Rectal Cancer: Clinical and Molecular Predictors of a Complete Response to Total Neoadjuvant Therapy.

BACKGROUND: Total neoadjuvant therapy in rectal cancer may increase pathological complete response rates, potentially allowing for a nonoperative approach. OBJECTIVE: The objective of this study was to identify patient and tumor characteristics that predict a complete response following total neoadjuvant therapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a university-based National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS: The patients include those with stage 2 or 3 rectal adenocarcinoma. INTERVENTIONS: Interventions included total neoadjuvant therapy, total mesorectal excision, and nonoperative management. MAIN OUTCOME MEASURES: Complete response was defined as either patients with a clinical complete response undergoing nonoperative management who remained cancer-free or patients undergoing surgery with a pathological complete response. RESULTS: Among 102 patients, median age was 54 years, 69% were male, median carcinoembryonic antigen level was 3.0 ng/mL, and the median distance of the tumor above the anorectal ring was 3 cm. Thirty-eight (37%) patients had a complete response, including 15 of 18 (83%) nonoperative patients who remained cancer free at a median of 22 months (range, 7-48 months) and 23 of 84 (27%) patients who underwent surgery and had a pathological complete response. The incomplete response group consisted of 61 patients who underwent initial surgery and 3 nonoperative patients with regrowth. There were no differences in gender, T-stage, or tumor location between groups. Younger age (median, 49 vs 55 years), normal carcinoembryonic antigen (71% vs 41%), clinical node-negative (24% vs 9%), smaller tumors (median 3.9 vs 5.4 cm), and wild-type p53 (79% vs 47%) and SMAD4 (100% vs 81%) were more likely to have a complete response (all p < 0.05). LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSIONS: In patients with rectal cancer treated with total neoadjuvant therapy, more than one-third will achieve a pathological complete response or sustained clinical complete response with nonoperative management, making oncological resection superfluous in these patients. Smaller, wild-type p53 and SMAD4, and clinically node-negative cancers are predictive features of a complete response. See Video Abstract at http://links.lww.com/DCR/B889 . CNCER DE RECTO PREDICTORES CLNICOS Y MOLECULARES DE UNA RESPUESTA COMPLETA A LA TERAPIA NEOADYUVANTE TOTAL: ANTECEDENTES:La terapia neoadyuvante total en el cáncer de recto puede aumentar las tasas de respuesta patológica completa y permitir potencialmente un enfoque no quirúrgico.OBJETIVO:El objetivo fue identificar las características tanto del paciente y del tumor que logren predecir una respuesta completa después de la terapia neoadyuvante total.DISEÑO:Este fue un estudio de cohorte retrospectivo.AJUSTES:Este estudio se realizó en un Centro Integral de Cáncer designado por el Instituto Nacional del Cáncer con sede universitaria.PACIENTES:Los pacientes incluyen aquellos con adenocarcinoma de recto en estadio 2 o 3.INTERVENCIONES:Terapia neoadyuvante total, escisión total del mesorrecto, manejo conservador no quirúrgico.PRINCIPALES MEDIDAS DE RESULTADO:La respuesta completa se definió como pacientes con una respuesta clínica completa sometidos a tratamiento no quirúrgico que permanecieron libres de cáncer o pacientes sometidos a cirugía con una respuesta patológica completa.RESULTADOS:Entre 102 pacientes, la mediana de edad fue de 54 años, el 69% fueron hombres, la mediana del nivel de antígeno carcinoembrionario fue de 3.0 ng/ml y la mediana de la distancia del tumor por encima del anillo anorrectal fue de 3 cm. Thirty-eight (37%) pacientes tuvieron una respuesta completa que incluyó a 15 de 18 (83%) pacientes con manejo no operatorio y que permanecieron libres de cáncer en una mediana de 22 meses (rango 7- 48 meses) y 23 de 84 (27%) pacientes que fueron sometidos a cirugía y tuvieron una respuesta patológica completa. El grupo de respuesta incompleta consistió en 61 pacientes que fueron sometidos inicialmente a cirugía y 3 pacientes no quirúrgicos con recrecimiento. No se encontró diferencias de género, estadio T o ubicación del tumor entre los grupos. Edad más joven (mediana 49 frente a 55), antígeno carcinoembrionario normal (71% frente a 41%), ganglios clínicos negativos (24% frente a 9%), tumores más pequeños (mediana de 3,9 frente a 5,4 cm) y p53 de tipo salvaje (79 % vs 47%) y SMAD4 (100% vs 81%) tenían más probabilidades de tener una respuesta completa (todos p < 0,05).LIMITACIONES:Este fue un estudio retrospectivo y con un tamaño de muestra pequeño.CONCLUSIONES:En pacientes con cáncer de recto tratados con terapia neoadyuvante total, más de un tercio logrará una respuesta patológica completa o una respuesta clínica completa sostenida con manejo no operatorio, logrando que la resección oncológica sea superflua en estos pacientes. Los cánceres más pequeños, clínicamente con ganglios negativos, con p53 de tipo salvaje y SMAD4, son características predictoras de una respuesta completa. Consulte Video Resumen en http://links.lww.com/DCR/B889 . (Traducción-Dr. Osvaldo Gauto ).

Cardiac metabolic changes on 18 F-positron emission tomography after thoracic radiotherapy predict for overall survival in esophageal cancer patients.

PURPOSE: Heart doses have been shown to be predictive of cardiac toxicity and overall survival (OS) for esophageal cancer patients. There is potential for functional imaging to provide valuable cardiac information. The purpose of this study was to evaluate the cardiac metabolic dose-response using 18 F-deoxyglucose (FDG)-PET and to assess whether standard uptake value (SUV) changes in the heart were predictive of OS. METHODS: Fifty-one patients with esophageal cancer treated with radiation who underwent pre- and post-treatment FDG-PET scans were retrospectively evaluated. Pre- and post-treatment PET-scans were rigidly registered to the planning CT for each patient. Pre-treatment to post-treatment absolute mean SUV (SUVmean) changes in the heart were calculated to assess dose-response. A dose-response curve was generated by binning each voxel in the heart into 10 Gy dose-bins and analyzing the SUVmean changes in each dose-bin. Multivariate cox proportional hazard models were used to assess whether pre-to-post treatment cardiac SUVmean changes predicted for OS. RESULTS: The cardiac dose-response curve demonstrated a trend of increasing cardiac SUV changes as a function of dose with an average increase of 0.044 SUV for every 10 Gy dose bin. In multivariate analysis, disease stage and SUVmean change in the heart were predictive (p < 0.05) for OS. CONCLUSIONS: Changes in pre- to post-treatment cardiac SUV were predictive of OS with patients having a higher pre- to post-treatment cardiac SUV change surviving longer.

Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases.

PURPOSE: To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS: A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses. RESULTS: The median OS from first RE procedure was 10.7 months (95% confidence interval [CI], 9.4-12.7 months). Several pretreatment factors, including lower carcinoembryonic antigen (CEA; ≤20 ng/mL), lower aspartate transaminase (AST; ≤40 IU/L), neutrophil-lymphocyte ratio (NLR) <5, and absence of extrahepatic disease at baseline were associated with significantly improved OS after RE, compared with high CEA (>20 ng/mL), high AST (>40 IU/L), NLR ≥5, and extrahepatic metastases (P values of <.001, <.001, .0001, and .04, respectively). On multivariate analysis, higher CEA, higher AST, NLR ≥5, extrahepatic disease, and larger volume of liver metastases remained independently associated with risk of death (hazard ratios of 1.63, 2.06, 2.22, 1.48, and 1.02, respectively). CONCLUSIONS: The prognosis of patients with metastases from CRC is impacted by a complex set of clinical parameters. This analysis of pretreatment factors identified lower AST, lower CEA, lower NLR, and lower tumor burden (intra- or extrahepatic) to be independently associated with higher survival after hepatic RE. Optimal selection of patients with CRC liver metastases may improve survival rates after administration of yttrium-90.

Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy.

BACKGROUND: Onboard magnetic resonance imaging (OB-MRI) for daily localization and adaptive radiotherapy has been under development by several groups. However, no clinical studies have evaluated whether OB-MRI improves visualization of the target and organs at risk (OARs) compared to standard onboard computed tomography (OB-CT). This study compared visualization of patient anatomy on images acquired on the MRI-(60)Co ViewRay system to those acquired with OB-CT. MATERIAL AND METHODS: Fourteen patients enrolled on a protocol approved by the Institutional Review Board (IRB) and undergoing image-guided radiotherapy for cancer in the thorax (n = 2), pelvis (n = 6), abdomen (n = 3) or head and neck (n = 3) were imaged with OB-MRI and OB-CT. For each of the 14 patients, the OB-MRI and OB-CT datasets were displayed side-by-side and independently reviewed by three radiation oncologists. Each physician was asked to evaluate which dataset offered better visualization of the target and OARs. A quantitative contouring study was performed on two abdominal patients to assess if OB-MRI could offer improved inter-observer segmentation agreement for adaptive planning. RESULTS: In total 221 OARs and 10 targets were compared for visualization on OB-MRI and OB-CT by each of the three physicians. The majority of physicians (two or more) evaluated visualization on MRI as better for 71% of structures, worse for 10% of structures, and equivalent for 14% of structures. 5% of structures were not visible on either. Physicians agreed unanimously for 74% and in majority for > 99% of structures. Targets were better visualized on MRI in 4/10 cases, and never on OB-CT. CONCLUSION: Low-field MR provides better anatomic visualization of many radiotherapy targets and most OARs as compared to OB-CT. Further studies with OB-MRI should be pursued.

World's First Application of MR-Guidance for Radiotherapy.

Radiotherapy localization is the process by which patient treatments are aligned on a daily basis. Localization has hiistorically been accomplished using 2-dimensional x-ray images, or cone-beam CT- imaging which permits excellent visualization of bony anatomy, but suboptimal soft-tissue imaging. The Department of Radiation Oncology at Washington University recently implemented the world's first MR-Image Guided Radiation Therapy program (MR-IGRT), which utilizes a O.35T MR scanner integrated with three 6"Co heads for treatment delivery. A high-resolution volumetric MR image is acquired for each patient at the time of daily treatment setup, which allows localization based on soft-tissue anatomy, and modification to the treatment plan when required while the patient is on the treatment table. Herein, we review principles of radiotherapy localization, describe implementation of the world's first MR-IGRT program, and present future directions where MR-IGRT may be applied for patient treatments.

Tumor volume and subvolume concordance between FDG-PET/CT and diffusion-weighted MRI for squamous cell carcinoma of the cervix.

PURPOSE: To compare [(18)F]fluorodeoxyglucose (FDG)/positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) for evaluating patients with cervical cancer. We compared tumor characteristics on FDG-PET and apparent diffusion coefficient (ADC) maps on diffusion-weighted MRI (DWI) to evaluate concordance of two functional imaging techniques. MATERIALS AND METHODS: Twenty women with cervical cancer underwent pretreatment FDG-PET/CT and pelvic MRI. Images were rigidly fused by pelvic anatomy using coregistration software. Tumor contours on PET images were generated by autosegmentation of the region containing at least 40% of the maximum standardized uptake value (SUV). DWI contours were generated by manual segmentation. Tumor volume similarity was evaluated using the [PET]/[ADC] volume proportion, Dice's coefficient, and the mean SUV isothreshold at the surface of each ADC contour. Tumor subvolume similarity was evaluated with analysis of variance (ANOVA). RESULTS: The [PET]/[ADC] volume proportion was 0.88 ± 0.14. Dice's coefficient between PET and ADC tumor contours was 0.76 ± 0.06. The mean SUV isothreshold at the ADC-delineated tumor surface was 34 ± 4%. Subvolumes with increased metabolic activity on FDG-PET also had more restricted diffusion on DWI (P < 0.0001, ANOVA). CONCLUSION: Concordance of functional imaging was observed between FDG-PET and DWI for cervical cancer. Tumor subvolumes with increased metabolic activity on FDG-PET also have greater cell density by DWI.

Total Neoadjuvant Therapy in Rectal Cancer: Multi-center Comparison of Induction Chemotherapy and Long-Course Chemoradiation Versus Short-Course Radiation and Consolidative Chemotherapy.

BACKGROUND: Total neoadjuvant therapy for locally advanced rectal cancer may include induction chemotherapy and chemoradiation or short-course radiotherapy and consolidative chemotherapy. METHODS: Patients with clinical stage 2 or 3 rectal cancer who received induction chemotherapy followed by long-course chemoradiation at the University of Colorado (2016-2020) or short-course radiotherapy followed by consolidative chemotherapy at Washington University (2017-2020) were assessed. RESULTS: Eighty-four patients received induction chemotherapy and chemoradiation and 83 received short-course radiotherapy and consolidative chemotherapy. Among patients with complete re-staging evaluation, clinical complete response rates were similar, 49% (18/37) and 53% (44/83), respectively (p = 0.659). In the induction chemotherapy and chemoradiation group, 80% (n = 67) underwent surgery and 28% (n = 19) achieved a pathologic complete response. In the short-course radiotherapy and consolidative chemotherapy group, 44 (53%) patients underwent surgery and 11% (n = 5) had a pathologic complete response. Overall, a complete response was observed in 43% (n = 36) of patients who received induction chemotherapy and chemoradiation compared to 53% (n = 44) who received short-course radiotherapy and consolidative chemotherapy (p = 0.189). Perioperative outcomes were similar in patients who received induction chemotherapy and chemoradiation compared to short-course radiotherapy and consolidative chemotherapy: intraoperative complications (2% vs 7%), complete mesorectal specimen (85% vs 84%), anastomotic leak (9% vs 7%), organ/space infection (9% vs 5%), readmission (19% vs 21%), and reoperation (8% vs 9%), respectively (all p > 0.05). CONCLUSIONS: In patients with clinical stage 2 or 3 rectal cancer, total neoadjuvant therapy with either induction chemotherapy and chemoradiation or short-course radiotherapy followed by consolidative chemotherapy were associated with similar perioperative morbidity and complete response rates.

MR-Guided Radiation Therapy With Concurrent Gemcitabine/Nab-Paclitaxel Chemotherapy in Inoperable Pancreatic Cancer: A TITE-CRM Phase I Trial.

PURPOSE: Ablative radiation therapy for borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) may limit concurrent chemotherapy dosing and usually is only safely deliverable to tumors distant from gastrointestinal organs. Magnetic resonance guided radiation therapy may safely permit radiation and chemotherapy dose escalation. METHODS AND MATERIALS: We conducted a single-arm phase I study to determine the maximum tolerated dose of ablative hypofractionated radiation with full-dose gemcitabine/nab-paclitaxel in patients with BR/LA-PDAC. Patients were treated with gemcitabine/nab-paclitaxel (1000/125 mg/m2) x 1c then concurrent gemcitabine/nab-paclitaxel and radiation. Gemcitabine/nab-paclitaxel and radiation doses were escalated per time-to-event continual reassessment method from 40 to 45 Gy 25 fxs with chemotherapy (600-800/75 mg/m2) to 60 to 67.5 Gy/15 fractions and concurrent gemcitabine/nab-paclitaxel (1000/100 mg/m2). The primary endpoint was maximum tolerated dose of radiation as defined by 60-day dose limiting toxicity (DLT). DLT was treatment-related G5, G4 hematologic, or G3 gastrointestinal requiring hospitalization >3 days. Secondary endpoints included resection rates, local progression free survival (LPFS), distant metastasis free survival (DMFS), and overall survival (OS). RESULTS: Thirty patients enrolled (March 2015-February 2019), with 26 evaluable patients (2 progressed before radiation, 1 was determined ineligible for radiation during planning, 1 withdrew consent). One DLT was observed. The DLT rate was 14.1% (3.3%-24.9%) with a maximum tolerated dose of gemcitabine/nab-paclitaxel (1000/100 mg/m2) and 67.5 Gy/15 fractions. At a median follow-up of 40.6 months for living patients the median OS was 14.5 months (95% confidence interval [CI], 10.9-28.2 months). The median OS for patients with Eastern Collaborative Oncology Group 0 and carbohydrate antigen 19-9 <90 were 34.1 (95% CI, 13.6-54.1) and 43.0 (95% CI, 8.0-not reached) months, respectively. Two-year LPFS and DMFS were 85% (95% CI, 63%-94%) and 57% (95% CI, 34%-73%), respectively. CONCLUSIONS: Full-dose gemcitabine/nab-paclitaxel with ablative magnetic resonance guided radiation therapy dosing is safe in patients with BR/LA-PDAC, with promising LPFS and DMFS.

Consensus Quality Measures and Dose Constraints for Rectal Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology (ASTRO) Expert Panel.

PURPOSE: Ensuring high quality, evidence-based radiation therapy for patients with cancer is of the upmost importance. To address this need, the Veterans Affairs (VA) Radiation Oncology Program partnered with the American Society for Radiation Oncology and established the VA Radiation Oncology Quality Surveillance program. As part of this ongoing effort to provide the highest quality of care for patients with rectal cancer, a blue-ribbon panel comprised of rectal cancer experts was formed to develop clinical quality measures. METHODS AND MATERIALS: The Rectal Cancer Blue Ribbon panel developed quality, surveillance, and aspirational measures for (a) initial consultation and workup, (b) simulation, treatment planning, and treatment, and (c) follow-up. Twenty-two rectal cancer specific measures were developed (19 quality, 1 aspirational, and 2 surveillance). In addition, dose-volume histogram constraints for conventional and hypofractionated radiation therapy were created. CONCLUSIONS: The quality measures and dose-volume histogram for rectal cancer serves as a guideline to assess the quality of care for patients with rectal cancer receiving radiation therapy. These quality measures will be used for quality surveillance for veterans receiving care both inside and outside the VA system to improve the quality of care for these patients.

Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology.

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided.

Magnetic resonance biomarkers in radiation oncology: The report of AAPM Task Group 294.

PURPOSE: A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field.

Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

PURPOSE: This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer. METHODS: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal. CONCLUSIONS: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.

Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial.

PURPOSE: Short-course radiation therapy (SCRT) and nonoperative management are emerging paradigms for rectal cancer treatment. This clinical trial is the first to evaluate SCRT followed by chemotherapy as a nonoperative treatment modality. METHODS: Patients with nonmetastatic rectal adenocarcinoma were treated on the single-arm, Nonoperative Radiation Management of Adenocarcinoma of the Lower Rectum study of SCRT followed by chemotherapy. Patients received 25 Gy in 5 fractions to the pelvis followed by FOLFOX ×8 or CAPOX ×5 cycles. Patients with clinical complete response (cCR) underwent nonoperative surveillance. The primary end point was cCR at 1 year. Secondary end points included safety profile and anorectal function. RESULTS: From June 2016 to March 2019, 19 patients were treated (21% stage I, 32% stage II, and 47% stage III disease). At a median follow-up of 27.7 months for living patients, the 1-year cCR rate was 68%. Eighteen of 19 patients are alive without evidence of disease. Patients with cCR versus without had improved 2-year disease-free survival (93% vs 67%; P = .006), distant metastasis-free survival (100% vs 67%; P = .03), and overall survival (100% vs 67%; P = .03). Involved versus uninvolved circumferential resection margin on magnetic resonance imaging was associated with less initial cCR (40% vs 93%; P = .04). Anorectal function by Functional Assessment of Cancer Therapy-Colorectal cancer score at 1 year was not different than baseline. There were no severe late effects. CONCLUSIONS: Treatment with SCRT and chemotherapy resulted in high cCR rate, intact anorectal function, and no severe late effects. NCT02641691.

Anal Cancer in the Era of Dose Painted Intensity Modulated Radiation Therapy: Implications for Regional Nodal Therapy.

Since the initial development of 5-fluorouracil and mitomycin as a standard of care platform for definitive anal cancer chemoradiotherapy, multiple studies have evaluated the optimal chemotherapy regimen, and radiotherapy technique. Refinements in treatment technique have taken place during an era of improved diagnostic imaging, including incorporation of FDG-PET, with implications for a possible stage migration effect. This has introduced an opportunity to develop stage-specific recommendations for primary tumor, involved nodal, and elective nodal irradiation dose. Elective nodal irradiation remains standard given the low rates of elective nodal failure with current practice, although may be subject to evolving controversy for patients with early stage disease. In this review, development of the current standard of care for anal cancer chemoradiotherapy is reviewed in the context of modern staging and dose-painted radiotherapy treatment techniques.

Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer.

BACKGROUND: Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. METHODS: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high-dose (biologically effective dose [BED10 ] >70) and standard-dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan-Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT. RESULTS: Median follow-up was 17 months. High-dose patients (n = 24, 55%) had statistically significant improvement in 2-year OS (49% vs 30%, P = 0.03) and trended towards significance for 2-year FFLF (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). FFDF at 18 months in high-dose vs standard-dose groups was 24% vs 48%, respectively (P = 0.92). High-dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21-0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72-0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard-dose group and did not occur in the high-dose group. CONCLUSIONS: Patients treated with dose-escalated MRgRT demonstrated improved OS. Prospective evaluation of high-dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. METHODS AND MATERIALS: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. RESULTS: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. CONCLUSIONS: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

A Multi-Institutional Experience of MR-Guided Liver Stereotactic Body Radiation Therapy.

PURPOSE: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment. METHODS AND MATERIALS: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test. RESULTS: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively. CONCLUSIONS: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

Effect of novel amplitude/phase binning algorithm on commercial four-dimensional computed tomography quality.

PURPOSE: Respiratory motion is a significant source of anatomic uncertainty in radiotherapy planning and can result in errors of portal size and the subsequent radiation dose. Although four-dimensional computed tomography allows for more accurate analysis of the respiratory cycle, breathing irregularities during data acquisition can cause considerable image distortions. The aim of this study was to examine the effect of respiratory irregularities on four-dimensional computed tomography, and to evaluate a novel image reconstruction algorithm using percentile-based tagging of the respiratory cycle. METHODS AND MATERIALS: Respiratory-correlated helical computed tomography scans were acquired for 11 consecutive patients. The inspiration and expiration data sets were reconstructed using the default phase-based method, as well as a novel respiration percentile-based method with patient-specific metrics to define the ranges of the reconstruction. The image output was analyzed in a blinded fashion for the phase- and percentile-based reconstructions to determine the prevalence and severity of the image artifacts. RESULTS: The percentile-based algorithm resulted in a significant reduction in artifact severity compared with the phase-based algorithm, although the overall artifact prevalence did not differ between the two algorithms. The magnitude of differences in respiratory tag placement between the phase- and percentile-based algorithms correlated with the presence of image artifacts. CONCLUSION: The results of our study have indicated that our novel four-dimensional computed tomography reconstruction method could be useful in detecting clinically relevant image distortions that might otherwise go unnoticed and to reduce the image distortion associated with some respiratory irregularities. Additional work is necessary to assess the clinical impact on areas of possible irregular breathing.