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1.
Adv Radiat Oncol ; 9(7): 101509, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38799108

RESUMO

Background: Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics. Methods: Patients who received SRS for ≥15 BMs in 1 to 5 fractions from 2014 to 2022 were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. The Kaplan-Meier method was used for survival analysis and log-rank test for intergroup comparisons. Results: Overall, 118 patients underwent 124 courses of LINAC-based SRS. The median number of lesions treated per course was 20 (range, 15-94). Most patients received fractionated SRS to a dose of 24 Gy in 3 fractions (81.5%). At the time of SRS, 19.4% patients had received prior WBRT, and 24.2% had received prior SRS. The rate of any grade radiation necrosis (RN) and grade ≥3 RN were 15.3% and 3.2%, respectively. When evaluating longitudinal PROMIS score trends, 25 of 31 patients had a stable/improved PROMIS score. Patients who did not receive prior brain RT had a longer median survival (7.4 months vs 4.6 months, P = .034). The 12m local control was 97.6%, and the cumulative incidence of distant intracranial failure, with death as a competing event, was 46% (95% CI, 36%, 55%). One year freedom from neurologic death, leptomeningeal disease, and salvage WBRT were 89%, 94.6%, and 84%, respectively. Conclusion: We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population. Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies comparing SRS and hippocampal avoidance WBRT approaches for these patients.

2.
J Med Virol ; 96(5): e29665, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738582

RESUMO

The cause of cancer is attributed to the uncontrolled growth and proliferation of cells resulting from genetic changes and alterations in cell behavior, a phenomenon known as epigenetics. Telomeres, protective caps on the ends of chromosomes, regulate both cellular aging and cancer formation. In most cancers, telomerase is upregulated, with the telomerase reverse transcriptase (TERT) enzyme and telomerase RNA component (TERC) RNA element contributing to the maintenance of telomere length. Additionally, it is noteworthy that two viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), utilize telomerase for their replication or persistence in infected cells. Also, TERT and TERC may play major roles in cancer not related to telomere biology. They are involved in the regulation of gene expression, signal transduction pathways, cellular metabolism, or even immune response modulation. Furthermore, the crosstalk between TERT, TERC, RNA-binding proteins, and microRNAs contributes to a greater extent to cancer biology. To understand the multifaceted roles played by TERT and TERC in cancer and viral life cycles, and then to develop effective therapeutic strategies against these diseases, are fundamental for this goal. By investigating deeply, the complicated mechanisms and relationships between TERT and TERC, scientists will open the doors to new therapies. In its analysis, the review emphasizes the significance of gaining insight into the multifaceted roles that TERT and TERC play in cancer pathogenesis, as well as their involvement in the viral life cycle for designing effective anticancer therapy approaches.


Assuntos
Neoplasias , Telomerase , Telômero , Telomerase/metabolismo , Telomerase/genética , Humanos , Neoplasias/virologia , Neoplasias/genética , Telômero/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 4/fisiologia , RNA/metabolismo , RNA/genética
3.
Cancer Biol Ther ; 25(1): 2350249, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38722731

RESUMO

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.


Assuntos
Neoplasias de Cabeça e Pescoço , Microbiota , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Feminino , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/complicações , Masculino , Microbiota/genética , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Prognóstico , Pessoa de Meia-Idade , Papillomaviridae/genética , Idoso
4.
Cancers (Basel) ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38473406

RESUMO

OBJECTIVES: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. 'QuadShot' (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. MATERIALS AND METHODS: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. RESULTS: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9-77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60-70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073-0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. CONCLUSIONS: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.

5.
Cancers (Basel) ; 16(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38539538

RESUMO

BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. CONCLUSION: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

6.
Adv Radiat Oncol ; 9(2): 101337, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405310

RESUMO

Purpose: Recent advances to preserve neurocognitive function in patients treated for brain metastases include stereotactic radiosurgery, hippocampal avoidance whole brain radiation therapy (WBRT), and memantine administration. The hippocampus, corpus callosum, fornix, and amygdala are key neurocognitive substructures with a low propensity for brain metastases. Herein, we report our preliminary experience using a "memory-avoidance" WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases. Methods and Materials: Ten consecutive patients treated with MA-WBRT on a phase 2 clinical trial were reviewed. In each patient, the hippocampi, amygdalae, corpus callosum, and fornix were contoured. Patients were not eligible for MA-WBRT if they had metastases in these substructures. A memory-avoidance region was created using a 5-mm volumetric expansion around these substructures. Hotspots were avoided in the hypothalamus and pituitary gland. Coverage of brain metastases was prioritized over memory avoidance dose constraints. Dose constraints for these avoidance structures included a D100% ≤ 9 Gy and D0.03 cm3 ≤ 16 Gy (variation acceptable to 20 Gy). LINAC-based volumetric modulated arc therapy plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the memory avoidance structure volume was 37.1 cm3 (range, 25.2-44.6 cm3), occupying 2.5% of the entire whole brain target volume. All treatment plans met the D100% dose constraint, and 8 of 10 plans met the D0.03 cm3 constraint, with priority given to tumor coverage for the remaining 2 cases. Target coverage (D98% > 25 Gy) and homogeneity (D2% ≤ 37.5 Gy) were achieved for all plans. Conclusions: Modern volumetric modulated arc therapy techniques allow for sparing of the hippocampus, amygdala, corpus callosum, and fornix with good target coverage and homogeneity. After enrollment is completed, quality of life and cognitive data will be evaluated to assess the efficacy of MA-WBRT to mitigate declines in quality of life and cognition after whole brain radiation.

7.
Cancers (Basel) ; 16(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38398079

RESUMO

BACKGROUND AND PURPOSE: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. MATERIALS AND METHODS: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0-69.96). RESULTS: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25-90%). The median dose homogeneity index was 1.07 (range: 1.03-1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0-75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. CONCLUSIONS: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

8.
Adv Radiat Oncol ; 9(3): 101424, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379893

RESUMO

Introduction: Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral body sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD. We hypothesize that VBS CSI using volumetric modulated arc therapy (VMAT) could also effectively reduce dose to vertebral bodies and surrounding organs at risk, minimizing toxicity for adult patients with LMD and comparing favorably to proton-based CSI. Methods and Materials: Consecutive patients with LMD received VMAT VBS CSI, 30 Gy in 10 fractions, as a part of a prospective registry. Full VMAT arcs for the brain fields matched to 2 spine isocenters for the upper and lower spine were created using limited posterior arcs. To further decrease the vertebral body dose, an avoid entry and exit contour was created. Acute toxicity data were collected using Common Terminology Criteria for Adverse Events v5. Results: Ten adult patients were treated in this cohort. One patient experienced grade 2 neutropenia with the remaining 9 experiencing grade 1 hematologic toxicity. Three patients experienced grade 2 gastrointestinal toxicity with the remaining 7 experiencing grade 1 nausea. No patient experienced grade 3+ toxicities in this cohort. One patient experienced a 5-day delay in systemic therapy initiation due to neutropenia; otherwise, all patients planned for systemic therapy started without delay. Conclusions: In this study, VMAT VBS CSI led to acceptable toxicity compared with patients treated with proton CSI on a phase 2 clinical trial. Given its promising early results, future prospective evaluation of the technique is warranted.

9.
Neurosurgery ; 94(4): 797-804, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902322

RESUMO

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.


Assuntos
Fraturas por Compressão , Radiocirurgia , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/etiologia , Fraturas por Compressão/epidemiologia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/patologia
10.
Int J Radiat Oncol Biol Phys ; 118(5): 1282-1293, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914144

RESUMO

PURPOSE: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. METHODS AND MATERIALS: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). CONCLUSIONS: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.


Assuntos
Cisplatino , Neoplasias de Cabeça e Pescoço , Humanos , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carboplatina , Neoplasias de Cabeça e Pescoço/radioterapia , Estudos de Coortes , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Fluoruracila
11.
Int J Radiat Oncol Biol Phys ; 118(4): 979-985, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37871886

RESUMO

PURPOSE: The current standard for meningioma treatment planning involves magnetic resonance imaging-based guidance. Somatostatin receptor ligands such as 68Ga-DOTATATE are being explored for meningioma treatment planning due to near-universal expression of somatostatin receptors 1 and 2 in meningioma tissue. We hypothesized that 68Ga-DOTATATE positron emission tomography (PET)-guided treatment management for patients with meningiomas is safe and effective and can identify which patients benefit most from adjuvant radiation therapy. METHODS AND MATERIALS: A single-institution prospective registry study was created for inclusion of patients with intracranial meningiomas who received a 68Ga-DOTATATE PET/CT to assist with radiation oncologist decision making. Patients who received a PET scan from January 1, 2018, to February 25, 2022, were eligible for inclusion. RESULTS: Of the 60 patients included, 40%, 47%, and 5% had World Health Organization grades 1, 2, and 3 meningiomas, respectively, and 8% (5 patients) had no grade assigned. According to Radiation Therapy Oncology Group 0539 criteria, 22%, 72%, and 7% were categorized as high, intermediate, and low risk, respectively. After completing their PET scans, 48 patients, 11 patients, and 1 patient proceeded with radiation therapy, observation, and redo craniotomy, respectively. The median follow-up for the entire cohort was 19.5 months. Of the 3 patients (5%) who experienced local failure between 9.2 and 28.5 months after diagnosis, 2 had PET-avid disease in their postoperative cavity and elected for observation before recurrence, and 1 high-risk patient with multifocal disease experienced local failure 2 years after a second radiation course and multiple previous recurrences. Notably, 5 patients did not have any local PET uptake and were observed; none of these patients experienced recurrence. Only 1 grade 3 toxicity was attributed to PET-guided radiation. CONCLUSIONS: This study examined one of the largest known populations of patients with intracranial meningiomas followed by physicians who used 68Ga-DOTATATE PET-guided therapy. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision making and improve patient outcomes.


Assuntos
Neoplasias Meníngeas , Meningioma , Compostos Organometálicos , Cintilografia , Humanos , Meningioma/diagnóstico por imagem , Meningioma/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia
12.
J Med Virol ; 95(12): e29293, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38054393

RESUMO

The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing among elderly (≥70 years) patients and the optimal treatment approach is not known. In this study, we aimed to determine disease and toxicity outcomes in an elderly HPV-OPSCC population primarily treated with a chemoradiation (CRT) approach. We identified 70 elderly HPV-OPSCC patients who were treated with either surgery, radiotherapy, or CRT between 2011 and 2021. Time-to-event analysis for overall survival (OS), progression-free survival (PFS), and local control (LC) were conducted using the Kaplan-Meier method. Univariate and multivariable cox regression models were used to estimate the hazard ratio associated with covariates. The median follow-up for our cohort was 43.9 months. Of the 70 elderly patients, 55 (78.6%) receive CRT and 15 (22.4%) received RT alone. Two patients underwent TORS resection. Of the 55 patients treated with CRT, the most common systemic agents were weekly carboplatin/taxol (n = 18), cetuximab (n = 17), and weekly cisplatin (n = 11). The 5-year OS, PFS, and LC were 57%, 52%, and 91%, respectively. On univariate analysis, Eastern Cooperative Oncology Group performance status and Charlson Comorbidity Index (CCI) were significant predictors of OS, while on multivariate analysis only CCI was a significant predictor of OS (p = 0.006). The rate of late peg tube dependency, osteoradionecrosis, and aspiration was 10%, 4%, and 4%, respectively. Definitive local therapy in elderly HPV-OPSCC patients is associated with excellent LC and a low rate of late toxicities. Prospective studies are needed to further stratify subgroups of elderly patients who may benefit from aggressive definitive local therapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Idoso , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos
13.
Cancers (Basel) ; 15(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38001708

RESUMO

BACKGROUND: Despite recommendations for upfront total laryngectomy (TL), many patients with cT4a laryngeal cancer (LC) instead undergo definitive chemoradiation, which is associated with inferior survival. Sociodemographic and oncologic characteristics associated with TL utilization in this population are understudied. METHODS: This retrospective cohort study utilized hospital registry data from the National Cancer Database to analyze patients diagnosed with cT4a LC from 2004 to 2017. Patients were stratified by receipt of TL, and patient and facility characteristics were compared between the two groups. Logistic regression analyses and Cox proportional hazards methodology were performed to determine variables associated with receipt of TL and with overall survival (OS), respectively. OS was estimated using the Kaplan-Meier method and compared between treatment groups using log-rank testing. TL usage over time was assessed. RESULTS: There were 11,149 patients identified. TL utilization increased from 36% in 2004 to 55% in 2017. Treatment at an academic/research program (OR 3.06) or integrated network cancer program (OR 1.50), male sex (OR 1.19), and Medicaid insurance (OR 1.31) were associated with increased likelihood of undergoing TL on multivariate analysis (MVA), whereas age > 61 (OR 0.81), Charlson-Deyo comorbidity score ≥ 3 (OR 0.74), and clinically positive regional nodes (OR 0.78 [cN1], OR 0.67 [cN2], OR 0.21 [cN3]) were associated with decreased likelihood. Those undergoing TL with post-operative radiotherapy (+/- chemotherapy) had better survival than those receiving chemoradiation (median OS 121 vs. 97 months; p = 0.003), and TL + PORT was associated with lower risk of death compared to chemoradiation on MVA (HR 0.72; p = 0.024). CONCLUSIONS: Usage of TL for cT4a LC is increasing over time but remains below 60%. Patients seeking care at academic/research centers are significantly more likely to undergo TL, highlighting the importance of decreasing barriers to accessing these centers. Increased focus should be placed on understanding and addressing the additional patient-, physician-, and system-level factors that lead to decreased utilization of surgery.

14.
Reg Anesth Pain Med ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37813527

RESUMO

INTRODUCTION: Low back pain is a significant burden to society and the lack of reliable outcome measures, combined with a prevailing inability to quantify the biopsychosocial elements implicated in the disease, impedes clinical decision-making and distorts treatment efficacy. This paper aims to validate the utility of a biopsychosocial spine platform to provide standardized wearable sensor-derived functional motion assessments to assess spine function and differentiate between healthy controls and patients. Secondarily, we explored the correlation between these motion features and subjective biopsychosocial measures. METHODS: An observational study was conducted on healthy controls (n=50) and patients with low back pain (n=50) to validate platform utility. The platform was used to conduct functional assessments along with patient-reported outcome assessments to holistically document cohort differences. Our primary outcomes were motion features; and our secondary outcomes were biopsychosocial measures (pain, function, etc). RESULTS: Our results demonstrated statistically significant differences in motion features between healthy and patient cohorts across anatomical planes. Importantly, we found velocity and acceleration in the axial plane showed the largest difference, with healthy controls having 49.7% and 55.7% higher values, respectively, than patients. In addition, we found significant correlations between motion features and biopsychosocial measures for pain, physical function and social role only. CONCLUSIONS: Our study validated the use of wearable sensor-derived functional motion metrics in differentiating healthy controls and patients. Collectively, this technology has the potential to facilitate holistic biopsychosocial evaluations to enhance spine care and improve patient outcomes. TRIAL REGISTRATION NUMBER: NCT05776771.

15.
Pract Radiat Oncol ; 13(6): 510-516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37516957

RESUMO

Carbon-fiber reinforced (CFR) polyetheretherketone hardware is an alternative to traditional metal hardware used for spinal fixation surgeries before postoperative radiation therapy for patients with spinal metastases. CFR hardware's radiolucency decreases metal artifact, improving visualization and accuracy of treatment planning. We present the first clinical use and proof of principle of CFR spinal hardware with tantalum markers used for successful tracking of intrafraction motion (IM) using Varian TrueBeam IMR (Intrafraction Motion Review) software module during postoperative spine stereotactic radiation. A 63-year-old woman with history of endometrial cancer presented with acute back pain. Imaging demonstrated pathologic T12 vertebral fracture with cord compression. She underwent T12 vertebrectomy with circumferential decompression and posterior instrumented T10-L2 fusion at our facility using CFR-polyetheretherketone hardware with tantalum screw markers followed by postoperative stereotactic body radiation therapy to 3000 cGy in 5 fractions delivered to T11-T12. Tantalum screw markers were used for IMR tracking. During irradiation, 260 kV images were acquired, and IMR software was able to identify and track markers. During the entire treatment, the IM motions were less than 3 mm. This is the first presented case of CFR spinal hardware with tantalum markers used for successful IMR tracking of IM during daily spine stereotactic treatment. Future work will be needed to improve workflow and create a spine-specific IMR protocol.


Assuntos
Radiocirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Fibra de Carbono , Tantálio/uso terapêutico , Polímeros , Polietilenoglicóis , Cetonas
16.
Surg Oncol Clin N Am ; 32(3): 569-586, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182993

RESUMO

Radiotherapy remains a cornerstone treatment of brain metastases. With new treatment advances, patients with brain metastases are living longer, and finding solutions for mitigating treatment-related neurotoxicity and improving quality of life is important. Historically, whole-brain radiation therapy (WBRT) was widely used but treatment options such as hippocampal sparing WBRT and stereotactic radiosurgery (SRS) have emerged as promising alternatives. Herein, we discuss the recent advances in radiotherapy for brain metastases including the sparing of critical structures that may improve long-term neurocognitive outcomes (eg, hippocampus, fornix) that may improve long-term neurocognitive outcome, evidence supporting preoperative and fractionated-SRS, and treatment strategies for managing radiation necrosis.


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Qualidade de Vida , Irradiação Craniana , Radiocirurgia/efeitos adversos , Hipocampo/patologia
17.
Adv Radiat Oncol ; 8(4): 101201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008254

RESUMO

Purpose: Increasing evidence suggests that ultra-high-dose-rate (UHDR) radiation could result in similar tumor control as conventional (CONV) radiation therapy (RT) while reducing toxicity to surrounding healthy tissues. Considering that radiation toxicity to gonadal tissues can cause hormone disturbances and infertility in young patients with cancer, the purpose of this study was to assess the possible role of UHDR-RT in reducing toxicity to healthy gonads in mice compared with CONV-RT. Methods and Materials: Radiation was delivered to the abdomen or pelvis of female (8 or 16 Gy) and male (5 Gy) C57BL/6J mice, respectively, at conventional (∼0.4 Gy/s) or ultrahigh (>100 Gy/s) dose rates using an IntraOp Mobetron linear accelerator. Organ weights along with histopathology and immunostaining of irradiated gonads were used to compare toxicity between radiation modalities. Results: CONV-RT and UHDR-RT induced a similar decrease in uterine weights at both studied doses (∼50% of controls), which indicated similarly reduced ovarian follicular activity. Histologically, ovaries of CONV- and UHDR-irradiated mice exhibited a comparable lack of follicles. Weights of CONV- and UHDR-irradiated testes were reduced to ∼30% of controls, and the percentage of degenerate seminiferous tubules was also similar between radiation modalities (∼80% above controls). Pairwise comparisons of all quantitative data indicated statistical significance between irradiated (CONV or UHDR) and control groups (from P ≤ .01 to P ≤ .0001) but not between radiation modalities. Conclusions: The data presented here suggest that the short-term effects of UHDR-RT on the mouse gonads are comparable to those of CONV-RT.

18.
Oral Oncol ; 141: 106402, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37094500

RESUMO

OBJECTIVES: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer. MATERIALS AND METHODS: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3). RESULTS: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %. CONCLUSION: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Neoplasias da Língua , Humanos , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Prognóstico , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/patologia , Neoplasias Bucais/patologia , Margens de Excisão
19.
Neurosurgery ; 93(2): 320-329, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36861971

RESUMO

BACKGROUND: Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control. OBJECTIVE: To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT). METHOD: A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level. RESULTS: Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort ( P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization ( P < .001). CONCLUSION: Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.


Assuntos
Radiocirurgia , Neoplasias da Coluna Vertebral , Humanos , Descompressão Cirúrgica , Terapia Neoadjuvante , Dor/cirurgia , Estudos Prospectivos , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/radioterapia , Resultado do Tratamento
20.
Phys Imaging Radiat Oncol ; 25: 100422, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36875327

RESUMO

Background and purpose: Mitigation of intrafraction motion (IM) is valuable in stereotactic radiotherapy (SRT) radiotherapy where submillimeter accuracy is desired. The purpose of this study was to investigate the application of triggered kilovoltage (kV) imaging for spine SRT patients with hardware by correlating kV imaging with patient motion and summarizing implications of tolerance for IM based on calculated dose. Materials and methods: Ten plans (33 fractions) were studied, correlating kV imaging during treatment with pre- and post-treatment cone beam computed tomography (CBCT). Images were taken at 20-degree gantry angle intervals during the arc-based treatment. The contour of the hardware with a 1 mm expansion was displayed at the treatment console to manually pause treatment delivery if the hardware was visually detected outside the contour. The treatment CBCTs were compared using retrospective image registration to assess the validity of contour-based method for pausing treatment. Finally, plans were generated to estimate dose volume objective differences in case of 1 mm deviation. Results: When kV imaging during treatment was used with the 1 mm contour, 100 % of the post-treatment CBCTs reported consistent results. One patient in the cohort exhibited motion greater than 1 mm during treatment which allowed intervention and re-setup during treatment. The average translational motion was 0.35 mm. Treatment plan comparison at 1 mm deviation showed little differences in calculated dose for the target and cord. Conclusions: Utilizing kV imaging during treatment is an effective method of assessing IM for SRT spine patients with hardware without increasing treatment time.

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