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13 result(s) for "Johnstone, Candice"
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Stereotactic body radiotherapy for metastatic sarcoma to the lung: adding to the arsenal of local therapy
Introduction Conventional treatment of pulmonary metastatic sarcoma primarily involves surgery, with systemic therapy added in select patients. However, broader applications of radiation therapy techniques have prompted investigation into the use of stereotactic body radiotherapy (SBRT) for treatment of metastatic sarcoma, an attractive non-invasive intervention with potential for lower rates of adverse events than surgery. Current data are limited to retrospective analyses. This study analyzed 2-year local control and overall survival and adverse events in patients prospectively treated with SBRT to pulmonary sarcoma metastases. Methods Patients prospectively treated with SBRT to the lung for biopsy-proven metastatic sarcoma at a single institution from 2010 to 2022 were included. SBRT dose/fractionation treatment regimens ranged from 34 to 54 Gy in 1–10 fractions using photons. Local recurrence, local progression-free survival (LPFS) and overall survival (OS) were calculated from the end of SBRT. Univariable analysis (UVA) was performed using the log-rank test. Multivariable analysis (MVA) was performed using the Cox proportional hazards model. Adverse events due to SBRT were graded based on the Common Terminology Criteria for Adverse Events, version 4.0. Results Eighteen patients with metastatic sarcoma were treated to 26 pulmonary metastases. The median local progression-free survival was not met. The median overall survival was not met. The local control rate at 2 years was 96%. 2-year LPFS was 95.5% and OS was 74%. Three patients (16.7%) developed grade 1 adverse events from SBRT. There were no adverse events attributed to radiation that were grade 2 or higher. Conclusion We report prospective data demonstrating that SBRT for sarcoma pulmonary metastases affords a high rate of local control and low toxicity, consistent with prior sarcoma SBRT retrospective data. This study adds to the wealth of information on SBRT in a radioresistant tumor. Though largely limited to retrospective reviews, current data indicate high rates of local control with favorable toxicity profiles. Therefore, SBRT for pulmonary sarcoma metastases may be considered for properly selected patients.
Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET
Background Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. Methods This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. Discussion This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. Trial registration Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.
Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall
Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS. Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used. Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p<0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p=0.08). Preoperative radiation (RT) (p=0.01) and use of any RT for UE (p=0.003) led to improved PFS. On MVA, preoperative RT (p=0.04) and performance status (p=0.01) led to improved PFS. Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.
Definitive Chemoradiation Associated with Improved Survival Outcomes in Patients with Synchronous Oligometastatic Esophageal Cancer
Background: The study of oligometastatic esophageal cancer (EC) is relatively new. Preliminary data suggests that more aggressive treatment regimens in select patients may improve survival rates in oligometastatic EC. However, the consensus recommends palliative treatment. We hypothesized that oligometastatic esophageal cancer patients treated with a definitive approach (chemoradiotherapy [CRT]) would have improved overall survival (OS) compared to those treated with a purely palliative intent and historical controls. Methods: Patients diagnosed with synchronous oligometastatic (any histology, ≤5 metastatic foci) esophageal cancer treated in a single academic hospital were retrospectively analyzed and divided into definitive and palliative treatment groups. Definitive CRT was defined as radiation therapy to the primary site with ≥40 Gy and ≥2 cycles of chemotherapy. Results: Of 78 Stage IVB (AJCC 8th ed.) patients, 36 met the pre-specified oligometastatic definition. Of these, 19 received definitive CRT, and 17 received palliative treatment. With a median follow-up of 16.5 months (Range: 2.3–95.0 months), median OS for definitive CRT and palliative groups were 90.2 and 8.1 months (p < 0.01), translating into 5-year OS of 50.5% (95%CI: 32.0–79.8%) vs. 7.5% (95%CI: 1.7–48.9%), respectively. Conclusions: Oligometastatic EC patients treated with definitive CRT benefited from that approach with survival rates (50.5%) that vastly exceeded historical standards of 5% at 5 years for metastatic EC. Oligometastatic EC patients treated with definitive CRT had significantly improved OS compared to those treated with palliative-only intent within our cohort. Notably, definitively treated patients were generally younger and with better performance status versus those palliatively treated. Further prospective evaluation of definitive CRT for oligometastatic EC is warranted.
Impact of Neoadjuvant Induction Chemotherapy Prior to Chemoradiation on Survival and Surgical Outcomes in Real-World Esophageal Adenocarcinoma Cohort
Background/objectives: Improvements in esophageal adenocarcinoma (EAC) treatment have reduced mortality. While chemoradiation before surgery was previously a standard of care, updated guidelines recommend peri-operative chemotherapy without chemoradiation. Continued investigation into optimal non-operative treatment paradigms for patients who defer surgery or are not candidates for surgery and certain chemotherapy regimens is needed. The impact of induction chemotherapy prior to chemoradiation on survival and surgical outcomes remains unclear. This study assessed survival and surgical outcomes in a real-world cohort of EAC patients receiving induction chemotherapy before chemoradiation. Methods: This single-institution, IRB-approved, retrospective cohort study included patients with newly diagnosed stage II-IVb (oligometastatic for IVb) EAC who received definitive chemoradiation (radiation ≥ 40 Gy and two cycles of chemotherapy) +/− esophagectomy from 2007 to 2022. Patients receiving induction chemotherapy were compared to those who did not. Endpoints included survival and surgical outcomes. Results: A total of 141 EAC patients received definitive chemoradiation; 83 received induction chemotherapy before chemoradiation. Patients receiving induction chemotherapy were younger (p < 0.01) with slightly lower performance status (p = 0.27) and presented at a more advanced stage (p < 0.001). Median OS was 3.5 years in the induction chemotherapy group compared to 2.2 years (p = 0.10). There was no difference in pathologic complete response (p = 0.81), esophagectomy frequency (p = 0.87), or surgical downstaging between treatment groups (p = 0.84). Conclusions: In this real-world, single-institutional patient cohort investigating induction chemotherapy prior to chemoradiation in EAC, patients receiving induction chemotherapy did well but did not have a statistically significant improvement in survival outcomes or surgical outcomes. This study showed that significant numbers of real-world patients may not receive esophagectomy. Thus, prospective, randomized clinical trials are warranted to better delineate the efficacy and selection of patients for induction chemotherapy when non-operative approaches are favored.
The influence of breast cancer subtype on survival after palliative radiation for osseous metastases
Background Among patients with osseous metastases, breast cancer (BC) patients typically have the best prognosis. In the palliative setting, BC is often considered a single disease, but based on receptor status there are four distinct subtypes: luminal A (LA), luminal B (LB), triple negative (TN), and HER2‐enriched (HER2). We hypothesize that survival and palliative outcomes following palliative RT for osseous metastases correlate with breast cancer subtype (BCS). Methods We identified 3,895 BC patients with known receptor status who received palliative RT for osseous metastases from 2004–2013 in the National Cancer Database. Kaplan–Meier method with log‐rank testing and univariate/multivariate Cox‐regression was used to identify survival factors. Incomplete radiation courses, 30‐day mortality rate, and percentage remaining life spent receiving RT (PRLSRT) were calculated. Results Subtypes were 54% LA, 33% LB, 8% TN, and 5% HER2 with median survival of 34.1, 28.2, 5.3, and 15.7 months, respectively (p < 0.001). Overall 82% of patients received ≥10 fractions. Although BCS had limited effect on radiation regimens, TN received nearly twice as many single or hypofractionated (≤5 fractions) treatments, but the overall rate of these fraction schemes was low at 3.7 and 13.7%, respectively. Compared to LA and LB, TN and HER2 patients had worse palliative outcomes; higher rates of incomplete courses at 18.8% and 18.3% versus 12.7%–14.4%; higher 30‐day mortality post‐radiotherapy at 21.5% and 16.0% versus 6.3%–7.9%, and higher median PRLSRT of 7.7% and 3.7% versus 2.2%–2.4% for LA and LB. On multivariate analysis, BCS was associated with overall survival with TN (HR 3.7), HER2 (HR 1.75), and LB (HR 1.28) fairing worse than LA (p < 0.001). Conclusions BCS correlated with survival and palliative outcome following radiation to osseous metastases. BCS should be considered by physicians when planning palliative RT to maximize quality‐of‐life, avoid unnecessary treatment, and ensure palliative benefits. This study demonstrates the impact of breast cancer subtype on survival and palliative outcomes after palliative radiation for osseous metastases. Patients with triple negative and HER2‐enriched subtypes had shorter survival, higher 30 and 90‐day mortality, had more incomplete treatments, spent more of their remaining lives receiving radiation treatments, but received similar radiation regimens compared to Luminal A and Luminal B patients. This correlation should be considered when selecting palliative radiotherapy regimens to avoid unnecessary treatment and improve palliative outcomes for poor‐prognosis patients.
Samarium-153-ethylene diamine tetramethylene phosphonate, a beta-emitting bone-targeted radiopharmaceutical, useful for patients with osteoblastic bone metastases
Bone metastases are prevalent among cancer patients and frequently cause significant morbidity. Oncology providers must mitigate complications associated with bone metastases while limiting therapy-related adverse effects and their impact on quality of life. Multiple treatment modalities, including chemotherapy, surgery, external beam radiation therapy, and radioisotopes, among others, have been recommended and utilized for palliative treatment of bone metastases. Radioisotopes such as samarium-153 are commonly used in the setting of multifocal bone metastases due to their systemic distribution, affinity for osteoblastic lesions, acceptable toxicity profile, and convenience of administration. This review focuses on samarium-153, first defining its radiobiologic and pharmacokinetic properties before describing many clinical trials that support its use as a safe and effective tool in the palliation of patients with bone metastases.
The Radiobiology of Palliative Radiation Oncology
The biologic basis for the effects of radiation on living cells dictates the potential benefits and limitations of radiotherapy for the palliation of end‐of‐life cancer symptoms. A basic understanding of radiobiology is needed to assess the most appropriate palliative radiotherapy fractionation schemes. Radiotherapy either directly or indirectly causes DNA strand breaks that can lead to cell death. Radiobiology principles that influence cell kill include DNA repair, tissue reoxygenation, cell cycle reassortment, and repopulation. The principles of radiobiology explain that the acute effects of treatment depend upon total dose while late effects depend upon both total dose and dose per fraction. Therefore, the choice of palliative radiotherapy fractionation scheme requires a rigorous review of the available data as well as an educated estimate of patient prognosis.
Colon and Rectal Cancer
Colorectal cancer is a major health issue for men and women. While colon and rectal cancers have much in common, there are also important distinguishing features. Multidisciplinary surgical, radiation, and chemotherapeutic approaches continue to improve outcomes.
Participatory research with a rural Aboriginal community controlled health organisation: Lessons learned using the consider statement
Context: In Australia, Aboriginal Community Controlled Health Organisations (ACCHOs) are geographically proximal to where Aboriginal and Torres Strait Islander People reside and are valued for providing holistic and culturally safe primary health care. Partnering with ACCHOs in research is appropriate for redressing health inequities experienced by Aboriginal and Torres Strait Islander People, which includes a high burden of chronic disease. Historically, some approaches to Aboriginal and Torres Strait Islander health research have been unethical. Greater accountability in the research process, transparency in reporting, and use of culturally appropriate research methodologies are key recommendations to improving the ethical integrity of research. The need for strengthening the reporting of health research involving Aboriginal and Torres Strait Islander People and Indigenous peoples globally led to the development of the CONSolIDated critERia for strengthening the reporting of health research involving Indigenous peoples (CONSIDER statement), which is a synthesis of international ethical guidelines. This project report uses the CONSIDER statement to critically reflect on participatory research undertaken in partnership with an ACCHO in the rural context and to identify lessons of value for future research. Issue: By using the CONSIDER statement as a tool for critical reflection, it was identified that processes used to establish a research partnership with an ACCHO were key to setting the research agenda, including identifying ethical issues, the needs of local Aboriginal and Torres Strait Islander People, and expectations from the research. The participation of Aboriginal community members throughout the entire research process was not only methodologically important but was also ethically appropriate. Research activities in this project included opportunities for Aboriginal community members to directly share their perspectives and experiences and develop local solutions to issues affecting them. Outcomes included evidence to support future funding applications, community-derived priorities that assisted with government reporting, and locally identified methods for addressing chronic disease management. Key to this was building the research capacity and capability of local Aboriginal community members, which also reflected the ethical principles of reciprocity and equity. This also provided opportunities for non-Indigenous researchers to learn from local Aboriginal community members and develop skills in culturally appropriate research. Lessons learned: Using the CONSIDER statement was beneficial in enabling researchers to critically reflect on a participatory research project undertaken in partnership with a rural ACCHO. Researchers identified that participatory approaches can be used to generate research of relevance to local Aboriginal community members and their ACCHOs, and to support health service reporting, and future funding applications. Research timelines and activities needed to be flexible and adaptable, to allow for staff turnover and unforeseen events of cultural significance. Similarly, it is important for researchers to be receptive to change and open to learning. Although research partnerships are established on trust and mutual respect, it is recommended that greater formal provisions are required to protect the intellectual property of Aboriginal and Torres Strait Islander communities involved in research. These lessons are likely to be transferrable to other settings and are of value to researchers seeking to partner with ACCHOs in research.