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Radiation therapy (RT) is utilized as a bridging strategy for patients with aggressive B-cell lymphoma prior to CD19-targeted chimeric antigen receptor (CAR T)-cell therapy. RT has been shown to provide local control without exacerbating the toxicities associated with subsequent CAR T-cell infusion. However, a consensus on the optimal radiation dose and fractionation for bridging purposes has yet to be established. We present a case of a patient with relapsed aggressive B-cell lymphoma who underwent bridging adaptive RT on a CT-linac prior to receiving CAR T-cell therapy. At month 6 post-CAR T infusion, the patient demonstrates no signs of disease recurrence or relapse, nor any unexpected toxicities attributable to the combined treatment. This underscores the feasibility and success of this innovative approach in treating lymphoma patients undergoing CAR T-cell therapy.
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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: In general, Multiple Myeloma (MM) patients are treated with systemic therapy including chemotherapy. Radiation therapy can have an important supportive role in the palliative management of MM-related osteolytic lesions. Our study aims to investigate the degree of radiation-induced remineralization in MM patients to gain a better understanding of its potential impact on bone mineral density and, consequently, fracture prevention. Our primary outcome measure was percent change in bone mineral density measured in Hounsfield Units (Δ% HU) between pre- and post-radiation measurements, compared to non-targeted vertebrae. METHODS: We included 119 patients with MM who underwent radiotherapy of the spine between January 2010 and June 2021 and who had a CT scan of the spine at baseline and between 3-24 months after radiation. A linear mixed effect model tested any differences in remineralization rate per month (ßdifference) between targeted and non-targeted vertebrae. RESULTS: Analyses of CT scans yielded 565 unique vertebrae (366 targeted and 199 non-targeted vertebrae). In both targeted and non-targeted vertebrae, there was an increase in bone density per month (ßoverall = .04; P = .002) with the largest effect being between 9-18 months post-radiation. Radiation did not cause a greater increase in bone density per month compared to non-targeted vertebrae (ßdifference = .67; P = .118). CONCLUSION: Our results demonstrate that following radiation, bone density increased over time for both targeted and non-targeted vertebrae. However, no conclusive evidence was found that targeted vertebrae have a higher remineralization rate than non-targeted vertebrae in patients with MM.
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Linfoma de Célula do Manto , Receptores de Antígenos Quiméricos , Adulto , Humanos , Linfoma de Célula do Manto/radioterapia , Linfoma de Célula do Manto/etiologia , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos de Linfócitos T/genética , Antígenos CD19 , Terapia Baseada em Transplante de Células e TecidosRESUMO
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for patients with relapsed/refractory large B-cell lymphoma (LBCL). However, data available concerning the impact of the prognostic value of quantitative 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) parameters on the CAR T-related outcomes and toxicities are limited. Therefore, we aimed to evaluate the predictive value of pre- and post-CAR T metabolic parameters on survival and toxicities following CAR T-cell therapy. Fifty-nine patients with PET/CT scans done pre-and post-CAR T infusion were retrospectively identified and analyzed in a single institution database of LBCL patients treated with commercial CD19-targeted CAR T-cell therapy. The median follow-up was 10.7 months [interquartile range (IQR): 2.6-25.5 months]. The overall response (complete response-CR and partial response) and CR rates post-CAR T were 76% (n = 45) and 53% (n = 31), respectively. On univariate analysis, low pre-CAR T total lesion glycolysis (TLG) and metabolic tumor volume (MTV) predicted improved overall response post-CAR T (OR = 4.7, p = 0.01, OR = 9.5, p = 0.03, respectively) and CR post-CAR T (OR = 12.4, p = 0.0004, OR = 10.9, p = 0.0001, respectively). High TLG pre-CAR T was correlated with cytokine release syndrome (CRS, OR = 3.25, p = 0.04). High MTV pre-CAR T was correlated with developing immune effector cell neurotoxicity syndrome (ICANS) events (OR = 4.3, p = 0.01), and high SUV pre-CAR T was associated with grade 3-4 neurological events (OR = 12, p = 0.01). High MTV/TLG/SUVmax post-CAR T were significantly associated with inferior Overall survival (OS). On multivariate analysis, high TLG pre-CAR T (HR = 2.4, p = 0.03), age ≥60 (HR = 2.7, p = 0.03), and bulky disease (≥5 cm) at the time of apheresis (HR = 2.5, p = 0.02) were identified to be independent prognostic factors for inferior PFS. High MTV post-CAR T was identified as the most prognostic factor associated with inferior OS.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Fluordesoxiglucose F18/metabolismo , Prognóstico , Terapia Baseada em Transplante de Células e TecidosRESUMO
BACKGROUND CONTEXT: Conventional external beam radiation therapy (cEBRT) is used in multiple myeloma (MM) to treat severe pain, spinal cord compression, and disease-related bone disease. However, radiation may be associated with an increased risk of vertebral compression fractures (VCFs), which could substantially impair survival and quality of life. Additionally, the use of the Spinal Instability Neoplastic Score (SINS) in MM is debated in MM. PURPOSE: To determine the incidence of VCFs after cEBRT in patients with MM and to assess the applicability of the SINS score in the prediction of VCFs in MM. STUDY DESIGN: Retrospective multicenter cohort study. PATIENT SAMPLE: MM patients with spinal myeloma lesions who underwent cEBRT between January 2010 and December 2021. OUTCOME MEASURES: Frequency of new or progressed VCFs and subdistribution hazard ratios for potentially associated factors. METHODS: Patient and treatment characteristics were manually collected from the patients' electronic medical records. Computed tomography (CT) scans from before and up to 3 years after the start of radiation were used to score radiographic variables at baseline and at follow-up. Multivariable Fine and Gray competing risk analyses were performed to evaluate the diagnostic value of the SINS score to predict the postradiation VCF rate. RESULTS: A total of 127 patients with 427 eligible radiated vertebrae were included in this study. The mean age at radiation was 64 years, and 66.1% of them were male. At the start of radiation, 57 patients (44.9%) had at least one VCF. There were 89 preexisting VCFs (18.4% of 483 vertebrae). Overall, 39 of 127 patients (30.7%) reported new fractures (number of vertebrae (n)=12) or showed progression of existing fractures (n=36). This number represented 11.2% of all radiated vertebrae. Five of the 39 (12.8%) patients with new or worsened VCFs received an unplanned secondary treatment (augmentation [n=2] or open surgery [n=3]) within 3 years. Both the total SINS score (SHR 1.77; 95% confidence interval (CI) 1.54-2.03; p<.001) and categorical SINS score (SHR 10.83; 95% CI 4.20-27.94; p<.001) showed an independent association with higher rates of new or progressed VCFs in adjusted analyses. The use of bisphosphonates was independently associated with a lower rate of new or progressed VCFs (SHR 0.47 [95% CI 0.24-0.92; p=.027]). CONCLUSIONS: This study demonstrated that new or progressed VCFs occurred in 30.7% of patients within 3 years, in a total of 11.2% of vertebrae. The SINS score was found to be independently associated with the development or progression of VCFs and could thus be applied in MM for fracture prediction and possibly prevention.
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Fraturas por Compressão , Mieloma Múltiplo , Fraturas da Coluna Vertebral , Humanos , Masculino , Feminino , 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/epidemiologia , Fraturas por Compressão/etiologia , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/radioterapia , Mieloma Múltiplo/complicações , Estudos de Coortes , Qualidade de Vida , Coluna Vertebral , Estudos RetrospectivosRESUMO
Radiation therapy (RT) may play an important role prior to and following BCMA-targeted CAR T-cell therapy in multiple myeloma (MM). We report a series of 13 patients: 5 patients received bridging RT pre-CAR T, 4 patients received salvage RT post-CAR T failure, and 4 patients received both. There was no worsening of CAR-T- or RT-related toxicities. The RT in-field local control rate was 100%, with a median follow-up after each RT course of 7.3 months. RT as a bridging and salvage strategy is safe, feasible, and offers excellent local control in MM patients treated with CAR T-cell therapy.
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Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/radioterapia , Mieloma Múltiplo/tratamento farmacológico , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/uso terapêutico , Antígeno de Maturação de Linfócitos B/uso terapêuticoRESUMO
Introduction: Approximately 1.6 million people in the US identify as transgender, many of whom undergo gender-affirming medical or surgical therapies. While transgender individuals are diagnosed with cancer at similar rates as those who are cisgender, the impacts of radiation therapy on outcomes of gender-affirming care in transgender, nonbinary, and gender-expansive people with cancer are understudied. We report on the experiences and outcomes of transgender and gender-expansive patients receiving radiation therapy for cancer treatment. Methods: This study is a multi-institutional retrospective review of patients evaluated from 2005-2019 identified as transgender or gender-expansive in the medical record and treated with radiation therapy. Results: We identified 23 patients who received radiation to 32 sites, including 12 (38%) to the brain, head, or neck, 8 (25%) to the thorax, and 7 (22%) to the pelvis. Seventeen patients (74%) received gender-affirming hormone therapy and 13 patients (57%) underwent gender-affirming surgery. Four patients had pelvic radiation before or after gender-affirming pelvic surgery, including two trans women who had pelvic radiation after vaginoplasty. Four patients had radiation to the chest or thorax and gender-affirming chest or breast surgery, including two trans men with breast cancer. Two pediatric patients developed hypopituitarism and hypogonadism secondary to radiation therapy and, as adults, changed their hormone replacement therapy to affirm their transgender identities. Discussion: Transgender people with cancer undergo radiation therapy for a wide range of cancers. Understanding their prior gender-affirming medical or surgical treatments and future gender affirmation goals may identify important considerations for their oncologic care.
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Pathways leading to osteoarthritis (OA) are diverse depending on the risk factors involved; thus, developing OA therapeutics has been challenging. Here we report that nuclear protein-1 (Nupr1), a stress-inducible protein/transcription factor, is activated by pathways associated with obesity and aging in chondrocytes. Treatment of human chondrocytes with free fatty acids (palmitate and oleate; a model for high-fat diet/obesity) induced PERK signaling and increased expression of caspase-3, TRB3, and Nupr1. On the other hand, treatment of chondrocytes with menadione (oxidative stress inducer) induced oxidation of IRE1, activated antioxidant response (higher Nrf2 expression), and increased expression of Nupr1 and matrix metalloproteinases. Experimental OA was induced by destabilization of the medial meniscus (DMM) in the knee joints of Nupr1+/+ and Nupr1-/- mice. Loss of Nupr1 expression reduced the severity of cartilage lesions in this model. Together, our findings suggest that Nupr1 is a common factor activated by signaling pathways activated by obesity (ER stress) and age (oxidative stress) and a potential drug target for OA resulting from various risk factors.
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Cartilagem Articular , Osteoartrite , Animais , Humanos , Camundongos , Envelhecimento , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Proteínas Nucleares/metabolismo , Obesidade/metabolismo , Osteoartrite/metabolismoRESUMO
The NCCN Guidelines for Survivorship are intended to help healthcare professionals address the complex and varied needs of cancer survivors. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for psychosocial and physical problems resulting from adult-onset cancer and its treatment; recommendations to help promote healthy behaviors and immunizations in survivors; and a framework for care coordination. These NCCN Guidelines Insights summarize recent guideline updates and panel discussions pertaining to sleep disorders, fatigue, and cognitive function in cancer survivors.
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Sobreviventes de Câncer , Neoplasias , Adulto , Humanos , Sobrevivência , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/psicologia , Sobreviventes , Sobreviventes de Câncer/psicologia , ImunizaçãoRESUMO
Despite the success of CD19-targeted chimeric antigen receptor (CAR T)-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), there is a need for effective salvage strategies post-CAR T-cell therapy failure. We conducted a multi-institutional retrospective study of patients who relapsed following CAR T-cell therapy (axicabtagene ciloleucel [axi-cel] or tisagenlecleucel [tisa-cel]) and received salvage therapies (radiation therapy [RT] alone, systemic therapy alone, or combined modality therapy [CMT]). A total of 120 patients with post-CAR T relapsed LBCL received salvage therapies (RT alone, 25 patients; CMT, 15 patients; systemic therapy alone, 80 patients). The median follow-up from CAR T-cell infusion was 10.2 months (interquartile range, 5.2-20.9 months). Failure occurred in previously involved sites prior to CAR T-cell therapy in 78% of patients (n=93). A total of 93 sites were irradiated in 54 patients who received any salvage RT post-CAR T failure. The median dose/fractionation were 30 Gy (range, 4-50.4 Gy) and 10 fractions (range, 1-28 fractions). The 1-year local control rate for the 81 assessable sites was 84%. On univariate analysis, the median overall survival (OS) from the start date of RT was significantly higher among patients who received comprehensive RT versus focal RT (19.1 months vs. 3.0 months; P=<0.001). Twenty-three of 29 patients who received comprehensive RT had limited-stage disease. Among these, there was no difference in median OS among the patients who received RT alone versus those who received RT followed by additional therapies (log-rank P=0.2). On multivariate survival analysis, achieving PR or CR post-CAR T (hazard ratio =0.5; 95% confidence interval: 0.3-0.9; P=0.01) was independently associated with superior OS. Our findings suggest that RT can provide local control for LBCL relapsed post-CAR T-cell therapy, particularly in patients with limited-stage relapsed disease treated with comprehensive RT.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/radioterapia , Análise de Sobrevida , Antígenos CD19RESUMO
PURPOSE: Impending and actual pathologic fractures secondary to metastatic bone disease, lymphoma, or multiple myeloma often require intramedullary fixation followed by radiation therapy. Because of carbon's low atomic number, there are reduced computed tomography (CT) imaging artifacts and dose perturbation when planning postoperative radiation for carbon fiber (CF) rods. Herein, we characterize the dosimetric properties of CF implants compared with titanium alloy (TA) for proton and photon. METHODS AND MATERIALS: TA and CF samples were acquired from an implant manufacturer. Material characteristics were evaluated by CT scans with and without metal artifact reduction (MAR). Relative stopping power (RSP) was determined from the range pull-back of each sample in a 20-cm range proton beam. Photon transmission measurements were made in a solid water phantom and compared with the modeled dosimetry from the RayStation planning system. RESULTS: CF caused no visible CT artifacts, and MAR was not necessary for Hounsfield unit (HU) determination (median, 364 HU) or contouring, whereas TA (median, 3071 HU) caused substantial artifacts, which were improved, but not eliminated by MAR. The proton RSP was measured as 3.204 for TA and 1.414 for CF. For 6 MV photons, the measured transmission was 89.3% for TA and 98% for CF. CF RSP calculation and transmission from CT HU showed a physical density overestimate compared with measurements, which would cause a slight, but acceptable, dose uncertainty (<10% proton range or 1% photon transmission). CONCLUSIONS: With a density similar to bone, CF implants did not cause imaging artifacts and minimal dose perturbation compared with TA. Although the CF proton RSP is underestimated and the photon attenuation is overestimated by the HU, both effects are relatively small and may be most easily accounted for by planning with a 2-mm expansion around organs at risk beyond or in close proximity to the implant.
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Terapia com Prótons , Titânio , Humanos , Fibra de Carbono , Prótons , Tomografia Computadorizada por Raios X/métodos , Radiometria/métodos , Imagens de Fantasmas , Artefatos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
The Centers for Disease Control and Prevention (CDC) developed and implemented the v-safe after vaccination health checker (v-safe) to monitor COVID-19 vaccine safety and as an active surveillance supplement to existing CDC vaccine safety monitoring programs. V-safe allows persons who received COVID-19 vaccines to report on post-vaccination experiences and how symptoms affected their health at daily, weekly, and monthly timepoints after vaccination. Text message reminders are sent linking to Internet-based health check-in surveys. Surveys include questions to identify v-safe participants who may be eligible to enroll in a separate pregnancy registry activity that evaluates maternal and infant outcomes in those pregnant at the time of vaccination or receiving vaccine in the periconception period. We describe the development of and enhancements to v-safe, data management, promotion and communication to vaccination sites and partners, publications, strengths and limitations, and implications for future systems. We also describe enrollment in v-safe over time and demographics of persons participating in v-safe during the first year of operation (December 14, 2020 - December 13, 2021). During this time, 9,342,582 persons submitted 131,543,087 v-safe surveys. The majority of participants were female (62.3 %) and non-Hispanic White (61.2 %); median age was 49.0 years. Most participants reported receiving an mRNA COVID-19 vaccine as their first recorded dose (95.0 %). V-safe contributed to CDC's vaccine safety assessments for FDA-authorized COVID-19 vaccines by enabling near real-time reporting of reactogenicity once the COVID-19 vaccination program began in the community, encouraging reports to the Vaccine Adverse Event Reporting System and facilitating enrollment in a large post-vaccination pregnancy registry. Given that v-safe is an integral component of the most comprehensive safety monitoring program in U.S. history, we believe that this approach has promise as a potential application for future pandemic response activities as well as rollout of novel vaccines in a non-pandemic context.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Gravidez , Centers for Disease Control and Prevention, U.S. , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Pandemias/prevenção & controle , Estados Unidos , Vacinação/efeitos adversos , VacinasRESUMO
PURPOSE: To systematically review all dosimetric studies investigating the impact of deep inspiration breath hold (DIBH) compared with free breathing (FB) in mediastinal lymphoma patients treated with proton therapy as compared to IMRT (intensity-modulated radiation therapy)-DIBH. MATERIALS AND METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database to identify studies of mediastinal lymphoma patients with dosimetric comparisons of proton-FB and/or proton-DIBH with IMRT-DIBH. Parameters included mean heart (MHD), lung (MLD), and breast (MBD) doses, among other parameters. Case reports were excluded. Absolute differences in mean dosesâ¯>â¯1â¯Gy between comparators were considered to be clinically meaningful. RESULTS: As of April 2021, eight studies fit these criteria (nâ¯=â¯8), with the following comparisons: proton-FB vs IMRT-DIBH (nâ¯=â¯5), proton-DIBH vs proton-FB (nâ¯=â¯5), and proton-DIBH vs IMRT-DIBH (nâ¯=â¯8). When comparing proton-FB with IMRT-DIBH in 5 studies, MHD was reduced with proton-FB in 2 studies, was similar (<1 Gy difference) in 2 studies, and increased in 1 study. On the other hand, MLD and MBD were reduced with proton-FB in 3 and 4 studies, respectively. When comparing proton-DIBH with proton-FB, MHD and MLD were reduced with proton DIBH in 4 and 3 studies, respectively, while MBD remained similar. Compared with IMRT-DIBH in 8 studies, proton-DIBH reduced the MHD in 7 studies and was similar in 1 study. Furthermore, MLD and MBD were reduced with proton-DIBH in 8 and 6 studies respectively. Integral dose was similar between proton-FB and proton-DIBH, and both were substantially lower than IMRT-DIBH. CONCLUSION: Accounting for heart, lung, breast, and integral dose, proton therapy (FB or DIBH) was superior to IMRT-DIBH. Proton-DIBH can lower dose to the lungs and heart even further compared with proton-FB, depending on disease location in the mediastinum, and organ-sparing and target coverage priorities.
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Linfoma , Neoplasias do Mediastino , Terapia com Prótons , Neoplasias Unilaterais da Mama , Humanos , Suspensão da Respiração , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador , Prótons , Neoplasias do Mediastino/radioterapia , Coração , Dosagem Radioterapêutica , Neoplasias Unilaterais da Mama/radioterapiaRESUMO
The NCCN Guidelines for Survivorship are intended to help healthcare professionals who work with survivors to ensure that the survivors' complex and varied needs are addressed. The NCCN Guidelines provide screening, evaluation, and treatment recommendations for the consequences of adult-onset cancer and its treatment; recommendations to help promote physical activity, weight management, and immunizations in survivors; and a framework for care coordination. This article summarizes updates to the NCCN Guidelines pertaining to preventive health for cancer survivors, including recommendations about alcohol consumption and vaccinations.