Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete ...response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.
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•Majority of progressions (88%) after CAR T-cell therapy for non-Hodgkin lymphoma have local component.•Bridging radiotherapy achieves excellent in-field local control (86% at ...1-year).•In-field recurrences are characterized by bulky disease, SUVmax >20, elevated LDH and extranodal involvement pre-CART infusion.
Analyze the pattern of disease failure after anti-CD19-directed chimeric antigen receptor T-cell therapy (CART) for non-Hodgkin lymphoma, assess the local control rate of bridging radiotherapy (bRT) and characterize in-field recurrences.
We retrospectively reviewed 120 patients with NHL who received CART between 2018 and 2020. Baseline characteristics and treatment outcomes were compared between patients who received bRT and those who did not (noRT).
Of the 118 patients included, 14 (12%) received bRT, while 104 (88%) did not. bRT group had more localized and extranodal disease. bRT was delivered with a median dose of 20 Gy (range: 15–36) in 5 fractions (range: 3–24).
Pattern of failure analysis revealed that progression involving pre-existing sites was the predominant pattern of failure in both the bRT and noRT groups (86% and 88%, respectively). Median duration of response was 128 days (range: 25–547) for bRT group and 93 days (range: 22–965) for noRT group (p = 0.78).
In the bRT group, only 2/15 sites irradiated had infield recurrence and where characterized by bulky disease, SUVmax >20, elevated LDH at the time of CART infusion, and extranodal involvement. The bRT 1-year LC was 86%. Median duration of local response was 257 days (range: 25–630) for radiation-bridged sites.
Majority of progressions after CART infusion involve pre-existing sites. Bridging RT prior to CART provides excellent in-field local control and durable response. Patients with bulky disease, SUVmax >20, elevated LDH, and extranodal involvement are likely at higher risk of in-field recurrence after bRT and may benefit from higher curative doses of bRT.
Anti‐CD19 chimeric antigen receptor T‐cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B‐cell non‐Hodgkin lymphoma. However, CART is still limited by its ...availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life‐threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre‐existing sites of disease present pre‐CART. Radiation therapy stands as a promising peri‐CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease‐free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post‐CART disease alters the pattern of relapse and improves local recurrence‐free and progression‐free survivals. Salvage radiotherapy for relapsed post‐CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri‐CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.
Radiation can be incorporated with anti‐CD19 chimeric antigen receptor T‐cell therapy (CART) in the bridging, consolidation, and salvage setting. Prior to CAR T‐cell infusion, patients with limited pre‐CART disease are encouraged to receive comprehensive bridging radiation to a definitive dose, if possible, while those with diffuse pre‐CART disease are encouraged to receive focal low dose/short course of bridging radiation. Post CAR T‐cell infusion, patients with limited residual fluorodeoxyglucose activity/disease on Day +30 and patients with limited relapsed post‐CART disease are encouraged to receive comprehensive consolidative and salvage radiation, respectively. However, patients with diffuse relapsed post‐CART disease are likely to proceed with a subsequent line of systemic therapy +/− palliative radiation. CT, computed tomography scan; EQD2, equivalent 2 Gy dose using an alpha/beta ratio of 10; FDG, fluorodeoxyglucose.
Purpose: Subtotal skin electron beam therapy may be an option for patients with cutaneous lymphoma receiving radiation therapy to treat large areas of their skin but may benefit from sparing specific ...areas that may have had previous radiation therapy, are of specific cosmetic concern, and/or show no evidence of disease. We report here on the design, implementation, and dosimetric characteristics of a reusable and transparent customizable shield for use with the large fields used to deliver total skin electron beam therapy at extended distance with a conventional linear accelerator.
A shield was designed and manufactured consisting of acrylic blocks that can be mounted on a steel frame to allow patient-specific shielding. The dosimetry of the device was measured using radiochromic film.
The shield is easy to use and well-tolerated for patient treatment, providing minimal electron transmission through the shield with a sharp penumbra at the field edge, with no increase in x-ray dose. We report on the dosimetry of a commercial device that has been used to treat more than 30 patients to date.
The customizable shield is well suited to providing patient-specific shielding for subtotal skin electron beam therapy.
Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of ...response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage.
One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023. Patients were stratified according to total dose, dose per fraction, and stage.
The median follow-up was 301 days (IQR, 141, 767). The median age at treatment was 69.9 years (range, 29.7-96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. American Joint Committee on Cancer eighth edition stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, and 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR, 23.0-70). The median time to skin progression for all patients was 107.5 days (IQR, 67.8-233.5).
This analysis demonstrated that CTCL patients treated with low-dose radiation therapy delivered over various fractionation schemes had similar overall response rates and median time to progression.
Healthcare personnel are at high risk for exposure to influenza by direct and indirect contact, droplets and aerosols, and by aerosol generating procedures. Information on air and surface influenza ...contamination is needed to assist in developing guidance for proper prevention and control strategies. To understand the vulnerabilities of healthcare personnel, we measured influenza in the breathing zone of healthcare personnel, in air and on surfaces within a healthcare setting, and on filtering facepiece respirators worn by healthcare personnel when conducting patient care.
Thirty participants were recruited from an adult emergency department during the 2015 influenza season. Participants wore personal bioaerosol samplers for six hours of their work shift, submitted used filtering facepiece respirators and medical masks and completed questionnaires to assess frequency and types of interactions with potentially infected patients. Room air samples were collected using bioaerosol samplers, and surface swabs were collected from high-contact surfaces within the adult emergency department. Personal and room bioaerosol samples, surface swabs, and filtering facepiece respirators were analyzed for influenza A by polymerase chain reaction.
Influenza was identified in 42% (53/125) of personal bioaerosol samples, 43% (28/ 96) of room bioaerosol samples, 76% (23/30) of pooled surface samples, and 25% (3/12) of the filtering facepiece respirators analyzed. Influenza copy numbers were greater in personal bioaerosol samples (17 to 631 copies) compared to room bioaerosol samples (16 to 323 copies). Regression analysis suggested that the amount of influenza in personal samples was approximately 2.3 times the amount in room samples (Wald χ2 = 16.21, p<0.001).
Healthcare personnel may encounter increased concentrations of influenza virus when in close proximity to patients. Occupations that require contact with patients are at an increased risk for influenza exposure, which may occur throughout the influenza season. Filtering facepiece respirators may become contaminated with influenza when used during patient care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To compare the dosimetric performances of small‐spot three‐dimensional (3D) and four‐dimensional (4D) robustly optimized intensity‐modulated proton (IMPT) plans in the presence of ...uncertainties and interplay effect simultaneously for distal esophageal carcinoma.
Method and Materials
Thirteen (13) patients were selected and re‐planned with small‐spot (σ ~ 2–6 mm) 3D and 4D robust optimization in IMPT, respectively. The internal clinical target volumes (CTVhigh3d, CTVlow3d) were used in 3D robust optimization. Different CTVs (CTVhigh4d, CTVlow4d) were generated by subtracting an inner margin of the motion amplitudes in three cardinal directions from the internal CTVs and used in 4D robust optimization. All patients were prescribed the same dose to CTVs (50 GyRBE for CTVhigh3d/CTVhigh4d and 45 GyRBE for CTVlow3d/CTVlow4d). Dose–volume histogram (DVH) indices were calculated to assess plan quality. Comprehensive plan robustness evaluations that consisted of 300 perturbed scenarios (10 different motion patterns to consider irregular motion (sampled from a Gaussian distribution) and 30 different uncertainties scenarios (sampled from a 4D uniform distribution) combined), were performed to quantify robustness to uncertainties and interplay effect simultaneously. Wilcoxon signed‐rank test was used for statistical analysis.
Results
Compared to 3D robustly optimized plans, 4D robustly optimized plans had statistically improved target coverage and better sparing of lungs and heart (heart Dmean, P = 0.001; heart V30GyRBE, P = 0.001) in the nominal scenario. 4D robustly optimized plans had better robustness in target dose coverage (CTVhigh4d V100%, P = 0.002) and the protection of lungs and heart (heart Dmean, P = 0.001; heart V30GyRBE, P = 0.001) when uncertainties and interplay effect were considered simultaneously.
Conclusions
Even with small spots in IMPT, 4D robust optimization outperformed 3D robust optimization in terms of normal tissue protection and robustness to uncertainties and interplay effect simultaneously. Our findings support the use of 4D robust optimization to treat distal esophageal carcinoma with small spots in IMPT.
Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling ...shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL.
A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT.
Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% IQR=8.6, 51.5%, 36.8% IQR=20, 68% at six months, and 57.9% IQR=38.5, 87.1% at one year. Low rates of toxicities were recorded.
This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.
Introduction: Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects. Authors aimed to ...review the recent literature on cardiac dosimetry and survival/cardiac endpoints.
Areas covered: Systematic review of the literature in the past 10 years (2008-2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints. Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma.
Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause. In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death. For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors. For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines. Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival. Symptomatic pericardial effusion typically occurs with doses >40 Gy. Close follow-up and mitigation of cardiovascular risk factors are necessary after thoracic radiotherapy.
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