Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
3.
Cancers (Basel) ; 16(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254893

RESUMO

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth's penalized likelihood approach was used to account for the low event rates. Fisher's exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors.

4.
Surg Endosc ; 38(1): 136-147, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935921

RESUMO

BACKGROUND: Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. METHOD: The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection and standard radiation dose (45 Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. RESULTS: We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2 months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63 years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). CONCLUSION: In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.


Assuntos
Neoplasias Gástricas , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Terapia Combinada , Quimioterapia Adjuvante , Quimiorradioterapia , Gastrectomia , Estadiamento de Neoplasias
5.
Ann Surg Oncol ; 31(3): 1898-1905, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37968411

RESUMO

OBJECTIVE: Postoperative pancreatic fistula is a potentially devastating complication after pancreatoduodenectomy (PD). The purpose of this study was to identify features on preoperative computed tomography (CT) imaging that correlate with an increased risk of postoperative pancreatic fistula (POPF). METHODS: Patients who underwent PD at our high-volume pancreatic surgery center from 2019 to 2021 were included if CT imaging was available within 8 weeks of surgical intervention. Pancreatic neck thickness (PNT), abdominal wall thickness (AWT), and intra-abdominal distance from pancreas to peritoneum (PTP) were measured by two board-certified radiologists who were blinded to the clinical outcomes. Radiographic measurements, as well as preoperative patient characteristics and intraoperative data, were assessed with univariate and multivariable analysis (MVA) to determine risk for clinically relevant POPF (CR-POPF, grades B and C). RESULTS: A total of 204 patients met inclusion criteria. Median PTP was 5.8 cm, AWT 1.9 cm, and PNT 1.3 cm. CR-POPF occurred in 33 of 204 (16.2%) patients. MVA revealed PTP > 5.8 cm (odds ratio [OR] 2.86, p = 0.023), PNT > 1.3 cm (OR 2.43, p = 0.047), soft pancreas consistency (OR 3.47, p = 0.012), and pancreatic duct size ≤ 3.0 mm (OR 4.55, p = 0.01) as independent risk factors for CR-POPF after PD. AWT and obesity were not associated with increased risk of CR-POPF. Patients with PTP > 5.8 cm or PNT > 1.3 cm were significantly more likely to suffer a major complication after PD (39.6% vs. 22.3% and 40% vs. 22.1%, p < 0.008). CONCLUSIONS: Patients with a thick pancreatic neck and increased intra-abdominal girth have a heightened risk of CR-POPF after pancreatoduodenectomy, and they experience more serious postoperative complications. We defined a simple CT scan-based measurement tool to identify patients at increased risk of CR-POPF.


Assuntos
Fístula Pancreática , Pancreaticoduodenectomia , Humanos , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pâncreas/cirurgia , Ductos Pancreáticos/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
7.
Cancers (Basel) ; 15(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37835467

RESUMO

In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations-EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022. The mutational statuses were determined from brain tissue biopsies, and survival analyses were conducted. Results from 95 patients (average age: 65.8 ± 10.6) showed that while 6.3% had anaplastic lymphoma kinase (ALK)-rearranged mutations and 20.0% had epidermal growth factor receptor (EGFR)-amplified mutations-with 9.5% receiving second-line therapies-these mutations did not significantly correlate with overall survival. Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.

8.
JAMA Netw Open ; 6(8): e2327637, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37552479

RESUMO

Importance: Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. Objective: To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. Design, Setting, and Participants: A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Exposures: Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Main Outcomes and Measures: Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. Results: A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. Conclusions and Relevance: In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Idoso , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco
9.
Oncologist ; 28(12): 1072-1078, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37285524

RESUMO

BACKGROUND: In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI. MATERIALS AND METHODS: In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox's proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models. RESULTS: The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB. CONCLUSION: Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE's may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Pacientes
10.
Mod Pathol ; 36(9): 100235, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37270155

RESUMO

Medullary thyroid carcinoma (MTC), an uncommon C cell thyroid malignancy, accounts for a disproportionate number of thyroid cancer deaths. To predict MTC clinical behavior, the recent international MTC grading system (IMTCGS) was published combining features from the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital grading systems that incorporates mitotic count, necrosis, and Ki67 proliferative index (Ki67PI). The IMTCGS appears promising, but independent validation data are limited. Here, we applied the IMTCGS to our institutional MTC cohort and assessed its ability to predict clinical outcomes. Our cohort comprised 87 MTCs (30 germline and 57 sporadic). Slides for each case were reviewed by 2 pathologists and histologic features recorded. Ki67 immunostaining was performed on all cases. Each MTC was graded with the IMTCGS based on tumor necrosis, Ki67PI, and mitotic count. Cox regression analysis was performed to assess the impact of various clinical and pathological data on disease outcomes, including overall survival (OS), disease-free survival, disease-specific survival (DSS), and distant metastasis-free survival. In our MTC cohort, 18.4% (n = 16/87) were IMTCGS high grade. IMTCGS grade was strongly prognostic for OS, disease-free survival, DSS, and distant metastasis-free survival on univariate analysis and multivariable analysis in both the entire MTC cohort and in the sporadic subset. Among the individual IMTCGS parameters, while all 3 were associated with poorer survival outcomes on univariate analysis, necrosis had the strongest association with all survival parameters on multivariable analysis, whereas Ki67PI or mitotic count was associated only with OS and DSS. This retrospective study independently demonstrates that the IMTCGS is valid for grading MTCs. Our findings support incorporating IMTCGS into routine pathology practice. IMTCGS grading may help clinicians to better predict the prognosis of MTC. Future studies may shed light on how MTC grading should impact treatment protocols.


Assuntos
Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Antígeno Ki-67 , Neoplasias da Glândula Tireoide/patologia , Carcinoma Neuroendócrino/patologia , Prognóstico , Necrose
11.
J Surg Oncol ; 128(2): 231-241, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37036147

RESUMO

BACKGROUND: Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus regarding the optimal multimodal treatment strategy. METHOD: We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan-Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed. RESULTS: We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort. CONCLUSION: OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Cárdia/patologia , Terapia Combinada , Quimioterapia Adjuvante , Quimiorradioterapia , Estudos Retrospectivos
12.
J Surg Oncol ; 128(2): 242-253, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37114465

RESUMO

BACKGROUND: Patients with resectable noncardia gastric cancer may be subjected to perioperative chemotherapy (PEC), postoperative chemoradiation (POCR), or postoperative chemotherapy (POC). We analyzed these treatment strategies to determine optimal therapy based on nodal status. METHOD: The National Cancer Database was used to identify patients with resected noncardia gastric cancer (2004-2016). Patients were stratified based on clinical nodal status-negative (cLN-), positive (cLN+) and pathological nodal status (pLN-, pLN+). In cLN- patients who underwent upfront resection and were upstaged to pLN+, POC, and POCR were compared. Overall survival (OS) with PEC, POCR, and POC were compared in cLN- and cLN+. RESULTS: We identified 6142 patients (cLN-: 3831; cLN+: 2311). In cLN- patients who underwent upfront resection (N = 3423), 69% were upstaged to pLN+ disease (N = 2499; POCR = 1796, POC = 703). On MVA, POCR was associated with significantly improved OS when compared to POC (hazard ratio [HR]: 0.75; p < 0.001). In patients with cLN- disease (PEC = 408; POCR = 2439; POC = 984), PEC(HR: 0.77; p = 0.01) and POCR(HR: 0.81; p < 0.001) were associated with improved OS compared with POC. In cLN+ group (PEC = 452; POCR = 1284; POC = 575), POCR was associated with improved OS compared with POC (HR: 0.81; p < 0.01), and trend towards improved OS was noted when PEC(HR: 0.83; p = 0.055) was compared with POC. CONCLUSION: Postoperative chemoradiation may be the preferred treatment strategy over postoperative chemotherapy in non-cardia gastric cancer patients who receive upfront resection and are upstaged from clinically node negative to pathologically node positive disease.


Assuntos
Neoplasias Gástricas , Humanos , Quimiorradioterapia , Terapia Combinada , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
13.
Int J Radiat Oncol Biol Phys ; 116(2): 404-412, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36889515

RESUMO

PURPOSE: We evaluated our institutional experience to assess potential racial inequities in insurance coverage for proton therapy in patients with head and neck (HN) cancer. METHODS AND MATERIALS: We examined the demographics of 1519 patients with HN cancer seen in consultation at our HN multidisciplinary clinic (HN MDC) and 805 patients for whom a proton insurance authorization was sought (PAS) from January 2020 to June 2022. The prospects for proton therapy insurance authorization were prospectively noted based on each patient's ICD-10 (International Classification of Diseases, 10th Revision) diagnosis code and their specific insurance plan. Proton-unfavorable (PU) insurance were those plans whose policy describes proton beam therapy as "experimental" or "not medically necessary" for the given diagnosis. RESULTS: For patients seen in our HN MDC, Black, Indigenous, and people of color (BIPOC) were significantly more likely to have PU insurance than non-Hispanic White (NHW) patients (24.9% vs 18.4%, P = .005). In multivariable analysis including race, average income of residence ZIP code, and Medicare eligibility age, BIPOC patients had an odds ratio of 1.25 for PU insurance (P = .041). In the PAS cohort, while there was no difference in the percentage of patients receiving insurance approval for proton therapy between NHW and BIPOC populations (88% vs 88.2%, P = .80), for patients with PU insurance, the median time to determination was significantly longer (median, 15.5 days), and the median time to start any radiation of any modality was longer (46 vs 35 days, P = .08). Compared with NHW patients, the median time from consultation to start of radiation therapy was longer for BIPOC patients (37 vs 43 days, P = .01). CONCLUSIONS: BIPOC patients were significantly more likely to have insurance plans unfavorable to proton therapy coverage. These PU insurance plans were associated with a longer median time to determination, a lower approval rate for proton therapy, and a longer time to start radiation of any modality.


Assuntos
Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Humanos , Idoso , Estados Unidos , Medicare , Prótons , Neoplasias de Cabeça e Pescoço/radioterapia , Renda , Cobertura do Seguro
14.
Res Sq ; 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36993444

RESUMO

The CD8+ T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1+ TCF1+ stem-like CD8+ T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS's impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8+ T cells at 3 days. However, CD8+ T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1+ stem-like population.

15.
Clin Nucl Med ; 48(4): e153-e159, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36754362

RESUMO

PURPOSE: We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. METHODS: Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. RESULTS: Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). CONCLUSIONS: Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/cirurgia , Ácidos Carboxílicos , Falha de Tratamento , Terapia de Salvação , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia
16.
Blood Adv ; 7(13): 2983-2993, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-36809796

RESUMO

To report the activity of venetoclax in patients with relapsed mantle cell lymphoma (MCL), we identified 81 patients treated with venetoclax monotherapy (n = 50, 62%) or in combination with a Bruton tyrosine kinase inhibitor (BTKi) (n = 16, 20%), an anti-CD20 monoclonal antibody (n = 11, 14%), or other active agents at 12 US academic medical centers. Patients had high-risk disease features including Ki67 >30% (61%), blastoid/pleomorphic histology (29%), complex karyotype (34%), and TP53 alterations (49%), and received a median of 3 prior treatments including BTKis in 91%. Venetoclax alone or in combination resulted in an overall response rate (ORR) of 40% and median progression-free (PFS) and overall survival (OS) of 3.7 and 12.5 months, respectively. The receipt of ≤3 prior treatments was associated with higher odds of response to venetoclax in a univariable analysis. In a multivariable analysis, having a high-risk Mantle Cell Lymphoma International Prognostic Index score before receiving venetoclax and disease relapse or progression within 24 months of diagnosis were associated with inferior OS whereas the use of venetoclax in combination was associated with superior OS. Although most patients (61%) had low risk for tumor lysis syndrome (TLS), 12.3% of patients developed TLS despite the implementation of several mitigation strategies. In conclusion, venetoclax resulted in good ORR but short PFS in patients with MCL who are at high risk, and may have a better role in earlier lines of treatment and/or in conation with other active agents. TLS remains an important risk in patients with MCL who initiate treatment with venetoclax.


Assuntos
Antineoplásicos , Linfoma de Célula do Manto , Síndrome de Lise Tumoral , Humanos , Adulto , Linfoma de Célula do Manto/tratamento farmacológico , Recidiva Local de Neoplasia , Antineoplásicos/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico
17.
J Nucl Med ; 64(4): 586-591, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36328489

RESUMO

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conventional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. ≥ 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 ± 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival benefits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Antagonistas de Androgênios , Recidiva Local de Neoplasia/patologia , Prostatectomia/métodos
18.
Leuk Lymphoma ; 64(3): 597-604, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35673767

RESUMO

Infections originating in the skin/soft tissue are a major cause of mortality in cutaneous T-cell lymphoma (CTCL). We performed a retrospective analysis to characterize cutaneous cultures and assess risk factors for bacteremia among 69 patients with CTCL. Cutaneous infections and antimicrobial resistance were common. Black race and lymph node involvement were associated with bacteremia. Mitigating strategies for invasive infections in CTCL remain unclear. HighlightsSkin/soft tissue infections are common in cutaneous T-cell lymphoma (CTCL).Black race, lymph node involvement, and positive cultures for S. aureus, Gram-negative bacteria, or multiple organisms were associated with an increased rate of bacteremia.The role of antimicrobial prophylaxis and staphylococcus decolonization is unclear.


Assuntos
Bacteriemia , Linfoma Cutâneo de Células T , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Staphylococcus aureus , Micose Fungoide/patologia , Síndrome de Sézary/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/patologia , Bacteriemia/etiologia
19.
Head Neck ; 44(12): 2854-2864, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36196859

RESUMO

BACKGROUND: Large analyses of T4 larynx cancer (LC) have raised concerns that larynx preservation (LP) contributes to reduced survival compared with laryngectomy (LGX). The role of operability has not been previously considered as a confounder. METHODS: We queried the National Cancer Database for T4M0 LC diagnosed 2004-2015. Patients were categorized as undergoing LGX, chemoradiotherapy but operable (LP-operable), and chemoradiotherapy inoperable (LP-inoperable). Overall survival (OS) was estimated by Kaplan-Meier. Cox multivariate analysis (MVA) identified variables associated with OS. RESULTS: We identified 1405 LGX, 164 LP-operable and 1969 LP-inoperable patients. Compared with LGX, MVA demonstrated worse OS among LP-inoperable (HR 1.28 95%CI 1.17-1.40, p < 0.01) but not LP-operable patients (HR 1.12 95%CI 0.91-1.39, p = 0.28). CONCLUSIONS: LP-operable patients did not have significantly worse OS than those undergoing LGX.


Assuntos
Neoplasias Laríngeas , Laringe , Humanos , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/tratamento farmacológico , Estadiamento de Neoplasias , Laringectomia , Laringe/cirurgia , Laringe/patologia , Quimiorradioterapia , Resultado do Tratamento , Estudos Retrospectivos
20.
JAMA Dermatol ; 158(11): 1293-1299, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069854

RESUMO

Importance: Mycosis fungoides and Sézary syndrome (MF/SS) has an increased incidence in Black patients, but clinical characteristics, treatments, and outcomes have been poorly characterized. Objective: To assess racial differences in presentation and outcome and identify drivers for racial disparities in MF/SS. Design, Setting, and Participants: A retrospective cohort analysis was conducted of 566 patients with MF/SS diagnosed from 1990 to 2020 and seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital, both in Atlanta, Georgia. Self-reported race and ethnicity were obtained from patient medical records and analyzed as 2 groups: non-Hispanic Black (Black) and all other races and ethnicities, including Asian, Hispanic, White, and unknown/undeclared (non-Black). Main Outcomes and Measures: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival and time to next treatment. The primary outcome was to assess differences in overall survival by racial and ethnic group. The hypotheses were formulated prior to data collection. Results: Of the 566 patients with MF/SS identified (mean [SD] age 55 [16.4] years; 270 (47.7%) female), 257 were Black and 309 were non-Black. Black race was associated with increased rates of progression to a higher TNMB stage (39.8% in Black patients vs 29.1% in non-Black patients; P < .001) but not survival. Black patients were younger and had increased female predominance, higher TNMB stage, higher tumor stage, nodal involvement, and higher lactate dehydrogenase level compared with non-Black patients with MF/SS. Hypopigmented MF (HMF) was found in 62 patients, who were mostly Black (n = 59). Hypopigmented MF was significantly associated with survival on univariate and multivariable models, with 10-year survival of 100% in patients with HMF compared with 51.8% in patients without HMF. Black race was only associated with inferior outcomes after excluding patients with HMF who were younger than 60 years (hazard ratio [HR], 1.61; 95% CI, 1.02-2.55; P = .04), but not in patients older than 60 years (HR, 1.20; 95% CI, 0.80-1.81; P = .37). On multivariate analysis, among the cohort without HMF who were younger than 60 years, Black race remained statistically significant when controlling for cancer stage and large-cell transformation (HR, 1.27; 95% CI, 1.08-2.87; P = .43). Conclusions and Relevance: In this cohort study, Black patients with MF/SS showed distinct clinical presentations and patterns of progression with heterogeneous outcomes depending on age at presentation and presence of HMF.


Assuntos
Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/terapia , Síndrome de Sézary/patologia , Etnicidade , Estudos Retrospectivos , Estudos de Coortes , Neoplasias Cutâneas/patologia , Prognóstico , Micose Fungoide/diagnóstico , Micose Fungoide/terapia , Micose Fungoide/patologia , Transformação Celular Neoplásica/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA