investigation in prospective studies.

Background: The objective of this study is to investigate the role and experience of early stage non-small cell lung cancer (NSCLC) patient in decision making process concerning treatment selection in the current clinical practice. Methods: Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68) were included in this prospective study and completed a questionnaire that explored: (1) perceived patient knowledge of the advantages and disadvantages of the treatment options, (2) experience with current clinical decision making, and (3) the information that the patient reported to have received from their treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and open questions. The Decisional Conflict Scale was used to assess the decisional conflict. Health related quality of life (HRQoL) was measured with SF-36 questionnaire. Results: In 19% of patients, there was self-reported perceived lack of knowledge about the advantages and disadvantages of the treatment options. Seventy-four percent of patients felt that they were sufficiently involved in decision-making by their physician, and 81% found it important to be involved in decision making. Forty percent experienced decisional conflict, and one-in-five patients to such an extent that it made them feel unsure about the decision. Subscores with regard to feeling uninformed and on uncertainty, contributed the most to decisional conflict, as 36% felt uninformed and 17% of patients were not satisfied with their decision. HRQoL was not influenced by patient experience with decision-making or patient preferences for shared decision making. Conclusions: Dutch early-stage NSCLC patients find it important to be involved in treatment decision making. Yet a substantial proportion experiences decisional conflict and feels uninformed. Better patient information and/or involvement in treatment-decision-making is needed in order to improve patient knowledge and hopefully reduce decisional

Aim: To investigate whether the impact of dose escalation in our patient population represented an improvement in local control without increasing treatment related toxicity. Materials and methods: A 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. cm, more than 3 metastases, and treatment delivered with other fractionation scheme than 3 times 12.5. Gy or 16.75. 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. Results: A total of 40 patients with 55 colorectal liver metastases were included in this study. We delivered 37.5. Gy to 32 lesions, and 50.25. 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. Conclusions: SBRT 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.

OBJECTIVES: To investigate the opinions of lung cancer clinicians concerning shared decision making (SDM) in early-stage non-small-cell lung cancer patients. METHODS: A survey was conducted among Dutch cardiothoracic surgeons and lung surgeons, pulmonologists and radiation oncologists. The opinions of clinicians on the involvement of patients in treatment decision making was assessed using a 1-5 Likert-type scale. Through open questions, we queried barriers to and drivers of SDM in clinical practice. Clinicians were asked to review 7 hypothetical cases and indicate which treatment strategy they would choose using a 1-7 Likert-type scale. RESULTS: Twenty-six percent of surgeons, 20% of pulmonologists and 12% of radiation oncol

Purpose: This article reports on the integration of a sliding-gantry CT-on-rails with a robotic linear accelerator. Methods: The system consists of a SOMATOM Definition AS CT scanner (Siemens Healthcare, Forchheim, Germany) and a CyberKnife M6 FIM (Accuray, Inc., Sunnyvale, CA, USA). Additional movement programs were implemented in the robotic treatment table (RoboCouch, Accuray Inc.) to move between CT and treatment position. Acceptance testing was performed on the CT scanner according to AAPM83 guidelines, as well as safety tests for collision avoidance and electromagnetic (EM) compatibility. For the first clinical application of the system, daily dose was evaluated in five pancreas SBRT patients. A second envisioned use is the optimal alignment of the treatment beams to soft-tissue targets without the use of implanted fiducials. To this end, an offset vector feature has been implemented, which shifts the treatment center according to the daily position of the tumor relative to the spine (established by a CT scan). This offset can be applied by either moving the treatment couch (physical couch shift) or by moving the CyberKnife robot (virtual couch shift). An End-to-End (E2E) test was specifically designed to evaluate the accuracy of this feature using the Xsight Lung Tracking Phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA). The position of the tumor with respect to the spine was varied by moving the insert inside the phantom and a CT scan was made for each position. The treatment plan was subsequently delivered to the phantom employing spine tracking. The test was repeated four times for a physical couch shift and four times for a virtual couch shift. Results: All acceptance, safety and EM compatibility testing was successful. For the first pancreas SBRT patients treated using daily CT imaging, the volume of stomach, duodenum, or small bowel receiving >35 Gy was found to increase or remain constant during treatment; however, the clinical

__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.

Purpose: To determine the long-term impact of stereotactic radiotherapy (SRT) on the quality of life (QoL) of inoperable patients with early-stage non-small cell lung cancer (NSCLC). Methods and materials: From January 2006 to February 2008, 39 patients with pathologically confirmed T1-2N0M0 NSCLC were treated with SRT. QoL, overall survival and local tumor control were assessed. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and the lung cancer-specific questionnaire QLQ-LC13 were used to investigate changes in QoL. Assessments were done before treatment, at 3weeks, every 2-3 months during the first two years, and then every 6months until 5years after the treatment or death or progressive disease. The median follow up was 38months. Results: During the 5years after treatment with SRT for stage I NSCLC, the level of QoL was maintained: There was a slow decline (slope: - 0.015) of the global health status over the 5years (p < 0.0001). The physical functioning and the role functioning improved slowly (slope: 0.006 and 0.004, resp.) over the years and this was also significant (p < 0.0001). The emotional functioning (EF) impro

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy3 (range: 42-420 Gy3). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy3, 98 Gy3 and 113 Gy3, respectively. No grades 5, 4 and 3 acute and late toxicity was observed. In conclusion: Re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Background: The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. Methods/Design. Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response. Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. Discussion. The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).

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.

__Abstract__ The third most common malignancy in the Netherlands is colorectal cancer. Rectal cancer affects every year around 2000 new patients. The highest incidence is found at an age above 70 years, and in men (sex ratio: 1.48). In Europe, the treatment of preference for locally advanced rectal cancer is surgery and preoperative radiotherapy. The addition of concurrent chemotherapy is currently investigated. However, these combined modality treatments induce side effects. Diarrhea is the major side effect of (neo-)adjuvant radiation therapy for rectal cancer [3, 15]. An overview of acute and late severe bowel toxicity is given in tables 1.1-1.3.