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Objective.To develop and validate a dose-of-the-day (DOTD) treatment plan verification procedure for liver and pancreas cancer patients treated with an magnetic resonance (MR)-Linac system.Approach.DOTD was implemented as an automated process that uses 3D datasets collected during treatment delivery. Particularly, the DOTD pipeline's input included the adapt-to-shape (ATS) plan-i.e. 3D-MR dataset acquired at beginning of online session, anatomical contours, dose distribution-and 3D-MR dataset acquired during beam-on (BON). The DOTD automated analysis included (a) ATS-to-BON image intensity-based deformable image registration (DIR), (b) ATS-to-BON contours mapping via DIR, (c) BON-to-ATS contours copying through rigid registration, (d) determining ATS-to-BON dosimetric differences, and (e) PDF report generation. The DIR process was validated by two expert reviewers. ATS-plans were recomputed on BON datasets to assess dose differences. DOTD analysis was performed retrospectively for 75 treatment fractions (12-liver and 5-pancreas patients).Main results.The accuracy of DOTD process relied on DIR and mapped contours quality. Most DIR-generated contours (99.6%) were clinically acceptable. DICE correlated with depreciation of DIR-based region of interest mapping process. The ATS-BON plan difference was found negligible (<1%). The duodenum and large bowel exhibited highest variations, 24% and 39% from fractional values, for 5-fraction liver and pancreas. For liver 1-fraction, a 62% variation was observed for duodenum.Significance.The DOTD methodology provides an automated approach to quantify 3D dosimetric differences between online plans and their delivery. This analysis offers promise as a valuable tool for plan quality assessment and decision-making in the verification stage of the online workflow.
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Imagen por Resonancia Magnética , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/métodos , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagen , Dosis de Radiación , Factores de Tiempo , Neoplasias Gastrointestinales/radioterapia , Neoplasias Gastrointestinales/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagenRESUMEN
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 65·5 years (IQR 58·3-71·8), 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.
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Dolor en Cáncer , Plexo Celíaco , Manejo del Dolor , Radiocirugia , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Radiocirugia/efectos adversos , Manejo del Dolor/métodos , Dolor en Cáncer/etiología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Dimensión del Dolor , Anciano de 80 o más Años , Resultado del Tratamiento , Adulto , Dolor Abdominal/etiologíaRESUMEN
Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment. Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics. Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%. Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac.
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â¢Stereotactic body radiotherapy (SBRT) is a safe and effective locoregional therapy for inoperable patients with HCC.â¢SBRT compares favorably with other local therapies in terms of local control, survival, morbidity, and cost-effectiveness.â¢SBRT should be considered and discussed in multidisciplinary management of appropriate HCC patients.â¢Advances in SBRT and novel combinations with systemic therapy may further widen the therapeutic index in HCC.
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In 2023, the Common Sense Oncology (CSO) movement was launched with the goal of recalibrating cancer care to focus on outcomes that matter to patients. We extend the three CSO pillars - evidence generation, interpretation and communication - to radiation oncology and advocate for better evidence demonstrating the value of our modality.
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Neoplasias , Oncología por Radiación , Humanos , Neoplasias/radioterapia , RadioterapiaRESUMEN
PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Consenso , Neoplasias Hepáticas/radioterapia , Instituciones de Atención Ambulatoria , CarbonoRESUMEN
The role of radiotherapy in the management of primary and metastatic liver malignancies has expanded in recent years due to advances such as IGRT and SBRT. MRI-guided radiotherapy (MRgRT) has arisen as an excellent option for the management of hepatocellular carcinoma, cholangiocarcinoma, and liver metastases due to the ability to combine improved hepatic imaging with conformal treatment planning paradigms like adaptive radiotherapy and advanced motion management techniques. Herein we review the data for MRgRT for liver malignancies, as well as describe workflow and technical considerations for the 2 commercially available MRgRT delivery platforms.
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Neoplasias Hepáticas , Radioterapia Guiada por Imagen , Humanos , Radioterapia Guiada por Imagen/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Imagen por Resonancia Magnética/métodosRESUMEN
PURPOSE: We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation. PATIENTS AND METHODS: Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board-approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting. RESULTS: A total of 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% [95% confidence interval (CI, 2.4-13.4)]. Twenty-one percent of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control [HR, 0.69; 95% CI (0.25-1.91); P = 0.48] and decreased toxicity [OR, 0.26; 95% CI (0.07-0.99); P = 0.048] compared with conventional SBRT. CONCLUSIONS: Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Dosificación Radioterapéutica , Radiocirugia/efectos adversos , Estudios RetrospectivosRESUMEN
PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.
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Hepatocellular carcinoma (HCC) is the most common liver tumor, with a continually rising incidence. The curative treatment for HCC is surgical resection or liver transplantation; however, only a small portion of patients are eligible due to local tumor burden or underlying liver dysfunction. Most HCC patients receive nonsurgical liver-directed therapies (LDTs), including thermal ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT). Stereotactic ablative body radiation (SABR) is a specific type of EBRT that can precisely deliver a high dose of radiation to ablate tumor cells using a small number of treatments (or fractions, typically 5 or less). With onboard MRI imaging, MRI-guided SABR can improve therapeutic dose while minimizing normal tissue exposure. In the current review, we discuss different LDTs and compare them with EBRT, specifically SABR. The emerging MRI-guided adaptive radiation therapy has been reviewed, highlighting its advantages and potential role in HCC management.
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BACKGROUND AND PURPOSE: Unexpected liver volume reductions occurred during trials of liver SBRT and concurrent sorafenib. The aims were to accumulate liver SBRT doses to assess the impact of these anatomic variations on normal tissue dose parameters and toxicity. MATERIALS AND METHODS: Thirty-two patients with hepatocellular carcinoma (HCC) or metastases treated on trials of liver SBRT (30-57 Gy, 6 fractions) and concurrent sorafenib were analyzed. SBRT doses were accumulated using biomechanical deformable registration of daily cone-beam CT. Dose deviations (accumulated-planned) for normal tissues were compared for patients with liver volume reductions > 100 cc versus stable volumes, and accumulated doses were reported for three patients with grade 3-5 luminal gastrointestinal toxicities. RESULTS: Patients with reduced (N = 12) liver volumes had larger mean deviations of 0.4-1.3 Gy in normal tissues, versus -0.2-0.4 Gy for stable cases (N = 20), P > 0.05. Deviations > 5% of the prescribed dose occurred in both groups. Two HCC patients with toxicities to small and large bowel had liver volume reductions and deviations to the maximum dose of 4% (accumulated 36.9 Gy) and 3% (accumulated 33.4 Gy) to these organs respectively. Another HCC patient with a toxicity of unknown location plus tumor rupture, had stable liver volumes and deviations to luminal organs of -6% to 4.5% (accumulated < 30.5 Gy). CONCLUSION: Liver volume reductions during SBRT and concurrent sorafenib were associated with larger increases in accumulated dose to normal tissues versus stable liver volumes. These dosimetric changes may have further contributed to toxicities in HCC patients who have higher baseline risks.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Humanos , Sorafenib/efectos adversos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Radiocirugia/efectos adversos , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Canadá , Quimioembolización Terapéutica/métodosRESUMEN
BACKGROUND: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). RESULTS: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. CONCLUSION: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.
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Neoplasias del Ano , Dermatitis , Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Fluorouracilo/efectos adversos , Mitomicina/efectos adversos , Diarrea/etiología , Neoplasias del Ano/tratamiento farmacológico , Dermatitis/tratamiento farmacológico , Dermatitis/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: NRG Oncology trial RTOG 1112 is a randomized phase 3 study of sorafenib with or without stereotactic body radiation therapy for locally advanced hepatocellular carcinoma. Image guided radiation therapy (IGRT) credentialing is essential for this study because of the high doses, respiratory motion, and variety of delivery technologies. This analysis presents the IGRT credentialing experience. METHODS AND MATERIALS: Credentialing of volumetric IGRT requires submission of planning and localization images, planning structures, and resulting IGRT shifts for a patient treated according to the study requirements. A study reviewer uses these data to repeat the registrations and compare to the actual clinical registrations. Agreement within 5 mm was considered acceptable for credentialing. RESULTS: Volumetric images of 130 fractions from 42 institutions between June 2013 and January 2018 were reviewed. The median agreement between clinical registrations and study reviewer was 3 mm, with 95% of all fractions within 5 mm. A subanalysis identified a statistically significant difference between the use of low-contrast soft tissue and high-contrast surrogates (eg, implanted fiducial markers, surgical clips, metallic stents) for registration. Soft tissue and high-contrast surrogate registrations both agreed within 3 mm in 50% of fractions. However, soft tissue registrations exceeded 10 mm in 3% of fractions, while no high-contrast surrogate registrations exceeded 5 mm. CONCLUSIONS: The RTOG 1112 credentialing experience suggests that most institutions perform liver IGRT with sufficient accuracy to deliver stereotactic body radiation therapy safely, as assessed by expert reviewers. Both soft tissue and high-contrast surrogates appear adequate for consistent registration in most instances; however, some disagreements were observed when using soft-tissue registration targets. The use of high-contrast surrogates appears to reduce the small risk of substantial geographic miss owing to mis-registration in liver IGRT.
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Radiocirugia , Radioterapia Guiada por Imagen , Humanos , Radioterapia Guiada por Imagen/métodos , Habilitación Profesional , Marcadores Fiduciales , Hígado , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
BACKGROUND: Family physicians' (FPs) long-term relationships with their oncology patients position them ideally to provide primary palliative care, yet their involvement is variable. We examined perceptions of FP involvement among outpatients receiving palliative care at a cancer center and identified factors associated with this involvement. METHODS: Patients with advanced cancer attending an oncology palliative care clinic (OPCC) completed a 25-item survey. Eligible patients had seen an FP within 5 years. Binary multivariable logistic regression analyses were conducted to identify factors associated with (1) having seen an FP for palliative care within 6 months, and (2) having a scheduled/planned FP appointment. RESULTS: Of 258 patients, 35.2% (89/253) had seen an FP for palliative care within the preceding 6 months, and 51.2% (130/254) had a scheduled/planned FP appointment. Shorter travel time to FP (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.48-0.93, p = 0.02), the FP having a 24-h support service (OR = 1.96, 95% CI = 1.02-3.76, p = 0.04), and a positive perception of FP's care (OR = 1.05, 95% CI = 1.01-1.09, p = 0.01) were associated with having seen the FP for palliative care. English as a first language (OR = 2.90, 95% CI = 1.04-8.11, p = 0.04) and greater ease contacting FP after hours (OR = 1.33, 95% CI = 1.08-1.64, p = 0.008) were positively associated, and female sex of patient (OR = 0.51, 95% CI = 0.30-0.87, p = 0.01) and travel time to FP (OR = 0.66, 95% CI = 0.47-0.93, p = 0.02) negatively associated with having a scheduled/planned FP appointment. Number of OPCC visits was not associated with either outcome. CONCLUSION: Most patients had not seen an FP for palliative care. Accessibility, availability, and equity are important factors to consider when planning interventions to encourage and facilitate access to FPs for palliative care.
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Neoplasias , Médicos de Familia , Humanos , Femenino , Cuidados Paliativos , Oncología Médica , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
Background: Imbalanced outcome is one of common characteristics of oncology datasets. Current machine learning approaches have limitation in learning from such datasets. Here, we propose to resolve this problem by utilizing a human-in-the-loop (HITL) approach, which we hypothesize will also lead to more accurate and explainable outcome prediction models. Methods: A total of 119 HCC patients with 163 tumors were used in the study. 81 patients with 104 tumors from the University of Michigan Hospital treated with SBRT were considered as a discovery dataset for radiation outcomes model building. The external testing dataset included 59 tumors from 38 patients with SBRT from Princess Margaret Hospital. In the discovery dataset, 100 tumors from 77 patients had local control (LC) (96% of 104 tumors) and 23 patients had at least one grade increment of ALBI (I-ALBI) during six-month follow up (28% of 81 patients). Each patient had a total of 110 features, where 15 or 20 features were identified by physicians as expert knowledge features (EKFs) for LC or I-ALBI prediction. We proposed a HITL based Bayesian network (HITL-BN) approach to enhance the capability of selecting important features from imbalanced data in terms of accuracy and explainability through humans' participation by integrating feature importance ranking and Markov blanket algorithms. A pure data-driven Bayesian network (PD-BN) method was applied to the same discovery dataset of HCC patients as a benchmark. Results: In the training and testing phases, the areas under receiver operating characteristic curves of the HITL-BN models for LC or I-ALBI prediction during SBRT are 0.85 (95% confidence interval: 0.75-0.95) or 0.89 (0.81-0.95) and 0.77 or 0.78, respectively. They significantly outperformed the during-treatment PD-BN model in predicting LC or I-ALBI based on the discovery cross-validation and testing datasets from the Delong tests. Conclusion: By allowing the human expert to be part of the model building process, the HITL-BN approach yielded significantly improved accuracy as well as better explainability when dealing with imbalanced outcomes in the prediction of post-SBRT treatment response of HCC patients when compared to the PD-BN method.
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Pancreatic ductal adenocarcinoma (PDAC) remains a therapeutic challenge in clinical oncology. Surgery is the only potentially curative treatment. However, the majority of PDAC patients present with locally advanced/unresectable or metastatic disease, where palliative multiagent chemotherapy is the first-line treatment with the therapeutic intent to delay progression and prolong survival. For locally advanced/unresectable pancreatic cancer patients who are treated with chemotherapy, consolidative radiotherapy in the form concurrent chemoradiation or stereotactic ablative radiotherapy improves locoregional control and pain/symptom control. To improve clinical outcomes of PDAC patients, there is a dire need for discoveries that will shed more light on the pathophysiology of the disease and lead to the development of more efficacious treatment strategies. Inflammatory cytokines are known to play a role in mediating tumor progression, chemoresistance, and radioresistance in PDAC. A PubMed search on published articles related to radiotherapy, inflammatory cytokines, and pancreatic cancer patients in the English language was performed. This article primarily focuses on reviewing the clinical literature that examines the association of inflammatory cytokines with clinical outcomes and the effects of radiotherapy on inflammatory cytokines in PDAC patients.
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Outcome modeling plays an important role in personalizing radiotherapy and finds applications in specialized areas such as adaptive radiotherapy. Conventional outcome models that are based on a simplified understanding of radiobiological effects or empirical fitting often only consider dosimetric information. However, it is recognized that response to radiotherapy is multi-factorial and involves a complex interaction of radiation therapy, patient and treatment factors, and the tumor microenvironment. Recently, large pools of patient-specific biological and imaging data have become available with the development of advanced biotechnology and multi-modality imaging techniques. Given this complexity, artificial intelligence (AI) and machine learning (ML) are valuable to make sense of such a plethora of heterogeneous data and to aid clinicians in their decision-making process. The role of AI/ML has been demonstrated in many retrospective studies and more recently prospective evidence has been emerging as well to support AI/ML for personalized and precision radiotherapy.
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Inteligencia Artificial , Oncología por Radiación , Humanos , Aprendizaje Automático , Estudios Prospectivos , Oncología por Radiación/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: To describe the long-term outcomes of a 5-fraction normal tissue tolerance adapted strategy for the management of oligometastases (OM). METHODS AND MATERIALS: Patients with histologically confirmed solid tumors, ≤5 extracranial metastases, suitable for a definitive approach for all metastatic lesions, at least one lesion suitable for Stereotactic Body Radiotherapy (SBRT), Eastern Coooperative Oncology Group Performance Status ≤2 were eligible. Treatment intervention was a 5-fraction (25-55 Gy) normal tissue adapted dosing strategy. The primary outcome was cumulative local progression rate at 12 months. RESULTS: Between March 2013 and January 2018, 137 patients started SBRT. Median follow-up was 35.7 months. In addition, 107 (78%) patients had a solitary OM. The mean planning target volume D95 was 39.6 (standard deviation, 8.8; biological effective dose using an alpha/beta ratio of 10, 70.8) Gy. Mean planning target volume D95 was highest for lung lesions (48.7 [standard deviation, 4.7]; biological effective dose using an alpha/beta ratio of 10, 96.1) Gy but was <40 Gy for all other anatomic sites. Two grade 3 toxicities (gastrointestinal bleed) were observed with stomach D0.05 30.3 Gy and 30.4 Gy. The cumulative local progression rate at 12 of 36 months was 16.1% (95% CI, 10-22) and 38.3% (95% CI 30-46.7); overall survival was 90% and 37%, and progression free survival was 58% and 19%, respectively. Mean symptom burden (Edmonton Symptom Assessment Total Score) worsened in patients with progressive disease (+8.8) at 12 months and was paralleled by changes in mean European Organization for Research and Treatment Quality of Life Core Questionnaire Summary Score and Global Health Quality of Life Score. Systemic therapy was initiated in 55% of patients at an average of 12.7 (standard deviation 12.4) months. CONCLUSIONS: If long-term progression free survival is the primary goal of therapy, SBRT for OM achieved this in <20% of patients attributable to a high risk of distant failure. Favorable local progression free survival is accompanied by preservation of quality of life, avoidance of symptom progression and reduced need of antineoplastic therapies at 12 months. Information on symptom burden, quality of life, as well as pattern of antineoplastic therapy use after progressive disease is useful to support conversations between patients, families, and health care providers. Strategies to improve patient selection and reduce distant progression rate remain a priority for further study.