Comparison of intravenous 5-Fluorouracil with Oral Capecitabine in the Treatment of Anal Squamous Cell Carcinoma Using Modern Radiation Techniques.

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.

Spine radiosurgery: lessons learned from the first 100 treatment sessions.

OBJECTIVE Local therapy to spine tumors has been shown to be effective in selected cases. Spinal radiosurgery (SRS) is an evolving radiotherapy regimen allowing for noninvasive, highly efficacious local treatment. The learning curve can compromise the results of any newly employed technology and should be studied to minimize its effects. In this paper the first 100 SRSs performed at several medical centers are presented and analyzed for the effects of the learning curve on outcome. METHODS A retrospective analysis was undertaken to evaluate data from patients treated with SRS at Sheba Medical Center and Assuta Medical Centers in the period from September 2011 to February 2016. Medical history, clinical and neurological findings, pathological diagnoses, SRS variables, complications, and follow-up data were collected and analyzed. Local control rates were calculated, and local treatment failure cases were qualitatively studied. RESULTS One hundred treatment sessions were performed for 118 lesions at 179 spinal levels in 80 patients. The complication rate was low and did not correlate with a learning curve. Mean follow-up time was 302 days, and the overall local control rate was 95%. The local control rate was dose dependent and increased from 87% (among 35 patients receiving a dose of 16 Gy) to 97% (among 65 patients receiving a dose of 18 Gy). The 6 treatment failure cases are discussed in detail. CONCLUSIONS Spinal radiosurgery is a safe and effective treatment. Comprehensive education of the treating team and continuous communication are essential to limit the effects of the learning curve on outcome.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

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.

Outcome of the first 200 patients with prostate cancer treated with MRI-Linac at Assuta MC.

Background: We present our experience with MR-guided stereotactic body radiotherapy (SBRT) for 200 consecutive patients with prostate cancer with minimum 3-month follow-up. Methods: Treatment 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. Results: Mean 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. Conclusion: MR-guided prostate SBRT shows low acute toxicity and excellent short-term outcomes. Real-time MRI ensures accurate positioning and SBRT delivery.

Pancreatic cancer outcome-local treatment with radiation using MRI-LINAC.

Introduction: Stereotactic 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. Methods: Patients 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. Results: A 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. Conclusion: SMART 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.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

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 attributed 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 consisted 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 toxicity 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 toxicity, quality of life, and long-term efficacy.

Real-time Online Matching in High Dose-per-Fraction Treatments: Do Radiation Therapists Perform as Well as Physicians?

PURPOSE: In our department, for high dose-per-fraction treatments such as stereotactic body radiation therapy, we require a physician to perform the pretreatment on-board imaging match. The purpose of this study was to determine whether patient-matching positioning performed by radiation therapists (RTTs) is as accurate as that performed by physicians. METHODS AND MATERIALS: Sixteen RTTs and 5 physicians participated in this study. Data were collected from 113 patients, totaling 324 measurements. A total of 60 patients were treated for bone lesions and 53 for soft-tissue lesions, such as lung and liver. Matching was performed using kV-kV imaging for bones and cone beam computed tomography for soft tissue. All treatments were delivered on Varian linear accelerators. The initial match was performed by the RTTs, and the shifts were noted. Subsequently, the match was reset, and the physician performed an independent match blinded to the RTT match. Physician shifts were applied for treatment. We used the Wilcoxon rank sum test to determine the statistical significance between RTT and physician shifts. RESULTS: The differences in patient shifts between physicians and RTTs were calculated in 3 translational 1 one rotational axis. The average vector shift was 0.88 ± 0.57 cm versus 0.91 ± 0.57 cm for RTTs versus physicians, respectively. Neither the average vector nor the individual axis shifts were statistically significantly different (P > .2). There was no significant difference when testing for bony or soft lesion matches separately. CONCLUSIONS: RTT on-board imaging matching is as accurate as physician matching for both bone and soft tissue lesions. On the basis of these results, RTTs are as qualified as physicians to perform a pretreatment match. Thus, it may be feasible for the RTTs to perform the match and the physician to review it offline after treatment without being present at the machine during treatment. Our results show that this approach does not compromise patient safety.

IMRT vs. 3D noncoplanar treatment plans for maxillary sinus tumors: a new tool for quantitative evaluation.

We compared 9-field, equispaced intensity modulated radiation therapy (IMRT), 4- to 5-field, directionally optimized IMRT, and 3-dimensional (3D) noncoplanar planning approaches for tumors of the maxillary sinus. Ten patients were planned retrospectively to compare the different treatment techniques. Prescription doses were 60 to 70 Gy. Critical structures contoured included optic nerves and chiasm, lacrimal glands, lenses, and retinas. As an aid for plan assessment, we introduced a new tool: Critical Organ Scoring Index (COSI), which allows quantitative evaluation of the tradeoffs between target coverage and critical organ sparing. This index was compared with other, commonly used conformity indices. For a reliable assessment of both tumor coverage and dose to critical organs in the different planning techniques, we introduced a 2D, graphical representation of COSI vs. conformity index (CI). Dose-volume histograms and mean, maximum, and minimum organ doses were also compared. IMRT plans delivered lower doses to ipsilateral structures, but were unable to spare them. 3D plans delivered less dose to contralateral structures, and were more homogeneous, as well. Both IMRT approaches gave similar results. In cases where choice of optimal plan was difficult, the novel 2D COSI-CI representation gave an accurate picture of the tradeoffs between target coverage and organ sparing, even in cases where other conformity indices failed. Due to their unique anatomy, maxillary sinus tumors may benefit more from a noncoplanar approach than from IMRT. The new graphical representation proposed is a quick, visual, reliable tool, which may facilitate the physician's choice of best treatment plan for a given patient.

Dosimetric comparison of tandem and Ovoids vs. tandem and ring for intracavitary gynecologic applications.

We evaluated dosimetric differences in tandem and ovoid (TO) and tandem and ring (TR) gynecologic brachytherapy applicators. Seventeen patients with cervical cancer (Stages II-IV) receiving 3 high-dose-rate (HDR) brachytherapy applications (both TO and TR) were studied. Patients underwent computed tomography (CT) scans with contrast in bladder, and were prescribed 8 Gy to ICRU points A, with additional optimization goals of maintaining the pear-shaped dose distribution and minimizing bladder and rectum doses. Bladder and rectum point doses, mean, and maximum doses were calculated. Total treatment time and volumes treated to 95%, 85%, 50%, and 20% or the prescription dose were compared. There were no significant differences between TO and TR applicators in doses to prescription points or critical organs. However, there were significant differences (p < 0.001) between the applicators in treated volumes and total treatment time. The TO treated larger volumes over a longer time. Within each patient, when the applicators were compared, treated volumes were also found to be significantly different (p < 0.01, chi(2)). Our results demonstrate that the 2 applicators, while delivering the prescribed dose to points A and keeping critical organ doses below tolerance, treat significantly different volumes. It is unclear if this difference is clinically meaningful. TO applicators may be treating surrounding healthy tissue unnecessarily, or TR applicators may be underdosing tumor tissue. Further investigation with appropriate imaging modalities is required for accurate delineation of target volumes. Clearly, the TO and TR are not identical, and should not be used interchangeably without further study.