Defining dysphagia - a modified multi-professional Danish Delphi study.

OBJECTIVE: To establish a generally accepted Danish definition of dysphagia to enhance collaboration across sectors and professions. METHODS: The study was initiated by a multi-professional group of experienced researchers and board members of the Danish Society for Dysphagia. We used a modified Delphi methodology to achieve consensus among experienced health care professionals from different professions and contexts. The initial stage consisted of a literature search leading to the draft of different definitions followed by two Delphi rounds between professionals and a stakeholder consultation round. RESULTS: We conducted two Delphi rounds until one definition was clearly preferred. A total of 194 participants responded in round one, and 279 in round two. Both rounds had a broad representation of sectors and geography and most participants had worked with dysphagia for more than four years. CONCLUSION: The preferred definition was 'Dysphagia is a functional impairment that either prevents or limits the intake of food and fluids, and which makes swallowing unsafe, inefficient, uncomfortable or affects quality of life'. The definition was widely accepted among different health professional groups, patients and across sectors.

Bone versus soft-tissue setup in proton therapy for patients with oesophageal cancer.

BACKGROUND: The aim of this study was to investigate the effect of patient positioning based on either bone or soft-tissue matching for PT in oesophageal cancer and its impact on plan adaptation. MATERIALS AND METHODS: Two retrospective patient cohorts treated with radiotherapy were included in the study. Cohort A consisted of 26 consecutive patients with a planning 4DCT scan (CT1) and a surveillance 4DCT scan (CT2) at fraction ten. Cohort B consisted of 17 patients selected based on large anatomical changes identified during treatment resulting in a rescan (CT2). Mean dose to the iCTV (sum of the CTVs in all respiratory phases) was 50.4 Gy (RBE) in 28 fractions or 41.4 Gy (RBE) in 23 fractions. A nominal pencil beam scanning plan was created using two posterior beams and robust optimization (5 mm setup, 3.5% range). For each patient, two rigid registrations were made between average (avg) CT1 and CT2: a match on the vertebral column (bone match) and a match on the iCTV (soft-tissue match). Robustness towards setup (5 mm) and range (3.5%) errors was evaluated at CT2. Robustness towards respiration was evaluated by recalculation of the plan on all phases of the CT2 scan. Dose coverage <96% would trigger adaptation. The statistical significance (p-value <0.05) between dose coverage for the two registration methods was assessed using the Wilcoxon signed rank test. RESULTS: All plans fulfilled V95%iCTV>99% for the nominal plan and V95%iCTV>97% for all respiratory phases and robustness scenarios at CT1. In two (8%) and three (18%) patients, V95%iCTV<96% on CT2 for Cohort A and B, respectively when bone match was used. For soft-tissue match, V95%iCTV >96% for all patients. V95%iCTV was significantly higher (p-value = 0.0001) for soft-tissue match than bone match. CONCLUSION: Anatomical changes during the treatment course led to target dose deterioration and a need for plan adaptation when using a bone match.

Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.

BACKGROUND: The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. MATERIAL AND METHODS: Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. RESULTS: The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. CONCLUSION: This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.

Survival and morbidity following stereotactic radiotherapy of hepatocellular carcinoma: a ten-year, single institution experience.

BACKGROUND AND AIM: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option in hepatocellular carcinoma (HCC) in patients ineligible for other local ablative therapies. This study reports on the safety and efficacy of SABR in a Danish cohort of HCC patients. MATERIALS AND METHODS: Between January 2009 and December 2018, 28 patients with HCCs were treated with SABR at our institution. The primary endpoint of this retrospective study was local control; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In 28 patients, 32 tumors (median size 3.7 cm, range 1.4-6.8 cm) were treated. The median follow-up time was 16 months. Most patients (68%) received previous liver-directed treatments. A dose of 48 Gy in three or six fractions were given to 43% of the patients. Grad 1 or 2 toxicity was reported in 13 patients (46%), whereas 4 patients (14%) needed hospitalization (grade 3). One-year local control and overall survivals were 90% and 71%, respectively. One-year progression-free survival was 32%, and 65% of patients with disease progression received further HCC therapy. In univariate analysis, none of the examined factors predicted recurrence or overall survival. CONCLUSION: SABR provides high local control to inoperable HCC. SABR can be delivered safely even after previous liver-directed therapies and subsequent therapies are feasible after treatment with SABR. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximize disease control.

Recent update of proton beam therapy for hepatocellular carcinoma: A systematic review and meta-analysis.

Backgrounds/Aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC. Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. Results: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

Intrafraction tumor motion monitoring and dose reconstruction for liver pencil beam scanning proton therapy.

Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D 2 %  -  D 98 % D 50 %   × 100 % . Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.

Strategies for Motion Robust Proton Therapy With Pencil Beam Scanning for Esophageal Cancer.

PURPOSE: Proton therapy of esophageal cancer is superior to photon radiation therapy in terms of normal tissue sparing. However, respiratory motion and anatomical changes may compromise target dose coverage owing to density changes, geometric misses, and interplay effects. Here we investigate the combined effect on clinical target volume (CTV) coverage and compare proton therapy with intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This study includes 26 patients with esophageal cancer previously treated with IMRT planned on 4-dimensional computed tomography (4D-CT). For each patient, 7 proton pencil beam scanning (PBS) plans were created with different field configurations and optimization strategies. The effect of respiration was investigated by calculating the phase doses, 4D dose, and 4D dynamic dose (including interplay effects). The effect of anatomical changes was investigated by recalculating all plans on all phases of a 4D-CT surveillance scan. RESULTS: The most robust PBS plans were achieved using 2 posterior beams requiring coverage of planning target volume (PTV) and simultaneously using robust optimization (RO) of CTV (2PAPTVRO), resulting in only 1 patient showing V95%CTV <97% in 1 or more phases of the planning CT. For the least robust PBS plans obtained using lateral + posterior beams and CTV-RO, but not requiring PTV coverage (2LPRO), 10 patients showed underdosage. For IMRT, 2 patients showed underdosage. Interplay effects reduced V95%CTV significantly when delivering only 1 fraction, but the effects generally averaged out after 10 fractions. The effect of interplay was significantly larger for RO-only plans compared with plans optimized with RO combined with PTV coverage. Combining the effect of anatomical changes and respiration on the 4D-CT surveillance scan resulted in V95%CTV <97% for 3 2PAPTVRO, 16 2LPRO, and 8 IMRT patients. CONCLUSIONS: PBS using posterior beam angles was more robust to anatomical changes and respiration than IMRT. The effect of respiration was enhanced when anatomical changes were present. Single fraction interplay effects deteriorated the dose distribution but were averaged out after 10 fractions.