PURPOSE:The study aimed to compare the effects of technological versus interpersonal psychoeducational interventions in reducing treatment-related anxiety in breast cancer patients undergoing radiation therapy. METHODS AND MATERIALS:This prospective randomized controlled trial enrolled 241 patients with breast cancer, randomly assigning them into 3 arms: video education (n = 51), medical physicist consultation (n = 92), and standard care (n = 98). The video education group viewed an informational video prior to simulation, whereas the physicist consultation group received personalized treatment plan explanations before their first treatment. Anxiety levels were assessed using the State-Trait Anxiety Inventory and distress thermometer at 4 time points: after initial consultation, after simulation, after first treatment, and at treatment completion. RESULTS:Baseline anxiety scores were comparable across all groups following initial consultation. Medical physicist consultation patients demonstrated significantly lower distress thermometer scores after first treatment compared with both video education (P < .0043) and standard care groups (P < .0051). Although video education and standard care groups showed significant anxiety reduction between first and last treatments through habituation, the medical physicist group maintained consistently lower anxiety levels throughout treatment, suggesting earlier anxiety resolution through interpersonal intervention. CONCLUSIONS:Direct patient education by medical physicists resulted in more rapid anxiety reduction compared with video-based education or standard care. The effectiveness of interpersonal intervention preceded the natural anxiety reduction observed through habituation in other groups. These findings support the integration of medical physicists into direct patient care and demonstrate the superior impact of human connection over technological interventions in managing radiation therapy-related anxiety.

Background Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. Methods This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external- beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete. Findings Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 655 years (IQR 583-718), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1]). Interpretation Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted. Funding Gateway for Cancer Research and the Israel Cancer Association.

Abstract Background Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes. Methods We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT. Treatment included auto-contour and structure deformation of Organs at Risk (OARs) and target structures, with adjustments by the treating physician. Two plans were generated: one based on the initial CT simulation with the edited structures (scheduled) and a re-optimized plan (adaptive). Both plans were evaluated and the superior one approved and delivered. Clinical and dosimetric outcomes were reviewed. Results Twenty two patients with head and neck cancers (7 Nasopharynx, 6 Oropharynx, 1 oral cavity, 8 larynx) stages I-IVA were treated with daily ART. 770 adaptive and scheduled radiotherapy plans were generated. 703 (91.3%) adaptive plans were chosen. Median time to deliver ART was 20 minutes (range: 18-23). Adaptive compared to scheduled plans demonstrated improved mean V95 values for the PTV70, PTV59.5, and PTV56 by 1.2%, 7.2%, and 6.0% respectively and a mean 1.4% lower maximum dose in PTV70. Fourteen of 17 OARs demonstrated improved dosimetry with adaptation, with select OARs reaching statistical significance. At a median follow up of 14.1 months, local control was 95.5%, two patients developed metastatic disease and four patients died. 9.1% of patients had acute grade 3 dysphagia and 13.6% had grade 2 chronic xerostomia. Discussion These findings provide real world evidence of the feasibility and dosimetric benefit of incorporating daily ART on CBCT in the treatment of head and neck cancer. Prospective study is needed to determine if these dosimetric improvements translate into improved outcomes.

Background:Stereotactic body radiation therapy (SBRT) is often delivered in patients with oligometastatic disease (OMD). However, the specific subset of patients with polymetastatic non-small cell lung cancer (NSCLC) on novel systemic therapies who develop induced oligopersistant disease (OpersisD) or oligoprogressive disease (OprogD), as defined by the European Organisation for Research and Treatment of Cancer (EORTC) OMD classification, has not been well described. This study explores the outcomes of patients treated with this strategy.Methods:Patients with stage IV NSCLC being treated with osimertinib or immune checkpoint inhibitors (ICIs) who received extracranial SBRT for OpersisD or OprogD were identified in our retrospective analysis. Outcomes reported include progression-free survival (PFS), time to change of systemic treatment (TTCST), overall survival (OS), local control (LC) and treatment-related toxicity.Results:Forty-nine patients received SBRT for OpersisD (34.7%) or OprogD (65.3%) at a median of 5.8 and 15.3 months after start of systemic therapy, respectively. 55.1% received concurrent osimertinib and 44.9% received ICI. Seventy-seven extracranial lesions were treated with various fractionation schemas. At a median of 18.8 months follow-up from first SBRT, LC was achieved in 92.2% of total lesions treated (71). The 1-year OS was 91.7% for OpersisD and 83.3% for OprogD. OpersisD compared to OprogD had a longer median PFS (18.3 vs. 6.1 months) and longer median TTCST (23.6 vs. 13.5 months), median OS was not reached for either cohort. On multivariate analysis, patients treated with osimertinib had shorter PFS (HR: 2.20; 95% CI: 1.01-4.82; P=0.048) and shorter TTCST (HR: 2.83; 95% CI: 1.09-7.33; P=0.032). One patient (2%) experienced grade 3 pneumonitis after SBRT, and no grade 4-5 toxicities were reported with SBRT treatment.Conclusions:This study indicates that SBRT for OpersisD or OprogD in Stage IV NSCLC patients on osimertinib or ICIs is safe, very well tolerated, and may prolong the time before needing a shift in systemic therapy. Further prospective research is needed to validate and expand upon these findings.

BACKGROUND:Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.OBJECTIVES:To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.METHODS:We reviewed charts of patients who were diagnosed with stage I-III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.RESULTS:In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.CONCLUSIONS:Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Purpose: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). Methods and Materials: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after >= 3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade >= 3 gastrointestinal (GI) toxicity definitely attrib-uted to SMART.Results: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly con-sisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade >= 3 GI tox-icity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade >= 3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%.Conclusions: The primary endpoint of this study was met with no acute grade >= 3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxic-ity, quality of life, and long-term efficacy. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

MR-guided radiotherapy allows the delivery of effective doses of radiation to tumors situated close to critical structures. An ESTRO-ASTRO consensus paper defining oligometastatic disease from a radiation oncology perspective states that “the feasibility of safely delivering curative intent metastasis directed radiotherapy (MDRT) determines the maximum number of sites that can be treated with radiotherapy in oligometastatic disease (OMD). The risk of toxicity impacts treatment indications for OMD” [1]. The main limitation on delivery of safe SBRT is the exposure of surrounding critical organs to radiation. Real-time imaging is crucial when there is a moving target (such as influenced by breathing or peristalsis) situated close to bowel or other major organs. We will discuss some rare tumors treated with MR-guided SBRT that we have treated in our institution or that have been reported in the literature.

Health disparities in the care of special populations is a major concern of cancer care organizations. World Cancer Day in February 2022 was dedicated to “Close the Gap,” a 2-year campaign to identify and correct inequities in cancer care. This chapter will address research on the availability and utilization of radiotherapy (RT) machines and RT expertise in special populations and on the outcome of treatment by geographical location (between countries and within countries) and by patient factors such as age, gender, and race. For some populations, there is some overlap between geographical and patient-centered factors such as socioeconomic status. General radiotherapy care disparities will be described as well as reviewing research on disparities in common cancer sites, especially those in which patient age has a significant impact.

662 Background: Upper abdominal / lower back pain characterizes celiac plexus involvement from pancreatic and other cancers which may impair HRQOL; its satisfactory treatment is an unmet clinical need. We hypothesized that ablative radiation delivered to the celiac plexus would decrease pain and improve HRQOL. Methods: An international single arm Phase II study included patients with an average pain level ≥ 5/11 on the brief pain inventory (BPI), ECOG 0-2, and anatomical involvement of the celiac axis. The intervention was a single fraction of 25Gy delivered to the celiac plexus. The primary endpoint was ‘complete or partial (≥2 points) pain response’ based upon the BPI ‘average pain’ 11-point scale. Changes in Health-related QOL at 3 & 6 weeks compared to baseline were secondary endpoints as measured by FACT-Hep, > 8 point change being the minimal clinically important difference (MCID). Evaluable patients included eligible irradiated subjects, who had stable pain levels pre-treatment, and were alive 3 weeks’ post-treatment. The sample size was 90 evaluable patients, giving 90% power to show response rate ≥ 40%. Opioid usage was assessed using intravenous morphine equivalent dose. Sensitivity HRQOL analyses imputed worsened outcomes (-9 for total FACT-Hep) for missing data. Results: Between 2018 and 2022, 149 patients were enrolled, 90/125 who received treatment were evaluable. Median age was 65.5 years (range 28-88), 65% were female, 92% had pancreatic cancer, and 86% had metastatic disease. Median Zubrod PS was 1, median number of systemic treatment lines was 1 (range 0-5), and median baseline opioid use 31 mg/d. At 3 weeks, 48 (53.3%, 95% CI 42.5-63.9) had at least a partial pain, the BPI ‘average pain’ score decreased by a mean of 2.5 points at 3 weeks (86/90 reported) and 3.2 points at 6 weeks (67/90 reported), both p < 0.001. Opioid usage decreased by 0.6 mg/d at 3 weeks (NS) and 16.9 mg/d at 6 weeks (p = 0.005). The FACT-Hep total score increased by 7.8 points at 3 weeks (54/90 reported, NS diff. from 8) and 16.6 points at 6 weeks (45/90 reported, sig. > 8, p = 0.01), showing an improvement in patients’ HRQOL. Changes in FACT-Hep were especially noted in the Physical Well Being subscale. The Trial Outcome Index (sum of physical, functional & disease-specific concerns) increased markedly at 3 weeks (6.6 points, p = 0.005) after treatment and even more after 6 weeks (14.5 points, p < 0.). Sensitivity analyses demonstrated improvements in HRQOL at 3 and 6 weeks (1.1, 3.8), but these were less than MCID. Conclusions: Celiac plexus SBRT decreases pain and opioid use amongst patients with pancreatic cancer and other tumors invading the celiac axis. The treatment appears to improve HRQOL. Supported by Gateway for Cancer Research and the Israel Cancer Association. Clinical trial information: NCT03323489 .

BackgroundWe present our experience with MR-guided stereotactic body radiotherapy (SBRT) for 200 consecutive patients with prostate cancer with minimum 3-month follow-up.MethodsTreatment planning included fusion of the 0.35-Tesla planning MRI with multiparametric MRI and PET-PSMA for Group Grade (GG) 2 or higher and contour review with an expert MRI radiologist. No fiducials or rectal spacers were used. Prescription dose was 36.25 Gy in 5 fractions over 2 weeks to the entire prostate with 3-mm margins. Daily plan was adapted if tumor and organs at risk (OAR) doses differed significantly from the original plan. The prostate was monitored during treatment that was automatically interrupted if the target moved out of the PTV range.ResultsMean age was 72 years. Clinical stage was T1c, 85.5%; T2, 13%; and T3, 1.5%. In addition, 20% were GG1, 50% were GG2, 14.5% were GG3, 13% were GG4, and one patient was GG5. PSA ranged from 1 to 77 (median, 6.2). Median prostate volume was 57cc, and 888/1000 (88%) fractions required plan adaptation. The most common acute GU toxicity was Grade I, 31%; dysuria and acute gastrointestinal toxicity were rare. Three patients required temporary catheterization. Prostate size of over 100cc was associated with acute fatigue, urinary hesitance, and catheter insertion. Prostate Specific Antigen (PSA) decreased in 99% of patients, and one patient had regional recurrence.ConclusionMR-guided prostate SBRT shows low acute toxicity and excellent short-term outcomes. Real-time MRI ensures accurate positioning and SBRT delivery.

Purpose: The aim of this study was to evaluate a formulation of pegylated liposomal mitomycin C lipidic prodrug (PL-MLP) in patients concomitantly undergoing external beam radiation therapy (RT). Methods and Materials: Patients with metastatic disease or inoperable primary solid tumors requiring RT for disease control or symptom relief were treated with 2 courses of PL-MLP (1.25, 1.5, or 1.8 mg/kg) at 21-day intervals, along with 10 fractions of conventional RT or 5 stereotactic body RT fractions initiated 1 to 3 days after the first PL-MLP dose and completed within 2 weeks. Treatment safety was monitored for 6 weeks, and disease status was re-evaluated at 6-week intervals thereafter. MLP levels were analyzed 1 hour and 24 hours after each PL-MLP infusion.Results: Overall, 19 patients with metastatic (18) or inoperable (1) disease received combination treatment, with 18 completing the full protocol. Most patients (16) had diagnoses of advanced gastrointestinal tract cancer. One grade 4 neutropenia event possibly related to study treatment was reported; other adverse events were mild or moderate. Of the 18 evaluable patients, 16 were free of RT target lesion progression at first re-evaluation. Median survival of the entire patient population was 63.3 weeks. Serum MLP level correlated with dose increases and similar long circulating profiles were observed before and after RT.Conclusions: PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL-MLP is potentially an attractive option for chemoradiation therapy that warrants further evaluation in randomized studies in the palliative and curative settings. & COPY; 2023 Elsevier Inc. All rights reserved.

IntroductionStereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART.MethodsPatients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival.ResultsA total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2–86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8–28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1–3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups.ConclusionSMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate long-term outcome and late toxicity.

BACKGROUND AND PURPOSE:Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS:This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS:Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS:Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

Supplementary Data from The Expression of Three Genes in Primary Non–Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain