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BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.
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PURPOSE: Small cell lung cancer (SCLC) often metastasizes to the brain and has poor prognosis. SCLC subtypes distinguished by expressing transcriptional factors ASCL1 or NEUROD1 have been identified. This study investigates the impact of transcription factor-defined SCLC subtype on incidence and outcomes of brain metastases (BMs). METHODS: Patients with SCLC with ASCL1 (A) and NEUROD1 (N) immunohistochemical expression status were identified and classified: (1) A+/N-, (2) A+/N+, (3) A-/N+, and (4) A-/N-. Cumulative incidence competing risk analyses were used to assess incidence of CNS progression. Cox proportional hazards models were used for multivariable analyses of overall survival (OS) and CNS progression-free survival (CNS-PFS). RESULTS: Of 164 patients, most were either A+/N- or A+/N+ (n = 62, n = 63, respectively). BMs were present at diagnosis in 24 patients (15%). Among them, the 12-month cumulative incidence of subsequent CNS progression was numerically highest for A+/N- (50% [95% CI, 10.5 to 74.7]; P = .47). Among those BM-free at diagnosis, the 12-month cumulative incidence of CNS progression was numerically the highest for A+/N- (16% [95% CI, 7.5 to 27.9]) and A-/N+ (9.1% [95% CI, 0.0 to 34.8]; P = .20). Both subtypes, A+/N- and A-/N+, had worse OS compared with A+/N+ (A+/N-: hazard ratio [HR], 1.62 [95% CI, 1.01 to 2.51]; P < .05; A-/N+: HR, 3.02 [95% CI, 1.35 to 6.76]; P = .007). Excellent response rates (28, 65% CR/PR) across subtypes were seen in patients who had CNS-directed radiotherapy versus systemic therapy alone (9, 36% CR/PR). CONCLUSION: To our knowledge, this report is the first to investigate CNS-specific outcomes based on transcription factor subtypes in patients with SCLC. BM-free patients at diagnosis with A+/N- or A-/N+ subtypes had worse outcomes compared with those with transcriptional factor coexpression. Further investigation into the mechanisms and implications of SCLC subtyping on CNS-specific outcomes is warranted to ultimately guide personalized care.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/secundário , Masculino , Feminino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Prognóstico , Idoso , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Adulto , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/genética , Estudos RetrospectivosRESUMO
Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.
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BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.
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Neoplasias do Sistema Nervoso Central , Medicare , Hipofracionamento da Dose de Radiação , Humanos , Idoso , Estados Unidos , Medicare/economia , Medicare/estatística & dados numéricos , Idoso de 80 Anos ou mais , Masculino , Feminino , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/economia , Neoplasias do Sistema Nervoso Central/mortalidade , Gastos em Saúde/estatística & dados numéricosRESUMO
BACKGROUND AND PURPOSE: A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS: We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS: Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION: In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.
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Radiocirurgia , Reirradiação , Terapia de Salvação , Neoplasias da Coluna Vertebral , Humanos , Radiocirurgia/métodos , Masculino , Feminino , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Reirradiação/métodos , Terapia de Salvação/métodos , Idoso de 80 Anos ou mais , Adulto , Fracionamento da Dose de Radiação , Resultado do TratamentoRESUMO
Background and Purpose: The lack of dedicated tools in commercial planning systems currently restricts efficient review and planning for re-irradiation. The aim of this study was to develop an automated re-irradiation planning framework based on cumulative doses. Materials and Methods: We performed a retrospective study of 14 patients who received spine SBRT re-irradiation near a previously irradiated treatment site. A fully-automated workflow, DART (Dose Accumulation-based Re-irradiation Tool), was implemented within Eclipse by leveraging a combination of a dose accumulation script and a proprietary automated optimization algorithm. First, we converted the prior treatment dose into equivalent dose in 2 Gy fractions (EQD2) and mapped it to the current anatomy, utilizing deformable image registration. Subsequently, the intersection of EQD2 isodose lines with relevant organs at risk defines a series of optimization structures. During plan optimization, the residual allowable dose at a specified tissue tolerance was treated as a hard constraint. Results: All DART plans met institutional physical and cumulative constraints and passed plan checks by qualified medical physicists. DART demonstrated significant improvements in target coverage over clinical plans, with an average increase in PTV D99% and V100% of 2.3 Gy [range -0.3-7.7 Gy] and 3.4 % [range -0.4 %-7.6 %] (p < 0.01, paired t-test), respectively. Moreover, high-dose spillage (>105 %) outside the PTV was reduced by up to 7 cm3. The homogeneity index for DART plans was improved by 19 % (p < 0.001). Conclusions: DART provides a powerful framework to achieve more tailored re-irradiation plans by accounting for dose distributions from the previous treatments. The superior plan quality could improve the therapeutic ratio for re-irradiation patients.
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Purpose: Colorectal liver metastases (CLMs) represent a radioresistant histology. We aimed to investigate CLM radiation therapy (RT) outcomes and explore the association with treatment parameters. Methods and Materials: This retrospective analysis of CLM treated with RT at Memorial Sloan Kettering Cancer Center used Kaplan-Meier analysis to estimate freedom from local progression (FFLP), hepatic progression-free, progression-free, and overall survival (OS). Cox proportional hazards regression was used to evaluate association with clinical factors. Dose-response relationship was further evaluated using a mechanistic tumor control probability (TCP) model. Results: Ninety patients with 122 evaluable CLMs treated 2006 to 2019 with a variety of RT fractionation schemes with a median biologically effective dose (α/ß = 10; BED10) of 97.9 Gy (range, 43.2-187.5 Gy) were included. Median lesion size was 3.5 cm (0.7-11.8 cm). Eighty-seven patients (97%) received prior systemic therapy, and 73 patients (81%) received prior liver-directed therapy. At a median follow-up of 26.4 months, rates of FFLP and OS were 62% (95% CI, 53%-72%) and 75% (66%-84%) at 1 year and 42% (95% CI, 32%-55%) and 44% (95% CI, 34%-57%) at 2 years, respectively. BED10 below 96 Gy and receipt of ≥3 lines of chemotherapy were associated with worse FFLP (hazard ratio [HR], 2.69; 95% CI, 1.54-4.68; P < .001 and HR, 2.67; 95% CI, 1.50-4.74; P < .001, respectively) and OS (HR, 2.35; 95% CI, 1.35-4.09; P = .002 and HR, 4.70; 95% CI, 2.37-9.31; P < .001) on univariate analyses, which remained significant or marginally significant on multivariate analyses. A mechanistic Tumor Control Probability (TCP) model showed a higher 2-Gy equivalent dose needed for local control in patients who had been exposed to ≥ 3 lines of chemotherapy versus 0 to 2 (250 ± 29 vs 185 ± 77 Gy for 70% TCP). Conclusions: In a large single-institution series of heavily pretreated patients with CLM undergoing liver RT, low BED10 and multiple prior lines of systemic therapy were associated with lower local control and OS. These results support continued dose escalation efforts for patients with CLM.
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BACKGROUND AND PURPOSE: Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure. MATERIALS AND METHODS: This retrospective study included 49 patients (mean age, 63 [SD, 13] years; 29 men) with metastatic lesions treated with radiation therapy who underwent dynamic contrast-enhanced MR imaging. The median time between radiation therapy and follow-up dynamic contrast-enhanced MR imaging was 62 days. We divided patients into 2 groups: clinical success (n = 38) and failure (n = 11). Failure was defined as PET recurrence (n = 5), biopsy-proved (n = 1) recurrence, or an increase in tumor size (n = 7), while their absence defined clinical success. A Mann-Whitney U test was performed to assess differences between groups. RESULTS: The reduction in plasma volume was greater in the success group than in the failure group (-57.3% versus +88.2%, respectively; P < .001). When we assessed the success of treatment, the sensitivity of plasma volume was 91% (10 of 11; 95% CI, 82%-97%) and the specificity was 87% (33 of 38; 95% CI, 73%-94%). The sensitivity of size measurements was 82% (9 of 11; 95% CI, 67%-90%) and the specificity was 47% (18 of 38; 95% CI, 37%-67%). CONCLUSIONS: The specificity of plasma volume was higher than that of conventional size measurements, suggesting that dynamic contrast-enhanced MR imaging is a powerful tool to discriminate between treatment success and failure.
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Neoplasias Encefálicas , Neoplasias da Coluna Vertebral , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão , Meios de Contraste , Neoplasias Encefálicas/patologiaRESUMO
Chordomas are rare tumors of the embryologic spinal cord remnant. They are locally aggressive and typically managed with surgery and either adjuvant or neoadjuvant radiation therapy. However, there is great variability in practice patterns including radiation type and fractionation regimen, and limited high-level data to drive decision making. The purpose of this manuscript was to summarize the current literature specific to radiotherapy in the management of spine and sacral chordoma and to provide practice recommendations on behalf of the Spine Tumor Academy. A systematic review of the literature was performed using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) approach. Medline and Embase databases were utilized. The primary outcome measure was the rate of local control. A detailed review and interpretation of eligible studies is provided in the manuscript tables and text. Recommendations were defined as follows: (1) consensus: approved by >75% of experts; (2) predominant: approved by >50% of experts; (3) controversial: not approved by a majority of experts. Expert consensus supports dose escalation as critical in optimizing local control following radiation therapy for chordoma. In addition, comprehensive target volumes including sites of potential microscopic involvement improve local control compared with focal targets. Level I and high-quality multi-institutional data comparing treatment modalities, sequencing of radiation and surgery, and dose/fractionation schedules are needed to optimize patient outcomes in this locally aggressive malignancy.
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Purpose: The management of patients with advanced solid malignancies increasingly uses stereotactic body radiation therapy (SBRT). Advanced cancer patients are at risk for developing leptomeningeal metastasis (LM), a fatal complication of metastatic cancer. Cerebrospinal fluid (CSF) is routinely collected during computed tomography (CT) myelography for spinal SBRT planning, offering an opportunity for early LM detection by CSF cytology in the absence of radiographic LM or LM symptoms (subclinical LM). This study tested the hypothesis that early detection of tumor cells in CSF in patients undergoing spine SBRT portends a similarly poor prognosis compared with clinically overt LM. Methods and Materials: We retrospectively analyzed clinical records for 495 patients with metastatic solid tumors who underwent CT myelography for spinal SBRT planning at a single institution from 2014 to 2019. Results: Among patients planned for SBRT, 51 (10.3%) developed LM. Eight patients (1.6%) had subclinical LM. Median survival with LM was similar between patients with subclinical versus clinically evident LM (3.6 vs 3.0 months, P = .30). Patients harboring both parenchymal brain metastases and LM (29/51) demonstrated shorter survival than those with LM alone (2.4 vs 7.1 months, P = .02). Conclusions: LM remains a fatal complication of metastatic cancer. Subclinical LM detected by CSF cytology in spine SBRT patients has a similarly poor prognosis compared with standardly detected LM and warrants consideration of central nervous system-directed therapies. As aggressive local therapies are increasingly used for metastatic patients, more sensitive CSF evaluation may further identify patients with subclinical LM and should be evaluated prospectively.
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PURPOSE: This updated report on intensity modulated radiation therapy (IMRT) is part of a series of consensus-based white papers previously published by the American Society for Radiation Oncology (ASTRO) addressing patient safety. Since the first white papers were published, IMRT went from widespread use to now being the main delivery technique for many treatment sites. IMRT enables higher radiation doses to be delivered to more precise targets while minimizing the dose to uninvolved normal tissue. Due to the associated complexity, IMRT requires additional planning and safety checks before treatment begins and, therefore, quality and safety considerations for this technique remain important areas of focus. METHODS AND MATERIALS: ASTRO convened an interdisciplinary task force to assess the original IMRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology, and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus. CONCLUSIONS: This IMRT white paper primarily focuses on quality and safety processes in planning and delivery. Building on the prior version, this consensus paper incorporates revised and new guidance documents and technology updates. IMRT requires an interdisciplinary team-based approach, staffed by appropriately trained individuals as well as significant personnel resources, specialized technology, and implementation time. A comprehensive quality assurance program must be developed, using established guidance, to ensure IMRT is performed in a safe and effective manner. Patient safety in the delivery of IMRT is everyone's responsibility, and professional organizations, regulators, vendors, and end-users must work together to ensure the highest levels of safety.
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Radioterapia (Especialidade) , Radioterapia de Intensidade Modulada , Humanos , Estados Unidos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia (Especialidade)/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Segurança do Paciente , SociedadesRESUMO
BACKGROUND: In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE: To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS: This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS: One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION: Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compressão da Medula Espinal , Adulto , Humanos , Adolescente , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Estudos Retrospectivos , Compressão da Medula Espinal/genética , Compressão da Medula Espinal/radioterapia , Mutação/genética , Receptores ErbB/genéticaRESUMO
BACKGROUND: Hybrid therapy, consisting of separation surgery followed by stereotactic body radiation therapy, has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study was to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS: This retrospective study was performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid therapy for high-grade epidural spinal cord or nerve root compression from 2005 to 2020 were included. Outcome variables evaluated included patient demographics, overall survival and progression-free survival, surgical and radiation complications, and clinical-genomic correlations. RESULTS: Inclusion criteria were met by 50 patients. Progression of disease occurred in 7 (14%) patients at the index level, requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. APC exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at other spinal levels. CONCLUSIONS: Hybrid therapy in patients with CRC resulted in 86.7% local control at 2 years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.
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Neoplasias Colorretais , Radiocirurgia , Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Adulto , Humanos , Resultado do Tratamento , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Compressão da Medula Espinal/cirurgia , Estudos Retrospectivos , Radiocirurgia/métodos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgiaRESUMO
BACKGROUND: Central tendency analysis studies demonstrate that surgery provides pain relief in spinal metastatic tumors. However, they preclude patient-specific probability of treatment outcome. OBJECTIVE: To use responder analysis to study the variability of pain improvement. METHODS: In this single-center, retrospective analysis, 174 patients were studied. Logistic regression modeling was used to associate preoperative characteristics with rating the Brief Pain Inventory (BPI) worst pain item 0 to 4. Linear regression modeling was used to associate preoperative characteristics with minimal clinically important improvement (MCI) in physical functioning defined by a 1-point decrease in the BPI Interference Construct score from preoperative baseline to 6 months postoperatively. RESULTS: Patient-level analysis revealed that 60% of patients experienced an improvement in pain. At least half experienced a decrease in pain resulting in MCI in physical functioning. Cutpoint analysis revealed that 48% were responders. Increasing scores on the preoperative pain intensity BPI items, the MD Anderson Symptom Inventory (MDASI) Core Symptom Severity Construct, the MDASI Spine Tumor-Specific Construct, the presence of preoperative neurologic deficits, and postoperative complications were associated with lower probability of treatment success while increasing severity in all BPI pain items, and MDASI constructs were associated with increased probability of MCI in physical function. Significant mortality and loss to follow-up intrinsic to this patient population limit the strength of these data. CONCLUSION: Although patients with milder preoperative symptoms are likely to achieve better pain relief after surgery, patients with worse preoperative symptom also benefit from surgery with adequate pain relief with an improvement in physical function.
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Neoplasias , Manejo da Dor , Humanos , Dor , Medição da Dor , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Each year, approximately 18 million new cancer cases are diagnosed worldwide, and about half must be treated with radiotherapy. A successful treatment requires treatment planning with the customization of penetrating radiation beams to sterilize cancerous cells without harming nearby normal organs and tissues. This process currently involves extensive manual tuning of parameters by an expert planner, making it a time-consuming and labor-intensive process, with quality and immediacy of critical care dependent on the planner's expertise. To improve the speed, quality, and availability of this highly specialized care, Memorial Sloan Kettering Cancer Center developed and applied advanced optimization tools to this problem (e.g., using hierarchical constrained optimization, convex approximations, and Lagrangian methods). This resulted in both a greatly improved radiotherapy treatment planning process and the generation of reliable and consistent high-quality plans that reflect clinical priorities. These improved techniques have been the foundation of high-quality treatments and have positively impacted over 4,000 patients to date, including numerous patients in severe pain and in urgent need of treatment who might have otherwise required longer hospital stays or undergone unnecessary surgery to control the progression of their disease. We expect that the wide distribution of the system we developed will ultimately impact patient care more broadly, including in resource-constrained countries.
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Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.
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PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.
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Ensaios Clínicos como Assunto , Hispânico ou Latino , Participação do Paciente , Humanos , Análise de Séries Temporais Interrompida , Médicos , PesquisadoresRESUMO
Purpose: The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy (EBRT) to 25 Gy in 5 fractions. Methods and Materials: Data were extracted from an institutional tumor registry for patients with spinal metastasis who were treated with EBRT to 25 Gy in 5 fractions to their spinal lesion(s). Cox regression and Kaplan-Meier analyses to determine local control and overall survival (OS) were employed. Results: Seventy-five patients with 86 total treated spinal metastatic tumors were identified. The median follow-up was 7 months. The median age was 66 years. Fifty-six patients (75.7%) experienced partial or complete pain relief for a median duration of 6 months (range, 1-33). Fifty-one (59.3%) cases were planned using intensity modulated radiation therapy while 19 (22.1%) employed 3-dimensional conformal radiation therapy and 16 (18.6%) cases used nonconformal radiation technique. Greater than 90% of cases had a point dose maximum to the spinal cord/cauda equina <27.5 Gy. No patient experienced treatment-related myelopathy. The most common toxicities were fatigue (23.3%), pain flare (14.0%), and nausea (8.1%). There were no grade 3 toxicities. One-year local control was 80.6%, and 1-year OS was 38.4%. Higher Karnofsky performance status (P = .001) and radiosensitive tumor histology (P = .014) were significant predictors for better OS. Conclusions: Our single-institutional retrospective analysis of patients with spinal metastasis suggested that palliative EBRT to 25 Gy in 5 fractions is safe, with a low toxicity profile and minimal risk for myelopathy with an achievable dose maximum to the spinal cord and cauda equina ≤27 Gy (equivalent total dose in 2-Gy fractions ≤50 Gy), and it may provide durable palliation and local control in cases where stereotactic body radiation therapy may not be indicated.
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This is the first study to investigate the use of an esophageal hydrogel spacer in spine stereotactic radiosurgery. The tolerability and the dose reduction to the esophagus are predicted to reduce the incidence of high-grade toxicities, which in turn can permit dose escalation to optimize tumor control.
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Radiocirurgia , Neoplasias da Coluna Vertebral , Esôfago , Humanos , Procedimentos Neurocirúrgicos , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/patologiaRESUMO
BACKGROUND: The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing. OBJECTIVE: To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC. METHODS: A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed. SBRT was delivered as high-dose single-fraction, high-dose hypofractionated, or low-dose hypofractionated. Extent of disease, clinical and operative outcomes, and complications data were collected, and associations with overall survival (OS) and progression-free survival were determined. RESULTS: Ninety patients with mRCC with high-grade epidural spinal cord compression (ESCC grades 2 and 3) were treated. Metastases were widespread, oligometastatic, and solitary in 56%, 33%, and 11% of patients, respectively. SBRT delivered was high-dose single-fraction, high-dose hypofractionated, and low-dose hypofractionated in 24%, 56%, and 20% of patients, respectively. The 1-yr cumulative incidence of major complications was 3.4% (95% confidence interval [CI]: 0.0%-7.2%). The median follow-up was 14.2 mo for the entire cohort and 38.3 mo for survivors. The 1-yr cumulative incidence of progression was 4.6% (95% CI: 0.2%-9.0%), which translates to a local control rate of 95.4% (95% CI: 91.0%-99.8%) 1 yr after surgery. The median OS for the cohort was 14.8 mo. CONCLUSION: These data support the use of hybrid therapy as a safe and effective strategy for the treatment of renal cell spine metastases.